Unnamed: 0
int64 0
350k
| ApplicationNumber
int64 9.75M
96.1M
| ArtUnit
int64 1.6k
3.99k
| Abstract
stringlengths 7
8.37k
| Claims
stringlengths 3
292k
| abstract-claims
stringlengths 68
293k
| TechCenter
int64 1.6k
3.9k
|
|---|---|---|---|---|---|---|
1,300 | 15,257,530 | 1,617 | A composition and method of treating patients diagnosed with NAFLD is disclosed. The composition contains n-3 polyunsaturated fatty acids (PUFAs) for treatment of NAFLD patients, wherein the amount of PCB 153 in the composition has been minimized. The composition is administered to a patient in a sufficient amount and for a sufficient time to increase the level of n-3 PUFAs or to correct a deficiency of n-3 PUFAs in the patient's blood. The method increases the level of n-3 PUFAs without contributing to the body burden of PCB 153. | 1. A method of treating a patient diagnosed with non-alcoholic fatty liver disease (NAFLD) comprising administering an n3 polyunsaturated fatty acids (n3 PUFAs) composition to the patient in a sufficient amount to increase a level of n3 PUFAs or to correct a deficiency of n3 PUFAs in the blood of the patient, wherein the composition comprises at least 40 weight % of at least one of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), or derivatives thereof, by weight of the fatty acids therein, and an amount of PCB 153 in the composition is less than 5.0 ng/g. 2. The method of claim 1 wherein the composition comprises at least 60% of at least one of EPA and DHA by weight of the fatty acids therein. 3. The method of claim 1 wherein a weight ratio of EPA:DHA in the composition ranges from about 1:10 to about 10:1. 4. The method of claim 1 wherein the composition originates from a marine oil. 5. The method of claim 1 wherein the PUFAs are present in at least one of a free fatty acid form; an esterified form; a phospholipid form; a mono/di/tri-glyceride form, and salts thereof. 6. The method of claim 1 wherein the composition comprises a sum of about 84 weight % EPA and DHA. 7. The method of claim 1 wherein the composition comprises 460 mg EPA-ethyl ester and 380 mg DHA-ethyl ester per gram. 8. The method of claim 1 wherein the amount of PCB 153 is less than 4.0 ng/g. 9. The method of claim 8 wherein the amount of PCB 153 is less than 3.0 ng/g. 10. The method of claim 9 wherein the amount of PCB 153 is less than 1.0 ng/g. 11. The method of claim 10 wherein the amount of PCB 153 is less than 0.7 ng/g. 12. The method of claim 1 wherein the increase of n3 PUFAs in the blood is at least 10%, measured as a change obtained in erythrocyte EPA and DHA as a percentage of total fatty acids. 13. The method of claim 1 wherein a level of n3 PUFAs in blood is increased to above about 8.0 wt % of total plasma or serum phospholipid fatty acid level in the blood. 14. The method of claim 1 wherein an Omega-3 Index (%) is increased by at least 20%. 15. The method of claim 1 wherein the composition is selected from the group of Enteral Formulas for Special Medical use, Foods for Specified Health Uses, Food for Special Medical Purposes (FSMP), Food for Special Dietary Use (FSDU), Medical Nutrition, and a Medical food. 16. The method of claim 1 wherein an Omega-3 Index (%) is increased to above about 6.0% of the total fatty acids in the blood. 17. The method of claim 1 wherein the method corrects an imbalance in a ratio of n-6 PUFAs to n3 PUFAs in the blood. 18. The method of claim 1 wherein the composition is administered to the patient over a sufficient time to increase a level of 3-PUFAs or correct a deficiency of 3-PUFAs in the blood of the patient. 19. An n3 polyunsaturated fatty acids (PUFAs) composition comprising at least 40% of at least one of EPA and DHA, or derivatives thereof, by weight of the fatty acids therein, wherein an amount of PCB 153 in the composition is less than 5.0 ng/g. 20. The composition of claim 19 further comprising an antioxidant. 21. The composition of claim 20 wherein the antioxidant comprises mixed tocopherol. 22. The composition of claim 19 comprising at least 60% of at least one of EPA and DHA, by weight of the fatty acids therein. 23. The composition of claim 19 wherein a weight ratio of EPA:DHA in the composition ranges from about 1:10 about 10:1. 24. The composition of claim 19 wherein the PUFAs are present in at least one of a free fatty acid form; an esterified form; a phospholipid form; a mono/di/tri-glyceride form, and salts thereof. 25. The composition of claim 19 wherein the amount of PCB 153 in the composition is less than 2.0 ng/g. 26. The composition of claim 25 wherein the amount of PCB 153 in the composition is less than 0.7 ng/g. | A composition and method of treating patients diagnosed with NAFLD is disclosed. The composition contains n-3 polyunsaturated fatty acids (PUFAs) for treatment of NAFLD patients, wherein the amount of PCB 153 in the composition has been minimized. The composition is administered to a patient in a sufficient amount and for a sufficient time to increase the level of n-3 PUFAs or to correct a deficiency of n-3 PUFAs in the patient's blood. The method increases the level of n-3 PUFAs without contributing to the body burden of PCB 153.1. A method of treating a patient diagnosed with non-alcoholic fatty liver disease (NAFLD) comprising administering an n3 polyunsaturated fatty acids (n3 PUFAs) composition to the patient in a sufficient amount to increase a level of n3 PUFAs or to correct a deficiency of n3 PUFAs in the blood of the patient, wherein the composition comprises at least 40 weight % of at least one of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), or derivatives thereof, by weight of the fatty acids therein, and an amount of PCB 153 in the composition is less than 5.0 ng/g. 2. The method of claim 1 wherein the composition comprises at least 60% of at least one of EPA and DHA by weight of the fatty acids therein. 3. The method of claim 1 wherein a weight ratio of EPA:DHA in the composition ranges from about 1:10 to about 10:1. 4. The method of claim 1 wherein the composition originates from a marine oil. 5. The method of claim 1 wherein the PUFAs are present in at least one of a free fatty acid form; an esterified form; a phospholipid form; a mono/di/tri-glyceride form, and salts thereof. 6. The method of claim 1 wherein the composition comprises a sum of about 84 weight % EPA and DHA. 7. The method of claim 1 wherein the composition comprises 460 mg EPA-ethyl ester and 380 mg DHA-ethyl ester per gram. 8. The method of claim 1 wherein the amount of PCB 153 is less than 4.0 ng/g. 9. The method of claim 8 wherein the amount of PCB 153 is less than 3.0 ng/g. 10. The method of claim 9 wherein the amount of PCB 153 is less than 1.0 ng/g. 11. The method of claim 10 wherein the amount of PCB 153 is less than 0.7 ng/g. 12. The method of claim 1 wherein the increase of n3 PUFAs in the blood is at least 10%, measured as a change obtained in erythrocyte EPA and DHA as a percentage of total fatty acids. 13. The method of claim 1 wherein a level of n3 PUFAs in blood is increased to above about 8.0 wt % of total plasma or serum phospholipid fatty acid level in the blood. 14. The method of claim 1 wherein an Omega-3 Index (%) is increased by at least 20%. 15. The method of claim 1 wherein the composition is selected from the group of Enteral Formulas for Special Medical use, Foods for Specified Health Uses, Food for Special Medical Purposes (FSMP), Food for Special Dietary Use (FSDU), Medical Nutrition, and a Medical food. 16. The method of claim 1 wherein an Omega-3 Index (%) is increased to above about 6.0% of the total fatty acids in the blood. 17. The method of claim 1 wherein the method corrects an imbalance in a ratio of n-6 PUFAs to n3 PUFAs in the blood. 18. The method of claim 1 wherein the composition is administered to the patient over a sufficient time to increase a level of 3-PUFAs or correct a deficiency of 3-PUFAs in the blood of the patient. 19. An n3 polyunsaturated fatty acids (PUFAs) composition comprising at least 40% of at least one of EPA and DHA, or derivatives thereof, by weight of the fatty acids therein, wherein an amount of PCB 153 in the composition is less than 5.0 ng/g. 20. The composition of claim 19 further comprising an antioxidant. 21. The composition of claim 20 wherein the antioxidant comprises mixed tocopherol. 22. The composition of claim 19 comprising at least 60% of at least one of EPA and DHA, by weight of the fatty acids therein. 23. The composition of claim 19 wherein a weight ratio of EPA:DHA in the composition ranges from about 1:10 about 10:1. 24. The composition of claim 19 wherein the PUFAs are present in at least one of a free fatty acid form; an esterified form; a phospholipid form; a mono/di/tri-glyceride form, and salts thereof. 25. The composition of claim 19 wherein the amount of PCB 153 in the composition is less than 2.0 ng/g. 26. The composition of claim 25 wherein the amount of PCB 153 in the composition is less than 0.7 ng/g. | 1,600 |
1,301 | 16,178,788 | 1,612 | An oral care composition containing a source of stannous ions, a source of fluoride ions and an insoluble source of zinc ions, such as zinc oxide. The composition contains an amount of citric acid sufficient to increase the level of soluble zinc ions. | 1. An oral care composition comprising in a single phase:
(a) an orally acceptable vehicle; (b) a source of fluoride ions; (c) a source of stannous ions; (d) an insoluble source of zinc ions; (e) a buffering system comprising citric acid wherein the amount of citric acid is 0.5-4% by weight of the composition, and wherein the composition has a total water content of less than 15% by weight, based on the weight of the composition. 2-5. (canceled) 6. The composition of claim 1 wherein the insoluble source of zinc ions comprises a zinc salt of an organic acid. 7. The composition of claim 3, wherein the insoluble source of zinc ions comprises zinc oxide, zinc phosphate, zinc pyrophosphate or a mixture thereof. 8. The composition of claim 1 wherein the source of fluoride ions and the source of stannous ions comprises stannous fluoride. 9. The composition of claim 1 comprising at least one polyphosphate salt selected from the group consisting of inorganic polyphosphate salts which have equal to or less than three phosphorous atoms. 10. The composition of claim 6, wherein the at least one polyphosphate is selected from the group consisting of tetrasodium pyrophosphate, sodium tripolyphosphate, and mixtures thereof; wherein the total polyphosphate comprises from 1 to 10 wt % of the composition 11. The composition of claim 1 wherein the buffering system comprises a mixture of citric acid and trisodium citrate. 12. The composition of claim 1 comprising polyvinylpyrrolidone, a gum, or a mixture thereof. 13. The composition of claim 1 comprising a modified cellulose such as carboxymethyl cellulose. 14. The composition of claim 1 further comprising at least one humectant selected from the group consisting of glycerin, polyethylene glycol, propylene glycol, and mixtures thereof. 15. The composition of claim 1 wherein the composition is a dentifrice comprising one or more of an abrasive, a surfactant, a foaming agent, a vitamin, a polymer, a whitening agent, an enzyme, a humectant, a thickener, an antimicrobial agent, a preservative, L-arginine, a flavoring, or a coloring agent. 16. The composition of claim 1 in a single phase. 17. An oral care composition comprising:
(a) 0.5-3 wt. % citric acid; (b) 0.5-10 wt % Trisodium citrate; (c) 0.1-5 wt % Zinc oxide; (d) 0.1-5 wt % Stannous fluoride; (e) 10-50 wt % Glycerin; (f) 1-25 wt. % Propylene glycol; optionally comprising one or more of: (g) 0.1-12 wt % xanthan gum; (h) 0.25-10 wt % polyvinylpyrrolidone (PVP); (i) 0.2-1.5% wt. % carboxymethylcellulose (CMC); (j) 5-60 wt % Silica (total); (k) 0.1-10 wt % Tetrasodium Pyrophosphate (TSPP); (l) 0- 5 wt % Sodium acid pyrophosphate (SAPP); (m) 0.1-10 wt % Sodium Tripolyphosphate (STPP); (n) 0.1-10 wt % Sodium lauryl sulfate (SLS); (o) 0.1-10 wt % Cocamidopropyl betaine. 18-19. (canceled) 20. A method of treating or preventing a disease or condition of the oral cavity comprising contacting an oral cavity surface of a patient in need thereof with the composition of claim 1 any one of the foregoing claims. 21. The method of claim 20, wherein the disease or condition of the oral cavity is biofilm formation, plaque formation, oral inflammation or a combination thereof | An oral care composition containing a source of stannous ions, a source of fluoride ions and an insoluble source of zinc ions, such as zinc oxide. The composition contains an amount of citric acid sufficient to increase the level of soluble zinc ions.1. An oral care composition comprising in a single phase:
(a) an orally acceptable vehicle; (b) a source of fluoride ions; (c) a source of stannous ions; (d) an insoluble source of zinc ions; (e) a buffering system comprising citric acid wherein the amount of citric acid is 0.5-4% by weight of the composition, and wherein the composition has a total water content of less than 15% by weight, based on the weight of the composition. 2-5. (canceled) 6. The composition of claim 1 wherein the insoluble source of zinc ions comprises a zinc salt of an organic acid. 7. The composition of claim 3, wherein the insoluble source of zinc ions comprises zinc oxide, zinc phosphate, zinc pyrophosphate or a mixture thereof. 8. The composition of claim 1 wherein the source of fluoride ions and the source of stannous ions comprises stannous fluoride. 9. The composition of claim 1 comprising at least one polyphosphate salt selected from the group consisting of inorganic polyphosphate salts which have equal to or less than three phosphorous atoms. 10. The composition of claim 6, wherein the at least one polyphosphate is selected from the group consisting of tetrasodium pyrophosphate, sodium tripolyphosphate, and mixtures thereof; wherein the total polyphosphate comprises from 1 to 10 wt % of the composition 11. The composition of claim 1 wherein the buffering system comprises a mixture of citric acid and trisodium citrate. 12. The composition of claim 1 comprising polyvinylpyrrolidone, a gum, or a mixture thereof. 13. The composition of claim 1 comprising a modified cellulose such as carboxymethyl cellulose. 14. The composition of claim 1 further comprising at least one humectant selected from the group consisting of glycerin, polyethylene glycol, propylene glycol, and mixtures thereof. 15. The composition of claim 1 wherein the composition is a dentifrice comprising one or more of an abrasive, a surfactant, a foaming agent, a vitamin, a polymer, a whitening agent, an enzyme, a humectant, a thickener, an antimicrobial agent, a preservative, L-arginine, a flavoring, or a coloring agent. 16. The composition of claim 1 in a single phase. 17. An oral care composition comprising:
(a) 0.5-3 wt. % citric acid; (b) 0.5-10 wt % Trisodium citrate; (c) 0.1-5 wt % Zinc oxide; (d) 0.1-5 wt % Stannous fluoride; (e) 10-50 wt % Glycerin; (f) 1-25 wt. % Propylene glycol; optionally comprising one or more of: (g) 0.1-12 wt % xanthan gum; (h) 0.25-10 wt % polyvinylpyrrolidone (PVP); (i) 0.2-1.5% wt. % carboxymethylcellulose (CMC); (j) 5-60 wt % Silica (total); (k) 0.1-10 wt % Tetrasodium Pyrophosphate (TSPP); (l) 0- 5 wt % Sodium acid pyrophosphate (SAPP); (m) 0.1-10 wt % Sodium Tripolyphosphate (STPP); (n) 0.1-10 wt % Sodium lauryl sulfate (SLS); (o) 0.1-10 wt % Cocamidopropyl betaine. 18-19. (canceled) 20. A method of treating or preventing a disease or condition of the oral cavity comprising contacting an oral cavity surface of a patient in need thereof with the composition of claim 1 any one of the foregoing claims. 21. The method of claim 20, wherein the disease or condition of the oral cavity is biofilm formation, plaque formation, oral inflammation or a combination thereof | 1,600 |
1,302 | 14,198,061 | 1,617 | The disclosure provides for methods of repelling, directing, altering the behavior, and controlling an insect by utilizing a compound or composition described herein. The disclosure also provides for methods of promoting the health of an insect by repelling a pest that preys on insect and/or by providing an antibiotic or nutritional supplement composition to an insect. The disclosure also provides for a composition including at least one repelling, controlling, or directing compound or composition described herein together with an insecticide, herbicide, fungicide, or miticide. Compounds, compositions, seeds, and plants useful in these methods are also described. | 1. A method of repelling, controlling, and/or directing an insect from a seed, plant part, or plant comprising
a) treating a seed, plant part, or plant with at least one compound of Formula (I)-(IX) selected from the group consisting of:
in which,
R1 and R2 are independently selected from methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, iso-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and substituted or non substituted C2-C14-alkyl, substituted or non substituted C2-C14 alkenyl, a substituted or non substituted C2-C14-alkynyl, alkyl substituted with halogen, F, Cl, Br, I, oxygen, hydroxyl, alkoxy, cyano, aryloxy, C═C, C≡C; nitrogen, NH2, alkyl amino, dialkyl amine trialkylamino; SH, alkylthio or where R1 and R2 are linked together to form a substituted or unsubstituted (CH2)3, (CH2)4, (CH2)5, (CH2)6, (CH2)7, (CH2)8, (CH2)9, (CH2)10, (CH2)11, (CH2)12, (CH2)13 ring structure;
R3 and R4 are individually selected from H, alkyl, methyl, ethyl, propyl, or butyl;
b) wherein said at least one compound repels, controls, and/or directs at least 80% of the insects for at least 8 hours. 2. The method according to claim 1, wherein R1 is methyl or ethyl and R2 is selected from the group consisting of methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, iso-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and substituted or non substituted C2-C14-alkyl, substituted or non substituted C2-C14 alkenyl, a substituted or non substituted C2-C14-alkynyl. 3. The method according to claim 1, wherein said at least one compound is a C7-C15 ketone. 4. The method according to claim 3, wherein said C7-C15 ketone is selected from the group consisting of 3-heptanone, 4-heptanone, cycloheptanone, 2-octanone, 3-octanone, cyclooctanone, 2-nonanone, cyclononanone, 2-decanone, 3-decanone, 4-decanone, 5-decanone, 2-undecanone, 2-dodecanone, 2-trideconone, 2-tetradecanone, 2-pentadecanone, 2-hexadecanone, 2-heptadecanone, cyclodeconone, and sulfur analogs of 2-decanone. 5. The method according to claim 1, wherein said insect is a pollinating insect and said pollinating insect is optionally honeybee. 6. The method according to claim 1, wherein said at least one compound repels at least 90% of the insects for at least 24 hours. 7. The method according to claim 1, wherein said at least one compound is formulated in a composition comprising an agent selected from the group consisting of camphor, camphor oil, camphor powder, tea tree oil, pine oil, rosemary powder, and rosemary oil. 8. The method according to claim 3, wherein said C7-C15 ketone compound repels a larger percentage of honeybees than an equal percent weight of a compound selected from the group consisting of camphor oil, ajowan oil, camphor powder, and rosemary oil. 9. The method according to claim 1, wherein said compound is formulated in a composition comprising an insecticide, herbicide, insecticide, and/or miticide. 10. The method according to claim 9, wherein said composition further comprises an active agent selected from the group consisting of acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, thiamethoxam, ethiprole, fipronil, Poncho, Gaucho, and Poncho/Votivo. 11. A method for promoting the health of an insect comprising
(a) treating a seed, plant, or plant part with a repelling, controlling, or directing compound or composition comprising a ketone, and wherein the compound or composition repels, controls, or directs at least 80% of the insects for at least 8 hours; and (b) treating a seed, plant, or plant part with one or more of a compound or composition formulated to repel, control, or direct a pest of said insect, formulated to provide an nutritional composition to said insect, or formulated to provide an antibiotic composition to said insect. 12. The method according to claim 11, wherein the ketone compound comprises a C7-C15 ketone. 13. The method according to claim 12, wherein said C7-C15 compound is selected from the group consisting of 3-heptanone, 4-heptanone, cycloheptanone, 2-octanone, 3-octanone, cyclooctanone, 2-nonanone, cyclononanone, 2-decanone, 3-decanone, 4-decanone, 5-decanone, 2-undecanone, 2-dodecanone, 2-trideconone, 2-tetradecanone, 2-pentadecanone, 2-hexadecanone, 2-heptadecanone, cyclodeconone, and sulfur analogs of 2-decanone. 14. The method according to claim 11, wherein said insect is a pollinating insect and said pollinating insect is optionally honeybee. 15. The method according to claim 11, wherein the compound or composition repels at least 90% of the insects for at least 24 hours. 16. The method according to claim 11, wherein the compound is formulated in a composition comprising an agent selected from the group consisting of camphor, camphor oil, camphor powder, tea tree oil, pine oil, rosemary powder, and rosemary oil. 17. The method according to claim 12, wherein said C7-C15 ketone compound repels, controls, or directs a larger percentage of an insect than a composition comprising a compound selected from the group consisting of camphor oil, ajowan oil, camphor powder, and rosemary oil. 18. The method according to claim 11, wherein the compound is formulated in a composition comprising an insecticide, herbicide, insecticide, or miticide. 19. The method according to claim 18, wherein said composition further comprises an active agent selected from the group consisting of acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, thiamethoxam, ethiprole, fipronil, Poncho, Gaucho, and Poncho/Votivo. 20. The method of claim 18, wherein said miticide is selected from the group consisting of 1-arylimidazole, 1-aryl pyrrole, and 1-arylpyrazole. 21. The method of claim 1, wherein said at least one compound of Formula (I)-(IX) comprises a decanone compound. 22. The method of claim 1, wherein said at least one compound of Formula (I)-(IX) comprises 2-decanone. 23. The method of claim 1, wherein said at least one compound of Formula (I)-(IX) comprises 3-decanone. 24. The method of claim 1, wherein said at least one compound of Formula (I)-(IX) comprises 4-decanone. 25. The method of claim 1, wherein said at least one compound of Formula (I)-(IX) comprises 5-decanone. 26. The method of claim 1, wherein said method comprises a synergistic mixture of at least one compound of Formula (I)-(IX). 27. A seed capable of repelling, controlling, or directing an insect, wherein said seed is coated with at least one compound of Formula (I)-(IX) selected from the group consisting of:
in which,
R1 and R2 are independently selected from methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, iso-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and substituted or non substituted C2-C14-alkyl, substituted or non substituted C2-C14 alkenyl, a substituted or non substituted C2-C14-alkynyl, alkyl substituted with halogen, F, Cl, Br, I, oxygen, hydroxyl, alkoxy, cyano, aryloxy, C═C, C≡C; nitrogen, NH2, alkyl amino, dialkyl amine trialkylamino; SH, alkylthio or where R1 and R2 are linked together to form a substituted or unsubstituted (CH2)3, (CH2)4, (CH2)5, (CH2)6, (CH2)7, (CH2)8, (CH2)9, (CH2)10, (CH2)11, (CH2)12, (CH2)13 ring structure; and
R3 and R4 are individually selected from H, alkyl, methyl, ethyl, propyl, or butyl; and
wherein said seed repels, controls, or directs at least 80% of the insects for at least 8 hours. 28. The seed of claim 27, wherein said at least one compound of Formula (I)-(IX) comprises a decanone compound. 29. The seed of claim 27, wherein said at least one compound of Formula (I)-(IX) comprises 2-decanone. 30. The seed of claim 27, wherein said at least one compound of Formula (I)-(IX) comprises 3-decanone. 31. The seed of claim 27, wherein said at least one compound of Formula (I)-(IX) comprises 4-decanone. 32. The seed of claim 27, wherein said at least one compound of Formula (I)-(IX) comprises 5-decanone. 33. The seed of claim 27, wherein said method comprises a synergistic mixture of at least one compound of Formula (I)-(IX). 34. A fertilizer composition comprising (1) fertilizer and (2) at least one compound of Formula (I)-(IX) selected from the group consisting of:
in which,
R1 and R2 are independently selected from methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, iso-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and substituted or non substituted C2-C14-alkyl, substituted or non substituted C2-C14 alkenyl, a substituted or non substituted C2-C14-alkynyl, alkyl substituted with halogen, F, Cl, Br, I, oxygen, hydroxyl, alkoxy, cyano, aryloxy, C═C, C≡C; nitrogen, NH2, alkyl amino, dialkyl amine trialkylamino; SH, alkylthio or where R1 and R2 are linked together to form a substituted or unsubstituted (CH2)3, (CH2)4, (CH2)5, (CH2)6, (CH2)7, (CH2)8, (CH2)9, (CH2)10, (CH2)11, (CH2)12, (CH2)13 ring structure; and
R3 and R4 are individually selected from H, alkyl, methyl, ethyl, propyl, or butyl; and
wherein said seed repels, controls, or directs at least 80% of the insects for at least 8 hours. 35. The fertilizer composition of claim 34, wherein said at least one compound of Formula (I)-(IX) comprises a decanone compound. 36. The fertilizer composition of claim 34, wherein said at least one compound of Formula (I)-(IX) comprises 2-decanone. 37. The fertilizer composition of claim 34, wherein said at least one compound of Formula (I)-(IX) comprises 3-decanone. 38. The fertilizer composition of claim 34, wherein said at least one compound of Formula (I)-(IX) comprises 4-decanone. 39. The seed of claim 34, wherein said at least one compound of Formula (I)-(IX) comprises 5-decanone. 40. The seed of claim 34, wherein said method comprises a synergistic mixture of at least one compound of Formula (I)-(IX). | The disclosure provides for methods of repelling, directing, altering the behavior, and controlling an insect by utilizing a compound or composition described herein. The disclosure also provides for methods of promoting the health of an insect by repelling a pest that preys on insect and/or by providing an antibiotic or nutritional supplement composition to an insect. The disclosure also provides for a composition including at least one repelling, controlling, or directing compound or composition described herein together with an insecticide, herbicide, fungicide, or miticide. Compounds, compositions, seeds, and plants useful in these methods are also described.1. A method of repelling, controlling, and/or directing an insect from a seed, plant part, or plant comprising
a) treating a seed, plant part, or plant with at least one compound of Formula (I)-(IX) selected from the group consisting of:
in which,
R1 and R2 are independently selected from methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, iso-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and substituted or non substituted C2-C14-alkyl, substituted or non substituted C2-C14 alkenyl, a substituted or non substituted C2-C14-alkynyl, alkyl substituted with halogen, F, Cl, Br, I, oxygen, hydroxyl, alkoxy, cyano, aryloxy, C═C, C≡C; nitrogen, NH2, alkyl amino, dialkyl amine trialkylamino; SH, alkylthio or where R1 and R2 are linked together to form a substituted or unsubstituted (CH2)3, (CH2)4, (CH2)5, (CH2)6, (CH2)7, (CH2)8, (CH2)9, (CH2)10, (CH2)11, (CH2)12, (CH2)13 ring structure;
R3 and R4 are individually selected from H, alkyl, methyl, ethyl, propyl, or butyl;
b) wherein said at least one compound repels, controls, and/or directs at least 80% of the insects for at least 8 hours. 2. The method according to claim 1, wherein R1 is methyl or ethyl and R2 is selected from the group consisting of methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, iso-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and substituted or non substituted C2-C14-alkyl, substituted or non substituted C2-C14 alkenyl, a substituted or non substituted C2-C14-alkynyl. 3. The method according to claim 1, wherein said at least one compound is a C7-C15 ketone. 4. The method according to claim 3, wherein said C7-C15 ketone is selected from the group consisting of 3-heptanone, 4-heptanone, cycloheptanone, 2-octanone, 3-octanone, cyclooctanone, 2-nonanone, cyclononanone, 2-decanone, 3-decanone, 4-decanone, 5-decanone, 2-undecanone, 2-dodecanone, 2-trideconone, 2-tetradecanone, 2-pentadecanone, 2-hexadecanone, 2-heptadecanone, cyclodeconone, and sulfur analogs of 2-decanone. 5. The method according to claim 1, wherein said insect is a pollinating insect and said pollinating insect is optionally honeybee. 6. The method according to claim 1, wherein said at least one compound repels at least 90% of the insects for at least 24 hours. 7. The method according to claim 1, wherein said at least one compound is formulated in a composition comprising an agent selected from the group consisting of camphor, camphor oil, camphor powder, tea tree oil, pine oil, rosemary powder, and rosemary oil. 8. The method according to claim 3, wherein said C7-C15 ketone compound repels a larger percentage of honeybees than an equal percent weight of a compound selected from the group consisting of camphor oil, ajowan oil, camphor powder, and rosemary oil. 9. The method according to claim 1, wherein said compound is formulated in a composition comprising an insecticide, herbicide, insecticide, and/or miticide. 10. The method according to claim 9, wherein said composition further comprises an active agent selected from the group consisting of acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, thiamethoxam, ethiprole, fipronil, Poncho, Gaucho, and Poncho/Votivo. 11. A method for promoting the health of an insect comprising
(a) treating a seed, plant, or plant part with a repelling, controlling, or directing compound or composition comprising a ketone, and wherein the compound or composition repels, controls, or directs at least 80% of the insects for at least 8 hours; and (b) treating a seed, plant, or plant part with one or more of a compound or composition formulated to repel, control, or direct a pest of said insect, formulated to provide an nutritional composition to said insect, or formulated to provide an antibiotic composition to said insect. 12. The method according to claim 11, wherein the ketone compound comprises a C7-C15 ketone. 13. The method according to claim 12, wherein said C7-C15 compound is selected from the group consisting of 3-heptanone, 4-heptanone, cycloheptanone, 2-octanone, 3-octanone, cyclooctanone, 2-nonanone, cyclononanone, 2-decanone, 3-decanone, 4-decanone, 5-decanone, 2-undecanone, 2-dodecanone, 2-trideconone, 2-tetradecanone, 2-pentadecanone, 2-hexadecanone, 2-heptadecanone, cyclodeconone, and sulfur analogs of 2-decanone. 14. The method according to claim 11, wherein said insect is a pollinating insect and said pollinating insect is optionally honeybee. 15. The method according to claim 11, wherein the compound or composition repels at least 90% of the insects for at least 24 hours. 16. The method according to claim 11, wherein the compound is formulated in a composition comprising an agent selected from the group consisting of camphor, camphor oil, camphor powder, tea tree oil, pine oil, rosemary powder, and rosemary oil. 17. The method according to claim 12, wherein said C7-C15 ketone compound repels, controls, or directs a larger percentage of an insect than a composition comprising a compound selected from the group consisting of camphor oil, ajowan oil, camphor powder, and rosemary oil. 18. The method according to claim 11, wherein the compound is formulated in a composition comprising an insecticide, herbicide, insecticide, or miticide. 19. The method according to claim 18, wherein said composition further comprises an active agent selected from the group consisting of acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, thiamethoxam, ethiprole, fipronil, Poncho, Gaucho, and Poncho/Votivo. 20. The method of claim 18, wherein said miticide is selected from the group consisting of 1-arylimidazole, 1-aryl pyrrole, and 1-arylpyrazole. 21. The method of claim 1, wherein said at least one compound of Formula (I)-(IX) comprises a decanone compound. 22. The method of claim 1, wherein said at least one compound of Formula (I)-(IX) comprises 2-decanone. 23. The method of claim 1, wherein said at least one compound of Formula (I)-(IX) comprises 3-decanone. 24. The method of claim 1, wherein said at least one compound of Formula (I)-(IX) comprises 4-decanone. 25. The method of claim 1, wherein said at least one compound of Formula (I)-(IX) comprises 5-decanone. 26. The method of claim 1, wherein said method comprises a synergistic mixture of at least one compound of Formula (I)-(IX). 27. A seed capable of repelling, controlling, or directing an insect, wherein said seed is coated with at least one compound of Formula (I)-(IX) selected from the group consisting of:
in which,
R1 and R2 are independently selected from methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, iso-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and substituted or non substituted C2-C14-alkyl, substituted or non substituted C2-C14 alkenyl, a substituted or non substituted C2-C14-alkynyl, alkyl substituted with halogen, F, Cl, Br, I, oxygen, hydroxyl, alkoxy, cyano, aryloxy, C═C, C≡C; nitrogen, NH2, alkyl amino, dialkyl amine trialkylamino; SH, alkylthio or where R1 and R2 are linked together to form a substituted or unsubstituted (CH2)3, (CH2)4, (CH2)5, (CH2)6, (CH2)7, (CH2)8, (CH2)9, (CH2)10, (CH2)11, (CH2)12, (CH2)13 ring structure; and
R3 and R4 are individually selected from H, alkyl, methyl, ethyl, propyl, or butyl; and
wherein said seed repels, controls, or directs at least 80% of the insects for at least 8 hours. 28. The seed of claim 27, wherein said at least one compound of Formula (I)-(IX) comprises a decanone compound. 29. The seed of claim 27, wherein said at least one compound of Formula (I)-(IX) comprises 2-decanone. 30. The seed of claim 27, wherein said at least one compound of Formula (I)-(IX) comprises 3-decanone. 31. The seed of claim 27, wherein said at least one compound of Formula (I)-(IX) comprises 4-decanone. 32. The seed of claim 27, wherein said at least one compound of Formula (I)-(IX) comprises 5-decanone. 33. The seed of claim 27, wherein said method comprises a synergistic mixture of at least one compound of Formula (I)-(IX). 34. A fertilizer composition comprising (1) fertilizer and (2) at least one compound of Formula (I)-(IX) selected from the group consisting of:
in which,
R1 and R2 are independently selected from methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, iso-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and substituted or non substituted C2-C14-alkyl, substituted or non substituted C2-C14 alkenyl, a substituted or non substituted C2-C14-alkynyl, alkyl substituted with halogen, F, Cl, Br, I, oxygen, hydroxyl, alkoxy, cyano, aryloxy, C═C, C≡C; nitrogen, NH2, alkyl amino, dialkyl amine trialkylamino; SH, alkylthio or where R1 and R2 are linked together to form a substituted or unsubstituted (CH2)3, (CH2)4, (CH2)5, (CH2)6, (CH2)7, (CH2)8, (CH2)9, (CH2)10, (CH2)11, (CH2)12, (CH2)13 ring structure; and
R3 and R4 are individually selected from H, alkyl, methyl, ethyl, propyl, or butyl; and
wherein said seed repels, controls, or directs at least 80% of the insects for at least 8 hours. 35. The fertilizer composition of claim 34, wherein said at least one compound of Formula (I)-(IX) comprises a decanone compound. 36. The fertilizer composition of claim 34, wherein said at least one compound of Formula (I)-(IX) comprises 2-decanone. 37. The fertilizer composition of claim 34, wherein said at least one compound of Formula (I)-(IX) comprises 3-decanone. 38. The fertilizer composition of claim 34, wherein said at least one compound of Formula (I)-(IX) comprises 4-decanone. 39. The seed of claim 34, wherein said at least one compound of Formula (I)-(IX) comprises 5-decanone. 40. The seed of claim 34, wherein said method comprises a synergistic mixture of at least one compound of Formula (I)-(IX). | 1,600 |
1,303 | 16,033,528 | 1,619 | The present invention provides sunscreen composition comprising a hydrophobically modified polyurethane, a viscosity increasing polymer, and glyceryl stearate. This composition has surprisingly light aesthetics while providing excellent UV protection. | 1. A sunscreen composition comprising:
(a) at least about 10 weight percent of one or more UV filters; (b) about 0.55 to about 1 weight percent of a hydrophobically modified polyurethane; (c) about 0.1 to about 0.6 weight percent of a viscosity increasing polymer selected from the group consisting of taurate copolymers and acrylate crosspolymers; and (d) at least about 0.1 weight percent of glyceryl stearate. 2. The composition of claim 1, wherein said viscosity increasing polymer is a taurate copolymer. 3. The composition of claim 1, wherein said viscosity increasing polymer is an acrylate crosspolymer. 4. The composition of claim 1 comprising at least about 0.1 weight percent avobenzone. 5. The composition of claim 4 further comprising octocrylene and homosalate. 6. The composition of claim 1 further comprising hyaluronic acid. 7. The composition of claim 1 further comprising silica. 8. The composition of claim 1 further comprising a humectant selected from the group consisting of glycerin, pentylene glycol, and mixtures thereof. 9. A sunscreen composition comprising at least about 10 weight percent of one or more UV filters and having a linear complex viscosity of about 1500 to about 5000 cP at 100 rad/s. 10. The composition of claim 9 comprising at least 0.1 weight percent avobenzone. 11. The composition of claim 10, further comprising octocrylene and homosalate. 12. The composition of claim 9 further comprising hyaluronic acid. 13. The composition of claim 9 further comprising silica. 14. The composition of claim 9 further comprising a humectant selected from the group consisting of glycerin, propylene glycol, and mixtures thereof. 15. A sunscreen composition comprising:
(a) at least about 10 weight percent of a combination of UV filters comprising avobenzone, octocrylene, homosalate, and octisalate; (b) about 0.55 to about 0.75 weight percent of a hydrophobically modified polyurethane; (c) about 0.4 to about 0.6 weight percent of a taurate copolymer; and (d) at least about 0.1 weight percent of glyceryl stearate; (e) silica; (f) a humectant selected from the group consisting of glycerin, propylene glycol, and mixtures thereof; and (g) ethanol. 16. A sunscreen composition comprising:
(a) at least about 10 weight percent of a combination of UV filters comprising avobenzone, octocrylene, homosalate, and a triazone derivative; (b) about 0.5 to about 1 weight percent of a hydrophobically modified polyurethane; (c) about 0.1 to about 0.3 weight percent of an acrylate crosspolymer; (d) at least about 0.1 weight percent of glyceryl stearate; (e) silica; (f) a humectant selected from the group consisting of glycerin, propylene glycol, and mixtures thereof; and (g) ethanol. | The present invention provides sunscreen composition comprising a hydrophobically modified polyurethane, a viscosity increasing polymer, and glyceryl stearate. This composition has surprisingly light aesthetics while providing excellent UV protection.1. A sunscreen composition comprising:
(a) at least about 10 weight percent of one or more UV filters; (b) about 0.55 to about 1 weight percent of a hydrophobically modified polyurethane; (c) about 0.1 to about 0.6 weight percent of a viscosity increasing polymer selected from the group consisting of taurate copolymers and acrylate crosspolymers; and (d) at least about 0.1 weight percent of glyceryl stearate. 2. The composition of claim 1, wherein said viscosity increasing polymer is a taurate copolymer. 3. The composition of claim 1, wherein said viscosity increasing polymer is an acrylate crosspolymer. 4. The composition of claim 1 comprising at least about 0.1 weight percent avobenzone. 5. The composition of claim 4 further comprising octocrylene and homosalate. 6. The composition of claim 1 further comprising hyaluronic acid. 7. The composition of claim 1 further comprising silica. 8. The composition of claim 1 further comprising a humectant selected from the group consisting of glycerin, pentylene glycol, and mixtures thereof. 9. A sunscreen composition comprising at least about 10 weight percent of one or more UV filters and having a linear complex viscosity of about 1500 to about 5000 cP at 100 rad/s. 10. The composition of claim 9 comprising at least 0.1 weight percent avobenzone. 11. The composition of claim 10, further comprising octocrylene and homosalate. 12. The composition of claim 9 further comprising hyaluronic acid. 13. The composition of claim 9 further comprising silica. 14. The composition of claim 9 further comprising a humectant selected from the group consisting of glycerin, propylene glycol, and mixtures thereof. 15. A sunscreen composition comprising:
(a) at least about 10 weight percent of a combination of UV filters comprising avobenzone, octocrylene, homosalate, and octisalate; (b) about 0.55 to about 0.75 weight percent of a hydrophobically modified polyurethane; (c) about 0.4 to about 0.6 weight percent of a taurate copolymer; and (d) at least about 0.1 weight percent of glyceryl stearate; (e) silica; (f) a humectant selected from the group consisting of glycerin, propylene glycol, and mixtures thereof; and (g) ethanol. 16. A sunscreen composition comprising:
(a) at least about 10 weight percent of a combination of UV filters comprising avobenzone, octocrylene, homosalate, and a triazone derivative; (b) about 0.5 to about 1 weight percent of a hydrophobically modified polyurethane; (c) about 0.1 to about 0.3 weight percent of an acrylate crosspolymer; (d) at least about 0.1 weight percent of glyceryl stearate; (e) silica; (f) a humectant selected from the group consisting of glycerin, propylene glycol, and mixtures thereof; and (g) ethanol. | 1,600 |
1,304 | 14,758,457 | 1,617 | A microgranule preparation for oral administration which is characterized in that an inert core coated with a drug layer is mixed with sugar or sugar alcohol is provided. | 1. A microgranule preparation for oral administration, which is characterized in that an inert core coated with a drug layer is mixed with sugar or sugar alcohol. 2. The microgranule preparation according to claim 1, wherein the inert core is sugar or sugar alcohol. 3. The microgranule preparation according to claim 1, wherein the sugar or sugar alcohol is selected from the group consisting of xylitol, mannitol, isomalt, sorbitol, maltitol, the refined white sucrose, lactose, inositol, erythritol, crystaline fructose, trehalose, ribitol, arabitol, galactitol, lactitol and maltotritol. 4. The microgranule preparation according to claim 2, wherein the sugar or sugar alcohol is selected from the group consisting of xylitol, mannitol, isomalt, sorbitol, maltitol, the refined white sucrose, lactose, inositol, erythritol, crystaline fructose, trehalose, ribitol, arabitol, galactitol, lactitol and maltotritol. | A microgranule preparation for oral administration which is characterized in that an inert core coated with a drug layer is mixed with sugar or sugar alcohol is provided.1. A microgranule preparation for oral administration, which is characterized in that an inert core coated with a drug layer is mixed with sugar or sugar alcohol. 2. The microgranule preparation according to claim 1, wherein the inert core is sugar or sugar alcohol. 3. The microgranule preparation according to claim 1, wherein the sugar or sugar alcohol is selected from the group consisting of xylitol, mannitol, isomalt, sorbitol, maltitol, the refined white sucrose, lactose, inositol, erythritol, crystaline fructose, trehalose, ribitol, arabitol, galactitol, lactitol and maltotritol. 4. The microgranule preparation according to claim 2, wherein the sugar or sugar alcohol is selected from the group consisting of xylitol, mannitol, isomalt, sorbitol, maltitol, the refined white sucrose, lactose, inositol, erythritol, crystaline fructose, trehalose, ribitol, arabitol, galactitol, lactitol and maltotritol. | 1,600 |
1,305 | 15,400,505 | 1,615 | A method of economically producing stable and bio-available glutathione comprising immersing glutathione particles in an edible oil preferably selected from at least one of almond, coconut, grapeseed and olive; reducing the average size of glutathione particles to not more than 50 microns and preferably 1 or less; and adding a de-agglomeration agent comprising at least one selected from surfactants or chelating agents. A method of administering bio-available glutathione, prepared according to the foregoing, to a patient in a desired dose by a method selected from oral, pulmonary, rectal, sublingual, transdermal, and vaginal. | 1. A method of economically producing stable and bio-available glutathione comprising:
a. immersing glutathione particles in an edible oil; b. reducing the average size of glutathione particles to not more than 50 microns; and c. adding a de-agglomeration agent. 2. The method of claim 1 further comprising:
a. the oil selected from at least one of almond, coconut, grapeseed, olive, and vegetable;
b. for the reducing step using a process selected from at least one of diamond chamber, grinding beads, and microfluidizer; and
c. the de-agglomeration agent comprising at least one selected from surfactants or chelating agents. 3. The method of claim 2 further comprising:
a. the reducing step comprising grinding beads have a media size from 0.4-1.3 mm to reduce the average size of glutathione particles to not more than 1 micron; and
b. the de-agglomeration agent comprising lecithin. 4. The method of claim 1 further comprising adding the de-agglomeration agent before the particle size reduction is complete, whereby the de-agglomeration agent serves to speed the reduction of size reduction by preventing agglomeration of particles during processing. 5. The method of claim 4 further comprising:
a. the oil selected from at least one of almond, coconut, grapeseed, olive, and vegetable;
b. for the reducing step, processing in a batch manner using a process selected from at least one of diamond chamber and grinding beads; and
c. the de-agglomeration agent comprising at least one selected from surfactants or chelating agents. 6. The method of claim 5 further comprising:
a. the reducing step using grinding beads have a media size from 0.4-1.3 mm to reduce the average size of glutathione particles to not more than 1 micron; and
b. the de-agglomeration agent comprising lecithin. 7. The method of claim 6 further comprising adding the lecithin during the reducing step in more than one batch at different stages during the size-reduction step. 8. A method of administering bio-available glutathione to a patient comprising:
a. immersing glutathione particles in an edible oil; b. reducing the average size of glutathione particles to not more than 50 microns; c. adding a de-agglomeration agent; d. administering a desired dose to the patient by a method selected from oral, pulmonary, rectal, sublingual, transdermal, and vaginal. 9. The method of claim 8 further comprising:
a. the oil selected from at least one of almond, coconut, grapeseed, olive, and vegetable;
b. for the reducing step using a process selected from at least one of diamond chamber, grinding beads, and microfluidizer; and
c. the de-agglomeration agent comprising at least one selected from surfactants or chelating agents. 10. The method of 9 further comprising transdermal application via a transdermal patch. | A method of economically producing stable and bio-available glutathione comprising immersing glutathione particles in an edible oil preferably selected from at least one of almond, coconut, grapeseed and olive; reducing the average size of glutathione particles to not more than 50 microns and preferably 1 or less; and adding a de-agglomeration agent comprising at least one selected from surfactants or chelating agents. A method of administering bio-available glutathione, prepared according to the foregoing, to a patient in a desired dose by a method selected from oral, pulmonary, rectal, sublingual, transdermal, and vaginal.1. A method of economically producing stable and bio-available glutathione comprising:
a. immersing glutathione particles in an edible oil; b. reducing the average size of glutathione particles to not more than 50 microns; and c. adding a de-agglomeration agent. 2. The method of claim 1 further comprising:
a. the oil selected from at least one of almond, coconut, grapeseed, olive, and vegetable;
b. for the reducing step using a process selected from at least one of diamond chamber, grinding beads, and microfluidizer; and
c. the de-agglomeration agent comprising at least one selected from surfactants or chelating agents. 3. The method of claim 2 further comprising:
a. the reducing step comprising grinding beads have a media size from 0.4-1.3 mm to reduce the average size of glutathione particles to not more than 1 micron; and
b. the de-agglomeration agent comprising lecithin. 4. The method of claim 1 further comprising adding the de-agglomeration agent before the particle size reduction is complete, whereby the de-agglomeration agent serves to speed the reduction of size reduction by preventing agglomeration of particles during processing. 5. The method of claim 4 further comprising:
a. the oil selected from at least one of almond, coconut, grapeseed, olive, and vegetable;
b. for the reducing step, processing in a batch manner using a process selected from at least one of diamond chamber and grinding beads; and
c. the de-agglomeration agent comprising at least one selected from surfactants or chelating agents. 6. The method of claim 5 further comprising:
a. the reducing step using grinding beads have a media size from 0.4-1.3 mm to reduce the average size of glutathione particles to not more than 1 micron; and
b. the de-agglomeration agent comprising lecithin. 7. The method of claim 6 further comprising adding the lecithin during the reducing step in more than one batch at different stages during the size-reduction step. 8. A method of administering bio-available glutathione to a patient comprising:
a. immersing glutathione particles in an edible oil; b. reducing the average size of glutathione particles to not more than 50 microns; c. adding a de-agglomeration agent; d. administering a desired dose to the patient by a method selected from oral, pulmonary, rectal, sublingual, transdermal, and vaginal. 9. The method of claim 8 further comprising:
a. the oil selected from at least one of almond, coconut, grapeseed, olive, and vegetable;
b. for the reducing step using a process selected from at least one of diamond chamber, grinding beads, and microfluidizer; and
c. the de-agglomeration agent comprising at least one selected from surfactants or chelating agents. 10. The method of 9 further comprising transdermal application via a transdermal patch. | 1,600 |
1,306 | 14,782,879 | 1,623 | The present invention relates to a method of deoxygenating tall oil pitch, yielding aliphatic and aromatic hydrocarbons. The invention even comprises turning the aliphates into polymerizable olefins by steam cracking, and turning the aromates into polymerizable terephthalic acid by oxygenation and, as necessary, rearrangement. The monomers can be used for the production of polymers of partially or completely biologic origin. According to the invention, tall oil pitch is first heated to turn it into liquid, which is then fed into a catalyst bed and catalytically deoxygenated with hydrogen. The deoxygenation catalyst is preferably a Ni—Mo catalyst and, in addition, a cracking catalyst can be used, such as an acidic zeolite catalyst. The deoxygenated product stream is cooled down so as to obtain a liquid, which is distilled for separation of the aliphatic and aromatic hydrocarbons for use in the production of the respective monomers and finally polymers. | 1. A method of deoxygenating tall oil pitch, wherein
tall oil pitch, which contains a share of fatty and resin acids and/or their derivatives, is heated to a temperature sufficient to turn it liquid; said liquid is fed into a catalyst bed, to bring it into contact with hydrogen and one or more catalysts in said catalyst bed; the feed is catalytically deoxygenated with hydrogen; and a gaseous effluent from the bed is cooled down, to yield a liquid product, which comprises aliphatic and aromatic hydrocarbons and which has been substantially completely deoxygenated. 2. The method of claim 1, wherein the tall oil pitch is heated to a temperature of at least 55° C. 3. The method of claim 1 wherein the liquid yield is divided into a fraction rich in aliphatic hydrocarbons and a fraction rich in aromatic hydrocarbons. 4. The method of claim 1 wherein the one or more catalysts comprise a deoxygenation catalyst and a cracking catalyst, which are different from each other and located sequentially apart from each other in the catalyst bed that is formed by a solid bed material. 5. The method of claim 1 wherein one of the catalysts of the deoxygenation stage is a sulfided metal catalyst. 6. The method of claim 1 wherein one of the catalysts of the cracking stage is acidic. 7. The method of claim 1 wherein the deoxygenation is carried out at a temperature of 300-450° C. 8. The method of claim 1 wherein the deoxygenation is carried out at a pressure of 50-100 bars. 9. The method of claim 1 wherein the weight hourly space velocity (WHSV) in the catalyst bed is 0.2-1.0 1/h. 10. The method of claim 1 wherein water contained in the liquid yield is separated from the produced liquid hydrocarbons. 11. The method of claim 1 wherein one or more aromatic hydrocarbons that can be converted into terephthalic acid are separated from the reaction yield by distillation. 12. The method of claim 1 wherein the aromatic hydrocarbon that is separated from the reaction yield is o-xylene, m-xylene or p-xylene, or a cymene. 13. A method of producing bio-based terephthalic acid, wherein
tall oil pitch, which contains a share of fatty and resin acids and/or their derivatives, is heated to a temperature sufficient to turn it liquid; said liquid is fed into a catalyst bed, to bring it into contact with hydrogen and one or more catalysts in said catalyst bed; the feed is catalytically deoxygenated with hydrogen; a gaseous effluent from the bed is cooled down, to yield a liquid intermediate product, which comprises aliphatic and aromatic hydrocarbons and which has been substantially completely deoxygenated; an aromatic hydrocarbon that can be converted into terephthalic acid is separated from said intermediate product; and the separated hydrocarbon is subjected to oxygenation and a possible rearrangement reaction, so that terephthalic acid is obtained as the end product. 14. The method of claim 13 wherein oxygenation of the separated hydrocarbon is carried out with a chemical or biochemical oxidizer. 15. The method of claim 13 wherein p-xylene is separated from the said intermediate product and oxidized into terephthalic acid. 16. The method of claim 13 wherein o-xylene is separated from the said intermediate product and oxidized into phthalic acid, which thereafter is converted by means of the Raecke or Henkel rearrangement reaction into terephthalic acid. 17. The method of claim 13 wherein in the re-arrangement, the reaction mixture is heated to a temperature of at least 300° C., in an inert gas atmosphere. 18. (canceled) 19. (canceled) 20. A method of producing olefinic monomers for the production of a polymer, wherein
tall oil pitch, which contains a share of fatty and resin acids and/or their derivatives, is heated to a temperature sufficient to turn it liquid; said liquid is fed into a catalyst bed, to bring it into contact with hydrogen and one or more catalysts in said catalyst bed; the feed is catalytically deoxygenated with hydrogen; a gaseous effluent from the bed is cooled down, to yield a liquid intermediate product, which comprises aliphatic and aromatic hydrocarbons and which has been substantially completely deoxygenated; a fraction rich in aliphatic hydrocarbons is separated from said intermediate product; and said fraction is subjected to steam cracking to obtain a product, which contains polymerizable olefins. 21. The method of claim 20, wherein ethylene and/or propylene are produced by the steam cracking. 22. (canceled) 23. (canceled) 24. The method of claim 5 wherein the sulfided metal catalyst comprises NiMoS. 25. The method of claim 6 wherein the acidic catalyst is a ZSM-5 zeolite catalyst. 26. The method of claim 7 wherein the deoxygenation is carried out by raising the temperature so as to be within 320-370° C. at the start of the process and within 370-430° C. at the end of the process. 27. The method of claim 14 wherein the oxidizer is chromic acid. 28. The method of claim 16 wherein the conversion into terephthalic acid is carried out by using a salt catalyst. 29. The method of claim 28, wherein the salt catalyst is a cobalt-magnesium salt. 30. The method of claim 17 wherein the reaction mixture is heated to a temperature of 330-500° C. | The present invention relates to a method of deoxygenating tall oil pitch, yielding aliphatic and aromatic hydrocarbons. The invention even comprises turning the aliphates into polymerizable olefins by steam cracking, and turning the aromates into polymerizable terephthalic acid by oxygenation and, as necessary, rearrangement. The monomers can be used for the production of polymers of partially or completely biologic origin. According to the invention, tall oil pitch is first heated to turn it into liquid, which is then fed into a catalyst bed and catalytically deoxygenated with hydrogen. The deoxygenation catalyst is preferably a Ni—Mo catalyst and, in addition, a cracking catalyst can be used, such as an acidic zeolite catalyst. The deoxygenated product stream is cooled down so as to obtain a liquid, which is distilled for separation of the aliphatic and aromatic hydrocarbons for use in the production of the respective monomers and finally polymers.1. A method of deoxygenating tall oil pitch, wherein
tall oil pitch, which contains a share of fatty and resin acids and/or their derivatives, is heated to a temperature sufficient to turn it liquid; said liquid is fed into a catalyst bed, to bring it into contact with hydrogen and one or more catalysts in said catalyst bed; the feed is catalytically deoxygenated with hydrogen; and a gaseous effluent from the bed is cooled down, to yield a liquid product, which comprises aliphatic and aromatic hydrocarbons and which has been substantially completely deoxygenated. 2. The method of claim 1, wherein the tall oil pitch is heated to a temperature of at least 55° C. 3. The method of claim 1 wherein the liquid yield is divided into a fraction rich in aliphatic hydrocarbons and a fraction rich in aromatic hydrocarbons. 4. The method of claim 1 wherein the one or more catalysts comprise a deoxygenation catalyst and a cracking catalyst, which are different from each other and located sequentially apart from each other in the catalyst bed that is formed by a solid bed material. 5. The method of claim 1 wherein one of the catalysts of the deoxygenation stage is a sulfided metal catalyst. 6. The method of claim 1 wherein one of the catalysts of the cracking stage is acidic. 7. The method of claim 1 wherein the deoxygenation is carried out at a temperature of 300-450° C. 8. The method of claim 1 wherein the deoxygenation is carried out at a pressure of 50-100 bars. 9. The method of claim 1 wherein the weight hourly space velocity (WHSV) in the catalyst bed is 0.2-1.0 1/h. 10. The method of claim 1 wherein water contained in the liquid yield is separated from the produced liquid hydrocarbons. 11. The method of claim 1 wherein one or more aromatic hydrocarbons that can be converted into terephthalic acid are separated from the reaction yield by distillation. 12. The method of claim 1 wherein the aromatic hydrocarbon that is separated from the reaction yield is o-xylene, m-xylene or p-xylene, or a cymene. 13. A method of producing bio-based terephthalic acid, wherein
tall oil pitch, which contains a share of fatty and resin acids and/or their derivatives, is heated to a temperature sufficient to turn it liquid; said liquid is fed into a catalyst bed, to bring it into contact with hydrogen and one or more catalysts in said catalyst bed; the feed is catalytically deoxygenated with hydrogen; a gaseous effluent from the bed is cooled down, to yield a liquid intermediate product, which comprises aliphatic and aromatic hydrocarbons and which has been substantially completely deoxygenated; an aromatic hydrocarbon that can be converted into terephthalic acid is separated from said intermediate product; and the separated hydrocarbon is subjected to oxygenation and a possible rearrangement reaction, so that terephthalic acid is obtained as the end product. 14. The method of claim 13 wherein oxygenation of the separated hydrocarbon is carried out with a chemical or biochemical oxidizer. 15. The method of claim 13 wherein p-xylene is separated from the said intermediate product and oxidized into terephthalic acid. 16. The method of claim 13 wherein o-xylene is separated from the said intermediate product and oxidized into phthalic acid, which thereafter is converted by means of the Raecke or Henkel rearrangement reaction into terephthalic acid. 17. The method of claim 13 wherein in the re-arrangement, the reaction mixture is heated to a temperature of at least 300° C., in an inert gas atmosphere. 18. (canceled) 19. (canceled) 20. A method of producing olefinic monomers for the production of a polymer, wherein
tall oil pitch, which contains a share of fatty and resin acids and/or their derivatives, is heated to a temperature sufficient to turn it liquid; said liquid is fed into a catalyst bed, to bring it into contact with hydrogen and one or more catalysts in said catalyst bed; the feed is catalytically deoxygenated with hydrogen; a gaseous effluent from the bed is cooled down, to yield a liquid intermediate product, which comprises aliphatic and aromatic hydrocarbons and which has been substantially completely deoxygenated; a fraction rich in aliphatic hydrocarbons is separated from said intermediate product; and said fraction is subjected to steam cracking to obtain a product, which contains polymerizable olefins. 21. The method of claim 20, wherein ethylene and/or propylene are produced by the steam cracking. 22. (canceled) 23. (canceled) 24. The method of claim 5 wherein the sulfided metal catalyst comprises NiMoS. 25. The method of claim 6 wherein the acidic catalyst is a ZSM-5 zeolite catalyst. 26. The method of claim 7 wherein the deoxygenation is carried out by raising the temperature so as to be within 320-370° C. at the start of the process and within 370-430° C. at the end of the process. 27. The method of claim 14 wherein the oxidizer is chromic acid. 28. The method of claim 16 wherein the conversion into terephthalic acid is carried out by using a salt catalyst. 29. The method of claim 28, wherein the salt catalyst is a cobalt-magnesium salt. 30. The method of claim 17 wherein the reaction mixture is heated to a temperature of 330-500° C. | 1,600 |
1,307 | 14,894,473 | 1,623 | The present invention relates to a process for producing a low endotoxin alkali chitosan, chitin, chitosan derivative or chitin derivative, and also to a process for producing low endotoxin neutral chitosan, chitosan salt and chitosan derivatives, and to the products of such processes. The process comprises contacting chitosan, chitin, chitosan derivative or chitin derivative with an alkali solution having a concentration of less than 0.25 M to form a mixture; leaving the mixture for a period of less than 12 hours and optionally drying the mixture. The low endotoxin alkali chitosan may be used in the manufacture of other useful chitosan based products. | 1. A process for producing a low endotoxin alkali chitosan, chitin or a derivative thereof, the process comprising the steps of:
(a) contacting chitosan, chitin, a chitosan derivative or a chitin derivative with an alkali solution having a concentration of less than 0.25M to form a mixture; and (b) leaving the mixture for a period of less than 12 hours. 2. A process as claimed in claim 1, wherein the process further comprises a step (c) of drying the mixture. 3. A process as claimed in claim 1, wherein the concentration of the alkali solution is around 0.2M or less and optionally around 0.1M. 4. (canceled) 5. (canceled) 6. A process as claimed in claim 1, wherein the alkali solution comprises an alkali or alkaline earth component selected from the following, either alone or in combination: metal hydroxides, metal carbonates, metal bisulphites, metal persilicates, conjugate bases and ammonium hydroxide, wherein the metal is optionally selected from sodium, potassium, calcium, or magnesium and wherein the alkali component is selected from sodium hydroxide, potassium hydroxide or sodium carbonate. 7. (canceled) 8. (canceled) 9. A process as claimed in claim 1, wherein the alkali solution is sprayed onto the chitosan, chitin, chitosan derivative or chitin derivative or the chitosan, chitin, chitosan derivative or chitin derivative is mixed with the alkali solution. 10. A process as claimed in claim 1, wherein the mixture is left for a period of less than ten hours. 11. (canceled) 12. (canceled) 13. A process as claimed in claim 1, wherein the mixture further comprises a preservative optionally selected from silver ions, zinc ions, chlorohexadine, or combinations thereof. 14. (canceled) 15. A low endotoxin alkali chitosan, chitin, chitosan derivative or chitin derivative obtainable by the process of claim 1. 16. An alkali chitosan, chitin, chitosan derivative or chitin derivative, or neutral chitosan, a chitosan salt or a chitosan derivative comprising an endotoxin concentration of less than 50 EU/g. 17. A process for producing a low endotoxin neutral chitosan, a chitosan salt or a chitosan derivative comprising the step of contacting an alkali chitosan prepared by the process of claim 1 with an acid. 18. A process as claimed in claim 17, wherein the step of contacting the alkali chitosan with an acid is performed before the drying step (c); and wherein the acid is optionally sprayed onto the alkali chitosan or the alkali chitosan is mixed with the acid. 19. (canceled) 20. A process as claimed in claim 17, wherein the acid is selected from the following, either alone or in combination: organic acids optionally selected from the following, either alone or in combination: acetic acid, tartaric acid, citric acid, ascorbic acid, acetylsalicylic acid, gluconic acid and lactic acid; carboxylic acids; fatty acids optionally selected from the following, either alone or in combination: myristoleic acid, palmitoleic acid, sapienic acid, oleic acid, elaidic acid, vaccenic acid, linoleic acid, linoelaidic acid, α-Linolenic acid, arachidonic acid, eicosapentaenoic acid, erucic acid, docosahexaenoic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, cerotic acid; amino acids optionally selected from the following, either alone or in combination: histidine, lysine, aspartic acid, glutamic acid, glutamine, glycine, proline, taurine; lewis acids; monoprotic acids; diprotic acids; polyprotic acids; nucleic acids; and mineral acids optionally selected from the following, either alone or in combination: hydrochloric acid, sulphuric acid and nitric acid. 21. (canceled) 22. (canceled) 23. (canceled) 24. (canceled) 25. A process as claimed in claim 17, wherein the acid has a concentration of about 1 M. 26. A process as claimed in claim 17, wherein the acid is present as an acid liquor comprising the acid and a non-solvent optionally selected from ethyl lactate, ethyl acetate, methyl acetate, ethanol, acetone, 80:20 mixture of ethanol:water or mixtures thereof. 27. (canceled) 28. A process as claimed in claim 26, wherein the ratio of chitosan to acid liquor is from about 5:1 to about 1:5; and/or wherein the alkali chitosan is mixed with the acid for around 5 minutes. 29. (canceled) 30. A process as claimed in claim 17, further comprising the step of drying the reaction product. 31. (canceled) 32. (canceled) 33. Use of a low endotoxin chitosan salt of claim 15 for stemming blood flow. 34. A low endotoxin chitosan salt of claim 15 for use as a haemostat for stemming blood flow or for use in a wound dressing for superficial non-life threatening bleeding or life threatening bleeding. 35. (canceled) 36. A haemostatic wound dressing comprising a low endotoxin chitosan salt of claim 15. 37. A method of stemming blood flow comprising the steps of: optionally cleaning a wound area where possible; applying to said wound area a haemostatic wound dressing comprising a low endotoxin chitosan salt of claim 15; and applying constant pressure to the wound area until a gel clot forms. 38. A low endotoxin neutral chitosan, a chitosan salt or a chitosan derivative obtainable by the process of claim 17. | The present invention relates to a process for producing a low endotoxin alkali chitosan, chitin, chitosan derivative or chitin derivative, and also to a process for producing low endotoxin neutral chitosan, chitosan salt and chitosan derivatives, and to the products of such processes. The process comprises contacting chitosan, chitin, chitosan derivative or chitin derivative with an alkali solution having a concentration of less than 0.25 M to form a mixture; leaving the mixture for a period of less than 12 hours and optionally drying the mixture. The low endotoxin alkali chitosan may be used in the manufacture of other useful chitosan based products.1. A process for producing a low endotoxin alkali chitosan, chitin or a derivative thereof, the process comprising the steps of:
(a) contacting chitosan, chitin, a chitosan derivative or a chitin derivative with an alkali solution having a concentration of less than 0.25M to form a mixture; and (b) leaving the mixture for a period of less than 12 hours. 2. A process as claimed in claim 1, wherein the process further comprises a step (c) of drying the mixture. 3. A process as claimed in claim 1, wherein the concentration of the alkali solution is around 0.2M or less and optionally around 0.1M. 4. (canceled) 5. (canceled) 6. A process as claimed in claim 1, wherein the alkali solution comprises an alkali or alkaline earth component selected from the following, either alone or in combination: metal hydroxides, metal carbonates, metal bisulphites, metal persilicates, conjugate bases and ammonium hydroxide, wherein the metal is optionally selected from sodium, potassium, calcium, or magnesium and wherein the alkali component is selected from sodium hydroxide, potassium hydroxide or sodium carbonate. 7. (canceled) 8. (canceled) 9. A process as claimed in claim 1, wherein the alkali solution is sprayed onto the chitosan, chitin, chitosan derivative or chitin derivative or the chitosan, chitin, chitosan derivative or chitin derivative is mixed with the alkali solution. 10. A process as claimed in claim 1, wherein the mixture is left for a period of less than ten hours. 11. (canceled) 12. (canceled) 13. A process as claimed in claim 1, wherein the mixture further comprises a preservative optionally selected from silver ions, zinc ions, chlorohexadine, or combinations thereof. 14. (canceled) 15. A low endotoxin alkali chitosan, chitin, chitosan derivative or chitin derivative obtainable by the process of claim 1. 16. An alkali chitosan, chitin, chitosan derivative or chitin derivative, or neutral chitosan, a chitosan salt or a chitosan derivative comprising an endotoxin concentration of less than 50 EU/g. 17. A process for producing a low endotoxin neutral chitosan, a chitosan salt or a chitosan derivative comprising the step of contacting an alkali chitosan prepared by the process of claim 1 with an acid. 18. A process as claimed in claim 17, wherein the step of contacting the alkali chitosan with an acid is performed before the drying step (c); and wherein the acid is optionally sprayed onto the alkali chitosan or the alkali chitosan is mixed with the acid. 19. (canceled) 20. A process as claimed in claim 17, wherein the acid is selected from the following, either alone or in combination: organic acids optionally selected from the following, either alone or in combination: acetic acid, tartaric acid, citric acid, ascorbic acid, acetylsalicylic acid, gluconic acid and lactic acid; carboxylic acids; fatty acids optionally selected from the following, either alone or in combination: myristoleic acid, palmitoleic acid, sapienic acid, oleic acid, elaidic acid, vaccenic acid, linoleic acid, linoelaidic acid, α-Linolenic acid, arachidonic acid, eicosapentaenoic acid, erucic acid, docosahexaenoic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, cerotic acid; amino acids optionally selected from the following, either alone or in combination: histidine, lysine, aspartic acid, glutamic acid, glutamine, glycine, proline, taurine; lewis acids; monoprotic acids; diprotic acids; polyprotic acids; nucleic acids; and mineral acids optionally selected from the following, either alone or in combination: hydrochloric acid, sulphuric acid and nitric acid. 21. (canceled) 22. (canceled) 23. (canceled) 24. (canceled) 25. A process as claimed in claim 17, wherein the acid has a concentration of about 1 M. 26. A process as claimed in claim 17, wherein the acid is present as an acid liquor comprising the acid and a non-solvent optionally selected from ethyl lactate, ethyl acetate, methyl acetate, ethanol, acetone, 80:20 mixture of ethanol:water or mixtures thereof. 27. (canceled) 28. A process as claimed in claim 26, wherein the ratio of chitosan to acid liquor is from about 5:1 to about 1:5; and/or wherein the alkali chitosan is mixed with the acid for around 5 minutes. 29. (canceled) 30. A process as claimed in claim 17, further comprising the step of drying the reaction product. 31. (canceled) 32. (canceled) 33. Use of a low endotoxin chitosan salt of claim 15 for stemming blood flow. 34. A low endotoxin chitosan salt of claim 15 for use as a haemostat for stemming blood flow or for use in a wound dressing for superficial non-life threatening bleeding or life threatening bleeding. 35. (canceled) 36. A haemostatic wound dressing comprising a low endotoxin chitosan salt of claim 15. 37. A method of stemming blood flow comprising the steps of: optionally cleaning a wound area where possible; applying to said wound area a haemostatic wound dressing comprising a low endotoxin chitosan salt of claim 15; and applying constant pressure to the wound area until a gel clot forms. 38. A low endotoxin neutral chitosan, a chitosan salt or a chitosan derivative obtainable by the process of claim 17. | 1,600 |
1,308 | 15,494,160 | 1,617 | Compositions including a quaternary ammonium compound (such as alkyl dimethyl benzyl ammonium chloride) and a linear monocarboxylic fatty acid are disclosed. The compositions are useful to inhibit the growth of an organism or to remove or reduce a stain resulting from the growth of an organism. Such compositions are useful as a biocidal agent or cleaning agent against algae, lichen, moss, mold, or mildew. | 1. A composition comprising:
a quaternary ammonium compound that comprises an alkyl chain; and a linear monocarboxylic fatty acid. 2. The composition of claim 1, wherein the quaternary ammonium compound comprises one or more of alkyl dimethyl benzyl ammonium chloride (“ADBAC”), alkyl dimethyl ethyl benzyl ammonium chloride (ADEBAC), alkyl dimethyl 1-naphtylmethyl ammonium chloride, dodecyl benzyl trimethyl ammonium chloride, alkyl trimethyl ammonium chloride, diisobutylphenoxyethyoxyethyl dimethyl benzyl ammonium chloride, and (trihydroxylsilyl) propyldimethyloctadecyl ammonium chloride. 3. The composition of claim 2, wherein the quaternary ammonium compound is ADBAC. 4. The composition of claim 1, wherein the quaternary ammonium compound comprises a C8-20 alkyl chain. 5. The composition of claim 1, wherein the linear monocarboxylic acid comprises one or more of a linear saturated monocarboxylic acid and a linear unsaturated monocarboxylic acid. 6. The composition of claim 1, wherein the linear monocarboxylic fatty acid comprises one or more of caprylic acid, pelargonic acid, capric acid, lauric acid, tridecylic acid, undecylenic acid, myristoleic acid, palmitoleic acid, oleic acid, and linoleic acid. 7. The composition of claim 1 further comprising a plant essential oil, the plant essential comprising one or more of thyme oil, thymol, geranium oil, geraniol, eugenol, peppermint oil, cinnamon oil, clove oil, lemongrass oil, mint oil, citronella oil, rosemary oil, citrus oil, garlic oil, pepper oil, d-limonene, and linalool. 8. The composition of claim 1 comprises an amount of the quaternary ammonium compound and the linear monocarboxylic acid sufficient to inhibit the growth of surface-growing organisms or remove stains resulting from the growth of the surface-growing organisms. 9. The composition of claim 1 comprises about 0.1% to about 20% w/w of the quaternary ammonium compound. 10. The composition of claim 1 comprises about 0.1% to about 25% w/w of the linear monocarboxylic acid. 11. The composition of claim 1 is contained in a spray bottle. 12. The composition of claim 1 further comprising a hydrophilic non-ionic surfactant. 13. The composition of claim 1 has a pH of about 6.5 to about 9.5. 14. The composition of claim 1 is clear and homogenous. 15. A method of inhibiting the growth of an organism or treating a stain resulting from the growth of an organism, comprising applying to the organism the composition of claim 1. 16. The method of claim 15, wherein the organism is on a hard surface of a man-made structure and the composition is applied onto the hard surface. 17. The method of claim 15, wherein the composition is applied by mixing the composition with a flowing solvent supply. 18. The method of claim 15, wherein the organism is one or more of algae, lichen, mold, mildew, and moss. 19. A method of preparing a diluted liquid composition, comprising adding a solvent to the composition of claim 1. 20. The method of claim 19, wherein about 1 part to about 10 parts of the solvent are mixed with about 1 part of the composition. | Compositions including a quaternary ammonium compound (such as alkyl dimethyl benzyl ammonium chloride) and a linear monocarboxylic fatty acid are disclosed. The compositions are useful to inhibit the growth of an organism or to remove or reduce a stain resulting from the growth of an organism. Such compositions are useful as a biocidal agent or cleaning agent against algae, lichen, moss, mold, or mildew.1. A composition comprising:
a quaternary ammonium compound that comprises an alkyl chain; and a linear monocarboxylic fatty acid. 2. The composition of claim 1, wherein the quaternary ammonium compound comprises one or more of alkyl dimethyl benzyl ammonium chloride (“ADBAC”), alkyl dimethyl ethyl benzyl ammonium chloride (ADEBAC), alkyl dimethyl 1-naphtylmethyl ammonium chloride, dodecyl benzyl trimethyl ammonium chloride, alkyl trimethyl ammonium chloride, diisobutylphenoxyethyoxyethyl dimethyl benzyl ammonium chloride, and (trihydroxylsilyl) propyldimethyloctadecyl ammonium chloride. 3. The composition of claim 2, wherein the quaternary ammonium compound is ADBAC. 4. The composition of claim 1, wherein the quaternary ammonium compound comprises a C8-20 alkyl chain. 5. The composition of claim 1, wherein the linear monocarboxylic acid comprises one or more of a linear saturated monocarboxylic acid and a linear unsaturated monocarboxylic acid. 6. The composition of claim 1, wherein the linear monocarboxylic fatty acid comprises one or more of caprylic acid, pelargonic acid, capric acid, lauric acid, tridecylic acid, undecylenic acid, myristoleic acid, palmitoleic acid, oleic acid, and linoleic acid. 7. The composition of claim 1 further comprising a plant essential oil, the plant essential comprising one or more of thyme oil, thymol, geranium oil, geraniol, eugenol, peppermint oil, cinnamon oil, clove oil, lemongrass oil, mint oil, citronella oil, rosemary oil, citrus oil, garlic oil, pepper oil, d-limonene, and linalool. 8. The composition of claim 1 comprises an amount of the quaternary ammonium compound and the linear monocarboxylic acid sufficient to inhibit the growth of surface-growing organisms or remove stains resulting from the growth of the surface-growing organisms. 9. The composition of claim 1 comprises about 0.1% to about 20% w/w of the quaternary ammonium compound. 10. The composition of claim 1 comprises about 0.1% to about 25% w/w of the linear monocarboxylic acid. 11. The composition of claim 1 is contained in a spray bottle. 12. The composition of claim 1 further comprising a hydrophilic non-ionic surfactant. 13. The composition of claim 1 has a pH of about 6.5 to about 9.5. 14. The composition of claim 1 is clear and homogenous. 15. A method of inhibiting the growth of an organism or treating a stain resulting from the growth of an organism, comprising applying to the organism the composition of claim 1. 16. The method of claim 15, wherein the organism is on a hard surface of a man-made structure and the composition is applied onto the hard surface. 17. The method of claim 15, wherein the composition is applied by mixing the composition with a flowing solvent supply. 18. The method of claim 15, wherein the organism is one or more of algae, lichen, mold, mildew, and moss. 19. A method of preparing a diluted liquid composition, comprising adding a solvent to the composition of claim 1. 20. The method of claim 19, wherein about 1 part to about 10 parts of the solvent are mixed with about 1 part of the composition. | 1,600 |
1,309 | 16,035,762 | 1,612 | Compositions comprising UV blocking agents, a film forming polymer containing acid groups and a neutralizing agent; compositions and methods for increasing the SPF of a composition by neutralizing at least a portion of the acid groups of the film forming agent with the neutralizing agent. | 1-40. (canceled) 41. A sprayable anhydrous sunscreen composition comprising
at least one UV absorbing active ingredient, a film forming polymer containing a plurality of acid groups, which film forming polymer is an Acrylates/Octylacrylamide Copolymer, and a volatile solvent, wherein the film forming polymer is present in an amount greater than 1% by weight of the composition and wherein at least a portion of the acid groups have been neutralized with a cosmetically acceptable amine-based neutralizing agent and the SPF of the sprayable anhydrous sunscreen composition is greater than 125% of a composition containing un-neutralized film forming polymer. 42. The composition of claim 41, wherein from about 5 to about 100 percent of the plurality of acid groups of the film forming polymer are neutralized by said amine-based neutralizing agent. 43. The composition of claim 41, wherein from about 5 to about 50 percent of the plurality of acid groups of the film forming polymer are neutralized by said amine-based neutralizing agent. 44. The composition of claim 41, wherein from about 5 to about 25 percent of the plurality of acid groups of the film forming polymer are neutralized by said amine-based neutralizing agent. 45. The composition according to claim 41, further comprising an inorganic pigment selected from titanium dioxide, zinc oxide, iron oxide, zirconium oxide, cerium oxide or mixtures thereof. 46. A method for reducing the deleterious effects of UV radiation that contacts a surface which comprises applying to the surface the composition of claim 41. 47. A method for reducing the occurrence of erythema on a subject due to exposure to UV radiation which comprises applying the composition of claim 41 to the subject prior to exposure to UV radiation. 48. A method for reducing photoaging of the skin of a subject due to exposure to UV radiation which comprises applying the composition of claim 41 to the subject prior to exposure to UV radiation. 49. A method for reducing the occurrence of phototoxic or photoallergic reactions in a subject due to exposure to UV radiation which comprises applying the composition of claim 41 to the subject prior to exposure to UV radiation. 50. A method for increasing the SPF for an anhydrous composition comprising at least one sunscreen active agent and at least one film forming polymer, wherein the film forming polymer comprises a plurality of acid groups, the method comprising
adding an amine-based neutralizing agent to the composition in an amount effective to neutralize at least a portion of the acid groups in said film forming polymer, wherein said film forming polymer is Acrylates/Octylacrylamide Copolymer and is present in an amount greater than 1% by weight of the final composition and wherein the resulting composition exhibits an SPF 125% of the SPF of the un-neutralized composition. 51. The method of claim 50, wherein the film forming polymer is present in an amount of from greater than 1% to about 5% by weight of the final composition. 52. The method of claim 50, wherein the film forming polymer is present in an amount of from greater than 1% to about 3% by weight of the final composition. | Compositions comprising UV blocking agents, a film forming polymer containing acid groups and a neutralizing agent; compositions and methods for increasing the SPF of a composition by neutralizing at least a portion of the acid groups of the film forming agent with the neutralizing agent.1-40. (canceled) 41. A sprayable anhydrous sunscreen composition comprising
at least one UV absorbing active ingredient, a film forming polymer containing a plurality of acid groups, which film forming polymer is an Acrylates/Octylacrylamide Copolymer, and a volatile solvent, wherein the film forming polymer is present in an amount greater than 1% by weight of the composition and wherein at least a portion of the acid groups have been neutralized with a cosmetically acceptable amine-based neutralizing agent and the SPF of the sprayable anhydrous sunscreen composition is greater than 125% of a composition containing un-neutralized film forming polymer. 42. The composition of claim 41, wherein from about 5 to about 100 percent of the plurality of acid groups of the film forming polymer are neutralized by said amine-based neutralizing agent. 43. The composition of claim 41, wherein from about 5 to about 50 percent of the plurality of acid groups of the film forming polymer are neutralized by said amine-based neutralizing agent. 44. The composition of claim 41, wherein from about 5 to about 25 percent of the plurality of acid groups of the film forming polymer are neutralized by said amine-based neutralizing agent. 45. The composition according to claim 41, further comprising an inorganic pigment selected from titanium dioxide, zinc oxide, iron oxide, zirconium oxide, cerium oxide or mixtures thereof. 46. A method for reducing the deleterious effects of UV radiation that contacts a surface which comprises applying to the surface the composition of claim 41. 47. A method for reducing the occurrence of erythema on a subject due to exposure to UV radiation which comprises applying the composition of claim 41 to the subject prior to exposure to UV radiation. 48. A method for reducing photoaging of the skin of a subject due to exposure to UV radiation which comprises applying the composition of claim 41 to the subject prior to exposure to UV radiation. 49. A method for reducing the occurrence of phototoxic or photoallergic reactions in a subject due to exposure to UV radiation which comprises applying the composition of claim 41 to the subject prior to exposure to UV radiation. 50. A method for increasing the SPF for an anhydrous composition comprising at least one sunscreen active agent and at least one film forming polymer, wherein the film forming polymer comprises a plurality of acid groups, the method comprising
adding an amine-based neutralizing agent to the composition in an amount effective to neutralize at least a portion of the acid groups in said film forming polymer, wherein said film forming polymer is Acrylates/Octylacrylamide Copolymer and is present in an amount greater than 1% by weight of the final composition and wherein the resulting composition exhibits an SPF 125% of the SPF of the un-neutralized composition. 51. The method of claim 50, wherein the film forming polymer is present in an amount of from greater than 1% to about 5% by weight of the final composition. 52. The method of claim 50, wherein the film forming polymer is present in an amount of from greater than 1% to about 3% by weight of the final composition. | 1,600 |
1,310 | 15,206,595 | 1,619 | A hair straightening and/or hair relaxing method comprising: applying a hair care composition to hair, wherein the composition comprises a sugar, a buffering agent and a cosmetically acceptable carrier; and wherein, where the composition is heated to a temperature of at least 100° C., the composition comprises from about 6% to about 20% reducing sugar; hair drying; providing a hair straightening appliance at a temperature of from about 100° C. to about 280° C. and mechanically straightening the hair with the appliance. | 1. A composition for straightening hair comprising:
from about 12% to about 18% reducing sugar, by weight of the formulation, wherein the reducing sugar is selected from the group consisting of: arabinose, ribose, and mixtures thereof; a buffering agent; a cosmetically acceptable carrier; a conditioning agent being the reaction product of: (a) an aminosilane; (b) polysiloxane; and (c) a polyether; and wherein the composition has a pH of from about pH 6 to about pH 10. 2. The composition according to claim 1, wherein the conditioning agent is selected from the group consisting of epoxyaminosilane copolymers, polysiloxane/polyurea block copolymers, and mixtures thereof. 3. The composition according to claim 1, wherein the reducing sugar is arabinose. 4. The composition according to claim 1, wherein the buffering agent is selected from the group consisting of glycine/sodium hydroxide, sodium carbonate/sodium hydrogen carbonate, sodium tetraborate/sodium hydroxide, sodium bicarbonate/sodium hydroxide, ammonium chloride/ammonia, and mixtures thereof. 5. The composition according to claim 1, wherein the composition has a pH of from about pH 6.5 to about pH 9.75. 6. The composition according to claim 1, wherein the composition has a pH of from about pH 7.0 to about pH 9.5. 7. The composition according to claim 1, wherein the composition has a pH of from about pH 8.0 to about pH 9.0. 8. The composition according to claim 1, wherein the composition is substantially free of a quaternary ammonium compound and/or a surfactant. 9. The composition according to claim 1, wherein the composition is substantially free of: ceramide compound, an alpha-hydroxy acid, a thioglycolate or thiolactate compound, a bisulfate compound, clay, a reducing agent. 10. A kit for straightening hair comprising: (i) a composition according to claim 1; (ii) a heating device comprising a flat iron. 11. The kit according to claim 10, wherein the composition is a composition for straightening hair comprising:
from about 12% to about 18% reducing sugar, by weight of the formulation, wherein the reducing sugar is arabinose; a buffering agent; a cosmetically acceptable carrier; a conditioning agent being the reaction product of: (a) an aminosilane; and (b) polysiloxane;
and wherein the composition has a pH of from about pH 6 to about pH 10. | A hair straightening and/or hair relaxing method comprising: applying a hair care composition to hair, wherein the composition comprises a sugar, a buffering agent and a cosmetically acceptable carrier; and wherein, where the composition is heated to a temperature of at least 100° C., the composition comprises from about 6% to about 20% reducing sugar; hair drying; providing a hair straightening appliance at a temperature of from about 100° C. to about 280° C. and mechanically straightening the hair with the appliance.1. A composition for straightening hair comprising:
from about 12% to about 18% reducing sugar, by weight of the formulation, wherein the reducing sugar is selected from the group consisting of: arabinose, ribose, and mixtures thereof; a buffering agent; a cosmetically acceptable carrier; a conditioning agent being the reaction product of: (a) an aminosilane; (b) polysiloxane; and (c) a polyether; and wherein the composition has a pH of from about pH 6 to about pH 10. 2. The composition according to claim 1, wherein the conditioning agent is selected from the group consisting of epoxyaminosilane copolymers, polysiloxane/polyurea block copolymers, and mixtures thereof. 3. The composition according to claim 1, wherein the reducing sugar is arabinose. 4. The composition according to claim 1, wherein the buffering agent is selected from the group consisting of glycine/sodium hydroxide, sodium carbonate/sodium hydrogen carbonate, sodium tetraborate/sodium hydroxide, sodium bicarbonate/sodium hydroxide, ammonium chloride/ammonia, and mixtures thereof. 5. The composition according to claim 1, wherein the composition has a pH of from about pH 6.5 to about pH 9.75. 6. The composition according to claim 1, wherein the composition has a pH of from about pH 7.0 to about pH 9.5. 7. The composition according to claim 1, wherein the composition has a pH of from about pH 8.0 to about pH 9.0. 8. The composition according to claim 1, wherein the composition is substantially free of a quaternary ammonium compound and/or a surfactant. 9. The composition according to claim 1, wherein the composition is substantially free of: ceramide compound, an alpha-hydroxy acid, a thioglycolate or thiolactate compound, a bisulfate compound, clay, a reducing agent. 10. A kit for straightening hair comprising: (i) a composition according to claim 1; (ii) a heating device comprising a flat iron. 11. The kit according to claim 10, wherein the composition is a composition for straightening hair comprising:
from about 12% to about 18% reducing sugar, by weight of the formulation, wherein the reducing sugar is arabinose; a buffering agent; a cosmetically acceptable carrier; a conditioning agent being the reaction product of: (a) an aminosilane; and (b) polysiloxane;
and wherein the composition has a pH of from about pH 6 to about pH 10. | 1,600 |
1,311 | 15,648,240 | 1,639 | The present disclosure is directed to a single-end sequencing method for improved detection of genomic rearrangements such as deletions, insertions, inversions, and translocations that are present in a polynucleotide. A first priming event allows for sequencing of a target sequence, and a second priming event on an adapter allows for identification of the sequences amplified and tagged by selective amplification. The combination of priming events in the same direction facilitates read alignment and the identification of any genomic rearrangements. | 1. A method of preparing a polynucleotide for sequencing by attaching a target-specific barcode, the method comprising:
amplifying a polynucleotide with a first amplification primer and a second amplification primer, wherein the first amplification primer hybridizes to a first priming site of the polynucleotide, and the first amplification primer comprises a target-specific barcode; wherein the amplifying generates polynucleotide amplicons, wherein the polynucleotide amplicons comprise sequences identical or complementary to the polynucleotide of interest and the target-specific barcode. 2. The method of claim 1, wherein the second amplification primer hybridizes to (1) a portion of an adapter attached to the polynucleotide at a distance from the first priming site, or (2) a second priming site of the polynucleotide, wherein the second priming site is at a distance from the first priming site. 3. The method of claim 1, further comprising attaching an adapter to the polynucleotide at a distance from the first priming site, wherein the adapter comprises a second priming site. 4. The method of claim 1, wherein the first priming site is a portion of a fusion gene, and the target-specific barcode is specific for the portion of the fusion gene. 5. The method of claim 4, wherein the portion of the fusion gene is a junction of the fusion gene. 6. The method of claim 1, wherein the polynucleotide of interest comprises a plurality of polynucleotides of interest, and the method comprises attaching a plurality of adapters to the plurality of polynucleotides, thereby forming a plurality of adapted polynucleotides, each of the plurality of adapted polynucleotides comprising a different molecular barcode. 7. The method of claim 1, wherein the polynucleotide of interest comprises a plurality of polynucleotides of interest, and the first amplification primer comprises a plurality of first amplification primers having different target-specific primers and different target-specific barcodes, thereby forming a plurality of adapted polynucleotide amplicons, each of the plurality of adapted polynucleotide amplicons comprising a different target-specific barcode. 8. The method of claim 1, wherein the polynucleotide amplicons or adapted polynucleotide comprise a binding partner, such as a biotin moiety. 9. The method of claim 1, further comprising sequencing the polynucleotide amplicons at first and second locations by performing a first primer extension and a second primer extension, wherein the first primer extension and the second primer extension are performed in a same direction. 10. The method of claim 9, wherein the first primer extension and the second primer extension are performed in the same direction on the polynucleotide during separate sequencing runs. 11. A composition or kit for detecting a genomic rearrangement in a polynucleotide having a first binding site, the composition or kit comprising:
a first amplification primer comprising a target-specific primer and a target-specific barcode; and a second amplification primer. 12. The composition or kit of claim 11, further comprising:
an adapter comprises a second priming site and an adapter barcode, and wherein the second amplification primer comprises a priming sequence complementary to or identical to a sequence within the adapter. 13. A method of detecting a genomic rearrangement in a polynucleotide, the method comprising:
amplifying a polynucleotide with a first amplification primer and a second amplification primer, wherein the first amplification primer hybridizes to a first priming site of the polynucleotide, and the first amplification primer further comprises a target-specific barcode, wherein the amplifying generates polynucleotide amplicons, comprising sequences identical or complementary to the polynucleotide of interest and the target-specific barcodes; and sequencing the polynucleotide amplicons at first and second locations by performing a first primer extension and a second primer extension, wherein the first primer extension and the second primer extension are performed in a same direction. 14. The method of claim 13, wherein the sequencing at the first location provides a sequence of at least a portion of the polynucleotide of interest and the sequencing at the second location provides a sequence of the target-specific barcode. 15. The method of claim 13, wherein the first primer extension and the second primer extension are performed in the same direction on the polynucleotide during separate sequencing runs. 16. The method of claim 13, wherein the sequencing is next generation sequencing (NGS) or massively parallel sequencing. 17. The method of claim 13, further comprising detecting a genomic rearrangement using single-end sequencing of at least one of the polynucleotide amplicons, such as by identifying that genomic rearrangement based on data generated from the sequencing of the first primer extension and the second primer extension. 18. The method of claim 17, wherein the genomic rearrangement has a frequency of about 10% or less. 19. The method of claim 17, wherein the genomic rearrangement is a translocation. 20. The method of claim 13, wherein the data generated from the sequencing of the first primer extension is compared with a known nucleic acid sequence such as a known gDNA sequence to determine a genomic rearrangement. | The present disclosure is directed to a single-end sequencing method for improved detection of genomic rearrangements such as deletions, insertions, inversions, and translocations that are present in a polynucleotide. A first priming event allows for sequencing of a target sequence, and a second priming event on an adapter allows for identification of the sequences amplified and tagged by selective amplification. The combination of priming events in the same direction facilitates read alignment and the identification of any genomic rearrangements.1. A method of preparing a polynucleotide for sequencing by attaching a target-specific barcode, the method comprising:
amplifying a polynucleotide with a first amplification primer and a second amplification primer, wherein the first amplification primer hybridizes to a first priming site of the polynucleotide, and the first amplification primer comprises a target-specific barcode; wherein the amplifying generates polynucleotide amplicons, wherein the polynucleotide amplicons comprise sequences identical or complementary to the polynucleotide of interest and the target-specific barcode. 2. The method of claim 1, wherein the second amplification primer hybridizes to (1) a portion of an adapter attached to the polynucleotide at a distance from the first priming site, or (2) a second priming site of the polynucleotide, wherein the second priming site is at a distance from the first priming site. 3. The method of claim 1, further comprising attaching an adapter to the polynucleotide at a distance from the first priming site, wherein the adapter comprises a second priming site. 4. The method of claim 1, wherein the first priming site is a portion of a fusion gene, and the target-specific barcode is specific for the portion of the fusion gene. 5. The method of claim 4, wherein the portion of the fusion gene is a junction of the fusion gene. 6. The method of claim 1, wherein the polynucleotide of interest comprises a plurality of polynucleotides of interest, and the method comprises attaching a plurality of adapters to the plurality of polynucleotides, thereby forming a plurality of adapted polynucleotides, each of the plurality of adapted polynucleotides comprising a different molecular barcode. 7. The method of claim 1, wherein the polynucleotide of interest comprises a plurality of polynucleotides of interest, and the first amplification primer comprises a plurality of first amplification primers having different target-specific primers and different target-specific barcodes, thereby forming a plurality of adapted polynucleotide amplicons, each of the plurality of adapted polynucleotide amplicons comprising a different target-specific barcode. 8. The method of claim 1, wherein the polynucleotide amplicons or adapted polynucleotide comprise a binding partner, such as a biotin moiety. 9. The method of claim 1, further comprising sequencing the polynucleotide amplicons at first and second locations by performing a first primer extension and a second primer extension, wherein the first primer extension and the second primer extension are performed in a same direction. 10. The method of claim 9, wherein the first primer extension and the second primer extension are performed in the same direction on the polynucleotide during separate sequencing runs. 11. A composition or kit for detecting a genomic rearrangement in a polynucleotide having a first binding site, the composition or kit comprising:
a first amplification primer comprising a target-specific primer and a target-specific barcode; and a second amplification primer. 12. The composition or kit of claim 11, further comprising:
an adapter comprises a second priming site and an adapter barcode, and wherein the second amplification primer comprises a priming sequence complementary to or identical to a sequence within the adapter. 13. A method of detecting a genomic rearrangement in a polynucleotide, the method comprising:
amplifying a polynucleotide with a first amplification primer and a second amplification primer, wherein the first amplification primer hybridizes to a first priming site of the polynucleotide, and the first amplification primer further comprises a target-specific barcode, wherein the amplifying generates polynucleotide amplicons, comprising sequences identical or complementary to the polynucleotide of interest and the target-specific barcodes; and sequencing the polynucleotide amplicons at first and second locations by performing a first primer extension and a second primer extension, wherein the first primer extension and the second primer extension are performed in a same direction. 14. The method of claim 13, wherein the sequencing at the first location provides a sequence of at least a portion of the polynucleotide of interest and the sequencing at the second location provides a sequence of the target-specific barcode. 15. The method of claim 13, wherein the first primer extension and the second primer extension are performed in the same direction on the polynucleotide during separate sequencing runs. 16. The method of claim 13, wherein the sequencing is next generation sequencing (NGS) or massively parallel sequencing. 17. The method of claim 13, further comprising detecting a genomic rearrangement using single-end sequencing of at least one of the polynucleotide amplicons, such as by identifying that genomic rearrangement based on data generated from the sequencing of the first primer extension and the second primer extension. 18. The method of claim 17, wherein the genomic rearrangement has a frequency of about 10% or less. 19. The method of claim 17, wherein the genomic rearrangement is a translocation. 20. The method of claim 13, wherein the data generated from the sequencing of the first primer extension is compared with a known nucleic acid sequence such as a known gDNA sequence to determine a genomic rearrangement. | 1,600 |
1,312 | 14,210,118 | 1,619 | According to the invention there is provided inter alia a medical device for delivering a therapeutic agent to a tissue, the device having a solid surfactant-free particulate coating layer applied to a surface of the device, the coating layer comprising a therapeutic agent and at least one non-polymeric organic additive which is hydrolytically stable; wherein at least a proportion of the particulate coating layer comprising the therapeutic agent and the at least one organic additive melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form; wherein the therapeutic agent is paclitaxel; and wherein the therapeutic agent, when formulated in the coating layer, is stable to sterilization. | 1. A medical device for delivering a therapeutic agent to a tissue, the device having a solid surfactant-free particulate coating layer applied to a surface of the device, the coating layer comprising a therapeutic agent and at least one non-polymeric organic additive which is hydrolytically stable; wherein at least a proportion of the particulate coating layer comprising the therapeutic agent and the at least one organic additive melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form; wherein the therapeutic agent is paclitaxel; and wherein the therapeutic agent, when formulated in the coating layer, is stable to sterilization. 2. A medical device for delivering a therapeutic agent to a tissue, the device having a solid surfactant-free particulate coating layer applied to a surface of the device, the coating layer comprising a therapeutic agent and at least one non-polymeric organic additive which is hydrolytically stable; wherein the particulate coating layer is formed by evaporation of a solution of the therapeutic agent and the at least one organic additive applied to the device to form a solid particulate composition, wherein at least a proportion of the particulate coating layer comprising the therapeutic agent and the at least one organic additive melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the organic additive when in pure form; wherein the therapeutic agent is paclitaxel; and wherein the therapeutic agent, when formulated in the coating layer, is stable to sterilization. 3. A medical device for delivering a therapeutic agent to a tissue, the device having a solid surfactant-free particulate coating layer applied to a surface of the device, the coating layer comprising a therapeutic agent and at least one non-polymeric organic additive which is hydrolytically stable; wherein the particulate coating layer is formed by combining the therapeutic agent and at least one organic additive in powder form, and then applying the powder to the device, with an optional subsequent step of thermal treatment, to form a solid particulate composition, wherein at least a proportion of the particulate coating layer comprising the therapeutic agent and the at least one organic additive melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the organic additive when in pure form; wherein the therapeutic agent is paclitaxel; and wherein the therapeutic agent, when formulated in the coating layer, is stable to sterilization. 4. A medical device according to claim 2 wherein the solution of the therapeutic agent and the at least one organic additive is a solution in a solvent selected from water, acetone and mixtures thereof. 5. A medical device according to any one of claims 1 to 4, wherein the therapeutic agent and the at least one organic additive in the particulate coating are in crystalline form. 6. A medical device according to any one of claims 1 to 5, wherein each at least one organic additive melts at a temperature of greater than about 80° C. when in pure form. 7. A medical device according to any one of claims 1 to 6, wherein the or each at least one organic additive is a substance having a value for the dispersion component of the Hansen solubility parameter determined at 25° C. substantially the same as that of the therapeutic agent. 8. A medical device according to claim 7 wherein the dispersion component of the Hansen solubility parameter determined at 25° C. of the or each at least one organic additive is between 16 and 21 MPa0.5. 9. A medical device according to any one of claims 1 to 8, wherein the coating layer comprises crystalline particles of the therapeutic agent and the at least one organic additive in a eutectic mixture. 10. A medical device according to any one of claims 1 to 8, wherein the coating layer comprises crystalline particles of the therapeutic agent and the at least one organic additive in co-crystalline form. 11. A medical device according to any one of claims 1 to 10, wherein substantially all of said particulate coating layer comprising the therapeutic agent and the at least one non-polymeric organic additive melts as a single phase at a lower temperature than the melting point of the therapeutic and the at least one organic additive when in pure form. 12. A medical device according to any one of claims 1 to 10, wherein a proportion of the particulate coating layer comprising the therapeutic agent and the at least one organic additive melts at a temperature at or close to the melting point of at least one of the at least one of the organic additives in pure form. 13. A medical device according to claim 12, wherein the proportion of the at least one organic additive which melts at a temperature at or close to the melting point of said organic additive in pure form is 1-70% (by weight), such as 1-50% or 1-20% of said organic additive in the coating layer. 14. A medical device according to any one of claims 1 to 13, wherein 20-100% (by weight) of the particulate coating layer exhibits a melting point which is at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive in pure form, such as 30-100%, 40-100%, 50-100%, 60-100%, 70-100%, 80-100% 90-100%. 15. A medical device according to anyone of claims 1 to 14, wherein each at least one organic additive has a molecular weight of less than 750 Da. 16. A medical device according to any one of claims 1 to 15, wherein each at least one organic additive is independently selected from the list consisting of p-aminobenzoic acid, saccharin, ascorbic acid, methyl paraben, caffeine, calcium salicylate, pentetic acid, creatinine, ethylurea, acetaminophen, aspirin, theobromine, tryptophan, succinic acid, adipic acid, glutaric acid, theophylline, and saccharin sodium. 17. A medical device according to claim 16, wherein each at least one organic additive is independently selected from the list consisting of p-aminobenzoic acid, methyl paraben, caffeine, calcium salicylate and succinic acid. 18. A medical device according to any one of claims 1 to 17, wherein the coating layer comprises one organic additive. 19. A medical device according to any one of claims 1 to 17, wherein the coating layer comprises two organic additives. 20. A medical device according to any one of claims 1 to 17, wherein the coating layer consists of the therapeutic agent and at least one organic additive. 21. A medical device according to any one of claims 1 to 17, wherein the coating layer consists of the therapeutic agent and one organic additive. 22. A medical device according to any one of claims 1 to 17, wherein the coating layer consists of the therapeutic agent and two organic additives. 23. A medical device according to claim 18 or claim 21, wherein the organic additive is succinic acid. 24. A medical device according to claim 19 or claim 22, wherein the two organic additives are caffeine and succinic acid. 25. A medical device according to any one of claims 1 to 24, wherein the concentration of the therapeutic agent in the solid coating layer is 5-95% by weight, for example 30-90 or 70-80%. 26. A medical device according to any one of claims 1 to 25, wherein the solid coating layer is applied to a surface of the device which is composed of nylon. 27. A medical device according to any one of claims 1 to 25, wherein the solid coating layer is applied to a surface of the device which is composed of ePTFE. 28. A medical device for delivering a therapeutic agent to a tissue, the device having a solid particulate coating layer applied to an exterior surface of the device, said surface being composed of a material selected from nylon and ePTFE, the coating layer comprising a therapeutic agent and at least one organic additive; wherein at least a proportion of the particulate coating layer comprising the therapeutic agent and the at least one organic additive melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form; wherein the therapeutic agent is paclitaxel and wherein the at least one organic additive is independently selected from the list consisting of calcium salicylate, caffeine, methyl paraben, p-aminobenzoic acid and succinic acid. 29. A medical device for delivering a therapeutic agent to a tissue, the device having a solid particulate coating layer applied to an exterior surface of the device, said surface being composed of a material selected from nylon and ePTFE, the coating layer comprising a therapeutic agent and at least one organic additive; wherein the coating layer is formed by evaporation of a solution of the therapeutic agent and the at least one organic additive applied to the device to form a solid particulate composition, wherein at least a proportion of the particulate coating layer melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form; wherein the therapeutic agent is paclitaxel, wherein the at least one organic additive is independently selected from the list consisting of calcium salicylate, caffeine, methyl paraben, p-aminobenzoic acid and succinic acid and wherein the solution of the therapeutic agent and the at least one organic additive is a solution in a solvent selected from water, acetone and mixtures thereof. 30. A medical device for delivering a therapeutic agent to a tissue, the device having a solid particulate coating layer applied to an exterior surface of the device, said surface being composed of a material selected from nylon and ePTFE, the coating layer comprising a therapeutic agent and at least one organic additive; wherein the coating layer is formed by combining the therapeutic agent and at least one organic additive in powder form, and then applying the powder to the device, with an optional subsequent step of thermal treatment, to form a solid particulate composition, wherein at least a proportion of the particulate coating layer melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form; wherein the therapeutic agent is paclitaxel, wherein the at least one organic additive is independently selected from the list consisting of calcium salicylate, caffeine, methyl paraben, p-aminobenzoic acid and succinic acid. 31. A medical device according to any one of claims 28 to 30, wherein substantially all of said particulate coating layer comprising the therapeutic agent and at least one organic additive melts as a single phase at a lower temperature than the melting point of the therapeutic and the at least one organic additive when in pure form. 32. A medical device according to any one of claims 28 to 30, wherein a proportion of the particulate coating layer comprises at least one organic additive which melts at a temperature at or close to the melting point of said organic additive in pure form. 33. A medical device according to claim 32, wherein the proportion of the at least one organic additive which melts at a temperature at or close to the melting point of the organic additive in pure form is 1-70%, such as 1-50% or 1-20% by weight of said organic additive in the coating layer. 34. A medical device according to any one of claims 28 to 34, wherein the coating layer comprises one organic additive. 35. A medical device according to any one of claims 28 to 34, wherein the coating layer comprises two organic additives. 36. A medical device according to any one of claims 28 to 34, wherein the coating layer consists of the therapeutic agent and at least one organic additive. 37. A medical device according to any one of claims 28 to 34, wherein the coating layer consists of the therapeutic agent and one organic additive. 38. A medical device according to any one of claims 28 to 34, wherein the coating layer consists of the therapeutic agent and two organic additives. 39. A medical device according to claim 34 or claim 37, wherein the organic additive is succinic acid. 40. A medical device according to claim 34 or claim 37, wherein the succinic acid is present in the coating layer in the form of its alpha crystalline polymorph. 41. A medical device according to claim 35 or claim 38, wherein the two organic additives are caffeine and succinic acid. 42. A medical device for delivering a therapeutic agent to a tissue, the device having a solid surfactant-free particulate coating layer applied to an exterior surface of the device, the coating layer comprising a therapeutic agent and at least one non-polymeric organic additive which is hydrolytically stable; wherein the particulate coating layer comprises a mixture of components (a) the therapeutic agent and at least one organic additive in a form which melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form and (b) the at least one organic additive in a form which melts at a temperature at or close to that of said organic additive in pure form; wherein the therapeutic agent is paclitaxel; and wherein the therapeutic agent, when formulated in the coating layer, is stable to ethylene oxide sterilization. 43. A medical device for delivering a therapeutic agent to a tissue, the device having a solid surfactant-free particulate coating layer applied to an exterior surface of the device, the coating layer comprising a therapeutic agent and at least one a non-polymeric organic additive which is hydrolytically stable; wherein the particulate coating layer is formed by evaporation of a solution of the therapeutic agent and the at least one organic additive applied to the device to form a solid particulate composition comprising (a) a component comprising the therapeutic agent and the at least one organic additive which melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form and (b) a component which melts at a temperature at or close to that of the at least one organic additive in pure form; wherein the therapeutic agent is paclitaxel and wherein the therapeutic agent, when formulated in the coating layer, is stable to sterilization. 44. A medical device for delivering a therapeutic agent to a tissue, the device having a solid surfactant-free particulate coating layer applied to an exterior surface of the device, the coating layer comprising a therapeutic agent and at least one non-polymeric organic additive which is hydrolytically stable; wherein the particulate coating layer is formed by combining the therapeutic agent and the at least one organic additive in powder form, and then applying the powder to the device, with an optional subsequent step of thermal treatment, to form a solid particulate composition comprising (a) a component comprising the therapeutic agent and the at least one organic additive which melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the organic additive when in pure form and (b) a component which melts at a temperature at or close to that of the at least one organic additive in pure form; wherein the therapeutic agent is paclitaxel and wherein the therapeutic agent, when formulated in the coating layer, is stable to sterilization. 45. A medical device according to any one of claims 42 to 44, wherein the proportion of the at least one organic additive in component (b) is 1-70%, such as 1-50% or 1-20% by weight of said organic additive in the coating layer 46. A medical device according to any one of claims 1 to 45, wherein an adherent layer is interposed between the solid coating layer comprising the therapeutic agent and the at least one organic additive, and the material of the surface of the device. 47. A medical device according to any one of claims 1 to 46 comprising a protective top-coat layer applied to the solid coating layer comprising the therapeutic agent and the at least one organic additive. 48. A medical device according to any one of claims 1 to 47, which is a balloon catheter. 49. A medical device according to any one of claims 1 to 47, which is a stent. 50. A medical device according to any one of claims 1 to 47, which is a stent-graft. 51. A medical device according to any one of claims 1 to 47, which is a graft. 52. A medical device according to any one of claims 1 to 51, which coating layer comprising the therapeutic agent and the at least one organic additive has suitable adherence such that less than 40% of the paclitaxel is lost during shaking, for example less than 30%, less than 25%, less than 20%, less than 15%, less than 10% or less than 5% using Test Method C. 53. A medical device according to claim 48, wherein the coating has suitable paclitaxel release and tissue transfer characteristics such that the measured drug concentration in the tissue at the 1 hr timepoint is at least 50 μg drug per g tissue (μg/g), for example at least 60 μg/g, at least 70 μg/g or at least 80 μg/g using Test Method A. 54. A medical device according to claim 49, wherein the coating has paclitaxel release and tissue transfer characteristics such that the measured drug concentration in the tissue at the 24 hr timepoint is at least 1 μg drug per g tissue (μg/g), for example at least 2.5 μg/g, at least 5 μg/g or at least 10 μg/g using Test Method B. 55. A medical device according to any one of claims 1 to 54, wherein the therapeutic agent, when formulated in the coating layer, is stable to ethylene oxide sterilization. 56. A medical device according to any one of claims 1 to 54, wherein at least 80%, such as at least 85%, 90% or 95% of the therapeutic agent chemical content is retained following sterilization using Test Method D. 57. A medical device according to any one of claims 1 to 56 for use in the prevention or treatment of stenosis or restenosis in a blood vessel of the human body. 58. A method for preparing a medical device according to claim 1, 28 or 42, which comprises the steps of dissolving the therapeutic agent and the at least one organic additive in a solvent to form a solution, coating the device with the solution and evaporating the solvent. 59. A method according to claim 58 wherein the solvent is selected from water, acetone and mixtures thereof. 60. A method for preparing a medical device according to claim 1, 28 or 42, which comprises the steps of combining the therapeutic agent and the at least one organic additive in powder form, and then applying the powder to the device to form a solid particulate composition and optionally applying a subsequent thermal treatment step. 61. A method for the prevention or treatment of stenosis or restenosis which comprises inserting transiently or permanently into said blood vessel in the human body a medical device according to any one of claims 1 to 60. 62. A solid particulate composition comprising a therapeutic agent and at least one organic additive, wherein at least a proportion of the particulate composition comprising the therapeutic agent and at least one organic additive melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form; wherein the therapeutic agent is paclitaxel and wherein the at least one organic additive is selected from the list consisting of p-aminobenzoic acid, saccharin, ascorbic acid, methyl paraben, caffeine, calcium salicylate, pentetic acid, creatinine, ethylurea, acetaminophen, aspirin, theobromine, tryptophan, succinic acid, adipic acid, glutaric acid, theophylline, and saccharin sodium. 63. A solid particulate composition comprising a mixture of components (a) a therapeutic agent and at least one organic additive in a particulate form which melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form and (b) a component which is the at least one organic additive in the form of particles which melt at a temperature at or close to that of the at least one organic additive in pure form; wherein the therapeutic agent is paclitaxel and wherein the at least one organic additive is independently selected from the list consisting of p-aminobenzoic acid, saccharin, ascorbic acid, methyl paraben, caffeine, calcium salicylate, pentetic acid, creatinine, ethylurea, acetaminophen, aspirin, theobromine, tryptophan, succinic acid, adipic acid, glutaric acid, theophylline, and saccharin sodium. 64. A solid particulate composition according to claim 62 or claim 63, wherein the at least one organic additive is selected from the list consisting of calcium salicylate, caffeine, methyl paraben, p-aminobenzoic acid and succinic acid. 65. A solid particulate composition according to any one of claims 62 to 64, comprising one organic additive. 66. A solid particulate composition according to any one of claims 62 to 64, comprising two organic additives. 67. A solid particulate composition according to any one of claims 62 to 64, which consists of the therapeutic agent and at least one organic additive. 68. A solid particulate composition according to any one of claims 62 to 64, which consists of the therapeutic agent and one organic additive. 69. A solid particulate composition according to any one of claims 62 to 64, which consists of the therapeutic agent and two organic additives. 70. A solid particulate composition according to claim 65 or claim 68, wherein the organic additive is succinic acid. 71. A solid particulate composition according to claim 66 or claim 69, wherein the organic additives are caffeine and succinic acid. 72. A solid particulate composition according to any one of claims 62 to 71 in the form of a coating applied to a surface. 73. A medical device for delivering a therapeutic agent to a tissue, the device having a solid surfactant-free particulate coating layer applied to an exterior surface of the device, the coating layer comprising a therapeutic agent and at least one organic additive is independently selected from the list consisting of p-aminobenzoic acid, saccharin, ascorbic acid, methyl paraben, caffeine, calcium salicylate, pentetic acid, creatinine, ethylurea, acetaminophen, aspirin, theobromine, tryptophan, succinic acid, adipic acid, glutaric acid, theophylline, and saccharin sodium; wherein at least a proportion of the particulate coating layer comprising the therapeutic agent and the at least one organic additive melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form; and wherein the therapeutic agent is paclitaxel. 74. A medical device according to claim 73, wherein each at least one organic additive is independently selected from the list consisting of calcium salicylate, caffeine, methyl paraben, p-aminobenzoic acid and succinic acid. 75. A medical device according to claim 73 or claim 74, wherein the coating layer comprises one organic additive. 76. A medical device according to claim 73 or claim 74, wherein the coating layer comprises one organic additive. 77. A medical device according to claim 73 or claim 74, wherein the coating layer comprises two organic additives. 78. A medical device according to claim 73 or claim 74, wherein the coating layer consists of the therapeutic agent and at least one organic additive. 79. A medical device according to claim 73 or claim 74, wherein the coating layer consists of the therapeutic agent and one organic additive. 80. A medical device according to claim 73 or claim 74, wherein the coating layer consists of the therapeutic agent and two organic additives. 81. A medical device according to claim 75 or claim 79, wherein the organic additive is succinic acid. 82. A medical device according to claim 76 or claim 80, wherein the two organic additives are caffeine and succinic acid. 83. A medical device according to any one of claims 73 to 82, wherein at least 80%, such as at least 85%, 90% or 95% of the therapeutic agent chemical content is retained following ethylene oxide sterilization using Test Method D. 84. A sterilized medical device or solid particulate composition according to any one of claims 1 to 83. 85. A sterilized medical device according to claim 84, which has been ethylene oxide sterilized. | According to the invention there is provided inter alia a medical device for delivering a therapeutic agent to a tissue, the device having a solid surfactant-free particulate coating layer applied to a surface of the device, the coating layer comprising a therapeutic agent and at least one non-polymeric organic additive which is hydrolytically stable; wherein at least a proportion of the particulate coating layer comprising the therapeutic agent and the at least one organic additive melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form; wherein the therapeutic agent is paclitaxel; and wherein the therapeutic agent, when formulated in the coating layer, is stable to sterilization.1. A medical device for delivering a therapeutic agent to a tissue, the device having a solid surfactant-free particulate coating layer applied to a surface of the device, the coating layer comprising a therapeutic agent and at least one non-polymeric organic additive which is hydrolytically stable; wherein at least a proportion of the particulate coating layer comprising the therapeutic agent and the at least one organic additive melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form; wherein the therapeutic agent is paclitaxel; and wherein the therapeutic agent, when formulated in the coating layer, is stable to sterilization. 2. A medical device for delivering a therapeutic agent to a tissue, the device having a solid surfactant-free particulate coating layer applied to a surface of the device, the coating layer comprising a therapeutic agent and at least one non-polymeric organic additive which is hydrolytically stable; wherein the particulate coating layer is formed by evaporation of a solution of the therapeutic agent and the at least one organic additive applied to the device to form a solid particulate composition, wherein at least a proportion of the particulate coating layer comprising the therapeutic agent and the at least one organic additive melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the organic additive when in pure form; wherein the therapeutic agent is paclitaxel; and wherein the therapeutic agent, when formulated in the coating layer, is stable to sterilization. 3. A medical device for delivering a therapeutic agent to a tissue, the device having a solid surfactant-free particulate coating layer applied to a surface of the device, the coating layer comprising a therapeutic agent and at least one non-polymeric organic additive which is hydrolytically stable; wherein the particulate coating layer is formed by combining the therapeutic agent and at least one organic additive in powder form, and then applying the powder to the device, with an optional subsequent step of thermal treatment, to form a solid particulate composition, wherein at least a proportion of the particulate coating layer comprising the therapeutic agent and the at least one organic additive melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the organic additive when in pure form; wherein the therapeutic agent is paclitaxel; and wherein the therapeutic agent, when formulated in the coating layer, is stable to sterilization. 4. A medical device according to claim 2 wherein the solution of the therapeutic agent and the at least one organic additive is a solution in a solvent selected from water, acetone and mixtures thereof. 5. A medical device according to any one of claims 1 to 4, wherein the therapeutic agent and the at least one organic additive in the particulate coating are in crystalline form. 6. A medical device according to any one of claims 1 to 5, wherein each at least one organic additive melts at a temperature of greater than about 80° C. when in pure form. 7. A medical device according to any one of claims 1 to 6, wherein the or each at least one organic additive is a substance having a value for the dispersion component of the Hansen solubility parameter determined at 25° C. substantially the same as that of the therapeutic agent. 8. A medical device according to claim 7 wherein the dispersion component of the Hansen solubility parameter determined at 25° C. of the or each at least one organic additive is between 16 and 21 MPa0.5. 9. A medical device according to any one of claims 1 to 8, wherein the coating layer comprises crystalline particles of the therapeutic agent and the at least one organic additive in a eutectic mixture. 10. A medical device according to any one of claims 1 to 8, wherein the coating layer comprises crystalline particles of the therapeutic agent and the at least one organic additive in co-crystalline form. 11. A medical device according to any one of claims 1 to 10, wherein substantially all of said particulate coating layer comprising the therapeutic agent and the at least one non-polymeric organic additive melts as a single phase at a lower temperature than the melting point of the therapeutic and the at least one organic additive when in pure form. 12. A medical device according to any one of claims 1 to 10, wherein a proportion of the particulate coating layer comprising the therapeutic agent and the at least one organic additive melts at a temperature at or close to the melting point of at least one of the at least one of the organic additives in pure form. 13. A medical device according to claim 12, wherein the proportion of the at least one organic additive which melts at a temperature at or close to the melting point of said organic additive in pure form is 1-70% (by weight), such as 1-50% or 1-20% of said organic additive in the coating layer. 14. A medical device according to any one of claims 1 to 13, wherein 20-100% (by weight) of the particulate coating layer exhibits a melting point which is at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive in pure form, such as 30-100%, 40-100%, 50-100%, 60-100%, 70-100%, 80-100% 90-100%. 15. A medical device according to anyone of claims 1 to 14, wherein each at least one organic additive has a molecular weight of less than 750 Da. 16. A medical device according to any one of claims 1 to 15, wherein each at least one organic additive is independently selected from the list consisting of p-aminobenzoic acid, saccharin, ascorbic acid, methyl paraben, caffeine, calcium salicylate, pentetic acid, creatinine, ethylurea, acetaminophen, aspirin, theobromine, tryptophan, succinic acid, adipic acid, glutaric acid, theophylline, and saccharin sodium. 17. A medical device according to claim 16, wherein each at least one organic additive is independently selected from the list consisting of p-aminobenzoic acid, methyl paraben, caffeine, calcium salicylate and succinic acid. 18. A medical device according to any one of claims 1 to 17, wherein the coating layer comprises one organic additive. 19. A medical device according to any one of claims 1 to 17, wherein the coating layer comprises two organic additives. 20. A medical device according to any one of claims 1 to 17, wherein the coating layer consists of the therapeutic agent and at least one organic additive. 21. A medical device according to any one of claims 1 to 17, wherein the coating layer consists of the therapeutic agent and one organic additive. 22. A medical device according to any one of claims 1 to 17, wherein the coating layer consists of the therapeutic agent and two organic additives. 23. A medical device according to claim 18 or claim 21, wherein the organic additive is succinic acid. 24. A medical device according to claim 19 or claim 22, wherein the two organic additives are caffeine and succinic acid. 25. A medical device according to any one of claims 1 to 24, wherein the concentration of the therapeutic agent in the solid coating layer is 5-95% by weight, for example 30-90 or 70-80%. 26. A medical device according to any one of claims 1 to 25, wherein the solid coating layer is applied to a surface of the device which is composed of nylon. 27. A medical device according to any one of claims 1 to 25, wherein the solid coating layer is applied to a surface of the device which is composed of ePTFE. 28. A medical device for delivering a therapeutic agent to a tissue, the device having a solid particulate coating layer applied to an exterior surface of the device, said surface being composed of a material selected from nylon and ePTFE, the coating layer comprising a therapeutic agent and at least one organic additive; wherein at least a proportion of the particulate coating layer comprising the therapeutic agent and the at least one organic additive melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form; wherein the therapeutic agent is paclitaxel and wherein the at least one organic additive is independently selected from the list consisting of calcium salicylate, caffeine, methyl paraben, p-aminobenzoic acid and succinic acid. 29. A medical device for delivering a therapeutic agent to a tissue, the device having a solid particulate coating layer applied to an exterior surface of the device, said surface being composed of a material selected from nylon and ePTFE, the coating layer comprising a therapeutic agent and at least one organic additive; wherein the coating layer is formed by evaporation of a solution of the therapeutic agent and the at least one organic additive applied to the device to form a solid particulate composition, wherein at least a proportion of the particulate coating layer melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form; wherein the therapeutic agent is paclitaxel, wherein the at least one organic additive is independently selected from the list consisting of calcium salicylate, caffeine, methyl paraben, p-aminobenzoic acid and succinic acid and wherein the solution of the therapeutic agent and the at least one organic additive is a solution in a solvent selected from water, acetone and mixtures thereof. 30. A medical device for delivering a therapeutic agent to a tissue, the device having a solid particulate coating layer applied to an exterior surface of the device, said surface being composed of a material selected from nylon and ePTFE, the coating layer comprising a therapeutic agent and at least one organic additive; wherein the coating layer is formed by combining the therapeutic agent and at least one organic additive in powder form, and then applying the powder to the device, with an optional subsequent step of thermal treatment, to form a solid particulate composition, wherein at least a proportion of the particulate coating layer melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form; wherein the therapeutic agent is paclitaxel, wherein the at least one organic additive is independently selected from the list consisting of calcium salicylate, caffeine, methyl paraben, p-aminobenzoic acid and succinic acid. 31. A medical device according to any one of claims 28 to 30, wherein substantially all of said particulate coating layer comprising the therapeutic agent and at least one organic additive melts as a single phase at a lower temperature than the melting point of the therapeutic and the at least one organic additive when in pure form. 32. A medical device according to any one of claims 28 to 30, wherein a proportion of the particulate coating layer comprises at least one organic additive which melts at a temperature at or close to the melting point of said organic additive in pure form. 33. A medical device according to claim 32, wherein the proportion of the at least one organic additive which melts at a temperature at or close to the melting point of the organic additive in pure form is 1-70%, such as 1-50% or 1-20% by weight of said organic additive in the coating layer. 34. A medical device according to any one of claims 28 to 34, wherein the coating layer comprises one organic additive. 35. A medical device according to any one of claims 28 to 34, wherein the coating layer comprises two organic additives. 36. A medical device according to any one of claims 28 to 34, wherein the coating layer consists of the therapeutic agent and at least one organic additive. 37. A medical device according to any one of claims 28 to 34, wherein the coating layer consists of the therapeutic agent and one organic additive. 38. A medical device according to any one of claims 28 to 34, wherein the coating layer consists of the therapeutic agent and two organic additives. 39. A medical device according to claim 34 or claim 37, wherein the organic additive is succinic acid. 40. A medical device according to claim 34 or claim 37, wherein the succinic acid is present in the coating layer in the form of its alpha crystalline polymorph. 41. A medical device according to claim 35 or claim 38, wherein the two organic additives are caffeine and succinic acid. 42. A medical device for delivering a therapeutic agent to a tissue, the device having a solid surfactant-free particulate coating layer applied to an exterior surface of the device, the coating layer comprising a therapeutic agent and at least one non-polymeric organic additive which is hydrolytically stable; wherein the particulate coating layer comprises a mixture of components (a) the therapeutic agent and at least one organic additive in a form which melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form and (b) the at least one organic additive in a form which melts at a temperature at or close to that of said organic additive in pure form; wherein the therapeutic agent is paclitaxel; and wherein the therapeutic agent, when formulated in the coating layer, is stable to ethylene oxide sterilization. 43. A medical device for delivering a therapeutic agent to a tissue, the device having a solid surfactant-free particulate coating layer applied to an exterior surface of the device, the coating layer comprising a therapeutic agent and at least one a non-polymeric organic additive which is hydrolytically stable; wherein the particulate coating layer is formed by evaporation of a solution of the therapeutic agent and the at least one organic additive applied to the device to form a solid particulate composition comprising (a) a component comprising the therapeutic agent and the at least one organic additive which melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form and (b) a component which melts at a temperature at or close to that of the at least one organic additive in pure form; wherein the therapeutic agent is paclitaxel and wherein the therapeutic agent, when formulated in the coating layer, is stable to sterilization. 44. A medical device for delivering a therapeutic agent to a tissue, the device having a solid surfactant-free particulate coating layer applied to an exterior surface of the device, the coating layer comprising a therapeutic agent and at least one non-polymeric organic additive which is hydrolytically stable; wherein the particulate coating layer is formed by combining the therapeutic agent and the at least one organic additive in powder form, and then applying the powder to the device, with an optional subsequent step of thermal treatment, to form a solid particulate composition comprising (a) a component comprising the therapeutic agent and the at least one organic additive which melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the organic additive when in pure form and (b) a component which melts at a temperature at or close to that of the at least one organic additive in pure form; wherein the therapeutic agent is paclitaxel and wherein the therapeutic agent, when formulated in the coating layer, is stable to sterilization. 45. A medical device according to any one of claims 42 to 44, wherein the proportion of the at least one organic additive in component (b) is 1-70%, such as 1-50% or 1-20% by weight of said organic additive in the coating layer 46. A medical device according to any one of claims 1 to 45, wherein an adherent layer is interposed between the solid coating layer comprising the therapeutic agent and the at least one organic additive, and the material of the surface of the device. 47. A medical device according to any one of claims 1 to 46 comprising a protective top-coat layer applied to the solid coating layer comprising the therapeutic agent and the at least one organic additive. 48. A medical device according to any one of claims 1 to 47, which is a balloon catheter. 49. A medical device according to any one of claims 1 to 47, which is a stent. 50. A medical device according to any one of claims 1 to 47, which is a stent-graft. 51. A medical device according to any one of claims 1 to 47, which is a graft. 52. A medical device according to any one of claims 1 to 51, which coating layer comprising the therapeutic agent and the at least one organic additive has suitable adherence such that less than 40% of the paclitaxel is lost during shaking, for example less than 30%, less than 25%, less than 20%, less than 15%, less than 10% or less than 5% using Test Method C. 53. A medical device according to claim 48, wherein the coating has suitable paclitaxel release and tissue transfer characteristics such that the measured drug concentration in the tissue at the 1 hr timepoint is at least 50 μg drug per g tissue (μg/g), for example at least 60 μg/g, at least 70 μg/g or at least 80 μg/g using Test Method A. 54. A medical device according to claim 49, wherein the coating has paclitaxel release and tissue transfer characteristics such that the measured drug concentration in the tissue at the 24 hr timepoint is at least 1 μg drug per g tissue (μg/g), for example at least 2.5 μg/g, at least 5 μg/g or at least 10 μg/g using Test Method B. 55. A medical device according to any one of claims 1 to 54, wherein the therapeutic agent, when formulated in the coating layer, is stable to ethylene oxide sterilization. 56. A medical device according to any one of claims 1 to 54, wherein at least 80%, such as at least 85%, 90% or 95% of the therapeutic agent chemical content is retained following sterilization using Test Method D. 57. A medical device according to any one of claims 1 to 56 for use in the prevention or treatment of stenosis or restenosis in a blood vessel of the human body. 58. A method for preparing a medical device according to claim 1, 28 or 42, which comprises the steps of dissolving the therapeutic agent and the at least one organic additive in a solvent to form a solution, coating the device with the solution and evaporating the solvent. 59. A method according to claim 58 wherein the solvent is selected from water, acetone and mixtures thereof. 60. A method for preparing a medical device according to claim 1, 28 or 42, which comprises the steps of combining the therapeutic agent and the at least one organic additive in powder form, and then applying the powder to the device to form a solid particulate composition and optionally applying a subsequent thermal treatment step. 61. A method for the prevention or treatment of stenosis or restenosis which comprises inserting transiently or permanently into said blood vessel in the human body a medical device according to any one of claims 1 to 60. 62. A solid particulate composition comprising a therapeutic agent and at least one organic additive, wherein at least a proportion of the particulate composition comprising the therapeutic agent and at least one organic additive melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form; wherein the therapeutic agent is paclitaxel and wherein the at least one organic additive is selected from the list consisting of p-aminobenzoic acid, saccharin, ascorbic acid, methyl paraben, caffeine, calcium salicylate, pentetic acid, creatinine, ethylurea, acetaminophen, aspirin, theobromine, tryptophan, succinic acid, adipic acid, glutaric acid, theophylline, and saccharin sodium. 63. A solid particulate composition comprising a mixture of components (a) a therapeutic agent and at least one organic additive in a particulate form which melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form and (b) a component which is the at least one organic additive in the form of particles which melt at a temperature at or close to that of the at least one organic additive in pure form; wherein the therapeutic agent is paclitaxel and wherein the at least one organic additive is independently selected from the list consisting of p-aminobenzoic acid, saccharin, ascorbic acid, methyl paraben, caffeine, calcium salicylate, pentetic acid, creatinine, ethylurea, acetaminophen, aspirin, theobromine, tryptophan, succinic acid, adipic acid, glutaric acid, theophylline, and saccharin sodium. 64. A solid particulate composition according to claim 62 or claim 63, wherein the at least one organic additive is selected from the list consisting of calcium salicylate, caffeine, methyl paraben, p-aminobenzoic acid and succinic acid. 65. A solid particulate composition according to any one of claims 62 to 64, comprising one organic additive. 66. A solid particulate composition according to any one of claims 62 to 64, comprising two organic additives. 67. A solid particulate composition according to any one of claims 62 to 64, which consists of the therapeutic agent and at least one organic additive. 68. A solid particulate composition according to any one of claims 62 to 64, which consists of the therapeutic agent and one organic additive. 69. A solid particulate composition according to any one of claims 62 to 64, which consists of the therapeutic agent and two organic additives. 70. A solid particulate composition according to claim 65 or claim 68, wherein the organic additive is succinic acid. 71. A solid particulate composition according to claim 66 or claim 69, wherein the organic additives are caffeine and succinic acid. 72. A solid particulate composition according to any one of claims 62 to 71 in the form of a coating applied to a surface. 73. A medical device for delivering a therapeutic agent to a tissue, the device having a solid surfactant-free particulate coating layer applied to an exterior surface of the device, the coating layer comprising a therapeutic agent and at least one organic additive is independently selected from the list consisting of p-aminobenzoic acid, saccharin, ascorbic acid, methyl paraben, caffeine, calcium salicylate, pentetic acid, creatinine, ethylurea, acetaminophen, aspirin, theobromine, tryptophan, succinic acid, adipic acid, glutaric acid, theophylline, and saccharin sodium; wherein at least a proportion of the particulate coating layer comprising the therapeutic agent and the at least one organic additive melts as a single phase at a lower temperature than the melting point of the therapeutic agent and the at least one organic additive when in pure form; and wherein the therapeutic agent is paclitaxel. 74. A medical device according to claim 73, wherein each at least one organic additive is independently selected from the list consisting of calcium salicylate, caffeine, methyl paraben, p-aminobenzoic acid and succinic acid. 75. A medical device according to claim 73 or claim 74, wherein the coating layer comprises one organic additive. 76. A medical device according to claim 73 or claim 74, wherein the coating layer comprises one organic additive. 77. A medical device according to claim 73 or claim 74, wherein the coating layer comprises two organic additives. 78. A medical device according to claim 73 or claim 74, wherein the coating layer consists of the therapeutic agent and at least one organic additive. 79. A medical device according to claim 73 or claim 74, wherein the coating layer consists of the therapeutic agent and one organic additive. 80. A medical device according to claim 73 or claim 74, wherein the coating layer consists of the therapeutic agent and two organic additives. 81. A medical device according to claim 75 or claim 79, wherein the organic additive is succinic acid. 82. A medical device according to claim 76 or claim 80, wherein the two organic additives are caffeine and succinic acid. 83. A medical device according to any one of claims 73 to 82, wherein at least 80%, such as at least 85%, 90% or 95% of the therapeutic agent chemical content is retained following ethylene oxide sterilization using Test Method D. 84. A sterilized medical device or solid particulate composition according to any one of claims 1 to 83. 85. A sterilized medical device according to claim 84, which has been ethylene oxide sterilized. | 1,600 |
1,313 | 13,847,453 | 1,613 | Antimicrobial skin prep solutions of the invention comprise: a major amount of at least one organic solvent, wherein at least about 80% by weight based on total weight of the solvent comprises at least one fugitive organic solvent; an antimicrobially effective amount of at least one antimicrobial agent; and an amount of at least one adhesive effective to increase adhesion of surgical drapes and medical dressings to skin prepped with the antimicrobial skin prep solution, wherein the at least one adhesive is distinct from the at least one antimicrobial agent and is a liquid at room temperature. Coated substrates, applicators, and related methods are also disclosed. | 1. An antimicrobial skin prep solution comprising:
a major amount of at least one organic solvent, wherein at least about 80% by weight based on total weight of the solvent comprises at least one fugitive organic solvent; an antimicrobially effective amount of at least one antimicrobial agent; and an amount of at least one adhesive effective to increase adhesion of surgical drapes and medical dressings to skin prepped with the antimicrobial skin prep solution, wherein the at least one adhesive is distinct from the at least one antimicrobial agent and is a liquid at room temperature. 2. The antimicrobial skin prep solution of claim 1, wherein the amount of at least one adhesive effective to increase adhesion of surgical drapes and medical dressings to skin prepped with the antimicrobial skin prep solution is about 2% by weight of the skin prep solution. 3. The antimicrobial skin prep solution of claim 1, wherein the amount of at least one adhesive effective to increase adhesion of surgical drapes and medical dressings to skin prepped with the antimicrobial skin prep solution is about 5.5% by weight of the skin prep solution. 4. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive is a hydrogel in the skin prep solution. 5. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive has a room temperature Brookfield viscosity of less than about 10,000 centiPoise. 6. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive has a room temperature Brookfield viscosity of less than about 5,000 centiPoise. 7. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive has a room temperature Brookfield viscosity of less than about 2,000 centiPoise. 8. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive has a room temperature Brookfield viscosity of about 400 centiPoise to about 1,500 centiPoise. 9. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive is based on (meth)acrylate chemistry. 10. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive is based on monomers that are essentially free of water-soluble monomers. 11. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive is a homopolymer. 12. The antimicrobial skin prep solution of claim 1, wherein the antimicrobial agent comprises chlorhexidine free base. 13. The antimicrobial skin prep solution of claim 1, wherein the antimicrobial agent comprises a chlorhexidine salt. 14. The antimicrobial skin prep solution of claim 1, wherein the antimicrobial agent comprises chlorhexidine gluconate. 15. The antimicrobial skin prep solution of claim 1, wherein at least about 2% by weight chlorhexidine salt is present in the skin prep solution. 16. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive comprises polar functional groups. 17. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive provides an increase in adhesion of surgical drapes and medical dressings to skin prepped with the antimicrobial skin prep solution of at least about 10 N/dm when tested according to a 90° Peel Adhesion Test Method described herein. 18. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive provides an increase in adhesion of surgical drapes and medical dressings to skin prepped with the antimicrobial skin prep solution of at least about 20 N/dm when tested according to a 90° Peel Adhesion Test Method described herein. 19. The antimicrobial skin prep solution of claim 1, wherein adhesion of surgical drapes and medical dressings to skin prepped with the antimicrobial skin prep solution is at least about 25 N/dm when tested according to a 90° Peel Adhesion Test Method described herein. 20. The antimicrobial skin prep solution of claim 1, wherein adhesion of surgical drapes and medical dressings to skin prepped with the antimicrobial skin prep solution is at least about 35 N/dm when tested according to a 90° Peel Adhesion Test Method described herein. 21. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive is skin-compatible. 22. An applicator comprising the antimicrobial skin prep solution of claim 1 in one or multiple parts. 23. A method of disinfecting a skin surface, comprising steps of:
applying the antimicrobial skin prep solution of claim 1 to the skin surface to provide a disinfected skin surface; and allowing the disinfected skin surface to dry. 24. The method of claim 23, wherein the skin surface has essentially no apparent tack after it is dry. 25. A method of sterilizing a skin surface, comprising steps of:
applying the antimicrobial skin prep solution of claim 1 to the skin surface to provide a disinfected skin surface; allowing the disinfected skin surface to dry; and adhering a medical dressing to the disinfected skin surface. 26. The method of claim 25, wherein the medical dressing comprises a surgical incise drape. 27. A coated substrate comprising a reduced skin prep solution formed by:
coating the skin prep solution of claim 1 thereon; and, drying the coating to form the reduced skin prep solution,
wherein the reduced skin prep solution has a liquid consistency. 28. The coated substrate of claim 27, further comprising a medical dressing adhered thereto such that the reduced skin prep solution forms an interfacial tie layer between the substrate and the medical dressing. | Antimicrobial skin prep solutions of the invention comprise: a major amount of at least one organic solvent, wherein at least about 80% by weight based on total weight of the solvent comprises at least one fugitive organic solvent; an antimicrobially effective amount of at least one antimicrobial agent; and an amount of at least one adhesive effective to increase adhesion of surgical drapes and medical dressings to skin prepped with the antimicrobial skin prep solution, wherein the at least one adhesive is distinct from the at least one antimicrobial agent and is a liquid at room temperature. Coated substrates, applicators, and related methods are also disclosed.1. An antimicrobial skin prep solution comprising:
a major amount of at least one organic solvent, wherein at least about 80% by weight based on total weight of the solvent comprises at least one fugitive organic solvent; an antimicrobially effective amount of at least one antimicrobial agent; and an amount of at least one adhesive effective to increase adhesion of surgical drapes and medical dressings to skin prepped with the antimicrobial skin prep solution, wherein the at least one adhesive is distinct from the at least one antimicrobial agent and is a liquid at room temperature. 2. The antimicrobial skin prep solution of claim 1, wherein the amount of at least one adhesive effective to increase adhesion of surgical drapes and medical dressings to skin prepped with the antimicrobial skin prep solution is about 2% by weight of the skin prep solution. 3. The antimicrobial skin prep solution of claim 1, wherein the amount of at least one adhesive effective to increase adhesion of surgical drapes and medical dressings to skin prepped with the antimicrobial skin prep solution is about 5.5% by weight of the skin prep solution. 4. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive is a hydrogel in the skin prep solution. 5. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive has a room temperature Brookfield viscosity of less than about 10,000 centiPoise. 6. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive has a room temperature Brookfield viscosity of less than about 5,000 centiPoise. 7. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive has a room temperature Brookfield viscosity of less than about 2,000 centiPoise. 8. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive has a room temperature Brookfield viscosity of about 400 centiPoise to about 1,500 centiPoise. 9. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive is based on (meth)acrylate chemistry. 10. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive is based on monomers that are essentially free of water-soluble monomers. 11. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive is a homopolymer. 12. The antimicrobial skin prep solution of claim 1, wherein the antimicrobial agent comprises chlorhexidine free base. 13. The antimicrobial skin prep solution of claim 1, wherein the antimicrobial agent comprises a chlorhexidine salt. 14. The antimicrobial skin prep solution of claim 1, wherein the antimicrobial agent comprises chlorhexidine gluconate. 15. The antimicrobial skin prep solution of claim 1, wherein at least about 2% by weight chlorhexidine salt is present in the skin prep solution. 16. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive comprises polar functional groups. 17. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive provides an increase in adhesion of surgical drapes and medical dressings to skin prepped with the antimicrobial skin prep solution of at least about 10 N/dm when tested according to a 90° Peel Adhesion Test Method described herein. 18. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive provides an increase in adhesion of surgical drapes and medical dressings to skin prepped with the antimicrobial skin prep solution of at least about 20 N/dm when tested according to a 90° Peel Adhesion Test Method described herein. 19. The antimicrobial skin prep solution of claim 1, wherein adhesion of surgical drapes and medical dressings to skin prepped with the antimicrobial skin prep solution is at least about 25 N/dm when tested according to a 90° Peel Adhesion Test Method described herein. 20. The antimicrobial skin prep solution of claim 1, wherein adhesion of surgical drapes and medical dressings to skin prepped with the antimicrobial skin prep solution is at least about 35 N/dm when tested according to a 90° Peel Adhesion Test Method described herein. 21. The antimicrobial skin prep solution of claim 1, wherein the at least one adhesive is skin-compatible. 22. An applicator comprising the antimicrobial skin prep solution of claim 1 in one or multiple parts. 23. A method of disinfecting a skin surface, comprising steps of:
applying the antimicrobial skin prep solution of claim 1 to the skin surface to provide a disinfected skin surface; and allowing the disinfected skin surface to dry. 24. The method of claim 23, wherein the skin surface has essentially no apparent tack after it is dry. 25. A method of sterilizing a skin surface, comprising steps of:
applying the antimicrobial skin prep solution of claim 1 to the skin surface to provide a disinfected skin surface; allowing the disinfected skin surface to dry; and adhering a medical dressing to the disinfected skin surface. 26. The method of claim 25, wherein the medical dressing comprises a surgical incise drape. 27. A coated substrate comprising a reduced skin prep solution formed by:
coating the skin prep solution of claim 1 thereon; and, drying the coating to form the reduced skin prep solution,
wherein the reduced skin prep solution has a liquid consistency. 28. The coated substrate of claim 27, further comprising a medical dressing adhered thereto such that the reduced skin prep solution forms an interfacial tie layer between the substrate and the medical dressing. | 1,600 |
1,314 | 12,527,417 | 1,635 | The present invention provides 5′-substituted-2′-F nucleoside analogs and oligomeric compounds comprising these nucleoside analogs. In one preferred embodiment the nucleoside analogs have either (R) or (5)-chirality at the 5′-position. These nucleoside analogs are expected to be useful for enhancing properties of oligomeric compounds including nuclease resistance. | 1. A compound having the formula:
wherein:
Bx is an optionally modified heterocyclic base moiety;
T1 is H or a hydroxyl protecting group;
T2 is H, a hydroxyl protecting group or a reactive phosphorus group;
Z is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, substituted C1-C6 alkyl, substituted C2-C6 alkenyl or substituted C2-C6 alkynyl, and
wherein each of the substituted groups, is, independently, mono or poly substituted with optionally protected substituent groups independently selected from halogen, oxo, hydroxyl, OJ1, NJ1J2, SJ1, N3, OC(═X)J1, OC(═X)NJ1J2, NJ3C(═X)NJ1J2 and CN, wherein each J1, J2 and J3 is, independently, H or C1-C6 alkyl, and X is O, S or NJ1. 2. The compound of claim 1 wherein Z is methyl, ethyl, vinyl, hydroxymethyl, aminomethylene, methoxymethylene, allyl, or propyl. 3. The compound of claim 2 wherein Z is methyl. 4. The compound of claim 1 having the configuration: 5. The compound of claim 1 having the configuration: 6. The compound of claim 1 wherein at least one of T1 and T2 is a hydroxyl protecting group. 7. The compound of claim 6 wherein each of said hydroxyl protecting groups is, independently, selected from acetyl, benzyl, benzoyl, 2,6-dichlorobenzyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, mesylate, tosylate, dimethoxytrityl (DMT), 9-phenylxanthine-9-yl (Pixyl) and 9-(p-methoxyphenyl)xanthine-9-yl (MOX). 8. The compound of claim 1 wherein T1 is a hydroxyl protecting group selected from acetyl, benzyl, t-butyldimethylsilyl, t-butyldiphenylsilyl and dimethoxytrityl. 9. The compound of claim 1 wherein T2 is a reactive phosphorus group. 10. The compound of claim 10 wherein said reactive phosphorus group is diisopropylcyanoethoxy phosphoramidite or H-phosphonate. 11. The compound of claim 1 wherein said T1 is 4,4′-dimethoxytrityl. 12. The compound of claim 11 wherein T2 is diisopropylcyanoethoxy phosphoramidite. 13. The compound of claim 1 wherein Bx is a pyrimidine, modified pyrimidine, purine or a modified purine. 14. The compound of claim 13 wherein Bx is uracil, 5-methyluracil, 5-thiazolo-uracil, 2-thio-uracil, 5-propynyl-uracil, thymine, 2′-thio-thymine, cytosine, 5-methylcytosine, 5-thiazolo-cytosine, 5-propynyl-cytosine, adenine, guanine or 2,6-diaminopurine. 15. The compound of claim 14 wherein Bx is uracil, 5-methyluracil, 5-propynyl-uracil, thymine, cytosine, 5-methylcytosine, 5-propynyl-cytosine, adenine or guanine. 16. An oligomeric compound comprising at least one monomer having formula I:
wherein independently for each of said at least one monomer of formula I:
Bx is an optionally modified heterocyclic base moiety;
T3 is hydroxyl, a protected hydroxyl, a phosphate moiety, a linked conjugate group or an internucleoside linking group attaching said monomer of formula I to a nucleoside, a nucleotide, a monomeric subunit, an oligonucleoside, an oligonucleotide or an oligomeric compound;
each T4 is, independently, is H, a hydroxyl protecting group, a linked conjugate group or an internucleoside linking group attaching said monomer of formula I to a nucleoside, a nucleotide, a monomeric subunit, an oligonucleoside, an oligonucleotide or an oligomeric compound;
wherein at least one of T3 and T4 is an internucleoside linking group attaching said monomer of formula I to a nucleoside, a nucleotide, a monomeric subunit, an oligonucleoside, an oligonucleotide, or an oligomeric compound;
Z is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, substituted C1-C6 alkyl, substituted C2-C6 alkenyl or substituted C2-C6 alkynyl, and
wherein each of the substituted groups, is, independently, mono or poly substituted with optionally protected substituent groups independently selected from halogen, oxo, hydroxyl, OJ1, NJ1J2, SJ1, N3, OC(═X)J1, OC(═X)NJ1J2, NJ3C(═X)NJ1J2 and CN, wherein each J1, J2 and J3 is, independently, H or C1-C6 alkyl, and X is O, S or NJ1. 17. The oligomeric compound of claim 16 comprising a plurality of monomers of formula I. 18. The oligomeric compound of claim 16 wherein each Z is, independently, methyl, ethyl, vinyl, hydroxymethyl, aminomethyl, methoxymethyl, allyl, or propyl. 19. The oligomeric compound of claim 16 wherein at least one Z is methyl. 20. The oligomeric compound of claim 19 wherein each Z is methyl. 21. The oligomeric compound of claim 16 wherein each Bx is, independently selected from uracil, 5-methyluracil, 5-propynyl-uracil, thymine, cytosine, 5-methylcytosine, 5-propynyl-cytosine, adenine and guanine. 22. The oligomeric compound of claim 16 wherein at least one monomer of formula I has the configuration: 23. The oligomeric compound of claim 22 wherein each monomer of formula I has said configuration. 24. The oligomeric compound of claim 16 wherein at least one monomer of formula I has the configuration: 25. The oligomeric compound of claim 24 wherein each monomer of formula I has said configuration. 26. The oligomeric compound of claim 16 wherein one T3 is H or a hydroxyl protecting group. 27. The oligomeric compound of claim 16 wherein one T3 is a phosphate group, substituted phosphate group, phosphorothioate group or a substituted phosphorothioate group. 28. The oligomeric compound of claim 16 wherein one T4 is H or a hydroxyl protecting group. 29. The oligomeric compound of claim 16 comprising at least one region of at least two contiguous monomers of formula I. 30. The oligomeric compound of claim 29 comprising at least two regions of at least two contiguous monomers of formula I. 31. The oligomeric compound of claim 30 comprising a gapped oligomeric compound. 32. The oligomeric compound claim 31 further comprising at least one region of from about 8 to about 14 contiguous β-D-2′-deoxyribofuranosyl nucleosides. 33. The oligomeric compound of claim 32 wherein said region of contiguous β-D-2′-deoxyribofuranosyl nucleosides is from about 8 to about 11 nucleosides. 34. The oligomeric compound of claim 16 comprising a first region of from 2 to 3 contiguous monomers, an optional third region having 1 monomer or 2 contiguous monomers, and a second region located between said first and said third regions comprising from 8 to 14 β-D-2′-deoxyribofuranosyl nucleosides wherein each of said monomers is a monomer of formula I. 35. The oligomeric compound of claim 34 wherein said second region comprises from 8 to 11 β-D-2′-deoxyribofuranosyl nucleosides. 36. The oligomeric compound of claim 34 comprising said third region having 2 contiguous monomers of formula I. 37. The oligomeric compound of claim 34 comprising said third region having one monomer of formula I. 38. The oligomeric compound of claim 34 where the Z group for each of said monomers of formula I are in the R configuration. 39. The oligomeric compound of claim 38 wherein each Z is methyl. 40. The oligomeric compound of claim 34 where the Z group for each of said monomers of formula I are in the S configuration. 41. The oligomeric compound of claim 40 wherein each Z is methyl. 42. The oligomeric compound of claim 16 comprising from about 8 to about 40 nucleosides and/or monomers in length. 43. The oligomeric compound of claim 16 comprising from about 8 to about 20 nucleosides and/or monomers in length. 44. The oligomeric compound of claim 16 comprising from about 10 to about 16 nucleosides and/or monomers in length. 45. The oligomeric compound of claim 16 comprising from about 10 to about 14 nucleosides and/or monomers in length. 46. A method of reducing target mRNA comprising contacting one or more cells, a tissue or an animal with an oligomeric compound of claim 16. 47. A composition comprising first and second chemically synthesized oligomeric compounds, wherein:
the first oligomeric compound is fully complementary to the second oligomeric compound; the first oligomeric compound is fully complementary to a selected nucleic acid target; at least one of said first and second oligomeric compounds comprises at least one monomer having formula I:
wherein independently for each of said at least one monomer of formula I:
Bx is an optionally modified heterocyclic base moiety;
T3 is hydroxyl, a protected hydroxyl, a phosphate moiety, a linked conjugate group or an internucleoside linking group attaching said monomer of formula I to a nucleoside, a nucleotide, a monomeric subunit, an oligonucleoside, an oligonucleotide or an oligomeric compound;
each T4 is, independently, is H, a hydroxyl protecting group, a linked conjugate group or an internucleoside linking group attaching said monomer of formula I to a nucleoside, a nucleotide, a monomeric subunit, an oligonucleoside, an oligonucleotide or an oligomeric compound;
wherein at least one of T3 and T4 is an internucleoside linking group attaching said monomer of formula I to a nucleoside, a nucleotide, a monomeric subunit, an oligonucleoside, an oligonucleotide, or an oligomeric compound;
Z is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, substituted C1-C6 alkyl, substituted C2-C6 alkenyl or substituted C2-C6 alkynyl, and
wherein each of the substituted groups, is, independently, mono or poly substituted with optionally protected substituent groups independently selected from halogen, oxo, hydroxyl, OJ1, NJ1J2, SJ1, N3, OC(═X)J1, OC(═X)NJ1J2, NJ3C(═X)NJ1J2 and CN, wherein each J1, J2 and J3 is, independently, H or C1-C6 alkyl, and X is O, S or NJ1. 48. The composition of claim 47 comprising a plurality of monomers of formula I. 49. The composition of claim 47 wherein each Z is, independently, methyl, ethyl, vinyl, hydroxymethyl, aminomethyl, methoxymethyl, allyl, or propyl. 50. The composition of claim 47 wherein at least one Z is methyl. 51. The composition of claim 50 wherein each Z is methyl. 52. The composition of claim 47 wherein each Bx is, independently selected from uracil, 5-methyluracil, 5-propynyl-uracil, thymine, cytosine, 5-methylcytosine, 5-propynyl-cytosine, adenine and guanine. 53. The composition of claim 47 wherein at least one monomer of formula I has the configuration: 54. The composition of claim 53 wherein each monomer of formula I has said configuration. 55. The composition of claim 47 wherein at least one monomer of formula I has the configuration: 56. The composition of claim 55 wherein each monomer of formula I has said configuration. 57. The composition of claim 47 wherein the first strand is an antisense strand and the second strand is a sense strand. 58. The composition of claim 57 comprising monomers of formula I in at least one strand wherein said strand comprises an alternating motif, a positional motif, a hemimer motif or a gapped motif. 59. The composition of claim 58 wherein the strand comprising an alternating motif, a positional motif or a gapped motif is the antisense strand. 60. The composition of claim 58 wherein the strand comprising an alternating motif, a positional motif or a gapped motif is the sense strand. 61. The composition of claim 47 further comprising a phosphate moiety. 62. The composition of claim 47 wherein each of said first and second oligomeric compounds comprises from about 17 to about 26 nucleosides and/or monomers in length. 63. The composition of claim 47 wherein each of said first and second oligomeric compounds comprises from about 19 to about 23 nucleosides and/or monomers in length. 64. The composition of claim 47 wherein each of said first and second oligomeric compounds comprises from about 19 to about 21 nucleosides and/or monomers in length. 65. A method of reducing target mRNA comprising contacting one or more cells, a tissue or an animal with a composition of claim 47. | The present invention provides 5′-substituted-2′-F nucleoside analogs and oligomeric compounds comprising these nucleoside analogs. In one preferred embodiment the nucleoside analogs have either (R) or (5)-chirality at the 5′-position. These nucleoside analogs are expected to be useful for enhancing properties of oligomeric compounds including nuclease resistance.1. A compound having the formula:
wherein:
Bx is an optionally modified heterocyclic base moiety;
T1 is H or a hydroxyl protecting group;
T2 is H, a hydroxyl protecting group or a reactive phosphorus group;
Z is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, substituted C1-C6 alkyl, substituted C2-C6 alkenyl or substituted C2-C6 alkynyl, and
wherein each of the substituted groups, is, independently, mono or poly substituted with optionally protected substituent groups independently selected from halogen, oxo, hydroxyl, OJ1, NJ1J2, SJ1, N3, OC(═X)J1, OC(═X)NJ1J2, NJ3C(═X)NJ1J2 and CN, wherein each J1, J2 and J3 is, independently, H or C1-C6 alkyl, and X is O, S or NJ1. 2. The compound of claim 1 wherein Z is methyl, ethyl, vinyl, hydroxymethyl, aminomethylene, methoxymethylene, allyl, or propyl. 3. The compound of claim 2 wherein Z is methyl. 4. The compound of claim 1 having the configuration: 5. The compound of claim 1 having the configuration: 6. The compound of claim 1 wherein at least one of T1 and T2 is a hydroxyl protecting group. 7. The compound of claim 6 wherein each of said hydroxyl protecting groups is, independently, selected from acetyl, benzyl, benzoyl, 2,6-dichlorobenzyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, mesylate, tosylate, dimethoxytrityl (DMT), 9-phenylxanthine-9-yl (Pixyl) and 9-(p-methoxyphenyl)xanthine-9-yl (MOX). 8. The compound of claim 1 wherein T1 is a hydroxyl protecting group selected from acetyl, benzyl, t-butyldimethylsilyl, t-butyldiphenylsilyl and dimethoxytrityl. 9. The compound of claim 1 wherein T2 is a reactive phosphorus group. 10. The compound of claim 10 wherein said reactive phosphorus group is diisopropylcyanoethoxy phosphoramidite or H-phosphonate. 11. The compound of claim 1 wherein said T1 is 4,4′-dimethoxytrityl. 12. The compound of claim 11 wherein T2 is diisopropylcyanoethoxy phosphoramidite. 13. The compound of claim 1 wherein Bx is a pyrimidine, modified pyrimidine, purine or a modified purine. 14. The compound of claim 13 wherein Bx is uracil, 5-methyluracil, 5-thiazolo-uracil, 2-thio-uracil, 5-propynyl-uracil, thymine, 2′-thio-thymine, cytosine, 5-methylcytosine, 5-thiazolo-cytosine, 5-propynyl-cytosine, adenine, guanine or 2,6-diaminopurine. 15. The compound of claim 14 wherein Bx is uracil, 5-methyluracil, 5-propynyl-uracil, thymine, cytosine, 5-methylcytosine, 5-propynyl-cytosine, adenine or guanine. 16. An oligomeric compound comprising at least one monomer having formula I:
wherein independently for each of said at least one monomer of formula I:
Bx is an optionally modified heterocyclic base moiety;
T3 is hydroxyl, a protected hydroxyl, a phosphate moiety, a linked conjugate group or an internucleoside linking group attaching said monomer of formula I to a nucleoside, a nucleotide, a monomeric subunit, an oligonucleoside, an oligonucleotide or an oligomeric compound;
each T4 is, independently, is H, a hydroxyl protecting group, a linked conjugate group or an internucleoside linking group attaching said monomer of formula I to a nucleoside, a nucleotide, a monomeric subunit, an oligonucleoside, an oligonucleotide or an oligomeric compound;
wherein at least one of T3 and T4 is an internucleoside linking group attaching said monomer of formula I to a nucleoside, a nucleotide, a monomeric subunit, an oligonucleoside, an oligonucleotide, or an oligomeric compound;
Z is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, substituted C1-C6 alkyl, substituted C2-C6 alkenyl or substituted C2-C6 alkynyl, and
wherein each of the substituted groups, is, independently, mono or poly substituted with optionally protected substituent groups independently selected from halogen, oxo, hydroxyl, OJ1, NJ1J2, SJ1, N3, OC(═X)J1, OC(═X)NJ1J2, NJ3C(═X)NJ1J2 and CN, wherein each J1, J2 and J3 is, independently, H or C1-C6 alkyl, and X is O, S or NJ1. 17. The oligomeric compound of claim 16 comprising a plurality of monomers of formula I. 18. The oligomeric compound of claim 16 wherein each Z is, independently, methyl, ethyl, vinyl, hydroxymethyl, aminomethyl, methoxymethyl, allyl, or propyl. 19. The oligomeric compound of claim 16 wherein at least one Z is methyl. 20. The oligomeric compound of claim 19 wherein each Z is methyl. 21. The oligomeric compound of claim 16 wherein each Bx is, independently selected from uracil, 5-methyluracil, 5-propynyl-uracil, thymine, cytosine, 5-methylcytosine, 5-propynyl-cytosine, adenine and guanine. 22. The oligomeric compound of claim 16 wherein at least one monomer of formula I has the configuration: 23. The oligomeric compound of claim 22 wherein each monomer of formula I has said configuration. 24. The oligomeric compound of claim 16 wherein at least one monomer of formula I has the configuration: 25. The oligomeric compound of claim 24 wherein each monomer of formula I has said configuration. 26. The oligomeric compound of claim 16 wherein one T3 is H or a hydroxyl protecting group. 27. The oligomeric compound of claim 16 wherein one T3 is a phosphate group, substituted phosphate group, phosphorothioate group or a substituted phosphorothioate group. 28. The oligomeric compound of claim 16 wherein one T4 is H or a hydroxyl protecting group. 29. The oligomeric compound of claim 16 comprising at least one region of at least two contiguous monomers of formula I. 30. The oligomeric compound of claim 29 comprising at least two regions of at least two contiguous monomers of formula I. 31. The oligomeric compound of claim 30 comprising a gapped oligomeric compound. 32. The oligomeric compound claim 31 further comprising at least one region of from about 8 to about 14 contiguous β-D-2′-deoxyribofuranosyl nucleosides. 33. The oligomeric compound of claim 32 wherein said region of contiguous β-D-2′-deoxyribofuranosyl nucleosides is from about 8 to about 11 nucleosides. 34. The oligomeric compound of claim 16 comprising a first region of from 2 to 3 contiguous monomers, an optional third region having 1 monomer or 2 contiguous monomers, and a second region located between said first and said third regions comprising from 8 to 14 β-D-2′-deoxyribofuranosyl nucleosides wherein each of said monomers is a monomer of formula I. 35. The oligomeric compound of claim 34 wherein said second region comprises from 8 to 11 β-D-2′-deoxyribofuranosyl nucleosides. 36. The oligomeric compound of claim 34 comprising said third region having 2 contiguous monomers of formula I. 37. The oligomeric compound of claim 34 comprising said third region having one monomer of formula I. 38. The oligomeric compound of claim 34 where the Z group for each of said monomers of formula I are in the R configuration. 39. The oligomeric compound of claim 38 wherein each Z is methyl. 40. The oligomeric compound of claim 34 where the Z group for each of said monomers of formula I are in the S configuration. 41. The oligomeric compound of claim 40 wherein each Z is methyl. 42. The oligomeric compound of claim 16 comprising from about 8 to about 40 nucleosides and/or monomers in length. 43. The oligomeric compound of claim 16 comprising from about 8 to about 20 nucleosides and/or monomers in length. 44. The oligomeric compound of claim 16 comprising from about 10 to about 16 nucleosides and/or monomers in length. 45. The oligomeric compound of claim 16 comprising from about 10 to about 14 nucleosides and/or monomers in length. 46. A method of reducing target mRNA comprising contacting one or more cells, a tissue or an animal with an oligomeric compound of claim 16. 47. A composition comprising first and second chemically synthesized oligomeric compounds, wherein:
the first oligomeric compound is fully complementary to the second oligomeric compound; the first oligomeric compound is fully complementary to a selected nucleic acid target; at least one of said first and second oligomeric compounds comprises at least one monomer having formula I:
wherein independently for each of said at least one monomer of formula I:
Bx is an optionally modified heterocyclic base moiety;
T3 is hydroxyl, a protected hydroxyl, a phosphate moiety, a linked conjugate group or an internucleoside linking group attaching said monomer of formula I to a nucleoside, a nucleotide, a monomeric subunit, an oligonucleoside, an oligonucleotide or an oligomeric compound;
each T4 is, independently, is H, a hydroxyl protecting group, a linked conjugate group or an internucleoside linking group attaching said monomer of formula I to a nucleoside, a nucleotide, a monomeric subunit, an oligonucleoside, an oligonucleotide or an oligomeric compound;
wherein at least one of T3 and T4 is an internucleoside linking group attaching said monomer of formula I to a nucleoside, a nucleotide, a monomeric subunit, an oligonucleoside, an oligonucleotide, or an oligomeric compound;
Z is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, substituted C1-C6 alkyl, substituted C2-C6 alkenyl or substituted C2-C6 alkynyl, and
wherein each of the substituted groups, is, independently, mono or poly substituted with optionally protected substituent groups independently selected from halogen, oxo, hydroxyl, OJ1, NJ1J2, SJ1, N3, OC(═X)J1, OC(═X)NJ1J2, NJ3C(═X)NJ1J2 and CN, wherein each J1, J2 and J3 is, independently, H or C1-C6 alkyl, and X is O, S or NJ1. 48. The composition of claim 47 comprising a plurality of monomers of formula I. 49. The composition of claim 47 wherein each Z is, independently, methyl, ethyl, vinyl, hydroxymethyl, aminomethyl, methoxymethyl, allyl, or propyl. 50. The composition of claim 47 wherein at least one Z is methyl. 51. The composition of claim 50 wherein each Z is methyl. 52. The composition of claim 47 wherein each Bx is, independently selected from uracil, 5-methyluracil, 5-propynyl-uracil, thymine, cytosine, 5-methylcytosine, 5-propynyl-cytosine, adenine and guanine. 53. The composition of claim 47 wherein at least one monomer of formula I has the configuration: 54. The composition of claim 53 wherein each monomer of formula I has said configuration. 55. The composition of claim 47 wherein at least one monomer of formula I has the configuration: 56. The composition of claim 55 wherein each monomer of formula I has said configuration. 57. The composition of claim 47 wherein the first strand is an antisense strand and the second strand is a sense strand. 58. The composition of claim 57 comprising monomers of formula I in at least one strand wherein said strand comprises an alternating motif, a positional motif, a hemimer motif or a gapped motif. 59. The composition of claim 58 wherein the strand comprising an alternating motif, a positional motif or a gapped motif is the antisense strand. 60. The composition of claim 58 wherein the strand comprising an alternating motif, a positional motif or a gapped motif is the sense strand. 61. The composition of claim 47 further comprising a phosphate moiety. 62. The composition of claim 47 wherein each of said first and second oligomeric compounds comprises from about 17 to about 26 nucleosides and/or monomers in length. 63. The composition of claim 47 wherein each of said first and second oligomeric compounds comprises from about 19 to about 23 nucleosides and/or monomers in length. 64. The composition of claim 47 wherein each of said first and second oligomeric compounds comprises from about 19 to about 21 nucleosides and/or monomers in length. 65. A method of reducing target mRNA comprising contacting one or more cells, a tissue or an animal with a composition of claim 47. | 1,600 |
1,315 | 13,860,897 | 1,644 | An anti-MHC removal device includes a serologically active, soluble MHC moiety covalently coupled to a solid support. Methods of production include covalently coupling the serologically active, soluble MHC moiety to the solid support. Methods of use of the anti-MHC removal device include contacting a biological sample with the device so that antibodies specific for the MHC moiety are removed from the biological sample. | 1. An anti-MHC removal device, comprising:
a solid support; a serologically active, soluble MHC moiety covalently coupled to the solid support and disposed on a surface of the anti-MHC removal device, the MHC moiety capable of interacting with a sample brought into contact with the surface of the device having the serologically active, soluble MHC moiety disposed thereon, whereby antibodies specific for the MHC moiety present in the sample will bind thereto, resulting in removal of said antibodies from the sample. 2. The anti-MHC removal device of claim 1, wherein the MHC moiety is further defined as a soluble class I HLA trimolecular complex produced by a method comprising the steps of:
cloning a nucleotide segment into a mammalian expression vector, the nucleotide segment encoding a desired individual class I MHC heavy chain that has the coding regions encoding the cytoplasmic and transmembrane domains of the desired individual class I MHC heavy chain allele removed such that the nucleotide segment encodes a truncated, soluble form of the desired individual class I MHC heavy chain molecule, thereby forming a construct that encodes the desired individual soluble class I MHC heavy chain molecule; transfecting a mammalian cell line with the construct to provide a mammalian cell line expressing a construct that encodes a recombinant, individual soluble class I MHC heavy chain molecule, wherein the mammalian cell line is able to naturally process proteins into peptide ligands for loading into antigen binding grooves of MHC molecules, and wherein the mammalian cell line expresses beta-2-microglobulin; culturing the mammalian cell line under conditions which allow for expression of the recombinant individual soluble class I MHC heavy chain molecule from the construct, such conditions also allowing for endogenous loading of a peptide ligand into the antigen binding groove of each recombinant, individual soluble class I MHC heavy chain molecule and non-covalent association of native, endogenously produced beta-2-microglobulin to form the individual soluble class I MHC trimolecular complexes prior to secretion of the individual soluble class I MHC trimolecular complexes from the cell; harvesting the soluble class I MHC trimolecular complexes from the culture while retaining the mammalian cell line in culture for production of additional soluble class I MHC trimolecular complexes; and purifying the individual, soluble class I MHC trimolecular complexes substantially away from other proteins, wherein the individual soluble class I MHC trimolecular complexes maintain the physical, functional and antigenic integrity of the native class I MHC trimolecular complex, and wherein each trimolecular complex so purified comprises identical recombinant, individual soluble class I MHC heavy chain molecules. 3. The anti-MHC removal device of claim 1, wherein the MHC moiety is further defined as a soluble class II HLA trimolecular complex produced by a method comprising the steps of:
inserting a first isolated nucleic acid segment and a second isolated nucleic acid segment into a mammalian cell line, the first isolated nucleic acid segment encoding a soluble form of an alpha chain of a HLA class II molecule having a first domain of a super secondary structural motif attached thereto, and the second isolated nucleic acid segment encoding a soluble form of a beta chain of the HLA class II molecule having a second domain of the super secondary structural motif attached thereto, wherein the mammalian cell line is a non-human mammalian cell line or a human cell line that does not express endogenous HLA class II, and wherein the mammalian cell line comprises glycosylation mechanisms required for glycosylation of proteins produced therein and chaperone complexes required for peptide ligand loading into HLA class II molecules; culturing the recombinant mammalian cell line under conditions that allow for expression of the soluble class II alpha and beta chains, association of the soluble class II alpha and beta chains through the first and second domains of the super secondary structural motif, glycosylation of the soluble class II alpha and beta chains, and loading of an antigen binding groove formed from the soluble class II alpha and beta chains with an endogenously produced, non-covalently associated peptide ligand, thereby producing soluble class II trimolecular complexes; isolating the soluble class II trimolecular complexes secreted from the recombinant mammalian cell line; and purifying the soluble class II trimolecular complexes substantially away from other proteins. 4. The anti-MHC removal device of claim 1, wherein the solid support is selected from the group consisting of a well, a bead, a membrane, a microtiter plate, a matrix, a pore, plastic, glass, a polymer, a polysaccharide, nylon, nitrocellulose, a paramagnetic compound, and combinations thereof. 5. The anti-MHC removal device of claim 4, wherein the solid support is further defined as an N-hydroxysuccinimide (NHS)-activated SEPHAROSE® matrix. 6. The anti-MHC removal device of claim 1, wherein the soluble MHC moiety is coupled to the solid support via a covalent amide bond formed between a primary amino group contained within the HLA moiety and an ester group contained in the solid support. 7. The anti-MHC removal device of claim 1, wherein the solid support further comprises a spacer arm. 8. The anti-MHC removal device of claim 1, further defined as a human use device. 9. The anti-MHC removal device of claim 8, further defined as an extracorporeal plasmapheresis human use device. 10. A kit containing the anti-MHC removal device of claim 1. 11. The kit of claim 10, further comprising at least one reagent for elution of antibodies from the anti-MHC removal device. 12. A method of removing anti-HLA antibodies from a biological sample, the method comprising the steps of:
(a) contacting a biological sample with the anti-MHC removal device of claim 1, whereby antibodies specific for the MHC moiety present on a surface of the anti-MHC removal device are removed from the biological sample; and (b) recovering the biological sample, whereby the antibodies specific for the MHC moiety are substantially reduced in the recovered biological sample. 13. The method of claim 12, wherein the biological sample is selected from the group consisting of serum, tissue, blood, plasma, cerebrospinal fluid, tears, saliva, lymph, dialysis fluid, organ or tissue culture derived fluids, fluids extracted from physiological tissues, and combinations thereof. 14. The method of claim 12, further comprising repeating steps (a) and (b). 15. The method of claim 12, further comprising the step of eluting antibodies from the anti-MHC removal device. 16. The method of claim 12, wherein the MHC moiety is a class I MHC trimolecular complex. 17. The method of claim 12, wherein the MHC moiety is a class II MHC trimolecular complex. 18. The method of claim 12, wherein the solid support of the anti-MHC removal device is selected from the group consisting of a well, a bead, a membrane, a microtiter plate, a matrix, a pore, plastic, glass, a polymer, a polysaccharide, nylon, nitrocellulose, a paramagnetic compound, and combinations thereof. 19. The method of claim 18, wherein the solid support is further defined as an N-hydroxysuccinimide (NHS)-activated SEPHAROSE® matrix. 20. The method of claim 12, further comprising the step of placing the recovered biological sample back into the patient. | An anti-MHC removal device includes a serologically active, soluble MHC moiety covalently coupled to a solid support. Methods of production include covalently coupling the serologically active, soluble MHC moiety to the solid support. Methods of use of the anti-MHC removal device include contacting a biological sample with the device so that antibodies specific for the MHC moiety are removed from the biological sample.1. An anti-MHC removal device, comprising:
a solid support; a serologically active, soluble MHC moiety covalently coupled to the solid support and disposed on a surface of the anti-MHC removal device, the MHC moiety capable of interacting with a sample brought into contact with the surface of the device having the serologically active, soluble MHC moiety disposed thereon, whereby antibodies specific for the MHC moiety present in the sample will bind thereto, resulting in removal of said antibodies from the sample. 2. The anti-MHC removal device of claim 1, wherein the MHC moiety is further defined as a soluble class I HLA trimolecular complex produced by a method comprising the steps of:
cloning a nucleotide segment into a mammalian expression vector, the nucleotide segment encoding a desired individual class I MHC heavy chain that has the coding regions encoding the cytoplasmic and transmembrane domains of the desired individual class I MHC heavy chain allele removed such that the nucleotide segment encodes a truncated, soluble form of the desired individual class I MHC heavy chain molecule, thereby forming a construct that encodes the desired individual soluble class I MHC heavy chain molecule; transfecting a mammalian cell line with the construct to provide a mammalian cell line expressing a construct that encodes a recombinant, individual soluble class I MHC heavy chain molecule, wherein the mammalian cell line is able to naturally process proteins into peptide ligands for loading into antigen binding grooves of MHC molecules, and wherein the mammalian cell line expresses beta-2-microglobulin; culturing the mammalian cell line under conditions which allow for expression of the recombinant individual soluble class I MHC heavy chain molecule from the construct, such conditions also allowing for endogenous loading of a peptide ligand into the antigen binding groove of each recombinant, individual soluble class I MHC heavy chain molecule and non-covalent association of native, endogenously produced beta-2-microglobulin to form the individual soluble class I MHC trimolecular complexes prior to secretion of the individual soluble class I MHC trimolecular complexes from the cell; harvesting the soluble class I MHC trimolecular complexes from the culture while retaining the mammalian cell line in culture for production of additional soluble class I MHC trimolecular complexes; and purifying the individual, soluble class I MHC trimolecular complexes substantially away from other proteins, wherein the individual soluble class I MHC trimolecular complexes maintain the physical, functional and antigenic integrity of the native class I MHC trimolecular complex, and wherein each trimolecular complex so purified comprises identical recombinant, individual soluble class I MHC heavy chain molecules. 3. The anti-MHC removal device of claim 1, wherein the MHC moiety is further defined as a soluble class II HLA trimolecular complex produced by a method comprising the steps of:
inserting a first isolated nucleic acid segment and a second isolated nucleic acid segment into a mammalian cell line, the first isolated nucleic acid segment encoding a soluble form of an alpha chain of a HLA class II molecule having a first domain of a super secondary structural motif attached thereto, and the second isolated nucleic acid segment encoding a soluble form of a beta chain of the HLA class II molecule having a second domain of the super secondary structural motif attached thereto, wherein the mammalian cell line is a non-human mammalian cell line or a human cell line that does not express endogenous HLA class II, and wherein the mammalian cell line comprises glycosylation mechanisms required for glycosylation of proteins produced therein and chaperone complexes required for peptide ligand loading into HLA class II molecules; culturing the recombinant mammalian cell line under conditions that allow for expression of the soluble class II alpha and beta chains, association of the soluble class II alpha and beta chains through the first and second domains of the super secondary structural motif, glycosylation of the soluble class II alpha and beta chains, and loading of an antigen binding groove formed from the soluble class II alpha and beta chains with an endogenously produced, non-covalently associated peptide ligand, thereby producing soluble class II trimolecular complexes; isolating the soluble class II trimolecular complexes secreted from the recombinant mammalian cell line; and purifying the soluble class II trimolecular complexes substantially away from other proteins. 4. The anti-MHC removal device of claim 1, wherein the solid support is selected from the group consisting of a well, a bead, a membrane, a microtiter plate, a matrix, a pore, plastic, glass, a polymer, a polysaccharide, nylon, nitrocellulose, a paramagnetic compound, and combinations thereof. 5. The anti-MHC removal device of claim 4, wherein the solid support is further defined as an N-hydroxysuccinimide (NHS)-activated SEPHAROSE® matrix. 6. The anti-MHC removal device of claim 1, wherein the soluble MHC moiety is coupled to the solid support via a covalent amide bond formed between a primary amino group contained within the HLA moiety and an ester group contained in the solid support. 7. The anti-MHC removal device of claim 1, wherein the solid support further comprises a spacer arm. 8. The anti-MHC removal device of claim 1, further defined as a human use device. 9. The anti-MHC removal device of claim 8, further defined as an extracorporeal plasmapheresis human use device. 10. A kit containing the anti-MHC removal device of claim 1. 11. The kit of claim 10, further comprising at least one reagent for elution of antibodies from the anti-MHC removal device. 12. A method of removing anti-HLA antibodies from a biological sample, the method comprising the steps of:
(a) contacting a biological sample with the anti-MHC removal device of claim 1, whereby antibodies specific for the MHC moiety present on a surface of the anti-MHC removal device are removed from the biological sample; and (b) recovering the biological sample, whereby the antibodies specific for the MHC moiety are substantially reduced in the recovered biological sample. 13. The method of claim 12, wherein the biological sample is selected from the group consisting of serum, tissue, blood, plasma, cerebrospinal fluid, tears, saliva, lymph, dialysis fluid, organ or tissue culture derived fluids, fluids extracted from physiological tissues, and combinations thereof. 14. The method of claim 12, further comprising repeating steps (a) and (b). 15. The method of claim 12, further comprising the step of eluting antibodies from the anti-MHC removal device. 16. The method of claim 12, wherein the MHC moiety is a class I MHC trimolecular complex. 17. The method of claim 12, wherein the MHC moiety is a class II MHC trimolecular complex. 18. The method of claim 12, wherein the solid support of the anti-MHC removal device is selected from the group consisting of a well, a bead, a membrane, a microtiter plate, a matrix, a pore, plastic, glass, a polymer, a polysaccharide, nylon, nitrocellulose, a paramagnetic compound, and combinations thereof. 19. The method of claim 18, wherein the solid support is further defined as an N-hydroxysuccinimide (NHS)-activated SEPHAROSE® matrix. 20. The method of claim 12, further comprising the step of placing the recovered biological sample back into the patient. | 1,600 |
1,316 | 15,525,173 | 1,627 | A nanosuspension comprising (a) a pharmaceutical active ingredient or nutraceutical active ingredient having low solubility; (b) at least one alginate selected from the group consisting of (i) sodium alginate having a viscosity of 100 mPa·s or less in a 1% solution in water at 20° C. and (ii) potassium alginate; and (c) water. Also, a drug dosage form prepared from such a nanosuspension. | 1. A nanosuspension comprising (a) a pharmaceutical active ingredient or nutraceutical active ingredient having low solubility; (b) at least one alginate selected from the group consisting of (i) sodium alginate having a viscosity of 100 mPa·s or less in a 1% solution in water at 20° C. and (ii) potassium alginate; and (c) water. 2. The nanosuspension of claim 1 wherein the pharmaceutical active ingredient or nutraceutical active ingredient having low solubility comprises between 0.1 and 10 percent by weight of the nanosuspension. 3. The nanosuspension of claim 2 wherein the pharmaceutical active ingredient or nutraceutical active ingredient having low solubility comprises between 0.5 and 5 percent by weight of the nanosuspension. 4. The nanosuspension of claim 3 wherein the pharmaceutical active ingredient or nutraceutical active ingredient having low solubility comprises between 0.5 and 3 percent by weight of the nanosuspension. 5. The nanosuspension of any of the preceding claims wherein the alginate is present in an amount between 0.1 and 20 percent by weight, based upon the weight of the pharmaceutical active ingredient or nutraceutical active ingredient having low solubility. 6. The nanosuspension of claim 5 wherein the alginate is present in an amount between 0.25 and 5 percent by weight, based upon the weight of the pharmaceutical active ingredient or nutraceutical active ingredient having low solubility. 7. The nanosuspension of claim 6 wherein the alginate is present in an amount between 0.35 and 2 percent by weight, based upon the weight of the pharmaceutical active ingredient or nutraceutical active ingredient having low solubility. 8. The nanosuspension of any of the preceding claims wherein the alginate comprises said sodium alginate. 9. The nanosuspension of any of the preceding claims wherein the alginate comprises said potassium alginate. 10. The nanosuspension of claim 9 wherein the potassium alginate has a viscosity of 500 mPa·s or less in a 1% solution in water at 20° C. 11. The nanosuspension of any of the preceding claims wherein the pharmaceutical active ingredient having low solubility is selected from the group consisting of a nonsteroidal anti-inflammatory drugs, immunosuppressant drugs, atopic dermatitis drugs, calcium channel blockers, angiotensin II antagonists, cholesterol synthesis-inhibiting hypolipidemic agents, cholesterol metabolism- and secretion-promoting hypolipidemic agents, antidiabetic drugs, lipase inhibitors, antifungal agents, hepatoprotective drugs, gastrointestinal drugs, antiplatelet agents, osteoporosis drugs, antiviral drugs, antibiotics, antiasthmatic or antihistamine drugs, hormone drugs and anticancer drugs. 12. The nanosuspension of any of claim 1-10 wherein the pharmaceutical active ingredient having low solubility is selected from the group consisting of acetaminophen, acetylsalicylic acid, ibuprofen, fenbuprofen, fenoprofen, flurbiprofen, indomethacin, naproxen, etodolac, ketoprofen, dexibuprofen, piroxicam, aceclofenac, cyclosporin, tacrolimus, rapamycin, mycophenolate, pimecrolimus, nifedipine, nimodipine, nitrendipine, nilvadipine, felodipine, amlodipine, isradipine, valsartan, eprosartan, irbesartan, candesartan, telmisartan, olmesartan, losartan, atorvastatin, lovastatin, simvastatin, fluvastatin, rosuvastatin, pravastatin, gemfibrozil, fenofibrate, etofibrate, bezafibrate, pioglitazone, rosiglitazone, metformin, orlistat, itraconazole, amphotericin B, terbinafine, nystatin, griseofulvin, fluconazole, ketoconazole, biphenyl dimethyl dicarboxylate, silymarin ursodeoxycholic acid, sofalcone, omeprazole, pantoprazole, famotidine, itopride, mesalazine, cilostazol, clopidogrel, raloxifene, acyclovir, famciclovir, lamivudine, oseltamivir, clarithromycin, ciprofloxacin, cefuroxime, pranlukast, budesonide, fexofenadine, testosterone, prednisolone, estrogen, cortisone, hydrocortisone, dexamethasone, docetaxel, paclitaxel derivatives, doxorubicin, adriamycin, daunomycin, camptothecin, etoposide, teniposide and busulfan; and pharmaceutical derivatives and salts thereof. 13. A pharmaceutical or nutraceutical dosage form produced from the nanosuspension of any of claims 1-12. | A nanosuspension comprising (a) a pharmaceutical active ingredient or nutraceutical active ingredient having low solubility; (b) at least one alginate selected from the group consisting of (i) sodium alginate having a viscosity of 100 mPa·s or less in a 1% solution in water at 20° C. and (ii) potassium alginate; and (c) water. Also, a drug dosage form prepared from such a nanosuspension.1. A nanosuspension comprising (a) a pharmaceutical active ingredient or nutraceutical active ingredient having low solubility; (b) at least one alginate selected from the group consisting of (i) sodium alginate having a viscosity of 100 mPa·s or less in a 1% solution in water at 20° C. and (ii) potassium alginate; and (c) water. 2. The nanosuspension of claim 1 wherein the pharmaceutical active ingredient or nutraceutical active ingredient having low solubility comprises between 0.1 and 10 percent by weight of the nanosuspension. 3. The nanosuspension of claim 2 wherein the pharmaceutical active ingredient or nutraceutical active ingredient having low solubility comprises between 0.5 and 5 percent by weight of the nanosuspension. 4. The nanosuspension of claim 3 wherein the pharmaceutical active ingredient or nutraceutical active ingredient having low solubility comprises between 0.5 and 3 percent by weight of the nanosuspension. 5. The nanosuspension of any of the preceding claims wherein the alginate is present in an amount between 0.1 and 20 percent by weight, based upon the weight of the pharmaceutical active ingredient or nutraceutical active ingredient having low solubility. 6. The nanosuspension of claim 5 wherein the alginate is present in an amount between 0.25 and 5 percent by weight, based upon the weight of the pharmaceutical active ingredient or nutraceutical active ingredient having low solubility. 7. The nanosuspension of claim 6 wherein the alginate is present in an amount between 0.35 and 2 percent by weight, based upon the weight of the pharmaceutical active ingredient or nutraceutical active ingredient having low solubility. 8. The nanosuspension of any of the preceding claims wherein the alginate comprises said sodium alginate. 9. The nanosuspension of any of the preceding claims wherein the alginate comprises said potassium alginate. 10. The nanosuspension of claim 9 wherein the potassium alginate has a viscosity of 500 mPa·s or less in a 1% solution in water at 20° C. 11. The nanosuspension of any of the preceding claims wherein the pharmaceutical active ingredient having low solubility is selected from the group consisting of a nonsteroidal anti-inflammatory drugs, immunosuppressant drugs, atopic dermatitis drugs, calcium channel blockers, angiotensin II antagonists, cholesterol synthesis-inhibiting hypolipidemic agents, cholesterol metabolism- and secretion-promoting hypolipidemic agents, antidiabetic drugs, lipase inhibitors, antifungal agents, hepatoprotective drugs, gastrointestinal drugs, antiplatelet agents, osteoporosis drugs, antiviral drugs, antibiotics, antiasthmatic or antihistamine drugs, hormone drugs and anticancer drugs. 12. The nanosuspension of any of claim 1-10 wherein the pharmaceutical active ingredient having low solubility is selected from the group consisting of acetaminophen, acetylsalicylic acid, ibuprofen, fenbuprofen, fenoprofen, flurbiprofen, indomethacin, naproxen, etodolac, ketoprofen, dexibuprofen, piroxicam, aceclofenac, cyclosporin, tacrolimus, rapamycin, mycophenolate, pimecrolimus, nifedipine, nimodipine, nitrendipine, nilvadipine, felodipine, amlodipine, isradipine, valsartan, eprosartan, irbesartan, candesartan, telmisartan, olmesartan, losartan, atorvastatin, lovastatin, simvastatin, fluvastatin, rosuvastatin, pravastatin, gemfibrozil, fenofibrate, etofibrate, bezafibrate, pioglitazone, rosiglitazone, metformin, orlistat, itraconazole, amphotericin B, terbinafine, nystatin, griseofulvin, fluconazole, ketoconazole, biphenyl dimethyl dicarboxylate, silymarin ursodeoxycholic acid, sofalcone, omeprazole, pantoprazole, famotidine, itopride, mesalazine, cilostazol, clopidogrel, raloxifene, acyclovir, famciclovir, lamivudine, oseltamivir, clarithromycin, ciprofloxacin, cefuroxime, pranlukast, budesonide, fexofenadine, testosterone, prednisolone, estrogen, cortisone, hydrocortisone, dexamethasone, docetaxel, paclitaxel derivatives, doxorubicin, adriamycin, daunomycin, camptothecin, etoposide, teniposide and busulfan; and pharmaceutical derivatives and salts thereof. 13. A pharmaceutical or nutraceutical dosage form produced from the nanosuspension of any of claims 1-12. | 1,600 |
1,317 | 14,240,617 | 1,615 | An adhesive composition comprising silicone adhesives and one or more absorbent fillers such as hydrocolloids is disclosed. The adhesive composition is particularly well suited for use in negative pressure wound therapies. | 1. An adhesive composition comprising:
a polysiloxane adhesive; and one or more absorbent fillers dispersed in the polysiloxane adhesive. 2. The adhesive of claim 1 wherein the polysiloxane adhesive is a one-part adhesive and at least partially crosslinked. 3. The adhesive of claim 1 wherein the polysiloxane adhesive is selected from the group consisting of (i) an adhesive having a solids content of about 60%, a viscosity of about 2600 mPA·s, and which exhibits a rheology at 0.01 rad/sec at 30° C. of about 5×106 P, (ii) an adhesive having a solids content of about 60%, a viscosity of about 1200 mPA·s, and which exhibits a rheology at 0.01 rad/sec at 30° C. of about 5×106 P, and (iii) a combination of (i) and (ii). 4. The adhesive of claim 1 wherein the polysiloxane adhesive constitutes at least about 40% by weight of the adhesive composition. 5. The adhesive of claim 1 wherein the absorbent filler is selected from the group consisting of guar gum, xanthan gum, karaya gum, locus gum, polyvinyl alcohol, pectin, gelatin, carboxymethyl cellulose, high molecular weight carbowax, carboxypolymethylene, maize starch, alginic acid, super absorbent polymers, and combinations thereof. 6. The adhesive of claim 1 wherein the absorbent filler is carboxymethyl cellulose. 7. The adhesive of claim 1 wherein the one or more absorbent fillers constitute from about 5% to about 60% by weight of the adhesive composition. 8. The adhesive of claim 7 wherein the one or more absorbent fillers constitute from about 25% to about 35% by weight of the adhesive composition. 9. The adhesive of claim 1 wherein the adhesive composition further comprises:
at least one tackifier. 10. The adhesive of claim 1 wherein the adhesive composition further comprises:
at least one plasticizer. 11. The adhesive of claim 1 wherein the adhesive composition further comprises:
at least one additive. 12. The adhesive of claim 1 wherein the adhesive composition further comprises:
at least one filler. 13. The adhesive of claim 1 wherein the adhesive composition further comprises:
at least one solvent. 14. An article comprising a layer of an adhesive composition comprising (i) a polysiloxane adhesive and (ii) one or more absorbent fillers dispersed in the polysiloxane adhesive. 15. The article of claim 14 wherein the polysiloxane adhesive is a one-part adhesive and at least partially crosslinked. 16. The article of claim 14 wherein the polysiloxane adhesive is selected from the group consisting of (i) an adhesive having a solids content of about 60%, a viscosity of about 2600 mPA·s, and which exhibits a rheology at 0.01 rad/sec at 30° C. of about 5×106 P, (ii) an adhesive having a solids content of about 60%, a viscosity of about 1200 mPA·s, and which exhibits a rheology at 0.01 rad/sec at 30° C. of about 5×106 P, and (iii) a combination of (i) and (ii). 17. The article of claim 14 wherein the polysiloxane adhesive constitutes at least about 40% by weight of the adhesive composition. 18. The article of claim 14 wherein the absorbent filler is selected from the group consisting of guar gum, xanthan gum, karaya gum, locus gum, polyvinyl alcohol, pectin, gelatin, carboxymethyl cellulose, high molecular weight carbowax, carboxypolymethylene, maize starch, alginic acid, super absorbent polymers, and combinations thereof. 19. The article of claim 14 wherein the absorbent filler is carboxymethyl cellulose. 20. The article of claim 14 wherein the one or more absorbent fillers constitute from about 5% to about 60% by weight of the adhesive composition. 21. The article of claim 20 wherein the one or more absorbent fillers constitute from about 25% to about 35% by weight of the adhesive composition. 22. The article of claim 14 wherein the adhesive composition further comprises:
at least one tackifier. 23. The article of claim 14 wherein the adhesive composition further comprises:
at least one plasticizer. 24. The article of claim 14 wherein the adhesive composition further comprises:
at least one additive. 25. The article of claim 14 wherein the adhesive composition further comprises:
at least one filler. 26. The article of claim 14 wherein the adhesive composition further comprises:
at least one solvent. 27. The article of claim 14 wherein the article is a dressing. 28. The article of claim 27 wherein the dressing further comprises a substrate on which the layer of the adhesive composition is disposed. 29. The article of claim 27 wherein the dressing defines at least one window providing viewing through the window. 30. The article of claim 29 wherein the dressing further comprises a thin barrier film extending over the at least one window and which allows transmission of light therethrough. 31. The article of claim 27 wherein the dressing is a NPWT dressing. 32. A method of sealingly securing an article to a substrate, the method comprising:
providing an adhesive composition including (i) a polysiloxane adhesive, and (ii) one or more absorbent fillers dispersed in the polysiloxane adhesive; and forming a layer of the adhesive composition between the article and the substrate. 33. The method of claim 32 wherein the substrate is biological skin. 34. The method of claim 32 wherein the method is used in negative pressure wound therapy. 35. The method of claim 32 wherein the layer of the adhesive composition is from about 50 microns to about 300 microns. 36. A method for performing at least one of (i) forming a seal about a wound, and (ii) securing an article to skin, the method comprising:
identifying a wound or area of interest on a user's skin; providing an adhesive composition including a polysiloxane adhesive and at least one absorbent filler dispersed in the polysiloxane adhesive; providing a layer of the adhesive composition either (i) about the wound, or (ii) between the article and skin. 37. The method of claim 36 wherein the layer of the adhesive composition is from about 50 microns to about 300 microns. | An adhesive composition comprising silicone adhesives and one or more absorbent fillers such as hydrocolloids is disclosed. The adhesive composition is particularly well suited for use in negative pressure wound therapies.1. An adhesive composition comprising:
a polysiloxane adhesive; and one or more absorbent fillers dispersed in the polysiloxane adhesive. 2. The adhesive of claim 1 wherein the polysiloxane adhesive is a one-part adhesive and at least partially crosslinked. 3. The adhesive of claim 1 wherein the polysiloxane adhesive is selected from the group consisting of (i) an adhesive having a solids content of about 60%, a viscosity of about 2600 mPA·s, and which exhibits a rheology at 0.01 rad/sec at 30° C. of about 5×106 P, (ii) an adhesive having a solids content of about 60%, a viscosity of about 1200 mPA·s, and which exhibits a rheology at 0.01 rad/sec at 30° C. of about 5×106 P, and (iii) a combination of (i) and (ii). 4. The adhesive of claim 1 wherein the polysiloxane adhesive constitutes at least about 40% by weight of the adhesive composition. 5. The adhesive of claim 1 wherein the absorbent filler is selected from the group consisting of guar gum, xanthan gum, karaya gum, locus gum, polyvinyl alcohol, pectin, gelatin, carboxymethyl cellulose, high molecular weight carbowax, carboxypolymethylene, maize starch, alginic acid, super absorbent polymers, and combinations thereof. 6. The adhesive of claim 1 wherein the absorbent filler is carboxymethyl cellulose. 7. The adhesive of claim 1 wherein the one or more absorbent fillers constitute from about 5% to about 60% by weight of the adhesive composition. 8. The adhesive of claim 7 wherein the one or more absorbent fillers constitute from about 25% to about 35% by weight of the adhesive composition. 9. The adhesive of claim 1 wherein the adhesive composition further comprises:
at least one tackifier. 10. The adhesive of claim 1 wherein the adhesive composition further comprises:
at least one plasticizer. 11. The adhesive of claim 1 wherein the adhesive composition further comprises:
at least one additive. 12. The adhesive of claim 1 wherein the adhesive composition further comprises:
at least one filler. 13. The adhesive of claim 1 wherein the adhesive composition further comprises:
at least one solvent. 14. An article comprising a layer of an adhesive composition comprising (i) a polysiloxane adhesive and (ii) one or more absorbent fillers dispersed in the polysiloxane adhesive. 15. The article of claim 14 wherein the polysiloxane adhesive is a one-part adhesive and at least partially crosslinked. 16. The article of claim 14 wherein the polysiloxane adhesive is selected from the group consisting of (i) an adhesive having a solids content of about 60%, a viscosity of about 2600 mPA·s, and which exhibits a rheology at 0.01 rad/sec at 30° C. of about 5×106 P, (ii) an adhesive having a solids content of about 60%, a viscosity of about 1200 mPA·s, and which exhibits a rheology at 0.01 rad/sec at 30° C. of about 5×106 P, and (iii) a combination of (i) and (ii). 17. The article of claim 14 wherein the polysiloxane adhesive constitutes at least about 40% by weight of the adhesive composition. 18. The article of claim 14 wherein the absorbent filler is selected from the group consisting of guar gum, xanthan gum, karaya gum, locus gum, polyvinyl alcohol, pectin, gelatin, carboxymethyl cellulose, high molecular weight carbowax, carboxypolymethylene, maize starch, alginic acid, super absorbent polymers, and combinations thereof. 19. The article of claim 14 wherein the absorbent filler is carboxymethyl cellulose. 20. The article of claim 14 wherein the one or more absorbent fillers constitute from about 5% to about 60% by weight of the adhesive composition. 21. The article of claim 20 wherein the one or more absorbent fillers constitute from about 25% to about 35% by weight of the adhesive composition. 22. The article of claim 14 wherein the adhesive composition further comprises:
at least one tackifier. 23. The article of claim 14 wherein the adhesive composition further comprises:
at least one plasticizer. 24. The article of claim 14 wherein the adhesive composition further comprises:
at least one additive. 25. The article of claim 14 wherein the adhesive composition further comprises:
at least one filler. 26. The article of claim 14 wherein the adhesive composition further comprises:
at least one solvent. 27. The article of claim 14 wherein the article is a dressing. 28. The article of claim 27 wherein the dressing further comprises a substrate on which the layer of the adhesive composition is disposed. 29. The article of claim 27 wherein the dressing defines at least one window providing viewing through the window. 30. The article of claim 29 wherein the dressing further comprises a thin barrier film extending over the at least one window and which allows transmission of light therethrough. 31. The article of claim 27 wherein the dressing is a NPWT dressing. 32. A method of sealingly securing an article to a substrate, the method comprising:
providing an adhesive composition including (i) a polysiloxane adhesive, and (ii) one or more absorbent fillers dispersed in the polysiloxane adhesive; and forming a layer of the adhesive composition between the article and the substrate. 33. The method of claim 32 wherein the substrate is biological skin. 34. The method of claim 32 wherein the method is used in negative pressure wound therapy. 35. The method of claim 32 wherein the layer of the adhesive composition is from about 50 microns to about 300 microns. 36. A method for performing at least one of (i) forming a seal about a wound, and (ii) securing an article to skin, the method comprising:
identifying a wound or area of interest on a user's skin; providing an adhesive composition including a polysiloxane adhesive and at least one absorbent filler dispersed in the polysiloxane adhesive; providing a layer of the adhesive composition either (i) about the wound, or (ii) between the article and skin. 37. The method of claim 36 wherein the layer of the adhesive composition is from about 50 microns to about 300 microns. | 1,600 |
1,318 | 15,767,493 | 1,613 | A method for protecting a plant from an arthropod may include applying an amount of a repellant composition including diatomaceous earth to a plant. According to some aspects, the repellent composition may render the plant unpalatable to the arthropod, resulting in death of the arthropod by starvation. A method for protecting a plant from an arthropod may include applying an amount of a repellant composition including diatomaceous earth to a plant. The arthropod may not include an exoskeleton, and the repellent composition may render the plant unpalatable to the arthropod, resulting in death of the arthropod by starvation. | 1. A method for protecting a plant from an arthropod, the method comprising:
applying an amount of a repellant composition comprising diatomaceous earth to a plant, wherein the repellent composition renders the plant unpalatable to the arthropod, resulting in death of the arthropod by starvation. 2. The method of claim 1, wherein the repellent composition does not directly cause mortality of the arthropod. 3. The method of claim 1, wherein the repellent composition causes the arthropod to avoid contact with the plant. 4. The method of claim 1, wherein the plant is one of a corn plant, a citrus tree, a chickpea plant, a broccoli plant, a lettuce plant, a cabbage plant, and a strawberry plant. 5. The method of claim 1, wherein the arthropod does not include an exoskeleton. 6. The method of claim 1, wherein the arthropod is a soft-bodied organism. 7. The method of claim 6, wherein the soft-bodied organism comprises a caterpillar. 8. The method of claim 7, wherein the caterpillar comprises at least one of a caterpillar of moths, a caterpillar of earworm, a caterpillar of armyworm, a caterpillar of looper, and a caterpillar of leafminer. 9. The method of claim 1, wherein the arthropod is one of a corn earworm, a psyllid, a thrip, an aphid, and a beetle. 10. The method of claim 1, wherein the repellent composition further comprises at least one of soap and a composition including at least one of pyrethins and azadirachtin mixed in water. 11. The method of claim 1, wherein the repellent composition is a slurry and comprises from 0.1 lbs. to 1.5 lbs. of diatomaceous earth per gallon of repellent composition. 12-19. (canceled) 20. The method of claim 1, wherein the plant comprises one of a cereal, an oilseed, a fruit tree, a berry plant, a vegetable, a pasture plant, a forage plant, and a fungi. 21. The method of claim 1, wherein the arthropod is a corn earworm, and the plant is a chickpea plant. 22. The method of claim 1, wherein the arthropod is a psyllid, and the plant is a citrus tree. 23. The method of claim 1, wherein the arthropod is one of a thrip and a beetle, and the plant is a strawberry plant. 24. The method of claim 1, wherein the arthropod is a thrip, and the plant is a broccoli plant. 25. The method of claim 1, wherein the arthropod is an aphid, and the plant is a lettuce plant. 26. The method of claim 1, wherein the arthropod is a beetle, and the plant is a cabbage plant. 27. The method of claim 1, wherein the arthropod is an earworm, and the plant is one of a corn plant, a tomato plant, and a cotton plant. 28. The method of claim 1, wherein the arthropod is a corn earworm, and the plant is a chickpea plant. 29. The method claim 1, wherein the diatomaceous earth has a water adsorption ranging from 125% by weight to 175% by weight. 30-32. (canceled) 33. The method of claim 1, wherein the diatomaceous earth has an oil adsorption ranging from 105% by weight to 155% by weight. 34-38. (canceled) 39. The method of claim 1, wherein the mineral composition is modified by silanization. 40. (canceled) 41. A method for protecting a plant from an arthropod, the method comprising:
applying an amount of a repellant composition comprising diatomaceous earth to a plant, wherein the arthropod does not include an exoskeleton, and wherein the repellent composition renders the plant unpalatable to the arthropod, resulting in death of the arthropod by starvation. 42-44. (canceled) | A method for protecting a plant from an arthropod may include applying an amount of a repellant composition including diatomaceous earth to a plant. According to some aspects, the repellent composition may render the plant unpalatable to the arthropod, resulting in death of the arthropod by starvation. A method for protecting a plant from an arthropod may include applying an amount of a repellant composition including diatomaceous earth to a plant. The arthropod may not include an exoskeleton, and the repellent composition may render the plant unpalatable to the arthropod, resulting in death of the arthropod by starvation.1. A method for protecting a plant from an arthropod, the method comprising:
applying an amount of a repellant composition comprising diatomaceous earth to a plant, wherein the repellent composition renders the plant unpalatable to the arthropod, resulting in death of the arthropod by starvation. 2. The method of claim 1, wherein the repellent composition does not directly cause mortality of the arthropod. 3. The method of claim 1, wherein the repellent composition causes the arthropod to avoid contact with the plant. 4. The method of claim 1, wherein the plant is one of a corn plant, a citrus tree, a chickpea plant, a broccoli plant, a lettuce plant, a cabbage plant, and a strawberry plant. 5. The method of claim 1, wherein the arthropod does not include an exoskeleton. 6. The method of claim 1, wherein the arthropod is a soft-bodied organism. 7. The method of claim 6, wherein the soft-bodied organism comprises a caterpillar. 8. The method of claim 7, wherein the caterpillar comprises at least one of a caterpillar of moths, a caterpillar of earworm, a caterpillar of armyworm, a caterpillar of looper, and a caterpillar of leafminer. 9. The method of claim 1, wherein the arthropod is one of a corn earworm, a psyllid, a thrip, an aphid, and a beetle. 10. The method of claim 1, wherein the repellent composition further comprises at least one of soap and a composition including at least one of pyrethins and azadirachtin mixed in water. 11. The method of claim 1, wherein the repellent composition is a slurry and comprises from 0.1 lbs. to 1.5 lbs. of diatomaceous earth per gallon of repellent composition. 12-19. (canceled) 20. The method of claim 1, wherein the plant comprises one of a cereal, an oilseed, a fruit tree, a berry plant, a vegetable, a pasture plant, a forage plant, and a fungi. 21. The method of claim 1, wherein the arthropod is a corn earworm, and the plant is a chickpea plant. 22. The method of claim 1, wherein the arthropod is a psyllid, and the plant is a citrus tree. 23. The method of claim 1, wherein the arthropod is one of a thrip and a beetle, and the plant is a strawberry plant. 24. The method of claim 1, wherein the arthropod is a thrip, and the plant is a broccoli plant. 25. The method of claim 1, wherein the arthropod is an aphid, and the plant is a lettuce plant. 26. The method of claim 1, wherein the arthropod is a beetle, and the plant is a cabbage plant. 27. The method of claim 1, wherein the arthropod is an earworm, and the plant is one of a corn plant, a tomato plant, and a cotton plant. 28. The method of claim 1, wherein the arthropod is a corn earworm, and the plant is a chickpea plant. 29. The method claim 1, wherein the diatomaceous earth has a water adsorption ranging from 125% by weight to 175% by weight. 30-32. (canceled) 33. The method of claim 1, wherein the diatomaceous earth has an oil adsorption ranging from 105% by weight to 155% by weight. 34-38. (canceled) 39. The method of claim 1, wherein the mineral composition is modified by silanization. 40. (canceled) 41. A method for protecting a plant from an arthropod, the method comprising:
applying an amount of a repellant composition comprising diatomaceous earth to a plant, wherein the arthropod does not include an exoskeleton, and wherein the repellent composition renders the plant unpalatable to the arthropod, resulting in death of the arthropod by starvation. 42-44. (canceled) | 1,600 |
1,319 | 16,451,625 | 1,615 | An extended release formulation is provided for use in a method for the treatment of Central Precocious Puberty (CPP) in pediatric patients 2 years of age or older. The extended release formulation comprises leuprolide or a pharmaceutically acceptable salt thereof, a biodegradable polymer, and a biocompatible organic solvent. The biodegradable polymer is comprised of poly(lactide-co-glycolide) (PLG) copolymer segments, poly(lactic acid-co-glycolic acid) (PLGA) copolymer segments, poly(lactide) (PL) polymer segments, poly(lactic acid) (PLA) polymer segments, or a combination thereof. The extended release formulation is administered as a subcutaneous injection of a flowable composition that forms a solid in situ depot. The extended release formulation releases leuprolide for a period of about 6 months for the effective treatment of CPP within a pediatric patient. | 1. A method of treating pediatric patients 2 years of age and older with central precocious puberty (CPP), the method comprising administering to a pediatric patient who has CPP, once per about six months, a subcutaneous injection of an extended release composition comprising:
a. an organic solvent; b. leuprolide or a pharmaceutically acceptable salt thereof, wherein the amount of leuprolide or the pharmaceutically acceptable salt thereof in the composition is independent from the weight of the pediatric patient and is not modified in subsequent administrations of the composition; c. a biodegradable polymer comprising polymer segments selected from 85:15 poly(lactide-co-glycolide) (PLG) copolymer segments, 85:15 poly(lactic acid-co-glycolic acid) (PLGA) copolymer segments, or a combination thereof, wherein one distal end group of the polymer is hydroxyl-terminated and the other distal end group of the polymer is either hydroxyl-terminated or ester-terminated; and
wherein upon contact of the extended release composition with a bodily fluid, the solvent dissipates and an in situ solid depot forms; and
wherein the extended release composition, when administered once per about six months, reduces the pediatric patient's peak stimulated blood serum LH concentration to a pre-pubertal concentration level of <4 IU/L. 2. The method of claim 1, wherein the amount of leuprolide or the pharmaceutically acceptable salt thereof in the extended release composition is about 40 mg to about 50 mg. 3. The method of claim 2, wherein the leuprolide or pharmaceutically acceptable salt thereof is leuprolide acetate and the amount of leuprolide acetate in the extended release composition is about 45 mg. 4. The method of claim 1, wherein the amount of leuprolide or the pharmaceutically acceptable salt thereof in the extended release composition is about 40 mg to 45 mg leuprolide free base equivalent. 5. The method of claim 4, wherein the amount of leuprolide or the pharmaceutically acceptable salt thereof in the extended release composition is about 42 mg leuprolide free base equivalent. 6. The method of claim 1, wherein a stimulation composition comprising GnRH or a GnRH agonist, or a pharmaceutically acceptable salt thereof, is administered subcutaneously to the pediatric patient for measuring the peak stimulated blood serum LH concentration within the pediatric patient prior to administration of the extended release composition to confirm a baseline peak stimulated blood serum LH concentration. 7. The method of claim 6, wherein the stimulation composition comprises at least one GnRH agonist or pharmaceutically salt thereof selected from a group consisting of leuprolide, gonadorelin, goserelin, histrelin, nafarelin, buserelin, and triptorelin. 8. The method of claim 7, wherein the stimulation composition comprises a leuprolide acetate solution administered subcutaneously at a dose of about 10 μg to about 20 per kg of the pediatric patient's body weight or at a dose of about 500 μg to about 1000 μg total. 9. The method of claim 1, wherein a stimulation composition comprising GnRH or a GnRH agonist, or a pharmaceutically acceptable salt thereof, is administered subcutaneously to the pediatric patient for measuring the peak stimulated blood serum LH concentration within the pediatric patient at about three to about six months after administering the extended release composition to confirm suppression of peak stimulated blood serum LH concentration to a pre-pubertal level of <4 IU/L. 10. The method of claim 9, wherein the stimulation composition comprises at least one GnRH agonist or pharmaceutically salt thereof selected from a group consisting of leuprolide, gonadorelin, goserelin, histrelin, nafarelin, buserelin, and triptorelin. 11. The method of claim 10, wherein the stimulation composition comprises a leuprolide acetate solution administered subcutaneously at a dose of about 10 μg to about 20 per kg of the pediatric patient's body weight or at a dose of about 500 μg to about 1000 μg total. 12. The method of claim 1, wherein the organic solvent is N-methyl-2-pyrrolidone (NMP). 13. The method of claim 1, further comprising measuring the peak stimulated blood serum concentration levels of one or more CPP-associated hormones selected from the group consisting of follicle stimulating hormone (FSH), testosterone, and estradiol. 14. The method of claim 13, wherein administration of the extended release composition reduces a peak stimulated blood serum FSH to a concentration of <2.5 IU/L. 15. The method of claim 13, wherein administration of the extended release composition reduces a peak stimulated blood serum estradiol in a female pediatric patient to a concentration of <73.4 pmol/L (<20 pg/mL). 16. The method of claim 13, wherein administration of the extended release composition reduces a peak stimulated blood serum testosterone in a male pediatric patient to a concentration of <1 nmol/L (<28.8 ng/dL). 17. The method of claim 1, wherein a dose of the extended release composition comprises:
a. about 165 mg of N-methyl-2-pyrrolidone (NMP); b. about 165 mg of about 85:15 poly(DL lactide-co-glycolide) (PLG) copolymer segment; and c. about 45 mg of leuprolide acetate. 18. The method of claim 1, wherein the biodegradable polymer has a weight average molecular weight of between 20-26 kDa. 19. The method of claim 1, wherein the biodegradable polymer comprises a polymer of the Formula:
HO—(P)—C(═O)O—Ra—O(O═)C—(P)—OH
wherein, Ra is an alkane diradical comprising about 4 to about 8 carbons and is a residue of an alkane diol; and
wherein, P are copolymer segments selected from poly(lactide-co-glycolide) (PLG) copolymer segments, poly(lactic acid-co-glycolic acid) (PLGA) copolymer segments, or a combination thereof. 20. The method of claim 1, wherein the extended release composition reduces the mean bone growth velocity in the pediatric patient with CPP by about 25% over about a twelve-month treatment period. 21. The method of claim 1, wherein administration of the extended release composition reduces the pediatric patient's mean ratio of bone age to chronological age at the time of measurement by about 5% over about a twelve-month treatment period. 22. The method of claim 1, wherein the extended release composition comprises an injection dose volume of about 0.5 mL or less. 23. The method of claim 22, wherein the extended release composition comprises an injection dose volume of about 0.375 mL. 24. The method of claim 1, wherein the pediatric patient with CPP is treated with the extended release composition for a time period of about 6 months, of about 12 months, of about 18 months, of about 24 months, or longer. 25. The method of claim 1, wherein the extended release composition is provided in a two-syringe system comprising:
a. a first syringe containing about 45 mg of lyophilized leuprolide acetate or an equivalent amount of a different pharmaceutically acceptable salt of leuprolide; b. a second syringe containing a solution of about 165 mg of about 85:15 poly(lactide-co-glycolide) (PLG) copolymer segment dissolved in about 165 mg of N-methyl-2-pyrrolidone (NMP); and
wherein, the first syringe is connected to the second syringe such that a passageway is formed between the first syringe and the second syringe to allow the passage of a flowable composition from one syringe to the other syringe; and
wherein the extended release composition is prepared by continuously mixing the contents of the second syringe back and forth into the contents of the first syringe of the connected two-syringe system for at least about 45 seconds to about at least 60 seconds or longer to form a uniform suspension. 26. A method of treating a pediatric patient 2 years of age and older with CPP, the method comprising the steps of:
(a) administering an injection of a stimulation composition comprising GnRH or a GnRH agonist, or a pharmaceutically acceptable salt thereof, to a pediatric patient 2 years of age or older who has CPP, wherein a blood sample from the pediatric patient is obtained within about at least thirty minutes of administering the stimulation composition for measuring a peak stimulated blood serum LH concentration; (b) administering a subcutaneous dose of an extended release composition effective to treat CPP for about six months, if the pediatric patient has a peak stimulated blood serum LH concentration of >5 IU/L, wherein the extended release composition comprises:
i. N-methyl-2-pyrrolidone (NMP);
ii. leuprolide or a pharmaceutically acceptable salt thereof; and
iii. a biodegradable polymer comprising polymer segments selected from 85:15 poly(lactide-co-glycolide) (PLG) copolymer segments, 85:15 poly(lactic acid-co-glycolic acid) (PLGA) copolymer segments, or a combination thereof, wherein one distal end group of the polymer is hydroxyl-terminated and the other distal end group of the polymer is either hydroxyl-terminated or ester-terminated;
(c) administering an additional injection of the stimulation composition to the pediatric patient at about three to about six months after administering the extended release composition of step (b) to confirm suppression of blood serum LH concentration to pre-pubertal level of <4 IU/L, wherein a blood sample from the pediatric patient is obtained within about at least thirty minutes of administering the subsequent stimulation composition for measuring a peak stimulated blood serum LH concentration; and (d) repeating steps (b) and (c) as necessary to treat CPP if the peak stimulated blood serum LH concentration of step (c) at about three to about six months after step (b) of administering is <4 IU/L;
wherein the dose of the extended release composition is not individualized for the pediatric patient;
wherein upon contact of the extended release composition with a bodily fluid, the solvent dissipates and an in situ solid depot forms; and
wherein the extended release formulation reduces the peak stimulated blood serum LH concentration of the pediatric patient to a pre-pubertal concentration level of <4 IU/L. 27. A kit comprising:
(a) at least one dose of an injectable stimulation composition comprising a solution of GnRH or a GnRH agonist, or a pharmaceutically acceptable salt thereof, effective for measuring the peak stimulated blood serum LH concentration within a pediatric patient 2 years of age or older who has CPP; (b) at least one dose of an injectable extended release composition effective for the treatment of CPP in the pediatric patient by reducing the peak stimulated blood serum LH concentration to a pre-pubertal concentration level of <4 IU/L when administered about once every six months and comprising:
i. N-methyl-2-pyrrolidone (NMP);
ii. about 40 mg to about 50 mg of leuprolide acetate or an equivalent amount of a different pharmaceutically acceptable salt of leuprolide;
iii. a biodegradable polymer comprising polymer segments selected from 85/15 poly(lactide-co-glycolide) (PLG) copolymer segments, 85/15 poly(lactic acid-co-glycolic acid) (PLGA) copolymer segments, poly(lactide) (PL) polymer segments, poly(lactic acid) (PLA) polymer segments, or a combination thereof, wherein one distal end group of the polymer is hydroxyl-terminated and the other distal end group of the polymer is either hydroxyl-terminated or ester-terminated; wherein upon contact of the extended release composition with a bodily fluid, NMP dissipates and an in situ solid depot forms; and
(c) instructions for the use thereof for treating CPP in the pediatric patient. | An extended release formulation is provided for use in a method for the treatment of Central Precocious Puberty (CPP) in pediatric patients 2 years of age or older. The extended release formulation comprises leuprolide or a pharmaceutically acceptable salt thereof, a biodegradable polymer, and a biocompatible organic solvent. The biodegradable polymer is comprised of poly(lactide-co-glycolide) (PLG) copolymer segments, poly(lactic acid-co-glycolic acid) (PLGA) copolymer segments, poly(lactide) (PL) polymer segments, poly(lactic acid) (PLA) polymer segments, or a combination thereof. The extended release formulation is administered as a subcutaneous injection of a flowable composition that forms a solid in situ depot. The extended release formulation releases leuprolide for a period of about 6 months for the effective treatment of CPP within a pediatric patient.1. A method of treating pediatric patients 2 years of age and older with central precocious puberty (CPP), the method comprising administering to a pediatric patient who has CPP, once per about six months, a subcutaneous injection of an extended release composition comprising:
a. an organic solvent; b. leuprolide or a pharmaceutically acceptable salt thereof, wherein the amount of leuprolide or the pharmaceutically acceptable salt thereof in the composition is independent from the weight of the pediatric patient and is not modified in subsequent administrations of the composition; c. a biodegradable polymer comprising polymer segments selected from 85:15 poly(lactide-co-glycolide) (PLG) copolymer segments, 85:15 poly(lactic acid-co-glycolic acid) (PLGA) copolymer segments, or a combination thereof, wherein one distal end group of the polymer is hydroxyl-terminated and the other distal end group of the polymer is either hydroxyl-terminated or ester-terminated; and
wherein upon contact of the extended release composition with a bodily fluid, the solvent dissipates and an in situ solid depot forms; and
wherein the extended release composition, when administered once per about six months, reduces the pediatric patient's peak stimulated blood serum LH concentration to a pre-pubertal concentration level of <4 IU/L. 2. The method of claim 1, wherein the amount of leuprolide or the pharmaceutically acceptable salt thereof in the extended release composition is about 40 mg to about 50 mg. 3. The method of claim 2, wherein the leuprolide or pharmaceutically acceptable salt thereof is leuprolide acetate and the amount of leuprolide acetate in the extended release composition is about 45 mg. 4. The method of claim 1, wherein the amount of leuprolide or the pharmaceutically acceptable salt thereof in the extended release composition is about 40 mg to 45 mg leuprolide free base equivalent. 5. The method of claim 4, wherein the amount of leuprolide or the pharmaceutically acceptable salt thereof in the extended release composition is about 42 mg leuprolide free base equivalent. 6. The method of claim 1, wherein a stimulation composition comprising GnRH or a GnRH agonist, or a pharmaceutically acceptable salt thereof, is administered subcutaneously to the pediatric patient for measuring the peak stimulated blood serum LH concentration within the pediatric patient prior to administration of the extended release composition to confirm a baseline peak stimulated blood serum LH concentration. 7. The method of claim 6, wherein the stimulation composition comprises at least one GnRH agonist or pharmaceutically salt thereof selected from a group consisting of leuprolide, gonadorelin, goserelin, histrelin, nafarelin, buserelin, and triptorelin. 8. The method of claim 7, wherein the stimulation composition comprises a leuprolide acetate solution administered subcutaneously at a dose of about 10 μg to about 20 per kg of the pediatric patient's body weight or at a dose of about 500 μg to about 1000 μg total. 9. The method of claim 1, wherein a stimulation composition comprising GnRH or a GnRH agonist, or a pharmaceutically acceptable salt thereof, is administered subcutaneously to the pediatric patient for measuring the peak stimulated blood serum LH concentration within the pediatric patient at about three to about six months after administering the extended release composition to confirm suppression of peak stimulated blood serum LH concentration to a pre-pubertal level of <4 IU/L. 10. The method of claim 9, wherein the stimulation composition comprises at least one GnRH agonist or pharmaceutically salt thereof selected from a group consisting of leuprolide, gonadorelin, goserelin, histrelin, nafarelin, buserelin, and triptorelin. 11. The method of claim 10, wherein the stimulation composition comprises a leuprolide acetate solution administered subcutaneously at a dose of about 10 μg to about 20 per kg of the pediatric patient's body weight or at a dose of about 500 μg to about 1000 μg total. 12. The method of claim 1, wherein the organic solvent is N-methyl-2-pyrrolidone (NMP). 13. The method of claim 1, further comprising measuring the peak stimulated blood serum concentration levels of one or more CPP-associated hormones selected from the group consisting of follicle stimulating hormone (FSH), testosterone, and estradiol. 14. The method of claim 13, wherein administration of the extended release composition reduces a peak stimulated blood serum FSH to a concentration of <2.5 IU/L. 15. The method of claim 13, wherein administration of the extended release composition reduces a peak stimulated blood serum estradiol in a female pediatric patient to a concentration of <73.4 pmol/L (<20 pg/mL). 16. The method of claim 13, wherein administration of the extended release composition reduces a peak stimulated blood serum testosterone in a male pediatric patient to a concentration of <1 nmol/L (<28.8 ng/dL). 17. The method of claim 1, wherein a dose of the extended release composition comprises:
a. about 165 mg of N-methyl-2-pyrrolidone (NMP); b. about 165 mg of about 85:15 poly(DL lactide-co-glycolide) (PLG) copolymer segment; and c. about 45 mg of leuprolide acetate. 18. The method of claim 1, wherein the biodegradable polymer has a weight average molecular weight of between 20-26 kDa. 19. The method of claim 1, wherein the biodegradable polymer comprises a polymer of the Formula:
HO—(P)—C(═O)O—Ra—O(O═)C—(P)—OH
wherein, Ra is an alkane diradical comprising about 4 to about 8 carbons and is a residue of an alkane diol; and
wherein, P are copolymer segments selected from poly(lactide-co-glycolide) (PLG) copolymer segments, poly(lactic acid-co-glycolic acid) (PLGA) copolymer segments, or a combination thereof. 20. The method of claim 1, wherein the extended release composition reduces the mean bone growth velocity in the pediatric patient with CPP by about 25% over about a twelve-month treatment period. 21. The method of claim 1, wherein administration of the extended release composition reduces the pediatric patient's mean ratio of bone age to chronological age at the time of measurement by about 5% over about a twelve-month treatment period. 22. The method of claim 1, wherein the extended release composition comprises an injection dose volume of about 0.5 mL or less. 23. The method of claim 22, wherein the extended release composition comprises an injection dose volume of about 0.375 mL. 24. The method of claim 1, wherein the pediatric patient with CPP is treated with the extended release composition for a time period of about 6 months, of about 12 months, of about 18 months, of about 24 months, or longer. 25. The method of claim 1, wherein the extended release composition is provided in a two-syringe system comprising:
a. a first syringe containing about 45 mg of lyophilized leuprolide acetate or an equivalent amount of a different pharmaceutically acceptable salt of leuprolide; b. a second syringe containing a solution of about 165 mg of about 85:15 poly(lactide-co-glycolide) (PLG) copolymer segment dissolved in about 165 mg of N-methyl-2-pyrrolidone (NMP); and
wherein, the first syringe is connected to the second syringe such that a passageway is formed between the first syringe and the second syringe to allow the passage of a flowable composition from one syringe to the other syringe; and
wherein the extended release composition is prepared by continuously mixing the contents of the second syringe back and forth into the contents of the first syringe of the connected two-syringe system for at least about 45 seconds to about at least 60 seconds or longer to form a uniform suspension. 26. A method of treating a pediatric patient 2 years of age and older with CPP, the method comprising the steps of:
(a) administering an injection of a stimulation composition comprising GnRH or a GnRH agonist, or a pharmaceutically acceptable salt thereof, to a pediatric patient 2 years of age or older who has CPP, wherein a blood sample from the pediatric patient is obtained within about at least thirty minutes of administering the stimulation composition for measuring a peak stimulated blood serum LH concentration; (b) administering a subcutaneous dose of an extended release composition effective to treat CPP for about six months, if the pediatric patient has a peak stimulated blood serum LH concentration of >5 IU/L, wherein the extended release composition comprises:
i. N-methyl-2-pyrrolidone (NMP);
ii. leuprolide or a pharmaceutically acceptable salt thereof; and
iii. a biodegradable polymer comprising polymer segments selected from 85:15 poly(lactide-co-glycolide) (PLG) copolymer segments, 85:15 poly(lactic acid-co-glycolic acid) (PLGA) copolymer segments, or a combination thereof, wherein one distal end group of the polymer is hydroxyl-terminated and the other distal end group of the polymer is either hydroxyl-terminated or ester-terminated;
(c) administering an additional injection of the stimulation composition to the pediatric patient at about three to about six months after administering the extended release composition of step (b) to confirm suppression of blood serum LH concentration to pre-pubertal level of <4 IU/L, wherein a blood sample from the pediatric patient is obtained within about at least thirty minutes of administering the subsequent stimulation composition for measuring a peak stimulated blood serum LH concentration; and (d) repeating steps (b) and (c) as necessary to treat CPP if the peak stimulated blood serum LH concentration of step (c) at about three to about six months after step (b) of administering is <4 IU/L;
wherein the dose of the extended release composition is not individualized for the pediatric patient;
wherein upon contact of the extended release composition with a bodily fluid, the solvent dissipates and an in situ solid depot forms; and
wherein the extended release formulation reduces the peak stimulated blood serum LH concentration of the pediatric patient to a pre-pubertal concentration level of <4 IU/L. 27. A kit comprising:
(a) at least one dose of an injectable stimulation composition comprising a solution of GnRH or a GnRH agonist, or a pharmaceutically acceptable salt thereof, effective for measuring the peak stimulated blood serum LH concentration within a pediatric patient 2 years of age or older who has CPP; (b) at least one dose of an injectable extended release composition effective for the treatment of CPP in the pediatric patient by reducing the peak stimulated blood serum LH concentration to a pre-pubertal concentration level of <4 IU/L when administered about once every six months and comprising:
i. N-methyl-2-pyrrolidone (NMP);
ii. about 40 mg to about 50 mg of leuprolide acetate or an equivalent amount of a different pharmaceutically acceptable salt of leuprolide;
iii. a biodegradable polymer comprising polymer segments selected from 85/15 poly(lactide-co-glycolide) (PLG) copolymer segments, 85/15 poly(lactic acid-co-glycolic acid) (PLGA) copolymer segments, poly(lactide) (PL) polymer segments, poly(lactic acid) (PLA) polymer segments, or a combination thereof, wherein one distal end group of the polymer is hydroxyl-terminated and the other distal end group of the polymer is either hydroxyl-terminated or ester-terminated; wherein upon contact of the extended release composition with a bodily fluid, NMP dissipates and an in situ solid depot forms; and
(c) instructions for the use thereof for treating CPP in the pediatric patient. | 1,600 |
1,320 | 14,848,390 | 1,662 | The invention relates to methods and compositions for identifying and selecting maize plants with enhanced resistance to northern leaf blight. Maize plants generated by the methods of the invention are also a feature of the invention. | 1. A recombinant DNA construct comprising an isolated polynucleotide operably linked to at least one regulatory sequence, wherein said isolated polynucleotide comprises:
a. at least one nucleotide sequence encoding a polypeptide capable of conferring or enhancing resistance to northern leaf blight, wherein the polypeptide has an amino acid sequence of at least 90% sequence identity, based on the Clustal V method of alignment, when compared to SEQ ID NO: 95 or 97; or b. a full complement of the nucleotide sequence of (a), wherein the full complement and the nucleotide sequence consist of the same number of nucleotides and are 100% complementary. 2. The recombinant DNA construct of claim 1, wherein said isolated polynucleotide comprises a nucleotide sequence encoding a polypeptide having the amino acid sequence of SEQ ID NO:95 or 97. 3. The recombinant DNA construct of claim 1, wherein said isolated polynucleotide comprises the nucleotide sequence of SEQ ID NO:94 or 96. 4. A maize cell comprising the recombinant DNA construct of claim 1. 5. A process for producing a maize plant comprising transforming a plant cell with the recombinant DNA construct of claim 1. 6. A maize plant comprising the recombinant DNA construct of claim 1. 7. A maize seed comprising the recombinant DNA construct of claim 1. 8. A process of conferring or improving resistance to northern leaf blight, comprising transforming a plant with the recombinant DNA construct of claim 1. 9. A process of altering the level of expression of a protein capable of conferring resistance to northern leaf blight in a maize cell comprising:
a. transforming a maize cell with the recombinant DNA construct of claim 1; and b. growing the transformed maize cell under conditions that are suitable for expression of the recombinant DNA construct, wherein expression of the recombinant DNA construct results in production of altered levels of a protein capable of conferring resistance to northern leaf blight in the transformed maize cell when compared to levels of expression in a wild-type maize plant having resistance to northern leaf blight. 10. A process of altering the level of expression of a protein capable of conferring resistance to northern leaf blight in a maize plant comprising:
a. transforming a maize plant cell with the recombinant DNA construct of claim 1; b. regenerating a transformed maize plant from the transformed maize plant cell; and c. growing the transformed maize plant under conditions that are suitable for expression of the recombinant DNA construct wherein expression of the recombinant DNA construct results in production of altered levels of a protein capable of conferring resistance to northern leaf blight in the transformed maize plant when compared to levels of expression in a wild-type maize plant having resistance to northern leaf blight. | The invention relates to methods and compositions for identifying and selecting maize plants with enhanced resistance to northern leaf blight. Maize plants generated by the methods of the invention are also a feature of the invention.1. A recombinant DNA construct comprising an isolated polynucleotide operably linked to at least one regulatory sequence, wherein said isolated polynucleotide comprises:
a. at least one nucleotide sequence encoding a polypeptide capable of conferring or enhancing resistance to northern leaf blight, wherein the polypeptide has an amino acid sequence of at least 90% sequence identity, based on the Clustal V method of alignment, when compared to SEQ ID NO: 95 or 97; or b. a full complement of the nucleotide sequence of (a), wherein the full complement and the nucleotide sequence consist of the same number of nucleotides and are 100% complementary. 2. The recombinant DNA construct of claim 1, wherein said isolated polynucleotide comprises a nucleotide sequence encoding a polypeptide having the amino acid sequence of SEQ ID NO:95 or 97. 3. The recombinant DNA construct of claim 1, wherein said isolated polynucleotide comprises the nucleotide sequence of SEQ ID NO:94 or 96. 4. A maize cell comprising the recombinant DNA construct of claim 1. 5. A process for producing a maize plant comprising transforming a plant cell with the recombinant DNA construct of claim 1. 6. A maize plant comprising the recombinant DNA construct of claim 1. 7. A maize seed comprising the recombinant DNA construct of claim 1. 8. A process of conferring or improving resistance to northern leaf blight, comprising transforming a plant with the recombinant DNA construct of claim 1. 9. A process of altering the level of expression of a protein capable of conferring resistance to northern leaf blight in a maize cell comprising:
a. transforming a maize cell with the recombinant DNA construct of claim 1; and b. growing the transformed maize cell under conditions that are suitable for expression of the recombinant DNA construct, wherein expression of the recombinant DNA construct results in production of altered levels of a protein capable of conferring resistance to northern leaf blight in the transformed maize cell when compared to levels of expression in a wild-type maize plant having resistance to northern leaf blight. 10. A process of altering the level of expression of a protein capable of conferring resistance to northern leaf blight in a maize plant comprising:
a. transforming a maize plant cell with the recombinant DNA construct of claim 1; b. regenerating a transformed maize plant from the transformed maize plant cell; and c. growing the transformed maize plant under conditions that are suitable for expression of the recombinant DNA construct wherein expression of the recombinant DNA construct results in production of altered levels of a protein capable of conferring resistance to northern leaf blight in the transformed maize plant when compared to levels of expression in a wild-type maize plant having resistance to northern leaf blight. | 1,600 |
1,321 | 15,035,161 | 1,632 | The present invention relates to a pharmaceutical composition comprising, as active substance, Saccharomyces boulardii yeast cells, for use for reducing body fat in an individual. | 1. A method for reducing body fat in an individual, comprising administering an effective amount of a pharmaceutical composition comprising, as active substance, Saccharomyces boulardii yeast cells to the individual. 2. The method according to claim 1, wherein the individual has an excess body fat. 3. The method according to claim 1, wherein the individual is obese. 4. The method according to claim 1, wherein the individual presents with abdominal obesity. 5. The method according to claim 1, wherein the individual suffers from type 2 diabetes. 6. The method according to claim 1, wherein the individual suffers from a metabolic syndrome. 7. The method according to claim 1, for further treating hepatic steatosis in the individual. 8. The method according to claim 1, for further treating a liver and/or systemic inflammation in the individual. 9. The method according to claim 1, for further reducing the body weight of the individual. 10. The method according to claim 1, wherein yeast cells are lyophilized. 11. A method for reducing body fat in an individual, comprising administering an effective amount of Saccharomyces boulardii yeast cells to the individual. 12. The method according to claim 11, wherein the individual has excess body fat. 13. The method according to claim 11, wherein the individual is obese. 14. (canceled) 15. (canceled) 16. The method according to claim 11, wherein the individual presents with abdominal obesity. 17. The method according to claim 11, wherein the individual suffers from type 2 diabetes. 18. The method according to claim 11, wherein the individual suffers from a metabolic syndrome. | The present invention relates to a pharmaceutical composition comprising, as active substance, Saccharomyces boulardii yeast cells, for use for reducing body fat in an individual.1. A method for reducing body fat in an individual, comprising administering an effective amount of a pharmaceutical composition comprising, as active substance, Saccharomyces boulardii yeast cells to the individual. 2. The method according to claim 1, wherein the individual has an excess body fat. 3. The method according to claim 1, wherein the individual is obese. 4. The method according to claim 1, wherein the individual presents with abdominal obesity. 5. The method according to claim 1, wherein the individual suffers from type 2 diabetes. 6. The method according to claim 1, wherein the individual suffers from a metabolic syndrome. 7. The method according to claim 1, for further treating hepatic steatosis in the individual. 8. The method according to claim 1, for further treating a liver and/or systemic inflammation in the individual. 9. The method according to claim 1, for further reducing the body weight of the individual. 10. The method according to claim 1, wherein yeast cells are lyophilized. 11. A method for reducing body fat in an individual, comprising administering an effective amount of Saccharomyces boulardii yeast cells to the individual. 12. The method according to claim 11, wherein the individual has excess body fat. 13. The method according to claim 11, wherein the individual is obese. 14. (canceled) 15. (canceled) 16. The method according to claim 11, wherein the individual presents with abdominal obesity. 17. The method according to claim 11, wherein the individual suffers from type 2 diabetes. 18. The method according to claim 11, wherein the individual suffers from a metabolic syndrome. | 1,600 |
1,322 | 15,678,337 | 1,653 | An implant for promoting accelerated wound healing. The implant comprises a non-flocculating fiber material, admixed with a settable fluid. The fiber component typically will have short fiber lengths, so as to avoid forming entangled masses or clumps when mixed with a fluid. In an embodiment, the fiber material is native collagen fibers and the settable fluid is an isolated blood fraction, such as platelet rich plasma and platelet poor plasma. The native collagen fiber retaining the native crosslinks of the source tissue and providing an architectural and structural scaffolding for advancing cellular infiltration. The wound healing implant will accelerate the bodies healing process, to provide better healing and less scar tissue of the wound site. | 1)-16) (canceled) 17) A method of preparing an implantable tissue scaffold comprising the steps of:
a. introducing into a mold a composition comprising at least one blood fraction and a collagen fiber component; and b. allowing the composition to set to form a fiber reinforced clot having the shape of the mold, and c. separating the fiber reinforced clot and the mold, thereby forming an implantable tissue scaffold that is suturable,
wherein the at least one blood fraction comprises bone marrow aspirate or the at least one blood fraction has been separated from whole blood and comprises platelet poor plasma or platelet rich plasma, and
wherein the collagen fiber component comprises a non-flocculating distribution of collagen fibers having a length of less than 4 mm. 18) The method of claim 17, wherein the non-flocculating distribution of collagen fibers comprises native insoluble fibrous collagen that has been mechanically milled into a non-flocculating form. 19) The method of claim 17, wherein the collagen fiber component comprises a non-flocculating distribution of native collagen fibers having a length of less than 2 mm. 20) The method of claim 17, wherein the collagen fiber component comprises a non-flocculating distribution of native collagen fibers having a length of between 0.01 mm and 1 mm. 21) The method of claim 17, wherein the at least one blood fraction comprises platelets and plasma at a ratio of from 1:2 to 1:10. 22) The method of claim 17, wherein the composition further comprises a biologically active agent comprising a drug or a growth factor incorporated into the material as an additive. 23) The method of claim 17, wherein the collagen fiber component is cross-linked. 24) The method of claim 17, further comprising the step of:
d. implanting the implantable tissue scaffold into a wound site of a living being. 25) The method of claim 24, further comprising the step of:
e. securing the implantable tissue scaffold to the living being. 26) The method of claim 24, further comprising the step of:
e. securing the implantable tissue scaffold to the living being with a suture. 27) The method of claim 17, wherein the at least one blood fraction is formed by placing said blood sample in said centrifuge device and operating said centrifuge device to fractionate the blood sample into a plurality of blood fractions. 28) The method of claim 17, wherein the at least one blood fraction comprises platelet-rich plasma, and the method further comprising the step of adding an anti-coagulant to the platelet-rich plasma prior to contacting the at least one blood fraction and the collagen fiber component. 29) The method of claim 28, further comprising adding a source of calcium ion to the at least one blood fraction prior to contacting the at least one blood fraction and the collagen fiber component. 30) The method of claim 17, further comprising the step of partially hydrating the collagen fiber component with a non-settable fluid prior to contacting the at least one blood fraction and the collagen fiber component. 31) An implantable tissue scaffold formed from the method of claim 17. 32) The method of claim 19, wherein the non-flocculating distribution of collagen fibers comprises native insoluble fibrous collagen that has been mechanically milled into a non-flocculating form. 33) An implantable tissue scaffold formed from the method of claim 32. 34) The method of claim 20, wherein the non-flocculating distribution of collagen fibers comprises native insoluble fibrous collagen that has been mechanically milled into a non-flocculating form. 35) An implantable tissue scaffold formed from the method of claim 34. 36) A method of treating a wound in a living being comprising the steps of:
a. providing an implantable tissue scaffold formed from the method of claim 17, and b. suturing the implantable tissue scaffold to implanting a wound site of a living being. | An implant for promoting accelerated wound healing. The implant comprises a non-flocculating fiber material, admixed with a settable fluid. The fiber component typically will have short fiber lengths, so as to avoid forming entangled masses or clumps when mixed with a fluid. In an embodiment, the fiber material is native collagen fibers and the settable fluid is an isolated blood fraction, such as platelet rich plasma and platelet poor plasma. The native collagen fiber retaining the native crosslinks of the source tissue and providing an architectural and structural scaffolding for advancing cellular infiltration. The wound healing implant will accelerate the bodies healing process, to provide better healing and less scar tissue of the wound site.1)-16) (canceled) 17) A method of preparing an implantable tissue scaffold comprising the steps of:
a. introducing into a mold a composition comprising at least one blood fraction and a collagen fiber component; and b. allowing the composition to set to form a fiber reinforced clot having the shape of the mold, and c. separating the fiber reinforced clot and the mold, thereby forming an implantable tissue scaffold that is suturable,
wherein the at least one blood fraction comprises bone marrow aspirate or the at least one blood fraction has been separated from whole blood and comprises platelet poor plasma or platelet rich plasma, and
wherein the collagen fiber component comprises a non-flocculating distribution of collagen fibers having a length of less than 4 mm. 18) The method of claim 17, wherein the non-flocculating distribution of collagen fibers comprises native insoluble fibrous collagen that has been mechanically milled into a non-flocculating form. 19) The method of claim 17, wherein the collagen fiber component comprises a non-flocculating distribution of native collagen fibers having a length of less than 2 mm. 20) The method of claim 17, wherein the collagen fiber component comprises a non-flocculating distribution of native collagen fibers having a length of between 0.01 mm and 1 mm. 21) The method of claim 17, wherein the at least one blood fraction comprises platelets and plasma at a ratio of from 1:2 to 1:10. 22) The method of claim 17, wherein the composition further comprises a biologically active agent comprising a drug or a growth factor incorporated into the material as an additive. 23) The method of claim 17, wherein the collagen fiber component is cross-linked. 24) The method of claim 17, further comprising the step of:
d. implanting the implantable tissue scaffold into a wound site of a living being. 25) The method of claim 24, further comprising the step of:
e. securing the implantable tissue scaffold to the living being. 26) The method of claim 24, further comprising the step of:
e. securing the implantable tissue scaffold to the living being with a suture. 27) The method of claim 17, wherein the at least one blood fraction is formed by placing said blood sample in said centrifuge device and operating said centrifuge device to fractionate the blood sample into a plurality of blood fractions. 28) The method of claim 17, wherein the at least one blood fraction comprises platelet-rich plasma, and the method further comprising the step of adding an anti-coagulant to the platelet-rich plasma prior to contacting the at least one blood fraction and the collagen fiber component. 29) The method of claim 28, further comprising adding a source of calcium ion to the at least one blood fraction prior to contacting the at least one blood fraction and the collagen fiber component. 30) The method of claim 17, further comprising the step of partially hydrating the collagen fiber component with a non-settable fluid prior to contacting the at least one blood fraction and the collagen fiber component. 31) An implantable tissue scaffold formed from the method of claim 17. 32) The method of claim 19, wherein the non-flocculating distribution of collagen fibers comprises native insoluble fibrous collagen that has been mechanically milled into a non-flocculating form. 33) An implantable tissue scaffold formed from the method of claim 32. 34) The method of claim 20, wherein the non-flocculating distribution of collagen fibers comprises native insoluble fibrous collagen that has been mechanically milled into a non-flocculating form. 35) An implantable tissue scaffold formed from the method of claim 34. 36) A method of treating a wound in a living being comprising the steps of:
a. providing an implantable tissue scaffold formed from the method of claim 17, and b. suturing the implantable tissue scaffold to implanting a wound site of a living being. | 1,600 |
1,323 | 15,720,373 | 1,633 | Methods for the isolation of CD271 + stem cell populations are important in the prevention or treatment of cardiovascular diseases and repair of cardiac tissue. The methods are applicable to stem cells from different sources and can be used to treat or prevent diseases or repair of tissues elsewhere in the organism's body. | 1. A method of preventing or treating a cardiovascular disease or disorder in a patient comprising:
isolating CD271+ mesenchymal stem cell precursors from bone marrow of a subject, wherein the subject is the same or different than the patient; administering to the patient a therapeutically effective amount of isolated CD271+ mesenchymal stem cell precursors; and, preventing or treating the cardiovascular disease or disorder in the patient. 2. The method of claim 1, wherein the CD271+ mesenchymal stem cell precursors are isolated from bone marrow cells having a low affinity nerve growth receptor (NGFR; CD271). 3. The method of claim 1, wherein the CD271+ mesenchymal stem cell precursors are isolated from donors comprising: autologous, syngeneic, allogeneic, or xenogeneic. 4. The method of claim 1, wherein the CD271+ mesenchymal stem cell precursors differentiate into myocytes, cardiomyocytes, endothelial cells, myocardial cells, epicardial cells, vascular endothelial cells, or smooth muscle cells after administration to the patient. 5. The method of claim 1, wherein the CD271+ mesenchymal stem cell precursors differentiate into lineages comprising: myocardial, vascular, or endothelial lineages after administration to the patient. 6. The method of claim 4, wherein the cardiomyocytes are identified by markers comprising: GATA-4, Nkx2.5 or α-sarcomeric actin. 7. The method of claim 4, wherein the smooth muscle cells are identified by markers comprising: α-smooth muscle actin or SMA22. 8. The method of claim 4, wherein the endothelial cells are identified by markers comprising: CD31 or vimentin. 9. The method of claim 1, wherein one or more agents are administered to the patient with the CD271+ mesenchymal stem cell precursors, the agents comprising at least one of: cytokines, chemotactic factors, growth factors, or differentiation factors. 10. The method of claim 1, wherein the cardiovascular disease or disorder comprises: heart failure, atherosclerosis, ischemia, myocardial infarction, transplantation, hypertension, restenosis, angina pectoris, rheumatic heart disease, congenital cardiovascular defect, ischemic cardiomyopathy, or age-related cardiomyopathy. 11. The method of claim 1, wherein the CD271+ mesenchymal stem cell precursors are administered to the patient in varying concentrations over a period of time. 12. The method of claim 1, wherein the CD271+ mesenchymal stem cell precursors engraft in the heart of the patient in infarct and border zones. 13. The method of claim 1, wherein the CD271+ mesenchymal stem cell precursors are conditioned with media conditioned by heart derived stromal cells before administration to the patient. 14. The method of claim 1, wherein the CD271+ mesenchymal stem cell precursors are cultured ex vivo before administration to the patient. 15. The method of claim 1, wherein freshly isolated CD271+ mesenchymal stem cell precursors are administered to the patient. 16. The method of claim 4, wherein the myocytes are identified by markers comprising: troponin I, α-sarcomeric actin, cardiac myocyte, desmin, α-cardiac actinin, connexin-43, GATA-4, Nkx-2.5, or MEF2. | Methods for the isolation of CD271 + stem cell populations are important in the prevention or treatment of cardiovascular diseases and repair of cardiac tissue. The methods are applicable to stem cells from different sources and can be used to treat or prevent diseases or repair of tissues elsewhere in the organism's body.1. A method of preventing or treating a cardiovascular disease or disorder in a patient comprising:
isolating CD271+ mesenchymal stem cell precursors from bone marrow of a subject, wherein the subject is the same or different than the patient; administering to the patient a therapeutically effective amount of isolated CD271+ mesenchymal stem cell precursors; and, preventing or treating the cardiovascular disease or disorder in the patient. 2. The method of claim 1, wherein the CD271+ mesenchymal stem cell precursors are isolated from bone marrow cells having a low affinity nerve growth receptor (NGFR; CD271). 3. The method of claim 1, wherein the CD271+ mesenchymal stem cell precursors are isolated from donors comprising: autologous, syngeneic, allogeneic, or xenogeneic. 4. The method of claim 1, wherein the CD271+ mesenchymal stem cell precursors differentiate into myocytes, cardiomyocytes, endothelial cells, myocardial cells, epicardial cells, vascular endothelial cells, or smooth muscle cells after administration to the patient. 5. The method of claim 1, wherein the CD271+ mesenchymal stem cell precursors differentiate into lineages comprising: myocardial, vascular, or endothelial lineages after administration to the patient. 6. The method of claim 4, wherein the cardiomyocytes are identified by markers comprising: GATA-4, Nkx2.5 or α-sarcomeric actin. 7. The method of claim 4, wherein the smooth muscle cells are identified by markers comprising: α-smooth muscle actin or SMA22. 8. The method of claim 4, wherein the endothelial cells are identified by markers comprising: CD31 or vimentin. 9. The method of claim 1, wherein one or more agents are administered to the patient with the CD271+ mesenchymal stem cell precursors, the agents comprising at least one of: cytokines, chemotactic factors, growth factors, or differentiation factors. 10. The method of claim 1, wherein the cardiovascular disease or disorder comprises: heart failure, atherosclerosis, ischemia, myocardial infarction, transplantation, hypertension, restenosis, angina pectoris, rheumatic heart disease, congenital cardiovascular defect, ischemic cardiomyopathy, or age-related cardiomyopathy. 11. The method of claim 1, wherein the CD271+ mesenchymal stem cell precursors are administered to the patient in varying concentrations over a period of time. 12. The method of claim 1, wherein the CD271+ mesenchymal stem cell precursors engraft in the heart of the patient in infarct and border zones. 13. The method of claim 1, wherein the CD271+ mesenchymal stem cell precursors are conditioned with media conditioned by heart derived stromal cells before administration to the patient. 14. The method of claim 1, wherein the CD271+ mesenchymal stem cell precursors are cultured ex vivo before administration to the patient. 15. The method of claim 1, wherein freshly isolated CD271+ mesenchymal stem cell precursors are administered to the patient. 16. The method of claim 4, wherein the myocytes are identified by markers comprising: troponin I, α-sarcomeric actin, cardiac myocyte, desmin, α-cardiac actinin, connexin-43, GATA-4, Nkx-2.5, or MEF2. | 1,600 |
1,324 | 14,007,549 | 1,628 | The invention relates to a composition comprising, in a physiologically acceptable oily medium, 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone and a solvent with solubility parameters in the Hansen solubility space such that 4.5<δ a <7 and 14<δ d <22. Use for caring for, making up and cleansing keratin materials. | 1. Composition comprising, in a physiologically acceptable oily medium, 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone and an organic solvent with solubility parameters in the Hansen solubility space such that 4.5<δa<7 and 14<δd<22. 2. Composition according to claim 1, wherein the organic solvent is chosen from isopropyl N-lauroyl sarcosinate, capric/caprylic acid triglycerides, 2-phenylethyl benzoate, isopropyl palmitate and isopropyl myristate. 3. Composition according to claim 1, wherein the organic solvent is chosen from isopropyl N-lauroyl sarcosinate and capric/caprylic acid triglycerides. 4. Composition according to claim 1, wherein the organic solvent is present in a content ranging from 0.05% to 30% by weight, relative to the total weight of the composition. 5. Composition according to claim 1, wherein the 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone is present in a content ranging from 0.01% to 10% by weight, relative to the total weight of the composition. 6. Composition according to claim 1, wherein the said organic solvent and the 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone are present in an organic solvent/4-(3-ethoxy-4-hydroxyphenyl)-2-butanone mass ratio of less than or equal to 10. 7. Composition according to claim 1, wherein it comprises an additional oil. 8. Composition according to claim 1, wherein it is in the form of a water-in-oil or oil-in-water emulsion, preferably an oil-in-water emulsion. 9. Non-therapeutic cosmetic treatment process for caring for and/or making up and/or cleansing keratin materials, comprising the application to the said keratin materials of a composition according to claim 1. 10. Composition according to claim 2, wherein the organic solvent is present in a content ranging from 0.05% to 30% by weight relative to the total weight of the composition. 11. Composition according to claim 3, wherein the organic solvent is present in a content ranging from 0.05% to 30% by weight relative to the total weight of the composition. 12. Composition according to claim 1, wherein the organic solvent is present in a content ranging from 0.05% to 10% by weight relative to the total weight of the composition. 13. Composition according to claim 2, wherein the organic solvent is present in a content ranging from 0.1% to 5% by weight relative to the total weight of the composition. 14. Composition according to claim 2, wherein the organic solvent is present in a content ranging from 0.1% to 2.5% by weight relative to the total weight of the composition. 15. Composition according to claim 2, wherein the 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone is present in a content ranging from 0.01% to 10% by weight, relative to the total weight of the composition. 16. Composition according to claim 3, wherein the 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone is present in a content ranging from 0.01% to 10% by weight, relative to the total weight of the composition. 17. Composition according to claim 4, wherein the 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone is present in a content ranging from 0.01% to 10% by weight, relative to the total weight of the composition. 18. Composition according to claim 2, wherein the said organic solvent and the 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone are present in a solvent/4-(3-ethoxy-4-hydroxyphenyl)-2-butanone mass ratio of less than or equal to 10. 19. Composition according to claim 3, wherein the said organic solvent and the 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone are present in a solvent/4-(3-ethoxy-4-hydroxyphenyl)-2-butanone mass ratio of less than or equal to 10. 20. Composition according to claim 4, wherein the said organic solvent and the 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone are present in a solvent/4-(3-ethoxy-4-hydroxyphenyl)-2-butanone mass ratio of less than or equal to 10. | The invention relates to a composition comprising, in a physiologically acceptable oily medium, 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone and a solvent with solubility parameters in the Hansen solubility space such that 4.5<δ a <7 and 14<δ d <22. Use for caring for, making up and cleansing keratin materials.1. Composition comprising, in a physiologically acceptable oily medium, 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone and an organic solvent with solubility parameters in the Hansen solubility space such that 4.5<δa<7 and 14<δd<22. 2. Composition according to claim 1, wherein the organic solvent is chosen from isopropyl N-lauroyl sarcosinate, capric/caprylic acid triglycerides, 2-phenylethyl benzoate, isopropyl palmitate and isopropyl myristate. 3. Composition according to claim 1, wherein the organic solvent is chosen from isopropyl N-lauroyl sarcosinate and capric/caprylic acid triglycerides. 4. Composition according to claim 1, wherein the organic solvent is present in a content ranging from 0.05% to 30% by weight, relative to the total weight of the composition. 5. Composition according to claim 1, wherein the 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone is present in a content ranging from 0.01% to 10% by weight, relative to the total weight of the composition. 6. Composition according to claim 1, wherein the said organic solvent and the 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone are present in an organic solvent/4-(3-ethoxy-4-hydroxyphenyl)-2-butanone mass ratio of less than or equal to 10. 7. Composition according to claim 1, wherein it comprises an additional oil. 8. Composition according to claim 1, wherein it is in the form of a water-in-oil or oil-in-water emulsion, preferably an oil-in-water emulsion. 9. Non-therapeutic cosmetic treatment process for caring for and/or making up and/or cleansing keratin materials, comprising the application to the said keratin materials of a composition according to claim 1. 10. Composition according to claim 2, wherein the organic solvent is present in a content ranging from 0.05% to 30% by weight relative to the total weight of the composition. 11. Composition according to claim 3, wherein the organic solvent is present in a content ranging from 0.05% to 30% by weight relative to the total weight of the composition. 12. Composition according to claim 1, wherein the organic solvent is present in a content ranging from 0.05% to 10% by weight relative to the total weight of the composition. 13. Composition according to claim 2, wherein the organic solvent is present in a content ranging from 0.1% to 5% by weight relative to the total weight of the composition. 14. Composition according to claim 2, wherein the organic solvent is present in a content ranging from 0.1% to 2.5% by weight relative to the total weight of the composition. 15. Composition according to claim 2, wherein the 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone is present in a content ranging from 0.01% to 10% by weight, relative to the total weight of the composition. 16. Composition according to claim 3, wherein the 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone is present in a content ranging from 0.01% to 10% by weight, relative to the total weight of the composition. 17. Composition according to claim 4, wherein the 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone is present in a content ranging from 0.01% to 10% by weight, relative to the total weight of the composition. 18. Composition according to claim 2, wherein the said organic solvent and the 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone are present in a solvent/4-(3-ethoxy-4-hydroxyphenyl)-2-butanone mass ratio of less than or equal to 10. 19. Composition according to claim 3, wherein the said organic solvent and the 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone are present in a solvent/4-(3-ethoxy-4-hydroxyphenyl)-2-butanone mass ratio of less than or equal to 10. 20. Composition according to claim 4, wherein the said organic solvent and the 4-(3-ethoxy-4-hydroxyphenyl)-2-butanone are present in a solvent/4-(3-ethoxy-4-hydroxyphenyl)-2-butanone mass ratio of less than or equal to 10. | 1,600 |
1,325 | 16,048,004 | 1,628 | A method of improving sexual function in premenopausal women, who have low Female Sexual Function Index (FSFI) baseline of less than or equal to 25.7. The method includes providing information to premenopausal women to provide input for calculating the FSFI score and, if the score is low, providing dehydroepiandrosterone (DHEA) supplementation to be taken in 25 mg dosages daily once, twice, thrice or four times over a period of time of four to six weeks. By the end of the period of time, the FSFI baselines of the premenopausal women improves by at least seven percent, serum androgen levels of the premenopausal women increase and follicle-stimulating hormone (FSH) levels of the premenopausal women decrease. | 1. A method of improving female sexual function through dehydroepiandrosterone (DHEA) supplementation, comprising the steps of:
giving a premenopausal woman access to information for her to provide input necessary for computing a Female Sexual Function Index (FSFI) baseline; confirming that the computed FSFI baseline of the premenopausal woman is less than or equal to 25.7 derived from the input; and supplying DHEA supplementation to the premenopausal woman to allow the premenopausal woman to consume the DHEA supplementation in 25 mg micronized dosages daily over a period of time of four to six weeks to improve the female sexual function. 2. The method of claim 1, further comprising:
increasing the FSFI baseline of the premenopausal woman by at least seven percent as a result of her consumption over the period of time of the DHEA supplementation supplied, the increasing of the FSFI baseline constituting an improvement in the female sexual function. 3. The method of claim 1, further comprising:
increasing a serum androgen level of the premenopausal woman over the period of time and decreasing a follicle-stimulating hormone (FSH) level of the premenopausal woman over the period of time, the increasing in the serum androgen level and the decreasing in the FSH level both arising as a result of the premenopausal woman consuming the DHEA supplementation supplied over the period of time and constituting an improvement in the female sexual function. 4. The method of claim 1, wherein the DHEA supplementation supplied is in 100 mg sizes, but splitting the DHEA supplementation into four results in realizing the micronized dosages of 25 mg each. 5. The method of claim 1, wherein at least one of six domain scores of the premenopausal woman increases after the DHEA supplementation is taken daily for the period of time, wherein the six domains are desire, arousal, lubrication, orgasm, satisfaction, and pain and an increase in any one of the sex domain scores over the period of time constitutes an improvement in the female sexual function. 6. The method of claim 5, wherein at least one of the six domain scores increase in accord with at least an increase of 40%, 46%, 33%, 54%, 24% and 25% respectively, corresponding to that for the desire, the arousal, the lubrication, the orgasm, the satisfaction, and the pain. 7. The method of claim 1, further comprising:
calculating the FSFI baseline based upon the input from the premenopausal woman that reflects her answers to queries that are part of the information provided. 8. The method of claim 1, wherein the information is provided online and the FSFI baseline is calculated online. 9. A method of improving female sexual function through dehydroepiandrosterone (DHEA) supplementation, comprising the steps of:
confirming that a Female Sexual Function Index (FSFI) baseline of a premenopausal woman is no more than 25.7 or that a Female Sexual Distress Scale-Revised (FSDS-R) baseline is no less than 11; and prescribing, administering or giving to the premenopausal woman micronized oral dosages of 25 mg of DHEA supplement and repeating as necessary to that the premenopausal woman swallows the micronized oral dosages daily for a period of time of four to six weeks and which results in:
an increase in a serum androgen level of the premenopausal woman over a period of time as a consequence of the premenopausal woman taking or being administered the micronized oral dosages of the DHEA supplement daily over the period of time; and
a decrease in follicle-stimulating hormone (FSH) level of the premenopausal woman over the period of time as a consequence of the premenopausal woman taking or being administered the micronized oral dosages of the DHEA supplement daily over the period of time,
wherein the increase in the serum androgen level and decrease in the FSH level improve the female sexual function of the premenopausal woman. 10. The method of claim 9, further comprising the steps of:
confirming that the serum androgen level increased by having measurements made of a serum androgen level of the premenopausal woman before and after the DHEA supplement is taken daily for the period of time and then making a comparison of the measurements of the androgen level before and after; and confirming that the follicle-stimulating hormone (FSH) level decreased by having measurements made of the FSH level of the premenopausal woman before and after the DHEA supplement is taken daily for the period of time and then making a comparison of the measurements of the FSH level before and after. 11. The method of claim 9, wherein the micronized oral dosage is 100 mg, further comprising the step of:
splitting the micronized oral dosage of 100 mg into 25 mg dosages, which are taken once, twice, thrice or four times daily. 12. The method of claim 9, further comprising the step of:
determining that the FSFI baseline increased by at least seven percent after the DHEA is taken daily for the period of time. 13. The method of claim 9, further comprising the step of:
determining that domain scores increased percent after the DHEA is taken daily for the period of time. 14. The method of claim 9, further comprising the step of:
determining that at least one of a plurality of the scores of domains selected from the group consisting of desire, arousal, lubrication, orgasm, satisfaction, and pain increase at least by 40%, 46%, 33%, 54%, 24% and 25% respectively. 15. The method of claim 15, further comprising:
prescribing, administering or giving the premenopausal woman 0.05 mg transdermal by pump between once to 2-times per day for the period of time. 16. A method of improving female sexual function through dehydroepiandrosterone (DHEA) supplementation, comprising the steps of:
giving a premenopausal woman access to information for her to provide input necessary for computing a Female Sexual Distress Scale-Revised (FSDS-R) baseline; confirming that the computed FSDS-R baseline of the premenopausal woman is equal to or greater than 11 derived from the input; and supplying DHEA supplementation to the premenopausal woman to allow the premenopausal woman to consume the DHEA supplementation in 25 mg micronized dosages daily over a period of time of four to six weeks to improve the female sexual function. 17. The method of claim 16, further comprising:
increasing the FSDS-R baseline of the premenopausal woman as a result of her consumption over the period of time of the DHEA supplementation supplied, the increasing of the FSDS-R baseline constituting an improvement in the female sexual function. 18. The method of claim 16, further comprising:
increasing a serum androgen level of the premenopausal woman over the period of time and decreasing a follicle-stimulating hormone (FSH) level of the premenopausal woman over the period of time, the increasing in the serum androgen level and the decreasing in the FSH level both arising as a result of the premenopausal woman consuming the DHEA supplementation supplied over the period of time and constituting an improvement in the female sexual function. 19. The method of claim 16, wherein the DHEA supplementation supplied is in 100 mg sizes, but splitting the DHEA supplementation into four results in realizing the micronized dosages of 25 mg each. 20. The method of claim 16, wherein at least one of six domain scores of the premenopausal woman increases after the DHEA supplementation is taken daily for the period of time, wherein the six domains are desire, arousal, lubrication, orgasm, satisfaction, and pain and an increase in any one of the sex domain scores over the period of time constitutes an improvement in the female sexual function. 21. The method of claim 16, wherein the information is provided online and the FSDS-R baseline is calculated online. | A method of improving sexual function in premenopausal women, who have low Female Sexual Function Index (FSFI) baseline of less than or equal to 25.7. The method includes providing information to premenopausal women to provide input for calculating the FSFI score and, if the score is low, providing dehydroepiandrosterone (DHEA) supplementation to be taken in 25 mg dosages daily once, twice, thrice or four times over a period of time of four to six weeks. By the end of the period of time, the FSFI baselines of the premenopausal women improves by at least seven percent, serum androgen levels of the premenopausal women increase and follicle-stimulating hormone (FSH) levels of the premenopausal women decrease.1. A method of improving female sexual function through dehydroepiandrosterone (DHEA) supplementation, comprising the steps of:
giving a premenopausal woman access to information for her to provide input necessary for computing a Female Sexual Function Index (FSFI) baseline; confirming that the computed FSFI baseline of the premenopausal woman is less than or equal to 25.7 derived from the input; and supplying DHEA supplementation to the premenopausal woman to allow the premenopausal woman to consume the DHEA supplementation in 25 mg micronized dosages daily over a period of time of four to six weeks to improve the female sexual function. 2. The method of claim 1, further comprising:
increasing the FSFI baseline of the premenopausal woman by at least seven percent as a result of her consumption over the period of time of the DHEA supplementation supplied, the increasing of the FSFI baseline constituting an improvement in the female sexual function. 3. The method of claim 1, further comprising:
increasing a serum androgen level of the premenopausal woman over the period of time and decreasing a follicle-stimulating hormone (FSH) level of the premenopausal woman over the period of time, the increasing in the serum androgen level and the decreasing in the FSH level both arising as a result of the premenopausal woman consuming the DHEA supplementation supplied over the period of time and constituting an improvement in the female sexual function. 4. The method of claim 1, wherein the DHEA supplementation supplied is in 100 mg sizes, but splitting the DHEA supplementation into four results in realizing the micronized dosages of 25 mg each. 5. The method of claim 1, wherein at least one of six domain scores of the premenopausal woman increases after the DHEA supplementation is taken daily for the period of time, wherein the six domains are desire, arousal, lubrication, orgasm, satisfaction, and pain and an increase in any one of the sex domain scores over the period of time constitutes an improvement in the female sexual function. 6. The method of claim 5, wherein at least one of the six domain scores increase in accord with at least an increase of 40%, 46%, 33%, 54%, 24% and 25% respectively, corresponding to that for the desire, the arousal, the lubrication, the orgasm, the satisfaction, and the pain. 7. The method of claim 1, further comprising:
calculating the FSFI baseline based upon the input from the premenopausal woman that reflects her answers to queries that are part of the information provided. 8. The method of claim 1, wherein the information is provided online and the FSFI baseline is calculated online. 9. A method of improving female sexual function through dehydroepiandrosterone (DHEA) supplementation, comprising the steps of:
confirming that a Female Sexual Function Index (FSFI) baseline of a premenopausal woman is no more than 25.7 or that a Female Sexual Distress Scale-Revised (FSDS-R) baseline is no less than 11; and prescribing, administering or giving to the premenopausal woman micronized oral dosages of 25 mg of DHEA supplement and repeating as necessary to that the premenopausal woman swallows the micronized oral dosages daily for a period of time of four to six weeks and which results in:
an increase in a serum androgen level of the premenopausal woman over a period of time as a consequence of the premenopausal woman taking or being administered the micronized oral dosages of the DHEA supplement daily over the period of time; and
a decrease in follicle-stimulating hormone (FSH) level of the premenopausal woman over the period of time as a consequence of the premenopausal woman taking or being administered the micronized oral dosages of the DHEA supplement daily over the period of time,
wherein the increase in the serum androgen level and decrease in the FSH level improve the female sexual function of the premenopausal woman. 10. The method of claim 9, further comprising the steps of:
confirming that the serum androgen level increased by having measurements made of a serum androgen level of the premenopausal woman before and after the DHEA supplement is taken daily for the period of time and then making a comparison of the measurements of the androgen level before and after; and confirming that the follicle-stimulating hormone (FSH) level decreased by having measurements made of the FSH level of the premenopausal woman before and after the DHEA supplement is taken daily for the period of time and then making a comparison of the measurements of the FSH level before and after. 11. The method of claim 9, wherein the micronized oral dosage is 100 mg, further comprising the step of:
splitting the micronized oral dosage of 100 mg into 25 mg dosages, which are taken once, twice, thrice or four times daily. 12. The method of claim 9, further comprising the step of:
determining that the FSFI baseline increased by at least seven percent after the DHEA is taken daily for the period of time. 13. The method of claim 9, further comprising the step of:
determining that domain scores increased percent after the DHEA is taken daily for the period of time. 14. The method of claim 9, further comprising the step of:
determining that at least one of a plurality of the scores of domains selected from the group consisting of desire, arousal, lubrication, orgasm, satisfaction, and pain increase at least by 40%, 46%, 33%, 54%, 24% and 25% respectively. 15. The method of claim 15, further comprising:
prescribing, administering or giving the premenopausal woman 0.05 mg transdermal by pump between once to 2-times per day for the period of time. 16. A method of improving female sexual function through dehydroepiandrosterone (DHEA) supplementation, comprising the steps of:
giving a premenopausal woman access to information for her to provide input necessary for computing a Female Sexual Distress Scale-Revised (FSDS-R) baseline; confirming that the computed FSDS-R baseline of the premenopausal woman is equal to or greater than 11 derived from the input; and supplying DHEA supplementation to the premenopausal woman to allow the premenopausal woman to consume the DHEA supplementation in 25 mg micronized dosages daily over a period of time of four to six weeks to improve the female sexual function. 17. The method of claim 16, further comprising:
increasing the FSDS-R baseline of the premenopausal woman as a result of her consumption over the period of time of the DHEA supplementation supplied, the increasing of the FSDS-R baseline constituting an improvement in the female sexual function. 18. The method of claim 16, further comprising:
increasing a serum androgen level of the premenopausal woman over the period of time and decreasing a follicle-stimulating hormone (FSH) level of the premenopausal woman over the period of time, the increasing in the serum androgen level and the decreasing in the FSH level both arising as a result of the premenopausal woman consuming the DHEA supplementation supplied over the period of time and constituting an improvement in the female sexual function. 19. The method of claim 16, wherein the DHEA supplementation supplied is in 100 mg sizes, but splitting the DHEA supplementation into four results in realizing the micronized dosages of 25 mg each. 20. The method of claim 16, wherein at least one of six domain scores of the premenopausal woman increases after the DHEA supplementation is taken daily for the period of time, wherein the six domains are desire, arousal, lubrication, orgasm, satisfaction, and pain and an increase in any one of the sex domain scores over the period of time constitutes an improvement in the female sexual function. 21. The method of claim 16, wherein the information is provided online and the FSDS-R baseline is calculated online. | 1,600 |
1,326 | 15,463,665 | 1,645 | The present invention is directed to improved microbial antigen vaccines, pharmaceutical compositions, immunogenic compositions and antibodies and their use in the treatment of microbial infections, particularly those of bacterial origin, including Staphylococcal origin. Ideally, the present invention is directed to a recombinant staphylococcal MSCRAMM or MSCRAMM-like proteins, or fragment thereof, with reduced binding to its host ligand, for use in therapy. | 1. An immunogenic pharmaceutical composition comprising a recombinant staphylococcal clumping factor A (ClfA), or fragment thereof comprising at least amino acid residues 221 to 531 of the fibrinogen binding region, characterized by at least one amino acid residue substitution or deletion at amino acid residue Ala254, Tyr256, Pro336, Tyr338, Ile387, Lys389, Glu526 and/or Val527 to result in a recombinant fibrinogen binding protein with reduced ability or lacking the ability to non-covalently bind fibrinogen; and stimulating a greater antibody immune response than the wild type ClfA protein. 2. A vaccine comprising a recombinant staphylococcal clumping factor A (ClfA), or fragment thereof comprising at least amino acid residues 221 to 531 of the fibrinogen binding region, characterized by at least one amino acid residue substitution or deletion at amino acid residue Ala254, Tyr256, Pro336, Tyr338, Ile387, Lys389, Glu526 and/or Val527 to result in a recombinant fibrinogen binding protein with reduced ability or lacking the ability to non-covalently bind fibrinogen; and stimulating a greater antibody immune response than the wild type ClfA protein. | The present invention is directed to improved microbial antigen vaccines, pharmaceutical compositions, immunogenic compositions and antibodies and their use in the treatment of microbial infections, particularly those of bacterial origin, including Staphylococcal origin. Ideally, the present invention is directed to a recombinant staphylococcal MSCRAMM or MSCRAMM-like proteins, or fragment thereof, with reduced binding to its host ligand, for use in therapy.1. An immunogenic pharmaceutical composition comprising a recombinant staphylococcal clumping factor A (ClfA), or fragment thereof comprising at least amino acid residues 221 to 531 of the fibrinogen binding region, characterized by at least one amino acid residue substitution or deletion at amino acid residue Ala254, Tyr256, Pro336, Tyr338, Ile387, Lys389, Glu526 and/or Val527 to result in a recombinant fibrinogen binding protein with reduced ability or lacking the ability to non-covalently bind fibrinogen; and stimulating a greater antibody immune response than the wild type ClfA protein. 2. A vaccine comprising a recombinant staphylococcal clumping factor A (ClfA), or fragment thereof comprising at least amino acid residues 221 to 531 of the fibrinogen binding region, characterized by at least one amino acid residue substitution or deletion at amino acid residue Ala254, Tyr256, Pro336, Tyr338, Ile387, Lys389, Glu526 and/or Val527 to result in a recombinant fibrinogen binding protein with reduced ability or lacking the ability to non-covalently bind fibrinogen; and stimulating a greater antibody immune response than the wild type ClfA protein. | 1,600 |
1,327 | 15,641,114 | 1,653 | Aquafeed, animal feed, and other food products, as well as nutritional and pharmaceutical compounds, chemicals and biomaterials are important commodities that can be produced at commercial scale by fermentation of microorganisms. The present invention provides a method for producing these valuable multi-carbon compounds from simple gas feedstocks, such as carbon dioxide, hydrogen and oxygen, by cultivating a consortium of microbial cells specially selected for this purpose in an aqueous culture medium. In addition to exploiting inexpensive feedstocks, such as waste industrial gas for this cultivation, the platform described herein also provides the advantage of removing carbon dioxide and other waste gases from industrial emissions, which would otherwise contribute to global climate change. Furthermore, the cultivation of a microbial consortium can provide highly nutritious components to a feed blend that might not be available from a monoculture. | 1. A food or feed additive product comprising:
a consortium of chemoautotrophic and photoautotrophic bacteria and heterotrophic microbes, the consortium including chemoautotrophic bacteria from the genera Cupriavidus, Methylococcus, or Rhodococcus, photoautotrophic bacteria from the genera Rhodobacter, Rhodospirillum, Rhodopseudomonas, or Arthrospira, and heterotrophic microbes from the genera Bacillus, Bacteroides, Lactococcus, Leuconostoc, Pediococcus, Acidilactici, Pediococcus, Propionibacterium, Streptococcus, Bifidobacterium, or Lactobacillus. 2. A method comprising:
providing a consortium of chemoautotrophic and photoautotrophic bacteria and heterotrophic microbes within a system, the system including a fermentation vessel filled with an aqueous medium comprising the consortium, the fermentation vessel having an input port into which gaseous substrates are introduced into the aqueous medium, the fermentation vessel further having an exhaust port through which gases exit the fermentation vessel, wherein the aqueous medium comprises inorganic anions and inorganic cations, and wherein the aqueous medium contains a concentration of no more than 0.05% of each of added sugars, yeast extract, tryptone, and organic carbon compounds, the consortium including chemoautotrophic bacteria from the genera Cupriavidus, Rhodococcus, or Methylococcus,
photoautotrophic bacteria from the genera Rhodobacter, Rhodospirillum, Rhodopseudomonas, or Arthrospira, and
heterotrophic microbes from the genera of Bacillus, Bacteroides, Bifidobacterium, Lactobacillus, Lactococcus, Leuconostoc, Acidilactici, Pediococcus, Propionibacterium, or Streptococcus;
introducing a first gaseous substrate into the input port, the first gaseous substrate including carbon predominantly in the form of single-carbon atom molecules; introducing a second gaseous substrate into the aqueous medium, the second gaseous substrate including predominantly hydrogen gas (H2) or methane gas (CH4) or a mixture thereof, wherein either of the first or second substrates additionally includes oxygen gas (O2); and harvesting cells of the bacteria from the system. 3. The method of claim 2, wherein
the chemoautotrophic bacteria include one or more of Cupriavidus necator, Cupriavidus basilensis, Methylococcus capsulatus, the photoautotrophic bacteria include one or more of Rhodobacter capsulatus, Rhodospirillum rubrum, Rhodobacter sphaeroides, Rhodopseudomonas palustris, and the heterotrophic microbes include one or more of
Aspergillus niger, Aspergillus oryzae, Bacillus coagulans, Bacillus lentus, Bacillus licheniformis, Bacillus megaterium, Bacillus pumilus, Bacillus subtilis, Bacteroides amylophilus, Bacteroides capillosus, Bacteroides ruminocola, Bacteroides suis, Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium thermophilum, Bifidobacterium breve, Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus cellobiosus, Lactobacillus curvatus, Lactobacillus delbruekii, Lactobacillus fermentum, Lactobacillus helveticus, Lactobacillus johnsonii, Lactobacillus lactis, Lactobacillus paracasei, Lactobacillus parafarraginis, Lactobacillus plantarum, Lactobacillus reuterii, Lactobacillus rhamnosus, Lactobacillus salivarius, Lactobacillus sporogenes, Lactococcus lactis, Leuconostoc mesenteroides, Pediococcus acidilactici, Pediococcus cerevisiae, Pediococcus pentosaceus, Propionibacterium shermanii, Propionibacterium freudenreichii, Saccharomyces boulardii, Saccharomyces cerevisiae, Streptococcus cremoris, Streptococcus diacetylactis, Streptococcus faecium, Streptococcus intermedius, Streptococcus lactis, Streptococcus thermophiles. 4. The method of claim 2, wherein the chemoautotrophic bacteria comprise Cupriavidus necator. 5. The method of claim 2, wherein the photoautotrophic bacteria comprise Rhodobacter capsulatus. 6. The method of claim 2, wherein the heterotrophic microbes comprise Bifidobacterium animalis. 7. The method of claim 2, wherein the heterotrophic microbes comprise Lactobacillus parafarraginis. 8. The method of claim 2, wherein the heterotrophic microbes comprise Lactobacillus acidophilus or Lactobacillus casei. 9. The method of claim 2, wherein the heterotrophic microbes comprise Bacillus megaterium. 10. The method of claim 2, wherein heterotrophic microbes comprise Bacillus subtilis. 11. The method of claim 2, wherein providing the consortium includes adding the chemoautotrophic bacteria into the fermentation vessel and then adding the photoautotrophic bacteria and heterotrophic microbes into the fermentation vessel. 12. The method of claim 2, wherein providing the consortium of chemoautotrophic and photoautotrophic bacteria and heterotrophic microbes includes adding the chemoautotrophic and photoautotrophic bacteria and heterotrophic microbes into the fermentation vessel simultaneously. 13. The method of claim 2, wherein a concentration of single-carbon atom molecules in the first gaseous substrate and a concentration of hydrogen gas in the second gaseous substrate are both higher concentrations than are found in the ambient atmosphere. 14. The method of claim 2, wherein the single-carbon atom molecules comprise CO2 and the first gaseous substrate includes a concentration of CO2 and a concentration of CH4, wherein the second substrate includes a concentration of hydrogen gas, and wherein all three concentrations are higher concentrations than are found in the ambient atmosphere. 15. The method of claim 2, wherein the single-carbon atom molecules comprise CO, CO2, and CH4, and the first gaseous substrate includes a concentration of CO2, a concentration of CH4, and a concentration of CO, wherein the second substrate includes a concentration of hydrogen gas, and wherein all four concentrations are higher concentrations than are found in the ambient atmosphere. 16. The method of claim 2, wherein the single-carbon atom molecules comprise CO and CH4 and the first gaseous substrate includes a concentration of CO and a concentration of CH4, wherein the second substrate includes a concentration of hydrogen gas, and wherein all three concentrations are higher concentrations than are found in the ambient atmosphere. 17. The method of claim 2, wherein the single-carbon atom molecules comprise CH4, CO, and CO2. 18. The method of claim 2, wherein the single-carbon atom molecules comprise CO and CH4 and the first gaseous substrate includes a concentration of CO and a concentration of CH4, wherein the second substrate includes a concentration of hydrogen gas, and wherein all three concentrations are higher concentrations than are found in the ambient atmosphere. 19. The method of claim 2, wherein the single-carbon atom molecules comprise CO and CH4 and the first gaseous substrate includes a concentration of CO and a concentration of CH4, and wherein both concentrations are higher concentrations than are found in the ambient atmosphere. 20. (canceled) 21. A product made by the method of claim 2. 22. The method of claim 2, wherein the inorganic anions comprise phosphate, nitrate, sulfate, carbonate, or ammonium. 23. The method of claim 2, wherein the inorganic cations comprise iron, nickel, calcium, magnesium, manganese, or cobalt. 24. The method of claim 2, wherein one of the bacteria of the consortium has been genetically modified. 25. The method of claim 2, wherein one of the bacteria of the consortium produces a carotenoid. 26. The method of claim 2, wherein one of the bacteria of the consortium produces a vitamin. 27. The method of claim 2, wherein one of the bacteria of the consortium produces a protein. 28. The method of claim 2, wherein one of the bacteria of the consortium produces an astaxanthin. | Aquafeed, animal feed, and other food products, as well as nutritional and pharmaceutical compounds, chemicals and biomaterials are important commodities that can be produced at commercial scale by fermentation of microorganisms. The present invention provides a method for producing these valuable multi-carbon compounds from simple gas feedstocks, such as carbon dioxide, hydrogen and oxygen, by cultivating a consortium of microbial cells specially selected for this purpose in an aqueous culture medium. In addition to exploiting inexpensive feedstocks, such as waste industrial gas for this cultivation, the platform described herein also provides the advantage of removing carbon dioxide and other waste gases from industrial emissions, which would otherwise contribute to global climate change. Furthermore, the cultivation of a microbial consortium can provide highly nutritious components to a feed blend that might not be available from a monoculture.1. A food or feed additive product comprising:
a consortium of chemoautotrophic and photoautotrophic bacteria and heterotrophic microbes, the consortium including chemoautotrophic bacteria from the genera Cupriavidus, Methylococcus, or Rhodococcus, photoautotrophic bacteria from the genera Rhodobacter, Rhodospirillum, Rhodopseudomonas, or Arthrospira, and heterotrophic microbes from the genera Bacillus, Bacteroides, Lactococcus, Leuconostoc, Pediococcus, Acidilactici, Pediococcus, Propionibacterium, Streptococcus, Bifidobacterium, or Lactobacillus. 2. A method comprising:
providing a consortium of chemoautotrophic and photoautotrophic bacteria and heterotrophic microbes within a system, the system including a fermentation vessel filled with an aqueous medium comprising the consortium, the fermentation vessel having an input port into which gaseous substrates are introduced into the aqueous medium, the fermentation vessel further having an exhaust port through which gases exit the fermentation vessel, wherein the aqueous medium comprises inorganic anions and inorganic cations, and wherein the aqueous medium contains a concentration of no more than 0.05% of each of added sugars, yeast extract, tryptone, and organic carbon compounds, the consortium including chemoautotrophic bacteria from the genera Cupriavidus, Rhodococcus, or Methylococcus,
photoautotrophic bacteria from the genera Rhodobacter, Rhodospirillum, Rhodopseudomonas, or Arthrospira, and
heterotrophic microbes from the genera of Bacillus, Bacteroides, Bifidobacterium, Lactobacillus, Lactococcus, Leuconostoc, Acidilactici, Pediococcus, Propionibacterium, or Streptococcus;
introducing a first gaseous substrate into the input port, the first gaseous substrate including carbon predominantly in the form of single-carbon atom molecules; introducing a second gaseous substrate into the aqueous medium, the second gaseous substrate including predominantly hydrogen gas (H2) or methane gas (CH4) or a mixture thereof, wherein either of the first or second substrates additionally includes oxygen gas (O2); and harvesting cells of the bacteria from the system. 3. The method of claim 2, wherein
the chemoautotrophic bacteria include one or more of Cupriavidus necator, Cupriavidus basilensis, Methylococcus capsulatus, the photoautotrophic bacteria include one or more of Rhodobacter capsulatus, Rhodospirillum rubrum, Rhodobacter sphaeroides, Rhodopseudomonas palustris, and the heterotrophic microbes include one or more of
Aspergillus niger, Aspergillus oryzae, Bacillus coagulans, Bacillus lentus, Bacillus licheniformis, Bacillus megaterium, Bacillus pumilus, Bacillus subtilis, Bacteroides amylophilus, Bacteroides capillosus, Bacteroides ruminocola, Bacteroides suis, Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium thermophilum, Bifidobacterium breve, Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus cellobiosus, Lactobacillus curvatus, Lactobacillus delbruekii, Lactobacillus fermentum, Lactobacillus helveticus, Lactobacillus johnsonii, Lactobacillus lactis, Lactobacillus paracasei, Lactobacillus parafarraginis, Lactobacillus plantarum, Lactobacillus reuterii, Lactobacillus rhamnosus, Lactobacillus salivarius, Lactobacillus sporogenes, Lactococcus lactis, Leuconostoc mesenteroides, Pediococcus acidilactici, Pediococcus cerevisiae, Pediococcus pentosaceus, Propionibacterium shermanii, Propionibacterium freudenreichii, Saccharomyces boulardii, Saccharomyces cerevisiae, Streptococcus cremoris, Streptococcus diacetylactis, Streptococcus faecium, Streptococcus intermedius, Streptococcus lactis, Streptococcus thermophiles. 4. The method of claim 2, wherein the chemoautotrophic bacteria comprise Cupriavidus necator. 5. The method of claim 2, wherein the photoautotrophic bacteria comprise Rhodobacter capsulatus. 6. The method of claim 2, wherein the heterotrophic microbes comprise Bifidobacterium animalis. 7. The method of claim 2, wherein the heterotrophic microbes comprise Lactobacillus parafarraginis. 8. The method of claim 2, wherein the heterotrophic microbes comprise Lactobacillus acidophilus or Lactobacillus casei. 9. The method of claim 2, wherein the heterotrophic microbes comprise Bacillus megaterium. 10. The method of claim 2, wherein heterotrophic microbes comprise Bacillus subtilis. 11. The method of claim 2, wherein providing the consortium includes adding the chemoautotrophic bacteria into the fermentation vessel and then adding the photoautotrophic bacteria and heterotrophic microbes into the fermentation vessel. 12. The method of claim 2, wherein providing the consortium of chemoautotrophic and photoautotrophic bacteria and heterotrophic microbes includes adding the chemoautotrophic and photoautotrophic bacteria and heterotrophic microbes into the fermentation vessel simultaneously. 13. The method of claim 2, wherein a concentration of single-carbon atom molecules in the first gaseous substrate and a concentration of hydrogen gas in the second gaseous substrate are both higher concentrations than are found in the ambient atmosphere. 14. The method of claim 2, wherein the single-carbon atom molecules comprise CO2 and the first gaseous substrate includes a concentration of CO2 and a concentration of CH4, wherein the second substrate includes a concentration of hydrogen gas, and wherein all three concentrations are higher concentrations than are found in the ambient atmosphere. 15. The method of claim 2, wherein the single-carbon atom molecules comprise CO, CO2, and CH4, and the first gaseous substrate includes a concentration of CO2, a concentration of CH4, and a concentration of CO, wherein the second substrate includes a concentration of hydrogen gas, and wherein all four concentrations are higher concentrations than are found in the ambient atmosphere. 16. The method of claim 2, wherein the single-carbon atom molecules comprise CO and CH4 and the first gaseous substrate includes a concentration of CO and a concentration of CH4, wherein the second substrate includes a concentration of hydrogen gas, and wherein all three concentrations are higher concentrations than are found in the ambient atmosphere. 17. The method of claim 2, wherein the single-carbon atom molecules comprise CH4, CO, and CO2. 18. The method of claim 2, wherein the single-carbon atom molecules comprise CO and CH4 and the first gaseous substrate includes a concentration of CO and a concentration of CH4, wherein the second substrate includes a concentration of hydrogen gas, and wherein all three concentrations are higher concentrations than are found in the ambient atmosphere. 19. The method of claim 2, wherein the single-carbon atom molecules comprise CO and CH4 and the first gaseous substrate includes a concentration of CO and a concentration of CH4, and wherein both concentrations are higher concentrations than are found in the ambient atmosphere. 20. (canceled) 21. A product made by the method of claim 2. 22. The method of claim 2, wherein the inorganic anions comprise phosphate, nitrate, sulfate, carbonate, or ammonium. 23. The method of claim 2, wherein the inorganic cations comprise iron, nickel, calcium, magnesium, manganese, or cobalt. 24. The method of claim 2, wherein one of the bacteria of the consortium has been genetically modified. 25. The method of claim 2, wherein one of the bacteria of the consortium produces a carotenoid. 26. The method of claim 2, wherein one of the bacteria of the consortium produces a vitamin. 27. The method of claim 2, wherein one of the bacteria of the consortium produces a protein. 28. The method of claim 2, wherein one of the bacteria of the consortium produces an astaxanthin. | 1,600 |
1,328 | 15,549,877 | 1,623 | A process for preparing an ester of a cellulose ether comprises the steps of reacting a cellulose ether with a dicarboxylic acid anhydride or with a combination of a dicarboxylic acid anhydride and an aliphatic monocarboxylic acid anhydride, wherein the esterification is conducted i) in the absence of an esterification catalyst or in the presence of no more than 0.1 mole of an esterification catalyst per mole of anhydroglucose units of cellulose ether, and ii) in the presence of an aliphatic carboxylic acid, wherein the molar ratio [aliphatic carboxylic acid/anhydroglucose units of cellulose ether] is up to 12/1. | 1. A process for preparing an ester of a cellulose ether comprising the steps of
reacting a cellulose ether with a dicarboxylic acid anhydride or with a combination of a dicarboxylic acid anhydride and an aliphatic monocarboxylic acid anhydride, wherein the esterification is conducted
i) in the absence of an esterification catalyst or in the presence of no more than 0.1 mole of an esterification catalyst per mole of anhydroglucose units of cellulose ether, and
ii) in the presence of an aliphatic carboxylic acid, wherein the molar ratio [aliphatic carboxylic acid/anhydroglucose units of cellulose ether] is up to 12/1. 2. The process of claim 1 wherein the molar ratio [aliphatic carboxylic acid/anhydroglucose units of cellulose ether] is from [0.7/1] to [9.0/1]. 3. The process of claim 2 wherein the molar ratio [aliphatic carboxylic acid/anhydroglucose units of cellulose ether] is from [3.0/1] to [9.0/1]. 4. The process of claim 1 wherein the esterification is conducted in the absence of an esterification catalyst or in the presence of no more than 0.02 mole of an esterification catalyst per mole of anhydroglucose units of cellulose ether. 5. The process of claim 1 wherein the esterification catalyst is an alkali metal carboxylate. 6. The process of claim 1 wherein the esterification is conducted in the absence of an esterification catalyst. 7. The process of claim 1 wherein the cellulose ether has a viscosity of from 1.2 to 200 mPa·s, measured as a 2 weight-% solution in water at 20° C. according to ASTM D2363-79 (Reapproved 2006). 8. The process of claim 7 wherein the cellulose ether has a viscosity of from 2.4 to 5 mPa·s, measured as a 2 weight-% solution in water at 20° C. according to ASTM D2363-79 (Reapproved 2006). 9. The process of claim 1 wherein the cellulose ether is an alkyl cellulose, a hydroxyalkylcellulose or a hydroxyalkyl alkylcellulose. 10. The process of claim 9 wherein the cellulose ether is hydroxypropyl methylcellulose. 11. The process of claim 1 wherein the cellulose ether is reacted with a) succinic anhydride in combination with b) an aliphatic monocarboxylic acid anhydride selected from the group consisting of acetic anhydride, butyric anhydride and propionic anhydride. 12. The process of claim 11 wherein hydroxypropyl methylcellulose is reacted with succinic anhydride and acetic anhydride to produce hydroxypropyl methyl cellulose acetate succinate. 13. The process of claim 1 wherein the molar ratio between the anhydride of an aliphatic monocarboxylic acid and the anhydroglucose units of the cellulose ether is from 0.1/1 to 7/1. 14. The process of claim 1 wherein the molar ratio between the anhydride of a dicarboxylic acid and the anhydroglucose units of cellulose ether is from 0.1/1 to 3.2/1. 15. The process of claim 1 wherein the esterification is conducted at a temperature of from 70° C. to 110° C. | A process for preparing an ester of a cellulose ether comprises the steps of reacting a cellulose ether with a dicarboxylic acid anhydride or with a combination of a dicarboxylic acid anhydride and an aliphatic monocarboxylic acid anhydride, wherein the esterification is conducted i) in the absence of an esterification catalyst or in the presence of no more than 0.1 mole of an esterification catalyst per mole of anhydroglucose units of cellulose ether, and ii) in the presence of an aliphatic carboxylic acid, wherein the molar ratio [aliphatic carboxylic acid/anhydroglucose units of cellulose ether] is up to 12/1.1. A process for preparing an ester of a cellulose ether comprising the steps of
reacting a cellulose ether with a dicarboxylic acid anhydride or with a combination of a dicarboxylic acid anhydride and an aliphatic monocarboxylic acid anhydride, wherein the esterification is conducted
i) in the absence of an esterification catalyst or in the presence of no more than 0.1 mole of an esterification catalyst per mole of anhydroglucose units of cellulose ether, and
ii) in the presence of an aliphatic carboxylic acid, wherein the molar ratio [aliphatic carboxylic acid/anhydroglucose units of cellulose ether] is up to 12/1. 2. The process of claim 1 wherein the molar ratio [aliphatic carboxylic acid/anhydroglucose units of cellulose ether] is from [0.7/1] to [9.0/1]. 3. The process of claim 2 wherein the molar ratio [aliphatic carboxylic acid/anhydroglucose units of cellulose ether] is from [3.0/1] to [9.0/1]. 4. The process of claim 1 wherein the esterification is conducted in the absence of an esterification catalyst or in the presence of no more than 0.02 mole of an esterification catalyst per mole of anhydroglucose units of cellulose ether. 5. The process of claim 1 wherein the esterification catalyst is an alkali metal carboxylate. 6. The process of claim 1 wherein the esterification is conducted in the absence of an esterification catalyst. 7. The process of claim 1 wherein the cellulose ether has a viscosity of from 1.2 to 200 mPa·s, measured as a 2 weight-% solution in water at 20° C. according to ASTM D2363-79 (Reapproved 2006). 8. The process of claim 7 wherein the cellulose ether has a viscosity of from 2.4 to 5 mPa·s, measured as a 2 weight-% solution in water at 20° C. according to ASTM D2363-79 (Reapproved 2006). 9. The process of claim 1 wherein the cellulose ether is an alkyl cellulose, a hydroxyalkylcellulose or a hydroxyalkyl alkylcellulose. 10. The process of claim 9 wherein the cellulose ether is hydroxypropyl methylcellulose. 11. The process of claim 1 wherein the cellulose ether is reacted with a) succinic anhydride in combination with b) an aliphatic monocarboxylic acid anhydride selected from the group consisting of acetic anhydride, butyric anhydride and propionic anhydride. 12. The process of claim 11 wherein hydroxypropyl methylcellulose is reacted with succinic anhydride and acetic anhydride to produce hydroxypropyl methyl cellulose acetate succinate. 13. The process of claim 1 wherein the molar ratio between the anhydride of an aliphatic monocarboxylic acid and the anhydroglucose units of the cellulose ether is from 0.1/1 to 7/1. 14. The process of claim 1 wherein the molar ratio between the anhydride of a dicarboxylic acid and the anhydroglucose units of cellulose ether is from 0.1/1 to 3.2/1. 15. The process of claim 1 wherein the esterification is conducted at a temperature of from 70° C. to 110° C. | 1,600 |
1,329 | 14,537,057 | 1,632 | A method for producing a polyunsaturated fatty acid (PUFA) or a lipid containing a PUFA, a microbial cell containing a PUFA, and use of the microbial cell are provided. A method for producing a polyunsaturated fatty acid (PUFA) or a lipid containing a PUFA including culture of a microorganism capable of producing arachidonic acid (ARA) and/or dihomo-gamma-linolenic acid (DGLA) is provided, the method including at least one of the following steps: (a) adding an organic acid in an amount of 0.01 to 5 w/v % to a culture medium after the beginning of main culture; (b) increasing the pH of the culture medium to a range effective for culture after the beginning of the main culture; and (c) adding a metal sulfate in an amount of 0.01 to 0.5 w/w % to the main culture medium. | 1-7. (canceled) 8. A method for producing arachidonic acid (ARA) comprising cultivating Mortierella alpina by an aeration-spinner culture process in a liquid culture medium, and the method further comprising at least the following steps:
adding at least one organic acid selected from the group consisting of succinic acid, fumaric acid, pyruvic acid, and malic acid, or a mixture thereof to the liquid culture medium in an amount of 0.2 to 5 w/v % at least three days from the beginning of the culture process, increasing the pH of the culture medium to the range of 6.6 to 7.5 at least three days from the beginning of the culture process, and adding a metal sulfate selected from the group consisting of MgSO4, CaSO4, K2SO4, FeSO4, and MnSO4, or a mixture thereof in an amount of 0.01 to 0.5 w/w % to the culture medium. 9. The method according to claim 8, further comprising drying the Mortierella alpina, and then adding either dry cells or the ARA derived from the cells to food or to drink. 10. The method according to claim 8, wherein addition of the organic acid and pH adjustment are carried out at different time points from an addition of an initial carbon source to the culture medium. 11. The method according to claim 8, wherein the metal sulfate is added before the beginning of the culture process. | A method for producing a polyunsaturated fatty acid (PUFA) or a lipid containing a PUFA, a microbial cell containing a PUFA, and use of the microbial cell are provided. A method for producing a polyunsaturated fatty acid (PUFA) or a lipid containing a PUFA including culture of a microorganism capable of producing arachidonic acid (ARA) and/or dihomo-gamma-linolenic acid (DGLA) is provided, the method including at least one of the following steps: (a) adding an organic acid in an amount of 0.01 to 5 w/v % to a culture medium after the beginning of main culture; (b) increasing the pH of the culture medium to a range effective for culture after the beginning of the main culture; and (c) adding a metal sulfate in an amount of 0.01 to 0.5 w/w % to the main culture medium.1-7. (canceled) 8. A method for producing arachidonic acid (ARA) comprising cultivating Mortierella alpina by an aeration-spinner culture process in a liquid culture medium, and the method further comprising at least the following steps:
adding at least one organic acid selected from the group consisting of succinic acid, fumaric acid, pyruvic acid, and malic acid, or a mixture thereof to the liquid culture medium in an amount of 0.2 to 5 w/v % at least three days from the beginning of the culture process, increasing the pH of the culture medium to the range of 6.6 to 7.5 at least three days from the beginning of the culture process, and adding a metal sulfate selected from the group consisting of MgSO4, CaSO4, K2SO4, FeSO4, and MnSO4, or a mixture thereof in an amount of 0.01 to 0.5 w/w % to the culture medium. 9. The method according to claim 8, further comprising drying the Mortierella alpina, and then adding either dry cells or the ARA derived from the cells to food or to drink. 10. The method according to claim 8, wherein addition of the organic acid and pH adjustment are carried out at different time points from an addition of an initial carbon source to the culture medium. 11. The method according to claim 8, wherein the metal sulfate is added before the beginning of the culture process. | 1,600 |
1,330 | 15,393,026 | 1,658 | The present invention relates to pharmaceutical compositions having improved stability. | 1-37. (canceled) 38. A liquid composition, comprising:
a pharmaceutically active compound selected from:
a compound having the formula (I):
wherein: n is selected from 0, 1 and 2; p is selected from 0, 1, 2, 3, 4, 5 and 6; R1 is selected from aryl optionally substituted with at least one OH, F, Cl, Br, alkyl or O-alkyl substituent; R2 is selected from R4, H, alkyl, cycloalkyl, aryl and 5- and 6-membered heteroaromatic ring systems; R3 is selected from H and a covalent bond to R2, when R2 is R4, to form a ring structure; R4 is C1-6 alkylene moiety substituted with at least one O-alkyl, S-alkyl or OH substituent; W and X are each independently selected from CH2 and S, but may not both be CH2; alkyl is selected from C1-6 straight and C4-8 branched chain alkyl and optionally has at least one hydroxyl substituent; aryl is selected from phenyl and mono- or poly-substituted phenyl; with the proviso that when R2 is H, p is 1, R3 is H, n is 1 and W and X are both S, R1 is not 4-hydroxyphenyl, or a solvate or pharmaceutically acceptable salt thereof; and
a compound having structure of formula (II):
or a pharmaceutically acceptable salt thereof;
and an anti-oxidant;
wherein the pH of the composition is from 5.0 to 6.0. 39. The composition of claim 38, wherein the pH of the composition is from 5.1 to 6. 40. The composition of claim 38, wherein the pH of the composition is from 5.2 to 5.65. 41. The composition of claim 38, wherein the pH of the composition is from 5.26 to 5.8. 42. The composition of claim 38, further comprising a buffering agent. 43. The composition of claim 38, wherein the anti-oxidant is methionine, EDTA, or a combination of methionine and EDTA. 44. The composition of claim 38, further comprising an isotonicity agent. 45. The composition of claim 38, wherein the pharmaceutically active compound is the compound of formula (II):
or a pharmaceutically acceptable salt thereof. 46. The composition of claim 45, wherein the pH of the composition is from 5.0 to 5.9. 47. The composition of claim 45, wherein the pH of the composition is from 5.1 to 5.9. 48. The composition of claim 45, wherein the pH of the composition is from 5.2 to 5.8. 49. The composition of claim 45, further comprising a buffer. 50. The composition of claim 49, wherein the buffer is a citrate/phosphate buffer. 51. The composition of claim 45, wherein the concentration of the compound of formula (II) in the liquid composition is from 0.01 to 4 mg/mL. 52. The composition of claim 45, wherein the concentration of the compound of formula (II) in the liquid composition is from 0.05 to 2 mg/mL. 53. The composition of claim 45, wherein the concentration of the compound of formula (II) in the liquid composition is from 0.1 to 1.4 mg/mL. 54. The composition of claim 45, wherein the concentration of the compound of formula (II) in the liquid composition is from 0.2 to 0.7 mg/mL. 55. The composition of claim 45, further comprising an anti-oxidant. 56. The composition of claim 45, further comprising an isotonicity agent. 57. The composition of claim 56, wherein the isotonicity agent is NaCl. 58. A method of treatment of compromised lactation conditions, labour induction impairment, uterine atony conditions, excessive bleeding, inflammation, pain, abdominal pain, back pain, male and female sexual dysfunction, irritable bowel syndrome (IBS), constipation, gastrointestinal obstruction, autism, stress, anxiety, depression, anxiety disorder, surgical blood loss, post-partum haemorrhage, wound healing, infection, mastitis, placenta delivery impairment, or osteoporosis, or a method for the diagnosis of cancer and placental insufficiency, comprising administration to a patient in need thereof the composition of claim 38. 59. The method of claim 58, wherein the method is for the treatment of uterine atony conditions or excessive bleeding. 60. The method of claim 59, wherein the method is for the treatment of uterine atony conditions following vaginal delivery of the infant or delivery of the infant by Caesarean section, or in a patient who is at risk of developing post-partum haemorrhage. 61. The method of claim 59, wherein the method is for the treatment of excessive bleeding following vaginal delivery. 62. A kit, comprising:
a liquid pharmaceutical composition of claim 38; and a container for the composition. 63. The kit of claim 62, wherein the pharmaceutically active compound is the compound of formula (II). | The present invention relates to pharmaceutical compositions having improved stability.1-37. (canceled) 38. A liquid composition, comprising:
a pharmaceutically active compound selected from:
a compound having the formula (I):
wherein: n is selected from 0, 1 and 2; p is selected from 0, 1, 2, 3, 4, 5 and 6; R1 is selected from aryl optionally substituted with at least one OH, F, Cl, Br, alkyl or O-alkyl substituent; R2 is selected from R4, H, alkyl, cycloalkyl, aryl and 5- and 6-membered heteroaromatic ring systems; R3 is selected from H and a covalent bond to R2, when R2 is R4, to form a ring structure; R4 is C1-6 alkylene moiety substituted with at least one O-alkyl, S-alkyl or OH substituent; W and X are each independently selected from CH2 and S, but may not both be CH2; alkyl is selected from C1-6 straight and C4-8 branched chain alkyl and optionally has at least one hydroxyl substituent; aryl is selected from phenyl and mono- or poly-substituted phenyl; with the proviso that when R2 is H, p is 1, R3 is H, n is 1 and W and X are both S, R1 is not 4-hydroxyphenyl, or a solvate or pharmaceutically acceptable salt thereof; and
a compound having structure of formula (II):
or a pharmaceutically acceptable salt thereof;
and an anti-oxidant;
wherein the pH of the composition is from 5.0 to 6.0. 39. The composition of claim 38, wherein the pH of the composition is from 5.1 to 6. 40. The composition of claim 38, wherein the pH of the composition is from 5.2 to 5.65. 41. The composition of claim 38, wherein the pH of the composition is from 5.26 to 5.8. 42. The composition of claim 38, further comprising a buffering agent. 43. The composition of claim 38, wherein the anti-oxidant is methionine, EDTA, or a combination of methionine and EDTA. 44. The composition of claim 38, further comprising an isotonicity agent. 45. The composition of claim 38, wherein the pharmaceutically active compound is the compound of formula (II):
or a pharmaceutically acceptable salt thereof. 46. The composition of claim 45, wherein the pH of the composition is from 5.0 to 5.9. 47. The composition of claim 45, wherein the pH of the composition is from 5.1 to 5.9. 48. The composition of claim 45, wherein the pH of the composition is from 5.2 to 5.8. 49. The composition of claim 45, further comprising a buffer. 50. The composition of claim 49, wherein the buffer is a citrate/phosphate buffer. 51. The composition of claim 45, wherein the concentration of the compound of formula (II) in the liquid composition is from 0.01 to 4 mg/mL. 52. The composition of claim 45, wherein the concentration of the compound of formula (II) in the liquid composition is from 0.05 to 2 mg/mL. 53. The composition of claim 45, wherein the concentration of the compound of formula (II) in the liquid composition is from 0.1 to 1.4 mg/mL. 54. The composition of claim 45, wherein the concentration of the compound of formula (II) in the liquid composition is from 0.2 to 0.7 mg/mL. 55. The composition of claim 45, further comprising an anti-oxidant. 56. The composition of claim 45, further comprising an isotonicity agent. 57. The composition of claim 56, wherein the isotonicity agent is NaCl. 58. A method of treatment of compromised lactation conditions, labour induction impairment, uterine atony conditions, excessive bleeding, inflammation, pain, abdominal pain, back pain, male and female sexual dysfunction, irritable bowel syndrome (IBS), constipation, gastrointestinal obstruction, autism, stress, anxiety, depression, anxiety disorder, surgical blood loss, post-partum haemorrhage, wound healing, infection, mastitis, placenta delivery impairment, or osteoporosis, or a method for the diagnosis of cancer and placental insufficiency, comprising administration to a patient in need thereof the composition of claim 38. 59. The method of claim 58, wherein the method is for the treatment of uterine atony conditions or excessive bleeding. 60. The method of claim 59, wherein the method is for the treatment of uterine atony conditions following vaginal delivery of the infant or delivery of the infant by Caesarean section, or in a patient who is at risk of developing post-partum haemorrhage. 61. The method of claim 59, wherein the method is for the treatment of excessive bleeding following vaginal delivery. 62. A kit, comprising:
a liquid pharmaceutical composition of claim 38; and a container for the composition. 63. The kit of claim 62, wherein the pharmaceutically active compound is the compound of formula (II). | 1,600 |
1,331 | 16,596,680 | 1,617 | The present invention relates to a method of stabilising a tear film in an individual having an ocular surface inflammatory disorder by providing a compound to an ocular surface of the individual to reduce the synthesis of a cholesterol by a meibum-producing tissue. | 1. A method of stabilising a tear film in an individual having an ocular surface inflammatory disorder including:
providing an individual having an ocular surface inflammatory disorder that is characterised by an unstable tear film, wherein the disorder is selected from dry eye and blepharitis; and providing a compound to an ocular surface of the individual to reduce the synthesis of a cholesterol by a meibum-producing tissue, wherein the compound is atorvastatin; thereby stabilising the tear film in the individual. 2-8. (canceled) 9. The method of claim 1, wherein atorvastatin is applied in an amount of 1 to 15 drops per day from a 50 μM atorvastatin solution. 10. The method of claim 9, wherein the application is for 1 to 4 weeks. 11. (canceled) 12. The method of claim 1, further including the step of:
providing an anti-inflammatory compound and/or an immunosuppressant to an ocular surface of the individual. 13. The method of claim 12, wherein the anti-inflammatory compound is a steroid. 14. The method of claim 12, wherein the immunosuppressant is a cyclosporin. 15. The method of claim 12, wherein the atorvastatin and the anti-inflammatory compound and/or immunosuppressant are provided in separate dosage units. 16. The method of claim 1, further including the step of:
providing an antibiotic to an ocular surface of the individual. 17. The method of claim 16, wherein the antibiotic is bacteriostatic or bacteriocidal. 18. The method of claim 16, wherein the antibiotic is bacteriocidal for Staphylococcus and Streptococcus species. 19. The method of claim 1, wherein the disorder is posterior blepharitis. 20. A method of reducing the synthesis of a cholesterol by a meibum-producing tissue, comprising administering a composition formulated for ophthalmic administration, wherein the composition comprises atorvastatin. 21. (canceled) 22. The method of claim 20, further including an anti-inflammatory and/or immunosuppressant in the composition. 23. The method of claim 22, wherein the anti-inflammatory compound is a steroid. 24. The method of claim 22, wherein the immunosuppressant is cyclosporin. 25. The method of claim 13, wherein the anti-inflammatory compound is selected from the group consisting of prednisolone, fluorometholone, triamcinolone, rimexolone, and betamethasone. 26. The method of claim 23, wherein the anti-inflammatory compound is selected from the group consisting of prednisolone, fluorometholone, triamcinolone, rimexolone, and betamethasone. 27. The method of claim 12, further including the step of:
providing an antibiotic to an ocular surface of the individual. | The present invention relates to a method of stabilising a tear film in an individual having an ocular surface inflammatory disorder by providing a compound to an ocular surface of the individual to reduce the synthesis of a cholesterol by a meibum-producing tissue.1. A method of stabilising a tear film in an individual having an ocular surface inflammatory disorder including:
providing an individual having an ocular surface inflammatory disorder that is characterised by an unstable tear film, wherein the disorder is selected from dry eye and blepharitis; and providing a compound to an ocular surface of the individual to reduce the synthesis of a cholesterol by a meibum-producing tissue, wherein the compound is atorvastatin; thereby stabilising the tear film in the individual. 2-8. (canceled) 9. The method of claim 1, wherein atorvastatin is applied in an amount of 1 to 15 drops per day from a 50 μM atorvastatin solution. 10. The method of claim 9, wherein the application is for 1 to 4 weeks. 11. (canceled) 12. The method of claim 1, further including the step of:
providing an anti-inflammatory compound and/or an immunosuppressant to an ocular surface of the individual. 13. The method of claim 12, wherein the anti-inflammatory compound is a steroid. 14. The method of claim 12, wherein the immunosuppressant is a cyclosporin. 15. The method of claim 12, wherein the atorvastatin and the anti-inflammatory compound and/or immunosuppressant are provided in separate dosage units. 16. The method of claim 1, further including the step of:
providing an antibiotic to an ocular surface of the individual. 17. The method of claim 16, wherein the antibiotic is bacteriostatic or bacteriocidal. 18. The method of claim 16, wherein the antibiotic is bacteriocidal for Staphylococcus and Streptococcus species. 19. The method of claim 1, wherein the disorder is posterior blepharitis. 20. A method of reducing the synthesis of a cholesterol by a meibum-producing tissue, comprising administering a composition formulated for ophthalmic administration, wherein the composition comprises atorvastatin. 21. (canceled) 22. The method of claim 20, further including an anti-inflammatory and/or immunosuppressant in the composition. 23. The method of claim 22, wherein the anti-inflammatory compound is a steroid. 24. The method of claim 22, wherein the immunosuppressant is cyclosporin. 25. The method of claim 13, wherein the anti-inflammatory compound is selected from the group consisting of prednisolone, fluorometholone, triamcinolone, rimexolone, and betamethasone. 26. The method of claim 23, wherein the anti-inflammatory compound is selected from the group consisting of prednisolone, fluorometholone, triamcinolone, rimexolone, and betamethasone. 27. The method of claim 12, further including the step of:
providing an antibiotic to an ocular surface of the individual. | 1,600 |
1,332 | 14,768,267 | 1,658 | The present invention provides novel and improved protein purification processes which incorporate certain types of carbonaceous materials and result in effective and selective removal of certain undesirable impurities without adversely effecting the yield of the desired protein product. | 1. A method of selectively removing of a protein from a sample comprising at least two proteins, the method comprising the steps of:
(a) providing a sample comprising at least two proteins, one of which is to be selectively removed; (b) adjusting the solution pH of the sample, such that the pH is within 2.0 pH units of the isoelectric point of the protein to be selectively removed; (c) contacting the sample with activated carbon, wherein the activated carbon binds the protein to be selectively removed; and (d) removing the activated carbon from the sample, thereby resulting in selective removal of the activated carbon bound protein from the sample. 2. A method of increasing the purity of a target protein in a sample comprising the target protein and at least one undesirable proteins, the method comprising the steps of:
(a) providing a sample comprising the target protein and at least one undesirable proteins; (b) adjusting the solution pH of the sample, such that the pH is within 2.0 pH units of the isoelectric point of the at least one undesirable protein; (c) contacting the sample with activated carbon, wherein the activated carbon binds the at least one undesirable protein; (d) removing the activated carbon from the sample, wherein the activated carbon is bound to the at least one undesirable protein; thereby increasing the purity of the target protein in the sample. 3. The method of claim 1, wherein the pH is within 1.0 pH unit of the isoelectric point of the protein to be selectively removed. 4. The method of claim 2, wherein the pH is within 1.0 pH unit of the isoelectric point of the at least one undesirable protein. 5. The method of claim 1, wherein the protein which is selectively removed is a proteinaceous impurity. 6. The method of claim 2, wherein the at least one undesirable protein is a proteinaceous impurity. 7. The method of claim 2, wherein the target protein is an immunoglobulin. 8. The method of claim 7, wherein the immunoglobulin is a monoclonal antibody. 9. The method of claim 7, wherein the immunoglobulin is a polyclonal antibody. 10. The method of claim 1, wherein the removing step comprises filtration or centrifugation. 11. The method of claim 2, wherein the removing step comprises filtration or centrifugation. 12. The method of claim 2, wherein the target protein is a recombinant protein. 13. The method of claim 2, wherein the purity of the target protein is increased by at least 50%, or at least 60%, or at least 70%, or at least 80%, or at least 90% or more. 14. The method of claim 1, wherein the sample comprises a cell culture feed. 15. The method of claim 2, wherein the sample comprises a cell culture feed. 16. The method of claim 14, wherein the cell culture feed is a CHO cell culture feed. 17. The method of claim 15, wherein the cell culture feed is a CHO cell culture feed. 18. The method of claim 1, wherein the sample comprises a protein expressed in a mammalian expression system. 19. The method of claim 2, wherein the sample comprises a protein expressed in a mammalian expression system. 20. The method of claim 1, wherein the sample comprises a protein expressed in a non-mammalian expression system. 21. The method of claim 2, wherein the sample comprises a protein expressed in a non-mammalian expression system. 22. The method of claim 1, wherein the sample is subjected to a clarification step prior to the adjusting step. 23. The method of claim 2, wherein the sample is subjected to a clarification step prior to the adjusting step. 24. The method of claim 22, wherein the clarification step is selected from the group consisting of centrifugation, settling, depth or screen filtration, complexing with flocculants, and pH change. 25. The method of claim 23, wherein the clarification step is selected from the group consisting of centrifugation, settling, depth or screen filtration, complexing with flocculants, and pH change. | The present invention provides novel and improved protein purification processes which incorporate certain types of carbonaceous materials and result in effective and selective removal of certain undesirable impurities without adversely effecting the yield of the desired protein product.1. A method of selectively removing of a protein from a sample comprising at least two proteins, the method comprising the steps of:
(a) providing a sample comprising at least two proteins, one of which is to be selectively removed; (b) adjusting the solution pH of the sample, such that the pH is within 2.0 pH units of the isoelectric point of the protein to be selectively removed; (c) contacting the sample with activated carbon, wherein the activated carbon binds the protein to be selectively removed; and (d) removing the activated carbon from the sample, thereby resulting in selective removal of the activated carbon bound protein from the sample. 2. A method of increasing the purity of a target protein in a sample comprising the target protein and at least one undesirable proteins, the method comprising the steps of:
(a) providing a sample comprising the target protein and at least one undesirable proteins; (b) adjusting the solution pH of the sample, such that the pH is within 2.0 pH units of the isoelectric point of the at least one undesirable protein; (c) contacting the sample with activated carbon, wherein the activated carbon binds the at least one undesirable protein; (d) removing the activated carbon from the sample, wherein the activated carbon is bound to the at least one undesirable protein; thereby increasing the purity of the target protein in the sample. 3. The method of claim 1, wherein the pH is within 1.0 pH unit of the isoelectric point of the protein to be selectively removed. 4. The method of claim 2, wherein the pH is within 1.0 pH unit of the isoelectric point of the at least one undesirable protein. 5. The method of claim 1, wherein the protein which is selectively removed is a proteinaceous impurity. 6. The method of claim 2, wherein the at least one undesirable protein is a proteinaceous impurity. 7. The method of claim 2, wherein the target protein is an immunoglobulin. 8. The method of claim 7, wherein the immunoglobulin is a monoclonal antibody. 9. The method of claim 7, wherein the immunoglobulin is a polyclonal antibody. 10. The method of claim 1, wherein the removing step comprises filtration or centrifugation. 11. The method of claim 2, wherein the removing step comprises filtration or centrifugation. 12. The method of claim 2, wherein the target protein is a recombinant protein. 13. The method of claim 2, wherein the purity of the target protein is increased by at least 50%, or at least 60%, or at least 70%, or at least 80%, or at least 90% or more. 14. The method of claim 1, wherein the sample comprises a cell culture feed. 15. The method of claim 2, wherein the sample comprises a cell culture feed. 16. The method of claim 14, wherein the cell culture feed is a CHO cell culture feed. 17. The method of claim 15, wherein the cell culture feed is a CHO cell culture feed. 18. The method of claim 1, wherein the sample comprises a protein expressed in a mammalian expression system. 19. The method of claim 2, wherein the sample comprises a protein expressed in a mammalian expression system. 20. The method of claim 1, wherein the sample comprises a protein expressed in a non-mammalian expression system. 21. The method of claim 2, wherein the sample comprises a protein expressed in a non-mammalian expression system. 22. The method of claim 1, wherein the sample is subjected to a clarification step prior to the adjusting step. 23. The method of claim 2, wherein the sample is subjected to a clarification step prior to the adjusting step. 24. The method of claim 22, wherein the clarification step is selected from the group consisting of centrifugation, settling, depth or screen filtration, complexing with flocculants, and pH change. 25. The method of claim 23, wherein the clarification step is selected from the group consisting of centrifugation, settling, depth or screen filtration, complexing with flocculants, and pH change. | 1,600 |
1,333 | 14,705,150 | 1,637 | This disclosure describes kits, reagents and methods for Recombinase Polymerase Amplification (RPA) of a target DNA that exploit the properties of recombinase and related proteins, to invade double-stranded DNA with single stranded homologous DNA permitting sequence specific priming of DNA polymerase reactions. The disclosed kits, reagents and methods have the advantage of not requiring thermocycling or thermophilic enzymes, thus offering easy and affordable implementation and portability relative to other amplification methods. | 1-39. (canceled) 40. A frieze dried pellet for a recombinase polymerase amplification process of DNA amplification of a target nucleic acid molecule, comprising: trehalose, and wherein said pellet does not contain polyethylene glycol. 41. The frieze dried pellet of claim 40, wherein said pellet comprises 2.5%-7.5% weight/lyophilization mixture volume of trehalose. | This disclosure describes kits, reagents and methods for Recombinase Polymerase Amplification (RPA) of a target DNA that exploit the properties of recombinase and related proteins, to invade double-stranded DNA with single stranded homologous DNA permitting sequence specific priming of DNA polymerase reactions. The disclosed kits, reagents and methods have the advantage of not requiring thermocycling or thermophilic enzymes, thus offering easy and affordable implementation and portability relative to other amplification methods.1-39. (canceled) 40. A frieze dried pellet for a recombinase polymerase amplification process of DNA amplification of a target nucleic acid molecule, comprising: trehalose, and wherein said pellet does not contain polyethylene glycol. 41. The frieze dried pellet of claim 40, wherein said pellet comprises 2.5%-7.5% weight/lyophilization mixture volume of trehalose. | 1,600 |
1,334 | 16,796,940 | 1,654 | The disclosure provides methods of preventing or treating heart failure in a mammalian subject. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to subjects in need thereof. | 1-13. (canceled) 14. A method of treating hypertrophic cardiomyopathy in a mammalian subject, comprising administering to the mammalian subject in need thereof a therapeutically effective amount of the peptide D-Arg-2′6′-Dmt-Lys-Phe-NH2. 15. The method of claim 14, wherein the subject is suffering from heart failure. 16. The method of claim 14, wherein the hypertrophic cardiomyopathy results from a genetic defect. 17. The method of claim 14, wherein myocardial contractility and cardiac output in the subject administered the peptide are increased compared to a control subject not administered the peptide. 18. The method of claim 17, wherein the myocardial contractility and cardiac output in the subject are increased at least 10% compared to a control subject not administered the peptide. 19. The method of claim 14, wherein the subject is a human. 20. The method of claim 14, wherein the peptide is administered orally, topically, systemically, intravenously, intraperitoneally, or intramuscularly. 21. The method of claim 14, wherein the peptide is administered subcutaneously. 22. The method of claim 14, further comprising separately, sequentially or simultaneously administering a cardiovascular agent to the subject. 23. The method of claim 22, wherein the cardiovascular agent is selected from the group consisting of: an anti-arrhthymia agent, a vasodilator, an anti-anginal agent, a corticosteroid, a cardioglycoside, a diuretic, a sedative, an angiotensin converting enzyme (ACE) inhibitor, an angiotensin II antagonist, a thrombolytic agent, a calcium channel blocker, a throboxane receptor antagonist, a radical scavenger, an anti-platelet drug, a β-adrenaline receptor blocking drug, α-receptor blocking drug, a sympathetic nerve inhibitor, a digitalis formulation, an inotrope, and an antihyperlipidemic drug. | The disclosure provides methods of preventing or treating heart failure in a mammalian subject. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to subjects in need thereof.1-13. (canceled) 14. A method of treating hypertrophic cardiomyopathy in a mammalian subject, comprising administering to the mammalian subject in need thereof a therapeutically effective amount of the peptide D-Arg-2′6′-Dmt-Lys-Phe-NH2. 15. The method of claim 14, wherein the subject is suffering from heart failure. 16. The method of claim 14, wherein the hypertrophic cardiomyopathy results from a genetic defect. 17. The method of claim 14, wherein myocardial contractility and cardiac output in the subject administered the peptide are increased compared to a control subject not administered the peptide. 18. The method of claim 17, wherein the myocardial contractility and cardiac output in the subject are increased at least 10% compared to a control subject not administered the peptide. 19. The method of claim 14, wherein the subject is a human. 20. The method of claim 14, wherein the peptide is administered orally, topically, systemically, intravenously, intraperitoneally, or intramuscularly. 21. The method of claim 14, wherein the peptide is administered subcutaneously. 22. The method of claim 14, further comprising separately, sequentially or simultaneously administering a cardiovascular agent to the subject. 23. The method of claim 22, wherein the cardiovascular agent is selected from the group consisting of: an anti-arrhthymia agent, a vasodilator, an anti-anginal agent, a corticosteroid, a cardioglycoside, a diuretic, a sedative, an angiotensin converting enzyme (ACE) inhibitor, an angiotensin II antagonist, a thrombolytic agent, a calcium channel blocker, a throboxane receptor antagonist, a radical scavenger, an anti-platelet drug, a β-adrenaline receptor blocking drug, α-receptor blocking drug, a sympathetic nerve inhibitor, a digitalis formulation, an inotrope, and an antihyperlipidemic drug. | 1,600 |
1,335 | 15,684,226 | 1,612 | An oral care composition comprising zinc phosphate, stannous fluoride and a salicylamide, as well as methods of using the same. | 1. A high water oral care composition comprising an orally acceptable carrier, zinc phosphate, stannous fluoride, and a salicylamide. 2. The composition of claim 1, wherein the salicylamide is a non-halogenated salicylamide. 3. The composition of claim 2, wherein the salicylamide has the formula:
wherein R1 and R2 are independently selected from H, and C1-10alkyl. 4. The composition of claim 3, wherein R1 and R2 are independently selected from H, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl and tert-butyl. 5. The composition of claim 4, wherein R1 is H and R2 is H. 6. The composition of claim 1 wherein the zinc phosphate is a preformed salt of zinc phosphate. 7. The composition of claim 1 wherein the amount of zinc phosphate is from 0.05 to 10% by weight, relative to the weight of the oral care composition. 8. The composition of claim 1 wherein the salicylamide is present in an antibacterially-effective amount or an anti-plaque effective amount. 9. The composition of claim 1 wherein the amount of the salicylamide is from 0.001 to 10% by weight of the composition. 10. The composition of claim 1 wherein the amount of the water is 10% by weight or more, relative to the weight of the oral care composition. 11. The composition of claim 1 further comprising an organic buffer system. 12. The composition of claim 1, further comprising one or more humectants. 13. The composition of claim 1, further comprising an effective amount of one or more alkali phosphate salts. 14. The composition of claim 1 wherein the oral care composition is a dentifrice. 15. The composition of claim 1 wherein the composition does not contain any halogenated biphenyl ether antibacterial agents. 16. A method of treatment or prevention of erosive tooth demineralization, gingivitis, plaque, and/or dental caries, the method comprising the application to the oral cavity of a person in need thereof a composition according to claim 1. 17. A method to (i) reduce or inhibit formation of dental caries, (ii) reduce, repair or inhibit pre-carious lesions of the enamel, e.g., as detected by quantitative light-induced fluorescence (QLF) or electrical caries measurement (ECM), (iii) reduce or inhibit demineralization and promote remineralization of the teeth, (iv) reduce hypersensitivity of the teeth, (v) reduce or inhibit gingivitis, (vi) promote healing of sores or cuts in the mouth, (vii) reduce levels of acid producing bacteria, (viii) to increase relative levels of arginolytic bacteria, (ix) inhibit microbial biofilm formation in the oral cavity, (x) raise and/or maintain plaque pH at levels of at least pH 5.5 following sugar challenge, (xi) reduce plaque accumulation, (xii) treat, relieve or reduce dry mouth, (xiii) clean the teeth and oral cavity (xiv) reduce erosion, (xv) prevents stains and/or whiten teeth, (xvi) immunize the teeth against cariogenic bacteria; and/or (xvii) promote systemic health, including cardiovascular health, comprising the application to the oral cavity of a person in need thereof a composition according to claim 1. | An oral care composition comprising zinc phosphate, stannous fluoride and a salicylamide, as well as methods of using the same.1. A high water oral care composition comprising an orally acceptable carrier, zinc phosphate, stannous fluoride, and a salicylamide. 2. The composition of claim 1, wherein the salicylamide is a non-halogenated salicylamide. 3. The composition of claim 2, wherein the salicylamide has the formula:
wherein R1 and R2 are independently selected from H, and C1-10alkyl. 4. The composition of claim 3, wherein R1 and R2 are independently selected from H, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl and tert-butyl. 5. The composition of claim 4, wherein R1 is H and R2 is H. 6. The composition of claim 1 wherein the zinc phosphate is a preformed salt of zinc phosphate. 7. The composition of claim 1 wherein the amount of zinc phosphate is from 0.05 to 10% by weight, relative to the weight of the oral care composition. 8. The composition of claim 1 wherein the salicylamide is present in an antibacterially-effective amount or an anti-plaque effective amount. 9. The composition of claim 1 wherein the amount of the salicylamide is from 0.001 to 10% by weight of the composition. 10. The composition of claim 1 wherein the amount of the water is 10% by weight or more, relative to the weight of the oral care composition. 11. The composition of claim 1 further comprising an organic buffer system. 12. The composition of claim 1, further comprising one or more humectants. 13. The composition of claim 1, further comprising an effective amount of one or more alkali phosphate salts. 14. The composition of claim 1 wherein the oral care composition is a dentifrice. 15. The composition of claim 1 wherein the composition does not contain any halogenated biphenyl ether antibacterial agents. 16. A method of treatment or prevention of erosive tooth demineralization, gingivitis, plaque, and/or dental caries, the method comprising the application to the oral cavity of a person in need thereof a composition according to claim 1. 17. A method to (i) reduce or inhibit formation of dental caries, (ii) reduce, repair or inhibit pre-carious lesions of the enamel, e.g., as detected by quantitative light-induced fluorescence (QLF) or electrical caries measurement (ECM), (iii) reduce or inhibit demineralization and promote remineralization of the teeth, (iv) reduce hypersensitivity of the teeth, (v) reduce or inhibit gingivitis, (vi) promote healing of sores or cuts in the mouth, (vii) reduce levels of acid producing bacteria, (viii) to increase relative levels of arginolytic bacteria, (ix) inhibit microbial biofilm formation in the oral cavity, (x) raise and/or maintain plaque pH at levels of at least pH 5.5 following sugar challenge, (xi) reduce plaque accumulation, (xii) treat, relieve or reduce dry mouth, (xiii) clean the teeth and oral cavity (xiv) reduce erosion, (xv) prevents stains and/or whiten teeth, (xvi) immunize the teeth against cariogenic bacteria; and/or (xvii) promote systemic health, including cardiovascular health, comprising the application to the oral cavity of a person in need thereof a composition according to claim 1. | 1,600 |
1,336 | 15,789,716 | 1,612 | The present invention provides an aqueous oral rinse composition which includes zinc chloride, sorbitol, one or more pyrophosphates, and water. Methods of providing such an oral rinse composition are also provided herein. | 1. An oral rinse composition comprising:
zinc chloride; water, wherein the amount of water present in the composition is at least about 80%, based on the total weight of the composition; one or more sugar alcohols; and optionally, one or more pyrophosphates; wherein the oral rinse composition is substantially free of one or both of zinc oxychloride and zinc phosphate. 2. The oral rinse composition of claim 1, wherein one or more of the following conditions is met:
the zinc chloride is present in an amount in the range of about 0.01 to about 5 weight percent, based on the total weight of the oral rinse composition; the one or more pyrophosphates are present in amounts in the range of about 0.01 to about 5 weight percent, based on the total weight of the oral rinse composition; the one or more sugar alcohols are present in amounts in the range of about 15 to about 35 weight percent, based on the total weight of the oral rinse composition. 3. The oral rinse composition of claim 1, wherein the one or more pyrophosphates comprise at least one of tetrasodium pyrophosphate and disodium pyrophosphate. 4. The oral rinse composition of claim 1, wherein the one or more sugar alcohols comprise sorbitol. 5. A method of making an oral rinse composition comprising:
providing a zinc chloride solution; forming a premix comprising the zinc chloride solution, one or more sugar alcohols, and deionized water; optionally mixing the premix with one or more pyrophosphates until the pyrophosphates are dissolved in an intermediate solution; and mixing additional ingredients into the intermediate solution to form the oral rinse composition; wherein the oral rinse composition is substantially free of zinc oxychloride and zinc phosphate. 6. The method of claim 5, wherein the zinc chloride solution is a 50% zinc chloride in water solution. 7. The method of claim 5, further comprising adjusting the pH of the premix to a pH in the range of about 5-7. 8. The method of claim 5, further comprising:
heating water to an increased temperature; and mixing zinc chloride with the heated water to form the zinc chloride solution. 9. The method of claim 8, wherein the increased temperature is at least about 30° C. 10. The method of claim 5, wherein the one or more pyrophosphates comprise at least one of tetrasodium pyrophosphate and disodium pyrophosphate. 11. The method of claim 5, wherein the one or more sugar alcohols comprise sorbitol. 12. The method of claim 5, wherein one or more of the following conditions is met:
the zinc chloride is present in an amount in the range of about 0.01 to about 5 weight percent, based on the total weight of the oral rinse composition; the one or more pyrophosphates are present in amounts in the range of about 0.01 to about 5 weight percent, based on the total weight of the oral rinse composition; the one or more sugar alcohols are present in amounts in the range of about 15 to about 35 weight percent, based on the total weight of the oral rinse composition. 13. The method of claim 5, wherein the oral rinse composition is manufactured in the form of a final oral rinse product having a desired dosage size, shape and weight. | The present invention provides an aqueous oral rinse composition which includes zinc chloride, sorbitol, one or more pyrophosphates, and water. Methods of providing such an oral rinse composition are also provided herein.1. An oral rinse composition comprising:
zinc chloride; water, wherein the amount of water present in the composition is at least about 80%, based on the total weight of the composition; one or more sugar alcohols; and optionally, one or more pyrophosphates; wherein the oral rinse composition is substantially free of one or both of zinc oxychloride and zinc phosphate. 2. The oral rinse composition of claim 1, wherein one or more of the following conditions is met:
the zinc chloride is present in an amount in the range of about 0.01 to about 5 weight percent, based on the total weight of the oral rinse composition; the one or more pyrophosphates are present in amounts in the range of about 0.01 to about 5 weight percent, based on the total weight of the oral rinse composition; the one or more sugar alcohols are present in amounts in the range of about 15 to about 35 weight percent, based on the total weight of the oral rinse composition. 3. The oral rinse composition of claim 1, wherein the one or more pyrophosphates comprise at least one of tetrasodium pyrophosphate and disodium pyrophosphate. 4. The oral rinse composition of claim 1, wherein the one or more sugar alcohols comprise sorbitol. 5. A method of making an oral rinse composition comprising:
providing a zinc chloride solution; forming a premix comprising the zinc chloride solution, one or more sugar alcohols, and deionized water; optionally mixing the premix with one or more pyrophosphates until the pyrophosphates are dissolved in an intermediate solution; and mixing additional ingredients into the intermediate solution to form the oral rinse composition; wherein the oral rinse composition is substantially free of zinc oxychloride and zinc phosphate. 6. The method of claim 5, wherein the zinc chloride solution is a 50% zinc chloride in water solution. 7. The method of claim 5, further comprising adjusting the pH of the premix to a pH in the range of about 5-7. 8. The method of claim 5, further comprising:
heating water to an increased temperature; and mixing zinc chloride with the heated water to form the zinc chloride solution. 9. The method of claim 8, wherein the increased temperature is at least about 30° C. 10. The method of claim 5, wherein the one or more pyrophosphates comprise at least one of tetrasodium pyrophosphate and disodium pyrophosphate. 11. The method of claim 5, wherein the one or more sugar alcohols comprise sorbitol. 12. The method of claim 5, wherein one or more of the following conditions is met:
the zinc chloride is present in an amount in the range of about 0.01 to about 5 weight percent, based on the total weight of the oral rinse composition; the one or more pyrophosphates are present in amounts in the range of about 0.01 to about 5 weight percent, based on the total weight of the oral rinse composition; the one or more sugar alcohols are present in amounts in the range of about 15 to about 35 weight percent, based on the total weight of the oral rinse composition. 13. The method of claim 5, wherein the oral rinse composition is manufactured in the form of a final oral rinse product having a desired dosage size, shape and weight. | 1,600 |
1,337 | 15,102,572 | 1,612 | Disclosed is a dental bleaching gel composition with high electric conductivity. It was the object of the present invention to provide a bleaching gel composition that is less initating than prior art gels, and is highly efficient such that it can bleach within shorter time. The composition includes a peroxide, or a peroxide releasing compound such as carbamide peroxide, sodium perborate, or sodium percarbonate as a bleaching agent, a cross-linked polyacrylate polymer as a thickening component, and electrial conductivity enhancing ingredients such as electrolytes. | 1. A dental bleaching gel composition comprising:
a peroxide or peroxide releasing compound, a cross-linked polyacrylate polymer, an aqueous vehicle; and at least one electrical conductivity enhancing ingredient; wherein the electrical conductivity of the gel is at least 250 microsiemens/cm. 2. The dental bleaching gel composition according to claim 1 wherein the electrical conductivity enhancing ingredient is at least one of a group consisting of alkali nitrate in an amount of 1 to 5% w/w and alkali hydroxide in amount of 1 to 5% w/w. 3. The dental bleaching gel composition according to claim 1 wherein the amount of alkali hydroxide is such that the gel pH is adjusted to 5-7. 4. The dental bleaching gel composition according to claim 1 wherein the aqueous vehicle comprises at least one alcohol, in particular one of glycerin, propylene glycol, or a mixture of them. 5. The dental bleaching gel composition according to claim 1 wherein the alkali hydroxide is potassium hydroxide and/or wherein the alkali nitrate is potassium nitrate. 6. The dental bleaching gel composition according to claim 1 wherein the amount of glycerin is 20 to 30% w/w;
and/or wherein the amount of water is 25 to 50% w/w. 7. The dental bleaching gel composition according to claim 1 wherein the amount of peroxide is 3 to 35% w/w. 8. The dental bleaching gel composition according to claim 1 wherein the amount of a cross-linked polyacrylate polymer is 1 to 5% w/w. 9. The dental bleaching gel composition according to claim 1 wherein the dental bleaching gel additionally includes a fluoride in amount of 0.1 to 1.0% w/w. 10. The dental bleaching gel composition according to claim 1 wherein the dental bleaching gel additionally includes at least one alkali hydroxide w/w in amount of 0.5 to 3.0% w/w. 11. The dental bleaching gel composition according to claim 1 wherein the dental bleach gel additionally includes a polymeric binder, preferably polyvinylpyrrolidone in an amount of 0.5 to 2.0% w/w. 12. The dental bleaching gel composition according to claim 1 wherein the dental bleaching gel additionally includes a complexing agent, preferably disodium ethylenediamine tetraacetic salt (EDTA) in an amount of 0.1 to 2.0% w/w. 13. The dental bleaching gel composition according to claim 1 wherein the dental bleaching gel additionally includes flavoring ingredients in an amount of 0.1 to 0.5% w/w. 14. The dental bleaching gel composition according to claim 1 wherein the flavoring ingredients are at least one of a group consisting of saccharin sodium salt hydrate and peppermint oil and a mix of both of them. 15. A teeth bleaching method comprising:
applying to the teeth to be bleached a layer of gel with electrical conductivity higher than 250 microsiemens/cm; applying to the teeth covered by a layer of gel with electrical conductivity higher than 250 microsimens/cm electric current of at least 1 milliampere; and bleaching the teeth. 16. Use of a dental bleaching gel as defined in claim 1 for bleaching teeth by applying the gel to the teeth and applying a micro-current of at least 1 milliampere. | Disclosed is a dental bleaching gel composition with high electric conductivity. It was the object of the present invention to provide a bleaching gel composition that is less initating than prior art gels, and is highly efficient such that it can bleach within shorter time. The composition includes a peroxide, or a peroxide releasing compound such as carbamide peroxide, sodium perborate, or sodium percarbonate as a bleaching agent, a cross-linked polyacrylate polymer as a thickening component, and electrial conductivity enhancing ingredients such as electrolytes.1. A dental bleaching gel composition comprising:
a peroxide or peroxide releasing compound, a cross-linked polyacrylate polymer, an aqueous vehicle; and at least one electrical conductivity enhancing ingredient; wherein the electrical conductivity of the gel is at least 250 microsiemens/cm. 2. The dental bleaching gel composition according to claim 1 wherein the electrical conductivity enhancing ingredient is at least one of a group consisting of alkali nitrate in an amount of 1 to 5% w/w and alkali hydroxide in amount of 1 to 5% w/w. 3. The dental bleaching gel composition according to claim 1 wherein the amount of alkali hydroxide is such that the gel pH is adjusted to 5-7. 4. The dental bleaching gel composition according to claim 1 wherein the aqueous vehicle comprises at least one alcohol, in particular one of glycerin, propylene glycol, or a mixture of them. 5. The dental bleaching gel composition according to claim 1 wherein the alkali hydroxide is potassium hydroxide and/or wherein the alkali nitrate is potassium nitrate. 6. The dental bleaching gel composition according to claim 1 wherein the amount of glycerin is 20 to 30% w/w;
and/or wherein the amount of water is 25 to 50% w/w. 7. The dental bleaching gel composition according to claim 1 wherein the amount of peroxide is 3 to 35% w/w. 8. The dental bleaching gel composition according to claim 1 wherein the amount of a cross-linked polyacrylate polymer is 1 to 5% w/w. 9. The dental bleaching gel composition according to claim 1 wherein the dental bleaching gel additionally includes a fluoride in amount of 0.1 to 1.0% w/w. 10. The dental bleaching gel composition according to claim 1 wherein the dental bleaching gel additionally includes at least one alkali hydroxide w/w in amount of 0.5 to 3.0% w/w. 11. The dental bleaching gel composition according to claim 1 wherein the dental bleach gel additionally includes a polymeric binder, preferably polyvinylpyrrolidone in an amount of 0.5 to 2.0% w/w. 12. The dental bleaching gel composition according to claim 1 wherein the dental bleaching gel additionally includes a complexing agent, preferably disodium ethylenediamine tetraacetic salt (EDTA) in an amount of 0.1 to 2.0% w/w. 13. The dental bleaching gel composition according to claim 1 wherein the dental bleaching gel additionally includes flavoring ingredients in an amount of 0.1 to 0.5% w/w. 14. The dental bleaching gel composition according to claim 1 wherein the flavoring ingredients are at least one of a group consisting of saccharin sodium salt hydrate and peppermint oil and a mix of both of them. 15. A teeth bleaching method comprising:
applying to the teeth to be bleached a layer of gel with electrical conductivity higher than 250 microsiemens/cm; applying to the teeth covered by a layer of gel with electrical conductivity higher than 250 microsimens/cm electric current of at least 1 milliampere; and bleaching the teeth. 16. Use of a dental bleaching gel as defined in claim 1 for bleaching teeth by applying the gel to the teeth and applying a micro-current of at least 1 milliampere. | 1,600 |
1,338 | 16,226,804 | 1,654 | A histidine-free composition comprising: a high purity factor VIII (r-factor VIII); arginine and/or sucrose; a surface-active agent to prevent or at least inhibit surface adsorption of factor VIII; an amount of calcium chloride for specific stabilization of factor VIII. | 1. A cryo/lyo protected histidine-free composition comprising:
(a) a non-native purified recombinant factor VIII (r-factor VIII); (b) 3-15 mg/ml arginine and 3-15 mg/ml sucrose combined as cryo/lyoprotectant, and 10-40 mg/ml sodium chloride as a bulking agent; (c) a surface-active agent in a concentration effective to prevent loss due to surface adsorption of the r-factor VIII and equal or less than 5 mg/ml, wherein the surface-active agent is Poloxamer 188; and; (d) 0.5-10 mM calcium chloride sufficient for specific stabilization of the r-factor VIII. 2-3. (canceled) 4. The composition according to claim 1, wherein the r-factor VIII is a deletion derivative of native factor VIII partially, or entirely lacking the B-domain of native factor VIII. 5-7. (canceled) 8. The composition according to claim 1, wherein sucrose is present at 3 mg/ml to 10 mg/ml, and arginine is present at 3 mg/ml to 8 mg/ml. 9-17. (canceled) 18. The composition of claim 1, wherein Polyxamer 188 is present at 0.1 mg/ml to 5 mg/ml. 19. The composition according to claim 1, wherein the specific activity of r-factor VIII is ≥5000 lU/mg protein. 20. The composition according to claim 1, wherein sucrose is present at 4.5 mg/ml to 9 mg/ml, arginine is present at 4.5 mg/ml to 6.8 mg/ml, and sodium chloride is present at 15 mg/ml to 23 mg/ml. | A histidine-free composition comprising: a high purity factor VIII (r-factor VIII); arginine and/or sucrose; a surface-active agent to prevent or at least inhibit surface adsorption of factor VIII; an amount of calcium chloride for specific stabilization of factor VIII.1. A cryo/lyo protected histidine-free composition comprising:
(a) a non-native purified recombinant factor VIII (r-factor VIII); (b) 3-15 mg/ml arginine and 3-15 mg/ml sucrose combined as cryo/lyoprotectant, and 10-40 mg/ml sodium chloride as a bulking agent; (c) a surface-active agent in a concentration effective to prevent loss due to surface adsorption of the r-factor VIII and equal or less than 5 mg/ml, wherein the surface-active agent is Poloxamer 188; and; (d) 0.5-10 mM calcium chloride sufficient for specific stabilization of the r-factor VIII. 2-3. (canceled) 4. The composition according to claim 1, wherein the r-factor VIII is a deletion derivative of native factor VIII partially, or entirely lacking the B-domain of native factor VIII. 5-7. (canceled) 8. The composition according to claim 1, wherein sucrose is present at 3 mg/ml to 10 mg/ml, and arginine is present at 3 mg/ml to 8 mg/ml. 9-17. (canceled) 18. The composition of claim 1, wherein Polyxamer 188 is present at 0.1 mg/ml to 5 mg/ml. 19. The composition according to claim 1, wherein the specific activity of r-factor VIII is ≥5000 lU/mg protein. 20. The composition according to claim 1, wherein sucrose is present at 4.5 mg/ml to 9 mg/ml, arginine is present at 4.5 mg/ml to 6.8 mg/ml, and sodium chloride is present at 15 mg/ml to 23 mg/ml. | 1,600 |
1,339 | 15,631,003 | 1,612 | This invention relates to oral care compositions comprising a first source of stannous, a second source of stannous, wherein the second source of stannous contains stannous pyrophosphate, and a zinc source selected from the group consisting of: zinc oxide, zinc citrate, zinc lactate, and combinations thereof, as well as to methods of using and of making these compositions. | 1. An oral care composition comprising:
a zinc source selected from the group consisting of: zinc oxide, zinc citrate, zinc lactate, and combinations thereof; a first source of stannous; and a second source of stannous, wherein the second source of stannous comprises stannous pyrophosphate. 2. The oral care composition of claim 1, wherein the zinc source comprises zinc oxide. 3. The oral care composition of claim 1, wherein the zinc source comprises zinc oxide and zinc citrate. 4. The oral care composition of claim 3, wherein the ratio of the amount of zinc oxide to zinc citrate is from 1.5:1 to 4.5:1. 5. The oral care composition of claim 3, comprising zinc citrate and zinc oxide, wherein the zinc citrate is present in an amount of from 0.25 to 1.0 wt %, and the zinc oxide may be present in an amount of from 0.75 to 1.25 wt %, based on the total weight of the composition. 6. The oral care composition of claim 1, wherein the zinc source comprises zinc oxide and zinc lactate. 7. The oral care composition of claim 6, wherein the ratio of the amount of zinc oxide to zinc lactate is from 1.2:1 to 4.5:1. 8. The oral care composition of claim 6, wherein the zinc lactate is in an amount of from 0.5 to 0.9 wt %, and zinc oxide may be present in an amount of from 0.75 to 1.25 wt %, based on the total weight of the composition. 9. The oral care composition of claim 1, wherein the first stannous ion source is stannous fluoride, other stannous halides such as stannous chloride dihydrate, stannous pyrophosphate, organic stannous carboxylate salts such as stannous formate, acetate, gluconate, lactate, tartrate, oxalate, malonate and citrate, stannous ethylene glyoxide, or a mixture thereof 10. The oral care composition of claim 1, wherein the first stannous ion source is stannous fluoride. 11. The oral care composition of claim 1, wherein the composition comprises one or more alkali phosphate salts selected from sodium phosphate dibasic, potassium phosphate dibasic, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, disodium hydrogen orthophosphate, monosodium phosphate, pentapotassium triphosphate and mixtures thereof. 12. The oral care composition of claim 11, wherein the composition comprises an alkali phosphate salt in an amount of from 1-20% by weight, based on the total weight of the composition. 13. The oral care composition of claim 11, wherein the alkali phosphate salt is tetrapotassium pyrophosphate. 14. The oral care composition of claim 11, wherein the alkali phosphate salt is sodium tripolyphosphate. 15. The composition of claim 1, wherein the composition comprises:
a. Zinc Oxide at about 1.0 wt. %; b. Zinc Citrate at about 0.5 wt %; c. Stannous pyrophosphate at about 1.0 wt %; d. Tetrasodium pyrophosphate at about 2.0 wt %. 16. A The composition of claim 1, wherein the composition comprises:
a. Zinc Oxide at about 1.0 wt. %; b. Zinc lactate at about 0.5 wt %; c. Stannous pyrophosphate at about 1.0 wt %; d. Sodium tripolyphosphate at about 2.0 wt %. 17. The composition of claim 15, further comprising a citrate buffer system, wherein the buffer system comprises tri-sodium citrate and citric acid. 18. The composition of claim 1, wherein the composition may be any of the following selected from: a toothpaste, transparent paste, gel, mouth rinse, spray and chewing gum. 19. A method to improve oral health comprising applying an effective amount of the oral composition of claim 1, wherein the oral care composition is applied to the oral cavity of a subject in need thereof. | This invention relates to oral care compositions comprising a first source of stannous, a second source of stannous, wherein the second source of stannous contains stannous pyrophosphate, and a zinc source selected from the group consisting of: zinc oxide, zinc citrate, zinc lactate, and combinations thereof, as well as to methods of using and of making these compositions.1. An oral care composition comprising:
a zinc source selected from the group consisting of: zinc oxide, zinc citrate, zinc lactate, and combinations thereof; a first source of stannous; and a second source of stannous, wherein the second source of stannous comprises stannous pyrophosphate. 2. The oral care composition of claim 1, wherein the zinc source comprises zinc oxide. 3. The oral care composition of claim 1, wherein the zinc source comprises zinc oxide and zinc citrate. 4. The oral care composition of claim 3, wherein the ratio of the amount of zinc oxide to zinc citrate is from 1.5:1 to 4.5:1. 5. The oral care composition of claim 3, comprising zinc citrate and zinc oxide, wherein the zinc citrate is present in an amount of from 0.25 to 1.0 wt %, and the zinc oxide may be present in an amount of from 0.75 to 1.25 wt %, based on the total weight of the composition. 6. The oral care composition of claim 1, wherein the zinc source comprises zinc oxide and zinc lactate. 7. The oral care composition of claim 6, wherein the ratio of the amount of zinc oxide to zinc lactate is from 1.2:1 to 4.5:1. 8. The oral care composition of claim 6, wherein the zinc lactate is in an amount of from 0.5 to 0.9 wt %, and zinc oxide may be present in an amount of from 0.75 to 1.25 wt %, based on the total weight of the composition. 9. The oral care composition of claim 1, wherein the first stannous ion source is stannous fluoride, other stannous halides such as stannous chloride dihydrate, stannous pyrophosphate, organic stannous carboxylate salts such as stannous formate, acetate, gluconate, lactate, tartrate, oxalate, malonate and citrate, stannous ethylene glyoxide, or a mixture thereof 10. The oral care composition of claim 1, wherein the first stannous ion source is stannous fluoride. 11. The oral care composition of claim 1, wherein the composition comprises one or more alkali phosphate salts selected from sodium phosphate dibasic, potassium phosphate dibasic, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, disodium hydrogen orthophosphate, monosodium phosphate, pentapotassium triphosphate and mixtures thereof. 12. The oral care composition of claim 11, wherein the composition comprises an alkali phosphate salt in an amount of from 1-20% by weight, based on the total weight of the composition. 13. The oral care composition of claim 11, wherein the alkali phosphate salt is tetrapotassium pyrophosphate. 14. The oral care composition of claim 11, wherein the alkali phosphate salt is sodium tripolyphosphate. 15. The composition of claim 1, wherein the composition comprises:
a. Zinc Oxide at about 1.0 wt. %; b. Zinc Citrate at about 0.5 wt %; c. Stannous pyrophosphate at about 1.0 wt %; d. Tetrasodium pyrophosphate at about 2.0 wt %. 16. A The composition of claim 1, wherein the composition comprises:
a. Zinc Oxide at about 1.0 wt. %; b. Zinc lactate at about 0.5 wt %; c. Stannous pyrophosphate at about 1.0 wt %; d. Sodium tripolyphosphate at about 2.0 wt %. 17. The composition of claim 15, further comprising a citrate buffer system, wherein the buffer system comprises tri-sodium citrate and citric acid. 18. The composition of claim 1, wherein the composition may be any of the following selected from: a toothpaste, transparent paste, gel, mouth rinse, spray and chewing gum. 19. A method to improve oral health comprising applying an effective amount of the oral composition of claim 1, wherein the oral care composition is applied to the oral cavity of a subject in need thereof. | 1,600 |
1,340 | 14,367,635 | 1,634 | The present invention relates to a method for the in vitro diagnosis or prognosis of prostate cancer, which includes a step of detecting at least one expression product of at least one HERV nucleic acid sequence, the use of said nucleic acid sequences, once isolated, as one or more molecular marker(s) and a kit comprising at least one specific binding partner of at least one of the expression products of the HERV nucleic acid sequences. | 1. A method for the in vitro diagnosis or prognosis of prostate cancer in a biological sample taken from a patient, which comprises a step of detecting at least two expression products respectively of at least two nucleic acid sequences, said nucleic acid sequences being chosen from the sequences identified in SEQ ID NOs: 1 to 75 or from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 1 to 75. 2. The method as claimed in claim 1, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 3, 4, 8, 10, 11, 15, 16, 21 and 32 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 3, 4, 8, 10, 11, 15, 16, 21 and 32. 3. The method as claimed in claim 2, in which the expression product of at least two nucleic acid sequences is detected, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 4 and 10, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 4 and 10. 4. The method as claimed in claim 1, in which the expression product detected is at least one RNA transcript or at least one polypeptide. 5. The method as claimed in claim 4, wherein the RNA transcript is at least one mRNA. 6. The method as claimed in claim 4, in which the RNA transcript, in particular the mRNA, is detected by hybridization, by amplification or by sequencing. 7. The method as claimed in claim 6, in which the mRNA is brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and the presence or absence of hybridization to the mRNA is detected. 8. The method as claimed in claim 5, wherein DNA copies of the mRNA are prepared, the DNA copies are brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and in that the presence or absence of hybridization to said DNA copies is detected. 9. The method as claimed in claim 4, in which the polypeptide expressed is detected by bringing into contact with at least one specific binding partner of said polypeptide, an affinity protein or an aptamer. 10. A method for in vitro diagnosis or prognosis of prostate cancer comprising at least two nucleic acid sequences, once isolated, the two nucleic acid sequences consist of:
(i) at least two DNA sequences chosen from the sequences SEQ ID NOs: 1 to 75, or (ii) at least two DNA sequences respectively complementary to at least two sequences chosen from the sequences SEQ ID NOs: 1 to 75, or (iii) at least two DNA sequences which exhibit at least 99% identity with two sequences as defined in (i) and (ii), or (iv) at least two RNA sequences which are respectively the transcription product of two sequences chosen from the sequences as defined in (i), or (v) at least two RNA sequences which are the transcription product of at least two sequences chosen from the sequences which exhibit at least 99% identity with the sequences as defined in (i). 11. A kit for the in vitro diagnosis or prognosis of prostate cancer in a biological sample taken from a patient, which comprises at least two respectively specific binding partners of at least two expression products of at least two nucleic acid sequences chosen from the sequences identified in SEQ ID NOs: 1 to 75 or from the sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 75 and no more than 75 specific binding partners of the expression products of the nucleic acid sequences identified in SEQ ID NOs: 1 to 75 or of the nucleic acid sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 75. 12. The kit as claimed in claim 11, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 1, 3, 4, 8, 10, 11, 15, 16, 21 and 32 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 3, 4, 8, 10, 11, 15, 16, 21 and 32. 13. The kit as claimed in claim 12, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 1, 4 and 10 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 4 and 10. 14. The kit as claimed in claim 12, which comprises two or three respectively specific binding partners of the expression products of the nucleic acid sequences identified in SEQ ID NOs: 1, 4 and 10 or of the nucleic acid sequences which exhibit at least 99% identity, with the sequences identified in SEQ ID NOs: 1, 4 and 10. 15. The kit as claimed in claim 11, in which the at least two respectively specific binding partners of the expression products are respectively at least one hybridization probe and/or at least one amplification primer, or at least one antibody, or at least one antibody analog, or at least one affinity protein, or at least one aptamer. 16. A method for evaluating the efficacy of a treatment and/or a progression in prostate cancer, which comprises a step of detecting at least two expression products respectively of at least two nucleic acid sequences, said two nucleic acid sequences being chosen from the sequences identified in SEQ ID NOs: 1 to 75 or from the sequences which exhibit at least 99% identity respectively with the sequences identified in SEQ ID NOs: 1 to 75. 17. The method as claimed in claim 16, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 3, 4, 8, 10, 11, 15, 16, 21 and 32 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 3, 4, 8, 10, 11, 15, 16, 21 and 32. 18. The method as claimed in claim 17, in which the expression product of at least two nucleic acid sequences, preferably of three nucleic acid sequences, is detected, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 4 and 10, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs 1, 4 and 10. | The present invention relates to a method for the in vitro diagnosis or prognosis of prostate cancer, which includes a step of detecting at least one expression product of at least one HERV nucleic acid sequence, the use of said nucleic acid sequences, once isolated, as one or more molecular marker(s) and a kit comprising at least one specific binding partner of at least one of the expression products of the HERV nucleic acid sequences.1. A method for the in vitro diagnosis or prognosis of prostate cancer in a biological sample taken from a patient, which comprises a step of detecting at least two expression products respectively of at least two nucleic acid sequences, said nucleic acid sequences being chosen from the sequences identified in SEQ ID NOs: 1 to 75 or from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 1 to 75. 2. The method as claimed in claim 1, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 3, 4, 8, 10, 11, 15, 16, 21 and 32 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 3, 4, 8, 10, 11, 15, 16, 21 and 32. 3. The method as claimed in claim 2, in which the expression product of at least two nucleic acid sequences is detected, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 4 and 10, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 4 and 10. 4. The method as claimed in claim 1, in which the expression product detected is at least one RNA transcript or at least one polypeptide. 5. The method as claimed in claim 4, wherein the RNA transcript is at least one mRNA. 6. The method as claimed in claim 4, in which the RNA transcript, in particular the mRNA, is detected by hybridization, by amplification or by sequencing. 7. The method as claimed in claim 6, in which the mRNA is brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and the presence or absence of hybridization to the mRNA is detected. 8. The method as claimed in claim 5, wherein DNA copies of the mRNA are prepared, the DNA copies are brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and in that the presence or absence of hybridization to said DNA copies is detected. 9. The method as claimed in claim 4, in which the polypeptide expressed is detected by bringing into contact with at least one specific binding partner of said polypeptide, an affinity protein or an aptamer. 10. A method for in vitro diagnosis or prognosis of prostate cancer comprising at least two nucleic acid sequences, once isolated, the two nucleic acid sequences consist of:
(i) at least two DNA sequences chosen from the sequences SEQ ID NOs: 1 to 75, or (ii) at least two DNA sequences respectively complementary to at least two sequences chosen from the sequences SEQ ID NOs: 1 to 75, or (iii) at least two DNA sequences which exhibit at least 99% identity with two sequences as defined in (i) and (ii), or (iv) at least two RNA sequences which are respectively the transcription product of two sequences chosen from the sequences as defined in (i), or (v) at least two RNA sequences which are the transcription product of at least two sequences chosen from the sequences which exhibit at least 99% identity with the sequences as defined in (i). 11. A kit for the in vitro diagnosis or prognosis of prostate cancer in a biological sample taken from a patient, which comprises at least two respectively specific binding partners of at least two expression products of at least two nucleic acid sequences chosen from the sequences identified in SEQ ID NOs: 1 to 75 or from the sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 75 and no more than 75 specific binding partners of the expression products of the nucleic acid sequences identified in SEQ ID NOs: 1 to 75 or of the nucleic acid sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 75. 12. The kit as claimed in claim 11, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 1, 3, 4, 8, 10, 11, 15, 16, 21 and 32 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 3, 4, 8, 10, 11, 15, 16, 21 and 32. 13. The kit as claimed in claim 12, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 1, 4 and 10 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 4 and 10. 14. The kit as claimed in claim 12, which comprises two or three respectively specific binding partners of the expression products of the nucleic acid sequences identified in SEQ ID NOs: 1, 4 and 10 or of the nucleic acid sequences which exhibit at least 99% identity, with the sequences identified in SEQ ID NOs: 1, 4 and 10. 15. The kit as claimed in claim 11, in which the at least two respectively specific binding partners of the expression products are respectively at least one hybridization probe and/or at least one amplification primer, or at least one antibody, or at least one antibody analog, or at least one affinity protein, or at least one aptamer. 16. A method for evaluating the efficacy of a treatment and/or a progression in prostate cancer, which comprises a step of detecting at least two expression products respectively of at least two nucleic acid sequences, said two nucleic acid sequences being chosen from the sequences identified in SEQ ID NOs: 1 to 75 or from the sequences which exhibit at least 99% identity respectively with the sequences identified in SEQ ID NOs: 1 to 75. 17. The method as claimed in claim 16, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 3, 4, 8, 10, 11, 15, 16, 21 and 32 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 3, 4, 8, 10, 11, 15, 16, 21 and 32. 18. The method as claimed in claim 17, in which the expression product of at least two nucleic acid sequences, preferably of three nucleic acid sequences, is detected, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 4 and 10, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs 1, 4 and 10. | 1,600 |
1,341 | 15,876,892 | 1,644 | Disclosed are methods and compositions for determining immunodominant peptides of target enzymes used in enzyme replacement therapy for lysosomal storage disorders. More specifically disclosed are immunodominant peptides for N-acetylgalactosamine-6-sulfatase (GALNS). Also disclosed are methods of inducing oral tolerance towards a target enzyme through oral administration of immunodominant peptides prior to commencing enzyme replacement therapy. More specifically disclosed is a method of inducing oral tolerance for GALNS, by orally administering specific immunodominant peptides for GALNS; in subjects suffering from mucopolysaccharidosis type IVA prior to commencing enzyme replacement therapy using GALNS. | 1-35. (canceled) 36. A method for treating mucopolysaccharidosis type IVA in a subject suffering from mucopolysaccharidosis type IVA, the method comprising: administering to the subject an effective amount of a polypeptide selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12 and combinations thereof. 37. The method of claim 36, wherein the polypeptide is SEQ ID NO:12. 38. The method of claim 36, wherein the effective amount ranges from about 50 μg per administration to about 500 μg per administration. 39. The method of claim 36, wherein the polypeptide is administered for 10 weeks. 40. The method of claim 39, wherein the polypeptide is administered about every other day for 10 weeks. 41. The method of claim 36, wherein the administering is oral administration. 42. The method of claim 36, further comprising administering to the subject N-acetyl galactosamine-6-sulfate sulfatase. 43. The method of claim 42, wherein the N-acetyl galactosamine-6-sulfate sulfatase is N-acetyl galactosamine-6-sulfate sulfatase enzyme replacement therapy. 44. the method of claim 42, wherein the administering is infusion. 45. The method of claim 42, wherein the N-acetyl galactosamine-6-sulfate sulfatase ranges from about 50 μg per administration to about 500 μg per administration. 46. The method of claim 36, wherein the subject is or has received N-acetyl galactosamine-6-sulfate sulfatase. 47. The method of claim 46, wherein the N-acetyl galactosamine-6-sulfate sulfatase is N-acetyl galactosamine-6-sulfate sulfatase enzyme replacement therapy. 48. the method of claim 46, wherein the administering is infusion. | Disclosed are methods and compositions for determining immunodominant peptides of target enzymes used in enzyme replacement therapy for lysosomal storage disorders. More specifically disclosed are immunodominant peptides for N-acetylgalactosamine-6-sulfatase (GALNS). Also disclosed are methods of inducing oral tolerance towards a target enzyme through oral administration of immunodominant peptides prior to commencing enzyme replacement therapy. More specifically disclosed is a method of inducing oral tolerance for GALNS, by orally administering specific immunodominant peptides for GALNS; in subjects suffering from mucopolysaccharidosis type IVA prior to commencing enzyme replacement therapy using GALNS.1-35. (canceled) 36. A method for treating mucopolysaccharidosis type IVA in a subject suffering from mucopolysaccharidosis type IVA, the method comprising: administering to the subject an effective amount of a polypeptide selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12 and combinations thereof. 37. The method of claim 36, wherein the polypeptide is SEQ ID NO:12. 38. The method of claim 36, wherein the effective amount ranges from about 50 μg per administration to about 500 μg per administration. 39. The method of claim 36, wherein the polypeptide is administered for 10 weeks. 40. The method of claim 39, wherein the polypeptide is administered about every other day for 10 weeks. 41. The method of claim 36, wherein the administering is oral administration. 42. The method of claim 36, further comprising administering to the subject N-acetyl galactosamine-6-sulfate sulfatase. 43. The method of claim 42, wherein the N-acetyl galactosamine-6-sulfate sulfatase is N-acetyl galactosamine-6-sulfate sulfatase enzyme replacement therapy. 44. the method of claim 42, wherein the administering is infusion. 45. The method of claim 42, wherein the N-acetyl galactosamine-6-sulfate sulfatase ranges from about 50 μg per administration to about 500 μg per administration. 46. The method of claim 36, wherein the subject is or has received N-acetyl galactosamine-6-sulfate sulfatase. 47. The method of claim 46, wherein the N-acetyl galactosamine-6-sulfate sulfatase is N-acetyl galactosamine-6-sulfate sulfatase enzyme replacement therapy. 48. the method of claim 46, wherein the administering is infusion. | 1,600 |
1,342 | 16,002,199 | 1,617 | The present disclosure provides pharmaceutical compositions that provide immediate release of active ingredients and have abuse deterrent properties. In particular, the pharmaceutical compositions comprise at least one pharmaceutically active ingredient, at least one non-cellulose polysaccharide, at least one hydrophilic gelling polymer, and an effervescent system. | 1. A process for preparing a solid dosage form, the process comprising:
a) blending at least one active pharmaceutical ingredient (API) or pharmaceutically acceptable salt thereof, at least one natural gum, a combination of hydrophilic gelling polymers, and an effervescent system to form a mixture; b) forming the mixture into a solid dosage unit; and c) heating the solid dosage unit at a temperature less than about 90° C. to form the solid dosage form; wherein the solid dosage form deters abuse and provides immediate release of the at least one API. 2. The process of claim 1, wherein the at least one API is an opioid or a combination of an opioid and a non-opioid analgesic, and the opioid is oxycodone, oxymorphone, hydrocodone, hydromorphone, codeine, or morphine. 3. The process of claim 1, wherein the at least one natural gum is alginate, alginic acid, carrageenan, dextran, diutan gum, gellan gum, glucomannan, guar gum, gum arabic, gum tragacanth, karaya gum, pullulan, xanthan gum, or welan gum; and the at least one natural gum is present in an amount from about 5% to about 40% by weight of the solid dosage form. 4. The process of claim 1, wherein the combination of hydrophilic gelling polymers comprises at least one cellulose ether and at least one polyethylene oxide having an average molecular weight from about 100,000 to about 10,000,000; and the combination of hydrophilic gelling polymers is present in an amount from about 10% to about 50% by weight of the solid dosage form. 5. The process of claim 4, wherein the at least one cellulose ether is hydroxypropylmethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, or a combination thereof, and the at least one polyethylene oxide having an average molecular weight from about 100,000 to about 10,000,000 comprises two polyethylene oxides having different molecular weights. 6. The process of claim 1, wherein the effervescent system comprises a) an acid component chosen from an organic acid, an inorganic acid, or a combination thereof, and b) a base component chosen from an alkali metal bicarbonate, an alkaline earth metal bicarbonate, an alkali metal carbonate, an organic carbonate, or a combination thereof; and the effervescent system is present in an amount from about 25% to 70% by weight of the solid dosage form. 7. The process of claim 1, wherein the mixture at step (a) further comprises a lubricant, and the lubricant is present in an amount of less than about 1% by weight of the solid dosage form. 8. The process of claim 1, wherein the temperature at step (c) is from about 50° C. to about 80° C. 9. The process of claim 1, further comprising applying a film coating to the solid dosage unit before step (c) or applying a film coating to the solid dosage form after step (c). 10. The process of claim 1, wherein the solid dosage form is a tablet, compact, pellet, caplet, pill, or capsule. 11. The process of claim 1, wherein the at least one API is oxycodone, oxymorphone, hydrocodone, hydromorphone, codeine, or morphine; the at least one natural gum is glucomannan, xanthan gum, or a combination thereof; the combination of hydrophilic gelling polymers comprises at least one cellulose ether and at least one polyethylene oxide having an average molecular weight from about 100,000 to about 10,000,000; and the effervescent system comprises a) an acid component comprising an organic acid and b) a base component comprising an alkali metal bicarbonate. 12. The process of claim 11, wherein the at least one cellulose ether is hydroxypropylmethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, or a combination thereof; and the at least one polyethylene oxide having an average molecular weight from about 100,000 to about 10,000,000 comprise a polyethylene oxide having an average molecular weight of about 100,000 and a polyethylene oxide having an average molecular weight of about 4,000,000. 13. The process of claim 11, wherein the at least one at least one natural gum is present in an amount from about 6% to about 30% by weight of the solid dosage form; the combination of hydrophilic gelling polymers is present in an amount from about 15% to about 40% by weight of the solid dosage form; and the effervescent system is present in an amount about 30% to 60% by weight of the solid dosage form. 14. The process of claim 13, wherein the mixture at step (a) further comprises a lubricant, and the lubricant is present in an amount of less than about 1% by weight of the solid dosage form. 15. The process of claim 14, wherein the at least one API is oxycodone hydrochloride, oxymorphone hydrochloride, or morphine sulfate. 16. The process of claim 14, further comprising applying a film coating to the solid dosage unit before step (c) or applying a film coating to the solid dosage form after step (c). 17. The process of claim 14, wherein the solid dosage form is a compressed tablet. 18. The process of claim 17, wherein the solid dosage form deters abuse by breaking into a plurality of particles having an average diameter of greater than about 250 microns when crushed, ground, or pulverized. 19. The process of claim 17, wherein the solid dosage form deters abuse by forming a viscous mixture or gel when in contact with about 3 mL to about 10 mL of an aqueous solvent. 20. The process of claim 17, wherein the solid dosage form releases at least about 80% of the at least one API within about 30 minutes when measured using an USP-approved in vitro release procedure. | The present disclosure provides pharmaceutical compositions that provide immediate release of active ingredients and have abuse deterrent properties. In particular, the pharmaceutical compositions comprise at least one pharmaceutically active ingredient, at least one non-cellulose polysaccharide, at least one hydrophilic gelling polymer, and an effervescent system.1. A process for preparing a solid dosage form, the process comprising:
a) blending at least one active pharmaceutical ingredient (API) or pharmaceutically acceptable salt thereof, at least one natural gum, a combination of hydrophilic gelling polymers, and an effervescent system to form a mixture; b) forming the mixture into a solid dosage unit; and c) heating the solid dosage unit at a temperature less than about 90° C. to form the solid dosage form; wherein the solid dosage form deters abuse and provides immediate release of the at least one API. 2. The process of claim 1, wherein the at least one API is an opioid or a combination of an opioid and a non-opioid analgesic, and the opioid is oxycodone, oxymorphone, hydrocodone, hydromorphone, codeine, or morphine. 3. The process of claim 1, wherein the at least one natural gum is alginate, alginic acid, carrageenan, dextran, diutan gum, gellan gum, glucomannan, guar gum, gum arabic, gum tragacanth, karaya gum, pullulan, xanthan gum, or welan gum; and the at least one natural gum is present in an amount from about 5% to about 40% by weight of the solid dosage form. 4. The process of claim 1, wherein the combination of hydrophilic gelling polymers comprises at least one cellulose ether and at least one polyethylene oxide having an average molecular weight from about 100,000 to about 10,000,000; and the combination of hydrophilic gelling polymers is present in an amount from about 10% to about 50% by weight of the solid dosage form. 5. The process of claim 4, wherein the at least one cellulose ether is hydroxypropylmethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, or a combination thereof, and the at least one polyethylene oxide having an average molecular weight from about 100,000 to about 10,000,000 comprises two polyethylene oxides having different molecular weights. 6. The process of claim 1, wherein the effervescent system comprises a) an acid component chosen from an organic acid, an inorganic acid, or a combination thereof, and b) a base component chosen from an alkali metal bicarbonate, an alkaline earth metal bicarbonate, an alkali metal carbonate, an organic carbonate, or a combination thereof; and the effervescent system is present in an amount from about 25% to 70% by weight of the solid dosage form. 7. The process of claim 1, wherein the mixture at step (a) further comprises a lubricant, and the lubricant is present in an amount of less than about 1% by weight of the solid dosage form. 8. The process of claim 1, wherein the temperature at step (c) is from about 50° C. to about 80° C. 9. The process of claim 1, further comprising applying a film coating to the solid dosage unit before step (c) or applying a film coating to the solid dosage form after step (c). 10. The process of claim 1, wherein the solid dosage form is a tablet, compact, pellet, caplet, pill, or capsule. 11. The process of claim 1, wherein the at least one API is oxycodone, oxymorphone, hydrocodone, hydromorphone, codeine, or morphine; the at least one natural gum is glucomannan, xanthan gum, or a combination thereof; the combination of hydrophilic gelling polymers comprises at least one cellulose ether and at least one polyethylene oxide having an average molecular weight from about 100,000 to about 10,000,000; and the effervescent system comprises a) an acid component comprising an organic acid and b) a base component comprising an alkali metal bicarbonate. 12. The process of claim 11, wherein the at least one cellulose ether is hydroxypropylmethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, or a combination thereof; and the at least one polyethylene oxide having an average molecular weight from about 100,000 to about 10,000,000 comprise a polyethylene oxide having an average molecular weight of about 100,000 and a polyethylene oxide having an average molecular weight of about 4,000,000. 13. The process of claim 11, wherein the at least one at least one natural gum is present in an amount from about 6% to about 30% by weight of the solid dosage form; the combination of hydrophilic gelling polymers is present in an amount from about 15% to about 40% by weight of the solid dosage form; and the effervescent system is present in an amount about 30% to 60% by weight of the solid dosage form. 14. The process of claim 13, wherein the mixture at step (a) further comprises a lubricant, and the lubricant is present in an amount of less than about 1% by weight of the solid dosage form. 15. The process of claim 14, wherein the at least one API is oxycodone hydrochloride, oxymorphone hydrochloride, or morphine sulfate. 16. The process of claim 14, further comprising applying a film coating to the solid dosage unit before step (c) or applying a film coating to the solid dosage form after step (c). 17. The process of claim 14, wherein the solid dosage form is a compressed tablet. 18. The process of claim 17, wherein the solid dosage form deters abuse by breaking into a plurality of particles having an average diameter of greater than about 250 microns when crushed, ground, or pulverized. 19. The process of claim 17, wherein the solid dosage form deters abuse by forming a viscous mixture or gel when in contact with about 3 mL to about 10 mL of an aqueous solvent. 20. The process of claim 17, wherein the solid dosage form releases at least about 80% of the at least one API within about 30 minutes when measured using an USP-approved in vitro release procedure. | 1,600 |
1,343 | 14,964,868 | 1,653 | An apparatus for perfusing an organ or tissue includes a perfusion circuit for perfusing the organ or tissue; an oxygenator for oxygenating perfusate that circulates through the perfusion circuit; and an oxygen supply device such as an oxygen concentrator or an oxygen generator configured to supply oxygen to the oxygenator. A method of perfusing an organ or tissue includes producing oxygen from a device such as an oxygen concentrator and an oxygen generator; supplying the produced oxygen, preferably as the oxygen is produced, to a perfusate to oxygenate the perfusate; and perfusing the organ or tissue with the oxygenated perfusate. The produced oxygen preferably has a concentration greater than the oxygen concentration in air. | 1. An apparatus for perfusing an organ or tissue, the apparatus comprising:
a perfusion circuit configured to perfuse the organ or tissue with liquid perfusate; an oxygenator connected to the perfusion circuit; and an oxygen supply device configured to supply produced oxygen to the oxygenator, wherein the oxygenator is configured to oxygenate the perfusate as the oxygen is produced. 2. The apparatus according to claim 1, wherein the oxygenator is configured to oxygenate the perfusate after the perfusing of the organ or tissue. 3. The apparatus according to claim 1, wherein oxygen is not stored in the apparatus. 4. The apparatus according to claim 1, wherein the produced oxygen has a concentration greater than the oxygen concentration of air. 5. The apparatus according to claim 1, wherein the oxygen supply device is configured to supply the produced oxygen by starting with an oxygen supply with relatively low oxygen concentration and outputting oxygen with a concentration that is higher relative to the oxygen supply. 6. The apparatus according to claim 5, wherein the oxygen supply device is configured to operate with the oxygen supply being air. 7. The apparatus according to claim 6, wherein the air is compressed air. 8. The apparatus according to claim 6, wherein the air is ambient air. 9. The apparatus according to claim 5, wherein the oxygen supply device is configured to operate with the oxygen supply being water. 10. The apparatus according to claim 1, wherein the oxygen supply device is configured to supply the produced oxygen based on feedback detected from the organ or tissue. 11. The apparatus according to claim 5, further comprising:
a bubble trap disposed within the perfusion circuit downstream of the oxygenator relative to a direction of perfusate flow. 12. The apparatus according to claim 1, wherein the apparatus does not include an oxygen storage device. 13. The apparatus according to claim 1, wherein the apparatus is transportable and weighs less than 90 pounds. 14. The apparatus according to claim 1, wherein the apparatus is configured to sterilize or prevent contamination of the produced oxygen supplied by the oxygen supply device. 15. A method of perfusing an organ or tissue, the method comprising:
producing oxygen from an oxygen supply device; supplying the oxygen, as the oxygen is produced, to a liquid perfusate to oxygenate the perfusate; and perfusing the organ or tissue with the perfusate, wherein the oxygen has a concentration greater than the oxygen concentration in air and the perfusate is recirculated. 16. The method according the claim 15, wherein the oxygen is supplied based on feedback detected from the organ or tissue. 17. The method according to claim 15, wherein the oxygen is produced from water. 18. The method according the claim 15, wherein the oxygen is supplied based on feedback detected from the organ or tissue. 19. The method according the claim 15, wherein the oxygen is produced on board a portable organ perfusion apparatus. 20. The method according to claim 15, wherein the oxygen is produced by starting with an oxygen supply with relatively low oxygen concentration and outputting the oxygen with a concentration that is higher relative to the oxygen supply. | An apparatus for perfusing an organ or tissue includes a perfusion circuit for perfusing the organ or tissue; an oxygenator for oxygenating perfusate that circulates through the perfusion circuit; and an oxygen supply device such as an oxygen concentrator or an oxygen generator configured to supply oxygen to the oxygenator. A method of perfusing an organ or tissue includes producing oxygen from a device such as an oxygen concentrator and an oxygen generator; supplying the produced oxygen, preferably as the oxygen is produced, to a perfusate to oxygenate the perfusate; and perfusing the organ or tissue with the oxygenated perfusate. The produced oxygen preferably has a concentration greater than the oxygen concentration in air.1. An apparatus for perfusing an organ or tissue, the apparatus comprising:
a perfusion circuit configured to perfuse the organ or tissue with liquid perfusate; an oxygenator connected to the perfusion circuit; and an oxygen supply device configured to supply produced oxygen to the oxygenator, wherein the oxygenator is configured to oxygenate the perfusate as the oxygen is produced. 2. The apparatus according to claim 1, wherein the oxygenator is configured to oxygenate the perfusate after the perfusing of the organ or tissue. 3. The apparatus according to claim 1, wherein oxygen is not stored in the apparatus. 4. The apparatus according to claim 1, wherein the produced oxygen has a concentration greater than the oxygen concentration of air. 5. The apparatus according to claim 1, wherein the oxygen supply device is configured to supply the produced oxygen by starting with an oxygen supply with relatively low oxygen concentration and outputting oxygen with a concentration that is higher relative to the oxygen supply. 6. The apparatus according to claim 5, wherein the oxygen supply device is configured to operate with the oxygen supply being air. 7. The apparatus according to claim 6, wherein the air is compressed air. 8. The apparatus according to claim 6, wherein the air is ambient air. 9. The apparatus according to claim 5, wherein the oxygen supply device is configured to operate with the oxygen supply being water. 10. The apparatus according to claim 1, wherein the oxygen supply device is configured to supply the produced oxygen based on feedback detected from the organ or tissue. 11. The apparatus according to claim 5, further comprising:
a bubble trap disposed within the perfusion circuit downstream of the oxygenator relative to a direction of perfusate flow. 12. The apparatus according to claim 1, wherein the apparatus does not include an oxygen storage device. 13. The apparatus according to claim 1, wherein the apparatus is transportable and weighs less than 90 pounds. 14. The apparatus according to claim 1, wherein the apparatus is configured to sterilize or prevent contamination of the produced oxygen supplied by the oxygen supply device. 15. A method of perfusing an organ or tissue, the method comprising:
producing oxygen from an oxygen supply device; supplying the oxygen, as the oxygen is produced, to a liquid perfusate to oxygenate the perfusate; and perfusing the organ or tissue with the perfusate, wherein the oxygen has a concentration greater than the oxygen concentration in air and the perfusate is recirculated. 16. The method according the claim 15, wherein the oxygen is supplied based on feedback detected from the organ or tissue. 17. The method according to claim 15, wherein the oxygen is produced from water. 18. The method according the claim 15, wherein the oxygen is supplied based on feedback detected from the organ or tissue. 19. The method according the claim 15, wherein the oxygen is produced on board a portable organ perfusion apparatus. 20. The method according to claim 15, wherein the oxygen is produced by starting with an oxygen supply with relatively low oxygen concentration and outputting the oxygen with a concentration that is higher relative to the oxygen supply. | 1,600 |
1,344 | 14,441,311 | 1,619 | The present invention relates to a cosmetic composition, in particular a hair composition, comprising i) one or more dicarbonyl compounds corresponding to formula (I) below, and/or derivatives thereof and/or hydrates thereof and/or salts thereof: in which formula (I): R represents an atom or group chosen from i) hydrogen, ii) carboxyl —C(O)OH, iii) linear or branched C 1 -C 6 alkyl which is optionally substituted, preferably with at least one hydroxyl —OH radical, carboxyl —C(O)—OH radical or halogen such as Br, iv) optionally substituted phenyl, v) optionally substituted benzyl, iv) and v) preferably being optionally substituted with at least one —OH or —C(O)OH radical, vi) an indolyl radical and vii) an imidazolylmethyl radical and tautomers thereof such as with * representing the part linked to the rest of the molecule, and ii) at least one amino silicone, the composition having a pH of less than or equal to 4, and also to a process for straightening the hair using this composition. | 1. Process for straightening keratin fibres such as the hair, which comprises the application to the said fibres of a cosmetic composition comprising:
i) one or more dicarbonyl compounds corresponding to formula (I) below, and/or derivatives thereof and/or hydrates thereof and/or salts thereof:
in which formula (I):
R represents an atom or group chosen from i) hydrogen, ii) carboxyl-C(O)OH, iii) linear or branched C1-C6 alkyl which is optionally substituted, preferably with at least one hydroxyl —OH radical, carboxyl —C(O)—OH radical or halogen such as Br, iv) optionally substituted phenyl, v) optionally substituted benzyl, iv) and v) preferably being optionally substituted with at least one —OH or —C(O)OH radical, vi) an indolyl radical and vii) an imidazolylmethyl radical and tautomers thereof such as:
with * representing the part linked to the rest of the molecule, and
ii) at least one amino silicone,
the composition having a pH of less than or equal to 4,
followed by a straightening step using a straightening iron. 2. Process according to claim 1, in which the dicarbonyl compound(s) are of formula (I) with R representing i) a hydrogen atom or ii) a linear or branched C1-C6 alkyl group optionally substituted with a carboxyl group. 3. Process according to either one of the preceding claims, in which the dicarbonyl compound(s) of formula (I) and/or derivatives thereof and/or hydrates thereof and/or salts thereof are chosen from glyoxylic acid and pyruvic acid, a derivative thereof, salts thereof and hydrates thereof, preferably from glyoxylic acid, a derivative thereof and the hydrate forms of these compounds. 4. Process according to any one of the preceding claims, in which the dicarbonyl compound(s) of formula (I) and/or derivatives thereof are chosen from glyoxylic acid esters, glyoxylic acid amides, glyoxylic acid (thio)acetals and hemi(thio)acetals, and glyoxylic acid ester (thio)acetals and hemi(thio)acetals. 5. Process according to claim 3, in which the glyoxylic acid is in its hydrate form. 6. Process according to any one of the preceding claims, in which the composition comprises from 0.1% to 20% by weight of one or more dicarbonyl compounds corresponding to formula (I) and/or derivatives thereof and/or hydrates thereof and/or salts thereof, preferably from 3% to 10% by weight relative to the total weight of the composition. 7. Process according to any one of the preceding claims, in which the amino silicone(s) are chosen from the silicones (a) to (e) below:
(a) the compounds corresponding to formula (Ia) below:
(R1)a(T)3-a-Si[OSi(T)2]n-[OSi(T)b(R1)2-b]m—OSi(T)3-a-(R1)a (Ia)
in which formula (Ia):
T represents a hydrogen atom or a phenyl, hydroxyl (—OH) or C1-C8 alkyl group, and preferably methyl, or a C1-C8 alkoxy, preferably methoxy;
a denotes the number 0 or an integer from 1 to 3, and preferably 0;
b denotes 0 or 1, and in particular 1;
m and n are integers such that the sum (n+m) can range especially from 1 to 2000 and in particular from 50 to 150, it being possible for n to denote a number from 0 to 1999 and in particular from 49 to 149, and for m to denote a number from 1 to 2000 and in particular from 1 to 10;
R1 is a monovalent group of formula —CqH2qL in which q is an integer from 2 to 8 and L is an optionally quaternized amino group chosen from the following groups:
—N(R2)—CH2—CH2—N(R2)2,
—N(R2)2,
—N(R2)3 Q−,
—N(R2) (H)2 Q−,
—N+(R2)2HQ−,
—N(R2)—CH2—CH2—N+(R2)(H)2 Q−;
in which R2 may denote a hydrogen atom, a phenyl group, a benzyl group or a saturated monovalent hydrocarbon-based group, for example a C1-C20 alkyl group, and Q− represents an anionic counterion such as a halide ion, for instance fluoride, chloride, bromide or iodide;
(b) the compounds corresponding to formula (Ib) below:
in which formula (Ib):
R3 represents a monovalent C1-C18 hydrocarbon-based group, and in particular a C1-C18 alkyl or C2-C18 alkenyl group, for example methyl;
R4 represents a divalent hydrocarbon-based group, in particular a C1-C18 alkylene group or a divalent C1-C18, for example C1-C8, alkylenoxy group;
Q− represents an anionic counterion such as that chosen from halide ions, especially chloride;
r represents a mean statistical value from 2 to 20 and in particular from 2 to 8;
s represents a mean statistical value between 20 and 200 inclusive and in particular between 20 and 50 inclusive;
(c) the quaternary ammonium silicones, especially of formula (Ic):
in which formula (Ic):
R6 represents a divalent hydrocarbon-based group, especially a C1-C18 alkylene group or a divalent C1-C18, for example C1-C8, alkylenoxy group linked to the Si atom via an Si—C bond;
R7, which may be identical or different, represent a monovalent hydrocarbon-based group containing from 1 to 18 carbon atoms, and in particular a C1-C18 alkyl group, a C2-C18 alkenyl group or a ring comprising 5 or 6 carbon atoms, for example methyl;
R8, which may be identical or different, each represent a hydrogen atom, a monovalent hydrocarbon-based group containing from 1 to 18 carbon atoms, and in particular a C1-C18 alkyl group, a C2-C18 alkenyl group or a group —R6—N(H)—C(O)—R7 with R6 and R7 as defined previously;
X−, which may be identical or different, represents an anionic counterion such as a halide ion, especially chloride, or an anionic counterion derived from an organic acid such as (C1-C6)alkylcarboxylate;
r represents a mean statistical value between 2 and 200 inclusive and in particular between 5 and 100;
(d) the amino silicones of formula (Id):
in which formula (Id):
R1, R2, R3 and R4, which may be identical or different, each denote a C1-C4 alkyl group or an aryl group such as phenyl,
R5 denotes a C1-C4 alkyl group or a hydroxyl group,
n and m, which may be identical or different, represent an integer between 1 and 5 inclusive, and
x is such that the amine number is between 0.01 and 1 meq/g;
(e) the amino silicones containing polyalkoxylene groups of formula (Ie):
in which formula (Ie):
Ra, Rb, Rc and Rd, which may be identical or different, represent a hydroxyl or linear or branched (C1-C10)alkyl group, and preferably Ra, Rb, Rc and Rd represent a (C1-C6)alkyl group, which is more particularly linear, such as methyl;
ALK and ALK′, which may be identical or different, represent a linear or branched (C1-C10)alkylene group, which is preferably linear, such as propylene;
A and B, which may be identical or different, represent an aminopolyalkoxy group below:
ReRfN-[ALK″-O]z-[ALK′″-O]w-ALKa—N(Rg)—[ALKb—O]q-*
with:
representing the point of attachment of the radical to the rest of the molecule via ALK or ALK′;
Re, Rf and Rg, which may be identical or different, representing a hydrogen atom or a linear or branched (C1-C10)alkyl group, and preferably Re, Rf and Rg represent a hydrogen atom;
ALK″ and ALK′″, which may be identical or different, represent a linear or branched (C1-C10)alkylene group, preferably of C2 or C3; more particularly, ALK″ represents a divalent group —CH2—CH(CH3)— and ALK′″ represents an ethylene group;
ALKa and ALKb, which may be identical or different, represent a linear or branched (C1-C10)alkylene group, which is optionally substituted preferably with a hydroxyl group, and is preferably of C2 or C3; more particularly, ALKa represents an ethylene or propylene group or a divalent group —CH2—CH(CH3)— and ALKb represents a divalent group —CH2—CH(OH)—CH2—;
q, which may be identical or different, represent 0 or 1, preferably 1;
w, which may be identical or different, represent an integer, preferably the sum of the w values (w of A+w of B) having a mean value inclusively between 10 and 100, more particularly inclusively between 20 and 60 and more preferentially between 30 and 50, such as 40-41;
z, which may be identical or different, represent an integer, preferably the sum of the z values (z of A+z of B) having a mean value inclusively between 1 and 20, more particularly inclusively between 1 and 10 and more preferentially between 2 and 5, such as 3;
(I′e) the amino silicones containing polyalkoxylene groups consisting of polysiloxane block(s) and of polyalkoxylene block(s) comprising at least one amine group, in particular:
those of formula (I′e):
in which formula (I′e):
Ra, Rb, Rc and Rd, which may be identical or different, represent a hydroxyl or linear or branched (C1-C10)alkyl group, and preferably Ra, Rb, Rc and Rd represent a (C1-C4)alkyl group, which is more particularly linear, such as methyl;
R and R″, which may be identical or different, represent a linear or branched, optionally hydroxylated C2-C6 alkylene radical, optionally interrupted with an oxygen atom;
a and b, which may be identical or different, represent a number ranging from 0 to 100;
R′ and R′″, which may be identical or different, represent a hydrogen atom or a C1-C4 alkyl radical such as a methyl radical;
x denotes an integer ranging from 1 to 500 and y denotes an integer ranging from 1 to 10;
that containing units of formula (IIe)
in which formula (IIe)
R1 to R4, which may be identical or different, represent a C1-C4 alkyl radical, preferably methyl;
R and R″, which may be identical or different, represent a linear or branched, optionally hydroxylated C2-C6 alkylene radical, optionally interrupted with an oxygen atom;
a and b, which may be identical or different, represent an integer ranging from 0 to 100;
R′ and R′″, which may be identical or different, represent a hydrogen atom or a C1-C4 alkyl radical such as a methyl radical; and
x denotes a number ranging from 1 to 500 and y denotes a number ranging from 1 to 10. 8. Process according to any one of the preceding claims, in which the amino silicone(s) are chosen from amino silicones bearing polyalkoxylene groups consisting of polysiloxane block(s) and polyalkoxylene block(s) comprising at least one amine group, in particular those of formula (Ie) or (Ie′) as defined in the preceding claim, and particularly the amino silicone(s) are chosen from:
i) the amino silicones bisamino PolyEthyleneGlycol/PolyPropyleneGlycol-41-3 aminoethyl PG(glycidopropyl)-propyl dimethicone in particular of formula (IIe) below:
in which formula (IIe) m and n, which may be identical or different, represent an integer with the sum m+n having a mean value of 41 and o and p, which may be identical or different, represent an integer with the sum o+p having a mean value of 3. 9. Process according to any one of the preceding claims, in which the amino silicone(s) are chosen from amino silicones derived from the reaction between one or more copolymers of PEG-40/PPG-8 terminating with a 2-aminopropyl group and of bis-glycidoxypropyl dimethicone. 10. Process according to any one of the preceding claims, in which the amino silicone(s) are present in an amount ranging from 0.01% to 10%, better still from 0.1% to 5% by weight, preferably from 0.5% to 3% by weight and even more preferentially from 0.5% to 1.5% by weight relative to the total weight of the composition. 11. Process according to any one of the preceding claims, in which the weight ratio between the amount of amino silicone(s) as defined in claims 1 and 7 to 9, on the one hand, and the amount of dicarbonyl compounds corresponding to formula (I) and/or derivatives thereof and/or hydrates thereof and/or salts thereof as defined in claims 1 to 6 ranges from 0.01 to 100, even more preferentially from 0.01 to 20, better still from 0.05 to 10 and even better still from 0.05 to 1. 12. Process according to any one of the preceding claims, characterized in that it is aqueous and comprises water in a concentration preferably ranging from 5% to 98%, better still from 5% to 90% and even better still from 10% to 90% by weight relative to the total weight of the composition. 13. Process according to any one of the preceding claims, characterized in that the composition results from the mixing of several compositions. 14. Process according to any one of the preceding claims, wherein the time of contact of the composition with the hair is of between 10 and 60 minutes. 15. Process according to any one of the preceding claims, wherein the hair is straightened using a straightening iron at a temperature of at least 150° C. and preferably between 150 and 250° C. 16. Use of a composition comprising:
i) one or more dicarbonyl compounds corresponding to formula (I) below, and/or derivatives thereof and/or hydrates thereof and/or salts thereof:
in which formula (I):
R represents an atom or group chosen from i) hydrogen, ii) carboxyl-C(O)OH, iii) linear or branched C1-C6 alkyl which is optionally substituted, preferably with at least one hydroxyl —OH radical, carboxyl —C(O)—OH radical or halogen such as Br, iv) optionally substituted phenyl, v) optionally substituted benzyl, iv) and v) preferably being optionally substituted with at least one —OH or —C(O)OH radical, vi) an indolyl radical and vii) an imidazolylmethyl radical and tautomers thereof such as:
with * representing the part linked to the rest of the molecule, and
ii) at least one amino silicone,
the composition having a pH of less than or equal to 4, for straightening/relaxing keratin fibres, especially the hair. 17. Cosmetic composition, in particular a hair composition, comprising
i) one or more dicarbonyl compounds corresponding to formula (I) below, and/or derivatives thereof and/or hydrates thereof and/or salts thereof:
in which formula (I):
R represents an atom or group chosen from i) hydrogen, ii) carboxyl —C(O)OH, iii) linear or branched C1-C6 alkyl which is optionally substituted, preferably with at least one hydroxyl —OH radical or halogen such as Br, iv) optionally substituted phenyl, v) optionally substituted benzyl, iv) and v) preferably being optionally substituted with at least one —OH or —C(O)OH radical, vi) an indolyl radical and vii) an imidazolylmethyl radical and tautomers thereof such as
with * representing the part linked to the rest of the molecule, preferably one or more dicarbonyl compounds according to any one of claims 3 to 6,
and ii) at least one amino silicone, preferably at least one amino silicone according to any one of claims 7 to 10, the composition having a pH of less than or equal to 4. | The present invention relates to a cosmetic composition, in particular a hair composition, comprising i) one or more dicarbonyl compounds corresponding to formula (I) below, and/or derivatives thereof and/or hydrates thereof and/or salts thereof: in which formula (I): R represents an atom or group chosen from i) hydrogen, ii) carboxyl —C(O)OH, iii) linear or branched C 1 -C 6 alkyl which is optionally substituted, preferably with at least one hydroxyl —OH radical, carboxyl —C(O)—OH radical or halogen such as Br, iv) optionally substituted phenyl, v) optionally substituted benzyl, iv) and v) preferably being optionally substituted with at least one —OH or —C(O)OH radical, vi) an indolyl radical and vii) an imidazolylmethyl radical and tautomers thereof such as with * representing the part linked to the rest of the molecule, and ii) at least one amino silicone, the composition having a pH of less than or equal to 4, and also to a process for straightening the hair using this composition.1. Process for straightening keratin fibres such as the hair, which comprises the application to the said fibres of a cosmetic composition comprising:
i) one or more dicarbonyl compounds corresponding to formula (I) below, and/or derivatives thereof and/or hydrates thereof and/or salts thereof:
in which formula (I):
R represents an atom or group chosen from i) hydrogen, ii) carboxyl-C(O)OH, iii) linear or branched C1-C6 alkyl which is optionally substituted, preferably with at least one hydroxyl —OH radical, carboxyl —C(O)—OH radical or halogen such as Br, iv) optionally substituted phenyl, v) optionally substituted benzyl, iv) and v) preferably being optionally substituted with at least one —OH or —C(O)OH radical, vi) an indolyl radical and vii) an imidazolylmethyl radical and tautomers thereof such as:
with * representing the part linked to the rest of the molecule, and
ii) at least one amino silicone,
the composition having a pH of less than or equal to 4,
followed by a straightening step using a straightening iron. 2. Process according to claim 1, in which the dicarbonyl compound(s) are of formula (I) with R representing i) a hydrogen atom or ii) a linear or branched C1-C6 alkyl group optionally substituted with a carboxyl group. 3. Process according to either one of the preceding claims, in which the dicarbonyl compound(s) of formula (I) and/or derivatives thereof and/or hydrates thereof and/or salts thereof are chosen from glyoxylic acid and pyruvic acid, a derivative thereof, salts thereof and hydrates thereof, preferably from glyoxylic acid, a derivative thereof and the hydrate forms of these compounds. 4. Process according to any one of the preceding claims, in which the dicarbonyl compound(s) of formula (I) and/or derivatives thereof are chosen from glyoxylic acid esters, glyoxylic acid amides, glyoxylic acid (thio)acetals and hemi(thio)acetals, and glyoxylic acid ester (thio)acetals and hemi(thio)acetals. 5. Process according to claim 3, in which the glyoxylic acid is in its hydrate form. 6. Process according to any one of the preceding claims, in which the composition comprises from 0.1% to 20% by weight of one or more dicarbonyl compounds corresponding to formula (I) and/or derivatives thereof and/or hydrates thereof and/or salts thereof, preferably from 3% to 10% by weight relative to the total weight of the composition. 7. Process according to any one of the preceding claims, in which the amino silicone(s) are chosen from the silicones (a) to (e) below:
(a) the compounds corresponding to formula (Ia) below:
(R1)a(T)3-a-Si[OSi(T)2]n-[OSi(T)b(R1)2-b]m—OSi(T)3-a-(R1)a (Ia)
in which formula (Ia):
T represents a hydrogen atom or a phenyl, hydroxyl (—OH) or C1-C8 alkyl group, and preferably methyl, or a C1-C8 alkoxy, preferably methoxy;
a denotes the number 0 or an integer from 1 to 3, and preferably 0;
b denotes 0 or 1, and in particular 1;
m and n are integers such that the sum (n+m) can range especially from 1 to 2000 and in particular from 50 to 150, it being possible for n to denote a number from 0 to 1999 and in particular from 49 to 149, and for m to denote a number from 1 to 2000 and in particular from 1 to 10;
R1 is a monovalent group of formula —CqH2qL in which q is an integer from 2 to 8 and L is an optionally quaternized amino group chosen from the following groups:
—N(R2)—CH2—CH2—N(R2)2,
—N(R2)2,
—N(R2)3 Q−,
—N(R2) (H)2 Q−,
—N+(R2)2HQ−,
—N(R2)—CH2—CH2—N+(R2)(H)2 Q−;
in which R2 may denote a hydrogen atom, a phenyl group, a benzyl group or a saturated monovalent hydrocarbon-based group, for example a C1-C20 alkyl group, and Q− represents an anionic counterion such as a halide ion, for instance fluoride, chloride, bromide or iodide;
(b) the compounds corresponding to formula (Ib) below:
in which formula (Ib):
R3 represents a monovalent C1-C18 hydrocarbon-based group, and in particular a C1-C18 alkyl or C2-C18 alkenyl group, for example methyl;
R4 represents a divalent hydrocarbon-based group, in particular a C1-C18 alkylene group or a divalent C1-C18, for example C1-C8, alkylenoxy group;
Q− represents an anionic counterion such as that chosen from halide ions, especially chloride;
r represents a mean statistical value from 2 to 20 and in particular from 2 to 8;
s represents a mean statistical value between 20 and 200 inclusive and in particular between 20 and 50 inclusive;
(c) the quaternary ammonium silicones, especially of formula (Ic):
in which formula (Ic):
R6 represents a divalent hydrocarbon-based group, especially a C1-C18 alkylene group or a divalent C1-C18, for example C1-C8, alkylenoxy group linked to the Si atom via an Si—C bond;
R7, which may be identical or different, represent a monovalent hydrocarbon-based group containing from 1 to 18 carbon atoms, and in particular a C1-C18 alkyl group, a C2-C18 alkenyl group or a ring comprising 5 or 6 carbon atoms, for example methyl;
R8, which may be identical or different, each represent a hydrogen atom, a monovalent hydrocarbon-based group containing from 1 to 18 carbon atoms, and in particular a C1-C18 alkyl group, a C2-C18 alkenyl group or a group —R6—N(H)—C(O)—R7 with R6 and R7 as defined previously;
X−, which may be identical or different, represents an anionic counterion such as a halide ion, especially chloride, or an anionic counterion derived from an organic acid such as (C1-C6)alkylcarboxylate;
r represents a mean statistical value between 2 and 200 inclusive and in particular between 5 and 100;
(d) the amino silicones of formula (Id):
in which formula (Id):
R1, R2, R3 and R4, which may be identical or different, each denote a C1-C4 alkyl group or an aryl group such as phenyl,
R5 denotes a C1-C4 alkyl group or a hydroxyl group,
n and m, which may be identical or different, represent an integer between 1 and 5 inclusive, and
x is such that the amine number is between 0.01 and 1 meq/g;
(e) the amino silicones containing polyalkoxylene groups of formula (Ie):
in which formula (Ie):
Ra, Rb, Rc and Rd, which may be identical or different, represent a hydroxyl or linear or branched (C1-C10)alkyl group, and preferably Ra, Rb, Rc and Rd represent a (C1-C6)alkyl group, which is more particularly linear, such as methyl;
ALK and ALK′, which may be identical or different, represent a linear or branched (C1-C10)alkylene group, which is preferably linear, such as propylene;
A and B, which may be identical or different, represent an aminopolyalkoxy group below:
ReRfN-[ALK″-O]z-[ALK′″-O]w-ALKa—N(Rg)—[ALKb—O]q-*
with:
representing the point of attachment of the radical to the rest of the molecule via ALK or ALK′;
Re, Rf and Rg, which may be identical or different, representing a hydrogen atom or a linear or branched (C1-C10)alkyl group, and preferably Re, Rf and Rg represent a hydrogen atom;
ALK″ and ALK′″, which may be identical or different, represent a linear or branched (C1-C10)alkylene group, preferably of C2 or C3; more particularly, ALK″ represents a divalent group —CH2—CH(CH3)— and ALK′″ represents an ethylene group;
ALKa and ALKb, which may be identical or different, represent a linear or branched (C1-C10)alkylene group, which is optionally substituted preferably with a hydroxyl group, and is preferably of C2 or C3; more particularly, ALKa represents an ethylene or propylene group or a divalent group —CH2—CH(CH3)— and ALKb represents a divalent group —CH2—CH(OH)—CH2—;
q, which may be identical or different, represent 0 or 1, preferably 1;
w, which may be identical or different, represent an integer, preferably the sum of the w values (w of A+w of B) having a mean value inclusively between 10 and 100, more particularly inclusively between 20 and 60 and more preferentially between 30 and 50, such as 40-41;
z, which may be identical or different, represent an integer, preferably the sum of the z values (z of A+z of B) having a mean value inclusively between 1 and 20, more particularly inclusively between 1 and 10 and more preferentially between 2 and 5, such as 3;
(I′e) the amino silicones containing polyalkoxylene groups consisting of polysiloxane block(s) and of polyalkoxylene block(s) comprising at least one amine group, in particular:
those of formula (I′e):
in which formula (I′e):
Ra, Rb, Rc and Rd, which may be identical or different, represent a hydroxyl or linear or branched (C1-C10)alkyl group, and preferably Ra, Rb, Rc and Rd represent a (C1-C4)alkyl group, which is more particularly linear, such as methyl;
R and R″, which may be identical or different, represent a linear or branched, optionally hydroxylated C2-C6 alkylene radical, optionally interrupted with an oxygen atom;
a and b, which may be identical or different, represent a number ranging from 0 to 100;
R′ and R′″, which may be identical or different, represent a hydrogen atom or a C1-C4 alkyl radical such as a methyl radical;
x denotes an integer ranging from 1 to 500 and y denotes an integer ranging from 1 to 10;
that containing units of formula (IIe)
in which formula (IIe)
R1 to R4, which may be identical or different, represent a C1-C4 alkyl radical, preferably methyl;
R and R″, which may be identical or different, represent a linear or branched, optionally hydroxylated C2-C6 alkylene radical, optionally interrupted with an oxygen atom;
a and b, which may be identical or different, represent an integer ranging from 0 to 100;
R′ and R′″, which may be identical or different, represent a hydrogen atom or a C1-C4 alkyl radical such as a methyl radical; and
x denotes a number ranging from 1 to 500 and y denotes a number ranging from 1 to 10. 8. Process according to any one of the preceding claims, in which the amino silicone(s) are chosen from amino silicones bearing polyalkoxylene groups consisting of polysiloxane block(s) and polyalkoxylene block(s) comprising at least one amine group, in particular those of formula (Ie) or (Ie′) as defined in the preceding claim, and particularly the amino silicone(s) are chosen from:
i) the amino silicones bisamino PolyEthyleneGlycol/PolyPropyleneGlycol-41-3 aminoethyl PG(glycidopropyl)-propyl dimethicone in particular of formula (IIe) below:
in which formula (IIe) m and n, which may be identical or different, represent an integer with the sum m+n having a mean value of 41 and o and p, which may be identical or different, represent an integer with the sum o+p having a mean value of 3. 9. Process according to any one of the preceding claims, in which the amino silicone(s) are chosen from amino silicones derived from the reaction between one or more copolymers of PEG-40/PPG-8 terminating with a 2-aminopropyl group and of bis-glycidoxypropyl dimethicone. 10. Process according to any one of the preceding claims, in which the amino silicone(s) are present in an amount ranging from 0.01% to 10%, better still from 0.1% to 5% by weight, preferably from 0.5% to 3% by weight and even more preferentially from 0.5% to 1.5% by weight relative to the total weight of the composition. 11. Process according to any one of the preceding claims, in which the weight ratio between the amount of amino silicone(s) as defined in claims 1 and 7 to 9, on the one hand, and the amount of dicarbonyl compounds corresponding to formula (I) and/or derivatives thereof and/or hydrates thereof and/or salts thereof as defined in claims 1 to 6 ranges from 0.01 to 100, even more preferentially from 0.01 to 20, better still from 0.05 to 10 and even better still from 0.05 to 1. 12. Process according to any one of the preceding claims, characterized in that it is aqueous and comprises water in a concentration preferably ranging from 5% to 98%, better still from 5% to 90% and even better still from 10% to 90% by weight relative to the total weight of the composition. 13. Process according to any one of the preceding claims, characterized in that the composition results from the mixing of several compositions. 14. Process according to any one of the preceding claims, wherein the time of contact of the composition with the hair is of between 10 and 60 minutes. 15. Process according to any one of the preceding claims, wherein the hair is straightened using a straightening iron at a temperature of at least 150° C. and preferably between 150 and 250° C. 16. Use of a composition comprising:
i) one or more dicarbonyl compounds corresponding to formula (I) below, and/or derivatives thereof and/or hydrates thereof and/or salts thereof:
in which formula (I):
R represents an atom or group chosen from i) hydrogen, ii) carboxyl-C(O)OH, iii) linear or branched C1-C6 alkyl which is optionally substituted, preferably with at least one hydroxyl —OH radical, carboxyl —C(O)—OH radical or halogen such as Br, iv) optionally substituted phenyl, v) optionally substituted benzyl, iv) and v) preferably being optionally substituted with at least one —OH or —C(O)OH radical, vi) an indolyl radical and vii) an imidazolylmethyl radical and tautomers thereof such as:
with * representing the part linked to the rest of the molecule, and
ii) at least one amino silicone,
the composition having a pH of less than or equal to 4, for straightening/relaxing keratin fibres, especially the hair. 17. Cosmetic composition, in particular a hair composition, comprising
i) one or more dicarbonyl compounds corresponding to formula (I) below, and/or derivatives thereof and/or hydrates thereof and/or salts thereof:
in which formula (I):
R represents an atom or group chosen from i) hydrogen, ii) carboxyl —C(O)OH, iii) linear or branched C1-C6 alkyl which is optionally substituted, preferably with at least one hydroxyl —OH radical or halogen such as Br, iv) optionally substituted phenyl, v) optionally substituted benzyl, iv) and v) preferably being optionally substituted with at least one —OH or —C(O)OH radical, vi) an indolyl radical and vii) an imidazolylmethyl radical and tautomers thereof such as
with * representing the part linked to the rest of the molecule, preferably one or more dicarbonyl compounds according to any one of claims 3 to 6,
and ii) at least one amino silicone, preferably at least one amino silicone according to any one of claims 7 to 10, the composition having a pH of less than or equal to 4. | 1,600 |
1,345 | 15,512,322 | 1,612 | Provided is an antimicrobial coating material comprising one or more biocides encapsulated in inorganic-organic shells. The antimicrobial coating material can be applied on porous materials or porous media to form and antimicrobial coating without changing the physical properties and the functions of porous materials or porous media. The coating provides a durable, multi-level antimicrobial performance at high temperature through contact-killing, release-killing, anti-adhesion and self-cleaning. Also provided is a method of producing the antimicrobial coating material. | 1. An antimicrobial coating material for surface coating comprising of:
(a) biocides comprising at least one antimicrobial component selected from the group consisting of chlorine dioxide, hydrogen peroxide, peroxy acids, alcoholic compounds, phenolic compounds, essential oils, antimicrobial components of essential oils, bleach, antibiotics, antimicrobial phytochemicals, and combinations thereof; and (b) inorganic-organic shells permeable to the biocides, comprising:
inorganic materials selected from the group consisting of metal oxides, metal complexes, metal salts, metal particles and combinations thereof; and
organic materials comprising a nonionic polymer;
wherein the inorganic materials are present in a concentration of 0.5-95 wt % of the inorganic-organic shells; and wherein the inorganic-organic shells enclose and contain the biocides permitting storage and release. 2. The coating material according to claim 1, wherein the essential oil is selected from one or more of the group consisting of agarwood oil, cajuput oil, cananga oil, cinnamon bark oil, citronella oil, clove oil, eucalyptus oil, fennel oil, ginger oil, kaffir lime oil, nutmeg oil, olliumxanthorrhiza oil, origanum oil, patchouli oil, rosemary oil, sandalwood oil, tea tree oil, thyme oil, vetiver oil and combinations thereof. 3. The coating material according to claim 2, wherein the essential oil is diluted in a solvent selected from the group consisting of ethylene glycol, propylene glycol, glycerol, dipropylene glycol, polyethylene glycol, and combinations thereof. 4. The coating material according to claim 1, wherein the nonionic polymer is selected from the group consisting of polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, polyetherimide, and polyethyleneimine. 5. The coating material according to claim 1, wherein nonionic polymer is selected from the group consisting of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), and poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol). 6. The coating material according to claim 1, further comprising at least one additional nonionic polymer, the at least one additional nonionic polymer being selected from the group consisting of polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, polyetherimide, polyethyleneimine, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), and poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) and combinations thereof. 7. A method of producing antimicrobial coating material for application to porous materials or porous media, the method comprising:
(a) preparing a biocide mixture; (b) preparing a suspension/solution of nonionic polymers and inorganic materials, the inorganic material being selected from the group consisting of metal oxides, metal complexes, metal salts, metal particles and combinations thereof; (c) preparing a stable sol suspension comprising the biocide mixture encapsulated within inorganic-organic shells, the inorganic-organic shells comprising the suspension/solution of the nonionic polymer and the inorganic material; and (d) applying the antimicrobial coating material on a porous material or in a porous medium. 8. The method according to claim 7, wherein the inorganic material is a metal oxide, the method further comprising preparing the metal oxide sol from a water-soluble metal salt, metal alkoxide or commercial colloidal metal oxide. 9. The method according to claim 8, wherein the metal oxide sol is selected from the group consisting of alumina sol, copper oxide sol, silica sol, silver oxide sol, titania sol, zinc sol, zirconia sol and combinations thereof. 10. The method according to claim 7, wherein the inorganic material is a metal complex, the method further comprising preparing a metal complex sol from a water-soluble metal salt and metal hydroxide. 11. The method according to claim 10, wherein the metal complex is selected from the group consisting of copper complex, silver complex, titanium complex, zinc complex and combinations thereof. 12. The method according to claim 7, wherein the inorganic material is a metal oxide selected from the group consisting of nitrates, sulfates and halides of silver, copper, zinc and combinations thereof. 13. The method according to claim 7, wherein during the preparation of the stable sol suspension, the inorganic material interacts with the organic material to form an inorganic-organic shell. 14. The method of claim 7, wherein applying the antimicrobial coating further comprises at least one of wiping, brushing, casting, dip-coating, spin-coating and spraying the antimicrobial material onto a porous material or a porous medium. 15. The method according to claim 14, wherein the application is to a porous material and the porous material is selected from the group consisting of personal protective equipment, household products, clothes and infant products. 16. The method according to claim 14, wherein the application is to a porous medium and the porous material is selected from a porous membrane and porous filter. 17. The method according to claim 16, wherein the porous medium is comprised of a material selected from the group consisting of metals, polymers, ceramics and combinations thereof. 18. A porous antimicrobial object, comprising a porous material or a porous medium with an antimicrobial coating produced by the method of claim 7. 19. Any one or more of the embodiments, or elements thereof, described herein, or permutation or combination of some or all of the embodiments, or the elements thereof, described herein. | Provided is an antimicrobial coating material comprising one or more biocides encapsulated in inorganic-organic shells. The antimicrobial coating material can be applied on porous materials or porous media to form and antimicrobial coating without changing the physical properties and the functions of porous materials or porous media. The coating provides a durable, multi-level antimicrobial performance at high temperature through contact-killing, release-killing, anti-adhesion and self-cleaning. Also provided is a method of producing the antimicrobial coating material.1. An antimicrobial coating material for surface coating comprising of:
(a) biocides comprising at least one antimicrobial component selected from the group consisting of chlorine dioxide, hydrogen peroxide, peroxy acids, alcoholic compounds, phenolic compounds, essential oils, antimicrobial components of essential oils, bleach, antibiotics, antimicrobial phytochemicals, and combinations thereof; and (b) inorganic-organic shells permeable to the biocides, comprising:
inorganic materials selected from the group consisting of metal oxides, metal complexes, metal salts, metal particles and combinations thereof; and
organic materials comprising a nonionic polymer;
wherein the inorganic materials are present in a concentration of 0.5-95 wt % of the inorganic-organic shells; and wherein the inorganic-organic shells enclose and contain the biocides permitting storage and release. 2. The coating material according to claim 1, wherein the essential oil is selected from one or more of the group consisting of agarwood oil, cajuput oil, cananga oil, cinnamon bark oil, citronella oil, clove oil, eucalyptus oil, fennel oil, ginger oil, kaffir lime oil, nutmeg oil, olliumxanthorrhiza oil, origanum oil, patchouli oil, rosemary oil, sandalwood oil, tea tree oil, thyme oil, vetiver oil and combinations thereof. 3. The coating material according to claim 2, wherein the essential oil is diluted in a solvent selected from the group consisting of ethylene glycol, propylene glycol, glycerol, dipropylene glycol, polyethylene glycol, and combinations thereof. 4. The coating material according to claim 1, wherein the nonionic polymer is selected from the group consisting of polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, polyetherimide, and polyethyleneimine. 5. The coating material according to claim 1, wherein nonionic polymer is selected from the group consisting of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), and poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol). 6. The coating material according to claim 1, further comprising at least one additional nonionic polymer, the at least one additional nonionic polymer being selected from the group consisting of polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, polyetherimide, polyethyleneimine, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), and poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) and combinations thereof. 7. A method of producing antimicrobial coating material for application to porous materials or porous media, the method comprising:
(a) preparing a biocide mixture; (b) preparing a suspension/solution of nonionic polymers and inorganic materials, the inorganic material being selected from the group consisting of metal oxides, metal complexes, metal salts, metal particles and combinations thereof; (c) preparing a stable sol suspension comprising the biocide mixture encapsulated within inorganic-organic shells, the inorganic-organic shells comprising the suspension/solution of the nonionic polymer and the inorganic material; and (d) applying the antimicrobial coating material on a porous material or in a porous medium. 8. The method according to claim 7, wherein the inorganic material is a metal oxide, the method further comprising preparing the metal oxide sol from a water-soluble metal salt, metal alkoxide or commercial colloidal metal oxide. 9. The method according to claim 8, wherein the metal oxide sol is selected from the group consisting of alumina sol, copper oxide sol, silica sol, silver oxide sol, titania sol, zinc sol, zirconia sol and combinations thereof. 10. The method according to claim 7, wherein the inorganic material is a metal complex, the method further comprising preparing a metal complex sol from a water-soluble metal salt and metal hydroxide. 11. The method according to claim 10, wherein the metal complex is selected from the group consisting of copper complex, silver complex, titanium complex, zinc complex and combinations thereof. 12. The method according to claim 7, wherein the inorganic material is a metal oxide selected from the group consisting of nitrates, sulfates and halides of silver, copper, zinc and combinations thereof. 13. The method according to claim 7, wherein during the preparation of the stable sol suspension, the inorganic material interacts with the organic material to form an inorganic-organic shell. 14. The method of claim 7, wherein applying the antimicrobial coating further comprises at least one of wiping, brushing, casting, dip-coating, spin-coating and spraying the antimicrobial material onto a porous material or a porous medium. 15. The method according to claim 14, wherein the application is to a porous material and the porous material is selected from the group consisting of personal protective equipment, household products, clothes and infant products. 16. The method according to claim 14, wherein the application is to a porous medium and the porous material is selected from a porous membrane and porous filter. 17. The method according to claim 16, wherein the porous medium is comprised of a material selected from the group consisting of metals, polymers, ceramics and combinations thereof. 18. A porous antimicrobial object, comprising a porous material or a porous medium with an antimicrobial coating produced by the method of claim 7. 19. Any one or more of the embodiments, or elements thereof, described herein, or permutation or combination of some or all of the embodiments, or the elements thereof, described herein. | 1,600 |
1,346 | 14,770,873 | 1,613 | Microcapsules comprised of a core comprising one or more sunscreen agents and a shell of a wall-forming polymeric material, which are non-rupturable upon rubbing or pressing on the skin, and processes of preparing same are disclosed. Topical formulations comprising the microcapsules, which can be, for example, sunscreen formulations or skin care formulations, are also provided. | 1. A microcapsule comprising a core comprising at least one sunscreen agent and a shell enveloping the core, the shell being comprised of a wall-forming polymeric material comprising at least one polymer or copolymer selected from the group consisting of a polyacrylate, a polymethacrylate, a cellulose ether, a cellulose ester, or any combination thereof, said shell being devoid of a plasticizer, the microcapsule being non-breakable when subjected to homogenization at 2000 rpm for 10 minutes and/or to ultrasonication at 15 W and 28 kHz for 1 minute, and is having a size within a range selected from about 1 μm to about 100 μm. 2-4. (canceled) 5. The microcapsule of claim 1, wherein the shell is transparent. 6. The microcapsule according to claim 1, wherein the sunscreen agent is a water insoluble or water immiscible sunscreen agent. 7. The microcapsule according to claim 6, wherein the sunscreen agent is selected from the group consisting of TiO2, avobenzone, p-aminobenzoic acid, bemotrizinol, benzophenone-9, bexophenome-3, bisoctrizole, 3-(4-methylbenzylidene)-camphor, cinoxate, diethylamino hydroxybenzoyl hexyl benzoate, dioxybenzone, drometrizole trisiloxane, ecamsule, ethylhexyl triazone, homosalate, menthyl anthranilate, octocrylene, octyl salicylate, iscotrizinol, isopentenyl-4-methoxycinnamate, octyl-dimethyl-p-aminobenzoic acid, octyl-methoxycinnamate, oxybenzone, polysilicone-15, trolamine salicylate, ZnO, and any combination thereof. 8. The microcapsule according to claim 7, wherein the sunscreen agent is TiO2. 9. (canceled) 10. The microcapsule according to claim 7, wherein the sunscreen agent is avobenzone. 11-12. (canceled) 13. The microcapsule according to claim 7, wherein the sunscreen agent is a blend of TiO2 and one or more of avobenzone, p-aminobenzoic acid, cinoxate, dioxybenzone, ecamsule, homosalate, menthyl anthranilate, octocrylene, octyl salicylate, octyl-methoxycinnamate, oxybenzone, trolamine salicylate, or ZnO. 14-15. (canceled) 16. The microcapsule according to claim 1, wherein the amount of the wall-forming polymeric material is within a range selected from about 20% to about 70%, from about 20% to about 50%, from about 20% to about 40%, or from about 20% to about 30%, or about 20% or 50%, by weight. 17. (canceled) 18. The microcapsule according to claim 1, further comprising a photostabilizer. 19. The microcapsule according to claim 18, wherein the photostabilizer is selected from the group consisting of diethylhexyl-2,6-naphthalate, octocrylene, ethylhexyl methoxycrylene and 4-methylbenzylidene camphor. 20. The microcapsule according to claim 18, wherein the amount of the photostabilizer in the microcapsule is within a range selected from about 5% to about 50%, from about 5% to about 40%, from about 5% to about 30%, or from about 10% to about 25%, or about 10% by weight. 21-22. (canceled) 23. A composition comprising a plurality of microcapsules, at least a portion of the microcapsules comprising a plurality of sunscreen agent-containing microcapsules according to claim 1. 24. The composition of claim 23, wherein the microcapsules in the plurality of sunscreen agent-containing microcapsules are the same or different. 25. (canceled) 26. The composition according to claim 23, further comprising a photostabilizer. 27. The composition according to claim 23, wherein at least a portion of microcapsules in the plurality of sunscreen agent-containing microcapsules further comprise a photo stabilizer. 28. A process of preparing sunscreen agent-containing microcapsule of claim 1, the process comprising:
(a) mixing a solution comprising the sunscreen agent, a wall-forming polymeric material and an organic solvent, to thereby obtain a homogeneous solution; (b) mixing the homogeneous solution with an aqueous solution containing an emulsifier, under high shear stirring, to thereby form an emulsion; and (c) adding to the formed emulsion an amount of water which initiates extraction of the organic solvent from the emulsion, thereby obtaining the microcapsules. 29. The process of claim 28, further comprising isolating the microcapsules. 30. The process of claim 28, further comprising drying and sifting the microcapsules, to thereby obtain a free flowing powder of the microcapsules. 31-32. (canceled) 33. A cosmetic or cosmaceutical formulation comprising the composition according to claim 23. 34. The cosmetic or cosmaceutical formulation according to claim 33, further comprising a cosmetically or cosmaceutically acceptable carrier. | Microcapsules comprised of a core comprising one or more sunscreen agents and a shell of a wall-forming polymeric material, which are non-rupturable upon rubbing or pressing on the skin, and processes of preparing same are disclosed. Topical formulations comprising the microcapsules, which can be, for example, sunscreen formulations or skin care formulations, are also provided.1. A microcapsule comprising a core comprising at least one sunscreen agent and a shell enveloping the core, the shell being comprised of a wall-forming polymeric material comprising at least one polymer or copolymer selected from the group consisting of a polyacrylate, a polymethacrylate, a cellulose ether, a cellulose ester, or any combination thereof, said shell being devoid of a plasticizer, the microcapsule being non-breakable when subjected to homogenization at 2000 rpm for 10 minutes and/or to ultrasonication at 15 W and 28 kHz for 1 minute, and is having a size within a range selected from about 1 μm to about 100 μm. 2-4. (canceled) 5. The microcapsule of claim 1, wherein the shell is transparent. 6. The microcapsule according to claim 1, wherein the sunscreen agent is a water insoluble or water immiscible sunscreen agent. 7. The microcapsule according to claim 6, wherein the sunscreen agent is selected from the group consisting of TiO2, avobenzone, p-aminobenzoic acid, bemotrizinol, benzophenone-9, bexophenome-3, bisoctrizole, 3-(4-methylbenzylidene)-camphor, cinoxate, diethylamino hydroxybenzoyl hexyl benzoate, dioxybenzone, drometrizole trisiloxane, ecamsule, ethylhexyl triazone, homosalate, menthyl anthranilate, octocrylene, octyl salicylate, iscotrizinol, isopentenyl-4-methoxycinnamate, octyl-dimethyl-p-aminobenzoic acid, octyl-methoxycinnamate, oxybenzone, polysilicone-15, trolamine salicylate, ZnO, and any combination thereof. 8. The microcapsule according to claim 7, wherein the sunscreen agent is TiO2. 9. (canceled) 10. The microcapsule according to claim 7, wherein the sunscreen agent is avobenzone. 11-12. (canceled) 13. The microcapsule according to claim 7, wherein the sunscreen agent is a blend of TiO2 and one or more of avobenzone, p-aminobenzoic acid, cinoxate, dioxybenzone, ecamsule, homosalate, menthyl anthranilate, octocrylene, octyl salicylate, octyl-methoxycinnamate, oxybenzone, trolamine salicylate, or ZnO. 14-15. (canceled) 16. The microcapsule according to claim 1, wherein the amount of the wall-forming polymeric material is within a range selected from about 20% to about 70%, from about 20% to about 50%, from about 20% to about 40%, or from about 20% to about 30%, or about 20% or 50%, by weight. 17. (canceled) 18. The microcapsule according to claim 1, further comprising a photostabilizer. 19. The microcapsule according to claim 18, wherein the photostabilizer is selected from the group consisting of diethylhexyl-2,6-naphthalate, octocrylene, ethylhexyl methoxycrylene and 4-methylbenzylidene camphor. 20. The microcapsule according to claim 18, wherein the amount of the photostabilizer in the microcapsule is within a range selected from about 5% to about 50%, from about 5% to about 40%, from about 5% to about 30%, or from about 10% to about 25%, or about 10% by weight. 21-22. (canceled) 23. A composition comprising a plurality of microcapsules, at least a portion of the microcapsules comprising a plurality of sunscreen agent-containing microcapsules according to claim 1. 24. The composition of claim 23, wherein the microcapsules in the plurality of sunscreen agent-containing microcapsules are the same or different. 25. (canceled) 26. The composition according to claim 23, further comprising a photostabilizer. 27. The composition according to claim 23, wherein at least a portion of microcapsules in the plurality of sunscreen agent-containing microcapsules further comprise a photo stabilizer. 28. A process of preparing sunscreen agent-containing microcapsule of claim 1, the process comprising:
(a) mixing a solution comprising the sunscreen agent, a wall-forming polymeric material and an organic solvent, to thereby obtain a homogeneous solution; (b) mixing the homogeneous solution with an aqueous solution containing an emulsifier, under high shear stirring, to thereby form an emulsion; and (c) adding to the formed emulsion an amount of water which initiates extraction of the organic solvent from the emulsion, thereby obtaining the microcapsules. 29. The process of claim 28, further comprising isolating the microcapsules. 30. The process of claim 28, further comprising drying and sifting the microcapsules, to thereby obtain a free flowing powder of the microcapsules. 31-32. (canceled) 33. A cosmetic or cosmaceutical formulation comprising the composition according to claim 23. 34. The cosmetic or cosmaceutical formulation according to claim 33, further comprising a cosmetically or cosmaceutically acceptable carrier. | 1,600 |
1,347 | 14,399,157 | 1,644 | There is provided a method of treating an inflammatory response to infection and complications associated therewith, by administering a proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor to a subject, in need thereof. There is also provided a method of treating or preventing treating or preventing renal failure; renal dysfunction; respiratory failure; respiratory dysfunction; or acute lung injury. Provided herein are uses, pharmaceutical compositions, and commercial packages associated therewith. | 1. A method of treating an inflammatory response to infection, the method comprising: administering a proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor to a subject in need thereof. 2. The method of claim 1, wherein the PCSK9 inhibitor is an antibody or antigen-binding fragment thereof. 3. The method of claim 1 or 2, wherein the PCSK9 inhibitor is a monoclonal antibody or antigen-binding fragment thereof. 4. The method of claim 1, 2, or 3, wherein the PCSK9 inhibitor is: AMG145; 1D05-IgG2; SAR236553/REGN727 (Alirocumab); RN-316; LGT209; or RG7652. 5. The method of claim 1, wherein the PCSK9 inhibitor is a peptide mimetic. 6. The method of claim 1 or 5, wherein the PCSK9 inhibitor is an EGFA domain mimic, EGF-A peptide, a fibronectin based scaffold domain proteins, or a neutralizing PCSK9 variant. 7. The method of claim 1, wherein the PCSK9 inhibitor is an antisense oligonucleotide. 8. The method of claim 1 or 7, wherein the PCSK9 inhibitor is BMS-PCSK9Rx. 9. The method of claim 1, wherein the PCSK9 inhibitor is an RNAi molecule. 10. The method of claim 1 or 9, wherein the PCSK9 inhibitor is LNA ASO or ALN-PCS. 11. The method of any one of claims 1-10, wherein the subject is a human. 12. The method of any one of claims 1-11, wherein the inflammatory response to infection, is one or more of: sepsis, septicemia, pneumonia, septic shock, systemic inflammatory response syndrome (SIRS), Acute Respiratory Distress Syndrome (ARDS), acute lung injury, infection, pancreatitis, bacteremia, peritonitis, abdominal abscess, bowel infection, opportunistic infections, HIV/AIDS, endocarditis, bronchiectasis, chronic bronchitis, meningitis, septic arthritis, urinary tract infection, pyelonephritis, necrotizing fasciitis, Group A streptococcus infection, enterococcus infection, Gram positive sepsis, Gram negative sepsis, culture negative sepsis, fungal sepsis, meningococcemia, epiglotittis, E. coli 0157117 infection, gas gangrene, toxic shock syndrome, mycobacterial tuberculosis, Pneumocystic carinii infection, pelvic inflammatory disease, Legionella infection, Influenza A infection, Epstein-Barr virus infection, or encephalitis. 13. The method of any one of claims 1-12, wherein the subject has septic shock. 14. The method of any one of claims 1-13, wherein the subject has sepsis. 15. A pharmaceutical composition for treating an inflammatory response to infection, comprising a PCSK9 inhibitor and a pharmaceutically acceptable carrier. 16. The pharmaceutical composition of claim 15, wherein the PCSK9 inhibitor is selected from one or more of the following: an antibody or antigen-binding fragment thereof; a peptide mimetic; an antisense oligonucleotide; an RNAi molecule. 17. The pharmaceutical composition of claim 15 or 16, wherein the PCSK9 inhibitor is a monoclonal antibody or antigen-binding fragment thereof. 18. The pharmaceutical composition of claim 15, 16, or 17, wherein the PCSK9 inhibitor is: AMG145; 1D05-IgG2; SAR236553/REGN727 (Alirocumab); RN-316; LGT209; or RG7652. 19. The pharmaceutical composition of claim 15 or 16, wherein the PCSK9 inhibitor is an EGFA domain mimic, EGF-A peptide, a fibronectin based scaffold domain proteins, or a neutralizing PCSK9 variant. 20. The pharmaceutical composition of claim 15, 16, or 19, wherein the PCSK9 inhibitor is BMS-PCSK9Rx. 21. The pharmaceutical composition of claim 15 or 16, wherein the PCSK9 inhibitor is LNA ASO or ALN-PCS. 22. The pharmaceutical composition of any one of claims 15-21, wherein the subject is a human. 23. The pharmaceutical composition of any one of claims 15-22, wherein the inflammatory response to infection, is one or more of: sepsis, septicemia, pneumonia, septic shock, systemic inflammatory response syndrome (SIRS), Acute Respiratory Distress Syndrome (ARDS), acute lung injury, infection, pancreatitis, bacteremia, peritonitis, abdominal abscess, bowel infection, opportunistic infections, HIV/AIDS, endocarditis, bronchiectasis, chronic bronchitis, meningitis, septic arthritis, urinary tract infection, pyelonephritis, necrotizing fasciitis, Group A streptococcus infection, enterococcus infection, Gram positive sepsis, Gram negative sepsis, culture negative sepsis, fungal sepsis, meningococcemia, epiglotittis, E. coli 0157:H7 infection, gas gangrene, toxic shock syndrome, mycobacterial tuberculosis, Pneumocystic carinii infection, pelvic inflammatory disease, Legionella infection, Influenza A infection, Epstein-Barr virus infection, or encephalitis. 24. A PCSK9 inhibitor for treating an inflammatory response to infection. 25. The PCSK9 inhibitor of claim 24, wherein the PCSK9 inhibitor is selected from one or more of the following: an antibody or antigen-binding fragment thereof; a peptide mimetic; an antisense oligonucleotide; an RNAi molecule. 26. The PCSK9 inhibitor of claim 24 or 25, wherein the PCSK9 inhibitor is a monoclonal antibody or antigen-binding fragment thereof. 27. The PCSK9 inhibitor of claim 24, 25, or 26, wherein the PCSK9 inhibitor is: AMG145; 1D05-IgG2; SAR236553/REGN727 (Alirocumab); RN-316; LGT209; or RG7652. 28. The PCSK9 inhibitor of claim 24 or 25, wherein the PCSK9 inhibitor is an EGFA domain mimic, EGF-A peptide, a fibronectin based scaffold domain proteins, or a neutralizing PCSK9 variant. 29. The PCSK9 inhibitor of claim 24, 25, or 28, wherein the PCSK9 inhibitor is BMS-PCSK9Rx. 30. The PCSK9 inhibitor of claim 24 or 25, wherein the PCSK9 inhibitor is LNA ASO or ALN-PCS. 31. The PCSK9 inhibitor of any one of claims 24-21, wherein the subject is a human. 32. The PCSK9 inhibitor of any one of claims 24-31, wherein the inflammatory response to infection, is one or more of: sepsis, septicemia, pneumonia, septic shock, systemic inflammatory response syndrome (SIRS), Acute Respiratory Distress Syndrome (ARDS), acute lung injury, infection, pancreatitis, bacteremia, peritonitis, abdominal abscess, bowel infection, opportunistic infections, HIV/AIDS, endocarditis, bronchiectasis, chronic bronchitis, meningitis, septic arthritis, urinary tract infection, pyelonephritis, necrotizing fasciitis, Group A streptococcus infection, enterococcus infection, Gram positive sepsis, Gram negative sepsis, culture negative sepsis, fungal sepsis, meningococcemia, epiglotittis, E. coli 0157:H7 infection, gas gangrene, toxic shock syndrome, mycobacterial tuberculosis, Pneumocystic carinii infection, pelvic inflammatory disease, Legionella infection, Influenza A infection, Epstein-Barr virus infection, or encephalitis. 33. Use of a PCSK9 inhibitor for treating an inflammatory response to infection. 34. Use of a pharmaceutical composition comprising a PCSK9 inhibitor and a pharmaceutically acceptable carrier for treating an inflammatory response to infection. 35. Use of a PCSK9 inhibitor in the manufacture of a medicament for treating an inflammatory response to infection. 36. The use of claim 33, 34, or 35, wherein the PCSK9 inhibitor is selected from one or more of the following: an antibody or antigen-binding fragment thereof; a peptide mimetic; an antisense oligonucleotide; an RNAi molecule. 37. The use of any one of claims 33-36, wherein the PCSK9 inhibitor is a monoclonal antibody or antigen-binding fragment thereof. 38. The use of any one of claims 33-37, wherein the PCSK9 inhibitor is: AMG145; 1D05-IgG2; SAR236553/REGN727 (Alirocumab); RN-316; LGT209; or RG7652. 39. The use of any one of claims 33-36, wherein the PCSK9 inhibitor is an EGFA domain mimic, EGF-A peptide, a fibronectin based scaffold domain proteins, or a neutralizing PCSK9 variant. 40. The use of any one of claims 33-36, and 39, wherein the PCSK9 inhibitor is BMS-PCSK9Rx. 41. The use of any one of claims 33-36, wherein the PCSK9 inhibitor is LNA ASO or ALN-PCS. 42. The use of any one of claims 33-41, wherein the subject is a human. 43. The use of any one of claims 33-42, wherein the inflammatory response to infection, is one or more of: sepsis, septicemia, pneumonia, septic shock, systemic inflammatory response syndrome (SIRS), Acute Respiratory Distress Syndrome (ARDS), acute lung injury, infection, pancreatitis, bacteremia, peritonitis, abdominal abscess, bowel infection, opportunistic infections, HIV/AIDS, endocarditis, bronchiectasis, chronic bronchitis, meningitis, septic arthritis, urinary tract infection, pyelonephritis, necrotizing fasciitis, Group A streptococcus infection, enterococcus infection, Gram positive sepsis, Gram negative sepsis, culture negative sepsis, fungal sepsis, meningococcemia, epiglotittis, E. coli 0157:H7 infection, gas gangrene, toxic shock syndrome, mycobacterial tuberculosis, Pneumocystic carinii infection, pelvic inflammatory disease, Legionella infection, Influenza A infection, Epstein-Barr virus infection, or encephalitis. 44. A commercial package comprising (a) a PCSK9 inhibitor; and (b) instructions for the use thereof for treating and an inflammatory response to infection. 45. A commercial package comprising (a) a pharmaceutical composition comprising a PCSK9 inhibitor and a pharmaceutically acceptable carrier; and (b) instructions for the use thereof for treating an inflammatory response to infection. 46. The commercial package of claim 44 or 45, wherein the PCSK9 inhibitor is selected from one or more of the following: an antibody or antigen-binding fragment thereof; a peptide mimetic; an antisense oligonucleotide; an RNAi molecule. 47. The commercial package of claim 44, 45, or 46, wherein the PCSK9 inhibitor is a monoclonal antibody or antigen-binding fragment thereof. 48. The commercial package of any one of claims 44-47, wherein the PCSK9 inhibitor is: AMG145; 1D05-IgG2; SAR236553/REGN727 (Alirocumab); RN-316; LGT209; or RG7652. 49. The commercial package of claim 44, 45, or 46, wherein the PCSK9 inhibitor is an EGFA domain mimic, EGF-A peptide, a fibronectin based scaffold domain proteins, or a neutralizing PCSK9 variant. 50. The commercial package of any one of claims 44-46, and 49, wherein the PCSK9 inhibitor is BMS-PCSK9Rx. 51. The commercial package of any one of claims 44-46, wherein the PCSK9 inhibitor is LNA ASO or ALN-PCS. 52. The commercial package of any one of claims 44-51, wherein the subject is a human. 53. The commercial package of any one of claims 44-52, wherein the inflammatory response to infection, is one or more of: sepsis, septicemia, pneumonia, septic shock, systemic inflammatory response syndrome (SIRS), Acute Respiratory Distress Syndrome (ARDS), acute lung injury, infection, pancreatitis, bacteremia, peritonitis, abdominal abscess, bowel infection, opportunistic infections, HIV/AIDS, endocarditis, bronchiectasis, chronic bronchitis, meningitis, septic arthritis, urinary tract infection, pyelonephritis, necrotizing fasciitis, Group A streptococcus infection, enterococcus infection, Gram positive sepsis, Gram negative sepsis, culture negative sepsis, fungal sepsis, meningococcemia, epiglotittis, E. coli 0157:H7 infection, gas gangrene, toxic shock syndrome, mycobacterial tuberculosis, Pneumocystic carinii infection, pelvic inflammatory disease, Legionella infection, Influenza A infection, Epstein-Barr virus infection, or encephalitis. 54. A method of treating renal failure, renal dysfunction, respiratory failure, respiratory dysfunction, or acute lung injury, the method comprising: administering a proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor to a subject in need thereof. 55. A method of preventing renal failure, renal dysfunction, respiratory failure, respiratory dysfunction, or acute lung injury, the method comprising: administering a proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor to a subject in need thereof. 56. The method of claim 54 or 55, wherein the subject has an inflammatory response to infection. 57. The method of claim 54, 55 or 56, wherein the PCSK9 inhibitor is selected from one or more of the following: an antibody or antigen-binding fragment thereof; a peptide mimetic; an antisense oligonucleotide; an RNAi molecule. 58. The method of any one of claims 54-57, wherein the PCSK9 inhibitor is a monoclonal antibody or antigen-binding fragment thereof. 59. The method of any one of claims 54-58, wherein the PCSK9 inhibitor is: AMG145; 1D05-IgG2; SAR236553/REGN727 (Alirocumab); RN-316; LGT209; or RG7652. 60. The method of any one of claims 54-57, wherein the PCSK9 inhibitor is an EGFA domain mimic, EGF-A peptide, a fibronectin based scaffold domain proteins, or a neutralizing PCSK9 variant. 61. The method of any one of claims 54-57, and 60, wherein the PCSK9 inhibitor is BMS-PCSK9Rx. 62. The method of any one of claims 54-57, wherein the PCSK9 inhibitor is LNA ASO or ALN-PCS. 63. The method of any one of claims 54-62, wherein the subject is a human. 64. The method of any one of claims 56-63, wherein the inflammatory response to infection, is one or more of: sepsis, septicemia, pneumonia, septic shock, systemic inflammatory response syndrome (SIRS), Acute Respiratory Distress Syndrome (ARDS), acute lung injury, infection, pancreatitis, bacteremia, peritonitis, abdominal abscess, bowel infection, opportunistic infections, HIV/AIDS, endocarditis, bronchiectasis, chronic bronchitis, meningitis, septic arthritis, urinary tract infection, pyelonephritis, necrotizing fasciitis, Group A streptococcus infection, enterococcus infection, Gram positive sepsis, Gram negative sepsis, culture negative sepsis, fungal sepsis, meningococcemia, epiglotittis, E. coli 0157:H7 infection, gas gangrene, toxic shock syndrome, mycobacterial tuberculosis, Pneumocystic carinii infection, pelvic inflammatory disease, Legionella infection, Influenza A infection, Epstein-Barr virus infection, or encephalitis. | There is provided a method of treating an inflammatory response to infection and complications associated therewith, by administering a proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor to a subject, in need thereof. There is also provided a method of treating or preventing treating or preventing renal failure; renal dysfunction; respiratory failure; respiratory dysfunction; or acute lung injury. Provided herein are uses, pharmaceutical compositions, and commercial packages associated therewith.1. A method of treating an inflammatory response to infection, the method comprising: administering a proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor to a subject in need thereof. 2. The method of claim 1, wherein the PCSK9 inhibitor is an antibody or antigen-binding fragment thereof. 3. The method of claim 1 or 2, wherein the PCSK9 inhibitor is a monoclonal antibody or antigen-binding fragment thereof. 4. The method of claim 1, 2, or 3, wherein the PCSK9 inhibitor is: AMG145; 1D05-IgG2; SAR236553/REGN727 (Alirocumab); RN-316; LGT209; or RG7652. 5. The method of claim 1, wherein the PCSK9 inhibitor is a peptide mimetic. 6. The method of claim 1 or 5, wherein the PCSK9 inhibitor is an EGFA domain mimic, EGF-A peptide, a fibronectin based scaffold domain proteins, or a neutralizing PCSK9 variant. 7. The method of claim 1, wherein the PCSK9 inhibitor is an antisense oligonucleotide. 8. The method of claim 1 or 7, wherein the PCSK9 inhibitor is BMS-PCSK9Rx. 9. The method of claim 1, wherein the PCSK9 inhibitor is an RNAi molecule. 10. The method of claim 1 or 9, wherein the PCSK9 inhibitor is LNA ASO or ALN-PCS. 11. The method of any one of claims 1-10, wherein the subject is a human. 12. The method of any one of claims 1-11, wherein the inflammatory response to infection, is one or more of: sepsis, septicemia, pneumonia, septic shock, systemic inflammatory response syndrome (SIRS), Acute Respiratory Distress Syndrome (ARDS), acute lung injury, infection, pancreatitis, bacteremia, peritonitis, abdominal abscess, bowel infection, opportunistic infections, HIV/AIDS, endocarditis, bronchiectasis, chronic bronchitis, meningitis, septic arthritis, urinary tract infection, pyelonephritis, necrotizing fasciitis, Group A streptococcus infection, enterococcus infection, Gram positive sepsis, Gram negative sepsis, culture negative sepsis, fungal sepsis, meningococcemia, epiglotittis, E. coli 0157117 infection, gas gangrene, toxic shock syndrome, mycobacterial tuberculosis, Pneumocystic carinii infection, pelvic inflammatory disease, Legionella infection, Influenza A infection, Epstein-Barr virus infection, or encephalitis. 13. The method of any one of claims 1-12, wherein the subject has septic shock. 14. The method of any one of claims 1-13, wherein the subject has sepsis. 15. A pharmaceutical composition for treating an inflammatory response to infection, comprising a PCSK9 inhibitor and a pharmaceutically acceptable carrier. 16. The pharmaceutical composition of claim 15, wherein the PCSK9 inhibitor is selected from one or more of the following: an antibody or antigen-binding fragment thereof; a peptide mimetic; an antisense oligonucleotide; an RNAi molecule. 17. The pharmaceutical composition of claim 15 or 16, wherein the PCSK9 inhibitor is a monoclonal antibody or antigen-binding fragment thereof. 18. The pharmaceutical composition of claim 15, 16, or 17, wherein the PCSK9 inhibitor is: AMG145; 1D05-IgG2; SAR236553/REGN727 (Alirocumab); RN-316; LGT209; or RG7652. 19. The pharmaceutical composition of claim 15 or 16, wherein the PCSK9 inhibitor is an EGFA domain mimic, EGF-A peptide, a fibronectin based scaffold domain proteins, or a neutralizing PCSK9 variant. 20. The pharmaceutical composition of claim 15, 16, or 19, wherein the PCSK9 inhibitor is BMS-PCSK9Rx. 21. The pharmaceutical composition of claim 15 or 16, wherein the PCSK9 inhibitor is LNA ASO or ALN-PCS. 22. The pharmaceutical composition of any one of claims 15-21, wherein the subject is a human. 23. The pharmaceutical composition of any one of claims 15-22, wherein the inflammatory response to infection, is one or more of: sepsis, septicemia, pneumonia, septic shock, systemic inflammatory response syndrome (SIRS), Acute Respiratory Distress Syndrome (ARDS), acute lung injury, infection, pancreatitis, bacteremia, peritonitis, abdominal abscess, bowel infection, opportunistic infections, HIV/AIDS, endocarditis, bronchiectasis, chronic bronchitis, meningitis, septic arthritis, urinary tract infection, pyelonephritis, necrotizing fasciitis, Group A streptococcus infection, enterococcus infection, Gram positive sepsis, Gram negative sepsis, culture negative sepsis, fungal sepsis, meningococcemia, epiglotittis, E. coli 0157:H7 infection, gas gangrene, toxic shock syndrome, mycobacterial tuberculosis, Pneumocystic carinii infection, pelvic inflammatory disease, Legionella infection, Influenza A infection, Epstein-Barr virus infection, or encephalitis. 24. A PCSK9 inhibitor for treating an inflammatory response to infection. 25. The PCSK9 inhibitor of claim 24, wherein the PCSK9 inhibitor is selected from one or more of the following: an antibody or antigen-binding fragment thereof; a peptide mimetic; an antisense oligonucleotide; an RNAi molecule. 26. The PCSK9 inhibitor of claim 24 or 25, wherein the PCSK9 inhibitor is a monoclonal antibody or antigen-binding fragment thereof. 27. The PCSK9 inhibitor of claim 24, 25, or 26, wherein the PCSK9 inhibitor is: AMG145; 1D05-IgG2; SAR236553/REGN727 (Alirocumab); RN-316; LGT209; or RG7652. 28. The PCSK9 inhibitor of claim 24 or 25, wherein the PCSK9 inhibitor is an EGFA domain mimic, EGF-A peptide, a fibronectin based scaffold domain proteins, or a neutralizing PCSK9 variant. 29. The PCSK9 inhibitor of claim 24, 25, or 28, wherein the PCSK9 inhibitor is BMS-PCSK9Rx. 30. The PCSK9 inhibitor of claim 24 or 25, wherein the PCSK9 inhibitor is LNA ASO or ALN-PCS. 31. The PCSK9 inhibitor of any one of claims 24-21, wherein the subject is a human. 32. The PCSK9 inhibitor of any one of claims 24-31, wherein the inflammatory response to infection, is one or more of: sepsis, septicemia, pneumonia, septic shock, systemic inflammatory response syndrome (SIRS), Acute Respiratory Distress Syndrome (ARDS), acute lung injury, infection, pancreatitis, bacteremia, peritonitis, abdominal abscess, bowel infection, opportunistic infections, HIV/AIDS, endocarditis, bronchiectasis, chronic bronchitis, meningitis, septic arthritis, urinary tract infection, pyelonephritis, necrotizing fasciitis, Group A streptococcus infection, enterococcus infection, Gram positive sepsis, Gram negative sepsis, culture negative sepsis, fungal sepsis, meningococcemia, epiglotittis, E. coli 0157:H7 infection, gas gangrene, toxic shock syndrome, mycobacterial tuberculosis, Pneumocystic carinii infection, pelvic inflammatory disease, Legionella infection, Influenza A infection, Epstein-Barr virus infection, or encephalitis. 33. Use of a PCSK9 inhibitor for treating an inflammatory response to infection. 34. Use of a pharmaceutical composition comprising a PCSK9 inhibitor and a pharmaceutically acceptable carrier for treating an inflammatory response to infection. 35. Use of a PCSK9 inhibitor in the manufacture of a medicament for treating an inflammatory response to infection. 36. The use of claim 33, 34, or 35, wherein the PCSK9 inhibitor is selected from one or more of the following: an antibody or antigen-binding fragment thereof; a peptide mimetic; an antisense oligonucleotide; an RNAi molecule. 37. The use of any one of claims 33-36, wherein the PCSK9 inhibitor is a monoclonal antibody or antigen-binding fragment thereof. 38. The use of any one of claims 33-37, wherein the PCSK9 inhibitor is: AMG145; 1D05-IgG2; SAR236553/REGN727 (Alirocumab); RN-316; LGT209; or RG7652. 39. The use of any one of claims 33-36, wherein the PCSK9 inhibitor is an EGFA domain mimic, EGF-A peptide, a fibronectin based scaffold domain proteins, or a neutralizing PCSK9 variant. 40. The use of any one of claims 33-36, and 39, wherein the PCSK9 inhibitor is BMS-PCSK9Rx. 41. The use of any one of claims 33-36, wherein the PCSK9 inhibitor is LNA ASO or ALN-PCS. 42. The use of any one of claims 33-41, wherein the subject is a human. 43. The use of any one of claims 33-42, wherein the inflammatory response to infection, is one or more of: sepsis, septicemia, pneumonia, septic shock, systemic inflammatory response syndrome (SIRS), Acute Respiratory Distress Syndrome (ARDS), acute lung injury, infection, pancreatitis, bacteremia, peritonitis, abdominal abscess, bowel infection, opportunistic infections, HIV/AIDS, endocarditis, bronchiectasis, chronic bronchitis, meningitis, septic arthritis, urinary tract infection, pyelonephritis, necrotizing fasciitis, Group A streptococcus infection, enterococcus infection, Gram positive sepsis, Gram negative sepsis, culture negative sepsis, fungal sepsis, meningococcemia, epiglotittis, E. coli 0157:H7 infection, gas gangrene, toxic shock syndrome, mycobacterial tuberculosis, Pneumocystic carinii infection, pelvic inflammatory disease, Legionella infection, Influenza A infection, Epstein-Barr virus infection, or encephalitis. 44. A commercial package comprising (a) a PCSK9 inhibitor; and (b) instructions for the use thereof for treating and an inflammatory response to infection. 45. A commercial package comprising (a) a pharmaceutical composition comprising a PCSK9 inhibitor and a pharmaceutically acceptable carrier; and (b) instructions for the use thereof for treating an inflammatory response to infection. 46. The commercial package of claim 44 or 45, wherein the PCSK9 inhibitor is selected from one or more of the following: an antibody or antigen-binding fragment thereof; a peptide mimetic; an antisense oligonucleotide; an RNAi molecule. 47. The commercial package of claim 44, 45, or 46, wherein the PCSK9 inhibitor is a monoclonal antibody or antigen-binding fragment thereof. 48. The commercial package of any one of claims 44-47, wherein the PCSK9 inhibitor is: AMG145; 1D05-IgG2; SAR236553/REGN727 (Alirocumab); RN-316; LGT209; or RG7652. 49. The commercial package of claim 44, 45, or 46, wherein the PCSK9 inhibitor is an EGFA domain mimic, EGF-A peptide, a fibronectin based scaffold domain proteins, or a neutralizing PCSK9 variant. 50. The commercial package of any one of claims 44-46, and 49, wherein the PCSK9 inhibitor is BMS-PCSK9Rx. 51. The commercial package of any one of claims 44-46, wherein the PCSK9 inhibitor is LNA ASO or ALN-PCS. 52. The commercial package of any one of claims 44-51, wherein the subject is a human. 53. The commercial package of any one of claims 44-52, wherein the inflammatory response to infection, is one or more of: sepsis, septicemia, pneumonia, septic shock, systemic inflammatory response syndrome (SIRS), Acute Respiratory Distress Syndrome (ARDS), acute lung injury, infection, pancreatitis, bacteremia, peritonitis, abdominal abscess, bowel infection, opportunistic infections, HIV/AIDS, endocarditis, bronchiectasis, chronic bronchitis, meningitis, septic arthritis, urinary tract infection, pyelonephritis, necrotizing fasciitis, Group A streptococcus infection, enterococcus infection, Gram positive sepsis, Gram negative sepsis, culture negative sepsis, fungal sepsis, meningococcemia, epiglotittis, E. coli 0157:H7 infection, gas gangrene, toxic shock syndrome, mycobacterial tuberculosis, Pneumocystic carinii infection, pelvic inflammatory disease, Legionella infection, Influenza A infection, Epstein-Barr virus infection, or encephalitis. 54. A method of treating renal failure, renal dysfunction, respiratory failure, respiratory dysfunction, or acute lung injury, the method comprising: administering a proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor to a subject in need thereof. 55. A method of preventing renal failure, renal dysfunction, respiratory failure, respiratory dysfunction, or acute lung injury, the method comprising: administering a proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor to a subject in need thereof. 56. The method of claim 54 or 55, wherein the subject has an inflammatory response to infection. 57. The method of claim 54, 55 or 56, wherein the PCSK9 inhibitor is selected from one or more of the following: an antibody or antigen-binding fragment thereof; a peptide mimetic; an antisense oligonucleotide; an RNAi molecule. 58. The method of any one of claims 54-57, wherein the PCSK9 inhibitor is a monoclonal antibody or antigen-binding fragment thereof. 59. The method of any one of claims 54-58, wherein the PCSK9 inhibitor is: AMG145; 1D05-IgG2; SAR236553/REGN727 (Alirocumab); RN-316; LGT209; or RG7652. 60. The method of any one of claims 54-57, wherein the PCSK9 inhibitor is an EGFA domain mimic, EGF-A peptide, a fibronectin based scaffold domain proteins, or a neutralizing PCSK9 variant. 61. The method of any one of claims 54-57, and 60, wherein the PCSK9 inhibitor is BMS-PCSK9Rx. 62. The method of any one of claims 54-57, wherein the PCSK9 inhibitor is LNA ASO or ALN-PCS. 63. The method of any one of claims 54-62, wherein the subject is a human. 64. The method of any one of claims 56-63, wherein the inflammatory response to infection, is one or more of: sepsis, septicemia, pneumonia, septic shock, systemic inflammatory response syndrome (SIRS), Acute Respiratory Distress Syndrome (ARDS), acute lung injury, infection, pancreatitis, bacteremia, peritonitis, abdominal abscess, bowel infection, opportunistic infections, HIV/AIDS, endocarditis, bronchiectasis, chronic bronchitis, meningitis, septic arthritis, urinary tract infection, pyelonephritis, necrotizing fasciitis, Group A streptococcus infection, enterococcus infection, Gram positive sepsis, Gram negative sepsis, culture negative sepsis, fungal sepsis, meningococcemia, epiglotittis, E. coli 0157:H7 infection, gas gangrene, toxic shock syndrome, mycobacterial tuberculosis, Pneumocystic carinii infection, pelvic inflammatory disease, Legionella infection, Influenza A infection, Epstein-Barr virus infection, or encephalitis. | 1,600 |
1,348 | 14,925,043 | 1,618 | A pharmaceutical formulation of therapeutically effective amounts of acetaminophen, ibuprofen, and a sympathomimetic drug, such as pseudoephedrine (or its prodrug), or phenylephrine used in the treatment of cold and flu-like symptoms. Such symptoms may include fever, pain, nasal congestion, sinus congestion, runny nose, sore throat, myalgia, ear pressure and fullness, and headache. The formulation further includes various excipients used in the formulation process. | 1. A method of treating one or more of symptoms selected from the group consisting of pain, headache, fever, nasal congestion, sinus congestion, runny nose, myalgia, ear fullness, otic barotrauma, said method comprising administering to a mammalian subject in need thereof as a single dosage form a pharmaceutical composition comprising an effective amount of (a) a phenylpropionate, (b) an acetanilide, and (c) a sympathomimetic drug. 2. The method of claim 1, wherein the phenylpropionate is ibuprofen, and/or wherein the acetanilide is acetaminophen, and/or wherein the sympathomimetic drug is pseudoephedrine or phenylephrine. 3. The method of claim 1, wherein the phenylpropionate is ibuprofen, the acetanilide is acetaminophen, the sympathomimetic drug is pseudoephedrine or phenylephrine. 4. The method of claim 3, wherein more than one of the symptoms is treated. 5. The method of claim 3, wherein symptoms comprising pain, fever, headache, runny nose, nasal congestion, sinus congestion, and ear fullness are all treated. 6. The method of claim 3, wherein the mammalian subject is in need of treatment of influenza. 7. The method of claim 5, wherein the mammalian subject is in need of treatment of influenza. 8. A pharmaceutical composition comprising (a) a phenylpropionate, (b) an acetanilide, and (c) a sympathomimetic drug. 9. The composition of claim 8, wherein phenylpropionate is ibuprofen, and/or wherein the acetanilide is acetaminophen, and/or wherein the sympathomimetic drug is pseudoephedrine or phenylephrine. 10. The composition of claim 9, wherein the phenylpropionate is ibuprofen, the acetanilide is acetaminophen, the sympathomimetic drug is pseudoephedrine or phenylephrine. 11. The composition of claim 9 comprising the ibuprofen, acetaminophen and phenylephrine, wherein the ratio of acetaminophen to ibuprofen is 0.8125:1 to 2.5:1 and phenylephrine is present at from 1.10 to 16.13% by weight of the total mass of ibuprofen, acetaminophen, and phenylephrine. | A pharmaceutical formulation of therapeutically effective amounts of acetaminophen, ibuprofen, and a sympathomimetic drug, such as pseudoephedrine (or its prodrug), or phenylephrine used in the treatment of cold and flu-like symptoms. Such symptoms may include fever, pain, nasal congestion, sinus congestion, runny nose, sore throat, myalgia, ear pressure and fullness, and headache. The formulation further includes various excipients used in the formulation process.1. A method of treating one or more of symptoms selected from the group consisting of pain, headache, fever, nasal congestion, sinus congestion, runny nose, myalgia, ear fullness, otic barotrauma, said method comprising administering to a mammalian subject in need thereof as a single dosage form a pharmaceutical composition comprising an effective amount of (a) a phenylpropionate, (b) an acetanilide, and (c) a sympathomimetic drug. 2. The method of claim 1, wherein the phenylpropionate is ibuprofen, and/or wherein the acetanilide is acetaminophen, and/or wherein the sympathomimetic drug is pseudoephedrine or phenylephrine. 3. The method of claim 1, wherein the phenylpropionate is ibuprofen, the acetanilide is acetaminophen, the sympathomimetic drug is pseudoephedrine or phenylephrine. 4. The method of claim 3, wherein more than one of the symptoms is treated. 5. The method of claim 3, wherein symptoms comprising pain, fever, headache, runny nose, nasal congestion, sinus congestion, and ear fullness are all treated. 6. The method of claim 3, wherein the mammalian subject is in need of treatment of influenza. 7. The method of claim 5, wherein the mammalian subject is in need of treatment of influenza. 8. A pharmaceutical composition comprising (a) a phenylpropionate, (b) an acetanilide, and (c) a sympathomimetic drug. 9. The composition of claim 8, wherein phenylpropionate is ibuprofen, and/or wherein the acetanilide is acetaminophen, and/or wherein the sympathomimetic drug is pseudoephedrine or phenylephrine. 10. The composition of claim 9, wherein the phenylpropionate is ibuprofen, the acetanilide is acetaminophen, the sympathomimetic drug is pseudoephedrine or phenylephrine. 11. The composition of claim 9 comprising the ibuprofen, acetaminophen and phenylephrine, wherein the ratio of acetaminophen to ibuprofen is 0.8125:1 to 2.5:1 and phenylephrine is present at from 1.10 to 16.13% by weight of the total mass of ibuprofen, acetaminophen, and phenylephrine. | 1,600 |
1,349 | 16,013,594 | 1,629 | This invention relates to oral care compositions comprising an effective amount of a basic amino acid in free or salt form, together with an anionic surfactant, and to methods of using and of making such compositions. | 1-41. (canceled) 42. A method of reducing the adhesion of bacteria to tooth surfaces in an oral cavity of a subject, the method comprising treating the oral cavity with an oral care composition comprising a basic amino acid, in free or salt form, and an anionic surfactant. 43. A method according to claim 42, wherein the oral care composition comprises
a. an effective amount of a basic amino acid, in free or salt form; b. an anionic surfactant; and c. an additional agent selected from an effective amount of an antibacterial agent; an effective amount of a fluoride source; an anionic polymer; and combinations thereof. 44. A method according to claim 42, wherein the basic amino acid is arginine. 45. A method according to claim 42, wherein the basic amino acid is in salt form and selected from arginine phosphate, arginine bicarbonate, and arginine hydrochloride. 46. A method according to claim 42, wherein the anionic surfactant is selected from sodium lauryl sulfate and sodium laureth sulfate and mixtures thereof. 47. A method according to claim 42, wherein the anionic surfactant is present in an amount of from about 0.01 to about 10 weight %. 48. A method according to claim 42, wherein the anionic surfactant is present in an amount of from about 0.3 to about 4.5 weight %. 49. A method according to claim 42, wherein the composition further comprises a fluoride source selected from sodium fluoride and sodium monofluorophosphate. 50. A method according to claim 42, further comprising an antibacterial agent. 51. A method according to claim 50, wherein the antibacterial agent is zinc citrate, zinc lactate or a combination thereof. 52. A method according to claim 42, further comprising an anionic polymer. 53. A method according to claim 52, wherein the anionic polymer is a copolymer of methyl vinyl ether and maleic anhydride. 54. A method according to claim 42, wherein the composition is a dentifrice comprising
a. an effective amount of a salt of a basic amino acid selected from arginine bicarbonate arginine phosphate and arginine hydrochloride; b. an effective amount of a soluble fluoride salt selected from sodium fluoride and sodium monofluophosphate; c. an anionic surfactant selected from sodium laurel sulfate and sodium laureth sulfate. 55. A method according to claim 42, wherein the composition further comprises xylitol. 56. A method according to claim 42, comprising a particulate material selected from dicalcium phosphate, silica and calcium carbonate. 57. A method according to claim 42, wherein the radioactive dentin abrasion (RDA) is less than about 150. 58. A method according to claim 42, wherein the composition is in the form of a toothpaste further comprising one or more of water; abrasives, surfactants, foaming agents, vitamins, polymers, enzymes, humectants, thickeners, antimicrobial agents, preservatives, flavorings, colorings and/or combinations thereof. | This invention relates to oral care compositions comprising an effective amount of a basic amino acid in free or salt form, together with an anionic surfactant, and to methods of using and of making such compositions.1-41. (canceled) 42. A method of reducing the adhesion of bacteria to tooth surfaces in an oral cavity of a subject, the method comprising treating the oral cavity with an oral care composition comprising a basic amino acid, in free or salt form, and an anionic surfactant. 43. A method according to claim 42, wherein the oral care composition comprises
a. an effective amount of a basic amino acid, in free or salt form; b. an anionic surfactant; and c. an additional agent selected from an effective amount of an antibacterial agent; an effective amount of a fluoride source; an anionic polymer; and combinations thereof. 44. A method according to claim 42, wherein the basic amino acid is arginine. 45. A method according to claim 42, wherein the basic amino acid is in salt form and selected from arginine phosphate, arginine bicarbonate, and arginine hydrochloride. 46. A method according to claim 42, wherein the anionic surfactant is selected from sodium lauryl sulfate and sodium laureth sulfate and mixtures thereof. 47. A method according to claim 42, wherein the anionic surfactant is present in an amount of from about 0.01 to about 10 weight %. 48. A method according to claim 42, wherein the anionic surfactant is present in an amount of from about 0.3 to about 4.5 weight %. 49. A method according to claim 42, wherein the composition further comprises a fluoride source selected from sodium fluoride and sodium monofluorophosphate. 50. A method according to claim 42, further comprising an antibacterial agent. 51. A method according to claim 50, wherein the antibacterial agent is zinc citrate, zinc lactate or a combination thereof. 52. A method according to claim 42, further comprising an anionic polymer. 53. A method according to claim 52, wherein the anionic polymer is a copolymer of methyl vinyl ether and maleic anhydride. 54. A method according to claim 42, wherein the composition is a dentifrice comprising
a. an effective amount of a salt of a basic amino acid selected from arginine bicarbonate arginine phosphate and arginine hydrochloride; b. an effective amount of a soluble fluoride salt selected from sodium fluoride and sodium monofluophosphate; c. an anionic surfactant selected from sodium laurel sulfate and sodium laureth sulfate. 55. A method according to claim 42, wherein the composition further comprises xylitol. 56. A method according to claim 42, comprising a particulate material selected from dicalcium phosphate, silica and calcium carbonate. 57. A method according to claim 42, wherein the radioactive dentin abrasion (RDA) is less than about 150. 58. A method according to claim 42, wherein the composition is in the form of a toothpaste further comprising one or more of water; abrasives, surfactants, foaming agents, vitamins, polymers, enzymes, humectants, thickeners, antimicrobial agents, preservatives, flavorings, colorings and/or combinations thereof. | 1,600 |
1,350 | 14,367,526 | 1,634 | The present invention relates to a method for in vitro diagnosis or prognosis of colon cancer, including a step of detecting at least one expression product of at least one HERV nucleic acid sequence, the use of said isolated nucleic acid sequences as a molecular marker/molecular markers, and a kit including at least one specific binding partner for at least one expression product of the HERV nucleic acid sequences. | 1. A method for the in vitro diagnosis or prognosis of colon cancer in a biological sample taken from a patient, which comprises a step of detecting at least two expression products respectively of at least two nucleic acid sequences, said nucleic acid sequences being chosen from the sequences identified in SEQ ID NOs: 1 to 285 or from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 1 to 285. 2. The method as claimed in claim 1, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 15 17, 19, 22, 24, 25, 27 and 97 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 17, 19, 22, 24, 25, 27 and 97. 3. The method as claimed in claim 2, in which the expression product of at least two nucleic acid sequences, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 2, 3 and 8, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 2, 3 and 8. 4. The method as claimed in claim 1, in which the expression product detected is at least one RNA transcript or at least one polypeptide. 5. The method as claimed in claim 4, wherein the RNA transcript is at least one mRNA. 6. The method as claimed in claim 4, in which the RNA transcript is detected by hybridization, by amplification or by sequencing. 7. The method as claimed in claim 6, in which the mRNA is brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and the presence or absence of hybridization to the mRNA is detected. 8. The method as claimed in claim 5, wherein DNA copies of the mRNA are prepared, the DNA copies are brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and in that the presence or absence of hybridization to said DNA copies is detected. 9. The method as claimed in claim 4, in which the polypeptide expressed is detected by bringing into contact with at least one specific binding partner of said polypeptide, an affinity protein or an aptamer. 10. The method of at least two nucleic acid sequences, which have been isolated, as a molecular marker for the in vitro diagnosis or prognosis of colon cancer, wherein the two nucleic acid sequences consist of:
(i) at least two DNA sequences chosen from the sequences SEQ ID NOs: 1 to 285, or (ii) at least two DNA sequences respectively complementary to at least two sequences chosen from the sequences SEQ ID NOs: 1 to 285, or (iii) at least two DNA sequences which exhibit at least 99% identity with two sequences as defined in (i) and (ii), or (iv) at least two RNA sequences which are respectively the transcription product of two sequences chosen from the sequences as defined in (i), or (v) at least two RNA sequences which are the transcription product of at least two sequences chosen from the sequences which exhibit at least 99% identity with the sequences as defined in (i). 11. A kit for the in vitro diagnosis or prognosis of colon cancer in a biological sample taken from a patient, which comprises at least two respectively specific binding partners of at least two expression products of at least two nucleic acid sequences chosen from the sequences identified in SEQ ID NOs: 1 to 285 or from the sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 285 and no more than 285 specific binding partners of the expression products of the nucleic acid sequences identified in SEQ ID NOs: 1 to 285 or of the nucleic acid sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 285. 12. The kit as claimed in claim 11, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 25 12, 13, 17, 19, 22, 24, 25, 27 and 97 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 17, 19, 22, 24, 25, 27 and 97. 13. The kit as claimed in claim 12, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 2, 3 and 8 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 2, 3 and 8. 14. The kit as claimed in claim 12, which comprises 2 or 3 respectively specific binding partners of the expression products of the nucleic acid sequences identified in SEQ ID NOs: 2, 3 and 8 or of the nucleic acid sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 2, 3 and 8. 15. The kit as claimed in claim 11, in which the at least two respectively specific binding partners of the expression products are respectively at least one hybridization probe and/or at least one amplification primer, or at least one antibody, or at least one antibody analog, or at least one affinity protein, or at least one aptamer. 16. A method for evaluating the efficacy of a treatment and/or a progression in colon cancer, which comprises a step of detecting at least two expression products respectively of at least two nucleic acid sequences, said two nucleic acid sequences being chosen from the sequences identified in SEQ ID NOs: 1 to 285 or from the sequences which exhibit at least 99% identity respectively with the sequences identified in SEQ ID NOs: 1 to 285. 17. The method as claimed in claim 16, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 17, 19, 22, 24, 25, 27 and 97 or from the sequences which 30 exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 17, 19, 22, 24, 25, 27 and 97. 18. The method as claimed in claim 17, in which the expression product of at least two nucleic acid sequences, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 2, 3 and 8, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 2, 3 and 8. | The present invention relates to a method for in vitro diagnosis or prognosis of colon cancer, including a step of detecting at least one expression product of at least one HERV nucleic acid sequence, the use of said isolated nucleic acid sequences as a molecular marker/molecular markers, and a kit including at least one specific binding partner for at least one expression product of the HERV nucleic acid sequences.1. A method for the in vitro diagnosis or prognosis of colon cancer in a biological sample taken from a patient, which comprises a step of detecting at least two expression products respectively of at least two nucleic acid sequences, said nucleic acid sequences being chosen from the sequences identified in SEQ ID NOs: 1 to 285 or from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 1 to 285. 2. The method as claimed in claim 1, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 15 17, 19, 22, 24, 25, 27 and 97 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 17, 19, 22, 24, 25, 27 and 97. 3. The method as claimed in claim 2, in which the expression product of at least two nucleic acid sequences, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 2, 3 and 8, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 2, 3 and 8. 4. The method as claimed in claim 1, in which the expression product detected is at least one RNA transcript or at least one polypeptide. 5. The method as claimed in claim 4, wherein the RNA transcript is at least one mRNA. 6. The method as claimed in claim 4, in which the RNA transcript is detected by hybridization, by amplification or by sequencing. 7. The method as claimed in claim 6, in which the mRNA is brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and the presence or absence of hybridization to the mRNA is detected. 8. The method as claimed in claim 5, wherein DNA copies of the mRNA are prepared, the DNA copies are brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and in that the presence or absence of hybridization to said DNA copies is detected. 9. The method as claimed in claim 4, in which the polypeptide expressed is detected by bringing into contact with at least one specific binding partner of said polypeptide, an affinity protein or an aptamer. 10. The method of at least two nucleic acid sequences, which have been isolated, as a molecular marker for the in vitro diagnosis or prognosis of colon cancer, wherein the two nucleic acid sequences consist of:
(i) at least two DNA sequences chosen from the sequences SEQ ID NOs: 1 to 285, or (ii) at least two DNA sequences respectively complementary to at least two sequences chosen from the sequences SEQ ID NOs: 1 to 285, or (iii) at least two DNA sequences which exhibit at least 99% identity with two sequences as defined in (i) and (ii), or (iv) at least two RNA sequences which are respectively the transcription product of two sequences chosen from the sequences as defined in (i), or (v) at least two RNA sequences which are the transcription product of at least two sequences chosen from the sequences which exhibit at least 99% identity with the sequences as defined in (i). 11. A kit for the in vitro diagnosis or prognosis of colon cancer in a biological sample taken from a patient, which comprises at least two respectively specific binding partners of at least two expression products of at least two nucleic acid sequences chosen from the sequences identified in SEQ ID NOs: 1 to 285 or from the sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 285 and no more than 285 specific binding partners of the expression products of the nucleic acid sequences identified in SEQ ID NOs: 1 to 285 or of the nucleic acid sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 285. 12. The kit as claimed in claim 11, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 25 12, 13, 17, 19, 22, 24, 25, 27 and 97 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 17, 19, 22, 24, 25, 27 and 97. 13. The kit as claimed in claim 12, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 2, 3 and 8 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 2, 3 and 8. 14. The kit as claimed in claim 12, which comprises 2 or 3 respectively specific binding partners of the expression products of the nucleic acid sequences identified in SEQ ID NOs: 2, 3 and 8 or of the nucleic acid sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 2, 3 and 8. 15. The kit as claimed in claim 11, in which the at least two respectively specific binding partners of the expression products are respectively at least one hybridization probe and/or at least one amplification primer, or at least one antibody, or at least one antibody analog, or at least one affinity protein, or at least one aptamer. 16. A method for evaluating the efficacy of a treatment and/or a progression in colon cancer, which comprises a step of detecting at least two expression products respectively of at least two nucleic acid sequences, said two nucleic acid sequences being chosen from the sequences identified in SEQ ID NOs: 1 to 285 or from the sequences which exhibit at least 99% identity respectively with the sequences identified in SEQ ID NOs: 1 to 285. 17. The method as claimed in claim 16, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 17, 19, 22, 24, 25, 27 and 97 or from the sequences which 30 exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 17, 19, 22, 24, 25, 27 and 97. 18. The method as claimed in claim 17, in which the expression product of at least two nucleic acid sequences, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 2, 3 and 8, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 2, 3 and 8. | 1,600 |
1,351 | 14,367,673 | 1,634 | The subject matter of the present invention is a method for the diagnosis or prognosis, in vitro, of testicular cancer, which includes a step of detecting at least one expression product of at least one HERV nucleic acid sequence, the use of said nucleic acid sequences, which have been isolated, as a molecular marker or molecular markers, and a kit including at least one binding partner specific for at least one of the expression products of the HERV nucleic acid sequences. | 1. A method for the in vitro diagnosis or prognosis of testicular cancer in a biological sample taken from a patient, which comprises a step of detecting at least two expression products respectively of at least two nucleic acid sequences, said nucleic acid sequences being chosen from the sequences identified in SEQ ID NOs: 1 to 775 or from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 1 to 775. 2. The method as claimed in claim 1, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 26, 27, 29, 31, 32, 33, 34, 36, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 50, 51, 52, 53, 57, 58, 59, 61, 63, 64, 65, 68, 70, 71, 72, 74, 75, 76, 77, 78, 79, 80, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 94, 96, 97, 102, 104, 106, 107, 109, 110, 115, 116, 118, 121, 122, 123, 127, 132, 133, 136, 137, 142, 147, 148, 150, 159, 160, 162, 163, 164, 165, 166, 167, 170, 171, 175, 182, 187, 191, 198, 199, 201, 207, 210, 216, 219, 222, 224, 228, 230, 234, 244, 256, 263, 265, 266, 269, 271, 281, 286, 288, 291, 292, 296, 298, 304, 308, 333, 341, 347, 403, 429, 452, 485, 513, 556, 574 and 755 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 26, 27, 29, 31, 32, 33, 34, 36, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 50, 51, 52, 53, 57, 58, 59, 61, 63, 64, 65, 68, 70, 71, 72, 74, 75, 76, 77, 78, 79, 80, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 94, 96, 97, 102, 104, 106, 107, 109, 110, 115, 116, 118, 121, 122, 123, 127, 132, 133, 136, 137, 142, 147, 148, 150, 159, 160, 162, 163, 164, 165, 166, 167, 170, 171, 175, 182, 187, 191, 198, 199, 201, 207, 210, 216, 219, 222, 224, 228, 230, 234, 244, 256, 263, 265, 266, 269, 271, 281, 286, 288, 291, 292, 296, 298, 304, 308, 333, 341, 347, 403, 429, 452, 485, 513, 556, 574 and 755. 3. The method as claimed in claim 2, in which the expression product of at least two nucleic acid sequences is detected, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 26 and 29, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 26 and 29. 4. The method as claimed in claim 1, in which the expression product detected is at least one RNA transcript or at least one polypeptide. 5. The method as claimed in claim 4, wherein the RNA transcript is at least one mRNA. 6. The method as claimed in claim 4, in which the RNA transcript is detected by hybridization, by amplification or by sequencing. 7. The method as claimed in claim 6, in which the mRNA is brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and in that the presence or absence of hybridization to the mRNA is detected. 8. The method as claimed in claim 5, wherein DNA copies of the mRNA are prepared, the DNA copies are brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and in that the presence or absence of hybridization to said DNA copies is detected. 9. The method as claimed in claim 4, in which the polypeptide expressed is detected by bringing into contact with at least one specific binding partner of said polypeptide, an affinity protein or an aptamer. 10. The method for the in vitro diagnosis or prognosis of testicular cancer comprising: isolating at least two nucleic acid sequences as a molecular marker wherein the two nucleic acid sequences consist of:
(i) at least two DNA sequences chosen from the sequences SEQ ID NOs: 1 to 775, or (ii) at least two DNA sequences respectively complementary to at least two sequences chosen from the sequences SEQ ID Nos: 1 to 775, or (ii) at least two DNA sequences which exhibit at least 99% identity with two sequences as defined in (i) and (ii), or (iv) at least two RNA sequences which are respectively the transcription product of two sequences chosen from the sequences as defined in (i), or (v) at least two RNA sequences which are the transcription product of at least two sequences chosen from the sequences which exhibit at least 99% identity with the sequences as defined in (i). 11. A kit for the in vitro diagnosis or prognosis of testicular cancer in a biological sample taken from a patient, which comprises at least two respectively specific binding partners of at least two expression products of at least two nucleic acid sequences chosen from the sequences identified in SEQ ID NOs: 1 to 775 or from the sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 775 and no more than 775 specific binding partners of the expression products of the nucleic acid sequences identified in SEQ ID NOs: 1 to 775 or of the nucleic acid sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 775. 12. The kit as claimed in claim 11, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 26, 27, 29, 31, 32, 33, 34, 36, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 50, 51, 52, 53, 57, 58, 59, 61, 63, 64, 65, 68, 70, 71, 72, 74, 75, 76, 77, 78, 79, 80, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 94, 96, 97, 102, 104, 106, 107, 109, 110, 115, 116, 118, 121, 122, 123, 127, 132, 133, 136, 137, 142, 147, 148, 150, 159, 160, 162, 163, 164, 165, 166, 167, 170, 171, 175, 182, 187, 191, 198, 199, 201, 207, 210, 216, 219, 222, 224, 228, 230, 234, 244, 256, 263, 265, 266, 269, 271, 281, 286, 288, 291, 292, 296, 298, 304, 308, 333, 341, 347, 403, 429, 452, 485, 513, 556, 574 and 755 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 26, 27, 29, 31, 32, 33, 34, 36, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 50, 51, 52, 53, 57, 58, 59, 61, 63, 64, 65, 68, 70, 71, 72, 74, 75, 76, 77, 78, 79, 80, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 94, 96, 97, 102, 104, 106, 107, 109, 110, 115, 116, 118, 121, 122, 123, 127, 132, 133, 136, 137, 142, 147, 148, 150, 159, 160, 162, 163, 164, 165, 166, 167, 170, 171, 175, 182, 187, 191, 198, 199, 201, 207, 210, 216, 219, 222, 224, 228, 230, 234, 244, 256, 263, 265, 266, 269, 271, 281, 286, 288, 291, 292, 296, 298, 304, 308, 333, 341, 347, 403, 429, 452, 485, 513, 556, 574 and 755. 13. The kit as claimed in claim 12, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 1, 26 and 29 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 26 and 29. 14. The kit as claimed in claim 12, which comprises 2 or 3 respectively specific binding partners of the expression products of the nucleic acid sequences identified in SEQ ID NOs: 1, 26 and 29 or of the nucleic acid sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 26 and 29. 15. The kit as claimed in claim 11, in which the at least two respectively specific binding partners of the expression products are respectively at least one hybridization probe and/or at least one amplification primer, or at least one antibody, or at least one antibody analog, or at least one affinity protein, or at least one aptamer. 16. A method for evaluating the efficacy of a treatment and/or a progression in testicular cancer, which comprises a step of detecting at least two expression products respectively of at least two nucleic acid sequences, said two nucleic acid sequences being chosen from the sequences identified in SEQ ID NOs: 1 to 775 or from the sequences which exhibit at least 99% identity respectively with the sequences identified in SEQ ID NOs: 1 to 775. 17. The method as claimed in claim 16, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 26, 27, 29, 31, 32, 33, 34, 36, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 50, 51, 52, 53, 57, 58, 59, 61, 63, 64, 65, 68, 70, 71, 72, 74, 75, 76, 77, 78, 79, 80, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 94, 96, 97, 102, 104, 106, 107, 109, 110, 115, 116, 118, 121, 122, 123, 127, 132, 133, 136, 137, 142, 147, 148, 150, 159, 160, 162, 163, 164, 165, 166, 167, 170, 171, 175, 182, 187, 191, 198, 199, 201, 207, 210, 216, 219, 222, 224, 228, 230, 234, 244, 256, 263, 265, 266, 269, 271, 281, 286, 288, 291, 292, 296, 298, 304, 308, 333, 341, 347, 403, 429, 452, 485, 513, 556, 574 and 755 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 2, 3,4, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 26, 27, 29, 31, 32, 33, 34, 36, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 50, 51, 52, 53, 57, 58, 59, 61, 63, 64, 65, 68, 70, 71, 72, 74, 75, 76, 77, 78, 79, 80, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 94, 96, 97, 102, 104, 106, 107, 109, 110, 115, 116, 118, 121, 122, 123, 127, 132, 133, 136, 137, 142, 147, 148, 150, 159, 160, 162, 163, 164, 165, 166, 167, 170, 171, 175, 182, 187, 191, 198, 199, 201, 207, 210, 216, 219, 222, 224, 228, 230, 234, 244, 256, 263, 265, 266, 269, 271, 281, 286, 288, 291, 292, 296, 298, 304, 308, 333, 341, 347, 403, 429, 452, 485, 513, 556, 574 and 755. 18. The method as claimed in claim 17, in which the expression product of at least two nucleic acid sequences is detected, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 26 and 29, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 26 and 29. | The subject matter of the present invention is a method for the diagnosis or prognosis, in vitro, of testicular cancer, which includes a step of detecting at least one expression product of at least one HERV nucleic acid sequence, the use of said nucleic acid sequences, which have been isolated, as a molecular marker or molecular markers, and a kit including at least one binding partner specific for at least one of the expression products of the HERV nucleic acid sequences.1. A method for the in vitro diagnosis or prognosis of testicular cancer in a biological sample taken from a patient, which comprises a step of detecting at least two expression products respectively of at least two nucleic acid sequences, said nucleic acid sequences being chosen from the sequences identified in SEQ ID NOs: 1 to 775 or from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 1 to 775. 2. The method as claimed in claim 1, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 26, 27, 29, 31, 32, 33, 34, 36, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 50, 51, 52, 53, 57, 58, 59, 61, 63, 64, 65, 68, 70, 71, 72, 74, 75, 76, 77, 78, 79, 80, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 94, 96, 97, 102, 104, 106, 107, 109, 110, 115, 116, 118, 121, 122, 123, 127, 132, 133, 136, 137, 142, 147, 148, 150, 159, 160, 162, 163, 164, 165, 166, 167, 170, 171, 175, 182, 187, 191, 198, 199, 201, 207, 210, 216, 219, 222, 224, 228, 230, 234, 244, 256, 263, 265, 266, 269, 271, 281, 286, 288, 291, 292, 296, 298, 304, 308, 333, 341, 347, 403, 429, 452, 485, 513, 556, 574 and 755 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 26, 27, 29, 31, 32, 33, 34, 36, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 50, 51, 52, 53, 57, 58, 59, 61, 63, 64, 65, 68, 70, 71, 72, 74, 75, 76, 77, 78, 79, 80, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 94, 96, 97, 102, 104, 106, 107, 109, 110, 115, 116, 118, 121, 122, 123, 127, 132, 133, 136, 137, 142, 147, 148, 150, 159, 160, 162, 163, 164, 165, 166, 167, 170, 171, 175, 182, 187, 191, 198, 199, 201, 207, 210, 216, 219, 222, 224, 228, 230, 234, 244, 256, 263, 265, 266, 269, 271, 281, 286, 288, 291, 292, 296, 298, 304, 308, 333, 341, 347, 403, 429, 452, 485, 513, 556, 574 and 755. 3. The method as claimed in claim 2, in which the expression product of at least two nucleic acid sequences is detected, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 26 and 29, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 26 and 29. 4. The method as claimed in claim 1, in which the expression product detected is at least one RNA transcript or at least one polypeptide. 5. The method as claimed in claim 4, wherein the RNA transcript is at least one mRNA. 6. The method as claimed in claim 4, in which the RNA transcript is detected by hybridization, by amplification or by sequencing. 7. The method as claimed in claim 6, in which the mRNA is brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and in that the presence or absence of hybridization to the mRNA is detected. 8. The method as claimed in claim 5, wherein DNA copies of the mRNA are prepared, the DNA copies are brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and in that the presence or absence of hybridization to said DNA copies is detected. 9. The method as claimed in claim 4, in which the polypeptide expressed is detected by bringing into contact with at least one specific binding partner of said polypeptide, an affinity protein or an aptamer. 10. The method for the in vitro diagnosis or prognosis of testicular cancer comprising: isolating at least two nucleic acid sequences as a molecular marker wherein the two nucleic acid sequences consist of:
(i) at least two DNA sequences chosen from the sequences SEQ ID NOs: 1 to 775, or (ii) at least two DNA sequences respectively complementary to at least two sequences chosen from the sequences SEQ ID Nos: 1 to 775, or (ii) at least two DNA sequences which exhibit at least 99% identity with two sequences as defined in (i) and (ii), or (iv) at least two RNA sequences which are respectively the transcription product of two sequences chosen from the sequences as defined in (i), or (v) at least two RNA sequences which are the transcription product of at least two sequences chosen from the sequences which exhibit at least 99% identity with the sequences as defined in (i). 11. A kit for the in vitro diagnosis or prognosis of testicular cancer in a biological sample taken from a patient, which comprises at least two respectively specific binding partners of at least two expression products of at least two nucleic acid sequences chosen from the sequences identified in SEQ ID NOs: 1 to 775 or from the sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 775 and no more than 775 specific binding partners of the expression products of the nucleic acid sequences identified in SEQ ID NOs: 1 to 775 or of the nucleic acid sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 775. 12. The kit as claimed in claim 11, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 26, 27, 29, 31, 32, 33, 34, 36, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 50, 51, 52, 53, 57, 58, 59, 61, 63, 64, 65, 68, 70, 71, 72, 74, 75, 76, 77, 78, 79, 80, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 94, 96, 97, 102, 104, 106, 107, 109, 110, 115, 116, 118, 121, 122, 123, 127, 132, 133, 136, 137, 142, 147, 148, 150, 159, 160, 162, 163, 164, 165, 166, 167, 170, 171, 175, 182, 187, 191, 198, 199, 201, 207, 210, 216, 219, 222, 224, 228, 230, 234, 244, 256, 263, 265, 266, 269, 271, 281, 286, 288, 291, 292, 296, 298, 304, 308, 333, 341, 347, 403, 429, 452, 485, 513, 556, 574 and 755 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 26, 27, 29, 31, 32, 33, 34, 36, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 50, 51, 52, 53, 57, 58, 59, 61, 63, 64, 65, 68, 70, 71, 72, 74, 75, 76, 77, 78, 79, 80, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 94, 96, 97, 102, 104, 106, 107, 109, 110, 115, 116, 118, 121, 122, 123, 127, 132, 133, 136, 137, 142, 147, 148, 150, 159, 160, 162, 163, 164, 165, 166, 167, 170, 171, 175, 182, 187, 191, 198, 199, 201, 207, 210, 216, 219, 222, 224, 228, 230, 234, 244, 256, 263, 265, 266, 269, 271, 281, 286, 288, 291, 292, 296, 298, 304, 308, 333, 341, 347, 403, 429, 452, 485, 513, 556, 574 and 755. 13. The kit as claimed in claim 12, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 1, 26 and 29 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 26 and 29. 14. The kit as claimed in claim 12, which comprises 2 or 3 respectively specific binding partners of the expression products of the nucleic acid sequences identified in SEQ ID NOs: 1, 26 and 29 or of the nucleic acid sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 26 and 29. 15. The kit as claimed in claim 11, in which the at least two respectively specific binding partners of the expression products are respectively at least one hybridization probe and/or at least one amplification primer, or at least one antibody, or at least one antibody analog, or at least one affinity protein, or at least one aptamer. 16. A method for evaluating the efficacy of a treatment and/or a progression in testicular cancer, which comprises a step of detecting at least two expression products respectively of at least two nucleic acid sequences, said two nucleic acid sequences being chosen from the sequences identified in SEQ ID NOs: 1 to 775 or from the sequences which exhibit at least 99% identity respectively with the sequences identified in SEQ ID NOs: 1 to 775. 17. The method as claimed in claim 16, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 26, 27, 29, 31, 32, 33, 34, 36, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 50, 51, 52, 53, 57, 58, 59, 61, 63, 64, 65, 68, 70, 71, 72, 74, 75, 76, 77, 78, 79, 80, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 94, 96, 97, 102, 104, 106, 107, 109, 110, 115, 116, 118, 121, 122, 123, 127, 132, 133, 136, 137, 142, 147, 148, 150, 159, 160, 162, 163, 164, 165, 166, 167, 170, 171, 175, 182, 187, 191, 198, 199, 201, 207, 210, 216, 219, 222, 224, 228, 230, 234, 244, 256, 263, 265, 266, 269, 271, 281, 286, 288, 291, 292, 296, 298, 304, 308, 333, 341, 347, 403, 429, 452, 485, 513, 556, 574 and 755 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 2, 3,4, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 26, 27, 29, 31, 32, 33, 34, 36, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 50, 51, 52, 53, 57, 58, 59, 61, 63, 64, 65, 68, 70, 71, 72, 74, 75, 76, 77, 78, 79, 80, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 94, 96, 97, 102, 104, 106, 107, 109, 110, 115, 116, 118, 121, 122, 123, 127, 132, 133, 136, 137, 142, 147, 148, 150, 159, 160, 162, 163, 164, 165, 166, 167, 170, 171, 175, 182, 187, 191, 198, 199, 201, 207, 210, 216, 219, 222, 224, 228, 230, 234, 244, 256, 263, 265, 266, 269, 271, 281, 286, 288, 291, 292, 296, 298, 304, 308, 333, 341, 347, 403, 429, 452, 485, 513, 556, 574 and 755. 18. The method as claimed in claim 17, in which the expression product of at least two nucleic acid sequences is detected, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 26 and 29, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 26 and 29. | 1,600 |
1,352 | 13,543,194 | 1,619 | Aerosol compositions propelled by compressed gas providing enhanced intensity of one or more active components (e.g., fragrance, malodor counteractant, insecticide, disinfectant, or antimicrobial) over an extended period of time in the environment of use consistently over the life of the product. This is provided by a selected combination of spray rate and average particle size of the composition. The increased intensity over time can be further enhanced by further selection of the initial and terminal pressure under which the composition is maintained, and the pressure drop ratio, with respect to the composition product and a suitable dispensing container. | 1. An aerosol article comprising
(a) a composition comprising
(i) at least one compressed gas propellant;
(ii) about 0.1 to about 2.5 wt. % of at least one active ingredient;
(iii) water as a solvent carrier and in an amount to serve as a major component of said composition;
wherein said composition has a volatile organic content (VOC) of 0 to 4%; and (b) a dispensing container with a spray nozzle; wherein (i) when said composition is dispensed from said container, said composition is under an initial pressure of about 100 to about 180 psig and when less than 10% by volume of said composition remains in said container, said composition is under a terminal pressure of about 30 to about 90 psig, (ii) said composition is dispensed at a spray rate in a range of greater than about 1.5 grams/seconds (g/s) to about 3.0 g/s, and an average particle size in a range of about 60 to about 100 microns. 2. The aerosol article of claim 1, wherein said compressed gas propellant is one or more of nitrogen, air, carbon dioxide, nitrous oxide, and an inert gas. 3. The aerosol article of claim 1, wherein said at least one active ingredient is one or more of a fragrance, an odor eliminating compound, an insecticide, an antimicrobial, and a disinfectant. 4. The aerosol article of claim 1, wherein said spray rate is in a range of from about 1.6 to about 2.5 g/s. 5. The aerosol composition of claim 1, wherein said average particle size is in a range of about 60 to about 90 microns. 6. The aerosol article of claim 1, wherein said average particle size is in a range of about 60 to about 80 microns. 7. An article for fragrance dispensing and/or odor treating comprising
(1) a composition comprising
(a) at least one compressed gas propellant;
(b) at least one active ingredient; and
(c) water as a solvent carrier and in an amount to serve as a major component of said composition,
wherein said compressed gas is present in relation to said composition in a ratio of about 50:50 to about 25:75 by volume; (2) an aerosol dispensing container adapted to contain and dispense said composition including (d) an initial pressure in said container of about 100 to about 180 psig; (e) a nozzle which dispenses said composition at a spray rate of greater than about 1.5 g/s to about 3.0 g/s and in an average particle size of about 60 to about 100 microns; and (f) a pressure drop ratio over a dispensing life of said composition from said container of less than 4:1 when said container has a headspace of 25% by volume and of 2:1 when said container has a headspace of 50% by volume. 8. The article of claim 7, wherein said compressed gas is one or more of air, nitrogen, carbon dioxide, nitrous oxide, and an inert gas. 9. The article of claim 7, wherein said at least one said active ingredient is one or more of a fragrance, an odor eliminating compound, an insecticide, an antimicrobial, and a disinfectant. 10. The article of claim 7, wherein said spray rate is from about 1.6 g/s to about 2.5 g/s. 11. The article of claim 7, wherein said average particle size is from about 60 to about 90 microns. 12. The article of claim 7, wherein said average particle size is from about 60 to about 80 microns. 13. An aerosol composition with enhanced intensity and longevity comprising
(a) a compressed gas propellant; (b) about 0.1 to about 2.5 wt. % of at least one active ingredient; and (c) water as a solvent carrier in an amount to serve as a major component of said composition; wherein said composition (i) has a ratio of said compressed gas propellant to said composition of about 50:50 to about 25:75 by volume, (ii) a spray rate upon dispensing of greater than about 1.5 to about 3.0 grams/second (g/s), and (iii) an average particle size in a range of about 60 to about 100 microns. 14. The aerosol composition of claim 13, wherein said compressed gas propellant is one or more of air, nitrogen, carbon dioxide, nitrous oxide, and an inert gas. 15. The aerosol composition of claim 13, wherein said at least one active ingredient is one or more of a fragrance, an odor eliminating compound, an insecticide, an antimicrobial, and a disinfectant. 16. The aerosol composition of claim 13, wherein the spray rate is about 1.6 to about 2.5 g/s. 17. The aerosol composition of claim 13, wherein the average particle size is about 60 to about 90 microns. 18. The aerosol composition of claim 13, wherein the average particle size is about 60 to about 80 microns. 19. A fragrance-containing composition with enhanced intensity over time comprising
(a) at least one compressed gas propellant; (b) a fragrance component and optionally at least one additional active compound; (c) water as a solvent carrier and in an amount to serve as a major component of said composition; wherein said fragrance has an intensity rating of about 10 to about 2 based on an intensity scale of 0 to 15 as determined according to Intensity Testing Protocol described herein based on a period of from greater than 0 to 200 minutes. 20. The composition of claim 19, wherein said compressed gas propellant is one or more of air, nitrogen, carbon dioxide, nitrous oxide, and an inert gas. 21. The composition of claim 19, wherein said additional active compound is one or more of a fragrance, an odor eliminating compound, an insecticide, an antimicrobial, and a disinfectant. 22. The composition of claim 19, wherein said fragrance has an intensity of about 8 to about 3. 23. A method of dispensing an active compound comprising dispensing a composition from an aerosol dispensing container at a spray rate of greater than about 1.5 grams/second (g/s) to about 3.0 g/s and with an average particle size in a range of about 60 to about 100 microns, wherein said composition comprises (a) at least one compressed gas propellant, (b) at least one active compound, and (c) water as a solvent carrier and in an amount to serve as a major component of said composition, and wherein said composition is under an initial pressure in said container of about 100 to about 180 psig and when less than 10% by volume of said composition remains in said container, said composition is under a terminal pressure of about 30 to about 90 psig. 24. The method of claim 23, wherein said at least one active compound is a fragrance and one or more of a odor reducing compound, insecticide, an antimicrobial, and a disinfectant; and said fragrance has an intensity rating of about 10 to about 2 based on an intensity scale of 0 to 15 as determined according to Intensity Testing Protocol as described herein based on a period of from greater than 0 to 200 minutes. | Aerosol compositions propelled by compressed gas providing enhanced intensity of one or more active components (e.g., fragrance, malodor counteractant, insecticide, disinfectant, or antimicrobial) over an extended period of time in the environment of use consistently over the life of the product. This is provided by a selected combination of spray rate and average particle size of the composition. The increased intensity over time can be further enhanced by further selection of the initial and terminal pressure under which the composition is maintained, and the pressure drop ratio, with respect to the composition product and a suitable dispensing container.1. An aerosol article comprising
(a) a composition comprising
(i) at least one compressed gas propellant;
(ii) about 0.1 to about 2.5 wt. % of at least one active ingredient;
(iii) water as a solvent carrier and in an amount to serve as a major component of said composition;
wherein said composition has a volatile organic content (VOC) of 0 to 4%; and (b) a dispensing container with a spray nozzle; wherein (i) when said composition is dispensed from said container, said composition is under an initial pressure of about 100 to about 180 psig and when less than 10% by volume of said composition remains in said container, said composition is under a terminal pressure of about 30 to about 90 psig, (ii) said composition is dispensed at a spray rate in a range of greater than about 1.5 grams/seconds (g/s) to about 3.0 g/s, and an average particle size in a range of about 60 to about 100 microns. 2. The aerosol article of claim 1, wherein said compressed gas propellant is one or more of nitrogen, air, carbon dioxide, nitrous oxide, and an inert gas. 3. The aerosol article of claim 1, wherein said at least one active ingredient is one or more of a fragrance, an odor eliminating compound, an insecticide, an antimicrobial, and a disinfectant. 4. The aerosol article of claim 1, wherein said spray rate is in a range of from about 1.6 to about 2.5 g/s. 5. The aerosol composition of claim 1, wherein said average particle size is in a range of about 60 to about 90 microns. 6. The aerosol article of claim 1, wherein said average particle size is in a range of about 60 to about 80 microns. 7. An article for fragrance dispensing and/or odor treating comprising
(1) a composition comprising
(a) at least one compressed gas propellant;
(b) at least one active ingredient; and
(c) water as a solvent carrier and in an amount to serve as a major component of said composition,
wherein said compressed gas is present in relation to said composition in a ratio of about 50:50 to about 25:75 by volume; (2) an aerosol dispensing container adapted to contain and dispense said composition including (d) an initial pressure in said container of about 100 to about 180 psig; (e) a nozzle which dispenses said composition at a spray rate of greater than about 1.5 g/s to about 3.0 g/s and in an average particle size of about 60 to about 100 microns; and (f) a pressure drop ratio over a dispensing life of said composition from said container of less than 4:1 when said container has a headspace of 25% by volume and of 2:1 when said container has a headspace of 50% by volume. 8. The article of claim 7, wherein said compressed gas is one or more of air, nitrogen, carbon dioxide, nitrous oxide, and an inert gas. 9. The article of claim 7, wherein said at least one said active ingredient is one or more of a fragrance, an odor eliminating compound, an insecticide, an antimicrobial, and a disinfectant. 10. The article of claim 7, wherein said spray rate is from about 1.6 g/s to about 2.5 g/s. 11. The article of claim 7, wherein said average particle size is from about 60 to about 90 microns. 12. The article of claim 7, wherein said average particle size is from about 60 to about 80 microns. 13. An aerosol composition with enhanced intensity and longevity comprising
(a) a compressed gas propellant; (b) about 0.1 to about 2.5 wt. % of at least one active ingredient; and (c) water as a solvent carrier in an amount to serve as a major component of said composition; wherein said composition (i) has a ratio of said compressed gas propellant to said composition of about 50:50 to about 25:75 by volume, (ii) a spray rate upon dispensing of greater than about 1.5 to about 3.0 grams/second (g/s), and (iii) an average particle size in a range of about 60 to about 100 microns. 14. The aerosol composition of claim 13, wherein said compressed gas propellant is one or more of air, nitrogen, carbon dioxide, nitrous oxide, and an inert gas. 15. The aerosol composition of claim 13, wherein said at least one active ingredient is one or more of a fragrance, an odor eliminating compound, an insecticide, an antimicrobial, and a disinfectant. 16. The aerosol composition of claim 13, wherein the spray rate is about 1.6 to about 2.5 g/s. 17. The aerosol composition of claim 13, wherein the average particle size is about 60 to about 90 microns. 18. The aerosol composition of claim 13, wherein the average particle size is about 60 to about 80 microns. 19. A fragrance-containing composition with enhanced intensity over time comprising
(a) at least one compressed gas propellant; (b) a fragrance component and optionally at least one additional active compound; (c) water as a solvent carrier and in an amount to serve as a major component of said composition; wherein said fragrance has an intensity rating of about 10 to about 2 based on an intensity scale of 0 to 15 as determined according to Intensity Testing Protocol described herein based on a period of from greater than 0 to 200 minutes. 20. The composition of claim 19, wherein said compressed gas propellant is one or more of air, nitrogen, carbon dioxide, nitrous oxide, and an inert gas. 21. The composition of claim 19, wherein said additional active compound is one or more of a fragrance, an odor eliminating compound, an insecticide, an antimicrobial, and a disinfectant. 22. The composition of claim 19, wherein said fragrance has an intensity of about 8 to about 3. 23. A method of dispensing an active compound comprising dispensing a composition from an aerosol dispensing container at a spray rate of greater than about 1.5 grams/second (g/s) to about 3.0 g/s and with an average particle size in a range of about 60 to about 100 microns, wherein said composition comprises (a) at least one compressed gas propellant, (b) at least one active compound, and (c) water as a solvent carrier and in an amount to serve as a major component of said composition, and wherein said composition is under an initial pressure in said container of about 100 to about 180 psig and when less than 10% by volume of said composition remains in said container, said composition is under a terminal pressure of about 30 to about 90 psig. 24. The method of claim 23, wherein said at least one active compound is a fragrance and one or more of a odor reducing compound, insecticide, an antimicrobial, and a disinfectant; and said fragrance has an intensity rating of about 10 to about 2 based on an intensity scale of 0 to 15 as determined according to Intensity Testing Protocol as described herein based on a period of from greater than 0 to 200 minutes. | 1,600 |
1,353 | 16,117,857 | 1,644 | Embodiments of this invention include methods for detecting in vitro the presence in peripheral blood mononuclear cells (PBMCs), and in serum or plasma, of antibodies reactive to and of lymphocytes that are responsive to CNS antigens associated with Multiple Sclerosis (MS). These CNS antigens include, but are not limited to whole brain lysate and the myelin antigens myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), MOG peptides (MOGps), proteolipid protein (PLP), and PLP peptides (PLPps). PBMCs obtained from patients with active MS produce antibodies specific for CNS antigen, and causes T-lymphocytes to produce T-lymphocyte-specific cytokines, including interferon gamma (IFN-γ), interleukin-2 (IL-2), or interleukin-17 (IL-17). In contrast, PBMCs from subjects without MS do not produce such responses. The magnitude of the CNS antigen-specific response in patients with definite MS or in patients with CIS or RIS can indicate the likelihood that a given patient will develop a relapse and can indicate the responsiveness to and the success of immune modulatory treatment. | 1. A method for detecting a cell that produces an antibody against a CNS-specific antigen, comprising the steps:
a) providing a cell culture well having a surface and a cell culture medium therein; b) attaching a CNS-specific antigen to said surface; c) introducing a sample of peripheral blood mononuclear cells (PBMCs), CNS cells, or cell liquor from a human being into said cell culture medium; d) permitting said PBMCs to produce an antibody against said CNS-specific antigen; and e) detecting the presence of said antibody using an anti-antibody specific reagent. 2. The method of claim 1, said step of detection being carried out using a method selected from the group consisting of enzyme linked immune spot assay (ELISPOT), enzyme-linked immunoassay (ELISA), bead array, or protein array. 3. The method of claim 1, said CNS-specific antigen selected from the group consisting of whole-brain lysate, human myelin antigens, human proteolipid protein (hPLP), human myelin basic protein (hMBP), myelin oligodendrocyte glycoprotein (hMOG), neuronal antigen, a peptide from hMOG (hMOGp) containing a sequence of hMOG, and a MOG/PLP fusion protein. 4. The method of claim 1, said method performed with PBMCs or cells isolated from the CNS. 5. The method of claim 1, where said CNS-specific hMOG antigen is SEQ ID NO.1. 6. The method of claim 1, where said CNS-specific MOGp antigen is human MOG 35-55 (SEQ ID NO.2). 7. The method of claim 1, where said CNS-specific antigen MBP is MBP isoform 3, 21.5 kDa (SEQ ID NO.3). 8. The method of claim 1, where said CNS-specific proteolipid protein antigen is ΔPLP4 (SEQ ID NO.4). 9. The method of claim 1, where said CNS-specific MOG/PLP antigen is fusion protein MP4 (SEQ ID NO.6). 10. A method for treating a patient having multiple sclerosis (MS), comprising the steps:
a) providing a cell culture well having a surface and a cell culture medium therein; b) attaching a CNS-specific antigen to said surface; c) introducing a sample of peripheral blood mononuclear cells (PBMCs), CNS cells, or cell liquor from a human being into said cell culture medium; d) permitting said PBMCs to produce an antibody against said CNS-specific antigen; e) detecting the presence of said antibody using an anti-antibody specific reagent; and f) if said antibody is detected in step e), administering to said patient an immune modulating agent. 11. The method of claim 10, wherein said immune modulating agent is a B-cell depleting agent. 12. The method of claim 11, wherein said B-cell depleting agent is an anti-CD20 antibody. 13. The method of claim 10, further comprising administering to said patient a therapeutic agent selected from the group consisting of glatiramer acetate, interferon beta-1a, interferon beta-1b, mitoxantrone, natalizumab, and FTY720 fingolimod. | Embodiments of this invention include methods for detecting in vitro the presence in peripheral blood mononuclear cells (PBMCs), and in serum or plasma, of antibodies reactive to and of lymphocytes that are responsive to CNS antigens associated with Multiple Sclerosis (MS). These CNS antigens include, but are not limited to whole brain lysate and the myelin antigens myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), MOG peptides (MOGps), proteolipid protein (PLP), and PLP peptides (PLPps). PBMCs obtained from patients with active MS produce antibodies specific for CNS antigen, and causes T-lymphocytes to produce T-lymphocyte-specific cytokines, including interferon gamma (IFN-γ), interleukin-2 (IL-2), or interleukin-17 (IL-17). In contrast, PBMCs from subjects without MS do not produce such responses. The magnitude of the CNS antigen-specific response in patients with definite MS or in patients with CIS or RIS can indicate the likelihood that a given patient will develop a relapse and can indicate the responsiveness to and the success of immune modulatory treatment.1. A method for detecting a cell that produces an antibody against a CNS-specific antigen, comprising the steps:
a) providing a cell culture well having a surface and a cell culture medium therein; b) attaching a CNS-specific antigen to said surface; c) introducing a sample of peripheral blood mononuclear cells (PBMCs), CNS cells, or cell liquor from a human being into said cell culture medium; d) permitting said PBMCs to produce an antibody against said CNS-specific antigen; and e) detecting the presence of said antibody using an anti-antibody specific reagent. 2. The method of claim 1, said step of detection being carried out using a method selected from the group consisting of enzyme linked immune spot assay (ELISPOT), enzyme-linked immunoassay (ELISA), bead array, or protein array. 3. The method of claim 1, said CNS-specific antigen selected from the group consisting of whole-brain lysate, human myelin antigens, human proteolipid protein (hPLP), human myelin basic protein (hMBP), myelin oligodendrocyte glycoprotein (hMOG), neuronal antigen, a peptide from hMOG (hMOGp) containing a sequence of hMOG, and a MOG/PLP fusion protein. 4. The method of claim 1, said method performed with PBMCs or cells isolated from the CNS. 5. The method of claim 1, where said CNS-specific hMOG antigen is SEQ ID NO.1. 6. The method of claim 1, where said CNS-specific MOGp antigen is human MOG 35-55 (SEQ ID NO.2). 7. The method of claim 1, where said CNS-specific antigen MBP is MBP isoform 3, 21.5 kDa (SEQ ID NO.3). 8. The method of claim 1, where said CNS-specific proteolipid protein antigen is ΔPLP4 (SEQ ID NO.4). 9. The method of claim 1, where said CNS-specific MOG/PLP antigen is fusion protein MP4 (SEQ ID NO.6). 10. A method for treating a patient having multiple sclerosis (MS), comprising the steps:
a) providing a cell culture well having a surface and a cell culture medium therein; b) attaching a CNS-specific antigen to said surface; c) introducing a sample of peripheral blood mononuclear cells (PBMCs), CNS cells, or cell liquor from a human being into said cell culture medium; d) permitting said PBMCs to produce an antibody against said CNS-specific antigen; e) detecting the presence of said antibody using an anti-antibody specific reagent; and f) if said antibody is detected in step e), administering to said patient an immune modulating agent. 11. The method of claim 10, wherein said immune modulating agent is a B-cell depleting agent. 12. The method of claim 11, wherein said B-cell depleting agent is an anti-CD20 antibody. 13. The method of claim 10, further comprising administering to said patient a therapeutic agent selected from the group consisting of glatiramer acetate, interferon beta-1a, interferon beta-1b, mitoxantrone, natalizumab, and FTY720 fingolimod. | 1,600 |
1,354 | 14,217,070 | 1,633 | Compositions can be used to stimulate growth of a hair shaft from a hair follicle. These compositions can include methylated polynucleotides useful in treatment of autoimmune diseases or conditions, including those, such as alopecia areata, that result in hair loss. | 1. A method of stimulating growth of a hair shaft from a hair follicle, comprising:
administering to a subject in need thereof an effective amount of a polynucleotide, wherein said polynucleotide comprises a sequence that encodes a pro-apoptotic protein, or a functional fragment thereof, and wherein the methylation level of CpG dinucleotides of the polynucleotide is about 2 fold to about 4 fold higher as compared to the average methylation level of CpG dinucleotides in a wild type Escherichia coli (E. coli) genome. 2. A method of stimulating growth of a hair shaft from a hair follicle, comprising:
administering to a subject in need thereof an effective amount of a polynucleotide, wherein said polynucleotide comprises a sequence that encodes a pro-apoptotic protein, or a functional fragment thereof, and wherein about 30% to about 60% of the CpG dinucleotides of the polynucleotide are methylated. 3. The method of claim 1, wherein said pro-apoptotic protein is selected from the group consisting of Bax, Bak, Bim, Puma, Bad, Bik, Noxa, Bmf, Hrk, Bid, FAS, a caspase, and a functional fragment thereof. 4. The method of claim 1, wherein said pro-apoptotic protein is BAX, or a functional fragment thereof. 5. The method of claim 1, wherein said polynucleotide is administered at least one of subcutaneously or intradermally. 6. The method of claim 1, wherein said polynucleotide is administered to a site of hair loss. 7. The method of claim 1, wherein said polynucleotide is produced in a bacterium, wherein said bacterium comprises an engineered methylase-coding sequence controlled by a constitutive promoter, and wherein said engineered methylase-coding sequence is stably incorporated into the chromosomal DNA of said bacterium. 8. The method of claim 7, wherein the bacterium is Escherichia coli (E. coli). 9. The method of claim 7, wherein the methylase is a CpG methylase. 10. A method of treating alopecia areata, comprising: administering to a subject in need thereof an effective amount of a polynucleotide,
wherein said polynucleotide comprises a sequence that encodes a pro-apoptotic protein, or a functional fragment thereof, and wherein the methylation level of CpG dinucleotides of the polynucleotide is about 2 fold to about 4 fold higher as compared to the average methylation level of CpG dinucleotides in a wild type Escherichia coli (E. coli) genome. 11. The method of claim 10, wherein said pro-apoptotic protein is selected from the group consisting of Bax, Bak, Bim, Puma, Bad, Bik, Noxa, Bmf, Hrk, Bid, FAS, a caspase, and a functional fragment thereof. 12. The method of claim 10, wherein said pro-apoptotic protein is BAX, or a functional fragment thereof. 13. The method of claim 10, wherein said polynucleotide is administered at least one of subcutaneously or intradermally. 14. The method of claim 10, wherein said polynucleotide is administered to a site of hair loss. 15. The method of claim 10, wherein said polynucleotide is produced in a bacterium, wherein said bacterium comprises an engineered methylase-coding sequence controlled by a constitutive promoter, and wherein said engineered methylase-coding sequence is stably incorporated into the chromosomal DNA of said bacterium. 16. The method of claim 15, wherein the bacterium is Escherichia coli (E. coli). 17. The method of claim 15, wherein the methylase is a CpG methylase. | Compositions can be used to stimulate growth of a hair shaft from a hair follicle. These compositions can include methylated polynucleotides useful in treatment of autoimmune diseases or conditions, including those, such as alopecia areata, that result in hair loss.1. A method of stimulating growth of a hair shaft from a hair follicle, comprising:
administering to a subject in need thereof an effective amount of a polynucleotide, wherein said polynucleotide comprises a sequence that encodes a pro-apoptotic protein, or a functional fragment thereof, and wherein the methylation level of CpG dinucleotides of the polynucleotide is about 2 fold to about 4 fold higher as compared to the average methylation level of CpG dinucleotides in a wild type Escherichia coli (E. coli) genome. 2. A method of stimulating growth of a hair shaft from a hair follicle, comprising:
administering to a subject in need thereof an effective amount of a polynucleotide, wherein said polynucleotide comprises a sequence that encodes a pro-apoptotic protein, or a functional fragment thereof, and wherein about 30% to about 60% of the CpG dinucleotides of the polynucleotide are methylated. 3. The method of claim 1, wherein said pro-apoptotic protein is selected from the group consisting of Bax, Bak, Bim, Puma, Bad, Bik, Noxa, Bmf, Hrk, Bid, FAS, a caspase, and a functional fragment thereof. 4. The method of claim 1, wherein said pro-apoptotic protein is BAX, or a functional fragment thereof. 5. The method of claim 1, wherein said polynucleotide is administered at least one of subcutaneously or intradermally. 6. The method of claim 1, wherein said polynucleotide is administered to a site of hair loss. 7. The method of claim 1, wherein said polynucleotide is produced in a bacterium, wherein said bacterium comprises an engineered methylase-coding sequence controlled by a constitutive promoter, and wherein said engineered methylase-coding sequence is stably incorporated into the chromosomal DNA of said bacterium. 8. The method of claim 7, wherein the bacterium is Escherichia coli (E. coli). 9. The method of claim 7, wherein the methylase is a CpG methylase. 10. A method of treating alopecia areata, comprising: administering to a subject in need thereof an effective amount of a polynucleotide,
wherein said polynucleotide comprises a sequence that encodes a pro-apoptotic protein, or a functional fragment thereof, and wherein the methylation level of CpG dinucleotides of the polynucleotide is about 2 fold to about 4 fold higher as compared to the average methylation level of CpG dinucleotides in a wild type Escherichia coli (E. coli) genome. 11. The method of claim 10, wherein said pro-apoptotic protein is selected from the group consisting of Bax, Bak, Bim, Puma, Bad, Bik, Noxa, Bmf, Hrk, Bid, FAS, a caspase, and a functional fragment thereof. 12. The method of claim 10, wherein said pro-apoptotic protein is BAX, or a functional fragment thereof. 13. The method of claim 10, wherein said polynucleotide is administered at least one of subcutaneously or intradermally. 14. The method of claim 10, wherein said polynucleotide is administered to a site of hair loss. 15. The method of claim 10, wherein said polynucleotide is produced in a bacterium, wherein said bacterium comprises an engineered methylase-coding sequence controlled by a constitutive promoter, and wherein said engineered methylase-coding sequence is stably incorporated into the chromosomal DNA of said bacterium. 16. The method of claim 15, wherein the bacterium is Escherichia coli (E. coli). 17. The method of claim 15, wherein the methylase is a CpG methylase. | 1,600 |
1,355 | 16,012,508 | 1,613 | Antimicrobial compositions for killing or deactivating microbes, such as viruses, bacteria, or fungi, include metal nanoparticles, a carrier, and a plurality of metal nanoparticles. The nanoparticles can be selected to have a particle size and particle size distribution to selectively and preferentially kill one of a virus, a bacterium, or a fungus. Antiviral compositions can include nanoparticles having a particle size of 8 nm or less, 1-7 nm, 2-6.5 nm, or 3-6 nm (or up to 10 nm for Ebola virus). Antibacterial compositions can include nanoparticles having a particle size of 3-14 nm, 5-13 nm, 7-12 nm, or 8-10 nm. Antifungal compositions can include nanoparticles having a particle size of 9-20 nm, 10-18 nm, 11-16 nm, or 12-15 nm. Exemplary methods of killing or deactivating microbes include: (1) applying an antimicrobial composition to a substrate containing microbes, and (2) the antimicrobial composition killing or deactivating the microbes. | 1. A method of selectively killing or deactivating a target microbe, comprising:
applying an antimicrobial composition to the target microbe or to a substrate containing the target microbe, the antimicrobial composition comprising:
a carrier; and
a plurality of spherical-shaped, nonionic metal nanoparticles formed by laser ablation having a mean diameter in a range of 1-20 nm so as to selectively kill or deactivate the target microbe, wherein at least 99% of the spherical metal nanoparticles have a diameter within ±3 nm of the mean diameter; and
the antimicrobial composition selectively killing or deactivating the target microbe, which is selected from a bacterium, a virus, or a fungus, and wherein:
when the microbe is a bacterium the metal nanoparticles have a mean diameter in a range of 3 nm to 14 nm to selectively kill the bacterium,
when the microbe is a virus the metal nanoparticles have a mean diameter in a range of 1 nm to 7 nm to selectively kill the virus, or
when the microbe is a fungus the metal nanoparticles have a mean diameter in a range of 9 nm to 20 nm to selectively kill the fungus. 2. The method of claim 1, wherein the substrate is a non-living object. 3. The method of claim 1, wherein the substrate is a living organism. 4. The method of claim 1, wherein the microbe is a bacterium and the metal nanoparticles have a mean diameter in a range of 5 nm to 13 nm to selectively kill the bacterium. 5. The method of claim 1, wherein the microbe is a bacterium and the metal nanoparticles have a mean diameter in a range of 7 nm to 12 nm to selectively kill the bacterium. 6. The method of claim 1, wherein the microbe is a bacterium and the metal nanoparticles have a mean diameter in a range of 8 nm to 10 nm to selectively kill the bacterium. 7. The method of claim 1, wherein the microbe is a virus and the metal nanoparticles have a mean diameter in a range of 2 nm to 6.5 nm to selectively kill the virus. 8. The method of claim 1, wherein the microbe is a virus and the metal nanoparticles have a mean diameter in a range of 3 nm to 6 nm to selectively kill the virus. 9. The method of claim 1, wherein the microbe is a fungus and the metal nanoparticles have a mean diameter in a range of 10 nm to 18 nm to selectively kill the fungus. 10. The method of claim 1, wherein the microbe is a fungus and the metal nanoparticles have a mean diameter in a range of 11 nm to 16 nm to selectively kill the fungus. 11. The method of claim 1, wherein the microbe is a fungus and the metal nanoparticles have a mean diameter in a range of 12 nm to 15 nm to selectively kill the fungus. 12. The method of claim 1, wherein at least 99% of the spherical metal nanoparticles have a diameter within ±1 nm of the mean diameter. 13. The method of claim 1, wherein the antimicrobial composition further comprises coral-shaped metal nanoparticles, each coral-shaped metal nanoparticle having a non-uniform cross section and a globular structure formed by multiple, non-linear strands joined together without right angles. 14. The method of claim 1, wherein the carrier is a liquid in which the metal nanoparticles are colloidally dispersed. 15. The method of claim 1, wherein the metal nanoparticles have a concentration in a range of about 10 ppb to about 100 ppm by weight of the antimicrobial composition. 16. The method of claim 1, wherein the metal nanoparticles have a concentration in a range of about 100 ppb to about 75 ppm by weight of the antimicrobial composition. 17. The method of claim 1, wherein the metal nanoparticles have a concentration in a range of about 1 ppm to about 50 ppm by weight of the antimicrobial composition. 18. The method of claim 1, wherein the spherical metal nanoparticles comprise silver, gold, or an alloy of silver and gold. 19. A method of selectively killing or deactivating a bacterium, comprising:
applying an antimicrobial composition to the bacterium or to a substrate containing the bacterium, the antimicrobial composition comprising:
a carrier; and
a plurality of spherical-shaped, nonionic metal nanoparticles formed from silver or a silver alloy and having a mean particle size in a range of 3-14 nm to selectively kill or deactivate the bacterium, wherein at least 99% of the spherical metal nanoparticles have a particle size within ±3 nm of the mean particle size; and
the antimicrobial composition selectively killing or deactivating the bacterium without release of silver ions. 20. A method of selectively killing or deactivating a virus, comprising:
applying an antimicrobial composition to the virus or to a substrate containing the virus, the antimicrobial composition comprising:
a carrier; and
a plurality of spherical-shaped, nonionic metal nanoparticles formed from silver or a silver alloy and having a mean particle size in a range of 1-7 nm to selectively kill or deactivate the virus, wherein at least 99% of the spherical metal nanoparticles have a particle size within ±1 nm of the mean particle size; and
the antimicrobial composition selectively killing or deactivating the virus without release of silver ions. | Antimicrobial compositions for killing or deactivating microbes, such as viruses, bacteria, or fungi, include metal nanoparticles, a carrier, and a plurality of metal nanoparticles. The nanoparticles can be selected to have a particle size and particle size distribution to selectively and preferentially kill one of a virus, a bacterium, or a fungus. Antiviral compositions can include nanoparticles having a particle size of 8 nm or less, 1-7 nm, 2-6.5 nm, or 3-6 nm (or up to 10 nm for Ebola virus). Antibacterial compositions can include nanoparticles having a particle size of 3-14 nm, 5-13 nm, 7-12 nm, or 8-10 nm. Antifungal compositions can include nanoparticles having a particle size of 9-20 nm, 10-18 nm, 11-16 nm, or 12-15 nm. Exemplary methods of killing or deactivating microbes include: (1) applying an antimicrobial composition to a substrate containing microbes, and (2) the antimicrobial composition killing or deactivating the microbes.1. A method of selectively killing or deactivating a target microbe, comprising:
applying an antimicrobial composition to the target microbe or to a substrate containing the target microbe, the antimicrobial composition comprising:
a carrier; and
a plurality of spherical-shaped, nonionic metal nanoparticles formed by laser ablation having a mean diameter in a range of 1-20 nm so as to selectively kill or deactivate the target microbe, wherein at least 99% of the spherical metal nanoparticles have a diameter within ±3 nm of the mean diameter; and
the antimicrobial composition selectively killing or deactivating the target microbe, which is selected from a bacterium, a virus, or a fungus, and wherein:
when the microbe is a bacterium the metal nanoparticles have a mean diameter in a range of 3 nm to 14 nm to selectively kill the bacterium,
when the microbe is a virus the metal nanoparticles have a mean diameter in a range of 1 nm to 7 nm to selectively kill the virus, or
when the microbe is a fungus the metal nanoparticles have a mean diameter in a range of 9 nm to 20 nm to selectively kill the fungus. 2. The method of claim 1, wherein the substrate is a non-living object. 3. The method of claim 1, wherein the substrate is a living organism. 4. The method of claim 1, wherein the microbe is a bacterium and the metal nanoparticles have a mean diameter in a range of 5 nm to 13 nm to selectively kill the bacterium. 5. The method of claim 1, wherein the microbe is a bacterium and the metal nanoparticles have a mean diameter in a range of 7 nm to 12 nm to selectively kill the bacterium. 6. The method of claim 1, wherein the microbe is a bacterium and the metal nanoparticles have a mean diameter in a range of 8 nm to 10 nm to selectively kill the bacterium. 7. The method of claim 1, wherein the microbe is a virus and the metal nanoparticles have a mean diameter in a range of 2 nm to 6.5 nm to selectively kill the virus. 8. The method of claim 1, wherein the microbe is a virus and the metal nanoparticles have a mean diameter in a range of 3 nm to 6 nm to selectively kill the virus. 9. The method of claim 1, wherein the microbe is a fungus and the metal nanoparticles have a mean diameter in a range of 10 nm to 18 nm to selectively kill the fungus. 10. The method of claim 1, wherein the microbe is a fungus and the metal nanoparticles have a mean diameter in a range of 11 nm to 16 nm to selectively kill the fungus. 11. The method of claim 1, wherein the microbe is a fungus and the metal nanoparticles have a mean diameter in a range of 12 nm to 15 nm to selectively kill the fungus. 12. The method of claim 1, wherein at least 99% of the spherical metal nanoparticles have a diameter within ±1 nm of the mean diameter. 13. The method of claim 1, wherein the antimicrobial composition further comprises coral-shaped metal nanoparticles, each coral-shaped metal nanoparticle having a non-uniform cross section and a globular structure formed by multiple, non-linear strands joined together without right angles. 14. The method of claim 1, wherein the carrier is a liquid in which the metal nanoparticles are colloidally dispersed. 15. The method of claim 1, wherein the metal nanoparticles have a concentration in a range of about 10 ppb to about 100 ppm by weight of the antimicrobial composition. 16. The method of claim 1, wherein the metal nanoparticles have a concentration in a range of about 100 ppb to about 75 ppm by weight of the antimicrobial composition. 17. The method of claim 1, wherein the metal nanoparticles have a concentration in a range of about 1 ppm to about 50 ppm by weight of the antimicrobial composition. 18. The method of claim 1, wherein the spherical metal nanoparticles comprise silver, gold, or an alloy of silver and gold. 19. A method of selectively killing or deactivating a bacterium, comprising:
applying an antimicrobial composition to the bacterium or to a substrate containing the bacterium, the antimicrobial composition comprising:
a carrier; and
a plurality of spherical-shaped, nonionic metal nanoparticles formed from silver or a silver alloy and having a mean particle size in a range of 3-14 nm to selectively kill or deactivate the bacterium, wherein at least 99% of the spherical metal nanoparticles have a particle size within ±3 nm of the mean particle size; and
the antimicrobial composition selectively killing or deactivating the bacterium without release of silver ions. 20. A method of selectively killing or deactivating a virus, comprising:
applying an antimicrobial composition to the virus or to a substrate containing the virus, the antimicrobial composition comprising:
a carrier; and
a plurality of spherical-shaped, nonionic metal nanoparticles formed from silver or a silver alloy and having a mean particle size in a range of 1-7 nm to selectively kill or deactivate the virus, wherein at least 99% of the spherical metal nanoparticles have a particle size within ±1 nm of the mean particle size; and
the antimicrobial composition selectively killing or deactivating the virus without release of silver ions. | 1,600 |
1,356 | 13,899,090 | 1,619 | In accordance with one aspect, embolic particles are provided that comprise a biodegradable polymer and a therapeutic agent, wherein the particles are configured such that, upon administration to a body lumen of a subject, the therapeutic agent is released from the time of administration up until a first point in time that ranges anywhere from about 1 week after administration to about 4 weeks after administration, at which point in time the therapeutic agent release ceases. The particles are also configured such that particles remain present in the body lumen from the first point in time at which therapeutic agent release ceases up to a second point in time that ranges anywhere from about 2 weeks to about 12 months after the first point in time, at which point the particles are completely degraded. Other aspects pertain to methods of making such particles. Still other aspects pertain to injectable compositions that comprise such particles and to methods of treatment that employ such injectable compositions. | 1. An embolic particle comprising a biodegradable polymer and a therapeutic agent, wherein the particle is configured such that, upon administration to an body lumen of a subject, the therapeutic agent is released from the time of administration up until a first point in time that ranges anywhere from about 1 week after administration to about 4 weeks after administration, at which point in time the therapeutic agent release ceases, and such that the particle remains present in the body lumen from the first point in time at which therapeutic agent release ceases up to a second point in time that ranges anywhere from about 2 weeks to about 12 months after the first point in time, at which point the particle is completely degraded. 2. The embolic particle of claim 1, wherein said particle ranges between 45 and 300 microns in longest linear cross-sectional dimension. 3. The embolic particle of claim 1, wherein said particle is spherical or where the particle is a cylindrical particle having an aspect ratio ranging from 2 to 10. 4. The embolic particle of claim 3, wherein said particle ranges between 45 and 300 microns in diameter. 5. The embolic particle of claim 1, wherein said embolic particle comprises a core and a shell. 6. The embolic particle of claim 5, wherein said shell comprises said therapeutic agent and said core does not comprise said therapeutic agent. 7. The embolic particle of claim 6, wherein said shell is a surface degradable shell that degrades from said administration up to said first point in time at which point only said core remains present in the body lumen. 8. The embolic particle of claim 5, wherein said shell comprises apertures but does not comprise said therapeutic agent, and wherein said core comprises said therapeutic agent and degrades more quickly than said shell. 9. The embolic particle of claim 1, wherein said polymer is an amino-acid-based poly(ester amide). 10. The embolic particle of claim 9, wherein said amino-acid-base poly(ester amide) comprises an α-amino acid moiety, a diol moiety and a diacid moiety. 11. The embolic particle of claim 10, wherein said amino-acid-based poly(ester amide) comprises:
(a) an α-amino acid moiety of the formula,
wherein R3 is selected from hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl(C1-C6)alkyl, hydroxy(C1-C6)alkyl, hydroxy(C6-C10)aryl(C1-C6)alkyl, carboxy(C1-C6)alkyl, carboxy(C6-C10)aryl(C1-C6)alkyl, amino(C1-C6)alkyl,
(C1-C6)alkyl-amide, and thio(C1-C6)alkyl,
(b) a diol moiety of the formula, —O—R4—O— wherein R4 is (C1-C20)alkyl, and
(c) a diacid moeity selected from a diacid moiety of the formula,
wherein R1 is (C1-C20)alkyl, (C2-C20)alkenyl, or (C1-C8)alkyloxy(C1-C8)alkyl, an oxo-diacid moiety of the formula,
wherein R6 is (C1-C20)alkyl, (C2-C20)alkenyl, or (C1-C8)alkyloxy(C1-C8)alkyl, and a combination of both said diacid moiety and said oxo-diacid moiety. 12. The embolic particle of claim 11, wherein said amino-acid-based poly(ester amide) further comprises an amino-acid moiety of the formula,
wherein R2 is hydrogen, (C1-C6)alkyl or (C6-C10)aryl(C1-C6)alkyl. 13. The embolic particle of claim 12, wherein said amino-acid-based poly(ester amide) comprises a unit of the formula,
and a unit of the formula, 14. The embolic particle of claim 12, wherein said amino-acid-based poly(ester amide) comprises a unit of the formula,
and a unit of the formula, 15. The embolic particle of claim 9, wherein said amino-acid-based poly(ester amide) is covalently crosslinked. 16. The embolic particle of claim 1, wherein said therapeutic agent is an anti-tumor agent. 17. An injectable medical composition comprising particles in accordance with claim 1. 18. The injectable medical composition of claim 18, comprising a tonicity adjusting agent. 19. The injectable medical composition of claim 18, wherein said injectable medical composition is disposed within a glass container or a preloaded medical device. 20. A method of embolization comprising injecting the injectable medical composition of claim 18 into a patient. | In accordance with one aspect, embolic particles are provided that comprise a biodegradable polymer and a therapeutic agent, wherein the particles are configured such that, upon administration to a body lumen of a subject, the therapeutic agent is released from the time of administration up until a first point in time that ranges anywhere from about 1 week after administration to about 4 weeks after administration, at which point in time the therapeutic agent release ceases. The particles are also configured such that particles remain present in the body lumen from the first point in time at which therapeutic agent release ceases up to a second point in time that ranges anywhere from about 2 weeks to about 12 months after the first point in time, at which point the particles are completely degraded. Other aspects pertain to methods of making such particles. Still other aspects pertain to injectable compositions that comprise such particles and to methods of treatment that employ such injectable compositions.1. An embolic particle comprising a biodegradable polymer and a therapeutic agent, wherein the particle is configured such that, upon administration to an body lumen of a subject, the therapeutic agent is released from the time of administration up until a first point in time that ranges anywhere from about 1 week after administration to about 4 weeks after administration, at which point in time the therapeutic agent release ceases, and such that the particle remains present in the body lumen from the first point in time at which therapeutic agent release ceases up to a second point in time that ranges anywhere from about 2 weeks to about 12 months after the first point in time, at which point the particle is completely degraded. 2. The embolic particle of claim 1, wherein said particle ranges between 45 and 300 microns in longest linear cross-sectional dimension. 3. The embolic particle of claim 1, wherein said particle is spherical or where the particle is a cylindrical particle having an aspect ratio ranging from 2 to 10. 4. The embolic particle of claim 3, wherein said particle ranges between 45 and 300 microns in diameter. 5. The embolic particle of claim 1, wherein said embolic particle comprises a core and a shell. 6. The embolic particle of claim 5, wherein said shell comprises said therapeutic agent and said core does not comprise said therapeutic agent. 7. The embolic particle of claim 6, wherein said shell is a surface degradable shell that degrades from said administration up to said first point in time at which point only said core remains present in the body lumen. 8. The embolic particle of claim 5, wherein said shell comprises apertures but does not comprise said therapeutic agent, and wherein said core comprises said therapeutic agent and degrades more quickly than said shell. 9. The embolic particle of claim 1, wherein said polymer is an amino-acid-based poly(ester amide). 10. The embolic particle of claim 9, wherein said amino-acid-base poly(ester amide) comprises an α-amino acid moiety, a diol moiety and a diacid moiety. 11. The embolic particle of claim 10, wherein said amino-acid-based poly(ester amide) comprises:
(a) an α-amino acid moiety of the formula,
wherein R3 is selected from hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl(C1-C6)alkyl, hydroxy(C1-C6)alkyl, hydroxy(C6-C10)aryl(C1-C6)alkyl, carboxy(C1-C6)alkyl, carboxy(C6-C10)aryl(C1-C6)alkyl, amino(C1-C6)alkyl,
(C1-C6)alkyl-amide, and thio(C1-C6)alkyl,
(b) a diol moiety of the formula, —O—R4—O— wherein R4 is (C1-C20)alkyl, and
(c) a diacid moeity selected from a diacid moiety of the formula,
wherein R1 is (C1-C20)alkyl, (C2-C20)alkenyl, or (C1-C8)alkyloxy(C1-C8)alkyl, an oxo-diacid moiety of the formula,
wherein R6 is (C1-C20)alkyl, (C2-C20)alkenyl, or (C1-C8)alkyloxy(C1-C8)alkyl, and a combination of both said diacid moiety and said oxo-diacid moiety. 12. The embolic particle of claim 11, wherein said amino-acid-based poly(ester amide) further comprises an amino-acid moiety of the formula,
wherein R2 is hydrogen, (C1-C6)alkyl or (C6-C10)aryl(C1-C6)alkyl. 13. The embolic particle of claim 12, wherein said amino-acid-based poly(ester amide) comprises a unit of the formula,
and a unit of the formula, 14. The embolic particle of claim 12, wherein said amino-acid-based poly(ester amide) comprises a unit of the formula,
and a unit of the formula, 15. The embolic particle of claim 9, wherein said amino-acid-based poly(ester amide) is covalently crosslinked. 16. The embolic particle of claim 1, wherein said therapeutic agent is an anti-tumor agent. 17. An injectable medical composition comprising particles in accordance with claim 1. 18. The injectable medical composition of claim 18, comprising a tonicity adjusting agent. 19. The injectable medical composition of claim 18, wherein said injectable medical composition is disposed within a glass container or a preloaded medical device. 20. A method of embolization comprising injecting the injectable medical composition of claim 18 into a patient. | 1,600 |
1,357 | 13,980,418 | 1,619 | The present invention relates to a cosmetic composition for eyelashes such as a mascara, comprising: at least one anionic surfactant including 2-amino-2-methyl-1,3-propanediol in combination with a C 16 -C 24 fatty acid; and at least one film-forming polymer present in the form of particles dispersed in an aqueous phase, wherein the weight ratio of the amount of 2-amino-2-methyl-1,3-propanediol in combination with the C 16 -C 24 fatty acid/the amount of the film forming polymer is 0.01 to 0.3, preferably 0.05 to 0.2, and more preferably 0.1 to 0.15. | 1.-15. (canceled) 16. A cosmetic composition for eyelashes, comprising:
at least one anionic surfactant comprising 2-amino-2-methyl-1,3-propanediol in combination with at least one C16-C24 fatty acid; and at least one film-forming polymer present in the form of particles dispersed in an aqueous phase, wherein the weight ratio of the at least one anionic surfactant comprising 2-amino-2-methyl-1,3-propanediol in combination with the at least one C16-C24 fatty acid to the at least one film forming polymer ranges from about 0.01 to about 0.3. 17. The cosmetic composition for eyelashes according to claim 16, wherein the weight ratio of the at least one anionic surfactant comprising 2-amino-2-methyl-1,3-propanediol in combination with the at least one C16-C24 fatty acid to the at least one film forming polymer ranges from about 0.1 to about 0.15. 18. The cosmetic composition for eyelashes according to claim 16, wherein the at least one C16-C24 fatty acid is stearic acid. 19. The cosmetic composition for eyelashes according to claim 16, wherein the at least one anionic surfactant is present in an amount ranging from about 0.01% to about 10% by weight, relative to the total weight of the cosmetic composition. 20. The cosmetic composition for eyelashes according to claim 16, wherein the at least one anionic surfactant is present in an amount ranging from about 0.5% to about 3% by weight, relative to the total weight of the cosmetic composition 21. The cosmetic composition for eyelashes according to claim 16, wherein the at least one film-forming polymer is chosen from free-radical synthetic polymers, polycondensate synthetic polymers, polymers of natural origin, and mixtures thereof. 22. The cosmetic composition for eyelashes according to claim 16, wherein the at least one film-forming polymer is chosen from vinyl (co)polymers, (meth)acrylic (co)polymers, urethanes (co)polymers, and mixtures thereof. 23. The cosmetic composition for eyelashes according to claim 16, wherein the at least one film-forming polymer is chosen from styrene-(meth)acrylic and (meth)acrylic copolymers, vinyl acetate and (meth)acrylic copolymers, and mixtures thereof. 24. The cosmetic composition for eyelashes according to claim 16, wherein the at least one film-forming polymer is present in an amount of dry matter ranging from about 10% to about 30% by weight, relative to the total weight of the cosmetic composition. 25. The cosmetic composition for eyelashes according to claim 16, wherein the at least one film-forming polymer is present in an amount of dry matter ranging from about 15% to about 20% by weight, relative to the total weight of the cosmetic composition. 26. The cosmetic composition for eyelashes according to claim 16, further comprising at least one nonionic surfactant with an HLB of less than about 8 at 25° C. 27. The cosmetic composition for eyelashes according to claim 26, wherein the at least one nonionic surfactant with an HLB of less than about 8 at 25° C. is chosen from saccharide esters and ethers, fatty acid esters, mixtures of cyclomethicone/dimethicone copolyol, and mixtures thereof. 28. The cosmetic composition for eyelashes according to claim 16, further comprising at least one nonionic surfactant with an HLB of greater than or equal to about 8 at 25° C. 29. The cosmetic composition for eyelashes according to claim 28, wherein the at least one nonionic surfactant with an HLB of greater than or equal to about 8 at 25° C. is chosen from oxyethylenated and/or oxypropylenated ethers of glycerol, oxyethylenated and/or oxypropylenated ethers of fatty alcohol, fatty acid esters of polyethylene glycol, fatty acid esters of oxyethylenated and/or oxypropylenated glyceryl ethers, fatty acid esters of oxyethylenated and/or oxypropylenated sorbitol ethers, dimethicone copolyol, dimethicone copolyol benzoate, copolymers of propylene oxide and of ethylene oxide, and mixtures thereof. 30. The cosmetic composition for eyelashes according to claim 16, comprising water in an amount ranging from about 15% to about 50% by weight, relative to the total weight of the cosmetic composition. 31. The cosmetic composition for eyelashes according to claim 16, comprising water in an amount ranging from about 25% to about 35% by weight, relative to the total weight of the cosmetic composition. 32. The cosmetic composition for eyelashes according to claim 16, further comprising at least one wax. 33. The cosmetic composition for eyelashes according to claim 16, further comprising at least one fiber. 34. A cosmetic process for making-up eyelashes, comprising:
loading an applicator with a cosmetic composition comprising
at least one anionic surfactant comprising 2-amino-2-methyl-1,3-propanediol in combination with at least one C16-C24 fatty acid; and
at least one film-forming polymer present in the form of particles dispersed in an aqueous phase,
wherein the weight ratio of the at least one anionic surfactant comprising 2-amino-2-methyl-1,3-propanediol in combination with the C16-C24 fatty acid to the at least one film forming polymer ranges from about 0.01 to about 0.3; and applying the cosmetic composition onto the eyelashes. | The present invention relates to a cosmetic composition for eyelashes such as a mascara, comprising: at least one anionic surfactant including 2-amino-2-methyl-1,3-propanediol in combination with a C 16 -C 24 fatty acid; and at least one film-forming polymer present in the form of particles dispersed in an aqueous phase, wherein the weight ratio of the amount of 2-amino-2-methyl-1,3-propanediol in combination with the C 16 -C 24 fatty acid/the amount of the film forming polymer is 0.01 to 0.3, preferably 0.05 to 0.2, and more preferably 0.1 to 0.15.1.-15. (canceled) 16. A cosmetic composition for eyelashes, comprising:
at least one anionic surfactant comprising 2-amino-2-methyl-1,3-propanediol in combination with at least one C16-C24 fatty acid; and at least one film-forming polymer present in the form of particles dispersed in an aqueous phase, wherein the weight ratio of the at least one anionic surfactant comprising 2-amino-2-methyl-1,3-propanediol in combination with the at least one C16-C24 fatty acid to the at least one film forming polymer ranges from about 0.01 to about 0.3. 17. The cosmetic composition for eyelashes according to claim 16, wherein the weight ratio of the at least one anionic surfactant comprising 2-amino-2-methyl-1,3-propanediol in combination with the at least one C16-C24 fatty acid to the at least one film forming polymer ranges from about 0.1 to about 0.15. 18. The cosmetic composition for eyelashes according to claim 16, wherein the at least one C16-C24 fatty acid is stearic acid. 19. The cosmetic composition for eyelashes according to claim 16, wherein the at least one anionic surfactant is present in an amount ranging from about 0.01% to about 10% by weight, relative to the total weight of the cosmetic composition. 20. The cosmetic composition for eyelashes according to claim 16, wherein the at least one anionic surfactant is present in an amount ranging from about 0.5% to about 3% by weight, relative to the total weight of the cosmetic composition 21. The cosmetic composition for eyelashes according to claim 16, wherein the at least one film-forming polymer is chosen from free-radical synthetic polymers, polycondensate synthetic polymers, polymers of natural origin, and mixtures thereof. 22. The cosmetic composition for eyelashes according to claim 16, wherein the at least one film-forming polymer is chosen from vinyl (co)polymers, (meth)acrylic (co)polymers, urethanes (co)polymers, and mixtures thereof. 23. The cosmetic composition for eyelashes according to claim 16, wherein the at least one film-forming polymer is chosen from styrene-(meth)acrylic and (meth)acrylic copolymers, vinyl acetate and (meth)acrylic copolymers, and mixtures thereof. 24. The cosmetic composition for eyelashes according to claim 16, wherein the at least one film-forming polymer is present in an amount of dry matter ranging from about 10% to about 30% by weight, relative to the total weight of the cosmetic composition. 25. The cosmetic composition for eyelashes according to claim 16, wherein the at least one film-forming polymer is present in an amount of dry matter ranging from about 15% to about 20% by weight, relative to the total weight of the cosmetic composition. 26. The cosmetic composition for eyelashes according to claim 16, further comprising at least one nonionic surfactant with an HLB of less than about 8 at 25° C. 27. The cosmetic composition for eyelashes according to claim 26, wherein the at least one nonionic surfactant with an HLB of less than about 8 at 25° C. is chosen from saccharide esters and ethers, fatty acid esters, mixtures of cyclomethicone/dimethicone copolyol, and mixtures thereof. 28. The cosmetic composition for eyelashes according to claim 16, further comprising at least one nonionic surfactant with an HLB of greater than or equal to about 8 at 25° C. 29. The cosmetic composition for eyelashes according to claim 28, wherein the at least one nonionic surfactant with an HLB of greater than or equal to about 8 at 25° C. is chosen from oxyethylenated and/or oxypropylenated ethers of glycerol, oxyethylenated and/or oxypropylenated ethers of fatty alcohol, fatty acid esters of polyethylene glycol, fatty acid esters of oxyethylenated and/or oxypropylenated glyceryl ethers, fatty acid esters of oxyethylenated and/or oxypropylenated sorbitol ethers, dimethicone copolyol, dimethicone copolyol benzoate, copolymers of propylene oxide and of ethylene oxide, and mixtures thereof. 30. The cosmetic composition for eyelashes according to claim 16, comprising water in an amount ranging from about 15% to about 50% by weight, relative to the total weight of the cosmetic composition. 31. The cosmetic composition for eyelashes according to claim 16, comprising water in an amount ranging from about 25% to about 35% by weight, relative to the total weight of the cosmetic composition. 32. The cosmetic composition for eyelashes according to claim 16, further comprising at least one wax. 33. The cosmetic composition for eyelashes according to claim 16, further comprising at least one fiber. 34. A cosmetic process for making-up eyelashes, comprising:
loading an applicator with a cosmetic composition comprising
at least one anionic surfactant comprising 2-amino-2-methyl-1,3-propanediol in combination with at least one C16-C24 fatty acid; and
at least one film-forming polymer present in the form of particles dispersed in an aqueous phase,
wherein the weight ratio of the at least one anionic surfactant comprising 2-amino-2-methyl-1,3-propanediol in combination with the C16-C24 fatty acid to the at least one film forming polymer ranges from about 0.01 to about 0.3; and applying the cosmetic composition onto the eyelashes. | 1,600 |
1,358 | 14,999,688 | 1,611 | A fragrance slurry pad patterned sampler including a base material applied to one of coated and uncoated paper, flexible film and paper laminations, aluminum foil, thermal plastics, PET, OPP, BOPP, EVA, PE, and other commonly polymer films providing the base for the fragrance sampler, the sampler including a slurry formed from various aroma chemicals, one sampler formed of one or more aroma chemicals, and the other sampler formed of one or more aroma chemicals, each applied to the base material, in a patterned arrangement, so that when the microencapsulated chemicals are fractured upon opening of the sampler, the separate aromas will be delivered sequentially, or in combination, depending upon their patterned application to the base sheet of the sampler. | 1. A fragrant slurry pad patterned sampler including a substrate, a microencapsulated fragrance material applied to said substrate, fragrance material having discrete patterned applications to the substrate, said fragrance material comprised of select aroma chemicals, at least two portions of the fragrance material applied to the substrate, one of said fragrance material as applied in an initial pattern, and a second fragrance material applied in a separate pattern, such that when the sampler is opened, the various fragrance materials releasing one of sequentially or simultaneously their separate aromas for providing a fragrance for sampling by the user. 2. The sampler of claim 1, wherein the first segment of aroma chemicals are applied to one side of the base substrate, while the second segment of the aroma chemicals are applied to an adjacent side of the base substrate of the sampler, whereby when the cover sheet is removed from the sampler, initially one segment of the sampler will deliver its fragrance to the atmosphere, and subsequently, as the cover sheet is fully removed, the second segment of the aroma chemicals will he released to the atmosphere. 3. The sampler of claim 2, and including a fold line provided between the first and second segments of the aroma chemicals, and the base substrate is folded along said fold line, such that when the sampler is opened, both segments of the aroma chemicals are released into the atmosphere simultaneously to provide its fragrance. 4. The sampler of claim 1, wherein the first segment of aroma chemicals is interspaced amongst a second segment of aroma chemicals, such that when the cover sheet is removed, the microencapsulated fragrances are released simultaneously to present their fragrance to the atmosphere. | A fragrance slurry pad patterned sampler including a base material applied to one of coated and uncoated paper, flexible film and paper laminations, aluminum foil, thermal plastics, PET, OPP, BOPP, EVA, PE, and other commonly polymer films providing the base for the fragrance sampler, the sampler including a slurry formed from various aroma chemicals, one sampler formed of one or more aroma chemicals, and the other sampler formed of one or more aroma chemicals, each applied to the base material, in a patterned arrangement, so that when the microencapsulated chemicals are fractured upon opening of the sampler, the separate aromas will be delivered sequentially, or in combination, depending upon their patterned application to the base sheet of the sampler.1. A fragrant slurry pad patterned sampler including a substrate, a microencapsulated fragrance material applied to said substrate, fragrance material having discrete patterned applications to the substrate, said fragrance material comprised of select aroma chemicals, at least two portions of the fragrance material applied to the substrate, one of said fragrance material as applied in an initial pattern, and a second fragrance material applied in a separate pattern, such that when the sampler is opened, the various fragrance materials releasing one of sequentially or simultaneously their separate aromas for providing a fragrance for sampling by the user. 2. The sampler of claim 1, wherein the first segment of aroma chemicals are applied to one side of the base substrate, while the second segment of the aroma chemicals are applied to an adjacent side of the base substrate of the sampler, whereby when the cover sheet is removed from the sampler, initially one segment of the sampler will deliver its fragrance to the atmosphere, and subsequently, as the cover sheet is fully removed, the second segment of the aroma chemicals will he released to the atmosphere. 3. The sampler of claim 2, and including a fold line provided between the first and second segments of the aroma chemicals, and the base substrate is folded along said fold line, such that when the sampler is opened, both segments of the aroma chemicals are released into the atmosphere simultaneously to provide its fragrance. 4. The sampler of claim 1, wherein the first segment of aroma chemicals is interspaced amongst a second segment of aroma chemicals, such that when the cover sheet is removed, the microencapsulated fragrances are released simultaneously to present their fragrance to the atmosphere. | 1,600 |
1,359 | 15,561,130 | 1,649 | This disclosure describes, in one aspect, immunogens effective for treating and/or diagnosing tauopathy, and immunotherapeutic compositions and methods involving those immunogens. Generally, the immunogen includes an antigen presentation component and a microtubule-associated tau protein (MAPT) component linked to at least a portion of the antigen presentation component. This disclosure describes, in another aspect, a transgenic mouse. Generally, the transgenic mouse possesses brain cells that have a polynucleotide that encodes human microtubule-associated protein tau (MAPT). The polynucleotide further exhibits a deletion of at least a portion of endogenous mouse MAPT. The transgenic mouse also includes a forebrain neuron-specific deletion of a polynucleotide that encodes Myeloid Differentiation Primary Response Gene 88 (MyD88). In a further aspect, this disclosure describes a method of producing the transgenic mouse. | 1. An immunogen comprising:
an antigen presentation component; and a microtubule-associated tau protein (MAPT) component linked to at least a portion of the antigen presentation component. 2. The immunogen of claim 1 wherein the MAPT component comprises at least one amino acid residue modified to comprise a PO3H2 group. 3. The immunogen of claim 2 wherein the MAPT component comprises the amino acid sequence of any one of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, or SEQ ID NO:33. 4. The immunogen of any preceding claim wherein the antigen presentation component comprises a virus-like particle (VLP). 5. The immunogen of any preceding claim wherein the VLP comprises bacteriophage Qβ or MS2. 6. The immunogen of any preceding claim wherein the antigen presenting component and the MAPT component are linked covalently. 7. The immunogen of claim 6 wherein the covalent link comprises a succinimidyl-6-[β-maleimidopropionamido]hexanoate (SMPH) linkage. 8. A pharmaceutical composition comprising the immunogen of any preceding claim. 9. The pharmaceutical composition of claim 8 further comprising an adjuvant. 10. A method of treating a subject having or at risk of having a tauopathic condition, the method comprising:
administering to the subject an amount of the immunogen of any one of claims 1-7 effective to ameliorate at least one symptom or clinical sign of the tauopathic condition. 11. The method of claim 10 wherein the tauopathic condition comprises Alzheimer's disease, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Pick's disease (PiD), frontotemporal dementia and Parkinsonism linked to chromosome-17 Tau Type (FTDP-17T), argyrophilic grain dementia (AGD), traumatic brain injury (TBI), or chronic traumatic encephalopathy (CTE). 12. The method of claim 10 or claim 11 wherein the symptom or clinical sign of the tauopathic condition comprises neurodegeneration or cognitive impairment. 13. The method of any one of claims 10-12 further comprising at least one anti-inflammatory strategy. 14. The method of claim 13 wherein the anti-inflammatory strategy comprises:
enrichment of IgG4 immunoglobulins;
removing RNA from the VLP component; or
enrichment of regulatory B cells that express IL-10. 15. The method of any one of claims 10-14 wherein the treatment is prophylactic. 16. The method of any one of claims 10-14 wherein the treatment is therapeutic. 17. A polynucleotide that encodes the immunogen of any one of claims 1-7. 18. A cell comprising the polynucleotide of claim 17. 19. A transgenic mouse line comprising:
brain cells that comprise:
a polynucleotide that encodes human microtubule-associated protein tau (MAPT); and
a deletion of at least a portion of endogenous mouse MAPT; and
a forebrain neuron-specific deletion of a polynucleotide that encodes Myeloid Differentiation Primary Response Gene 88 (MyD88). 20. The transgenic mouse of claim 19 wherein brain neurons exhibit reduced response to IL-1β. | This disclosure describes, in one aspect, immunogens effective for treating and/or diagnosing tauopathy, and immunotherapeutic compositions and methods involving those immunogens. Generally, the immunogen includes an antigen presentation component and a microtubule-associated tau protein (MAPT) component linked to at least a portion of the antigen presentation component. This disclosure describes, in another aspect, a transgenic mouse. Generally, the transgenic mouse possesses brain cells that have a polynucleotide that encodes human microtubule-associated protein tau (MAPT). The polynucleotide further exhibits a deletion of at least a portion of endogenous mouse MAPT. The transgenic mouse also includes a forebrain neuron-specific deletion of a polynucleotide that encodes Myeloid Differentiation Primary Response Gene 88 (MyD88). In a further aspect, this disclosure describes a method of producing the transgenic mouse.1. An immunogen comprising:
an antigen presentation component; and a microtubule-associated tau protein (MAPT) component linked to at least a portion of the antigen presentation component. 2. The immunogen of claim 1 wherein the MAPT component comprises at least one amino acid residue modified to comprise a PO3H2 group. 3. The immunogen of claim 2 wherein the MAPT component comprises the amino acid sequence of any one of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, or SEQ ID NO:33. 4. The immunogen of any preceding claim wherein the antigen presentation component comprises a virus-like particle (VLP). 5. The immunogen of any preceding claim wherein the VLP comprises bacteriophage Qβ or MS2. 6. The immunogen of any preceding claim wherein the antigen presenting component and the MAPT component are linked covalently. 7. The immunogen of claim 6 wherein the covalent link comprises a succinimidyl-6-[β-maleimidopropionamido]hexanoate (SMPH) linkage. 8. A pharmaceutical composition comprising the immunogen of any preceding claim. 9. The pharmaceutical composition of claim 8 further comprising an adjuvant. 10. A method of treating a subject having or at risk of having a tauopathic condition, the method comprising:
administering to the subject an amount of the immunogen of any one of claims 1-7 effective to ameliorate at least one symptom or clinical sign of the tauopathic condition. 11. The method of claim 10 wherein the tauopathic condition comprises Alzheimer's disease, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Pick's disease (PiD), frontotemporal dementia and Parkinsonism linked to chromosome-17 Tau Type (FTDP-17T), argyrophilic grain dementia (AGD), traumatic brain injury (TBI), or chronic traumatic encephalopathy (CTE). 12. The method of claim 10 or claim 11 wherein the symptom or clinical sign of the tauopathic condition comprises neurodegeneration or cognitive impairment. 13. The method of any one of claims 10-12 further comprising at least one anti-inflammatory strategy. 14. The method of claim 13 wherein the anti-inflammatory strategy comprises:
enrichment of IgG4 immunoglobulins;
removing RNA from the VLP component; or
enrichment of regulatory B cells that express IL-10. 15. The method of any one of claims 10-14 wherein the treatment is prophylactic. 16. The method of any one of claims 10-14 wherein the treatment is therapeutic. 17. A polynucleotide that encodes the immunogen of any one of claims 1-7. 18. A cell comprising the polynucleotide of claim 17. 19. A transgenic mouse line comprising:
brain cells that comprise:
a polynucleotide that encodes human microtubule-associated protein tau (MAPT); and
a deletion of at least a portion of endogenous mouse MAPT; and
a forebrain neuron-specific deletion of a polynucleotide that encodes Myeloid Differentiation Primary Response Gene 88 (MyD88). 20. The transgenic mouse of claim 19 wherein brain neurons exhibit reduced response to IL-1β. | 1,600 |
1,360 | 15,294,869 | 1,617 | The present invention provides novel insecticidal formulations comprising an effective concentration of: 1) at least one or more essential oils and an insecticidal soap; 2) at least one or more essential oils, an insecticidal soap, and pyrethrins; 3) at least one or more essential oils and pyrethrins; 4) at least one or more essential oils, an insecticidal soap and a synergist, such as sodium lauryl sulfate, sodium dodecyl sulfate or lecithin; 5) at least one or more essential oils, an insecticidal soap, a synergist, and pyrethrins; and 6) at least one or more essential oils, a synergist, and pyrethrins. A carrier oil, such as mineral oil, may be added to any of the foregoing formulations. | 1-39. (canceled) 40: An insecticidal composition comprising neem oil, pyrethrins, and an antioxidant selected from the group consisting of ethoxyquin, a tocopherol, and BHT. 41: The insecticidal composition of claim 40, wherein the amount of neem oil is about 0.25% to about 12% by weight, the amount of pyrethrins is about 0.01% to about 0.5% by weight, and the remainder is water and the antioxidant. 42: The insecticidal composition of claim 41, further comprising a carrier oil, and wherein the antioxidant is ethoxyquin. 43: A method of killing insects comprising applying the insecticidal composition of claim 40 to one or more insects. 44: A method of killing insects comprising applying the insecticidal composition of claim 41 to one or more insects. 45: A method of killing insects comprising applying the insecticidal composition of claim 42 to one or more insects. 46: An insecticidal composition comprising neem oil, pyrethrins, and an antioxidant selected from the group consisting of ethoxyquin, a tocopherol, and BHT, wherein the composition is sprayable. 47: The insecticidal composition of claim 46, wherein the amount of neem oil is about 0.25% to about 12% by weight, the amount of pyrethrins is about 0.01% to about 0.5% by weight, and the remainder is water and the antioxidant. 48: The insecticidal composition of claim 47, further comprising a carrier oil, and wherein the antioxidant is ethoxyquin. 49: A method of killing insects comprising spraying the insecticidal composition of claim 46 on one or more insects. 50: A method of killing insects comprising spraying the insecticidal composition of claim 47 to one or more insects. 51: A method of killing insects comprising spraying the insecticidal composition of claim 48 to one or more insects. 52: An insecticidal composition comprising neem oil, soap, pyrethrins, and an antioxidant selected from the group consisting of ethoxyquin, a tocopherol, and BHT. 53: The insecticidal composition of claim 52, wherein the amount of neem oil is about 0.25% to about 12% by weight, the amount of soap is about 0.5% to about 4% by weight, the amount of pyrethrins is about 0.01% to about 0.5% by weight, and the remainder is water and the antioxidant. 54: The insecticidal composition of claim 53, further comprising a carrier oil, and wherein the antioxidant is ethoxyquin. 55: A method of killing insects comprising applying the insecticidal composition of claim 52 to one or more insects. 56: A method of killing insects comprising applying the insecticidal composition of claim 53 to one or more insects. 57: A method of killing insects comprising applying the insecticidal composition of claim 54 to one or more insects. | The present invention provides novel insecticidal formulations comprising an effective concentration of: 1) at least one or more essential oils and an insecticidal soap; 2) at least one or more essential oils, an insecticidal soap, and pyrethrins; 3) at least one or more essential oils and pyrethrins; 4) at least one or more essential oils, an insecticidal soap and a synergist, such as sodium lauryl sulfate, sodium dodecyl sulfate or lecithin; 5) at least one or more essential oils, an insecticidal soap, a synergist, and pyrethrins; and 6) at least one or more essential oils, a synergist, and pyrethrins. A carrier oil, such as mineral oil, may be added to any of the foregoing formulations.1-39. (canceled) 40: An insecticidal composition comprising neem oil, pyrethrins, and an antioxidant selected from the group consisting of ethoxyquin, a tocopherol, and BHT. 41: The insecticidal composition of claim 40, wherein the amount of neem oil is about 0.25% to about 12% by weight, the amount of pyrethrins is about 0.01% to about 0.5% by weight, and the remainder is water and the antioxidant. 42: The insecticidal composition of claim 41, further comprising a carrier oil, and wherein the antioxidant is ethoxyquin. 43: A method of killing insects comprising applying the insecticidal composition of claim 40 to one or more insects. 44: A method of killing insects comprising applying the insecticidal composition of claim 41 to one or more insects. 45: A method of killing insects comprising applying the insecticidal composition of claim 42 to one or more insects. 46: An insecticidal composition comprising neem oil, pyrethrins, and an antioxidant selected from the group consisting of ethoxyquin, a tocopherol, and BHT, wherein the composition is sprayable. 47: The insecticidal composition of claim 46, wherein the amount of neem oil is about 0.25% to about 12% by weight, the amount of pyrethrins is about 0.01% to about 0.5% by weight, and the remainder is water and the antioxidant. 48: The insecticidal composition of claim 47, further comprising a carrier oil, and wherein the antioxidant is ethoxyquin. 49: A method of killing insects comprising spraying the insecticidal composition of claim 46 on one or more insects. 50: A method of killing insects comprising spraying the insecticidal composition of claim 47 to one or more insects. 51: A method of killing insects comprising spraying the insecticidal composition of claim 48 to one or more insects. 52: An insecticidal composition comprising neem oil, soap, pyrethrins, and an antioxidant selected from the group consisting of ethoxyquin, a tocopherol, and BHT. 53: The insecticidal composition of claim 52, wherein the amount of neem oil is about 0.25% to about 12% by weight, the amount of soap is about 0.5% to about 4% by weight, the amount of pyrethrins is about 0.01% to about 0.5% by weight, and the remainder is water and the antioxidant. 54: The insecticidal composition of claim 53, further comprising a carrier oil, and wherein the antioxidant is ethoxyquin. 55: A method of killing insects comprising applying the insecticidal composition of claim 52 to one or more insects. 56: A method of killing insects comprising applying the insecticidal composition of claim 53 to one or more insects. 57: A method of killing insects comprising applying the insecticidal composition of claim 54 to one or more insects. | 1,600 |
1,361 | 13,824,533 | 1,613 | A cosmetic composition includes, in a physiologically acceptable medium: at least water, at least alkylcellulose, at least one first hydrocarbon-based non-volatile oil, chosen from: C10-C26 alcohols, preferably monoalcohols; optionally hydroxylated monoesters, diesters or triesters of a C2-C8 monocarboxylic or polycarboxylic acid and of a C2-C8 alcohol; esters of a C2-C8 polyol and of one or more C2-C8 carboxylic acids. At least one second non-volatile oil chosen from silicone oils and/or fluoro oils or hydrocarbon-based oils other than the said first oil; at least one stabilizer chosen from surfactants and/or hydrophilic gelling agents, preferably chosen from associative polymers, natural polymers and their mixture. | 1. Cosmetic composition comprising, in a physiologically acceptable medium:
at least 5% by weight of water; at least alkylcellulose, the alkyl residue of which comprises between 1 and 6 carbon atoms; at least one first hydrocarbon-based non-volatile oil, chosen from: C10-C26 alcohols, optionally hydroxylated monoesters, diesters or triesters of an optionally hydroxylated C2-C8 monocarboxylic or polycarboxylic acid and of a C2-C8 alcohol; esters of a C2-C8 polyol and of one or more C2-C8 carboxylic acids. at least one second non-volatile oil chosen from silicone oils and/or fluoro oils or hydrocarbon-based oils other than the said first oil; at least one stabilizer chosen from surfactants and/or hydrophilic gelling agents, natural polymers or their mixture. 2. Composition according to claim 1, wherein the surfactant is chosen from nonionic and anionic surfactants. 3. Composition according to claim 1, comprising at least sodium lauryl sulfate and optionally an additional non ionic or anionic surfactant. 4. Composition according to claim 1, wherein it is in the form of an oil-in-water emulsion. 5. Composition according to claim 1, wherein the surfactant(s), if present, are in a content ranging from 0.1% to 20% by weight relative to the total weight of the composition, and/or in that the hydrophilic gelling agent, if present, is in a content ranging from 0.1% to 10% by weight relative to the total weight of the composition. 6. Composition according to claim 1, wherein the alkylcellulose is present in a content of between 1% and 60% by weight, relative to the total weight of the composition. 7. Composition according to claim 1, wherein the alkylcellulose is chosen from methylcellulose, ethylcellulose and propylcellulose. 8. Composition according to claim 1, wherein the said second non-volatile oil is chosen from phenyl silicone oils. 9. Composition according to claim 1, wherein it comprises a content ranging from 5% to 75% by weight of second non-volatile silicone oil(s) and/or fluoro oil(s) or hydrocarbon-based oil(s) other than the said first oil, in particular from 10% to 40% by weight and more particularly from 15% to 30% by weight, relative to its total weight. 10. Composition according to claim 1, wherein the said non-volatile hydrocarbon-based “first oil” is chosen from: C10-C26 monoalcohols such as lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, palmityl alcohol, oleyl alcohol, cetearyl alcohol (mixture of cetyl alcohol and stearyl alcohol), behenyl alcohol, erucyl alcohol, arachidyl alcohol, 2-hexyldecyl alcohol, isocetyl alcohol and octyldodecanol, and mixtures thereof;
optionally hydroxylated monoesters of a C2-C8 carboxylic acid and of a C2-C8 alcohol;
optionally hydroxylated diesters of a C2-C8 dicarboxylic acid and of a C2-C8 alcohol, such as diisopropyl adipate, 2-diethylhexyl adipate, dibutyl adipate or diisostearyl adipate;
optionally hydroxylated triesters of a C2-C8 tricarboxylic acid and of a C2-C8 alcohol, such as citric acid esters, such as trioctyl citrate, triethyl citrate, acetyl tributyl citrate, tributyl citrate or acetyl tributyl citrate;
esters of a C2-C8 polyol and of one or more C2-C8 carboxylic acids, such as glycol diesters of monoacids, such as neopentyl glycol diheptanoate, or glycol triesters of monoacids, such as triacetin. 11. Composition according to claim 1, wherein the said first non-volatile hydrocarbon-based oil is present in a content ranging from 5%) to 75%) by weight, in particular from 10%> to 50% by weight) by weight relative to the total weight of the composition. 12. Composition according to claim 1, in which the first non-volatile hydrocarbon-based oil and the alkylcellulose are used in the composition according to the invention in a first non-volatile hydrocarbon-based oil(s)/ethylcellulose weight ratio of between 1 and 20. 13. Composition according to claim 1, wherein it comprises between 5% and 80% by weight of water, relative to the total weight of the composition. 14. Composition according to claim 1, wherein it comprises:
between 4% and 30% by weight of alkylcellulose, between 15% and 50% by weight of water, between 45% and 75% by weight of non-volatile oils. 15. Composition according to claim 1, wherein it comprises at least one dyestuff. 16. Composition according to claim 1, wherein it comprises at least one compound chosen from fillers, waxes, pasty fatty substances, semi-crystalline polymers and/or lipophilic gelling agents, silicone gums, organopolysiloxane elastomers and silicone resins, and mixtures thereof. 17. Composition according to claim 1, wherein it is in liquid form. 18. Composition according to claim 1, the said composition being a composition for making up and/or caring for the lips or the skin, in particular the lips, and more particularly a lipstick. 19-20. (canceled) 21. Cosmetic process for making up and/or caring for the skin and/or the lips, in particular the lips, comprising at least one step that consists in applying to the skin and/or the lips at least one composition as defined according to claim 1. 22. A cosmetic process for making up and/or caring for the lips, comprising at least one step that consists in applying to the lips at least one cosmetic composition comprising, in a physiologically acceptable medium:
at least water; at least alkylcellulose, the alkyl residue of which comprises between 1 and 6 carbon atoms; at least one first hydrocarbon-based non-volatile oil, chosen from: C10-C26 alcohols, optionally hydroxylated monoesters, diesters or triesters of an optionally hydroxylated C2-C8 monocarboxylic or polycarboxylic acid and of a C2-C8 alcohol; esters of a C2-C8 polyol and of one or more C2-C8 carboxylic acids. at least one second non-volatile oil chosen from silicone oils and/or fluoro oils or hydrocarbon-based oils other than the said first oil; at least one stabilizer chosen from surfactants and/or hydrophilic gelling agents. 23. A process for preparing a composition as defined according to claim 1, wherein the alkylcellulose is used therein in the form of a stable aqueous dispersion. | A cosmetic composition includes, in a physiologically acceptable medium: at least water, at least alkylcellulose, at least one first hydrocarbon-based non-volatile oil, chosen from: C10-C26 alcohols, preferably monoalcohols; optionally hydroxylated monoesters, diesters or triesters of a C2-C8 monocarboxylic or polycarboxylic acid and of a C2-C8 alcohol; esters of a C2-C8 polyol and of one or more C2-C8 carboxylic acids. At least one second non-volatile oil chosen from silicone oils and/or fluoro oils or hydrocarbon-based oils other than the said first oil; at least one stabilizer chosen from surfactants and/or hydrophilic gelling agents, preferably chosen from associative polymers, natural polymers and their mixture.1. Cosmetic composition comprising, in a physiologically acceptable medium:
at least 5% by weight of water; at least alkylcellulose, the alkyl residue of which comprises between 1 and 6 carbon atoms; at least one first hydrocarbon-based non-volatile oil, chosen from: C10-C26 alcohols, optionally hydroxylated monoesters, diesters or triesters of an optionally hydroxylated C2-C8 monocarboxylic or polycarboxylic acid and of a C2-C8 alcohol; esters of a C2-C8 polyol and of one or more C2-C8 carboxylic acids. at least one second non-volatile oil chosen from silicone oils and/or fluoro oils or hydrocarbon-based oils other than the said first oil; at least one stabilizer chosen from surfactants and/or hydrophilic gelling agents, natural polymers or their mixture. 2. Composition according to claim 1, wherein the surfactant is chosen from nonionic and anionic surfactants. 3. Composition according to claim 1, comprising at least sodium lauryl sulfate and optionally an additional non ionic or anionic surfactant. 4. Composition according to claim 1, wherein it is in the form of an oil-in-water emulsion. 5. Composition according to claim 1, wherein the surfactant(s), if present, are in a content ranging from 0.1% to 20% by weight relative to the total weight of the composition, and/or in that the hydrophilic gelling agent, if present, is in a content ranging from 0.1% to 10% by weight relative to the total weight of the composition. 6. Composition according to claim 1, wherein the alkylcellulose is present in a content of between 1% and 60% by weight, relative to the total weight of the composition. 7. Composition according to claim 1, wherein the alkylcellulose is chosen from methylcellulose, ethylcellulose and propylcellulose. 8. Composition according to claim 1, wherein the said second non-volatile oil is chosen from phenyl silicone oils. 9. Composition according to claim 1, wherein it comprises a content ranging from 5% to 75% by weight of second non-volatile silicone oil(s) and/or fluoro oil(s) or hydrocarbon-based oil(s) other than the said first oil, in particular from 10% to 40% by weight and more particularly from 15% to 30% by weight, relative to its total weight. 10. Composition according to claim 1, wherein the said non-volatile hydrocarbon-based “first oil” is chosen from: C10-C26 monoalcohols such as lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, palmityl alcohol, oleyl alcohol, cetearyl alcohol (mixture of cetyl alcohol and stearyl alcohol), behenyl alcohol, erucyl alcohol, arachidyl alcohol, 2-hexyldecyl alcohol, isocetyl alcohol and octyldodecanol, and mixtures thereof;
optionally hydroxylated monoesters of a C2-C8 carboxylic acid and of a C2-C8 alcohol;
optionally hydroxylated diesters of a C2-C8 dicarboxylic acid and of a C2-C8 alcohol, such as diisopropyl adipate, 2-diethylhexyl adipate, dibutyl adipate or diisostearyl adipate;
optionally hydroxylated triesters of a C2-C8 tricarboxylic acid and of a C2-C8 alcohol, such as citric acid esters, such as trioctyl citrate, triethyl citrate, acetyl tributyl citrate, tributyl citrate or acetyl tributyl citrate;
esters of a C2-C8 polyol and of one or more C2-C8 carboxylic acids, such as glycol diesters of monoacids, such as neopentyl glycol diheptanoate, or glycol triesters of monoacids, such as triacetin. 11. Composition according to claim 1, wherein the said first non-volatile hydrocarbon-based oil is present in a content ranging from 5%) to 75%) by weight, in particular from 10%> to 50% by weight) by weight relative to the total weight of the composition. 12. Composition according to claim 1, in which the first non-volatile hydrocarbon-based oil and the alkylcellulose are used in the composition according to the invention in a first non-volatile hydrocarbon-based oil(s)/ethylcellulose weight ratio of between 1 and 20. 13. Composition according to claim 1, wherein it comprises between 5% and 80% by weight of water, relative to the total weight of the composition. 14. Composition according to claim 1, wherein it comprises:
between 4% and 30% by weight of alkylcellulose, between 15% and 50% by weight of water, between 45% and 75% by weight of non-volatile oils. 15. Composition according to claim 1, wherein it comprises at least one dyestuff. 16. Composition according to claim 1, wherein it comprises at least one compound chosen from fillers, waxes, pasty fatty substances, semi-crystalline polymers and/or lipophilic gelling agents, silicone gums, organopolysiloxane elastomers and silicone resins, and mixtures thereof. 17. Composition according to claim 1, wherein it is in liquid form. 18. Composition according to claim 1, the said composition being a composition for making up and/or caring for the lips or the skin, in particular the lips, and more particularly a lipstick. 19-20. (canceled) 21. Cosmetic process for making up and/or caring for the skin and/or the lips, in particular the lips, comprising at least one step that consists in applying to the skin and/or the lips at least one composition as defined according to claim 1. 22. A cosmetic process for making up and/or caring for the lips, comprising at least one step that consists in applying to the lips at least one cosmetic composition comprising, in a physiologically acceptable medium:
at least water; at least alkylcellulose, the alkyl residue of which comprises between 1 and 6 carbon atoms; at least one first hydrocarbon-based non-volatile oil, chosen from: C10-C26 alcohols, optionally hydroxylated monoesters, diesters or triesters of an optionally hydroxylated C2-C8 monocarboxylic or polycarboxylic acid and of a C2-C8 alcohol; esters of a C2-C8 polyol and of one or more C2-C8 carboxylic acids. at least one second non-volatile oil chosen from silicone oils and/or fluoro oils or hydrocarbon-based oils other than the said first oil; at least one stabilizer chosen from surfactants and/or hydrophilic gelling agents. 23. A process for preparing a composition as defined according to claim 1, wherein the alkylcellulose is used therein in the form of a stable aqueous dispersion. | 1,600 |
1,362 | 14,841,898 | 1,619 | Formulations of mazindol having superior stability and methods of administering same are provided. The formulations may be immediate, enhanced, or otherwise delayed release formulations of mazindol. | 1. A modified release formulation of mazindol comprising mazindol as an active pharmaceutical ingredient, at least one release controlling polymer selected from pH-dependent polymers and pH-independent polymers, and at least one pharmaceutically acceptable excipient, wherein the total amount of water in the formulation is not more than 5% by weight of the formulation. 2. The formulation of claim 1 comprising: a first mazindol-containing component selected from an extended release component and a delayed release component and a second mazindol-containing component selected from an immediate release component, an extended release component and a delayed release component, wherein each delayed release component comprises from 5% to 99% by weight of the formulation of at least one pH-dependent polymer and said extended release component comprises from 5% to 99% by weight of the formulation of a pH-independent polymer. 3. The formulation of claim 1 for once-a-day administration or twice-a-day administration. 4. The formulation of claim 1 comprising from 0.1 mg to 20 mg of mazindol. 5. The formulation of claim 1, wherein said first component comprises a plurality of the delayed release mazindol-containing pellets, and said second component comprises a plurality of the mazindol-containing pellets selected from the immediate release pellets, extended release pellets and delayed release pellets, wherein said delayed release pellets comprise an immediate release core or an extended release core coated with a delayed release coating, and said extended release pellet comprises an extended release core or an immediate release core coated with a layer of a pH-independent polymer. 6. The formulation of claim 2, wherein said first component comprises a plurality of the extended release mazindol-containing pellets, and said second component comprises a plurality of the mazindol-containing pellets selected from the immediate release pellets and extended release pellets. 7. The formulation of claim 2, wherein said first component comprises a mazindol-containing core coated with a delayed release coating, and said second component comprises an immediate release drug layer or an extended release drug layer coated on top of the delayed release coating. 8. The formulation of claim 7, wherein said mazindol-containing core is an immediate release core or an extended release core. 9. The formulation of claim 8, wherein said extended release core comprises an immediate release core coated with a coating of the pH-independent polymer or mazindol admixed with at least one pH-independent polymer. 10. The formulation of claim 7, wherein said second component further comprises a coating of the pH-independent polymer on top of the immediate release drug layer. 11. The formulation of claim 7, wherein said extended release drug layer comprises mazindol admixed with at least one pH-independent polymer. 12. The formulation of claim 1 comprising an osmotic core comprising mazindol and at least one pharmaceutically acceptable excipient, and a semipermeable rate-controlling membrane immediately surrounding said core. 13. The formulation of claim 12 additionally comprising a mazindol-containing layer on top of the semipermeable rate-controlling membrane. 14. The formulation of claim 13, wherein said mazindol-containing layer is of an immediate release, extended release or delayed release. 15. The formulation of claim 1 additionally comprising a stabilizer selected from an acidifying agent or a hydrophobizing agent. 16. The formulation of claim 2, wherein at least one excipient is a low-moisture excipient selected from bulking agents, fillers, lubricants, wetting and solubility enhancing agents and dispersants. 17. The formulation of claim 1, wherein said pH-dependent polymer is selected from a group consisting of poly(methyl acrylate-co-methyl methacrylate-co-methacrylic acid), poly(methacrylic acid-co-methyl methacrylate), hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, shellac, and zein. 18. The formulation of claim 1, wherein said pH-independent polymer is selected from a group consisting of hydroxypropyl cellulose, hypromellose (hydroxypropyl methyl cellulose), methyl cellulose, polyethylene oxide, acacia, carbomer homopolymer type A NF; carbomer homopolymer type B NF, hydroxyethyl cellulose, carrageenan, tragacanth, xanthan gum, povidone, alginic acid and salts thereof, polyvinyl alcohol, carboxymethylcellulose; ethylcellulose, cellulose acetate, cellulose acetate butyrate, poly(ethyl acrylate-co-methyl methacrylate) ethyl acrylate methyl methacrylate copolymer, poly(ethyl acrylate-co-methyl methacrylate-cotrimethylammonioethyl methacrylate chloride), polyvinyl acetate, and cellulose acetate propionate. 19. The formulation of claim 1 further comprising 2-(2-Aminoethyl)-3-(4-chlorophenyl)-3-hydroxy-2,3-dihydro-1H-isoindol-1-one. 20. An immediate release formulation of mazindol comprising mazindol as an active pharmaceutical ingredient and at least one pharmaceutically acceptable excipient, wherein the total amount of water in the formulation is not more than 5% by weight of the formulation. 21. The formulation of claim 1 in a dosage form selected from tablets, osmotic tablets, matrix tablets, mini tablets, capsules, beads, granules, powders, caplets, troches, sachets, cachets, pouches, gums, sprinkles, solutions and suspensions. 22. A method of treating ADHD comprising administering to a subject in need thereof an effective amount of a dosage form of claim 21. 23. The formulation of claim 20 in a dosage form selected from tablets, osmotic tablets, matrix tablets, mini tablets, capsules, beads, granules, powders, caplets, troches, sachets, cachets, pouches, gums, sprinkles, solutions and suspensions. | Formulations of mazindol having superior stability and methods of administering same are provided. The formulations may be immediate, enhanced, or otherwise delayed release formulations of mazindol.1. A modified release formulation of mazindol comprising mazindol as an active pharmaceutical ingredient, at least one release controlling polymer selected from pH-dependent polymers and pH-independent polymers, and at least one pharmaceutically acceptable excipient, wherein the total amount of water in the formulation is not more than 5% by weight of the formulation. 2. The formulation of claim 1 comprising: a first mazindol-containing component selected from an extended release component and a delayed release component and a second mazindol-containing component selected from an immediate release component, an extended release component and a delayed release component, wherein each delayed release component comprises from 5% to 99% by weight of the formulation of at least one pH-dependent polymer and said extended release component comprises from 5% to 99% by weight of the formulation of a pH-independent polymer. 3. The formulation of claim 1 for once-a-day administration or twice-a-day administration. 4. The formulation of claim 1 comprising from 0.1 mg to 20 mg of mazindol. 5. The formulation of claim 1, wherein said first component comprises a plurality of the delayed release mazindol-containing pellets, and said second component comprises a plurality of the mazindol-containing pellets selected from the immediate release pellets, extended release pellets and delayed release pellets, wherein said delayed release pellets comprise an immediate release core or an extended release core coated with a delayed release coating, and said extended release pellet comprises an extended release core or an immediate release core coated with a layer of a pH-independent polymer. 6. The formulation of claim 2, wherein said first component comprises a plurality of the extended release mazindol-containing pellets, and said second component comprises a plurality of the mazindol-containing pellets selected from the immediate release pellets and extended release pellets. 7. The formulation of claim 2, wherein said first component comprises a mazindol-containing core coated with a delayed release coating, and said second component comprises an immediate release drug layer or an extended release drug layer coated on top of the delayed release coating. 8. The formulation of claim 7, wherein said mazindol-containing core is an immediate release core or an extended release core. 9. The formulation of claim 8, wherein said extended release core comprises an immediate release core coated with a coating of the pH-independent polymer or mazindol admixed with at least one pH-independent polymer. 10. The formulation of claim 7, wherein said second component further comprises a coating of the pH-independent polymer on top of the immediate release drug layer. 11. The formulation of claim 7, wherein said extended release drug layer comprises mazindol admixed with at least one pH-independent polymer. 12. The formulation of claim 1 comprising an osmotic core comprising mazindol and at least one pharmaceutically acceptable excipient, and a semipermeable rate-controlling membrane immediately surrounding said core. 13. The formulation of claim 12 additionally comprising a mazindol-containing layer on top of the semipermeable rate-controlling membrane. 14. The formulation of claim 13, wherein said mazindol-containing layer is of an immediate release, extended release or delayed release. 15. The formulation of claim 1 additionally comprising a stabilizer selected from an acidifying agent or a hydrophobizing agent. 16. The formulation of claim 2, wherein at least one excipient is a low-moisture excipient selected from bulking agents, fillers, lubricants, wetting and solubility enhancing agents and dispersants. 17. The formulation of claim 1, wherein said pH-dependent polymer is selected from a group consisting of poly(methyl acrylate-co-methyl methacrylate-co-methacrylic acid), poly(methacrylic acid-co-methyl methacrylate), hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, shellac, and zein. 18. The formulation of claim 1, wherein said pH-independent polymer is selected from a group consisting of hydroxypropyl cellulose, hypromellose (hydroxypropyl methyl cellulose), methyl cellulose, polyethylene oxide, acacia, carbomer homopolymer type A NF; carbomer homopolymer type B NF, hydroxyethyl cellulose, carrageenan, tragacanth, xanthan gum, povidone, alginic acid and salts thereof, polyvinyl alcohol, carboxymethylcellulose; ethylcellulose, cellulose acetate, cellulose acetate butyrate, poly(ethyl acrylate-co-methyl methacrylate) ethyl acrylate methyl methacrylate copolymer, poly(ethyl acrylate-co-methyl methacrylate-cotrimethylammonioethyl methacrylate chloride), polyvinyl acetate, and cellulose acetate propionate. 19. The formulation of claim 1 further comprising 2-(2-Aminoethyl)-3-(4-chlorophenyl)-3-hydroxy-2,3-dihydro-1H-isoindol-1-one. 20. An immediate release formulation of mazindol comprising mazindol as an active pharmaceutical ingredient and at least one pharmaceutically acceptable excipient, wherein the total amount of water in the formulation is not more than 5% by weight of the formulation. 21. The formulation of claim 1 in a dosage form selected from tablets, osmotic tablets, matrix tablets, mini tablets, capsules, beads, granules, powders, caplets, troches, sachets, cachets, pouches, gums, sprinkles, solutions and suspensions. 22. A method of treating ADHD comprising administering to a subject in need thereof an effective amount of a dosage form of claim 21. 23. The formulation of claim 20 in a dosage form selected from tablets, osmotic tablets, matrix tablets, mini tablets, capsules, beads, granules, powders, caplets, troches, sachets, cachets, pouches, gums, sprinkles, solutions and suspensions. | 1,600 |
1,363 | 16,228,996 | 1,612 | Disclosed is an anhydrous makeup removing composition and method for removing making using such a composition. The composition includes at least two esters having a molecular weight less than 350 g/mol and a polarity index of less than or equal to 24.2 mN/m, where the composition contains less than 5 w/w % of any esters having molecular weights greater than 350 g/mol or having a polarity index greater than 24.2 mN/m, or any non-ester hydrocarbons. The esters may have a surface tension as measured at 20° C. of less than 40 dynes/cm, and the composition may also include additional components, such as a filler particle, a dye, a polymeric thickener, a preservative, and/or a fragrance. In some embodiments, the composition may consist solely of between two and four such esters, and in various embodiments, may be a solution, a gel, or an emulsion. | 1. An anhydrous makeup removing composition, comprising:
at least three esters having a molecular weight less than 350 g/mol and a polarity index of less than or equal to 24.2 mN/m, wherein the composition contains less than 5 w/w % of any esters having molecular weights greater than 350 g/mol or having a polarity index greater than 24.2 mN/m, or any non-ester hydrocarbons, and wherein two of the at least three esters comprise are diisopropyl sebacate and isopropyl myristate. 2. (canceled) 3. The anhydrous makeup removing composition according to claim 1, wherein the composition is a solution, a gel, or an emulsion. 4. The anhydrous makeup removing composition according to claim 1, further comprising at least one additional material selected from the group consisting of a filler particle, a dye, a polymeric thickener, a preservative, and a fragrance. 5. The anhydrous makeup removing composition according to claim 1, wherein the at least three esters are present in the composition in a total amount greater than 50 w/w % of the entire composition. 6. The anhydrous makeup removing composition according to claim 1, wherein the at least three esters are present in the composition in a total amount greater than 90 w/w % of the entire composition. 7. The anhydrous makeup removing composition according to claim 1, wherein the composition consists of the at least three esters. 8. The anhydrous makeup removing composition according to claim 1, wherein the composition consists of the at least three esters and at least one filler particle. 9. The anhydrous makeup removing composition according to claim 1, wherein the composition does not contain any silicones. 10. The anhydrous makeup removing composition according to claim 1, wherein each of the at least three esters have a surface tension as measured at 20° C. of less than 40 dynes/cm. 11. A method for removing makeup, comprising the steps of:
applying an anhydrous makeup removing composition to a keratin material to which makeup has been applied, the makeup removing composition comprising at least three esters having a molecular weight less than 350 g/mol and a polarity index of less than or equal to 24.2 mN/m, and where the composition contains less than 5 w/w % of any esters having molecular weights greater than 350 g/mol or having a polarity index greater than 24.2 mN/m, or any non-ester hydrocarbons; and wiping the makeup and the makeup removing composition from the keratin material, wherein two of the at least three esters are diisopropyl sebacate and isopropyl myristate. 12. (canceled) 13. The method according to claim 11, wherein the anhydrous makeup removing composition is a solution, a gel, or an emulsion. 14. The method according to claim 11, wherein the anhydrous makeup removing composition further comprises at least one filler particle. 15. The method according to claim 11, wherein the at least three esters are present in the composition in an amount greater than 50 w/w % of the entire composition. 16. The method according to claim 11, wherein the at least three esters are present in the composition in an amount greater than 90 w/w % of the entire composition. 17. The method according to claim 11, wherein the anhydrous makeup removing composition consists of the at least three esters. 18. The anhydrous makeup removing composition according to claim 11, wherein the anhydrous makeup removing composition consists of the at least three esters and at least one filler particle. 19. The method according to claim 11, wherein the composition does not contain any silicones. 20. The method according to claim 11, wherein each of the at least three esters have a surface tension as measured at 20° C. of less than 40 dynes/cm. 21. An anhydrous makeup removing composition, comprising:
two or more esters having a molecular weight less than 350 g/mol and a polarity index of less than or equal to 24.2 mN/m, wherein the composition contains less than 5 w/w % of any esters having molecular weights greater than 350 g/mol or having a polarity index greater than 24.2 mN/m, or any non-ester hydrocarbons, wherein two of the two or more esters are diisopropyl sebacate and isopropyl myristate. 22. The anhydrous makeup removing composition according to claim 1, wherein each of the diisopropyl sebacate and isopropyl myristate are present in amounts of between 20% and 50% by weight in the formula. | Disclosed is an anhydrous makeup removing composition and method for removing making using such a composition. The composition includes at least two esters having a molecular weight less than 350 g/mol and a polarity index of less than or equal to 24.2 mN/m, where the composition contains less than 5 w/w % of any esters having molecular weights greater than 350 g/mol or having a polarity index greater than 24.2 mN/m, or any non-ester hydrocarbons. The esters may have a surface tension as measured at 20° C. of less than 40 dynes/cm, and the composition may also include additional components, such as a filler particle, a dye, a polymeric thickener, a preservative, and/or a fragrance. In some embodiments, the composition may consist solely of between two and four such esters, and in various embodiments, may be a solution, a gel, or an emulsion.1. An anhydrous makeup removing composition, comprising:
at least three esters having a molecular weight less than 350 g/mol and a polarity index of less than or equal to 24.2 mN/m, wherein the composition contains less than 5 w/w % of any esters having molecular weights greater than 350 g/mol or having a polarity index greater than 24.2 mN/m, or any non-ester hydrocarbons, and wherein two of the at least three esters comprise are diisopropyl sebacate and isopropyl myristate. 2. (canceled) 3. The anhydrous makeup removing composition according to claim 1, wherein the composition is a solution, a gel, or an emulsion. 4. The anhydrous makeup removing composition according to claim 1, further comprising at least one additional material selected from the group consisting of a filler particle, a dye, a polymeric thickener, a preservative, and a fragrance. 5. The anhydrous makeup removing composition according to claim 1, wherein the at least three esters are present in the composition in a total amount greater than 50 w/w % of the entire composition. 6. The anhydrous makeup removing composition according to claim 1, wherein the at least three esters are present in the composition in a total amount greater than 90 w/w % of the entire composition. 7. The anhydrous makeup removing composition according to claim 1, wherein the composition consists of the at least three esters. 8. The anhydrous makeup removing composition according to claim 1, wherein the composition consists of the at least three esters and at least one filler particle. 9. The anhydrous makeup removing composition according to claim 1, wherein the composition does not contain any silicones. 10. The anhydrous makeup removing composition according to claim 1, wherein each of the at least three esters have a surface tension as measured at 20° C. of less than 40 dynes/cm. 11. A method for removing makeup, comprising the steps of:
applying an anhydrous makeup removing composition to a keratin material to which makeup has been applied, the makeup removing composition comprising at least three esters having a molecular weight less than 350 g/mol and a polarity index of less than or equal to 24.2 mN/m, and where the composition contains less than 5 w/w % of any esters having molecular weights greater than 350 g/mol or having a polarity index greater than 24.2 mN/m, or any non-ester hydrocarbons; and wiping the makeup and the makeup removing composition from the keratin material, wherein two of the at least three esters are diisopropyl sebacate and isopropyl myristate. 12. (canceled) 13. The method according to claim 11, wherein the anhydrous makeup removing composition is a solution, a gel, or an emulsion. 14. The method according to claim 11, wherein the anhydrous makeup removing composition further comprises at least one filler particle. 15. The method according to claim 11, wherein the at least three esters are present in the composition in an amount greater than 50 w/w % of the entire composition. 16. The method according to claim 11, wherein the at least three esters are present in the composition in an amount greater than 90 w/w % of the entire composition. 17. The method according to claim 11, wherein the anhydrous makeup removing composition consists of the at least three esters. 18. The anhydrous makeup removing composition according to claim 11, wherein the anhydrous makeup removing composition consists of the at least three esters and at least one filler particle. 19. The method according to claim 11, wherein the composition does not contain any silicones. 20. The method according to claim 11, wherein each of the at least three esters have a surface tension as measured at 20° C. of less than 40 dynes/cm. 21. An anhydrous makeup removing composition, comprising:
two or more esters having a molecular weight less than 350 g/mol and a polarity index of less than or equal to 24.2 mN/m, wherein the composition contains less than 5 w/w % of any esters having molecular weights greater than 350 g/mol or having a polarity index greater than 24.2 mN/m, or any non-ester hydrocarbons, wherein two of the two or more esters are diisopropyl sebacate and isopropyl myristate. 22. The anhydrous makeup removing composition according to claim 1, wherein each of the diisopropyl sebacate and isopropyl myristate are present in amounts of between 20% and 50% by weight in the formula. | 1,600 |
1,364 | 13,490,852 | 1,631 | Methods for ex vivo perfusion of organs (and/or tissues) with a perfusate designed to condition the organ with the desired effect being that upon transplant, said organ, having been administered said perfusate, is less likely to experience delayed graft function, deleterious effects of ischemia/reperfusion injury, including inflammatory reactions, and/or other detrimental responses that can injure the organ or recipient including precipitating or enhancing an immunological reaction from the recipient with the potential of compromising the graft's and/or recipients short teen and/or long term health and proper functionality while monitoring, sustaining and/or restoring the viability of the organ and preserving the organ for storage and/or transport. | 1. A method of determining parameters for maintaining viability of at least one organ in at least one device selected from an organ transporter, perfusion apparatus, cassette, and organ diagnostic apparatus, the method comprising:
forming a data record by uploading to a processor compiled data comprising:
data relating to one or more qualitative and/or quantitative relationships of one or more predetermined biomarkers while organs were preserved, transported and/or stored in at least one device selected from an organ transporter, perfusion apparatus, cassette, and organ diagnostic apparatus; and events occurring while organs were transported and/or stored in at least one device selected from an organ transporter, perfusion apparatus, cassette, and organ diagnostic apparatus, and
data relating to outcomes of transplantation of said organs; and
using the same processor or a different processor to determine transport parameters of the at least one device or a different device, based on the data record, for maintaining viability of at least one other organ. 2. A method of monitoring, maintaining, and/or restoring viability of at least one organ in at least one device selected from an organ transporter, perfusion apparatus, cassette, and organ diagnostic apparatus, the method comprising:
monitoring data comprising information relating to one or more qualitative and/or quantitative relationships of one or more predetermined biomarkers while the at least one organ is preserved, transported and/or stored in at least one device selected from an organ transporter, perfusion apparatus, cassette, and organ diagnostic apparatus, and events occurring while the at least one organ is present in the at least one of an organ transporter, perfusion apparatus, cassette, and/or organ diagnostic apparatus to form a data record; and connecting the at least one of the organ transporter, perfusion apparatus, cassette, and/or organ diagnostic apparatus to a network through wiring or wirelessly, and uploading the data record to a database. 3. A method of transporting and/or storing at least one organ in at least one device selected from an organ transporter, perfusion apparatus, cassette, and/or organ diagnostic apparatus, the method comprising:
adjusting transport and/or storage parameters of at least one device for the transport and/or storage of at least one organ based on a data record of organ transport and/or storage, the data record comprising: information relating to one or more qualitative and/or quantitative relationships of one or more predetermined biomarkers while the at least one same or different organ was preserved, transported and/or stored in at least one device selected from an organ transporter, perfusion apparatus, cassette, and organ diagnostic apparatus, and events occurring while the at least one same or different organ was transported and/or stored in a least one same or different device, wherein the information is cross-referenced to outcome data relating to outcomes of transplantation of the at least one same or different organ that was transported and/or stored. 4. The method of claim 1, further comprising:
disseminating the data record. 5. The method of claim 1, further comprising:
storing the data record in a database. 6. The method of claim 1, further comprising:
transmitting the data record over a network. 7. The method of claim 6, wherein the network is at least one of a local area network and the World Wide Web. 8. The method of claim 1, wherein the same processor or different processor at least one of manages, tracks, monitors, and diagnoses the at least one other organ. 9. The method of claim 1, wherein the at least one same or different organ transporter is configured with a wireless communications setup to provide real-time data transfer. 10. The method of claim 1, further comprising:
producing an organ viability index for the at least one other organ. 11. The method of claim 2, further comprising:
transferring the data to a memory device, wherein the data record is transferred to the memory device before connecting at least one of the transporter, perfusion apparatus, cassette, and organ diagnostic apparatus to the network. 12. The method of claim 2, further comprising at least one of displaying, accessing, and uploading the data record from the database via either the same network or a different network connected to the database. 13. The method of claim 12, wherein the same or different network is at least one of a local area network and the World Wide Web. 14. The method of claim 2, further comprising:
transferring the data record to a remote location for at least one of managing, tracking, monitoring, and diagnosing the at least one organ. 15. The method of claim 2, wherein at least one of the transporter, perfusion apparatus, cassette, and organ diagnostic apparatus is configured with a wireless communications setup to provide real-time data transfer. 16. The method of claim 2, further comprising:
producing a first organ viability index based on the data record. 17. The method of claim 16, further comprising:
making organ therapy decisions based on the first organ viability index. 18. The method of claim 17, further comprising:
comparing the first organ viability index with a second organ viability index. 19. The method of claim 3, further comprising:
receiving the data record over a wireless network. 20. The method of claim 3, wherein the data record is obtained from a database computer. 21. The method of claim 19, wherein the database computer at least one of manages, tracks, monitors, and diagnoses the at least one organ in the at least one device in real-time. 22. The method of claim 3, further comprising at least one of displaying, accessing, and downloading the data record via a network. 23. The method of claim 3, wherein the at least one device is configured with a wireless communications setup to provide real-time data transfer. 24. The method of claim 3, wherein the information is cross-referenced to outcome data at the same location at which the at least one device is located. 25. The method of claim 2, further comprising:
producing an organ viability index of the at least one organ. | Methods for ex vivo perfusion of organs (and/or tissues) with a perfusate designed to condition the organ with the desired effect being that upon transplant, said organ, having been administered said perfusate, is less likely to experience delayed graft function, deleterious effects of ischemia/reperfusion injury, including inflammatory reactions, and/or other detrimental responses that can injure the organ or recipient including precipitating or enhancing an immunological reaction from the recipient with the potential of compromising the graft's and/or recipients short teen and/or long term health and proper functionality while monitoring, sustaining and/or restoring the viability of the organ and preserving the organ for storage and/or transport.1. A method of determining parameters for maintaining viability of at least one organ in at least one device selected from an organ transporter, perfusion apparatus, cassette, and organ diagnostic apparatus, the method comprising:
forming a data record by uploading to a processor compiled data comprising:
data relating to one or more qualitative and/or quantitative relationships of one or more predetermined biomarkers while organs were preserved, transported and/or stored in at least one device selected from an organ transporter, perfusion apparatus, cassette, and organ diagnostic apparatus; and events occurring while organs were transported and/or stored in at least one device selected from an organ transporter, perfusion apparatus, cassette, and organ diagnostic apparatus, and
data relating to outcomes of transplantation of said organs; and
using the same processor or a different processor to determine transport parameters of the at least one device or a different device, based on the data record, for maintaining viability of at least one other organ. 2. A method of monitoring, maintaining, and/or restoring viability of at least one organ in at least one device selected from an organ transporter, perfusion apparatus, cassette, and organ diagnostic apparatus, the method comprising:
monitoring data comprising information relating to one or more qualitative and/or quantitative relationships of one or more predetermined biomarkers while the at least one organ is preserved, transported and/or stored in at least one device selected from an organ transporter, perfusion apparatus, cassette, and organ diagnostic apparatus, and events occurring while the at least one organ is present in the at least one of an organ transporter, perfusion apparatus, cassette, and/or organ diagnostic apparatus to form a data record; and connecting the at least one of the organ transporter, perfusion apparatus, cassette, and/or organ diagnostic apparatus to a network through wiring or wirelessly, and uploading the data record to a database. 3. A method of transporting and/or storing at least one organ in at least one device selected from an organ transporter, perfusion apparatus, cassette, and/or organ diagnostic apparatus, the method comprising:
adjusting transport and/or storage parameters of at least one device for the transport and/or storage of at least one organ based on a data record of organ transport and/or storage, the data record comprising: information relating to one or more qualitative and/or quantitative relationships of one or more predetermined biomarkers while the at least one same or different organ was preserved, transported and/or stored in at least one device selected from an organ transporter, perfusion apparatus, cassette, and organ diagnostic apparatus, and events occurring while the at least one same or different organ was transported and/or stored in a least one same or different device, wherein the information is cross-referenced to outcome data relating to outcomes of transplantation of the at least one same or different organ that was transported and/or stored. 4. The method of claim 1, further comprising:
disseminating the data record. 5. The method of claim 1, further comprising:
storing the data record in a database. 6. The method of claim 1, further comprising:
transmitting the data record over a network. 7. The method of claim 6, wherein the network is at least one of a local area network and the World Wide Web. 8. The method of claim 1, wherein the same processor or different processor at least one of manages, tracks, monitors, and diagnoses the at least one other organ. 9. The method of claim 1, wherein the at least one same or different organ transporter is configured with a wireless communications setup to provide real-time data transfer. 10. The method of claim 1, further comprising:
producing an organ viability index for the at least one other organ. 11. The method of claim 2, further comprising:
transferring the data to a memory device, wherein the data record is transferred to the memory device before connecting at least one of the transporter, perfusion apparatus, cassette, and organ diagnostic apparatus to the network. 12. The method of claim 2, further comprising at least one of displaying, accessing, and uploading the data record from the database via either the same network or a different network connected to the database. 13. The method of claim 12, wherein the same or different network is at least one of a local area network and the World Wide Web. 14. The method of claim 2, further comprising:
transferring the data record to a remote location for at least one of managing, tracking, monitoring, and diagnosing the at least one organ. 15. The method of claim 2, wherein at least one of the transporter, perfusion apparatus, cassette, and organ diagnostic apparatus is configured with a wireless communications setup to provide real-time data transfer. 16. The method of claim 2, further comprising:
producing a first organ viability index based on the data record. 17. The method of claim 16, further comprising:
making organ therapy decisions based on the first organ viability index. 18. The method of claim 17, further comprising:
comparing the first organ viability index with a second organ viability index. 19. The method of claim 3, further comprising:
receiving the data record over a wireless network. 20. The method of claim 3, wherein the data record is obtained from a database computer. 21. The method of claim 19, wherein the database computer at least one of manages, tracks, monitors, and diagnoses the at least one organ in the at least one device in real-time. 22. The method of claim 3, further comprising at least one of displaying, accessing, and downloading the data record via a network. 23. The method of claim 3, wherein the at least one device is configured with a wireless communications setup to provide real-time data transfer. 24. The method of claim 3, wherein the information is cross-referenced to outcome data at the same location at which the at least one device is located. 25. The method of claim 2, further comprising:
producing an organ viability index of the at least one organ. | 1,600 |
1,365 | 14,229,624 | 1,612 | L-serine, L-serine precursors, L-serine derivatives and L-serine conjugates for treatment, amelioration and/or prevention of protein aggregation/tangles/plaques and diseases associated with protein aggregation/tangles/plaques. In particular, treatments and uses for L-serine, L-serine precursors, L-serine derivatives and L-serine conjugates include Alzheimer's disease (AD), Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), and Huntington disease (HD). | 1. A non-human primate model of a neurodegnerative disease, wherein the model is produced by administration of BMAA to the non-human primate. 2. The non-human primate model of claim 1, wherein the non-human primate is a vervet. 3. The non-human primate of claim 1, wherein the neurodegnerative disease comprises Alzheimer's disease. 4. The non-human primate model of claim 1, wherein neuroproteins of the non-human primate misfold or form aggregates. 5. A method for identifying an agent for treatment of a neurodegnerative disease comprising:
a) contacting the non-human primate model of claim 1 with a candidate agent; and b) determining if the candidate agent inhibits or reduces neuroprotein misfolding or neuroprotein aggregates in the non-human primate model of claim 1, wherein an inhibition or reduction neuroprotein misfolding or neuroprotein aggregates identifies the candidate agent as an agent for treatment of a neurodegnerative disease. 6. A method for identifying an agent for prophylactic treatment of a neurodegnerative disease comprising:
a) contacting a non-human primate prior to administration of BMAA with a candidate agent; b) administering BMAA to the non-human primate; and c) determining if the candidate agent inhibits or reduces neuroprotein misfolding or neuroprotein aggregates in the non-human primate administered, wherein an inhibition or reduction neuroprotein misfolding or neuroprotein aggregates identifies the candidate agent as an agent for prophylactic treatment of a neurodegnerative disease. 7. The method of claim 5 or 6, wherein the non-human primate is a vervet. 8. The method of claim 5 or 6, wherein the neurodegnerative disease comprises Alzheimer's disease. 9. The method of claim 5 or 6, comprising measuring neuroprotein misfolding or neuroprotein aggregates. 10. The method of claim 5 or 6, comprising measuring BMAA incorporation into neuroproteins. | L-serine, L-serine precursors, L-serine derivatives and L-serine conjugates for treatment, amelioration and/or prevention of protein aggregation/tangles/plaques and diseases associated with protein aggregation/tangles/plaques. In particular, treatments and uses for L-serine, L-serine precursors, L-serine derivatives and L-serine conjugates include Alzheimer's disease (AD), Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), and Huntington disease (HD).1. A non-human primate model of a neurodegnerative disease, wherein the model is produced by administration of BMAA to the non-human primate. 2. The non-human primate model of claim 1, wherein the non-human primate is a vervet. 3. The non-human primate of claim 1, wherein the neurodegnerative disease comprises Alzheimer's disease. 4. The non-human primate model of claim 1, wherein neuroproteins of the non-human primate misfold or form aggregates. 5. A method for identifying an agent for treatment of a neurodegnerative disease comprising:
a) contacting the non-human primate model of claim 1 with a candidate agent; and b) determining if the candidate agent inhibits or reduces neuroprotein misfolding or neuroprotein aggregates in the non-human primate model of claim 1, wherein an inhibition or reduction neuroprotein misfolding or neuroprotein aggregates identifies the candidate agent as an agent for treatment of a neurodegnerative disease. 6. A method for identifying an agent for prophylactic treatment of a neurodegnerative disease comprising:
a) contacting a non-human primate prior to administration of BMAA with a candidate agent; b) administering BMAA to the non-human primate; and c) determining if the candidate agent inhibits or reduces neuroprotein misfolding or neuroprotein aggregates in the non-human primate administered, wherein an inhibition or reduction neuroprotein misfolding or neuroprotein aggregates identifies the candidate agent as an agent for prophylactic treatment of a neurodegnerative disease. 7. The method of claim 5 or 6, wherein the non-human primate is a vervet. 8. The method of claim 5 or 6, wherein the neurodegnerative disease comprises Alzheimer's disease. 9. The method of claim 5 or 6, comprising measuring neuroprotein misfolding or neuroprotein aggregates. 10. The method of claim 5 or 6, comprising measuring BMAA incorporation into neuroproteins. | 1,600 |
1,366 | 15,772,846 | 1,616 | The invention relates to a cosmetic foam of a) an emulsion containing a combination of sodium cetearyl sulfate and glyceryl monostearate SE and b) a gas or gas mixture of propane, n-butane and/or isobutane, foaming the emulsion, the emulsion being free of polyethylene glycol derivatives (PEG derivatives). | 1.-17. (canceled) 18. A cosmetic foam, wherein the foam comprises
(i) an emulsion comprising (a) sodium cetearyl sulfate and (b) glyceryl monostearate SE and (ii) a gas or gas mixture of propane, n-butane and/or isobutane which foams the emulsion; and wherein (i) is free of polyethylene glycol derivatives (PEG derivatives). 19. The foam of claim 18, wherein (i) is free of soaps and surfactants having an HLB value of greater than 10, sodium cetearyl sulfate not being counted among these surfactants. 20. The foam of claim 18, wherein (a) is present in a concentration of from 0.1% to 2% by weight, based on a total weight of (i). 21. The foam of claim 18, wherein (b) is present in a concentration of from 0.1% to 5% by weight, based on a total weight of (i). 22. The foam of claim 18, wherein a weight ratio (a):(b) is from 1:1 to 1:20. 23. The foam of claim 18, wherein the foam comprises from 90% to 96% by weight of (i) and from 4% to 10% by weight of (ii). 24. The foam of claim 18, wherein the foam comprises from 92% to 94% by weight of (i) and from 6% to 8% by weight of (ii). 25. The foam of claim 18, wherein (i) is free of thickeners. 26. The foam of claim 18, wherein (i) is free of parabens, isothiazolinones and 3-iodopropargyl N-butylcarbamate (IPBC). 27. The foam of claim 18, wherein (i) comprises ethanol. 28. The foam of claim 18, wherein (i) comprises piroctone olamine (1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone monoethanolamine salt). 29. The foam of claim 18, wherein (i) comprises phenoxyethanol. 30. The foam of claim 18, wherein (i) comprises EDTA and/or betaine. 31. The foam of claim 18, wherein a lipid phase of (i) comprises at least one of stearyl alcohol, behenyl alcohol, almond oil, cocoa butter, shea butter. 32. The foam of claim 18, wherein (i) comprises from 7% to 25% by weight of lipid phase, based on a total weight of (i). 33. The foam of claim 18, wherein (i) is free of mineral oil and silicone oil. 34. The foam of claim 18, wherein (i) comprises tapioca starch modified with polymethylsilsesquioxane (INCI Tapioca starch+Polymethylsilsesquioxane). 35. The foam of claim 18, wherein (i) comprises from 5% to 15% by weight glycerol, based on a total weight of (i). 36. The foam of claim 18, wherein the foam is present in an aerosol can with release valve. 37. An aerosol can with release valve, wherein the can comprises the foam of claim 18. | The invention relates to a cosmetic foam of a) an emulsion containing a combination of sodium cetearyl sulfate and glyceryl monostearate SE and b) a gas or gas mixture of propane, n-butane and/or isobutane, foaming the emulsion, the emulsion being free of polyethylene glycol derivatives (PEG derivatives).1.-17. (canceled) 18. A cosmetic foam, wherein the foam comprises
(i) an emulsion comprising (a) sodium cetearyl sulfate and (b) glyceryl monostearate SE and (ii) a gas or gas mixture of propane, n-butane and/or isobutane which foams the emulsion; and wherein (i) is free of polyethylene glycol derivatives (PEG derivatives). 19. The foam of claim 18, wherein (i) is free of soaps and surfactants having an HLB value of greater than 10, sodium cetearyl sulfate not being counted among these surfactants. 20. The foam of claim 18, wherein (a) is present in a concentration of from 0.1% to 2% by weight, based on a total weight of (i). 21. The foam of claim 18, wherein (b) is present in a concentration of from 0.1% to 5% by weight, based on a total weight of (i). 22. The foam of claim 18, wherein a weight ratio (a):(b) is from 1:1 to 1:20. 23. The foam of claim 18, wherein the foam comprises from 90% to 96% by weight of (i) and from 4% to 10% by weight of (ii). 24. The foam of claim 18, wherein the foam comprises from 92% to 94% by weight of (i) and from 6% to 8% by weight of (ii). 25. The foam of claim 18, wherein (i) is free of thickeners. 26. The foam of claim 18, wherein (i) is free of parabens, isothiazolinones and 3-iodopropargyl N-butylcarbamate (IPBC). 27. The foam of claim 18, wherein (i) comprises ethanol. 28. The foam of claim 18, wherein (i) comprises piroctone olamine (1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone monoethanolamine salt). 29. The foam of claim 18, wherein (i) comprises phenoxyethanol. 30. The foam of claim 18, wherein (i) comprises EDTA and/or betaine. 31. The foam of claim 18, wherein a lipid phase of (i) comprises at least one of stearyl alcohol, behenyl alcohol, almond oil, cocoa butter, shea butter. 32. The foam of claim 18, wherein (i) comprises from 7% to 25% by weight of lipid phase, based on a total weight of (i). 33. The foam of claim 18, wherein (i) is free of mineral oil and silicone oil. 34. The foam of claim 18, wherein (i) comprises tapioca starch modified with polymethylsilsesquioxane (INCI Tapioca starch+Polymethylsilsesquioxane). 35. The foam of claim 18, wherein (i) comprises from 5% to 15% by weight glycerol, based on a total weight of (i). 36. The foam of claim 18, wherein the foam is present in an aerosol can with release valve. 37. An aerosol can with release valve, wherein the can comprises the foam of claim 18. | 1,600 |
1,367 | 14,367,608 | 1,634 | The present invention relates to a method for the in vitro diagnosis or prognosis of ovarian cancer, which includes a step of detecting at least one expression product of at least one HERV nucleic acid sequence, the use of said nucleic acid sequences, once isolated, as one or more molecular marker(s) and a kit including at least one specific binding partner of at least one of the expression products of the HERV nucleic acid sequences. | 1. A method for the in vitro diagnosis or prognosis of ovarian cancer in a biological sample taken from a patient, which comprises a step of detecting at least two expression products respectively of at least two nucleic acid sequences, said nucleic acid sequences being chosen from the sequences identified in SEQ ID NOs: 1 to 510 or from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 1 to 510. 2. The method as claimed in claim 1, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 4, 5, 7, 8, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 27, 28, 29, 31, 32, 33, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509 and 510 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 4, 5, 7, 8, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 27, 28, 29, 31, 32, 33, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509 and 510. 3. The method as claimed in claim 2, in which the expression product of at least two nucleic acid sequences is detected, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 17 and 29, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 17 and 29. 4. The method as claimed in claim 1, in which the expression product of at least two nucleic acid sequences chosen from the group consisting of the sequences identified in SEQ ID NOs: 2, 3, 6, 9, 10, 11, 20, 23, 24, 25, 26, 30, 34, 59 and 139 or chosen from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 2, 3, 6, 9, 10, 11, 20, 23, 24, 25, 26, 30, 34, 59 and 139, is detected. 5. The method as claimed in claim 4, in which the expression product of at least two nucleic acid sequences is detected, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID Nos: 2, 3 and 6 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 2, 3 and 6. 6. The method as claimed in claim 1, in which the expression product of at least one nucleic acid sequence being chosen from the group of sequences identified in SEQ ID NOs: 1, 4, 5, 7, 8, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 27, 28, 29, 31, 32, 33, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509 and 510 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 4, 5, 7, 8, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 27, 28, 29, 31, 32, 33, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 86, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509 and 510;
and the expression product of at least one nucleic acid sequence chosen from the group consisting of the sequences identified in SEQ ID NOs: 2, 3, 6, 9, 10, 11, 20, 23, 24, 25, 26, 30, 34, 59 and 139 or chosen from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 2, 3, 6, 9, 10, 11, 20, 23, 24, 25, 26, 30, 34, 59 and 139, are detected. 7. The method as claimed in claim 1, in which the expression product detected is at least one RNA transcript or at least one polypeptide. 8. The method as claimed in claim 7, wherein the RNA transcript is at least one mRNA. 9. The method as claimed in claim 7, in which the RNA transcript is detected by hybridization, by amplification or by sequencing. 10. The method as claimed in claim 8, in which the mRNA is brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and the presence or absence of hybridization to the mRNA is detected. 11. The method as claimed in claim 8, wherein DNA copies of the mRNA are prepared, the DNA copies are brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and in that the presence or absence of hybridization to said DNA copies is detected. 12. The method as claimed in claim 7, in which the polypeptide expressed is detected by bringing into contact with at least one specific binding partner of said polypeptide, an affinity protein or an aptamer. 13. A method of in vitro diagnosis or prognosis of ovarian cancer comprising: isolating at least two nucleic acid sequences as a molecular marker wherein the two nucleic acid sequences consist of:
(i) at least two DNA sequences chosen from the sequences SEQ ID NOs: 1 to 510, or (ii) at least two DNA sequences respectively complementary to at least two sequences as defined in (i), (iii) at least two DNA sequences which exhibit respectively at least 99% identity with two sequences as defined in (i) and (ii), or (iv) at least two RNA sequences which are respectively the transcription product of two sequences chosen from the sequences as defined in (i), or (v) at least two RNA sequences which are the transcription product of two sequences chosen from the sequences which exhibit at least 99% identity with the sequences as defined in (i). 14. A kit for the in vitro diagnosis or prognosis of ovarian cancer in a biological sample taken from a patient, which comprises at least two respectively specific binding partners of at least two expression products of at least two nucleic acid sequences chosen from the sequences identified in SEQ ID NOs: 1 to 510 or from the sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 510 and no more than 510 specific binding partners of the expression products of the nucleic acid sequences identified in SEQ ID NOs: 1 to 510 or of the nucleic acid sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 510. 15. The kit as claimed in claim 14, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 1, 4, 5, 7, 8, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 27, 28, 29, 31, 32, 33, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509 and 510 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 4, 5, 7, 8, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 27, 28, 29, 31, 32, 33, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509 and 510. 16. The kit as claimed in claim 15, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 17 and 29 or from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 1, 17 and 29. 17. The kit as claimed in claim 14, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 2, 3, 6, 9, 10, 11, 20, 23, 24, 25, 26, 30, 34, 59 and 139 or chosen from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 2, 3, 6, 9, 10, 11, 20, 23, 24, 25, 26, 30, 34, 59 and 139. 18. The kit as claimed in claim 17, which comprises at least two respectively specific binding partners of two or of three sequences chosen from the sequences identified in SEQ ID NOs: 2, 3 and 6 or chosen from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 2, 3 and 6. 19. The kit as claimed in claim 14, in which the at least two respectively specific binding partners of the expression products are respectively at least one hybridization probe and/or at least one amplification primer, or at least one antibody, or at least one antibody analog, or at least one affinity protein, or at least one aptamer. 20. A method for evaluating the efficacy of a treatment and/or a progression in ovarian cancer, which comprises a step of detecting at least two expression products respectively of at least two nucleic acid sequences, said two nucleic acid sequences being chosen from the sequences identified in SEQ ID NOs: 1 to 510 or from the sequences which exhibit at least 99% identity respectively with the sequences identified in SEQ ID NOs: 1 to 510. 21. The method as claimed in claim 20, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences as identified in SEQ ID NOs: 1, 4, 5, 7, 8, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 27, 28, 29, 31, 32, 33, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509 and 510 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID Nos: 1, 4, 5, 7, 8, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 27, 28, 29, 31, 32, 33, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 106, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509 and 510. 22. The method as claimed in claim 21, in which the expression product of at least two nucleic acid sequences chosen from the sequences identified in SEQ ID NOs: 1, 17 and 29, is detected. | The present invention relates to a method for the in vitro diagnosis or prognosis of ovarian cancer, which includes a step of detecting at least one expression product of at least one HERV nucleic acid sequence, the use of said nucleic acid sequences, once isolated, as one or more molecular marker(s) and a kit including at least one specific binding partner of at least one of the expression products of the HERV nucleic acid sequences.1. A method for the in vitro diagnosis or prognosis of ovarian cancer in a biological sample taken from a patient, which comprises a step of detecting at least two expression products respectively of at least two nucleic acid sequences, said nucleic acid sequences being chosen from the sequences identified in SEQ ID NOs: 1 to 510 or from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 1 to 510. 2. The method as claimed in claim 1, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 4, 5, 7, 8, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 27, 28, 29, 31, 32, 33, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509 and 510 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 4, 5, 7, 8, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 27, 28, 29, 31, 32, 33, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509 and 510. 3. The method as claimed in claim 2, in which the expression product of at least two nucleic acid sequences is detected, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 17 and 29, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 17 and 29. 4. The method as claimed in claim 1, in which the expression product of at least two nucleic acid sequences chosen from the group consisting of the sequences identified in SEQ ID NOs: 2, 3, 6, 9, 10, 11, 20, 23, 24, 25, 26, 30, 34, 59 and 139 or chosen from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 2, 3, 6, 9, 10, 11, 20, 23, 24, 25, 26, 30, 34, 59 and 139, is detected. 5. The method as claimed in claim 4, in which the expression product of at least two nucleic acid sequences is detected, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID Nos: 2, 3 and 6 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 2, 3 and 6. 6. The method as claimed in claim 1, in which the expression product of at least one nucleic acid sequence being chosen from the group of sequences identified in SEQ ID NOs: 1, 4, 5, 7, 8, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 27, 28, 29, 31, 32, 33, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509 and 510 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 4, 5, 7, 8, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 27, 28, 29, 31, 32, 33, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 86, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509 and 510;
and the expression product of at least one nucleic acid sequence chosen from the group consisting of the sequences identified in SEQ ID NOs: 2, 3, 6, 9, 10, 11, 20, 23, 24, 25, 26, 30, 34, 59 and 139 or chosen from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 2, 3, 6, 9, 10, 11, 20, 23, 24, 25, 26, 30, 34, 59 and 139, are detected. 7. The method as claimed in claim 1, in which the expression product detected is at least one RNA transcript or at least one polypeptide. 8. The method as claimed in claim 7, wherein the RNA transcript is at least one mRNA. 9. The method as claimed in claim 7, in which the RNA transcript is detected by hybridization, by amplification or by sequencing. 10. The method as claimed in claim 8, in which the mRNA is brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and the presence or absence of hybridization to the mRNA is detected. 11. The method as claimed in claim 8, wherein DNA copies of the mRNA are prepared, the DNA copies are brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and in that the presence or absence of hybridization to said DNA copies is detected. 12. The method as claimed in claim 7, in which the polypeptide expressed is detected by bringing into contact with at least one specific binding partner of said polypeptide, an affinity protein or an aptamer. 13. A method of in vitro diagnosis or prognosis of ovarian cancer comprising: isolating at least two nucleic acid sequences as a molecular marker wherein the two nucleic acid sequences consist of:
(i) at least two DNA sequences chosen from the sequences SEQ ID NOs: 1 to 510, or (ii) at least two DNA sequences respectively complementary to at least two sequences as defined in (i), (iii) at least two DNA sequences which exhibit respectively at least 99% identity with two sequences as defined in (i) and (ii), or (iv) at least two RNA sequences which are respectively the transcription product of two sequences chosen from the sequences as defined in (i), or (v) at least two RNA sequences which are the transcription product of two sequences chosen from the sequences which exhibit at least 99% identity with the sequences as defined in (i). 14. A kit for the in vitro diagnosis or prognosis of ovarian cancer in a biological sample taken from a patient, which comprises at least two respectively specific binding partners of at least two expression products of at least two nucleic acid sequences chosen from the sequences identified in SEQ ID NOs: 1 to 510 or from the sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 510 and no more than 510 specific binding partners of the expression products of the nucleic acid sequences identified in SEQ ID NOs: 1 to 510 or of the nucleic acid sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 510. 15. The kit as claimed in claim 14, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 1, 4, 5, 7, 8, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 27, 28, 29, 31, 32, 33, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509 and 510 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 4, 5, 7, 8, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 27, 28, 29, 31, 32, 33, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509 and 510. 16. The kit as claimed in claim 15, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 17 and 29 or from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 1, 17 and 29. 17. The kit as claimed in claim 14, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 2, 3, 6, 9, 10, 11, 20, 23, 24, 25, 26, 30, 34, 59 and 139 or chosen from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 2, 3, 6, 9, 10, 11, 20, 23, 24, 25, 26, 30, 34, 59 and 139. 18. The kit as claimed in claim 17, which comprises at least two respectively specific binding partners of two or of three sequences chosen from the sequences identified in SEQ ID NOs: 2, 3 and 6 or chosen from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 2, 3 and 6. 19. The kit as claimed in claim 14, in which the at least two respectively specific binding partners of the expression products are respectively at least one hybridization probe and/or at least one amplification primer, or at least one antibody, or at least one antibody analog, or at least one affinity protein, or at least one aptamer. 20. A method for evaluating the efficacy of a treatment and/or a progression in ovarian cancer, which comprises a step of detecting at least two expression products respectively of at least two nucleic acid sequences, said two nucleic acid sequences being chosen from the sequences identified in SEQ ID NOs: 1 to 510 or from the sequences which exhibit at least 99% identity respectively with the sequences identified in SEQ ID NOs: 1 to 510. 21. The method as claimed in claim 20, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences as identified in SEQ ID NOs: 1, 4, 5, 7, 8, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 27, 28, 29, 31, 32, 33, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509 and 510 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID Nos: 1, 4, 5, 7, 8, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 27, 28, 29, 31, 32, 33, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 106, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509 and 510. 22. The method as claimed in claim 21, in which the expression product of at least two nucleic acid sequences chosen from the sequences identified in SEQ ID NOs: 1, 17 and 29, is detected. | 1,600 |
1,368 | 14,415,894 | 1,619 | The present invention relates to a cosmetic composition for coating keratinous fibres of the emulsion type, comprising: an aqueous phase, at least one wax, an emulsifying system comprising at least one surfactant, at least one film-forming polymer present in a solids content of greater than or equal to 5% by weight, with respect to the total weight of the composition, at least one organic lipophilic gelling agent, in which the wax(es) and the emulsifying system are present at a respective total content such that the ratio by weight of the wax(es) to the emulsifying system is less than or equal to 1. The present invention also relates to a method for coating keratinous fibres, in particular for making up the eyelashes, comprising a stage of application of the said cosmetic composition for coating keratinous fibres. | 1. A cosmetic composition of an emulsion type, comprising:
an aqueous phase, a wax, an emulsifying system comprising a non-ionic surfactant exhibiting, at 25° C., an HLB balance within a Griffin meaning of greater than or equal to 8, a film-forming polymer present in a solids content of greater than or equal to 5% by weight, with respect to a total weight of the composition, an organic lipophilic gelling agent, wherein the wax and the emulsifying system are present at a respective total content such that a ratio by weight of the wax to the emulsifying system is less than or equal to 1. 2. The composition according to claim 1, in which the emulsifying system comprises an anionic surfactant comprising a cationic counterion. 3. The composition according to claim 2, wherein the anionic surfactant is a C12-C22 fatty acid. 4. The composition according to claim 2, wherein the anionic surfactant is present at a total content of greater than or equal to 1% by weight, with respect to the total weight of the composition. 5. The composition according to claim 2, wherein the cationic counterion is a cation of inorganic origin or of organic origin. 6. The composition according to claim 2, wherein the cationic counterion is ammonium, an amine or aminoalcohol derivative of ammonium, or magnesium. 7. The composition according to claim 2, wherein the cationic counterion comprises a primary (poly)hydroxyalkylamine. 8. The composition according to claim 2, wherein a total content of the cationic counterion is greater than or equal to 0.01% by weight, with respect to the total weight of the composition. 9. The composition according to claim 1, wherein the non-ionic surfactant exhibiting, at 25° C., an HLB balance within the Griffin meaning of greater than or equal to 8 is at least one member selected from the group consisting of:
an oxyethylenated and/or oxypropylenated glycerol ether comprising from 1 to 150 oxyethylene and/or oxypropylene units;
an oxyalkylenated alcohol comprising from 1 to 150 oxyethylene and/or oxypropylene units;
an ester of a fatty acid and of polyethylene glycol;
an ester of a fatty acid and of a glycerol ether that is oxyethylenated and/or oxypropylenated;
an ester of a fatty acid and of a sorbitol ether that is oxyethylenated and/or oxypropylenated;
dimethicone copolyol;
dimethicone copolyol benzoate; and
a copolymer of propylene oxide and of ethylene oxide. 10. The composition according to claim 1, wherein the non-ionic surfactant exhibiting, at 25° C., an HLB balance within the Griffin meaning of greater than or equal to 8 is present at a total content of greater than or equal to 1% by weight, with respect to the total weight of the composition. 11. The composition according to claim 1, wherein the emulsifying system further comprises a non-ionic surfactant exhibiting, at 25° C., an HLB balance within the Griffin meaning of less than 8. 12. The composition according to claim 11, wherein the non-ionic surfactant exhibiting, at 25° C., an HLB balance within the Griffin meaning of less than 8 is present at a total content of greater than or equal to 1% by weight, with respect to the total weight of the composition. 13. The composition according to claim 1, wherein the emulsifying system further comprises a co-surfactant that is a fatty alcohol comprising from 10 to 26 carbon atoms. 14. The composition according to claim 1, wherein the wax is present at a total content of less than or equal to 12% by weight, with respect to the total weight of the composition. 15. The composition according to claim 1, wherein the film-forming polymer comprises an aqueous dispersion of film-forming polymer. 16. The composition according to claim 1, wherein the film-forming polymer comprises at least two aqueous dispersions of film-forming polymer, at least one being an aqueous dispersion of acrylic polymer and at least the other being an aqueous dispersion of polyurethane, or their derivatives. 17. The composition according to claim 16, wherein the organic lipophilic gelling agent is at least one member selected from the group consisting of a semi-crystalline polymer; a polycondensate of a hydrocarbon polyamide type; ethylcellulose; a silicone polyamide of a polyorganosiloxane type; a galactomannan comprising from 1 to 6 hydroxyl groups per monosaccharide which are substituted by a saturated or unsaturated alkyl chain; a block copolymer of diblock, triblock or radial type; a non-emulsifying silicone elastomer; and an organic gelling agent. 18. The composition according to claim 1, wherein the organic lipophilic gelling agent is present at a content ranging from 0.5% to 6% by weight, on a dry basis, with respect to the total weight of the composition. 19. The composition according to claim 18, further comprising at least one inorganic filler selected from the group consisting of talc, mica, synthetic fluorphlogopite, and a clay. 20. A method for coating a keratinous fiber, comprising applying the cosmetic composition of claim 1 to the keratinous fiber. | The present invention relates to a cosmetic composition for coating keratinous fibres of the emulsion type, comprising: an aqueous phase, at least one wax, an emulsifying system comprising at least one surfactant, at least one film-forming polymer present in a solids content of greater than or equal to 5% by weight, with respect to the total weight of the composition, at least one organic lipophilic gelling agent, in which the wax(es) and the emulsifying system are present at a respective total content such that the ratio by weight of the wax(es) to the emulsifying system is less than or equal to 1. The present invention also relates to a method for coating keratinous fibres, in particular for making up the eyelashes, comprising a stage of application of the said cosmetic composition for coating keratinous fibres.1. A cosmetic composition of an emulsion type, comprising:
an aqueous phase, a wax, an emulsifying system comprising a non-ionic surfactant exhibiting, at 25° C., an HLB balance within a Griffin meaning of greater than or equal to 8, a film-forming polymer present in a solids content of greater than or equal to 5% by weight, with respect to a total weight of the composition, an organic lipophilic gelling agent, wherein the wax and the emulsifying system are present at a respective total content such that a ratio by weight of the wax to the emulsifying system is less than or equal to 1. 2. The composition according to claim 1, in which the emulsifying system comprises an anionic surfactant comprising a cationic counterion. 3. The composition according to claim 2, wherein the anionic surfactant is a C12-C22 fatty acid. 4. The composition according to claim 2, wherein the anionic surfactant is present at a total content of greater than or equal to 1% by weight, with respect to the total weight of the composition. 5. The composition according to claim 2, wherein the cationic counterion is a cation of inorganic origin or of organic origin. 6. The composition according to claim 2, wherein the cationic counterion is ammonium, an amine or aminoalcohol derivative of ammonium, or magnesium. 7. The composition according to claim 2, wherein the cationic counterion comprises a primary (poly)hydroxyalkylamine. 8. The composition according to claim 2, wherein a total content of the cationic counterion is greater than or equal to 0.01% by weight, with respect to the total weight of the composition. 9. The composition according to claim 1, wherein the non-ionic surfactant exhibiting, at 25° C., an HLB balance within the Griffin meaning of greater than or equal to 8 is at least one member selected from the group consisting of:
an oxyethylenated and/or oxypropylenated glycerol ether comprising from 1 to 150 oxyethylene and/or oxypropylene units;
an oxyalkylenated alcohol comprising from 1 to 150 oxyethylene and/or oxypropylene units;
an ester of a fatty acid and of polyethylene glycol;
an ester of a fatty acid and of a glycerol ether that is oxyethylenated and/or oxypropylenated;
an ester of a fatty acid and of a sorbitol ether that is oxyethylenated and/or oxypropylenated;
dimethicone copolyol;
dimethicone copolyol benzoate; and
a copolymer of propylene oxide and of ethylene oxide. 10. The composition according to claim 1, wherein the non-ionic surfactant exhibiting, at 25° C., an HLB balance within the Griffin meaning of greater than or equal to 8 is present at a total content of greater than or equal to 1% by weight, with respect to the total weight of the composition. 11. The composition according to claim 1, wherein the emulsifying system further comprises a non-ionic surfactant exhibiting, at 25° C., an HLB balance within the Griffin meaning of less than 8. 12. The composition according to claim 11, wherein the non-ionic surfactant exhibiting, at 25° C., an HLB balance within the Griffin meaning of less than 8 is present at a total content of greater than or equal to 1% by weight, with respect to the total weight of the composition. 13. The composition according to claim 1, wherein the emulsifying system further comprises a co-surfactant that is a fatty alcohol comprising from 10 to 26 carbon atoms. 14. The composition according to claim 1, wherein the wax is present at a total content of less than or equal to 12% by weight, with respect to the total weight of the composition. 15. The composition according to claim 1, wherein the film-forming polymer comprises an aqueous dispersion of film-forming polymer. 16. The composition according to claim 1, wherein the film-forming polymer comprises at least two aqueous dispersions of film-forming polymer, at least one being an aqueous dispersion of acrylic polymer and at least the other being an aqueous dispersion of polyurethane, or their derivatives. 17. The composition according to claim 16, wherein the organic lipophilic gelling agent is at least one member selected from the group consisting of a semi-crystalline polymer; a polycondensate of a hydrocarbon polyamide type; ethylcellulose; a silicone polyamide of a polyorganosiloxane type; a galactomannan comprising from 1 to 6 hydroxyl groups per monosaccharide which are substituted by a saturated or unsaturated alkyl chain; a block copolymer of diblock, triblock or radial type; a non-emulsifying silicone elastomer; and an organic gelling agent. 18. The composition according to claim 1, wherein the organic lipophilic gelling agent is present at a content ranging from 0.5% to 6% by weight, on a dry basis, with respect to the total weight of the composition. 19. The composition according to claim 18, further comprising at least one inorganic filler selected from the group consisting of talc, mica, synthetic fluorphlogopite, and a clay. 20. A method for coating a keratinous fiber, comprising applying the cosmetic composition of claim 1 to the keratinous fiber. | 1,600 |
1,369 | 15,015,968 | 1,662 | Methods and compositions for plastid transformation and regeneration or development of transplastomic plants are provided. Embryo explants may be excised from seeds, and their meristematic tissue may be transformed directly without initiation of any callus phase before and/or after transformation. The present methods may be performed with fewer culturing steps relative to conventional methods, thereby enabling more rapid and efficient production of targeted transplastomic events in plants. | 1. A method of transforming a plant plastid, comprising the steps of:
(a) preparing an explant from a seed of a plant, the explant comprising meristematic tissue of an embryo of the seed; and (b) transforming at least one plastid of a cell of the explant with an exogenous DNA molecule, the exogenous DNA molecule comprising:
(i) a first arm region homologous to a first plastid genome sequence;
(ii) a second arm region homologous to a second plastid genome sequence; and
(iii) an insertion sequence positioned between the first arm region and the second arm region of the exogenous DNA molecule,
wherein the cells of the explant do not form a callus tissue prior to the transforming step (b), and wherein the insertion sequence is incorporated into a plastid genome of the plant cell between the first plastid genome sequence and the second plastid genome sequence. 2. The method of claim 1, wherein the seed is dry seed comprising a mature embryo. 3. The method of claim 2, wherein the dry seed has a moisture content in a range from about 3% to about 25%. 4. The method of claim 1, wherein the plant is a dicotyledonous plant. 5. The method of claim 4, wherein the dicotyledonous plant is a soybean, canola, alfalfa, sugar beet or cotton plant. 6. The method of claim 1, wherein the at least one plastid is not photosynthetically active. 7. The method of claim 1, wherein the embryo is a mature embryo. 8. The method of claim 1, wherein the insertion sequence is incorporated into the plastid genome by homologous recombination. 9. The method of claim 1, wherein the transforming step (b) comprises introducing the exogenous DNA molecule into the explant via particle-mediated bombardment. 10. The method of claim 1, wherein the explant prepared in step (a) has a moisture content in a range from about 3% to about 20%. 11. The method of claim 1, wherein the plastid transformed in step (b) is a proplastid. 12. The method of claim 1, wherein the embryo is an immature embryo. 13. The method of claim 1, wherein the explant remains competent for plastid transformation and does not germinate prior to the transforming step (b). 14. The method of claim 1, wherein the explant transformed in step (b) is in a state of metabolic stasis. 15. The method of claim 1, further comprising:
preculturing the explant prior to the transforming step (b), the preculturing step comprising exposing the explant to an aqueous medium comprising at least one osmoticum. 16. The method of claim 15, wherein the aqueous medium comprises a sugar or polyethylene glycol (PEG). 17. The method of claim 1, further comprising:
germinating the explant after the transforming step (b). 18. The method of claim 17, further comprising:
developing a plastid transformed plant from the germinated explant. 19. The method of claim 18, further comprising:
obtaining a plastid transformed seed from the plastid transformed plant. 20. The method of claim 1, further comprising:
germinating the explant prior to the transforming step (b). 21. The method of claim 1, wherein the insertion sequence comprises a DNA expression cassette comprising a transgene operably linked to a plastid promoter. 22. The method of claim 21, wherein the transgene confers a trait of agronomic interest when expressed in a plant transformed with the transgene. 23. The method of claim 22, wherein the trait of agronomic interest comprises one of: modified carbon fixation, modified nitrogen fixation, herbicide tolerance, insect resistance, increased yield, fungal disease tolerance, virus tolerance, nematode tolerance, bacterial disease tolerance, modified starch production, modified oil production, modified fatty acid content, modified protein production, enhanced animal and human nutrition, environmental stress tolerance, improved processing traits, improved digestibility, modified enzyme production, and modified fiber production. 24. The method of claim 21, wherein the transgene is a plant selectable marker gene conferring tolerance to a selection agent. 25. The method of claim 24, further comprising:
selecting for development of plastid transformed cells of the explant by contacting the explant with the selection agent. 26. The method of claim 24, further comprising:
developing a plastid transformed plant from the explant transformed in step (b) under selection pressure by contacting the developing plant with the selection agent. 27. The method of claim 1, wherein the insertion sequence comprises a first DNA expression cassette and a second DNA expression cassette, the first DNA expression cassette comprising a first transgene operably linked to a first plastid promoter, and the second DNA expression cassette comprising a second transgene operably linked to a second plastid promoter, wherein the first transgene confers a trait of agronomic interest when expressed in a plant, and the second transgene is a plant selectable marker gene conferring tolerance to a selection agent. 28. The method of claim 1, further comprising:
storing the explant under dry conditions for about 1 hour to about 2 years prior to the transforming step (b), wherein the explant remains viable and competent for transformation during storage. 29. The method of claim 1, further comprising:
drying the explant prior to the transforming step (b). 30. The method of claim 1, further comprising:
excising the explant from the seed of the plant. 31. A plastid transformed plant produced by the method of claim 18. 32. The plastid transformed plant of claim 31, wherein one or more tissue samples taken from the plastid transformed plant are each at least 95% transplastomic. 33. A plastid transformed seed produced by the method of claim 19. 34. A method of transforming a plant plastid, comprising the steps of:
transforming at least one plastid of a meristematic cell of an explant with an exogenous DNA molecule, the exogenous DNA molecule comprising:
(i) a first arm region homologous to a first plastid genome sequence;
(ii) a second arm region homologous to a second plastid genome sequence; and
(iii) an insertion sequence positioned between the first arm region and the second arm region of the exogenous DNA molecule,
wherein the cells of the explant do not form a callus tissue prior to the transforming step, and wherein the insertion sequence is incorporated into the plastid genome of the plant cell between the first plastid genome sequence and the second plastid genome sequence. 35. The method of claim 34, further comprising:
excising the explant from a seed of a plant. | Methods and compositions for plastid transformation and regeneration or development of transplastomic plants are provided. Embryo explants may be excised from seeds, and their meristematic tissue may be transformed directly without initiation of any callus phase before and/or after transformation. The present methods may be performed with fewer culturing steps relative to conventional methods, thereby enabling more rapid and efficient production of targeted transplastomic events in plants.1. A method of transforming a plant plastid, comprising the steps of:
(a) preparing an explant from a seed of a plant, the explant comprising meristematic tissue of an embryo of the seed; and (b) transforming at least one plastid of a cell of the explant with an exogenous DNA molecule, the exogenous DNA molecule comprising:
(i) a first arm region homologous to a first plastid genome sequence;
(ii) a second arm region homologous to a second plastid genome sequence; and
(iii) an insertion sequence positioned between the first arm region and the second arm region of the exogenous DNA molecule,
wherein the cells of the explant do not form a callus tissue prior to the transforming step (b), and wherein the insertion sequence is incorporated into a plastid genome of the plant cell between the first plastid genome sequence and the second plastid genome sequence. 2. The method of claim 1, wherein the seed is dry seed comprising a mature embryo. 3. The method of claim 2, wherein the dry seed has a moisture content in a range from about 3% to about 25%. 4. The method of claim 1, wherein the plant is a dicotyledonous plant. 5. The method of claim 4, wherein the dicotyledonous plant is a soybean, canola, alfalfa, sugar beet or cotton plant. 6. The method of claim 1, wherein the at least one plastid is not photosynthetically active. 7. The method of claim 1, wherein the embryo is a mature embryo. 8. The method of claim 1, wherein the insertion sequence is incorporated into the plastid genome by homologous recombination. 9. The method of claim 1, wherein the transforming step (b) comprises introducing the exogenous DNA molecule into the explant via particle-mediated bombardment. 10. The method of claim 1, wherein the explant prepared in step (a) has a moisture content in a range from about 3% to about 20%. 11. The method of claim 1, wherein the plastid transformed in step (b) is a proplastid. 12. The method of claim 1, wherein the embryo is an immature embryo. 13. The method of claim 1, wherein the explant remains competent for plastid transformation and does not germinate prior to the transforming step (b). 14. The method of claim 1, wherein the explant transformed in step (b) is in a state of metabolic stasis. 15. The method of claim 1, further comprising:
preculturing the explant prior to the transforming step (b), the preculturing step comprising exposing the explant to an aqueous medium comprising at least one osmoticum. 16. The method of claim 15, wherein the aqueous medium comprises a sugar or polyethylene glycol (PEG). 17. The method of claim 1, further comprising:
germinating the explant after the transforming step (b). 18. The method of claim 17, further comprising:
developing a plastid transformed plant from the germinated explant. 19. The method of claim 18, further comprising:
obtaining a plastid transformed seed from the plastid transformed plant. 20. The method of claim 1, further comprising:
germinating the explant prior to the transforming step (b). 21. The method of claim 1, wherein the insertion sequence comprises a DNA expression cassette comprising a transgene operably linked to a plastid promoter. 22. The method of claim 21, wherein the transgene confers a trait of agronomic interest when expressed in a plant transformed with the transgene. 23. The method of claim 22, wherein the trait of agronomic interest comprises one of: modified carbon fixation, modified nitrogen fixation, herbicide tolerance, insect resistance, increased yield, fungal disease tolerance, virus tolerance, nematode tolerance, bacterial disease tolerance, modified starch production, modified oil production, modified fatty acid content, modified protein production, enhanced animal and human nutrition, environmental stress tolerance, improved processing traits, improved digestibility, modified enzyme production, and modified fiber production. 24. The method of claim 21, wherein the transgene is a plant selectable marker gene conferring tolerance to a selection agent. 25. The method of claim 24, further comprising:
selecting for development of plastid transformed cells of the explant by contacting the explant with the selection agent. 26. The method of claim 24, further comprising:
developing a plastid transformed plant from the explant transformed in step (b) under selection pressure by contacting the developing plant with the selection agent. 27. The method of claim 1, wherein the insertion sequence comprises a first DNA expression cassette and a second DNA expression cassette, the first DNA expression cassette comprising a first transgene operably linked to a first plastid promoter, and the second DNA expression cassette comprising a second transgene operably linked to a second plastid promoter, wherein the first transgene confers a trait of agronomic interest when expressed in a plant, and the second transgene is a plant selectable marker gene conferring tolerance to a selection agent. 28. The method of claim 1, further comprising:
storing the explant under dry conditions for about 1 hour to about 2 years prior to the transforming step (b), wherein the explant remains viable and competent for transformation during storage. 29. The method of claim 1, further comprising:
drying the explant prior to the transforming step (b). 30. The method of claim 1, further comprising:
excising the explant from the seed of the plant. 31. A plastid transformed plant produced by the method of claim 18. 32. The plastid transformed plant of claim 31, wherein one or more tissue samples taken from the plastid transformed plant are each at least 95% transplastomic. 33. A plastid transformed seed produced by the method of claim 19. 34. A method of transforming a plant plastid, comprising the steps of:
transforming at least one plastid of a meristematic cell of an explant with an exogenous DNA molecule, the exogenous DNA molecule comprising:
(i) a first arm region homologous to a first plastid genome sequence;
(ii) a second arm region homologous to a second plastid genome sequence; and
(iii) an insertion sequence positioned between the first arm region and the second arm region of the exogenous DNA molecule,
wherein the cells of the explant do not form a callus tissue prior to the transforming step, and wherein the insertion sequence is incorporated into the plastid genome of the plant cell between the first plastid genome sequence and the second plastid genome sequence. 35. The method of claim 34, further comprising:
excising the explant from a seed of a plant. | 1,600 |
1,370 | 16,049,310 | 1,611 | The instant disclosure relates to methods for treating skin, for example, methods for desquamation of the skin of the face. The methods use a two-step process of first treating the skin with an alkaline composition having a pH of at least 8 followed by a second step of treating the skin with an acidic composition having a pH of 5 of less. The acidic composition includes one or more α- and/or β-hydroxy acids, which react with the skin to cause desquamation and stimulate new skin cell growth. Treating the skin with the claimed alkaline compositions improves the efficacy of the treatment with the acidic composition while reducing skin irritation and discomfort. | 1. A method for treating skin comprising:
(a) applying an alkaline composition having a pH of at least 8 to the skin and allowing it to remain on the skin for a first period of time of at least 30 seconds, the alkaline composition comprising:
(i) about 0.05 to about 25 wt. %, based on the total weight of the alkaline composition, of one or more alkaline agents; and
(vi) optionally, about 0.05 to about 1 wt. %, based on the total weight of the alkaline composition, of one or more colorants;
(ii) optionally, about 0.5 to about 25 wt. %, based on the total weight of the alkaline composition, of one or more water-soluble solvents; and
(iii) water; and
(b) after allowing the alkaline composition to remain on the skin for the first period of time, subsequently applying an acidic composition having a pH of 5 or less to the skin and allowing it to remain on the skin for a second period of time of at least 30 seconds, the acidic composition comprising:
(i) about 1 to about 25 wt. %, based on the total weight of the acidic composition, of one or more α- and/or β-hydroxy acids;
(vii) optionally, about 0.1 to about 25 wt. %, based on the total weight of the acidic composition, of one or more whitening actives, such as arbutin, azelaic acid, linoleic acid, kojic acid, N-acetyl-4,S-cysteaminylphenol, niacinamide, resorcinol;
(viii) optionally, about 0.1 to about 25 wt. %, based on the total weight of the acidic composition, of one or more antioxidants, such as ascorbic acid, Vitamin E;
(ix) optionally, about 0.05 to about 1 wt. %, based on the total weight of the acidic composition, of one or more colorants;
(ii) about 1 to about 25 wt. %, based on the total weight of the acidic composition, of one or more water-soluble solvents; and
(iii) water. 2. The method of claim 1, wherein the alkaline composition has a pH of at least 9 and the acidic composition has a pH of 4 or less. 3. The method of claim 1, wherein the first period of time is at least 1 minute and the second period of time is at 1 minute. 4. The method of claim 1, wherein the alkaline composition is not rinsed from the skin prior to application of the acidic composition. 5. The method of claim 1, wherein the alkaline composition is rinsed from the skin prior to application of the acidic composition. 6. The method of claim 1, wherein the one or more alkaline agents of the alkaline composition are selected from:
alkali metal hydroxides, alkaline-earth metal hydroxides, alkali metal silicates, alkali metal carbonates, alkaline-earth metal carbonates, organic carbonates, basic amino acids, alkanolamines, and ammonium hydroxide. 7. The method of claim 1, wherein the one or more water-soluble solvents are selected from glycerin, mono-alcohols, polyols (polyhydric alcohols), glycols, and a mixture thereof. 8. The method of claim 1, wherein the alkaline composition is a non-emulsified liquid. 9. The method of claim 1, wherein the alkaline composition is a gel and further comprises:
about 0.1 to about 10 wt. % of one or more thickening agents. 10. The method of claim 9, wherein the one or more thickening agents are selected from carboxylic acid polymers, crosslinked polyacrylate polymers, polyacrylamide polymers, polysaccharides, gums, and a mixture thereof. 11. The method of claim 1, wherein the alkaline composition is an emulsion and further comprises:
about 30 to about 75 wt. % of one or more non-silicone fatty compounds; and about 0.1 to about 10 wt. % of one or more emulsifiers. 12. The method of claim 11, wherein the one or more non-silicone fatty compounds are selected from oils, mineral oil, alkanes (paraffins), fatty alcohols, fatty acids, fatty alcohol derivatives, fatty acid derivatives (such as alkoxylated fatty acids or polyethylene glycol esters of fatty acids or propylene glycol esters of fatty acids or butylene glycol esters of fatty acids or esters of neopentyl glycol and fatty acids or polyglycerol/glycerol esters of fatty acids or glycol diesters or diesters of ethylene glycol and fatty acids or esters of fatty acids and fatty alcohols, esters of short chain alcohols and fatty acids), esters of fatty alcohols, hydroxy-substituted fatty acids, waxes, triglyceride compounds, lanolin, and a mixture thereof. 13. The method of claim 11, wherein the one or more emulsifiers are selected from alkylpolyglycosides, glyceryl esters, ethylene glycol esters, propylene glycol esters and sucrose esters of fatty acids, ethoxylated fatty alcohols, ethoxylated fatty acids, partial glycerides of ethoxylated fatty acids, polyglycerolated fatty acid triglycerides, and a mixture thereof 14. The method of claim 1, wherein the one or more α- and/or β-hydroxy acids of the acidic composition are selected from lactic acid, glycolic acid, citric acid, ascorbic acid, phytic acid, mandelic acid, and salicylic acid. 15. The method of claim 1, wherein the one or more water-soluble solvents of the acidic composition are selected from glycerin, mono-alcohols, polyols (polyhydric alcohols), glycols, and a mixture thereof. 16. The method of claim 1, wherein the acidic composition is a non-emulsified liquid. 17. The method of claim 1, wherein the acidic composition is a gel and further comprises:
about 0.1 to about 10 wt. % of one or more thickening agents. 18. The method of claim 17, wherein the one or more thickening agents are selected from carboxylic acid polymers, crosslinked polyacrylate polymers, polyacrylamide polymers, polysaccharides, gums, and a mixture thereof. 19. The method of claim 1, wherein the acidic composition is an emulsion and further comprises:
about 5 to about 50 wt. % of one or more non-silicone fatty compounds; and about 0.1 to about 10 wt. % of one or more emulsifiers. 20. The method of claim 19, wherein the one or more non-silicone fatty compounds are selected from oils, mineral oil, alkanes (paraffins), fatty alcohols, fatty acids, fatty alcohol derivatives, fatty acid derivatives (such as alkoxylated fatty acids or polyethylene glycol esters of fatty acids or propylene glycol esters of fatty acids or butylene glycol esters of fatty acids or esters of neopentyl glycol and fatty acids or polyglycerol/glycerol esters of fatty acids or glycol diesters or diesters of ethylene glycol and fatty acids or esters of fatty acids and fatty alcohols, esters of short chain alcohols and fatty acids), esters of fatty alcohols, hydroxy-substituted fatty acids, waxes, triglyceride compounds, lanolin, and a mixture thereof. 21. The method of claim 20, wherein the one or more emulsifiers are selected from alkylpolyglycosides, glyceryl esters, ethylene glycol esters, propylene glycol esters and sucrose esters of fatty acids, ethoxylated fatty alcohols, ethoxylated fatty acids, partial glycerides of ethoxylated fatty acids, polyglycerolated fatty acid triglycerides, and a mixture thereof 22. The method of claim 1, wherein the acidic composition comprises at least 10 to about 25 wt. %, based on the total weight of the acidic composition, of the one or more α- and/or β-hydroxy acids. 23. The method of claim 1, wherein the method provides desquamation of the skin of the face. 24. The method of claim 1, wherein the method:
improves the radiance of skin; improves the evenness of skin tone; improves the clarity of skin; and/or improves the overall appearance of skin. | The instant disclosure relates to methods for treating skin, for example, methods for desquamation of the skin of the face. The methods use a two-step process of first treating the skin with an alkaline composition having a pH of at least 8 followed by a second step of treating the skin with an acidic composition having a pH of 5 of less. The acidic composition includes one or more α- and/or β-hydroxy acids, which react with the skin to cause desquamation and stimulate new skin cell growth. Treating the skin with the claimed alkaline compositions improves the efficacy of the treatment with the acidic composition while reducing skin irritation and discomfort.1. A method for treating skin comprising:
(a) applying an alkaline composition having a pH of at least 8 to the skin and allowing it to remain on the skin for a first period of time of at least 30 seconds, the alkaline composition comprising:
(i) about 0.05 to about 25 wt. %, based on the total weight of the alkaline composition, of one or more alkaline agents; and
(vi) optionally, about 0.05 to about 1 wt. %, based on the total weight of the alkaline composition, of one or more colorants;
(ii) optionally, about 0.5 to about 25 wt. %, based on the total weight of the alkaline composition, of one or more water-soluble solvents; and
(iii) water; and
(b) after allowing the alkaline composition to remain on the skin for the first period of time, subsequently applying an acidic composition having a pH of 5 or less to the skin and allowing it to remain on the skin for a second period of time of at least 30 seconds, the acidic composition comprising:
(i) about 1 to about 25 wt. %, based on the total weight of the acidic composition, of one or more α- and/or β-hydroxy acids;
(vii) optionally, about 0.1 to about 25 wt. %, based on the total weight of the acidic composition, of one or more whitening actives, such as arbutin, azelaic acid, linoleic acid, kojic acid, N-acetyl-4,S-cysteaminylphenol, niacinamide, resorcinol;
(viii) optionally, about 0.1 to about 25 wt. %, based on the total weight of the acidic composition, of one or more antioxidants, such as ascorbic acid, Vitamin E;
(ix) optionally, about 0.05 to about 1 wt. %, based on the total weight of the acidic composition, of one or more colorants;
(ii) about 1 to about 25 wt. %, based on the total weight of the acidic composition, of one or more water-soluble solvents; and
(iii) water. 2. The method of claim 1, wherein the alkaline composition has a pH of at least 9 and the acidic composition has a pH of 4 or less. 3. The method of claim 1, wherein the first period of time is at least 1 minute and the second period of time is at 1 minute. 4. The method of claim 1, wherein the alkaline composition is not rinsed from the skin prior to application of the acidic composition. 5. The method of claim 1, wherein the alkaline composition is rinsed from the skin prior to application of the acidic composition. 6. The method of claim 1, wherein the one or more alkaline agents of the alkaline composition are selected from:
alkali metal hydroxides, alkaline-earth metal hydroxides, alkali metal silicates, alkali metal carbonates, alkaline-earth metal carbonates, organic carbonates, basic amino acids, alkanolamines, and ammonium hydroxide. 7. The method of claim 1, wherein the one or more water-soluble solvents are selected from glycerin, mono-alcohols, polyols (polyhydric alcohols), glycols, and a mixture thereof. 8. The method of claim 1, wherein the alkaline composition is a non-emulsified liquid. 9. The method of claim 1, wherein the alkaline composition is a gel and further comprises:
about 0.1 to about 10 wt. % of one or more thickening agents. 10. The method of claim 9, wherein the one or more thickening agents are selected from carboxylic acid polymers, crosslinked polyacrylate polymers, polyacrylamide polymers, polysaccharides, gums, and a mixture thereof. 11. The method of claim 1, wherein the alkaline composition is an emulsion and further comprises:
about 30 to about 75 wt. % of one or more non-silicone fatty compounds; and about 0.1 to about 10 wt. % of one or more emulsifiers. 12. The method of claim 11, wherein the one or more non-silicone fatty compounds are selected from oils, mineral oil, alkanes (paraffins), fatty alcohols, fatty acids, fatty alcohol derivatives, fatty acid derivatives (such as alkoxylated fatty acids or polyethylene glycol esters of fatty acids or propylene glycol esters of fatty acids or butylene glycol esters of fatty acids or esters of neopentyl glycol and fatty acids or polyglycerol/glycerol esters of fatty acids or glycol diesters or diesters of ethylene glycol and fatty acids or esters of fatty acids and fatty alcohols, esters of short chain alcohols and fatty acids), esters of fatty alcohols, hydroxy-substituted fatty acids, waxes, triglyceride compounds, lanolin, and a mixture thereof. 13. The method of claim 11, wherein the one or more emulsifiers are selected from alkylpolyglycosides, glyceryl esters, ethylene glycol esters, propylene glycol esters and sucrose esters of fatty acids, ethoxylated fatty alcohols, ethoxylated fatty acids, partial glycerides of ethoxylated fatty acids, polyglycerolated fatty acid triglycerides, and a mixture thereof 14. The method of claim 1, wherein the one or more α- and/or β-hydroxy acids of the acidic composition are selected from lactic acid, glycolic acid, citric acid, ascorbic acid, phytic acid, mandelic acid, and salicylic acid. 15. The method of claim 1, wherein the one or more water-soluble solvents of the acidic composition are selected from glycerin, mono-alcohols, polyols (polyhydric alcohols), glycols, and a mixture thereof. 16. The method of claim 1, wherein the acidic composition is a non-emulsified liquid. 17. The method of claim 1, wherein the acidic composition is a gel and further comprises:
about 0.1 to about 10 wt. % of one or more thickening agents. 18. The method of claim 17, wherein the one or more thickening agents are selected from carboxylic acid polymers, crosslinked polyacrylate polymers, polyacrylamide polymers, polysaccharides, gums, and a mixture thereof. 19. The method of claim 1, wherein the acidic composition is an emulsion and further comprises:
about 5 to about 50 wt. % of one or more non-silicone fatty compounds; and about 0.1 to about 10 wt. % of one or more emulsifiers. 20. The method of claim 19, wherein the one or more non-silicone fatty compounds are selected from oils, mineral oil, alkanes (paraffins), fatty alcohols, fatty acids, fatty alcohol derivatives, fatty acid derivatives (such as alkoxylated fatty acids or polyethylene glycol esters of fatty acids or propylene glycol esters of fatty acids or butylene glycol esters of fatty acids or esters of neopentyl glycol and fatty acids or polyglycerol/glycerol esters of fatty acids or glycol diesters or diesters of ethylene glycol and fatty acids or esters of fatty acids and fatty alcohols, esters of short chain alcohols and fatty acids), esters of fatty alcohols, hydroxy-substituted fatty acids, waxes, triglyceride compounds, lanolin, and a mixture thereof. 21. The method of claim 20, wherein the one or more emulsifiers are selected from alkylpolyglycosides, glyceryl esters, ethylene glycol esters, propylene glycol esters and sucrose esters of fatty acids, ethoxylated fatty alcohols, ethoxylated fatty acids, partial glycerides of ethoxylated fatty acids, polyglycerolated fatty acid triglycerides, and a mixture thereof 22. The method of claim 1, wherein the acidic composition comprises at least 10 to about 25 wt. %, based on the total weight of the acidic composition, of the one or more α- and/or β-hydroxy acids. 23. The method of claim 1, wherein the method provides desquamation of the skin of the face. 24. The method of claim 1, wherein the method:
improves the radiance of skin; improves the evenness of skin tone; improves the clarity of skin; and/or improves the overall appearance of skin. | 1,600 |
1,371 | 14,994,169 | 1,619 | A capsule with a shell and a fill phase. The fill phase contains less than about 5% beeswax by weight of the capsule and a supercritical extract of an herb. The capsule can be both vegetarian and meet the non-GMO Project Standard. | 1. A capsule comprising:
a. a shell; b. a fill phase comprising beeswax, candelilla wax, and a supercritical extract of an herb;
wherein the capsule is vegetarian and meets the non-GMO Project Standards;
wherein the capsule comprises greater than 0% and less than about 5%, by weight of the capsule, beeswax; and
wherein at least 98% of the capsules pass the Cracking Test. 2. The capsule of claim 1 wherein the weight ratio of beeswax to candelilla wax is from about 1:3 to about 5:1. 3. The capsule of claim 1 wherein the capsule comprises a volume and wherein the volume is greater than about 0.34 mL. 4. The capsule of claim 1 wherein the supercritical extract of an herb comprises a supercritical extract of ginger. 5. The capsule of claim 4 wherein the supercritical extract of ginger is less than about 10% of the fill phase. 6. The capsule of claim 1 wherein the fill phase comprises from about 1% to about 15% candelilla wax. 7. The capsule of claim 1 further comprising olive oil. 8. The capsule of claim 7 wherein the olive oil to wax ratio in the fill phase is from about 4:1 to about 12:1. 9. A capsule comprising:
a. a shell; b. a fill phase comprising a wax, a supercritical extract of an herb, and an additional ingredient;
wherein the wax is selected from the group consisting of beeswax, candelilla wax and combinations thereof;
wherein the additional ingredient is selected from the group consisting of extra-virgin olive oil, organic olive oil, organic sunflower oil, maltodextrin, and combinations thereof;
wherein the capsule comprises less than about 5%, by weight of the capsule, beeswax;
wherein the capsule is vegetarian and meets the non-GMO Project Standards; and
wherein at least 98% of the capsules pass the Cracking Test. 10. The capsule of claim 9 wherein the weight ratio of beeswax to candelilla wax is from about 1:3 to about 5:1. 11. The capsule of claim 9 wherein the capsule comprises a volume and wherein the volume is greater than about 0.34 mL. 12. The capsule of claim 9 wherein the supercritical extract of an herb comprises a supercritical extract of ginger. | A capsule with a shell and a fill phase. The fill phase contains less than about 5% beeswax by weight of the capsule and a supercritical extract of an herb. The capsule can be both vegetarian and meet the non-GMO Project Standard.1. A capsule comprising:
a. a shell; b. a fill phase comprising beeswax, candelilla wax, and a supercritical extract of an herb;
wherein the capsule is vegetarian and meets the non-GMO Project Standards;
wherein the capsule comprises greater than 0% and less than about 5%, by weight of the capsule, beeswax; and
wherein at least 98% of the capsules pass the Cracking Test. 2. The capsule of claim 1 wherein the weight ratio of beeswax to candelilla wax is from about 1:3 to about 5:1. 3. The capsule of claim 1 wherein the capsule comprises a volume and wherein the volume is greater than about 0.34 mL. 4. The capsule of claim 1 wherein the supercritical extract of an herb comprises a supercritical extract of ginger. 5. The capsule of claim 4 wherein the supercritical extract of ginger is less than about 10% of the fill phase. 6. The capsule of claim 1 wherein the fill phase comprises from about 1% to about 15% candelilla wax. 7. The capsule of claim 1 further comprising olive oil. 8. The capsule of claim 7 wherein the olive oil to wax ratio in the fill phase is from about 4:1 to about 12:1. 9. A capsule comprising:
a. a shell; b. a fill phase comprising a wax, a supercritical extract of an herb, and an additional ingredient;
wherein the wax is selected from the group consisting of beeswax, candelilla wax and combinations thereof;
wherein the additional ingredient is selected from the group consisting of extra-virgin olive oil, organic olive oil, organic sunflower oil, maltodextrin, and combinations thereof;
wherein the capsule comprises less than about 5%, by weight of the capsule, beeswax;
wherein the capsule is vegetarian and meets the non-GMO Project Standards; and
wherein at least 98% of the capsules pass the Cracking Test. 10. The capsule of claim 9 wherein the weight ratio of beeswax to candelilla wax is from about 1:3 to about 5:1. 11. The capsule of claim 9 wherein the capsule comprises a volume and wherein the volume is greater than about 0.34 mL. 12. The capsule of claim 9 wherein the supercritical extract of an herb comprises a supercritical extract of ginger. | 1,600 |
1,372 | 15,345,991 | 1,653 | An organ perfusion system comprises: a perfusion fluid circuit ( 16 ) arranged to circulate perfusion fluid through the organ; a surrogate organ ( 126 ) arranged to be connected into the circuit in place of the organ so that the circuit can circulate fluid through the surrogate organ; and organ sensing means arranged to distinguish between the presence of the organ in the circuit and the presence of the surrogate organ in the circuit. The sensing means may comprise one or more pressure sensors ( 136, 137, 138 ), or a flow meter ( 125 ). Further aspects relate to adjusting the content of at least one component, such as oxygen or a nutrient, in the perfusion fluid. Bubble detection means ( 113 ), and means ( 74 ) to measure the amount of fluid secreted by or leaked from the organ, may also be provided. | 1. A method of operating a perfusion system to perfuse a bodily organ, the method comprising:
providing a perfusion system, the system comprising a perfusion fluid circuit arranged to circulate perfusion fluid through the bodily organ, a surrogate organ arranged to be connected into the circuit in place of the bodily organ so that the circuit can circulate fluid through the surrogate organ, and an organ sensing system arranged to distinguish between a presence of the bodily organ in the circuit and a presence of the surrogate organ in the circuit; sensing, using the sensing system, the presence of the surrogate organ in the circuit; circulating perfusion fluid through the circuit and the surrogate organ while adjusting at least one parameter of the perfusion fluid to bring it within a target range; disconnecting the surrogate organ from the circuit and connecting the bodily organ into the circuit; sensing, using the sensing system, the presence of the bodily organ in the circuit; and circulating the perfusion fluid through the circuit and the bodily organ. 2. The method of claim 1 wherein the bodily organ provides a first resistance to flow of the perfusion fluid through the circuit, the surrogate organ provides a second resistance to flow of perfusion fluid through the circuit, and the first resistance is greater than the second resistance. 3. The method of claim 2 wherein sensing the presence of the bodily organ in the circuit comprises sensing the change from the first resistance to flow to the second resistance to flow. 4. The method of claim 2 wherein the organ sensing system comprises at least one pressure sensor and the step of sensing the presence of the surrogate organ in the circuit comprises measuring the pressure of the perfusion fluid at at least one point in the circuit. 5. The method of claim 4 wherein the at least one pressure sensor is arranged to measure the pressure of the perfusion fluid at two points in the circuit and the step of sensing the surrogate organ in the circuit comprises measuring the difference in pressure between the two points in the circuit. 6. The method of claim 5 wherein the step of sensing the surrogate organ in the circuit comprises measuring the pressure of perfusion fluid flowing towards the surrogate organ, and measuring the pressure of perfusion fluid flowing away from the surrogate organ. 7. The method of claim 2 wherein the organ sensing system comprises a flow meter and the step of sensing the presence of the surrogate organ in the circuit comprises measuring a rate of flow of the perfusion fluid at at least one point in the circuit. 8. The method of claim 1 wherein, when the surrogate organ is present in the circuit, the perfusion fluid is pumped through the surrogate organ at a constant flow rate. 9. The method of claim 1 wherein, when the bodily organ is present in the circuit, the flow of the perfusion fluid through the circuit is controlled so as to maintain the pressure of the perfusion fluid at at least one point in the circuit within a target pressure range. 10. The method of claim 1 comprising measuring said at least one parameter of the perfusion fluid by measuring a content of at least one component of the perfusion fluid, wherein said component comprises at least one of oxygen, carbon dioxide, and a nutrient. 11. The method of claim 10 wherein the at least one component includes oxygen and the method further comprises adding oxygen into the fluid to maintain said content within said target range. 12. The method of claim 10 wherein the at least one component includes carbon dioxide and the method further comprises extracting carbon dioxide from the fluid to maintain said content within said target range. 13. The method of claim 10 wherein the at least one component is a nutrient and the method further comprises adding the nutrient if the content of the nutrient falls below said target range. 14. The method of claim 10 wherein the system includes a memory storing at least one limit of said target range, and the method comprises comparing the measured content of the at least one component with the at least one limit. 15. The method of claim 1 further comprising defining a target temperature range of the fluid, measuring the temperature of the fluid, and adjusting the temperature of the fluid to maintain the temperature of the fluid within the target temperature range. 16. The method of claim 1 wherein the perfusion system further comprises an analysis duct through which the fluid can flow to bypass the bodily organ, the method further comprising measuring said at least one parameter of the fluid as it passes through the analysis duct. 17. The method of claim 1 wherein the perfusion system further comprises a user interface, the method further comprising inputting at least one limit of said target range via the user interface. 18. The method of claim 1 wherein the perfusion system further comprises a bubble detector arranged to detect bubbles in the perfusion fluid during perfusion, and the method further comprises detecting bubbles in the perfusion fluid using the bubble detector and responding to detecting bubbles in the perfusion fluid by at least one of: producing a warning output, and reducing the fluid flow through at least one part of the circuit. 19. The method of claim 1 further comprising, in response to sensing the presence of the bodily organ in the circuit, switching the system from a preparation mode to a perfusion mode. | An organ perfusion system comprises: a perfusion fluid circuit ( 16 ) arranged to circulate perfusion fluid through the organ; a surrogate organ ( 126 ) arranged to be connected into the circuit in place of the organ so that the circuit can circulate fluid through the surrogate organ; and organ sensing means arranged to distinguish between the presence of the organ in the circuit and the presence of the surrogate organ in the circuit. The sensing means may comprise one or more pressure sensors ( 136, 137, 138 ), or a flow meter ( 125 ). Further aspects relate to adjusting the content of at least one component, such as oxygen or a nutrient, in the perfusion fluid. Bubble detection means ( 113 ), and means ( 74 ) to measure the amount of fluid secreted by or leaked from the organ, may also be provided.1. A method of operating a perfusion system to perfuse a bodily organ, the method comprising:
providing a perfusion system, the system comprising a perfusion fluid circuit arranged to circulate perfusion fluid through the bodily organ, a surrogate organ arranged to be connected into the circuit in place of the bodily organ so that the circuit can circulate fluid through the surrogate organ, and an organ sensing system arranged to distinguish between a presence of the bodily organ in the circuit and a presence of the surrogate organ in the circuit; sensing, using the sensing system, the presence of the surrogate organ in the circuit; circulating perfusion fluid through the circuit and the surrogate organ while adjusting at least one parameter of the perfusion fluid to bring it within a target range; disconnecting the surrogate organ from the circuit and connecting the bodily organ into the circuit; sensing, using the sensing system, the presence of the bodily organ in the circuit; and circulating the perfusion fluid through the circuit and the bodily organ. 2. The method of claim 1 wherein the bodily organ provides a first resistance to flow of the perfusion fluid through the circuit, the surrogate organ provides a second resistance to flow of perfusion fluid through the circuit, and the first resistance is greater than the second resistance. 3. The method of claim 2 wherein sensing the presence of the bodily organ in the circuit comprises sensing the change from the first resistance to flow to the second resistance to flow. 4. The method of claim 2 wherein the organ sensing system comprises at least one pressure sensor and the step of sensing the presence of the surrogate organ in the circuit comprises measuring the pressure of the perfusion fluid at at least one point in the circuit. 5. The method of claim 4 wherein the at least one pressure sensor is arranged to measure the pressure of the perfusion fluid at two points in the circuit and the step of sensing the surrogate organ in the circuit comprises measuring the difference in pressure between the two points in the circuit. 6. The method of claim 5 wherein the step of sensing the surrogate organ in the circuit comprises measuring the pressure of perfusion fluid flowing towards the surrogate organ, and measuring the pressure of perfusion fluid flowing away from the surrogate organ. 7. The method of claim 2 wherein the organ sensing system comprises a flow meter and the step of sensing the presence of the surrogate organ in the circuit comprises measuring a rate of flow of the perfusion fluid at at least one point in the circuit. 8. The method of claim 1 wherein, when the surrogate organ is present in the circuit, the perfusion fluid is pumped through the surrogate organ at a constant flow rate. 9. The method of claim 1 wherein, when the bodily organ is present in the circuit, the flow of the perfusion fluid through the circuit is controlled so as to maintain the pressure of the perfusion fluid at at least one point in the circuit within a target pressure range. 10. The method of claim 1 comprising measuring said at least one parameter of the perfusion fluid by measuring a content of at least one component of the perfusion fluid, wherein said component comprises at least one of oxygen, carbon dioxide, and a nutrient. 11. The method of claim 10 wherein the at least one component includes oxygen and the method further comprises adding oxygen into the fluid to maintain said content within said target range. 12. The method of claim 10 wherein the at least one component includes carbon dioxide and the method further comprises extracting carbon dioxide from the fluid to maintain said content within said target range. 13. The method of claim 10 wherein the at least one component is a nutrient and the method further comprises adding the nutrient if the content of the nutrient falls below said target range. 14. The method of claim 10 wherein the system includes a memory storing at least one limit of said target range, and the method comprises comparing the measured content of the at least one component with the at least one limit. 15. The method of claim 1 further comprising defining a target temperature range of the fluid, measuring the temperature of the fluid, and adjusting the temperature of the fluid to maintain the temperature of the fluid within the target temperature range. 16. The method of claim 1 wherein the perfusion system further comprises an analysis duct through which the fluid can flow to bypass the bodily organ, the method further comprising measuring said at least one parameter of the fluid as it passes through the analysis duct. 17. The method of claim 1 wherein the perfusion system further comprises a user interface, the method further comprising inputting at least one limit of said target range via the user interface. 18. The method of claim 1 wherein the perfusion system further comprises a bubble detector arranged to detect bubbles in the perfusion fluid during perfusion, and the method further comprises detecting bubbles in the perfusion fluid using the bubble detector and responding to detecting bubbles in the perfusion fluid by at least one of: producing a warning output, and reducing the fluid flow through at least one part of the circuit. 19. The method of claim 1 further comprising, in response to sensing the presence of the bodily organ in the circuit, switching the system from a preparation mode to a perfusion mode. | 1,600 |
1,373 | 13,186,017 | 1,649 | A laboratory method for screening, diagnosing, monitoring and/or staging early onset Alzheimer's disease which consists of mild cognitive impairment entails conducting a blood test after an oxidative exposure of serum to assay for the presence of an elevated level of redox-reactive autoantibodies. | 1. A laboratory method for screening, diagnosing, monitoring and/or staging early onset Alzheimer's disease which consists of mild cognitive impairment comprises conducting a blood test after an oxidative exposure of serum to assay for the presence of an elevated level of redox-reactive autoantibodies. 2. The method of claim 1, wherein the antiphospholipid autoantibody is anticardiolipin, antiphosphatidylcholine, antiphosphatidylethanolamine or antiphosphatidylserine. 3. The method of claim 1 wherein the subject is selected as exhibiting physical or cognitive symptoms of an early onset Alzheimer's disease. 4. The method of claim 1, wherein the subject has a family history of Alzheimer's disease. 5. The method of claim 1, wherein the subject has a family history of Alzheimer's disease and wherein the subject is at or beyond an average age of onset of family members having said Alzheimer's disease. 6. The method of claim 1, wherein an elevated level of at least one antiphospholipid autoantibody is determined relative to a baseline value. 7. The method of claim 1, wherein an elevated level of redox-reactive autoantibodies is determined relative to a baseline value or wherein the baseline value is an average or mean value of a level found in a population of control individuals. 8. A method of monitoring the development or progress of early onset Alzheimer's disease over a period of time, wherein the method comprises carrying out the method of claim 1 at the beginning of a period of time and then carrying out repetitions of the method at subsequent times. 9. A method of detecting or diagnosing early onset Alzheimer's disease in a subject, the method comprising the steps of assaying an oxidized first blood sample from the subject to determine a baseline level of oxidized autoantibodies having a selected specificities, treating a second longitudinal blood sample with an oxidizing agent and assaying the oxidized second sample to determine the level of autoantibodies having the selected specificities, and comparing the level of the autoantibodies in the first sample with the level of autoantibodies in the oxidized second sample, wherein an increase in the level of autoantibodies in the oxidized second sample as compared to the level of the oxidized first sample correlates with early onset Alzheimer's disease defined as mild cognitive impairment in said subject. 10. The method of claim 9, wherein the autoantibodies having selected specificities are anticardiolipin, antiphosphatidylcholine, antiphosphatidylethanolamine or antiphosphatidylserine. 11. A blood serum biomarker for diagnosing, monitoring and/or staging early onset Alzheimer's disease defined as mild cognitively impairment comprising redox-reactive autoantibodies. 12. A kit for diagnosing, monitoring and/or staging early onset Alzheimer's disease defined as mildly cognitively impaired individuals which comprises a laboratory assay which can detect redox reactive autoantibodies before and after exposure to an oxidative agent. | A laboratory method for screening, diagnosing, monitoring and/or staging early onset Alzheimer's disease which consists of mild cognitive impairment entails conducting a blood test after an oxidative exposure of serum to assay for the presence of an elevated level of redox-reactive autoantibodies.1. A laboratory method for screening, diagnosing, monitoring and/or staging early onset Alzheimer's disease which consists of mild cognitive impairment comprises conducting a blood test after an oxidative exposure of serum to assay for the presence of an elevated level of redox-reactive autoantibodies. 2. The method of claim 1, wherein the antiphospholipid autoantibody is anticardiolipin, antiphosphatidylcholine, antiphosphatidylethanolamine or antiphosphatidylserine. 3. The method of claim 1 wherein the subject is selected as exhibiting physical or cognitive symptoms of an early onset Alzheimer's disease. 4. The method of claim 1, wherein the subject has a family history of Alzheimer's disease. 5. The method of claim 1, wherein the subject has a family history of Alzheimer's disease and wherein the subject is at or beyond an average age of onset of family members having said Alzheimer's disease. 6. The method of claim 1, wherein an elevated level of at least one antiphospholipid autoantibody is determined relative to a baseline value. 7. The method of claim 1, wherein an elevated level of redox-reactive autoantibodies is determined relative to a baseline value or wherein the baseline value is an average or mean value of a level found in a population of control individuals. 8. A method of monitoring the development or progress of early onset Alzheimer's disease over a period of time, wherein the method comprises carrying out the method of claim 1 at the beginning of a period of time and then carrying out repetitions of the method at subsequent times. 9. A method of detecting or diagnosing early onset Alzheimer's disease in a subject, the method comprising the steps of assaying an oxidized first blood sample from the subject to determine a baseline level of oxidized autoantibodies having a selected specificities, treating a second longitudinal blood sample with an oxidizing agent and assaying the oxidized second sample to determine the level of autoantibodies having the selected specificities, and comparing the level of the autoantibodies in the first sample with the level of autoantibodies in the oxidized second sample, wherein an increase in the level of autoantibodies in the oxidized second sample as compared to the level of the oxidized first sample correlates with early onset Alzheimer's disease defined as mild cognitive impairment in said subject. 10. The method of claim 9, wherein the autoantibodies having selected specificities are anticardiolipin, antiphosphatidylcholine, antiphosphatidylethanolamine or antiphosphatidylserine. 11. A blood serum biomarker for diagnosing, monitoring and/or staging early onset Alzheimer's disease defined as mild cognitively impairment comprising redox-reactive autoantibodies. 12. A kit for diagnosing, monitoring and/or staging early onset Alzheimer's disease defined as mildly cognitively impaired individuals which comprises a laboratory assay which can detect redox reactive autoantibodies before and after exposure to an oxidative agent. | 1,600 |
1,374 | 15,821,146 | 1,642 | The present invention provides a novel cancer marker for testing a morbidity risk of a cancer. The cancer marker according to the present invention is a prorenin receptor. A test method for testing a morbidity risk of a cancer according to the present invention includes measuring a prorenin receptor expression in a biological specimen obtained from a subject and further includes, for example, a step of comparing a prorenin receptor expression level in the biological specimen obtained from the subject with a reference value to test the morbidity risk of the cancer in the subject. The reference value is a prorenin receptor expression level in a biological specimen obtained from a healthy subject or a cancer patient. When the expression level in the subject is higher than that in the healthy subject or identical to or higher than that in the cancer patient, it can be evaluated that the subject has the mobility risk of the cancer. | 1. A test and therapeutic method, comprising:
measuring a prorenin receptor expression level in a biological specimen obtained from a subject, wherein
the biological specimen is a blood specimen, and
a cancer to be tested is at least one of a pancreatic cancer and a brain tumor;
comparing the prorenin receptor expression level in the biological specimen obtained from the subject with a reference value to test the morbidity risk of the cancer in the subject, wherein
the reference value is a prorenin receptor expression level in a biological specimen obtained from a healthy subject or a cancer patient, and
when the prorenin receptor expression level in the biological specimen obtained from the subject is higher than that in the biological specimen obtained from the healthy subject, or identical to or higher than that in the biological specimen obtained from the cancer patient, determining the subject to have a morbidity risk from the pancreatic cancer or brain tumor; and
administering a therapeutic composition for the pancreatic cancer or brain tumor to the subject determined to have the high morbidity risk from the pancreatic cancer or brain tumor, the therapeutic composition comprising at least one of a binding substance for binding to a prorenin receptor and an expression suppressive substance for suppressing a prorenin receptor expression. 2. The test and therapeutic method according to claim 1, wherein
the cancer is a pancreatic cancer. 3. The test and therapeutic method according to claim 1, wherein
the brain tumor is at least one selected from the group consisting of glioma, astrocytoma, primary central nervous system malignant lymphoma, and cavernous hemangioma. 4-5. (canceled) 6. The test and therapeutic method according to claim 1, wherein
the prorenin receptor expression level is at least one of an expression level of mRNA of a prorenin receptor and an expression level of a prorenin receptor protein. 7-26. (canceled) 27. The test and therapeutic method according to claim 1, wherein
the binding substance for binding to a prorenin receptor comprises an antibody to a prorenin receptor or an antigen binding fragment of the antibody. 28. The test and therapeutic method according to claim 27, wherein
the antibody or the antigen binding fragment binds a region extending from the 200th to 213rd amino acid residues in an amino acid sequence (SEQ ID NO: 6) of a human prorenin receptor protein. 29. An antibody to a prorenin receptor or an antigen binding fragment of the antibody, wherein
the antibody or the antigen binding fragment binds a region extending from the 200th to 213rd amino acid residues in an amino acid sequence (SEQ ID NO: 6) of a human prorenin receptor protein. 30. A method for treating a pancreatic cancer, comprising the step of administrating an antibody to a prorenin receptor or an antigen binding fragment of the antibody to a subject. 31. The method for treating a pancreatic cancer according to claim 30, wherein
the antibody or the antigen binding fragment binds a region extending from the 200th to 213rd amino acid residues in an amino acid sequence (SEQ ID NO: 6) of a human prorenin receptor protein. 32. The method for treating a pancreatic cancer according to claim 30, wherein
the antibody or the antigen binding fragment is administrated in a pancreatic cancer. | The present invention provides a novel cancer marker for testing a morbidity risk of a cancer. The cancer marker according to the present invention is a prorenin receptor. A test method for testing a morbidity risk of a cancer according to the present invention includes measuring a prorenin receptor expression in a biological specimen obtained from a subject and further includes, for example, a step of comparing a prorenin receptor expression level in the biological specimen obtained from the subject with a reference value to test the morbidity risk of the cancer in the subject. The reference value is a prorenin receptor expression level in a biological specimen obtained from a healthy subject or a cancer patient. When the expression level in the subject is higher than that in the healthy subject or identical to or higher than that in the cancer patient, it can be evaluated that the subject has the mobility risk of the cancer.1. A test and therapeutic method, comprising:
measuring a prorenin receptor expression level in a biological specimen obtained from a subject, wherein
the biological specimen is a blood specimen, and
a cancer to be tested is at least one of a pancreatic cancer and a brain tumor;
comparing the prorenin receptor expression level in the biological specimen obtained from the subject with a reference value to test the morbidity risk of the cancer in the subject, wherein
the reference value is a prorenin receptor expression level in a biological specimen obtained from a healthy subject or a cancer patient, and
when the prorenin receptor expression level in the biological specimen obtained from the subject is higher than that in the biological specimen obtained from the healthy subject, or identical to or higher than that in the biological specimen obtained from the cancer patient, determining the subject to have a morbidity risk from the pancreatic cancer or brain tumor; and
administering a therapeutic composition for the pancreatic cancer or brain tumor to the subject determined to have the high morbidity risk from the pancreatic cancer or brain tumor, the therapeutic composition comprising at least one of a binding substance for binding to a prorenin receptor and an expression suppressive substance for suppressing a prorenin receptor expression. 2. The test and therapeutic method according to claim 1, wherein
the cancer is a pancreatic cancer. 3. The test and therapeutic method according to claim 1, wherein
the brain tumor is at least one selected from the group consisting of glioma, astrocytoma, primary central nervous system malignant lymphoma, and cavernous hemangioma. 4-5. (canceled) 6. The test and therapeutic method according to claim 1, wherein
the prorenin receptor expression level is at least one of an expression level of mRNA of a prorenin receptor and an expression level of a prorenin receptor protein. 7-26. (canceled) 27. The test and therapeutic method according to claim 1, wherein
the binding substance for binding to a prorenin receptor comprises an antibody to a prorenin receptor or an antigen binding fragment of the antibody. 28. The test and therapeutic method according to claim 27, wherein
the antibody or the antigen binding fragment binds a region extending from the 200th to 213rd amino acid residues in an amino acid sequence (SEQ ID NO: 6) of a human prorenin receptor protein. 29. An antibody to a prorenin receptor or an antigen binding fragment of the antibody, wherein
the antibody or the antigen binding fragment binds a region extending from the 200th to 213rd amino acid residues in an amino acid sequence (SEQ ID NO: 6) of a human prorenin receptor protein. 30. A method for treating a pancreatic cancer, comprising the step of administrating an antibody to a prorenin receptor or an antigen binding fragment of the antibody to a subject. 31. The method for treating a pancreatic cancer according to claim 30, wherein
the antibody or the antigen binding fragment binds a region extending from the 200th to 213rd amino acid residues in an amino acid sequence (SEQ ID NO: 6) of a human prorenin receptor protein. 32. The method for treating a pancreatic cancer according to claim 30, wherein
the antibody or the antigen binding fragment is administrated in a pancreatic cancer. | 1,600 |
1,375 | 16,267,301 | 1,618 | The subject invention concerns materials and methods for detecting and diagnosing conditions associated with accumulation of Aβ peptide in neural tissue, such as Alzheimer's disease and Parkinson's disease, using the chemical cotinine. In one embodiment, the method comprises administering cotinine labeled with a detectable label to a person or animal. The presence of labeled cotinine in neural tissue is then determined. The level and/or location of cotinine can be analyzed and a diagnosis made. The subject invention also concerns cotinine labeled with a detectable label. In one embodiment, the cotinine is labeled with a radioisotope that can be detected by Positron Emission Tomography (PET) or single photon emission computed tomography (SPECT). | 1. A method for treating and/or preventing a disease or condition associated with the accumulation and/or aggregation of Aβ peptide in neural tissue, or for treating and/or preventing a disorder or condition associated with Down's syndrome, or for treating and/or preventing a post-traumatic stress disorder or condition, said method comprising administering an effective amount of cotinine, or a composition comprising cotinine, or an isomer or racemate thereof, or a pharmaceutically acceptable salt thereof, to a person or animal so as to treat and/or prevent a disease or condition associated with the accumulation and/or aggregation of Aβ peptide in neural tissue, treat and/or prevent a disorder or condition associated with Down's syndrome, or treat and/or prevent a post-traumatic stress disorder or condition, wherein cotinine inhibits formation of soluble Aβ oligomer from Aβ monomers and protects neuron from Aβ toxicity associated with soluble Aβ oligomer and/or enhances the extinction of fear memory in a person or animal in need of treatment. 2. The method according to claim 1, wherein said method further comprises administering one or more drugs for the treatment or prevent of a neurodegenerative condition. 3. The method according to claim 2, wherein said one or more drug is donepezil (ARICEPT), galantamine (RAZADYNE), rivastigmine (EXELON), memantine (AKATINOL), rasagiline (AZILECT), selegiline (ELDEPRYL), L-dopa (LEVODOPA, SINEMET, PARCOPA, STALEVO, MADOPAR), carbidopa (LODOSYN), or benserazide, or an isomer or analog thereof, or a pharmaceutically acceptable salt thereof. 4. The method according to claim 1, wherein said method further comprises administering one or more drugs for the treatment of a stress disorder or condition. 5. The method according to claim 4, wherein said one or more drug is a selective serotonin reuptake inhibitor (SSRI); a serotonin-norepinephrine reuptake inhibitor (SNRI); a tricyclic antidepressants (TCA); 3,4-methylenedioxy-N-methylamphetamine (MDMA); propranolol; clonidine; or ziprasidone. 6. The method according to claim 5, wherein said SSRI is citalopram, escitalopram, fluvoxamine, paroxetine, or sertraline and/or said SNRI is venlafaxine, desvenlafaxine, duloxetine, sibutramine, or milnacripran. 7. A method for inhibiting or preventing Aβ oligomerization, or for increasing activity or expression of dopamine- and cyclic AMP-regulated phosphoprotein of 32 kDa (DARPP-32) and/or facilitating serotonin release in neural tissue or a cell, said method comprising contacting a cell with an effective amount of cotinine, or a composition comprising cotinine, or a pharmaceutically acceptable salt thereof; wherein cotinine inhibits formation of soluble Aβ oligomer from Aβ monomers and protects neuron from Aβ toxicity associated with soluble Aβ oligomer and/or increases activity or expression of donamine- and cyclic AMP-regulated phosphoprotein of 32 kDa (DARPP-32) and/or facilitates serotonin release in neural tissue or a cell. 8. The method according to claim 7, wherein said cell is a cortical cell. 9-24. (canceled) 25. The method according to claim 1, wherein interaction of cotinine with Aβ peptide comprises cotinine interacting with residues His-6, Tyr-10, and His-14 of Aβ peptide, 26. The method according to claim 25, wherein pyridine ring of cotinine is positioned between imidazole ring of His-6 and phenyl ring of Tyr-10 of Aβ peptide so as to permit strong π-π interactions and/or wherein methyl group of methylpyrrolidone ring of cotinine is positioned against imidazole ring of His-14 of Aβ peptide so as to permit C—H-π interaction. 27. The method according to claim 1, wherein the Aβ peptide is or comprises Aβ(1-42) peptide. | The subject invention concerns materials and methods for detecting and diagnosing conditions associated with accumulation of Aβ peptide in neural tissue, such as Alzheimer's disease and Parkinson's disease, using the chemical cotinine. In one embodiment, the method comprises administering cotinine labeled with a detectable label to a person or animal. The presence of labeled cotinine in neural tissue is then determined. The level and/or location of cotinine can be analyzed and a diagnosis made. The subject invention also concerns cotinine labeled with a detectable label. In one embodiment, the cotinine is labeled with a radioisotope that can be detected by Positron Emission Tomography (PET) or single photon emission computed tomography (SPECT).1. A method for treating and/or preventing a disease or condition associated with the accumulation and/or aggregation of Aβ peptide in neural tissue, or for treating and/or preventing a disorder or condition associated with Down's syndrome, or for treating and/or preventing a post-traumatic stress disorder or condition, said method comprising administering an effective amount of cotinine, or a composition comprising cotinine, or an isomer or racemate thereof, or a pharmaceutically acceptable salt thereof, to a person or animal so as to treat and/or prevent a disease or condition associated with the accumulation and/or aggregation of Aβ peptide in neural tissue, treat and/or prevent a disorder or condition associated with Down's syndrome, or treat and/or prevent a post-traumatic stress disorder or condition, wherein cotinine inhibits formation of soluble Aβ oligomer from Aβ monomers and protects neuron from Aβ toxicity associated with soluble Aβ oligomer and/or enhances the extinction of fear memory in a person or animal in need of treatment. 2. The method according to claim 1, wherein said method further comprises administering one or more drugs for the treatment or prevent of a neurodegenerative condition. 3. The method according to claim 2, wherein said one or more drug is donepezil (ARICEPT), galantamine (RAZADYNE), rivastigmine (EXELON), memantine (AKATINOL), rasagiline (AZILECT), selegiline (ELDEPRYL), L-dopa (LEVODOPA, SINEMET, PARCOPA, STALEVO, MADOPAR), carbidopa (LODOSYN), or benserazide, or an isomer or analog thereof, or a pharmaceutically acceptable salt thereof. 4. The method according to claim 1, wherein said method further comprises administering one or more drugs for the treatment of a stress disorder or condition. 5. The method according to claim 4, wherein said one or more drug is a selective serotonin reuptake inhibitor (SSRI); a serotonin-norepinephrine reuptake inhibitor (SNRI); a tricyclic antidepressants (TCA); 3,4-methylenedioxy-N-methylamphetamine (MDMA); propranolol; clonidine; or ziprasidone. 6. The method according to claim 5, wherein said SSRI is citalopram, escitalopram, fluvoxamine, paroxetine, or sertraline and/or said SNRI is venlafaxine, desvenlafaxine, duloxetine, sibutramine, or milnacripran. 7. A method for inhibiting or preventing Aβ oligomerization, or for increasing activity or expression of dopamine- and cyclic AMP-regulated phosphoprotein of 32 kDa (DARPP-32) and/or facilitating serotonin release in neural tissue or a cell, said method comprising contacting a cell with an effective amount of cotinine, or a composition comprising cotinine, or a pharmaceutically acceptable salt thereof; wherein cotinine inhibits formation of soluble Aβ oligomer from Aβ monomers and protects neuron from Aβ toxicity associated with soluble Aβ oligomer and/or increases activity or expression of donamine- and cyclic AMP-regulated phosphoprotein of 32 kDa (DARPP-32) and/or facilitates serotonin release in neural tissue or a cell. 8. The method according to claim 7, wherein said cell is a cortical cell. 9-24. (canceled) 25. The method according to claim 1, wherein interaction of cotinine with Aβ peptide comprises cotinine interacting with residues His-6, Tyr-10, and His-14 of Aβ peptide, 26. The method according to claim 25, wherein pyridine ring of cotinine is positioned between imidazole ring of His-6 and phenyl ring of Tyr-10 of Aβ peptide so as to permit strong π-π interactions and/or wherein methyl group of methylpyrrolidone ring of cotinine is positioned against imidazole ring of His-14 of Aβ peptide so as to permit C—H-π interaction. 27. The method according to claim 1, wherein the Aβ peptide is or comprises Aβ(1-42) peptide. | 1,600 |
1,376 | 14,315,140 | 1,637 | In some embodiments, the present teachings provide compositions, systems, methods and kits for generating a population of nucleic acid fragments. In some embodiments, nucleic acids can be fragmented enzymatically. For example, methods for generating a population of nucleic acid fragments can include a nucleic acid nicking reaction. In one embodiment, the methods can include a nick translation reaction. A nicking reaction can introduce nicks at random positions on either strand of a double-stranded nucleic acid. A nick translation reaction can move the position of nicks to a new position so that the new positions of two of the nicks are aligned to create a double-stranded break. In some embodiments, methods for generating a population of nucleic acid fragments can include joining at least one end of a fragmented nucleic acid to one or more oligonucleotide adaptors. | 1. A method for generating a population of nucleic acid fragments comprising:
(a) nicking a double stranded nucleic acid molecule at least once on each strand, wherein the nucleic acid molecule does not include uracil; and (b) fragmenting the nucleic acid molecule by nick translating at least one nick in each strand and generating at least one double-stranded break in the nucleic acid molecule, thereby producing two or more nucleic acid fragments. 2. The method of claim 1, wherein the nicking comprises enzymatic nicking. 3. The method of claim 1, wherein the nick translating comprises a 5′ to 3′ DNA polymerization/degradation reaction or a 5′ to 3′ DNA polymerization/strand displacement reaction. 4. The method of claim 1, wherein the nick translating includes polymerizing one or more unlabeled nucleotides onto the 3′ end of at least one nick. 5. The method of claim 1, wherein at least one of the nucleic acid fragments is not labeled. 6. The method of claim 1, wherein substantially all of the nucleic acid fragments are not labeled. 7. The method of claim 1, further including joining both strands of at least one end of a nucleic acid fragment to both strands of a double-stranded oligonucleotide adaptor. 8. The method of claim 1, further comprising adjusting the average size of the nucleic acid fragments by modulating the reaction conditions for the nicking conditions. 9. A population of nucleic acid fragments generated by the method of claim 1. 10. The method of claim 1, further including a single-stranded nucleic acid binding protein. 11. A method for nucleic acid fragmentation, comprising:
(a) providing a solution including a plurality of double stranded nucleic acid molecules that do not include uracil; and (b) subjecting at least two different nucleic acid molecules of the plurality to the methods of claim 1. 12. The method of claim 11, further including fragmenting that at least two different nucleic acid molecules of the plurality in the same reaction mixture. 13. The method of claim 11, further including a single-stranded nucleic acid binding protein. | In some embodiments, the present teachings provide compositions, systems, methods and kits for generating a population of nucleic acid fragments. In some embodiments, nucleic acids can be fragmented enzymatically. For example, methods for generating a population of nucleic acid fragments can include a nucleic acid nicking reaction. In one embodiment, the methods can include a nick translation reaction. A nicking reaction can introduce nicks at random positions on either strand of a double-stranded nucleic acid. A nick translation reaction can move the position of nicks to a new position so that the new positions of two of the nicks are aligned to create a double-stranded break. In some embodiments, methods for generating a population of nucleic acid fragments can include joining at least one end of a fragmented nucleic acid to one or more oligonucleotide adaptors.1. A method for generating a population of nucleic acid fragments comprising:
(a) nicking a double stranded nucleic acid molecule at least once on each strand, wherein the nucleic acid molecule does not include uracil; and (b) fragmenting the nucleic acid molecule by nick translating at least one nick in each strand and generating at least one double-stranded break in the nucleic acid molecule, thereby producing two or more nucleic acid fragments. 2. The method of claim 1, wherein the nicking comprises enzymatic nicking. 3. The method of claim 1, wherein the nick translating comprises a 5′ to 3′ DNA polymerization/degradation reaction or a 5′ to 3′ DNA polymerization/strand displacement reaction. 4. The method of claim 1, wherein the nick translating includes polymerizing one or more unlabeled nucleotides onto the 3′ end of at least one nick. 5. The method of claim 1, wherein at least one of the nucleic acid fragments is not labeled. 6. The method of claim 1, wherein substantially all of the nucleic acid fragments are not labeled. 7. The method of claim 1, further including joining both strands of at least one end of a nucleic acid fragment to both strands of a double-stranded oligonucleotide adaptor. 8. The method of claim 1, further comprising adjusting the average size of the nucleic acid fragments by modulating the reaction conditions for the nicking conditions. 9. A population of nucleic acid fragments generated by the method of claim 1. 10. The method of claim 1, further including a single-stranded nucleic acid binding protein. 11. A method for nucleic acid fragmentation, comprising:
(a) providing a solution including a plurality of double stranded nucleic acid molecules that do not include uracil; and (b) subjecting at least two different nucleic acid molecules of the plurality to the methods of claim 1. 12. The method of claim 11, further including fragmenting that at least two different nucleic acid molecules of the plurality in the same reaction mixture. 13. The method of claim 11, further including a single-stranded nucleic acid binding protein. | 1,600 |
1,377 | 16,292,406 | 1,699 | The invention features 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs, compositions containing them, and methods of using them as PPAR delta modulators to treat or inhibit the progression of, for example, dyslipidemia. | 1-56. (canceled) 57. A compound of Formula (II):
wherein
X is selected from a covalent bond, S, or O;
Y is S or O;
- - - - -W- - - - - represents a group selected from —CH═, —CH2—, —CH2—CH2—, —CH2—CH═, and —CH═CH—;
Z is selected from O, CH, and CH2, provided when Y is O, Z is O;
R1 and R2 are independently selected from H, C1-3 alkyl, C1-3 alkoxy, halo, and NRaRb wherein Ra and Rb are independently H or C1-3 alkyl;
R3 and R4 are independently selected from H, halo, cyano, hydroxy, acetyl, C1-5 alkyl, C1-4 alkoxy, and NRcRd wherein Rc and Rd are independently H or C1-3 alkyl, provided that R3 and R4 are not both H;
n is 1 or 2;
or a pharmaceutically acceptable salt thereof. 58. The compound of claim 57 wherein X is S or O. 59. The compound of claim 58 wherein X is O. 60. The compound of claim 57 wherein X is a covalent bond. 61. The compound of claim 57 wherein Y is O. 62. The compound of claim 57 wherein Y is S. 63. The compound of claim 57 wherein Z is O. 64. The compound of claim 57 wherein Z is CH or CH2. 65. The compound of claim 57 wherein - - - - -W- - - - - represents —CH2— or CH2—CH2—. 66. The compound of claim 65 wherein - - - - -W- - - - - represents —CH2—. 67. The compound of claim 57 wherein - - - - -W- - - - - represents —CH═, —CH2—CH═, or —CH═CH—. 68. The compound of claim 57 wherein R3 and R4 are independently selected from H, halo, cyano, C1-4 alkyl, and C1-3 alkoxy. 69. The compound of claim 57 wherein R1 and R2 are independently selected from H, C1-3 alkyl, C1-3 alkoxy, F, Cl, and Br. 70. The compound of claim 69 wherein R1 and R2 are independently selected from H, methyl, methoxy, F and Cl. 71. The compound of claim 57 wherein R3 and R4 are independently selected from H, halo, cyano, hydroxy, C2-4 acyl, C1-4 alkyl, and C1-3 alkoxy. 72. The compound of claim 71 wherein R3 is independently selected from H, F, Cl, methyl, and methoxy. 73. The compound of claim 71 wherein R4 is independently selected from F, Cl, methyl, methoxy, trifluoromethyl, fluoromethyl, difluoromethyl, chlorodifluoromethyl, dichlorofluoromethyl, fluoromethoxy, difluoromethoxy, chlorodifluoromethoxy, dichlorofluoromethoxy and trifluoromethoxy. 74. The compound of claim 57 wherein R3 is selected from methyl, methoxy, H, Cl, Br, I, OH, —CH(CF3)2, CF3, —OCF3, —N(CH3)2, —O—CH2COOH, and —COCH3, and R4 is selected from H, Cl, and methyl. 75. The compound of claim 57 wherein R3 is selected from H, F, Cl, methyl, and methoxy, and R4 is selected from F, Cl, methyl, fluoromethyl, difluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethyl, trifluoromethoxy, and methoxy. 76. The compound of claim 57 wherein R1 is selected from H, CF3, methyl, Cl, and methoxy, and R2 is selected from H, Cl, and methyl. 77-92. (canceled) 94. A pharmaceutical composition comprising a compound of of claims 57. 95. (canceled) | The invention features 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs, compositions containing them, and methods of using them as PPAR delta modulators to treat or inhibit the progression of, for example, dyslipidemia.1-56. (canceled) 57. A compound of Formula (II):
wherein
X is selected from a covalent bond, S, or O;
Y is S or O;
- - - - -W- - - - - represents a group selected from —CH═, —CH2—, —CH2—CH2—, —CH2—CH═, and —CH═CH—;
Z is selected from O, CH, and CH2, provided when Y is O, Z is O;
R1 and R2 are independently selected from H, C1-3 alkyl, C1-3 alkoxy, halo, and NRaRb wherein Ra and Rb are independently H or C1-3 alkyl;
R3 and R4 are independently selected from H, halo, cyano, hydroxy, acetyl, C1-5 alkyl, C1-4 alkoxy, and NRcRd wherein Rc and Rd are independently H or C1-3 alkyl, provided that R3 and R4 are not both H;
n is 1 or 2;
or a pharmaceutically acceptable salt thereof. 58. The compound of claim 57 wherein X is S or O. 59. The compound of claim 58 wherein X is O. 60. The compound of claim 57 wherein X is a covalent bond. 61. The compound of claim 57 wherein Y is O. 62. The compound of claim 57 wherein Y is S. 63. The compound of claim 57 wherein Z is O. 64. The compound of claim 57 wherein Z is CH or CH2. 65. The compound of claim 57 wherein - - - - -W- - - - - represents —CH2— or CH2—CH2—. 66. The compound of claim 65 wherein - - - - -W- - - - - represents —CH2—. 67. The compound of claim 57 wherein - - - - -W- - - - - represents —CH═, —CH2—CH═, or —CH═CH—. 68. The compound of claim 57 wherein R3 and R4 are independently selected from H, halo, cyano, C1-4 alkyl, and C1-3 alkoxy. 69. The compound of claim 57 wherein R1 and R2 are independently selected from H, C1-3 alkyl, C1-3 alkoxy, F, Cl, and Br. 70. The compound of claim 69 wherein R1 and R2 are independently selected from H, methyl, methoxy, F and Cl. 71. The compound of claim 57 wherein R3 and R4 are independently selected from H, halo, cyano, hydroxy, C2-4 acyl, C1-4 alkyl, and C1-3 alkoxy. 72. The compound of claim 71 wherein R3 is independently selected from H, F, Cl, methyl, and methoxy. 73. The compound of claim 71 wherein R4 is independently selected from F, Cl, methyl, methoxy, trifluoromethyl, fluoromethyl, difluoromethyl, chlorodifluoromethyl, dichlorofluoromethyl, fluoromethoxy, difluoromethoxy, chlorodifluoromethoxy, dichlorofluoromethoxy and trifluoromethoxy. 74. The compound of claim 57 wherein R3 is selected from methyl, methoxy, H, Cl, Br, I, OH, —CH(CF3)2, CF3, —OCF3, —N(CH3)2, —O—CH2COOH, and —COCH3, and R4 is selected from H, Cl, and methyl. 75. The compound of claim 57 wherein R3 is selected from H, F, Cl, methyl, and methoxy, and R4 is selected from F, Cl, methyl, fluoromethyl, difluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethyl, trifluoromethoxy, and methoxy. 76. The compound of claim 57 wherein R1 is selected from H, CF3, methyl, Cl, and methoxy, and R2 is selected from H, Cl, and methyl. 77-92. (canceled) 94. A pharmaceutical composition comprising a compound of of claims 57. 95. (canceled) | 1,600 |
1,378 | 15,873,284 | 1,615 | A hand powder composition, particularly useful for musicians of necked stringed instruments, comprising a fine moisture absorbing powder in an amount from about 90%-99% by weight of the total composition and a fine polytetrafluoroethylene powder in an amount from about 1%-7% by weight of the total composition. The polytetrafluoroethylene powder may have average particle sizes of about 18-22 μm. The moisture absorbing powder may be talcum powder or corn starch, or a combination thereof. A fine alkaline powder may be included to neutralize acidity of perspiration. A fine powdered colorant may be included for approximately matching the color of the composition to a desired color. | 1. A hand powder composition comprising: a fine moisture absorbing powder in an amount from about 90%-99% by weight of the total composition; and
a fine polytetrafluoroethylene powder in an amount from about 1%-7% by weight of the total composition. 2. The hand powder composition of claim 1 wherein the average particle sizes of the polytetrafluoroethylene powder are about 18-22 μm. 3. The hand powder composition of any one of claims 1-2 wherein the wherein the moisture absorbing powder is talcum powder. 4. The hand powder composition of any one of claims 1-2 wherein the moisture absorbing powder is corn starch. 5. The hand powder composition of any one of claims 1-4 wherein the amount of polytetrafluoroethylene is from about 2%-4% by weight of the composition. 6. The hand powder composition of any one of claims 1-4 wherein the amount of polytetrafluoroethylene is about 3.5% by weight of the composition. 7. The hand powder composition of any one of claims 1-6 further comprising a fine alkaline powder to neutralize acidity of perspiration. 8. The hand powder composition of claims 7 wherein the alkaline powder is sodium bicarbonate in an amount from about 0.25%-1.5% by weight of the composition. 9. The hand powder composition of claims 8 wherein the amount of sodium bicarbonate is about 1% by weight of the composition. 10. The hand powder composition of any one of claims 1-9 further comprising a fine powdered colorant for approximately matching the color of the composition to a desired color. 11. The use of a hand powder composition of any one of claims 1-10 for playing necked stringed musical instruments. 12. The use of a hand powder composition of any one of claims 1-10 on a hand for increasing glide feel between the hand and a neck of a stringed musical instrument. 13. The use of a hand powder composition of any one of claims 1-10 for playing billiards. 14. The use of a hand powder composition of any one of claims 1-10 on a hand for increasing glide feel between the hand and a billiard cue. | A hand powder composition, particularly useful for musicians of necked stringed instruments, comprising a fine moisture absorbing powder in an amount from about 90%-99% by weight of the total composition and a fine polytetrafluoroethylene powder in an amount from about 1%-7% by weight of the total composition. The polytetrafluoroethylene powder may have average particle sizes of about 18-22 μm. The moisture absorbing powder may be talcum powder or corn starch, or a combination thereof. A fine alkaline powder may be included to neutralize acidity of perspiration. A fine powdered colorant may be included for approximately matching the color of the composition to a desired color.1. A hand powder composition comprising: a fine moisture absorbing powder in an amount from about 90%-99% by weight of the total composition; and
a fine polytetrafluoroethylene powder in an amount from about 1%-7% by weight of the total composition. 2. The hand powder composition of claim 1 wherein the average particle sizes of the polytetrafluoroethylene powder are about 18-22 μm. 3. The hand powder composition of any one of claims 1-2 wherein the wherein the moisture absorbing powder is talcum powder. 4. The hand powder composition of any one of claims 1-2 wherein the moisture absorbing powder is corn starch. 5. The hand powder composition of any one of claims 1-4 wherein the amount of polytetrafluoroethylene is from about 2%-4% by weight of the composition. 6. The hand powder composition of any one of claims 1-4 wherein the amount of polytetrafluoroethylene is about 3.5% by weight of the composition. 7. The hand powder composition of any one of claims 1-6 further comprising a fine alkaline powder to neutralize acidity of perspiration. 8. The hand powder composition of claims 7 wherein the alkaline powder is sodium bicarbonate in an amount from about 0.25%-1.5% by weight of the composition. 9. The hand powder composition of claims 8 wherein the amount of sodium bicarbonate is about 1% by weight of the composition. 10. The hand powder composition of any one of claims 1-9 further comprising a fine powdered colorant for approximately matching the color of the composition to a desired color. 11. The use of a hand powder composition of any one of claims 1-10 for playing necked stringed musical instruments. 12. The use of a hand powder composition of any one of claims 1-10 on a hand for increasing glide feel between the hand and a neck of a stringed musical instrument. 13. The use of a hand powder composition of any one of claims 1-10 for playing billiards. 14. The use of a hand powder composition of any one of claims 1-10 on a hand for increasing glide feel between the hand and a billiard cue. | 1,600 |
1,379 | 15,516,038 | 1,651 | According to the invention, it has been found that a particulate biomass containing an oxidation-sensitive material of value can be converted into a particularly easy-to-handle product in a gentle manner if it is subjected to a granulation with the addition of an agglomeration auxiliary. | 1-17. (canceled) 18. A method for producing a particulate biomass having an oxidation-sensitive material of value, said method comprising granulating a particulate starting biomass in the presence of an agglomeration auxiliary. 19. The method of claim 18, wherein carbohydrates, or modified carbohydrates, are used as the agglomeration auxiliary. 20. The method of claim 18, wherein polysaccharides, or modified polysaccharides, are used as the agglomeration auxiliary. 21. The method of claim 18, wherein the agglomeration auxiliary is selected from the group consisting of: guaran; gum Arabic; guar gum; locust bean gum; xanthan gum; agar; carrageenan; a maltodextrin; starch; cellulose or its derivatives; hemicellulose or its derivatives; alginic acid; maltodextrin; and mixtures thereof. 22. The method of claim 21, wherein said agglomeration auxiliary is selected from the group consisting of: modified cellulose; maltodextrin; and mixtures thereof. 23. The method of claim 18, wherein proteins are used as the agglomeration auxiliary. 24. The method of claim 18, wherein organic polymers are used as the agglomeration auxiliary. 25. The method of claim 18, wherein inorganic substances are used as the agglomeration auxiliary. 26. The method of claim 18, wherein the starting biomass is obtained by spray drying a fermentation broth containing the biomass. 27. The method of claim 18, wherein the biomass comprises cells from the taxon Labyrinthulomycetes. 28. The method of claim 18, wherein the oxidation-sensitive material of value is a PUFA. 29. The method of claim 18, wherein:
a) the agglomeration auxiliary is selected from the group consisting of: guaran; gum Arabic; guar gum; locust bean gum; xanthan gum; agar; carrageenan; a maltodextrin; cornstarch; tapioca starch; potato starch,; cellulose or its derivatives; hemicellulose or its derivatives; alginic acid; maltodextrin; casein, gelatine, collagen; wheat gluten; lignosulphonate; polymethylolcarbamides; polyacrylic acids; polyvinyl alcohols; bentonites; hexametaphosphate and mixtures thereof; b) the particulate starting biomass has been obtained by spray drying a fermentation broth containing the biomass; c) the biomass comprises cells from family Thraustochytriaceae; d) the oxidation-sensitive material of value is an omega-3-fatty acid. 30. A particulate biomass having an oxidation-sensitive material of value, comprising an agglomeration auxiliary in an amount of from 0.05 to 6% by weight. 31. The particulate biomass of claim 30, wherein the agglomeration auxiliary is a carbohydrate or a modified carbohydrate. 32. The particulate biomass of claim 30, wherein said biomass comprises a hydrophilic or hydrophobic silicate in an amount of from 0.05 to 6% by weight. 33. The particulate biomass of claim 30, wherein at least 80% by weight of the particles have a particle diameter (grain size) of from 100 to 2000 μm. 34. The particulate biomass claim 30, wherein said biomass comprises cells from the taxon Labyrinthulomycetes. 35. The particulate biomass of claim 30, wherein the oxidation-sensitive material of value is a PUFA. 36. The particulate biomass of claim 30, comprising an agglomeration auxiliary in an amount of from 0.4 to 4% by weight, wherein:
a) the agglomeration auxiliary is selected from the group consisting of: carboxymethylcellulose; hydroxypropylmethylcellulose, maltodextrin; and a hydrophilic or hydrophobic silicate in an amount of from 0.1 to 5% by weight; b) at least 90% by weight of the particles have a particle diameter (grain size) of from 100 to 1000 μm; c) the biomass comprises cells selected from one or more genera selected from the group consisting of: Thraustochytrium; Schizochytrium; Aurantiochytrium; Oblongichytrium; and Ulkenia; and d) the oxidation-sensitive material of value is an omega-3-fatty acid. 37. A feedstuff or foodstuff comprising the particulate biomass of claim 30. | According to the invention, it has been found that a particulate biomass containing an oxidation-sensitive material of value can be converted into a particularly easy-to-handle product in a gentle manner if it is subjected to a granulation with the addition of an agglomeration auxiliary.1-17. (canceled) 18. A method for producing a particulate biomass having an oxidation-sensitive material of value, said method comprising granulating a particulate starting biomass in the presence of an agglomeration auxiliary. 19. The method of claim 18, wherein carbohydrates, or modified carbohydrates, are used as the agglomeration auxiliary. 20. The method of claim 18, wherein polysaccharides, or modified polysaccharides, are used as the agglomeration auxiliary. 21. The method of claim 18, wherein the agglomeration auxiliary is selected from the group consisting of: guaran; gum Arabic; guar gum; locust bean gum; xanthan gum; agar; carrageenan; a maltodextrin; starch; cellulose or its derivatives; hemicellulose or its derivatives; alginic acid; maltodextrin; and mixtures thereof. 22. The method of claim 21, wherein said agglomeration auxiliary is selected from the group consisting of: modified cellulose; maltodextrin; and mixtures thereof. 23. The method of claim 18, wherein proteins are used as the agglomeration auxiliary. 24. The method of claim 18, wherein organic polymers are used as the agglomeration auxiliary. 25. The method of claim 18, wherein inorganic substances are used as the agglomeration auxiliary. 26. The method of claim 18, wherein the starting biomass is obtained by spray drying a fermentation broth containing the biomass. 27. The method of claim 18, wherein the biomass comprises cells from the taxon Labyrinthulomycetes. 28. The method of claim 18, wherein the oxidation-sensitive material of value is a PUFA. 29. The method of claim 18, wherein:
a) the agglomeration auxiliary is selected from the group consisting of: guaran; gum Arabic; guar gum; locust bean gum; xanthan gum; agar; carrageenan; a maltodextrin; cornstarch; tapioca starch; potato starch,; cellulose or its derivatives; hemicellulose or its derivatives; alginic acid; maltodextrin; casein, gelatine, collagen; wheat gluten; lignosulphonate; polymethylolcarbamides; polyacrylic acids; polyvinyl alcohols; bentonites; hexametaphosphate and mixtures thereof; b) the particulate starting biomass has been obtained by spray drying a fermentation broth containing the biomass; c) the biomass comprises cells from family Thraustochytriaceae; d) the oxidation-sensitive material of value is an omega-3-fatty acid. 30. A particulate biomass having an oxidation-sensitive material of value, comprising an agglomeration auxiliary in an amount of from 0.05 to 6% by weight. 31. The particulate biomass of claim 30, wherein the agglomeration auxiliary is a carbohydrate or a modified carbohydrate. 32. The particulate biomass of claim 30, wherein said biomass comprises a hydrophilic or hydrophobic silicate in an amount of from 0.05 to 6% by weight. 33. The particulate biomass of claim 30, wherein at least 80% by weight of the particles have a particle diameter (grain size) of from 100 to 2000 μm. 34. The particulate biomass claim 30, wherein said biomass comprises cells from the taxon Labyrinthulomycetes. 35. The particulate biomass of claim 30, wherein the oxidation-sensitive material of value is a PUFA. 36. The particulate biomass of claim 30, comprising an agglomeration auxiliary in an amount of from 0.4 to 4% by weight, wherein:
a) the agglomeration auxiliary is selected from the group consisting of: carboxymethylcellulose; hydroxypropylmethylcellulose, maltodextrin; and a hydrophilic or hydrophobic silicate in an amount of from 0.1 to 5% by weight; b) at least 90% by weight of the particles have a particle diameter (grain size) of from 100 to 1000 μm; c) the biomass comprises cells selected from one or more genera selected from the group consisting of: Thraustochytrium; Schizochytrium; Aurantiochytrium; Oblongichytrium; and Ulkenia; and d) the oxidation-sensitive material of value is an omega-3-fatty acid. 37. A feedstuff or foodstuff comprising the particulate biomass of claim 30. | 1,600 |
1,380 | 14,414,326 | 1,639 | The present invention relates to complexes of oligonucleotide-encoded libraries and methods of tagging and using such libraries. In particular, the oligonucleotides and methods can include complexes having at least one linkage for which a polymerase has reduced ability to read or translocate through. | 1. A complex comprising:
(i) a chemical entity comprising one or more scaffolds or one or more building blocks; (ii) a first oligonucleotide tag encoding the identity of at least one of said one or more scaffolds or building blocks; and (iii) a headpiece having a first functional group and a second functional group, wherein said first functional group operatively associates with said chemical entity and said second functional group operatively associates with said first tag via a first linkage for which a polymerase has reduced ability to read or translocate through. 2. A complex comprising:
(i) a chemical entity comprising one or more scaffolds or one or more building blocks; (ii) n number of oligonucleotide tags having n−1 linkages, wherein n is an integer between 1 and 10, and wherein each of said linkages is between two adjacent tags and each tag encodes the identity of at least one of said one or more scaffolds or building blocks; and (iii) a headpiece having a first functional group operatively associated with said chemical entity and a second functional group operatively associated with at least one of said n number of tags via a first linkage, wherein a polymerase has reduced ability to read or translocate through at least one of said first linkage and n−1 linkages. 3. The complex of claim 2, wherein said polymerase has reduced ability to read or translocate through at least about 10% of said first linkage and n−1 linkages. 4. The complex of any one of claims 1 to 3, wherein one or more tags comprise a 5′-connector at the 5′-terminus of said one or more tags and a 3′-connector at the 3′-terminus of said one or more tags. 5-9. (canceled) 10. The complex of claim 1, wherein a DNA polymerase and/or an RNA polymerase has reduced ability to read or translocate through said first linkage and/or n−1 linkages. 11. The complex of claim 1, wherein less than about 50% of said first linkage and n−1 linkages comprise an enzymatic linkage. 12. The complex of claim 1, wherein said first linkage and/or n−1 linkages comprise a chemical linkage. 13-25. (canceled) 26. The complex of claim 1, wherein said chemical entity is operatively associated to said headpiece via a bifunctional spacer. 27. The complex of claim 1, wherein said chemical entity is covalently attached to said headpiece. 28. The complex of claim 1, wherein said headpiece comprises an oligonucleotide selected from the group consisting of a double-stranded oligonucleotide, a single-stranded oligonucleotide, or a hairpin oligonucleotide. 29. The complex of claim 28, wherein said headpiece comprises a primer-binding region. 30. The complex of claim 1, further comprising one or more first library-identifying tag(s), use tag(s), and/or origin tag(s). 31-33. (canceled) 34. The complex of claim 1, wherein said complex comprises RNA, DNA, modified DNA, and/or modified RNA. 35. (canceled) 36. The complex of claim 1, further comprising a tailpiece. 37. A library comprising one or more complexes of claim 1. 38-43. (canceled) 44. A method of tagging a first library comprising an encoded chemical entity, said method comprising:
(a) providing a headpiece having a first functional group and a second functional group; (b) binding said first functional group of said headpiece to a first component of said chemical entity, wherein said headpiece is directly connected to said first component or said headpiece is indirectly connected to said first component by a bifunctional spacer; and (c) binding said second functional group of said headpiece to a first oligonucleotide tag via a first linkage to form a complex, wherein a polymerase has reduced ability to read or translocate through said first linkage; wherein said steps (b) and (c) can be performed in any order and wherein said first tag encodes for the binding reaction of said step (b), thereby providing a tagged library. 45. The method of claim 44, further comprising:
(d) binding nc number of additional components of said chemical entity, wherein nc is an integer between 1 and 10; and (e) binding nt number of additional oligonucleotide tags having nt linkages to form a complex, wherein nt is an integer between 1 and 10 and wherein each of said linkages is between two adjacent tags and each tag encodes the identity of at least one of said components; wherein a polymerase has reduced ability to read or translocate through at least one of said first linkage and nt linkages; and wherein said steps (d) and (e) can be performed in any order and wherein each additional tag encodes for the binding reaction of each additional component of said step (d). 46-55. (canceled) 56. A method of screening a plurality of chemical entities, said method comprising:
(a) contacting a target with a complex of claim 1 and/or a library of claim 37; and (b) selecting one or more complexes having a predetermined characteristic for said target, as compared to a control, thereby screening said chemical entity. 57-58. (canceled) 59. A method of determining the nucleotide sequence of a complex of claim 1, said method comprising:
(a) annealing one or more relay primers with said complex, wherein said one or more relay primers span said first linkage and/or n−1 linkages; (b) extending said relay primers using a polymerase to produce oligonucleotide fragments; (c) ligating said oligonucleotide fragments to produce a template; (d) optionally amplifying said template by polymerase chain reaction to produce an amplified mix; and (e) sequencing said optionally amplified mix to determine the sequence of said complex. 60-65. (canceled) 66. A method of determining the nucleotide sequence of a complex of claim 1, said method comprising:
(a) providing said complex comprising the chemical linkage, wherein said chemical linkage is a cross-linking oligonucleotide that spans the junction between two adjacent tags and that operatively associates with said two adjacent tags via one or more reversible co-reactive groups; (b) releasing said cross-linking oligonucleotide to produce a template; (c) optionally amplifying said template by polymerase chain reaction to produce an amplified mix; and (d) sequencing said optionally amplified mix to determine the sequence of said complex. 67-74. (canceled) | The present invention relates to complexes of oligonucleotide-encoded libraries and methods of tagging and using such libraries. In particular, the oligonucleotides and methods can include complexes having at least one linkage for which a polymerase has reduced ability to read or translocate through.1. A complex comprising:
(i) a chemical entity comprising one or more scaffolds or one or more building blocks; (ii) a first oligonucleotide tag encoding the identity of at least one of said one or more scaffolds or building blocks; and (iii) a headpiece having a first functional group and a second functional group, wherein said first functional group operatively associates with said chemical entity and said second functional group operatively associates with said first tag via a first linkage for which a polymerase has reduced ability to read or translocate through. 2. A complex comprising:
(i) a chemical entity comprising one or more scaffolds or one or more building blocks; (ii) n number of oligonucleotide tags having n−1 linkages, wherein n is an integer between 1 and 10, and wherein each of said linkages is between two adjacent tags and each tag encodes the identity of at least one of said one or more scaffolds or building blocks; and (iii) a headpiece having a first functional group operatively associated with said chemical entity and a second functional group operatively associated with at least one of said n number of tags via a first linkage, wherein a polymerase has reduced ability to read or translocate through at least one of said first linkage and n−1 linkages. 3. The complex of claim 2, wherein said polymerase has reduced ability to read or translocate through at least about 10% of said first linkage and n−1 linkages. 4. The complex of any one of claims 1 to 3, wherein one or more tags comprise a 5′-connector at the 5′-terminus of said one or more tags and a 3′-connector at the 3′-terminus of said one or more tags. 5-9. (canceled) 10. The complex of claim 1, wherein a DNA polymerase and/or an RNA polymerase has reduced ability to read or translocate through said first linkage and/or n−1 linkages. 11. The complex of claim 1, wherein less than about 50% of said first linkage and n−1 linkages comprise an enzymatic linkage. 12. The complex of claim 1, wherein said first linkage and/or n−1 linkages comprise a chemical linkage. 13-25. (canceled) 26. The complex of claim 1, wherein said chemical entity is operatively associated to said headpiece via a bifunctional spacer. 27. The complex of claim 1, wherein said chemical entity is covalently attached to said headpiece. 28. The complex of claim 1, wherein said headpiece comprises an oligonucleotide selected from the group consisting of a double-stranded oligonucleotide, a single-stranded oligonucleotide, or a hairpin oligonucleotide. 29. The complex of claim 28, wherein said headpiece comprises a primer-binding region. 30. The complex of claim 1, further comprising one or more first library-identifying tag(s), use tag(s), and/or origin tag(s). 31-33. (canceled) 34. The complex of claim 1, wherein said complex comprises RNA, DNA, modified DNA, and/or modified RNA. 35. (canceled) 36. The complex of claim 1, further comprising a tailpiece. 37. A library comprising one or more complexes of claim 1. 38-43. (canceled) 44. A method of tagging a first library comprising an encoded chemical entity, said method comprising:
(a) providing a headpiece having a first functional group and a second functional group; (b) binding said first functional group of said headpiece to a first component of said chemical entity, wherein said headpiece is directly connected to said first component or said headpiece is indirectly connected to said first component by a bifunctional spacer; and (c) binding said second functional group of said headpiece to a first oligonucleotide tag via a first linkage to form a complex, wherein a polymerase has reduced ability to read or translocate through said first linkage; wherein said steps (b) and (c) can be performed in any order and wherein said first tag encodes for the binding reaction of said step (b), thereby providing a tagged library. 45. The method of claim 44, further comprising:
(d) binding nc number of additional components of said chemical entity, wherein nc is an integer between 1 and 10; and (e) binding nt number of additional oligonucleotide tags having nt linkages to form a complex, wherein nt is an integer between 1 and 10 and wherein each of said linkages is between two adjacent tags and each tag encodes the identity of at least one of said components; wherein a polymerase has reduced ability to read or translocate through at least one of said first linkage and nt linkages; and wherein said steps (d) and (e) can be performed in any order and wherein each additional tag encodes for the binding reaction of each additional component of said step (d). 46-55. (canceled) 56. A method of screening a plurality of chemical entities, said method comprising:
(a) contacting a target with a complex of claim 1 and/or a library of claim 37; and (b) selecting one or more complexes having a predetermined characteristic for said target, as compared to a control, thereby screening said chemical entity. 57-58. (canceled) 59. A method of determining the nucleotide sequence of a complex of claim 1, said method comprising:
(a) annealing one or more relay primers with said complex, wherein said one or more relay primers span said first linkage and/or n−1 linkages; (b) extending said relay primers using a polymerase to produce oligonucleotide fragments; (c) ligating said oligonucleotide fragments to produce a template; (d) optionally amplifying said template by polymerase chain reaction to produce an amplified mix; and (e) sequencing said optionally amplified mix to determine the sequence of said complex. 60-65. (canceled) 66. A method of determining the nucleotide sequence of a complex of claim 1, said method comprising:
(a) providing said complex comprising the chemical linkage, wherein said chemical linkage is a cross-linking oligonucleotide that spans the junction between two adjacent tags and that operatively associates with said two adjacent tags via one or more reversible co-reactive groups; (b) releasing said cross-linking oligonucleotide to produce a template; (c) optionally amplifying said template by polymerase chain reaction to produce an amplified mix; and (d) sequencing said optionally amplified mix to determine the sequence of said complex. 67-74. (canceled) | 1,600 |
1,381 | 14,923,430 | 1,618 | A biocompatible controlled release form of complexed iodine is achieved by a complexation of polyvinyl alcohol based foam and characterized by a residual starch component to optimize iodine release profiles. The resulting iodine complexed polyvinyl alcohol foam may be utilized locally as an antimicrobial agent that releases controlled amounts of iodine sufficient to kill microbes for extended durations without excessive bulk and rigidity. | 1-28. (canceled) 29. A method for treating a wound of a patient in need thereof, said method comprising:
(a) providing a polyvinyl alcohol (PVA) foam article comprised of PVA foam, which has a density of at least 0.074 g/cm3 before complexing with iodine, and iodine complexed at least in part to the PVA foam; and (b) applying the PVA foam article to a wound bed of the patient, wherein the PVA foam article exhibits controlled in vitro cumulative release of iodine in distilled water at 37 degrees Celsius at or near sink conditions of:
(i) between 50 ppm and 175 ppm at 3 hours,
(ii) between 100 ppm and 300 ppm at 6 hours, and
(iii) between 180 ppm and 400 ppm at 12 hours. 30. The method according to claim 29, wherein the PVA foam article releases iodine continuously for at least 24 hours. 31. The method according to claim 29, wherein the PVA foam article has a thickness of from 2 millimeters to 6 millimeters. 32. The method according to claim 29, wherein the PVA foam article is packaged before application with a moisture content of at least 40% (w/w). 33. The method according to claim 29, wherein the PVA foam article further comprises a lipid-based semisolid added to the PVA foam article prior to packaging or at the time of application to the patient. 34. The method according to claim 29 further comprising using negative pressure wound therapy in combination with the PVA foam article. 35. The method according to claim 29, wherein the PVA foam article is a sponge for treatment of an otitis condition. 36. A method for treating a wound of a patient in need thereof, said method comprising:
(a) providing a polyvinyl alcohol (PVA) foam article comprised of PVA foam, which has a density of at least 0.074 g/cm3 before complexing with iodine, and iodine complexed at least in part to the PVA foam; and (b) applying the PVA foam article to a wound bed of the patient for at least 24 hours. 37. The method according to claim 36, wherein the PVA foam article has a thickness of from 2 millimeters to 6 millimeters. 38. The method according to claim 36, wherein the PVA foam article is packaged before application with a moisture content of at least 40% (w/w). 39. The method according to claim 36, wherein the PVA foam article further comprises a lipid-based semisolid added to the PVA foam article prior to packaging or at the time of application to the patient. 40. The method according to claim 36 further comprising using negative pressure wound therapy in combination with the PVA foam article. 41. The method according to claim 36, wherein the PVA foam article is a sponge for treatment of an otitis condition. 42. A method for treating a wound of a patient in need thereof, said method comprising:
(a) providing a polyvinyl alcohol (PVA) foam article comprised of PVA foam, which has a density of at least 0.074 g/cm3, carbohydrate, and iodine complexed at least in part to the PVA foam or the carbohydrate; and (b) applying the PVA foam article to a wound bed of the patient. 43. The method according to claim 42, wherein the carbohydrate is a starch. 44. The method according to claim 43, wherein the starch has an average particle size of from 0.1 microns to 0.6 microns prior to hydration. 45. The method according to claim 42, wherein the PVA foam article has a thickness of from 2 millimeters to 6 millimeters. 46. The method according to claim 42, wherein the PVA foam article is packaged before application with a moisture content of at least 40% (w/w). 47. The method according to claim 42 further comprising using negative pressure wound therapy in combination with the PVA foam article. 48. The method according to claim 42, wherein the PVA foam article further comprises a lipid based semi-solid added to the PVA foam article prior to packaging or at the time of application to the patient. 49. The method according to claim 42, wherein the PVA foam article is a sponge for treatment of an otitis condition. 50. A method for treating a wound of a patient in need thereof, said method comprising:
(a) providing a polyvinyl alcohol (PVA) foam article comprised of PVA foam, carbohydrate, and iodine complexed at least in part to the PVA foam or the carbohydrate; and (b) applying the PVA foam article to a wound bed of the patient, wherein the PVA foam article exhibits controlled in vitro cumulative release of iodine in distilled water at 37 degrees Celsius at or near sink conditions of:
(i) between 50 ppm and 175 ppm at 3 hours,
(ii) between 100 ppm and 300 ppm at 6 hours, and
(iii) between 180 ppm and 400 ppm at 12 hours. 51. The method according to claim 50, wherein the carbohydrate is a starch. 52. The method according to claim 51, wherein the starch has an average particle size of from 0.1 microns to 0.6 microns. 53. The method according to claim 50, wherein the PVA foam article has a thickness of from 2 millimeters to 6 millimeters. 54. The method according to claim 50, wherein the PVA foam article is packaged before application with a moisture content of at least 40% (w/w). 55. The method according to claim 50, wherein the PVA foam article further comprises a lipid-based semisolid added to the PVA foam article prior to packaging or at the time of application to the patient. 56. The method according to claim 50 further comprising using negative pressure wound therapy in combination with the PVA foam article. 57. The method according to claim 50, wherein the PVA foam article is a sponge for treatment an otitis condition. | A biocompatible controlled release form of complexed iodine is achieved by a complexation of polyvinyl alcohol based foam and characterized by a residual starch component to optimize iodine release profiles. The resulting iodine complexed polyvinyl alcohol foam may be utilized locally as an antimicrobial agent that releases controlled amounts of iodine sufficient to kill microbes for extended durations without excessive bulk and rigidity.1-28. (canceled) 29. A method for treating a wound of a patient in need thereof, said method comprising:
(a) providing a polyvinyl alcohol (PVA) foam article comprised of PVA foam, which has a density of at least 0.074 g/cm3 before complexing with iodine, and iodine complexed at least in part to the PVA foam; and (b) applying the PVA foam article to a wound bed of the patient, wherein the PVA foam article exhibits controlled in vitro cumulative release of iodine in distilled water at 37 degrees Celsius at or near sink conditions of:
(i) between 50 ppm and 175 ppm at 3 hours,
(ii) between 100 ppm and 300 ppm at 6 hours, and
(iii) between 180 ppm and 400 ppm at 12 hours. 30. The method according to claim 29, wherein the PVA foam article releases iodine continuously for at least 24 hours. 31. The method according to claim 29, wherein the PVA foam article has a thickness of from 2 millimeters to 6 millimeters. 32. The method according to claim 29, wherein the PVA foam article is packaged before application with a moisture content of at least 40% (w/w). 33. The method according to claim 29, wherein the PVA foam article further comprises a lipid-based semisolid added to the PVA foam article prior to packaging or at the time of application to the patient. 34. The method according to claim 29 further comprising using negative pressure wound therapy in combination with the PVA foam article. 35. The method according to claim 29, wherein the PVA foam article is a sponge for treatment of an otitis condition. 36. A method for treating a wound of a patient in need thereof, said method comprising:
(a) providing a polyvinyl alcohol (PVA) foam article comprised of PVA foam, which has a density of at least 0.074 g/cm3 before complexing with iodine, and iodine complexed at least in part to the PVA foam; and (b) applying the PVA foam article to a wound bed of the patient for at least 24 hours. 37. The method according to claim 36, wherein the PVA foam article has a thickness of from 2 millimeters to 6 millimeters. 38. The method according to claim 36, wherein the PVA foam article is packaged before application with a moisture content of at least 40% (w/w). 39. The method according to claim 36, wherein the PVA foam article further comprises a lipid-based semisolid added to the PVA foam article prior to packaging or at the time of application to the patient. 40. The method according to claim 36 further comprising using negative pressure wound therapy in combination with the PVA foam article. 41. The method according to claim 36, wherein the PVA foam article is a sponge for treatment of an otitis condition. 42. A method for treating a wound of a patient in need thereof, said method comprising:
(a) providing a polyvinyl alcohol (PVA) foam article comprised of PVA foam, which has a density of at least 0.074 g/cm3, carbohydrate, and iodine complexed at least in part to the PVA foam or the carbohydrate; and (b) applying the PVA foam article to a wound bed of the patient. 43. The method according to claim 42, wherein the carbohydrate is a starch. 44. The method according to claim 43, wherein the starch has an average particle size of from 0.1 microns to 0.6 microns prior to hydration. 45. The method according to claim 42, wherein the PVA foam article has a thickness of from 2 millimeters to 6 millimeters. 46. The method according to claim 42, wherein the PVA foam article is packaged before application with a moisture content of at least 40% (w/w). 47. The method according to claim 42 further comprising using negative pressure wound therapy in combination with the PVA foam article. 48. The method according to claim 42, wherein the PVA foam article further comprises a lipid based semi-solid added to the PVA foam article prior to packaging or at the time of application to the patient. 49. The method according to claim 42, wherein the PVA foam article is a sponge for treatment of an otitis condition. 50. A method for treating a wound of a patient in need thereof, said method comprising:
(a) providing a polyvinyl alcohol (PVA) foam article comprised of PVA foam, carbohydrate, and iodine complexed at least in part to the PVA foam or the carbohydrate; and (b) applying the PVA foam article to a wound bed of the patient, wherein the PVA foam article exhibits controlled in vitro cumulative release of iodine in distilled water at 37 degrees Celsius at or near sink conditions of:
(i) between 50 ppm and 175 ppm at 3 hours,
(ii) between 100 ppm and 300 ppm at 6 hours, and
(iii) between 180 ppm and 400 ppm at 12 hours. 51. The method according to claim 50, wherein the carbohydrate is a starch. 52. The method according to claim 51, wherein the starch has an average particle size of from 0.1 microns to 0.6 microns. 53. The method according to claim 50, wherein the PVA foam article has a thickness of from 2 millimeters to 6 millimeters. 54. The method according to claim 50, wherein the PVA foam article is packaged before application with a moisture content of at least 40% (w/w). 55. The method according to claim 50, wherein the PVA foam article further comprises a lipid-based semisolid added to the PVA foam article prior to packaging or at the time of application to the patient. 56. The method according to claim 50 further comprising using negative pressure wound therapy in combination with the PVA foam article. 57. The method according to claim 50, wherein the PVA foam article is a sponge for treatment an otitis condition. | 1,600 |
1,382 | 15,753,497 | 1,617 | A personal care conditioning and/or styling synergistic composition for a keratin substrate comprising: (i) about 0.1 wt. % to about 20 wt. % of PolyAPTAC polymer; (ii) about 0.1 wt. % to about 5 wt. % of Polyquaternium-37; (iii) about 0.1 wt. % to about 5 wt. % of at least one cationic surfactants; (iv) about 0.1 wt. % to 99.9 wt. % of water; and (v) about 0.01 wt. % to 20 wt. % of at least one cosmetically acceptable excipient, wherein the composition is capable of providing immediate and prolonged benefit to a desired keratin substrate which is hair or skin. | 1. A personal care conditioning and/or styling synergistic composition for a keratin substrate comprising:
i. about 0.1 wt. % to about 20 wt. % of PolyAPTAC polymer; ii. about 0.1 wt. % to about 5 wt. % of Polyquaternium-37; iii. about 0.1 wt. % to about 5 wt. % of at least one cationic surfactants; iv. about 0.1 wt. % to 99.9 wt. % of water; and v. about 0.01 wt. % to 20 wt. % of at least one cosmetically acceptable excipient,
wherein the composition is capable of providing immediate and prolonged benefit to a desired keratin substrate which is hair or skin. 2. The composition according to claim 1, wherein said cosmetically acceptable excipient is selected from the group consisting of fatty substances, gelling agents, thickeners, surfactants, moisturizers, emollients, hydrophilic or lipophilic active agent, antioxidants, sequestering agents, preserving agents, acidifying or basifying agents, fragrances, fillers, dyestuffs, emulsifying agents, solvents, UV-A or UV-B blocker/filters, plant extracts, moisturizers, proteins, peptides, neutralizing agents, film forming agents, setting agents, wax materials, oils, solvents, silicones and/or reducing agents. 3. The composition according to claim 1, wherein the average molecular weight of PolyAPTAC is in the range of from about 100,000 to 1000,000 g/mol. 4. The composition according to claim 1, wherein said PolyAPTAC polymer has a cationic charge density of about 1 meq/g to about 8 meq/g. 5. The composition according to claim 1, wherein the pH of said personal care compositions is in the range of from about 3 to about 13. 6. The composition according to claim 1 wherein said personal care composition is an appropriate product selected from the group consisting of hair-care products, shampoos, hair conditioners, leave in and rinse off conditioners, styling and treating hair compositions, hair perming products, hair relaxants, hair straighteners, hair sprays and lacquers, permanent hair dyeing systems, hair styling mousses, hair gels, semi-permanent hair dyeing systems, temporary hair dyeing systems, hair bleaching systems, permanent hair wave systems, hair setting formulations, skin-care products, bath products, shower products, liquid soaps, bar soaps, fragrances and/or odoriferous ingredients consisting preparations, dentifrices, deodorizing and antiperspirant preparations, decorative preparations, light protection formulations, shaving lotions, body oils, body lotions, body gels, treatment creams, body cleaning products, skin protection ointments, shaving and aftershave preparations, skin powders, lipsticks, nail varnishes, eye shadows, mascaras, dry and moist make-up, rouge, powders, depilatory agents, sun care products, and/or compositions comprising UV blockers or UV protectors. 7. The composition according to claim 1, wherein said composition is formulated as an emulsion, a lotion, a gel, a vesicle dispersion, a paste, a cream, a solid stick, a mousse, a shampoo, powder, and/or a spray. 8. The composition according to claim 1, wherein the effective amount of composition used in the personal care composition is in the range of from about 0.01 wt. % to 5.0 wt. %. 9. A method for treating or fixing regular or damaged keratin substrate comprising contacting said keratin substrate with an effective amount of personal care composition of claim 1 comprising: (i) about 0.1 wt. % to about 20 wt. % of PolyAPTAC polymer; (ii) about 0.1 wt. % to about 5 wt. % of Polyquaternium-37; (iii) about 0.1 wt. % to about 5 wt. % of at least one cationic surfactants; (iv) about 0.1 wt. % to 99.9 wt. % of water; and (v) about 0.01 wt. % to about 20 wt. of at least one cosmetically acceptable excipient. 10. A method for washing or caring a keratin substrate comprising applying an effective amount of composition of claim 1 comprising: (i) about 0.1 wt. % to about 20 wt. % of PolyAPTAC polymer; (ii) about 0.1 wt. % to about 5 wt. % of Polyquaternium-37; (iii) about 0.1 wt. % to about 5 wt. % of at least one cationic surfactants; (iv) about 0.1 wt. % to 99.9 wt. % of water; and (v) about 0.01 wt. % to about 20 wt. of at least one cosmetically acceptable excipient. | A personal care conditioning and/or styling synergistic composition for a keratin substrate comprising: (i) about 0.1 wt. % to about 20 wt. % of PolyAPTAC polymer; (ii) about 0.1 wt. % to about 5 wt. % of Polyquaternium-37; (iii) about 0.1 wt. % to about 5 wt. % of at least one cationic surfactants; (iv) about 0.1 wt. % to 99.9 wt. % of water; and (v) about 0.01 wt. % to 20 wt. % of at least one cosmetically acceptable excipient, wherein the composition is capable of providing immediate and prolonged benefit to a desired keratin substrate which is hair or skin.1. A personal care conditioning and/or styling synergistic composition for a keratin substrate comprising:
i. about 0.1 wt. % to about 20 wt. % of PolyAPTAC polymer; ii. about 0.1 wt. % to about 5 wt. % of Polyquaternium-37; iii. about 0.1 wt. % to about 5 wt. % of at least one cationic surfactants; iv. about 0.1 wt. % to 99.9 wt. % of water; and v. about 0.01 wt. % to 20 wt. % of at least one cosmetically acceptable excipient,
wherein the composition is capable of providing immediate and prolonged benefit to a desired keratin substrate which is hair or skin. 2. The composition according to claim 1, wherein said cosmetically acceptable excipient is selected from the group consisting of fatty substances, gelling agents, thickeners, surfactants, moisturizers, emollients, hydrophilic or lipophilic active agent, antioxidants, sequestering agents, preserving agents, acidifying or basifying agents, fragrances, fillers, dyestuffs, emulsifying agents, solvents, UV-A or UV-B blocker/filters, plant extracts, moisturizers, proteins, peptides, neutralizing agents, film forming agents, setting agents, wax materials, oils, solvents, silicones and/or reducing agents. 3. The composition according to claim 1, wherein the average molecular weight of PolyAPTAC is in the range of from about 100,000 to 1000,000 g/mol. 4. The composition according to claim 1, wherein said PolyAPTAC polymer has a cationic charge density of about 1 meq/g to about 8 meq/g. 5. The composition according to claim 1, wherein the pH of said personal care compositions is in the range of from about 3 to about 13. 6. The composition according to claim 1 wherein said personal care composition is an appropriate product selected from the group consisting of hair-care products, shampoos, hair conditioners, leave in and rinse off conditioners, styling and treating hair compositions, hair perming products, hair relaxants, hair straighteners, hair sprays and lacquers, permanent hair dyeing systems, hair styling mousses, hair gels, semi-permanent hair dyeing systems, temporary hair dyeing systems, hair bleaching systems, permanent hair wave systems, hair setting formulations, skin-care products, bath products, shower products, liquid soaps, bar soaps, fragrances and/or odoriferous ingredients consisting preparations, dentifrices, deodorizing and antiperspirant preparations, decorative preparations, light protection formulations, shaving lotions, body oils, body lotions, body gels, treatment creams, body cleaning products, skin protection ointments, shaving and aftershave preparations, skin powders, lipsticks, nail varnishes, eye shadows, mascaras, dry and moist make-up, rouge, powders, depilatory agents, sun care products, and/or compositions comprising UV blockers or UV protectors. 7. The composition according to claim 1, wherein said composition is formulated as an emulsion, a lotion, a gel, a vesicle dispersion, a paste, a cream, a solid stick, a mousse, a shampoo, powder, and/or a spray. 8. The composition according to claim 1, wherein the effective amount of composition used in the personal care composition is in the range of from about 0.01 wt. % to 5.0 wt. %. 9. A method for treating or fixing regular or damaged keratin substrate comprising contacting said keratin substrate with an effective amount of personal care composition of claim 1 comprising: (i) about 0.1 wt. % to about 20 wt. % of PolyAPTAC polymer; (ii) about 0.1 wt. % to about 5 wt. % of Polyquaternium-37; (iii) about 0.1 wt. % to about 5 wt. % of at least one cationic surfactants; (iv) about 0.1 wt. % to 99.9 wt. % of water; and (v) about 0.01 wt. % to about 20 wt. of at least one cosmetically acceptable excipient. 10. A method for washing or caring a keratin substrate comprising applying an effective amount of composition of claim 1 comprising: (i) about 0.1 wt. % to about 20 wt. % of PolyAPTAC polymer; (ii) about 0.1 wt. % to about 5 wt. % of Polyquaternium-37; (iii) about 0.1 wt. % to about 5 wt. % of at least one cationic surfactants; (iv) about 0.1 wt. % to 99.9 wt. % of water; and (v) about 0.01 wt. % to about 20 wt. of at least one cosmetically acceptable excipient. | 1,600 |
1,383 | 15,553,267 | 1,617 | The invention relates to a plant protection and/or plant growth promotion system, comprising at least one anchor peptide for increased binding to a plant part, a support function, which is indirectly or directly bound to the anchor peptide, and an active substance for protecting the plant and/or promoting plant growth and yield. | 1. A plant protection and/or plant growth promotion system, comprising at least one anchor peptide for increased binding to a plant organ or a plant part, a support function, which is indirectly or directly bound to the anchor peptide, and an active substance for protecting the plant and/or promoting plant growth and/or yield. 2. The plant protection and/or plant growth promotion system according to claim 1, wherein the anchor peptide consists of 2 to 300 amino acids. 3. The plant protection and/or plant growth promotion system according to claim 1, wherein the active substance is selected from the group consisting of:
a pesticide, an herbicide, a bactericide, a fungicide, a safener a beneficial organisms, a means for promoting plant growth and/or colonization of beneficial organisms, and a plant growth agents. 4. The plant protection and/or plant growth promotion system according to claim 1, wherein the support function is selected from the group consisting of a nanogel, a microgel, a polysome, a polymerosome, a synthosome, a poly-amino acid-spacer, a colloidosome and a cubosome. 5. The plant protection and/or plant growth promotion system according to claim 1, wherein the anchor peptide binds to a leaf, trunk, stem, root, fruit, seed, bud, blossom and/or tuber of a plant. 6. The plant protection and/or plant growth promotion system according to claim 1, wherein the support function is a nano- or microgel and configured such that the active substance either remains on the support function or is directly, time delayed, and/or stimulation dependently released. 7. The plant protection and/or plant growth promotion system according to claim 6, wherein the support function is stimulation dependently released and the stimulus is selected from the group consisting of pH, temperature, humidity, light (including UV light), duration of irradiation, electric pulses, magnetic pulses, elicitors, enzymatic reactions, microbe associated molecular patterns, pathogen associated molecular patterns, damage associated molecular patterns, and herbivore associated molecular patterns. 8. The plant protection and/or plant growth promotion system according to claim 1, wherein the system is a fusion protein. 9. The plant protection and/or plant growth promotion system according to claim 8, wherein the support function is a spacer of 2-100 amino acids. 10. (canceled) 11. A method for protecting plants and/or promoting plant growth, comprising the following steps:
a) providing a plant protection and/or plant growth promotion system according to claim 1, and b) applying the plant protection and/or plant growth promotion system onto a plant. 12. The plant protection and/or plant growth promotion system according to claim 2, wherein the support function is selected from the group consisting of a nanogel, a microgel, a polysome, a polymerosome, a synthosome, a poly-amino acid-spacer, a colloidosome and a cubosome. 13. The plant protection and/or plant growth promotion system according to claim 3, wherein the support function is selected from the group consisting of a nanogel, a microgel, a polysome, a polymerosome, a synthosome, a poly-amino acid-spacer, a colloidosome and a cubosome. 14. The plant protection and/or plant growth promotion system according to claim 2, wherein the anchor peptide binds to a leaf, trunk, stem, root, fruit, seed, bud, blossom and/or tuber of a plant. 15. The plant protection and/or plant growth promotion system according to claim 3, wherein the anchor peptide binds to a leaf, trunk, stem, root, fruit, seed, bud, blossom and/or tuber of a plant. 16. The plant protection and/or plant growth promotion system according to claim 4, wherein the anchor peptide binds to a leaf, trunk, stem, root, fruit, seed, bud, blossom and/or tuber of a plant. 17. The plant protection and/or plant growth promotion system according to claim 2, wherein the system is a fusion protein. 18. The plant protection and/or plant growth promotion system according to claim 3, wherein the system is a fusion protein. 19. The plant protection and/or plant growth promotion system according to claim 4, wherein the system is a fusion protein. 20. The plant protection and/or plant growth promotion system according to claim 5, wherein the system is a fusion protein. 21. The plant protection and/or plant growth promotion system according to claim 20, wherein the support function is a spacer of 2-100 amino acids. | The invention relates to a plant protection and/or plant growth promotion system, comprising at least one anchor peptide for increased binding to a plant part, a support function, which is indirectly or directly bound to the anchor peptide, and an active substance for protecting the plant and/or promoting plant growth and yield.1. A plant protection and/or plant growth promotion system, comprising at least one anchor peptide for increased binding to a plant organ or a plant part, a support function, which is indirectly or directly bound to the anchor peptide, and an active substance for protecting the plant and/or promoting plant growth and/or yield. 2. The plant protection and/or plant growth promotion system according to claim 1, wherein the anchor peptide consists of 2 to 300 amino acids. 3. The plant protection and/or plant growth promotion system according to claim 1, wherein the active substance is selected from the group consisting of:
a pesticide, an herbicide, a bactericide, a fungicide, a safener a beneficial organisms, a means for promoting plant growth and/or colonization of beneficial organisms, and a plant growth agents. 4. The plant protection and/or plant growth promotion system according to claim 1, wherein the support function is selected from the group consisting of a nanogel, a microgel, a polysome, a polymerosome, a synthosome, a poly-amino acid-spacer, a colloidosome and a cubosome. 5. The plant protection and/or plant growth promotion system according to claim 1, wherein the anchor peptide binds to a leaf, trunk, stem, root, fruit, seed, bud, blossom and/or tuber of a plant. 6. The plant protection and/or plant growth promotion system according to claim 1, wherein the support function is a nano- or microgel and configured such that the active substance either remains on the support function or is directly, time delayed, and/or stimulation dependently released. 7. The plant protection and/or plant growth promotion system according to claim 6, wherein the support function is stimulation dependently released and the stimulus is selected from the group consisting of pH, temperature, humidity, light (including UV light), duration of irradiation, electric pulses, magnetic pulses, elicitors, enzymatic reactions, microbe associated molecular patterns, pathogen associated molecular patterns, damage associated molecular patterns, and herbivore associated molecular patterns. 8. The plant protection and/or plant growth promotion system according to claim 1, wherein the system is a fusion protein. 9. The plant protection and/or plant growth promotion system according to claim 8, wherein the support function is a spacer of 2-100 amino acids. 10. (canceled) 11. A method for protecting plants and/or promoting plant growth, comprising the following steps:
a) providing a plant protection and/or plant growth promotion system according to claim 1, and b) applying the plant protection and/or plant growth promotion system onto a plant. 12. The plant protection and/or plant growth promotion system according to claim 2, wherein the support function is selected from the group consisting of a nanogel, a microgel, a polysome, a polymerosome, a synthosome, a poly-amino acid-spacer, a colloidosome and a cubosome. 13. The plant protection and/or plant growth promotion system according to claim 3, wherein the support function is selected from the group consisting of a nanogel, a microgel, a polysome, a polymerosome, a synthosome, a poly-amino acid-spacer, a colloidosome and a cubosome. 14. The plant protection and/or plant growth promotion system according to claim 2, wherein the anchor peptide binds to a leaf, trunk, stem, root, fruit, seed, bud, blossom and/or tuber of a plant. 15. The plant protection and/or plant growth promotion system according to claim 3, wherein the anchor peptide binds to a leaf, trunk, stem, root, fruit, seed, bud, blossom and/or tuber of a plant. 16. The plant protection and/or plant growth promotion system according to claim 4, wherein the anchor peptide binds to a leaf, trunk, stem, root, fruit, seed, bud, blossom and/or tuber of a plant. 17. The plant protection and/or plant growth promotion system according to claim 2, wherein the system is a fusion protein. 18. The plant protection and/or plant growth promotion system according to claim 3, wherein the system is a fusion protein. 19. The plant protection and/or plant growth promotion system according to claim 4, wherein the system is a fusion protein. 20. The plant protection and/or plant growth promotion system according to claim 5, wherein the system is a fusion protein. 21. The plant protection and/or plant growth promotion system according to claim 20, wherein the support function is a spacer of 2-100 amino acids. | 1,600 |
1,384 | 14,367,872 | 1,634 | The subject matter of the present invention is a method for the diagnosis or prognosis, in vitro, of lung cancer, which includes a step of detecting at least one expression product of at least one HERV nucleic acid sequence, a method for use of said nucleic acid sequences, which have been isolated, as a molecular marker or molecular markers, and a kit including at least one binding partner specific for at least one of the expression products of the HERV nucleic acid sequences. | 1. A method for the in vitro diagnosis or prognosis of lung cancer in a biological sample taken from a patient, which comprises a step of detecting at least one expression product of at least one nucleic acid sequence, said nucleic acid sequence being chosen from the sequences identified in SEQ ID NOs: 1 to 242 or from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 1 to 242. 2. The method as claimed in claim 1, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 2, 3, 6, 8, 11, 13, 14, 15, 16, 17, 18, 15 19, 21, 22, 23, 24, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170,171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241 and 242 or from the group of sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 2, 3, 6, 8, 11, 13, 14, 15, 16,17, 18, 19, 21, 22, 23, 24, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 35 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101,102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241 and 242. 3. The method as claimed in claim 2, in which the expression product of at least two nucleic acid sequences is detected, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 6 and 50, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 6 and 50. 4. The method as claimed in claim 1, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 4, 5, 7, 9, 10, 12, 20, 25 and 40 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 4, 5, 7, 9, 10, 12, 20, 25 and 40. 5. The method as claimed in claim 4, in which the expression product of at least two nucleic acid sequences is detected, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 4, 5 and 7, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 4, 5 and 7. 6. The method as claimed in claim 1, in which the expression product of at least one nucleic acid sequence being chosen from the group of sequences identified in SEP ID NOs: 1, 2, 3, 6, 8, 11, 13, 14, 15, 16, 17, 18, 15 19, 21, 22, 23, 24, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 11,8, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241 and 242 or from the group of sequences which exhibit at least 99% identity with the sequences identified in SEP ID NOs: 1, 2, 3, 6, 8, 11, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 24, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 35 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 1,57, 158, 159, 160, 161, 162, 1,63, 164, 165, 166, 1,67, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241 and 242, and the expression product of at least one nucleic acid sequence being chosen from the group of sequences identified in SEP ID NOs: 4, 5, 7, 9, 10, 12, 20, 25 and 40 or from, the sequences which exhibit at least 99% identity with the sequences identified in SEP ID NOs: 4, 5, 7, 9, 10, 12, 20, 25 and 40, are detected. 7. The method as claimed in claim 1, in which the expression product detected is at least one RNA transcript or at least one polypeptide. 8. The method as claimed in claim 7, wherein the RNA transcript is at least one mRNA, 9. The method as claimed in claim 7, in which the RNA transcript, is detected by hybridization, by amplification or by sequencing, 10. The method as claimed in claim 6, in which the mRNA is brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and the presence or absence of hybridization to the mRNA is detected, 11. The method as claimed in claim 8, wherein DNA copies of the mRNA are prepared, the DNA copies are brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and in that the presence or absence of hybridization to said DNA copies is detected. 12. The method as claimed in claim 7, in which the polypeptide expressed is detected by bringing into contact with at least one specific binding partner of said polypeptide. 13. A method for the in vitro diagnosis or prognosis of lung cancer, comprising: isolating at least two nucleic acid sequences as a molecular marker wherein the two nucleic acid sequences consist of:
(i) at least two DNA sequences chosen from the sequences SEQ ID NOs: 1 to 242or (ii) at least two DNA sequences respectively complementary to at least two sequences chosen from at least two sequences as defined in (i), or (iii) at least two DNA sequences which exhibit respectively at least 99% identity, preferably at least 99.5% identity and advantageously at least 99.6% or at least 99.7% identity with two sequences as defined in (i) and (ii), or (iv) at least two RNA sequences which are respectively the transcription product of two sequences chosen from the sequences as defined in (i), or (v) at least two RNA sequences which are the transcription product of two sequences chosen from the sequences which exhibit at least 99% identity. 14. A kit for the in vitro diagnosis or prognosis of lung cancer in a biological sample taken from a patient, which comprises at least two respectively specific binding partners of at least two expression products of at least two nucleic acid sequences chosen from the sequences identified in SEQ ID NOs: 1 to 242 or from the sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 242 and no more than 242 specific binding partners of the expression products of the nucleic acid sequences identified in SEQ ID NOs: 1 to 242 or of the nucleic acid sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 242. 15. The kit as claimed in claim 14, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 1, 2, 3, 6, 8, 11, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 24, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241 and 242 or from the group of sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 2, 3, 6, 8, 11, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 24, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 5 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241 and 242. 16. The kit as claimed in claim 14, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 4, 5, 7, 9, 10, 12, 20, 25 and 40 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 4, 5, 7, 9, 10, 12, 20, 25 and 40. 17. The kit as claimed in claim 16, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 4, 5 and 7 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 4, 5 and 7. 18. The kit as claimed in claim 14, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 1, 6 and 50 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 6 and 50. 19. The kit as claimed in claim 18, which comprises 2 or 3 respectively specific binding partners of the expression products of the nucleic acid sequences identified in SEQ ID NOs: 1, 6 and 50 or of the nucleic acid sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 6 and 50. 20. The kit as claimed in claim 14, in which the at least two respectively specific binding partners of the expression products are respectively at least one hybridization probe and/or at least one amplification primer, or at least one antibody, or at least one antibody analog, or at least one affinity protein, or at least one aptamer. 21. A method for evaluating the efficacy of a treatment and/or a progression in lung cancer, which comprises a step of detecting at least two expression products respectively of at least two nucleic acid sequences, said two nucleic acid sequences being chosen from the sequences identified in SEQ ID NOs: 1 to 242 or from the sequences which exhibit at least 99% identity respectively with the sequences identified in SEQ ID NOs: 1 to 242. 22. The method as claimed in claim 21, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 4, 5, 7, 9, 10, 12, 20, 25 and 40 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 4, 5, 7, 9, 10, 12, 20, 25 and 40. 23. The method as claimed in claim 21, in which the expression product of at least two nucleic acid sequences is detected, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 6 and 50, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 6 and 50.35 | The subject matter of the present invention is a method for the diagnosis or prognosis, in vitro, of lung cancer, which includes a step of detecting at least one expression product of at least one HERV nucleic acid sequence, a method for use of said nucleic acid sequences, which have been isolated, as a molecular marker or molecular markers, and a kit including at least one binding partner specific for at least one of the expression products of the HERV nucleic acid sequences.1. A method for the in vitro diagnosis or prognosis of lung cancer in a biological sample taken from a patient, which comprises a step of detecting at least one expression product of at least one nucleic acid sequence, said nucleic acid sequence being chosen from the sequences identified in SEQ ID NOs: 1 to 242 or from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOs: 1 to 242. 2. The method as claimed in claim 1, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 2, 3, 6, 8, 11, 13, 14, 15, 16, 17, 18, 15 19, 21, 22, 23, 24, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170,171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241 and 242 or from the group of sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 2, 3, 6, 8, 11, 13, 14, 15, 16,17, 18, 19, 21, 22, 23, 24, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 35 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101,102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241 and 242. 3. The method as claimed in claim 2, in which the expression product of at least two nucleic acid sequences is detected, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 6 and 50, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 6 and 50. 4. The method as claimed in claim 1, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 4, 5, 7, 9, 10, 12, 20, 25 and 40 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 4, 5, 7, 9, 10, 12, 20, 25 and 40. 5. The method as claimed in claim 4, in which the expression product of at least two nucleic acid sequences is detected, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 4, 5 and 7, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 4, 5 and 7. 6. The method as claimed in claim 1, in which the expression product of at least one nucleic acid sequence being chosen from the group of sequences identified in SEP ID NOs: 1, 2, 3, 6, 8, 11, 13, 14, 15, 16, 17, 18, 15 19, 21, 22, 23, 24, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 11,8, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241 and 242 or from the group of sequences which exhibit at least 99% identity with the sequences identified in SEP ID NOs: 1, 2, 3, 6, 8, 11, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 24, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 35 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 1,57, 158, 159, 160, 161, 162, 1,63, 164, 165, 166, 1,67, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241 and 242, and the expression product of at least one nucleic acid sequence being chosen from the group of sequences identified in SEP ID NOs: 4, 5, 7, 9, 10, 12, 20, 25 and 40 or from, the sequences which exhibit at least 99% identity with the sequences identified in SEP ID NOs: 4, 5, 7, 9, 10, 12, 20, 25 and 40, are detected. 7. The method as claimed in claim 1, in which the expression product detected is at least one RNA transcript or at least one polypeptide. 8. The method as claimed in claim 7, wherein the RNA transcript is at least one mRNA, 9. The method as claimed in claim 7, in which the RNA transcript, is detected by hybridization, by amplification or by sequencing, 10. The method as claimed in claim 6, in which the mRNA is brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and the presence or absence of hybridization to the mRNA is detected, 11. The method as claimed in claim 8, wherein DNA copies of the mRNA are prepared, the DNA copies are brought into contact with at least one probe and/or at least one primer under predetermined conditions which allow hybridization, and in that the presence or absence of hybridization to said DNA copies is detected. 12. The method as claimed in claim 7, in which the polypeptide expressed is detected by bringing into contact with at least one specific binding partner of said polypeptide. 13. A method for the in vitro diagnosis or prognosis of lung cancer, comprising: isolating at least two nucleic acid sequences as a molecular marker wherein the two nucleic acid sequences consist of:
(i) at least two DNA sequences chosen from the sequences SEQ ID NOs: 1 to 242or (ii) at least two DNA sequences respectively complementary to at least two sequences chosen from at least two sequences as defined in (i), or (iii) at least two DNA sequences which exhibit respectively at least 99% identity, preferably at least 99.5% identity and advantageously at least 99.6% or at least 99.7% identity with two sequences as defined in (i) and (ii), or (iv) at least two RNA sequences which are respectively the transcription product of two sequences chosen from the sequences as defined in (i), or (v) at least two RNA sequences which are the transcription product of two sequences chosen from the sequences which exhibit at least 99% identity. 14. A kit for the in vitro diagnosis or prognosis of lung cancer in a biological sample taken from a patient, which comprises at least two respectively specific binding partners of at least two expression products of at least two nucleic acid sequences chosen from the sequences identified in SEQ ID NOs: 1 to 242 or from the sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 242 and no more than 242 specific binding partners of the expression products of the nucleic acid sequences identified in SEQ ID NOs: 1 to 242 or of the nucleic acid sequences which exhibit at least 99% identity with the nucleic acid sequences identified in SEQ ID NOs: 1 to 242. 15. The kit as claimed in claim 14, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 1, 2, 3, 6, 8, 11, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 24, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241 and 242 or from the group of sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 2, 3, 6, 8, 11, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 24, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 5 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241 and 242. 16. The kit as claimed in claim 14, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 4, 5, 7, 9, 10, 12, 20, 25 and 40 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 4, 5, 7, 9, 10, 12, 20, 25 and 40. 17. The kit as claimed in claim 16, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 4, 5 and 7 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 4, 5 and 7. 18. The kit as claimed in claim 14, which comprises at least two respectively specific binding partners of the expression product of at least two nucleic acid sequences chosen from the group of sequences identified in SEQ ID NOs: 1, 6 and 50 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 6 and 50. 19. The kit as claimed in claim 18, which comprises 2 or 3 respectively specific binding partners of the expression products of the nucleic acid sequences identified in SEQ ID NOs: 1, 6 and 50 or of the nucleic acid sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 6 and 50. 20. The kit as claimed in claim 14, in which the at least two respectively specific binding partners of the expression products are respectively at least one hybridization probe and/or at least one amplification primer, or at least one antibody, or at least one antibody analog, or at least one affinity protein, or at least one aptamer. 21. A method for evaluating the efficacy of a treatment and/or a progression in lung cancer, which comprises a step of detecting at least two expression products respectively of at least two nucleic acid sequences, said two nucleic acid sequences being chosen from the sequences identified in SEQ ID NOs: 1 to 242 or from the sequences which exhibit at least 99% identity respectively with the sequences identified in SEQ ID NOs: 1 to 242. 22. The method as claimed in claim 21, in which the expression product of at least two nucleic acid sequences is detected, said at least two nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 4, 5, 7, 9, 10, 12, 20, 25 and 40 or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 4, 5, 7, 9, 10, 12, 20, 25 and 40. 23. The method as claimed in claim 21, in which the expression product of at least two nucleic acid sequences is detected, said nucleic acid sequences being chosen from the group of sequences identified in SEQ ID NOs: 1, 6 and 50, or from the sequences which exhibit at least 99% identity with the sequences identified in SEQ ID NOs: 1, 6 and 50.35 | 1,600 |
1,385 | 14,428,057 | 1,617 | The present application is directed to a system and device for attraction of pests. This system comprises CO 2 -releasing microorganisms, and also nutrients specific to these microorganisms, and this system, or the device, comprises one or more biodegradable biopolymers and allows CO 2 , and optionally other attractants, to be released over a period of more than 20 days. Furthermore, the present application provides for the use of such a system or such a device for the attraction of pests, more particularly of maize or potato pests, such as larvae of the Western corn rootworm or wire worm. The present application is also directed, lastly, to methods for attracting pests, more particularly pests of maize or potatoes, such as the larvae of the Western corn rootworm, or for wire worms, with the systems or devices of the invention being positioned in the immediate vicinity of the plants, but preferably not directly on the plants. | 1. A system or device for attracting pests, comprising
CO2-releasing microorganisms and nutrients specific for these microorganisms, and one or more biodegradable biopolymers which fully surround other constituents of the system and which allow release of CO2 over a period of more than 20 days. 2. The system or device of claim 1, wherein the CO2-releasing microorganisms are selected from fungi or bacteria. 3. The system or device of claim 1 wherein the nutrients are selected from corn flour, corn protein, other corn constituents, starch, squash flour, and potato flour. 4. The system or device of claim 1, further comprising one or more pesticides. 5. The system or device of claim 17 wherein the insecticide or nematicide are selected from the group of chemical insecticides, plant extracts, and biological plant protection agents. 6. The system or device of claim 4, wherein the chemical insecticide is tefluthrin, and/or the plant extract is selected from the group consisting of neem oil, azadirachtin extract, and quassia extract, and/or the biological plant protection agent is selected from entomopathogenic fungi and entomopathogenic nematodes. 7. The system of claim 1, further comprising one or more of constituent fillers, drying assistants, glucose, sucrose, additional attractants, cellulose, lignin, and swelling aids. 8. The system or device of claim 1 wherein the one or more biodegradable biopolymers are selected from alginate, carrageenan, cellulose, hemicellulose, starch, chitin, chitosan, pectinate, guar gum, acacia gum, poly-D,L-lactic acid, gelatin, poly-amino acids, lignin, and derivatives, and mixtures thereof. 9. The system or device of claim 1 wherein the system or device is configured in the form of capsules or granules. 10. The system or device of claim 1, further comprising one or more auxiliary organisms. 11. The system or device of claim 10, wherein the auxiliary organisms are fungi, more particularly B. bassiana or M anisopliae. 12. (canceled) 13. A method for attracting pests of corn or potatoes, comprising the provision of a system or device of claim 1 in the immediate vicinity of corn or potato plants. 14. The method of claim 13, wherein an ascending CO2 gradient from the plant in the direction of the system is built up in the soil. 15. The method of claim 21 wherein the system or device permits immobilization or killing of the larvae of the Western corn rootworm or of the wireworm or of the black vine weevil. 16. The system or device of claim 2 wherein the CO2-releasing microorganisms are baker's yeast. 17. The system or device of claim 4 wherein said one or more pesticides are selected from the group consisting of an insecticide and a nematicide. 18. The system or device of claim 7 wherein said additional attractants includes cucurbitacin. 19. The system or device of claim 10 wherein the one or more auxiliary organisms support the supply of nutrients to the CO2-releasing microorganisms. 20. The system or device of claim 11 wherein the fungi are selected from the group consisting of B. bassiana or M anisopliae. 21. The method of claim 13 wherein the pests are selected from the group consisting of larvae of the Western corn rootworm, wireworms, and the black vine weevil. | The present application is directed to a system and device for attraction of pests. This system comprises CO 2 -releasing microorganisms, and also nutrients specific to these microorganisms, and this system, or the device, comprises one or more biodegradable biopolymers and allows CO 2 , and optionally other attractants, to be released over a period of more than 20 days. Furthermore, the present application provides for the use of such a system or such a device for the attraction of pests, more particularly of maize or potato pests, such as larvae of the Western corn rootworm or wire worm. The present application is also directed, lastly, to methods for attracting pests, more particularly pests of maize or potatoes, such as the larvae of the Western corn rootworm, or for wire worms, with the systems or devices of the invention being positioned in the immediate vicinity of the plants, but preferably not directly on the plants.1. A system or device for attracting pests, comprising
CO2-releasing microorganisms and nutrients specific for these microorganisms, and one or more biodegradable biopolymers which fully surround other constituents of the system and which allow release of CO2 over a period of more than 20 days. 2. The system or device of claim 1, wherein the CO2-releasing microorganisms are selected from fungi or bacteria. 3. The system or device of claim 1 wherein the nutrients are selected from corn flour, corn protein, other corn constituents, starch, squash flour, and potato flour. 4. The system or device of claim 1, further comprising one or more pesticides. 5. The system or device of claim 17 wherein the insecticide or nematicide are selected from the group of chemical insecticides, plant extracts, and biological plant protection agents. 6. The system or device of claim 4, wherein the chemical insecticide is tefluthrin, and/or the plant extract is selected from the group consisting of neem oil, azadirachtin extract, and quassia extract, and/or the biological plant protection agent is selected from entomopathogenic fungi and entomopathogenic nematodes. 7. The system of claim 1, further comprising one or more of constituent fillers, drying assistants, glucose, sucrose, additional attractants, cellulose, lignin, and swelling aids. 8. The system or device of claim 1 wherein the one or more biodegradable biopolymers are selected from alginate, carrageenan, cellulose, hemicellulose, starch, chitin, chitosan, pectinate, guar gum, acacia gum, poly-D,L-lactic acid, gelatin, poly-amino acids, lignin, and derivatives, and mixtures thereof. 9. The system or device of claim 1 wherein the system or device is configured in the form of capsules or granules. 10. The system or device of claim 1, further comprising one or more auxiliary organisms. 11. The system or device of claim 10, wherein the auxiliary organisms are fungi, more particularly B. bassiana or M anisopliae. 12. (canceled) 13. A method for attracting pests of corn or potatoes, comprising the provision of a system or device of claim 1 in the immediate vicinity of corn or potato plants. 14. The method of claim 13, wherein an ascending CO2 gradient from the plant in the direction of the system is built up in the soil. 15. The method of claim 21 wherein the system or device permits immobilization or killing of the larvae of the Western corn rootworm or of the wireworm or of the black vine weevil. 16. The system or device of claim 2 wherein the CO2-releasing microorganisms are baker's yeast. 17. The system or device of claim 4 wherein said one or more pesticides are selected from the group consisting of an insecticide and a nematicide. 18. The system or device of claim 7 wherein said additional attractants includes cucurbitacin. 19. The system or device of claim 10 wherein the one or more auxiliary organisms support the supply of nutrients to the CO2-releasing microorganisms. 20. The system or device of claim 11 wherein the fungi are selected from the group consisting of B. bassiana or M anisopliae. 21. The method of claim 13 wherein the pests are selected from the group consisting of larvae of the Western corn rootworm, wireworms, and the black vine weevil. | 1,600 |
1,386 | 14,422,868 | 1,619 | The invention relates to a cosmetic composition comprising a blue dye powder containing an anthocyan, a metal ion and tannic acid and a cosmetic additive. The invention also relates to a process for making up keratin materials by applying the cosmetic composition to the keratin materials. | 1. Process for making up keratin materials, comprising the application to the keratin materials of a dye powder having a blue colour comprising at least one anthocyan, metal ions chosen from the group of ions derived from Al(III), Ca(II), Cu(II), Fe(II), Fe(III), Mg(II), Mn(II) and Zn(II) and mixtures thereof, tannic acid or a gallotannin derivative thereof, or mixtures thereof. 2. Process according to the claim 1, wherein the anthocyan is a compound of formula (I):
in which R1, R2 and R4 independently denote H, OH, OMe, a sugar unit or an acylated sugar unit (acyl group derived from malonic acid, p-coumaric acid, ferulic acid or caffeic acid) and R3, R5, R6 and R7 independently denote H, OH or OMe. 3. Process according to claim 1, wherein the anthocyan is derived from plant matter chosen from red cabbage, red onion, purple potato, grape, cranberry, strawberry, raspberry, aronia, black soybean, blackcurrant, elderberry, hibiscus, radish, gooseberry, bilberry, cherry, aubergine, black carrot and black rice. 4. Process according to claim 1, wherein the metal ions are chosen from ions derived from Fe(II), Fe(III) and Mg(II), and mixtures thereof. 5. Process according to claim 1, wherein the anthocyan is present in the dye powder in a content ranging from 0.05% to 50% by weight relative to the total weight of solids of the dye powder. 6. Process according to claim 1, wherein the said metal ions are present in the dye powder in a metal ion/anthocyan weight ratio ranging from 0.01/1 to 10/1. 7. Process according to claim 1, wherein the tannic acid or a gallotannin derivative thereof, or mixtures thereof, is present in the dye powder in a tannic acid or gallotannin derivative/anthocyan weight ratio ranging from 0.05/1 to 20/1. 8. Process according to claim 1, wherein the dye powder comprises an additional ingredient chosen from:
an amino acid chosen from taurine, proline and arginine; a phospholipid; a monocarboxylic or dicarboxylic acid containing from 2 to 6 carbon atoms. 9. Cosmetic composition comprising, in a physiologically acceptable medium, (i) a dye powder having a blue colour comprising at least one anthocyan, metal ions chosen from the group of ions derived from Al(III), Ca(II), Cu(II), Fe(II), Fe(III), Mg(II), Mn(II) and Zn(II) and mixtures thereof, tannic acid or a gallotannin derivative thereof, or mixtures thereof, and (ii) a cosmetic additive chosen from fragrances, preserving agents, film-forming polymers, fillers, UV-screening agents, thickeners, silicone oils, plant oils, liquid paraffins, waxes, moisturizers, vitamins, proteins and hydrolysates thereof, ceramides, antioxidants, free-radical scavengers, organic solvents, mineral pigments and nacres. 10. Composition according to claim 9, wherein the anthocyan is a compound of formula (I):
in which R1, R2 and R4 independently denote H, OH, OMe, a sugar unit or an acylated sugar unit (acyl group derived from malonic acid, p-coumaric acid, ferulic acid or caffeic acid) and R3, R5, R6 and R7 independently denote H, OH or OMe. 11. Composition according to claim 9, wherein the anthocyan is derived from plant matter chosen from red cabbage, red onion, purple potato, grape, cranberry, strawberry, raspberry, aronia, black soybean, blackcurrant, elderberry, hibiscus, radish, gooseberry, bilberry, cherry, aubergine, black carrot and black rice. 12. Composition according to claim 9, wherein the metal ions are chosen from ions derived from Fe(II), Fe(III) and Mg(II), and mixtures thereof. 13. Composition according to claim 9, wherein the anthocyan is present in the dye powder in a content ranging from 0.05% to 50% by weight relative to the total weight of solids of the dye powder. 14. Composition according to claim 9, wherein the said metal ions are present in the dye powder in a metal ion/anthocyan weight ratio ranging from 0.01/1 to 10/1. 15. Composition according to claim 9, wherein the tannic acid or a gallotannin derivative thereof, and mixtures thereof, is present in the dye powder in a tannic acid or gallotannin derivative/anthocyan weight ratio ranging from 0.05/1 to 20/1. 16. Process according to claim 1, wherein the anthocyan is present in the dye powder in a content ranging from 0.3% to 25% by weight relative to the total weight of solids of the dye powder. 17. Process according to claim 1, wherein the anthocyan is present in the dye powder in a content ranging from 5% to 15% by weight relative to the total weight of solids of the dye powder. 18. Process according to claim 1, wherein the said metal ions are present in the dye powder in a metal ion/anthocyan weight ratio ranging from 0.05/1 to 5/1. 19. Process according to claim 1, wherein the tannic acid or a gallotannin derivative thereof, or mixtures thereof, is present in the dye powder in a tannic acid or gallotannin derivative/anthocyan weight ratio ranging from 0.1/1 to 10/1. 20. Composition according to claim 9, wherein the anthocyan is present in the dye powder in a content ranging from 0.3% to 25% by weight relative to the total weight of solids of the dye powder. | The invention relates to a cosmetic composition comprising a blue dye powder containing an anthocyan, a metal ion and tannic acid and a cosmetic additive. The invention also relates to a process for making up keratin materials by applying the cosmetic composition to the keratin materials.1. Process for making up keratin materials, comprising the application to the keratin materials of a dye powder having a blue colour comprising at least one anthocyan, metal ions chosen from the group of ions derived from Al(III), Ca(II), Cu(II), Fe(II), Fe(III), Mg(II), Mn(II) and Zn(II) and mixtures thereof, tannic acid or a gallotannin derivative thereof, or mixtures thereof. 2. Process according to the claim 1, wherein the anthocyan is a compound of formula (I):
in which R1, R2 and R4 independently denote H, OH, OMe, a sugar unit or an acylated sugar unit (acyl group derived from malonic acid, p-coumaric acid, ferulic acid or caffeic acid) and R3, R5, R6 and R7 independently denote H, OH or OMe. 3. Process according to claim 1, wherein the anthocyan is derived from plant matter chosen from red cabbage, red onion, purple potato, grape, cranberry, strawberry, raspberry, aronia, black soybean, blackcurrant, elderberry, hibiscus, radish, gooseberry, bilberry, cherry, aubergine, black carrot and black rice. 4. Process according to claim 1, wherein the metal ions are chosen from ions derived from Fe(II), Fe(III) and Mg(II), and mixtures thereof. 5. Process according to claim 1, wherein the anthocyan is present in the dye powder in a content ranging from 0.05% to 50% by weight relative to the total weight of solids of the dye powder. 6. Process according to claim 1, wherein the said metal ions are present in the dye powder in a metal ion/anthocyan weight ratio ranging from 0.01/1 to 10/1. 7. Process according to claim 1, wherein the tannic acid or a gallotannin derivative thereof, or mixtures thereof, is present in the dye powder in a tannic acid or gallotannin derivative/anthocyan weight ratio ranging from 0.05/1 to 20/1. 8. Process according to claim 1, wherein the dye powder comprises an additional ingredient chosen from:
an amino acid chosen from taurine, proline and arginine; a phospholipid; a monocarboxylic or dicarboxylic acid containing from 2 to 6 carbon atoms. 9. Cosmetic composition comprising, in a physiologically acceptable medium, (i) a dye powder having a blue colour comprising at least one anthocyan, metal ions chosen from the group of ions derived from Al(III), Ca(II), Cu(II), Fe(II), Fe(III), Mg(II), Mn(II) and Zn(II) and mixtures thereof, tannic acid or a gallotannin derivative thereof, or mixtures thereof, and (ii) a cosmetic additive chosen from fragrances, preserving agents, film-forming polymers, fillers, UV-screening agents, thickeners, silicone oils, plant oils, liquid paraffins, waxes, moisturizers, vitamins, proteins and hydrolysates thereof, ceramides, antioxidants, free-radical scavengers, organic solvents, mineral pigments and nacres. 10. Composition according to claim 9, wherein the anthocyan is a compound of formula (I):
in which R1, R2 and R4 independently denote H, OH, OMe, a sugar unit or an acylated sugar unit (acyl group derived from malonic acid, p-coumaric acid, ferulic acid or caffeic acid) and R3, R5, R6 and R7 independently denote H, OH or OMe. 11. Composition according to claim 9, wherein the anthocyan is derived from plant matter chosen from red cabbage, red onion, purple potato, grape, cranberry, strawberry, raspberry, aronia, black soybean, blackcurrant, elderberry, hibiscus, radish, gooseberry, bilberry, cherry, aubergine, black carrot and black rice. 12. Composition according to claim 9, wherein the metal ions are chosen from ions derived from Fe(II), Fe(III) and Mg(II), and mixtures thereof. 13. Composition according to claim 9, wherein the anthocyan is present in the dye powder in a content ranging from 0.05% to 50% by weight relative to the total weight of solids of the dye powder. 14. Composition according to claim 9, wherein the said metal ions are present in the dye powder in a metal ion/anthocyan weight ratio ranging from 0.01/1 to 10/1. 15. Composition according to claim 9, wherein the tannic acid or a gallotannin derivative thereof, and mixtures thereof, is present in the dye powder in a tannic acid or gallotannin derivative/anthocyan weight ratio ranging from 0.05/1 to 20/1. 16. Process according to claim 1, wherein the anthocyan is present in the dye powder in a content ranging from 0.3% to 25% by weight relative to the total weight of solids of the dye powder. 17. Process according to claim 1, wherein the anthocyan is present in the dye powder in a content ranging from 5% to 15% by weight relative to the total weight of solids of the dye powder. 18. Process according to claim 1, wherein the said metal ions are present in the dye powder in a metal ion/anthocyan weight ratio ranging from 0.05/1 to 5/1. 19. Process according to claim 1, wherein the tannic acid or a gallotannin derivative thereof, or mixtures thereof, is present in the dye powder in a tannic acid or gallotannin derivative/anthocyan weight ratio ranging from 0.1/1 to 10/1. 20. Composition according to claim 9, wherein the anthocyan is present in the dye powder in a content ranging from 0.3% to 25% by weight relative to the total weight of solids of the dye powder. | 1,600 |
1,387 | 14,381,366 | 1,634 | A method detects nucleic acid with high sensitivity even when the target nucleic acid is detected by sandwich hybridization using neither nucleic acid amplification nor a sensitization technique. The method includes sequentially or simultaneously bringing a target nucleic acid or fragmentation product thereof, a plurality of detection probes, and a capture probe immobilized on a support, into contact with each other to hybridize the capture probe with the target nucleic acid or fragmentation product thereof and to hybridize the target nucleic acid or fragmentation product thereof with the plurality of detection probes, thereby binding the plurality of detection probes to the support through the capture probe and the target nucleic acid or fragmentation product thereof; and then detecting the plurality of detection probes bound to the support. | 1. A method of detecting a target nucleic acid comprising:
sequentially or simultaneously bringing a fragmentation product a target nucleic acid, a plurality of detection probes, and a capture probe immobilized on a support, into contact with each other to hybridize said capture probe with said fragmentation product said target nucleic acid and to hybridize said fragmentation product with said plurality of detection probes, thereby binding said plurality of detection probes to said support through said capture probe and said fragmentation product said target nucleic acid; and detecting said plurality of detection probes bound to said support. 2. The method according to claim 1, wherein sequentially or simultaneously bringing a fragmentation product of the target nucleic acid, a plurality of detection probes, and a capture probe immobilized on a support, into contact with each other is sequentially carried out by hybridizing said fragmentation product of said target nucleic acid with said plurality of detection probes and then hybridizing said fragmentation product of said target nucleic acid hybridized with said plurality of detection probes with said capture probe. 3. The method according to claim 1, wherein, in said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe, a plurality of detection probes are hybridized at distances of not more than the mode of the nucleic acid length of said target nucleic acid or fragmentation product thereof from the binding position of said capture. 4. The method according to claim 1, wherein the mode of thenucleic acid length of said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe is 100 bases to 1500 bases. 5. The method according to claim 1, wherein, in said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe, a plurality of detection probes are hybridized at distances of not more than 1500 bases from the binding position of said capture probe. 6. The method according to claim 1, wherein a fragmentation product of said target nucleic acid prepared by carrying out a fragmentation treatment of said target nucleic acid such that the mode of the nucleic acid length is 100 bases to 1500 bases is hybridized with said capture probe. 7. The method according to claim 1, wherein said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe has not undergone amplification by a nucleic acid amplification method. 8. The method according to claim 1, wherein an animal-derived sample containing said target nucleic acid is subjected to said detection method, said detection method further comprising a step of detecting at least one type of repetitive sequences present in the animal genome as an internal standard, said repetitive sequences being contained in fragments of said animal genome. 9. The method according to claim 8, further comprising fragmenting said animal genome, wherein said repetitive sequences are contained in the fragmented animal genome. 10. The method according to claim 8, wherein said animal is human. 11. The method according to claim 8, wherein said repetitive sequences are short interspersed nuclear elements. 12. The method according to claim 11, wherein said short interspersed nuclear elements are Alu sequences. 13. The method according to claim 2, in said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe, a plurality of detection probes are hybridized at distances of not more than the mode of the nucleic acid length of said target nucleic acid or fragmentation product thereof from the binding position of said capture. 14. The method according to claim 2, wherein the mode of thenucleic acid length of said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe is 100 bases to 1500 bases. 15. The method according to claim 3, wherein the mode of thenucleic acid length of said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe is 100 bases to 1500 bases. 16. The method according to claim 2, wherein, in said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe, a plurality of detection probes are hybridized at distances of not more than 1500 bases from the binding position of said capture probe. 17. The method according to claim 3, wherein, in said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe, a plurality of detection probes are hybridized at distances of not more than 1500 bases from the binding position of said capture probe. 18. The method according to claim 4, wherein, in said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe, a plurality of detection probes are hybridized at distances of not more than 1500 bases from the binding position of said capture probe. 19. The method according to claim 9, wherein said animal is human. 20. The method according to claim 9, wherein said repetitive sequences are short interspersed nuclear elements. | A method detects nucleic acid with high sensitivity even when the target nucleic acid is detected by sandwich hybridization using neither nucleic acid amplification nor a sensitization technique. The method includes sequentially or simultaneously bringing a target nucleic acid or fragmentation product thereof, a plurality of detection probes, and a capture probe immobilized on a support, into contact with each other to hybridize the capture probe with the target nucleic acid or fragmentation product thereof and to hybridize the target nucleic acid or fragmentation product thereof with the plurality of detection probes, thereby binding the plurality of detection probes to the support through the capture probe and the target nucleic acid or fragmentation product thereof; and then detecting the plurality of detection probes bound to the support.1. A method of detecting a target nucleic acid comprising:
sequentially or simultaneously bringing a fragmentation product a target nucleic acid, a plurality of detection probes, and a capture probe immobilized on a support, into contact with each other to hybridize said capture probe with said fragmentation product said target nucleic acid and to hybridize said fragmentation product with said plurality of detection probes, thereby binding said plurality of detection probes to said support through said capture probe and said fragmentation product said target nucleic acid; and detecting said plurality of detection probes bound to said support. 2. The method according to claim 1, wherein sequentially or simultaneously bringing a fragmentation product of the target nucleic acid, a plurality of detection probes, and a capture probe immobilized on a support, into contact with each other is sequentially carried out by hybridizing said fragmentation product of said target nucleic acid with said plurality of detection probes and then hybridizing said fragmentation product of said target nucleic acid hybridized with said plurality of detection probes with said capture probe. 3. The method according to claim 1, wherein, in said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe, a plurality of detection probes are hybridized at distances of not more than the mode of the nucleic acid length of said target nucleic acid or fragmentation product thereof from the binding position of said capture. 4. The method according to claim 1, wherein the mode of thenucleic acid length of said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe is 100 bases to 1500 bases. 5. The method according to claim 1, wherein, in said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe, a plurality of detection probes are hybridized at distances of not more than 1500 bases from the binding position of said capture probe. 6. The method according to claim 1, wherein a fragmentation product of said target nucleic acid prepared by carrying out a fragmentation treatment of said target nucleic acid such that the mode of the nucleic acid length is 100 bases to 1500 bases is hybridized with said capture probe. 7. The method according to claim 1, wherein said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe has not undergone amplification by a nucleic acid amplification method. 8. The method according to claim 1, wherein an animal-derived sample containing said target nucleic acid is subjected to said detection method, said detection method further comprising a step of detecting at least one type of repetitive sequences present in the animal genome as an internal standard, said repetitive sequences being contained in fragments of said animal genome. 9. The method according to claim 8, further comprising fragmenting said animal genome, wherein said repetitive sequences are contained in the fragmented animal genome. 10. The method according to claim 8, wherein said animal is human. 11. The method according to claim 8, wherein said repetitive sequences are short interspersed nuclear elements. 12. The method according to claim 11, wherein said short interspersed nuclear elements are Alu sequences. 13. The method according to claim 2, in said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe, a plurality of detection probes are hybridized at distances of not more than the mode of the nucleic acid length of said target nucleic acid or fragmentation product thereof from the binding position of said capture. 14. The method according to claim 2, wherein the mode of thenucleic acid length of said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe is 100 bases to 1500 bases. 15. The method according to claim 3, wherein the mode of thenucleic acid length of said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe is 100 bases to 1500 bases. 16. The method according to claim 2, wherein, in said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe, a plurality of detection probes are hybridized at distances of not more than 1500 bases from the binding position of said capture probe. 17. The method according to claim 3, wherein, in said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe, a plurality of detection probes are hybridized at distances of not more than 1500 bases from the binding position of said capture probe. 18. The method according to claim 4, wherein, in said target nucleic acid or fragmentation product thereof to be hybridized with said capture probe, a plurality of detection probes are hybridized at distances of not more than 1500 bases from the binding position of said capture probe. 19. The method according to claim 9, wherein said animal is human. 20. The method according to claim 9, wherein said repetitive sequences are short interspersed nuclear elements. | 1,600 |
1,388 | 14,951,736 | 1,628 | The present invention provides compounds of Formula I:
pharmaceutical compositions comprising these compounds and methods of using these compounds to treat or prevent a disease or disorder mediated by FXR and/or TGR5. | 1. A compound represented by Formula I or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, solvate, or combination thereof:
wherein:
X is absent, —C(O)NH— or —NH—;
R1 is selected from the group consisting of:
1) Hydrogen;
2) Substituted or unsubstituted —C1-C8 alkyl;
3) Substituted or unsubstituted —C2-C8 alkenyl;
4) Substituted or unsubstituted —C2-C8 alkynyl;
5) Substituted or unsubstituted arylalkyl; and
6) Substituted or unsubstituted aryl;
m is 0, 1, 2 or 3;
R2 is hydrogen, hydroxyl, —OSO3H, —OSO3 −, —OAc, —OPO3H2 or —OPO3 2−; preferably R2 is hydrogen or hydroxyl;
R3 is hydrogen, halogen, CN, N3, hydroxyl, —OSO3H, —OSO3 −, —OAc, —OPO3H2, —OPO3 2−, —SR1 or —NHR1, wherein R1 is as defined previously;
Or R2 and R3 are taken together with the carbon atoms to which they are attached to form —CH═CH— or cycloalkyl ring or heterocycloalkyl ring such as, but not limited to cyclopropyl, or epoxide;
R4 and R5 are independently selected from hydrogen or hydroxyl protecting group; and
R6 is selected from the group consisting of:
1) Hydrogen;
2) Halogen;
3) Substituted or unsubstituted —C1-C8 alkyl;
4) Substituted or unsubstituted —C2-C8 alkenyl;
5) Substituted or unsubstituted —C2-C8 alkynyl; and
6) Substituted or unsubstituted —C3-C8 cycloalkyl. 2. The compound of claim 1, represented by Formula II or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, solvate, or combination thereof:
wherein R1, R2, R3, R6, X and m are as defined in claim 1. 3. The compound of claim 1, represented by Formula III or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, solvate, or combination thereof:
wherein R1, R2, R6, X and m are as defined in claim 1. 4. The compound of claim 1, represented by formula (III-1˜III-18), where R6 and m are as defined in claim 1: 5. The compound of claim 1, represented by Formula IV or a pharmaceutically acceptable salt thereof:
wherein m is as defined in claim 1. 6. The compound of claim 1, represented by Formula V or a pharmaceutically acceptable salt thereof:
wherein m is as defined in claim 1. 7. The compound of claim 1, represented by Formula VI or a pharmaceutically acceptable salt thereof:
wherein m is as defined in claim 1. 8. A method for the prevention or treatment of an FXR-mediated disease or condition in a mammal comprising administering to the mammal suffering from an FXR-mediated disease or condition a therapeutically effective amount of a compound of formula (I) according to claim 1. 9. The method according to claim 8, wherein the FXR-mediated disease or condition is selected from the group consisting of chronic liver disease, gastrointestinal disease, renal disease, cardiovascular disease, and metabolic disease. 10. The method according to claim 9, wherein the chronic liver disease is selected from the group consisting of primary biliary cirrhosis (PBC), cerebrotendinous xanthomatosis (CTX), primary sclerosing cholangitis (PSC), drug induced cholestasis, intrahepatic cholestasis of pregnancy, parenteral nutrition associated cholestasis (PNAC), bacterial overgrowth or sepsis associated cholestasis, autoimmune hepatitis, chronic viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), liver transplant associated graft versus host disease, living donor transplant liver regeneration, congenital hepatic fibrosis, choledocholithiasis, granulomatous liver disease, intra- or extrahepatic malignancy, Sjogren's syndrome, Sarcoidosis, Wilson's disease, Gaucher's disease, hemochromatosis, and alpha 1-antitrypsin deficiency. 11. The method according to claim 9, wherein the renal disease is selected from the group consisting of diabetic nephropathy, focal segmental glomerulosclerosis (FSGS), hypertensive nephrosclerosis, chronic glomerulonephritis, chronic transplant glomerulopathy, chronic interstitial nephritis, and polycystic kidney disease. 12. The method according to claim 9, wherein the cardiovascular disease is selected from the group consisting of atherosclerosis, arteriosclerosis, dyslipidemia, hypercholesterolemia, and hypertriglyceridemia. 13. The method according to claim 9, wherein the metabolic disease is selected from the group consisting of insulin resistance, Type I and Type II diabetes, and obesity. 14. A method for the prevention or treatment of an TGR5-mediated disease or condition in a mammal comprising administering to the mammal suffering from an TGR5-mediated disease or condition a therapeutically effective amount of a compound of formula (I) according to claim 1. 15. A pharmaceutical composition comprising a compound of formula (I) according to claim 1 and a pharmaceutically acceptable carrier. 16. Use of a compound of claim 1 for the preparation of pharmaceutical compositions for the prevention or treatment of FXR-mediated or TGR5-mediated diseases or conditions. | The present invention provides compounds of Formula I:
pharmaceutical compositions comprising these compounds and methods of using these compounds to treat or prevent a disease or disorder mediated by FXR and/or TGR5.1. A compound represented by Formula I or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, solvate, or combination thereof:
wherein:
X is absent, —C(O)NH— or —NH—;
R1 is selected from the group consisting of:
1) Hydrogen;
2) Substituted or unsubstituted —C1-C8 alkyl;
3) Substituted or unsubstituted —C2-C8 alkenyl;
4) Substituted or unsubstituted —C2-C8 alkynyl;
5) Substituted or unsubstituted arylalkyl; and
6) Substituted or unsubstituted aryl;
m is 0, 1, 2 or 3;
R2 is hydrogen, hydroxyl, —OSO3H, —OSO3 −, —OAc, —OPO3H2 or —OPO3 2−; preferably R2 is hydrogen or hydroxyl;
R3 is hydrogen, halogen, CN, N3, hydroxyl, —OSO3H, —OSO3 −, —OAc, —OPO3H2, —OPO3 2−, —SR1 or —NHR1, wherein R1 is as defined previously;
Or R2 and R3 are taken together with the carbon atoms to which they are attached to form —CH═CH— or cycloalkyl ring or heterocycloalkyl ring such as, but not limited to cyclopropyl, or epoxide;
R4 and R5 are independently selected from hydrogen or hydroxyl protecting group; and
R6 is selected from the group consisting of:
1) Hydrogen;
2) Halogen;
3) Substituted or unsubstituted —C1-C8 alkyl;
4) Substituted or unsubstituted —C2-C8 alkenyl;
5) Substituted or unsubstituted —C2-C8 alkynyl; and
6) Substituted or unsubstituted —C3-C8 cycloalkyl. 2. The compound of claim 1, represented by Formula II or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, solvate, or combination thereof:
wherein R1, R2, R3, R6, X and m are as defined in claim 1. 3. The compound of claim 1, represented by Formula III or a pharmaceutically acceptable salt, ester, stereoisomer, tautomer, solvate, or combination thereof:
wherein R1, R2, R6, X and m are as defined in claim 1. 4. The compound of claim 1, represented by formula (III-1˜III-18), where R6 and m are as defined in claim 1: 5. The compound of claim 1, represented by Formula IV or a pharmaceutically acceptable salt thereof:
wherein m is as defined in claim 1. 6. The compound of claim 1, represented by Formula V or a pharmaceutically acceptable salt thereof:
wherein m is as defined in claim 1. 7. The compound of claim 1, represented by Formula VI or a pharmaceutically acceptable salt thereof:
wherein m is as defined in claim 1. 8. A method for the prevention or treatment of an FXR-mediated disease or condition in a mammal comprising administering to the mammal suffering from an FXR-mediated disease or condition a therapeutically effective amount of a compound of formula (I) according to claim 1. 9. The method according to claim 8, wherein the FXR-mediated disease or condition is selected from the group consisting of chronic liver disease, gastrointestinal disease, renal disease, cardiovascular disease, and metabolic disease. 10. The method according to claim 9, wherein the chronic liver disease is selected from the group consisting of primary biliary cirrhosis (PBC), cerebrotendinous xanthomatosis (CTX), primary sclerosing cholangitis (PSC), drug induced cholestasis, intrahepatic cholestasis of pregnancy, parenteral nutrition associated cholestasis (PNAC), bacterial overgrowth or sepsis associated cholestasis, autoimmune hepatitis, chronic viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), liver transplant associated graft versus host disease, living donor transplant liver regeneration, congenital hepatic fibrosis, choledocholithiasis, granulomatous liver disease, intra- or extrahepatic malignancy, Sjogren's syndrome, Sarcoidosis, Wilson's disease, Gaucher's disease, hemochromatosis, and alpha 1-antitrypsin deficiency. 11. The method according to claim 9, wherein the renal disease is selected from the group consisting of diabetic nephropathy, focal segmental glomerulosclerosis (FSGS), hypertensive nephrosclerosis, chronic glomerulonephritis, chronic transplant glomerulopathy, chronic interstitial nephritis, and polycystic kidney disease. 12. The method according to claim 9, wherein the cardiovascular disease is selected from the group consisting of atherosclerosis, arteriosclerosis, dyslipidemia, hypercholesterolemia, and hypertriglyceridemia. 13. The method according to claim 9, wherein the metabolic disease is selected from the group consisting of insulin resistance, Type I and Type II diabetes, and obesity. 14. A method for the prevention or treatment of an TGR5-mediated disease or condition in a mammal comprising administering to the mammal suffering from an TGR5-mediated disease or condition a therapeutically effective amount of a compound of formula (I) according to claim 1. 15. A pharmaceutical composition comprising a compound of formula (I) according to claim 1 and a pharmaceutically acceptable carrier. 16. Use of a compound of claim 1 for the preparation of pharmaceutical compositions for the prevention or treatment of FXR-mediated or TGR5-mediated diseases or conditions. | 1,600 |
1,389 | 14,249,259 | 1,642 | The present invention concerns a method for predicting the potential for aggressive growth and/or the risk to progress to high grade cancer for tumors in cell based detection procedures. In one aspect the invention concerns the detection of overexpression of cyclin-dependent kinase inhibitor gene products as a tool for predicting the progression risk and/or potential for aggressive growth of tumors. In a second aspect the invention concerns predicting the progression risk and/or potential for aggressive growth in tumors on the basis of the simultaneous co-detection of the presence of overexpression of cyclin-dependent kinase inhibitor gene products together with the expression of markers for active cell proliferation. Further the invention concerns preparations of probes for diagnosis namely for predicting the progression risk and/or the potential for aggressive growth of tumors. | 1. A method for predicting a potential for breast tumors for aggressive growth and/or a risk to progress to high grade cancer, comprising:
obtaining a breast tumor sample of a subject; measuring by a cell based detection procedure whether at least one single cell of the breast tumor sample simultaneously overexpresses p16INK4a and expresses Ki67; and determining that the tumors have a potential for aggressive growth and/or a risk to progress to high grade cancer when there is at least one single cell in the sample having the simultaneous presence of overexpression of p16INK4a and the expression of Ki67. 2. The method of claim 1, wherein the cell based detection procedure is immunohistochemistry or immunocytochemistry. 3. The method of claim 1, said measuring uses antibodies against p16INK4a and Ki67. 4. The method of claim 1, wherein the sample is a tissue sample or a cell sample. 5. The method of claim 1, wherein said breast tumors are early cancer precursor lesions or low grade cancers. 6. The method of claim 1, wherein said breast tumors are carcinoma in situ, dysplasia, or neoplasia. | The present invention concerns a method for predicting the potential for aggressive growth and/or the risk to progress to high grade cancer for tumors in cell based detection procedures. In one aspect the invention concerns the detection of overexpression of cyclin-dependent kinase inhibitor gene products as a tool for predicting the progression risk and/or potential for aggressive growth of tumors. In a second aspect the invention concerns predicting the progression risk and/or potential for aggressive growth in tumors on the basis of the simultaneous co-detection of the presence of overexpression of cyclin-dependent kinase inhibitor gene products together with the expression of markers for active cell proliferation. Further the invention concerns preparations of probes for diagnosis namely for predicting the progression risk and/or the potential for aggressive growth of tumors.1. A method for predicting a potential for breast tumors for aggressive growth and/or a risk to progress to high grade cancer, comprising:
obtaining a breast tumor sample of a subject; measuring by a cell based detection procedure whether at least one single cell of the breast tumor sample simultaneously overexpresses p16INK4a and expresses Ki67; and determining that the tumors have a potential for aggressive growth and/or a risk to progress to high grade cancer when there is at least one single cell in the sample having the simultaneous presence of overexpression of p16INK4a and the expression of Ki67. 2. The method of claim 1, wherein the cell based detection procedure is immunohistochemistry or immunocytochemistry. 3. The method of claim 1, said measuring uses antibodies against p16INK4a and Ki67. 4. The method of claim 1, wherein the sample is a tissue sample or a cell sample. 5. The method of claim 1, wherein said breast tumors are early cancer precursor lesions or low grade cancers. 6. The method of claim 1, wherein said breast tumors are carcinoma in situ, dysplasia, or neoplasia. | 1,600 |
1,390 | 15,818,450 | 1,656 | Disclosed herein are biohybrid protein complexes capable of using light energy to photocatalyze the reduction of N 2 into NH 3 . Also provided are methods of using biohybrid protein complexes to enzymatically reduce N 2 to NH 3 using light rather than chemical energy as the driving force. These methods may also include the production and isolation of ammonia, hydrogen or both. | 1. A biohybrid complex, comprising a photoactive nanoparticle and an enzyme, wherein the photoactive nanoparticle produces electrons when exposed to light and the enzyme uses the electrons produced by the photoactive nanoparticle to catalyze an enzymatic reaction. 2. The biohybrid complex of claim 1, further comprising an electron donor. 3. The biohybrid complex of claim 2, wherein the electron donor is HEPES. 4. The biohybrid complex of claim 1, wherein the light has a wavelength of from about 380 nm to about 450 nm. 5. The biohybrid complex of claim 1, wherein the intensity of the light at the biohybrid complex is from about 1.8 mW cm−2 to about 25 mW cm−2. 6. The biohybrid complex of claim 1, wherein the photoactive nanoparticle comprises nanoparticles. 7. The biohybrid complex of claim 1, wherein the photoactive nanoparticle comprises CdS nanoparticles. 8. The biohybrid complex of claim 1, wherein the enzyme is a nitrogenase. 9. The biohybrid complex of claim 8, wherein the nitrogenase is MoFe protein. 10. The biohybrid complex of claim 9, wherein the enzymatic reaction produces up to about 86 mol NH3 mol MoFe protein−1 min−1. 11. The biohybrid complex of claim 9, wherein the enzymatic reaction produces up to about 827 mol H2 mol MoFe protein−1 min−1. 12. The biohybrid complex of claim 9, wherein the enzymatic reaction produces up to about 12000 mol NH3 mol MoFe protein−1 over about 300 minutes of exposure to light. 13. The biohybrid complex of claim 9, wherein the enzymatic reaction produces up to about 120000 mol H2 mol MoFe protein−1 over about 300 minutes of exposure to light. 14. The biohybrid complex of claim 9, wherein the photoactive nanoparticle comprises CdS nanoparticles. 15. A method of producing ammonia, comprising
a) contacting a nitrogenase biohybrid complex with nitrogen; b) exposing the nitrogenase biohybrid complex to light to generate ammonia; and c) isolating the generated ammonia. 16. The method of claim 15, wherein the light has a wavelength from about 380 nm to about 450 nm. 17. The method of claim 15, wherein the intensity of the light at the biohybrid complex is from about 1.8 mW cm−2 to about 25 mW cm2. 18. The method of claim 15, wherein the biohybrid complex comprises CdS nanoparticles. 19. The method of claim 15, wherein the isolated ammonia is about 86 mol NH3 mol biohybrid complex−1 min−1. 20. The method of claim 15, wherein the isolated ammonia is about 12000 mol NH3 mol biohybrid complex−1 after about 300 minutes of exposure to light. | Disclosed herein are biohybrid protein complexes capable of using light energy to photocatalyze the reduction of N 2 into NH 3 . Also provided are methods of using biohybrid protein complexes to enzymatically reduce N 2 to NH 3 using light rather than chemical energy as the driving force. These methods may also include the production and isolation of ammonia, hydrogen or both.1. A biohybrid complex, comprising a photoactive nanoparticle and an enzyme, wherein the photoactive nanoparticle produces electrons when exposed to light and the enzyme uses the electrons produced by the photoactive nanoparticle to catalyze an enzymatic reaction. 2. The biohybrid complex of claim 1, further comprising an electron donor. 3. The biohybrid complex of claim 2, wherein the electron donor is HEPES. 4. The biohybrid complex of claim 1, wherein the light has a wavelength of from about 380 nm to about 450 nm. 5. The biohybrid complex of claim 1, wherein the intensity of the light at the biohybrid complex is from about 1.8 mW cm−2 to about 25 mW cm−2. 6. The biohybrid complex of claim 1, wherein the photoactive nanoparticle comprises nanoparticles. 7. The biohybrid complex of claim 1, wherein the photoactive nanoparticle comprises CdS nanoparticles. 8. The biohybrid complex of claim 1, wherein the enzyme is a nitrogenase. 9. The biohybrid complex of claim 8, wherein the nitrogenase is MoFe protein. 10. The biohybrid complex of claim 9, wherein the enzymatic reaction produces up to about 86 mol NH3 mol MoFe protein−1 min−1. 11. The biohybrid complex of claim 9, wherein the enzymatic reaction produces up to about 827 mol H2 mol MoFe protein−1 min−1. 12. The biohybrid complex of claim 9, wherein the enzymatic reaction produces up to about 12000 mol NH3 mol MoFe protein−1 over about 300 minutes of exposure to light. 13. The biohybrid complex of claim 9, wherein the enzymatic reaction produces up to about 120000 mol H2 mol MoFe protein−1 over about 300 minutes of exposure to light. 14. The biohybrid complex of claim 9, wherein the photoactive nanoparticle comprises CdS nanoparticles. 15. A method of producing ammonia, comprising
a) contacting a nitrogenase biohybrid complex with nitrogen; b) exposing the nitrogenase biohybrid complex to light to generate ammonia; and c) isolating the generated ammonia. 16. The method of claim 15, wherein the light has a wavelength from about 380 nm to about 450 nm. 17. The method of claim 15, wherein the intensity of the light at the biohybrid complex is from about 1.8 mW cm−2 to about 25 mW cm2. 18. The method of claim 15, wherein the biohybrid complex comprises CdS nanoparticles. 19. The method of claim 15, wherein the isolated ammonia is about 86 mol NH3 mol biohybrid complex−1 min−1. 20. The method of claim 15, wherein the isolated ammonia is about 12000 mol NH3 mol biohybrid complex−1 after about 300 minutes of exposure to light. | 1,600 |
1,391 | 12,695,235 | 1,635 | Microorganisms are identified as present in a complex sample or mixed culture by acquiring a mass spectrum of the sample and comparing it to combination spectra, each of which is formed by combining at least two reference mass spectra of known microorganisms. Microorganisms corresponding to the reference spectra used to form the combination spectrum are identified as present in the sample if that combination spectrum exhibits a better match with the sample mass spectrum than any one of reference mass spectra used to form that combination spectrum. It is also possible to identify microorganisms by forming a difference spectrum by subtracting a reference mass spectrum from the sample mass spectrum and comparing the difference spectrum to the reference mass spectra. | 1. A method for identifying microorganisms present in a sample, comprising:
(a) acquiring a mass spectrum of the sample; (b) comparing the sample mass spectrum to each of a plurality of reference mass spectra, wherein each reference mass spectrum is a mass spectrum of a known microorganism; (c) selecting as a best set of reference mass spectra, those reference mass spectra that are found to most closely match the sample spectrum in the comparisons in step (b); (d) combining reference mass spectra of microorganisms of different species in the best set of reference mass spectra to form combination spectra; and (e) comparing the sample mass spectrum to the combination spectra. 2. The method of claim 1, wherein selected microorganisms are identified as present in the sample when a match between the sample mass spectrum and a combination spectrum formed from reference mass spectra of the selected microorganisms is better than any match between the sample spectrum and any single reference mass spectrum of the reference mass spectra combined to form the combination spectrum. 3. The method of claim 1, wherein step (d) comprises:
(d1) combining reference mass spectra with a weighting factor for each reference mass spectrum to form a combination spectrum; (d2) determining a similarity indicator between the combination spectrum formed in step (d1) and the sample mass spectrum; and (d3) repeating steps (d1) and (d2) while modifying the weighting factors until the similarity indicator is maximized. 4. The method of claim 1, wherein selected microorganisms are identified as present in the sample when a match between the sample mass spectrum and a combination spectrum formed from reference mass spectra of the selected microorganisms is better than any match between the sample spectrum and any single reference mass spectrum in the best set of reference spectra. 5. The method of claim 1, wherein selected microorganisms are identified as present in the sample when a similarity indicator for a match between the sample mass spectrum and a combination spectrum formed from reference mass spectra of the selected microorganisms is greater than a predetermined minimum value. 6. The method of claim 1, wherein in step (c), reference mass spectra are selected manually to form the best set of reference mass spectra. 7. The method of claim 1, wherein step (c) comprises ranking each reference mass spectra by closeness of a match between that reference mass spectra and the sample mass spectra and selecting a predefined number of highest ranking reference mass spectra to form the best set of reference mass spectra. 8. The method of claim 7, wherein the predefined number is between 3 and 20. 9. The method of claim 1, wherein step (c) comprises ranking each reference mass spectra by closeness of a match between that reference mass spectra and the sample mass spectra and selecting 0.01 to 0.1 percent of highest ranking reference mass spectra to form the best set of reference mass spectra. 10. The method of claim 1, wherein step (c) comprises computing for each reference mass spectra a similarity factor that indicates the closeness of a match between that reference mass spectra and the sample mass spectra and selecting reference mass spectra with a similarity indicator greater than a predetermined minimum value as the best set of reference mass spectra. 11. A method for identifying microorganisms present in a sample, comprising:
(a) acquiring a mass spectrum of the sample; (b) obtaining a plurality of reference mass spectra, wherein each reference mass spectrum is a mass spectrum of a known microorganism; (c) combining reference mass spectra of microorganisms of different species to form combination spectra; and (d) comparing the sample mass spectrum to the combination spectra. 12. The method of claim 11, wherein step (c) comprises combining reference mass spectra of microorganisms that are commonly found in the same location to form combination spectra. 13. The method of claim 11, wherein step (c) comprises combining reference mass spectra that exhibit the closest matches to the sample mass spectrum. 14. The method of any one of claims 11 to 13, wherein selected microorganisms are identified as present in the sample when a match between the sample mass spectrum and a combination spectrum formed from reference mass spectra of the selected microorganisms is better than any match between the sample spectrum and any single reference mass spectrum. 15. A method for identifying microorganisms present in a sample, comprising:
(a) acquiring a mass spectrum of the sample; (b) obtaining a plurality of reference mass spectra, wherein each reference mass spectrum is a mass spectrum of a known microorganism; (c) subtracting at least one reference mass spectra from the sample mass spectrum to form a difference spectrum; and (d) comparing the difference mass spectrum to the reference mass spectra. 16. The method of claim 15, wherein in step (d), a microorganism is identified as present in the sample when a similarity indicator for the match between a reference mass spectrum of that microorganism and the difference mass spectrum is greater than a predetermined minimum value. | Microorganisms are identified as present in a complex sample or mixed culture by acquiring a mass spectrum of the sample and comparing it to combination spectra, each of which is formed by combining at least two reference mass spectra of known microorganisms. Microorganisms corresponding to the reference spectra used to form the combination spectrum are identified as present in the sample if that combination spectrum exhibits a better match with the sample mass spectrum than any one of reference mass spectra used to form that combination spectrum. It is also possible to identify microorganisms by forming a difference spectrum by subtracting a reference mass spectrum from the sample mass spectrum and comparing the difference spectrum to the reference mass spectra.1. A method for identifying microorganisms present in a sample, comprising:
(a) acquiring a mass spectrum of the sample; (b) comparing the sample mass spectrum to each of a plurality of reference mass spectra, wherein each reference mass spectrum is a mass spectrum of a known microorganism; (c) selecting as a best set of reference mass spectra, those reference mass spectra that are found to most closely match the sample spectrum in the comparisons in step (b); (d) combining reference mass spectra of microorganisms of different species in the best set of reference mass spectra to form combination spectra; and (e) comparing the sample mass spectrum to the combination spectra. 2. The method of claim 1, wherein selected microorganisms are identified as present in the sample when a match between the sample mass spectrum and a combination spectrum formed from reference mass spectra of the selected microorganisms is better than any match between the sample spectrum and any single reference mass spectrum of the reference mass spectra combined to form the combination spectrum. 3. The method of claim 1, wherein step (d) comprises:
(d1) combining reference mass spectra with a weighting factor for each reference mass spectrum to form a combination spectrum; (d2) determining a similarity indicator between the combination spectrum formed in step (d1) and the sample mass spectrum; and (d3) repeating steps (d1) and (d2) while modifying the weighting factors until the similarity indicator is maximized. 4. The method of claim 1, wherein selected microorganisms are identified as present in the sample when a match between the sample mass spectrum and a combination spectrum formed from reference mass spectra of the selected microorganisms is better than any match between the sample spectrum and any single reference mass spectrum in the best set of reference spectra. 5. The method of claim 1, wherein selected microorganisms are identified as present in the sample when a similarity indicator for a match between the sample mass spectrum and a combination spectrum formed from reference mass spectra of the selected microorganisms is greater than a predetermined minimum value. 6. The method of claim 1, wherein in step (c), reference mass spectra are selected manually to form the best set of reference mass spectra. 7. The method of claim 1, wherein step (c) comprises ranking each reference mass spectra by closeness of a match between that reference mass spectra and the sample mass spectra and selecting a predefined number of highest ranking reference mass spectra to form the best set of reference mass spectra. 8. The method of claim 7, wherein the predefined number is between 3 and 20. 9. The method of claim 1, wherein step (c) comprises ranking each reference mass spectra by closeness of a match between that reference mass spectra and the sample mass spectra and selecting 0.01 to 0.1 percent of highest ranking reference mass spectra to form the best set of reference mass spectra. 10. The method of claim 1, wherein step (c) comprises computing for each reference mass spectra a similarity factor that indicates the closeness of a match between that reference mass spectra and the sample mass spectra and selecting reference mass spectra with a similarity indicator greater than a predetermined minimum value as the best set of reference mass spectra. 11. A method for identifying microorganisms present in a sample, comprising:
(a) acquiring a mass spectrum of the sample; (b) obtaining a plurality of reference mass spectra, wherein each reference mass spectrum is a mass spectrum of a known microorganism; (c) combining reference mass spectra of microorganisms of different species to form combination spectra; and (d) comparing the sample mass spectrum to the combination spectra. 12. The method of claim 11, wherein step (c) comprises combining reference mass spectra of microorganisms that are commonly found in the same location to form combination spectra. 13. The method of claim 11, wherein step (c) comprises combining reference mass spectra that exhibit the closest matches to the sample mass spectrum. 14. The method of any one of claims 11 to 13, wherein selected microorganisms are identified as present in the sample when a match between the sample mass spectrum and a combination spectrum formed from reference mass spectra of the selected microorganisms is better than any match between the sample spectrum and any single reference mass spectrum. 15. A method for identifying microorganisms present in a sample, comprising:
(a) acquiring a mass spectrum of the sample; (b) obtaining a plurality of reference mass spectra, wherein each reference mass spectrum is a mass spectrum of a known microorganism; (c) subtracting at least one reference mass spectra from the sample mass spectrum to form a difference spectrum; and (d) comparing the difference mass spectrum to the reference mass spectra. 16. The method of claim 15, wherein in step (d), a microorganism is identified as present in the sample when a similarity indicator for the match between a reference mass spectrum of that microorganism and the difference mass spectrum is greater than a predetermined minimum value. | 1,600 |
1,392 | 15,754,073 | 1,627 | The invention relates to biocidal mixtures comprising penflufen-containing polymer particles, copper compounds and specific alkanolamines and to the use thereof for protecting wood and wood products, and also to wood preservatives comprising biocidal mixtures and optionally further active ingredients. | 1. A biocidal mixture comprising:
penflufen-containing polymer particles, at least one alkanolamine selected from the group consisting of monoalkylmonoamines, monoalkyldiamines, dialkylamines and trialkylamines, substituted by one, two or three hydroxyl groups, and at least one copper compound or copper complexes of the alkanolamine. 2. The biocidal mixture as claimed in claim 1, wherein the penflufen-containing polymer particles comprise at least one styrene polymer, styrene copolymer, acrylic polymer or acrylic copolymer. 3. The biocidal mixture as claimed in claim 1, wherein the penflufen-containing polymer particles comprise at least one polyalkyl acrylate, polyalkyl methacrylates, or copolymers of alkyl acrylates and alkyl methacrylates. 4. The biocidal mixture as claimed in claim 1, wherein the penflufen-containing polymer particles are produced by radical oil-in-water emulsion polymerization wherein at least one ethylenically unsaturated monomer is polymerized in the presence of penflufen or its salts and acid addition compounds and in the presence of a radical initiator. 5. The biocidal mixture as claimed in claim 4, wherein the ethylenically unsaturated monomers are styrene, divinylbenzene, C1-C20 alkyl acrylates, C1-C18 alkyl methacrylates, or mixtures of these monomers. 6. The biocidal mixture as claimed in claim 1, wherein the copper compounds comprise water-soluble inorganic copper compounds. 7. The biocidal mixture as claimed in claim 1, wherein the copper compounds comprise copper sulfate, copper acetate, copper carbonate, copper hydroxide, copper borate, copper fluoride, copper oxide, copper chloride, copper hydroxide carbonate, or mixtures of these compounds. 8. The biocidal mixture as claimed in claim 1, wherein the alkanolamines comprise C1-C8 monoalkylmonoamines, C1-C8 monoalkyldiamines, or secondary C1-C8 dialkylamines substituted by one or two hydroxyl groups. 9. The biocidal mixture as claimed in claim 1, wherein the alkanolamines comprise isopropanolamine, 1,1- and 1,2-diaminoethanol, aminoethylethanolamine, diethanolamine, triethanolamine, methylethanolamine, monoethanolamine, or mixtures of these compounds. 10. The biocidal mixture as claimed in claim 1, wherein the molar amount of copper compounds used, based on the molar amount of penflufen in the penflufen-containing polymer particles, is 90:1 to 10:1. 11. The biocidal mixture as claimed in claim 1, wherein the amount of penflufen, based on the total amount of the penflufen-containing polymer particles, is 0.5% by weight to 15% by weight. 12. A wood preservative comprising biocidal mixtures as claimed in claim 1 and at least one solvent or diluent, and also optionally thickeners, optionally defoamers, optionally in-container preservatives, and optionally further biocides. 13. A method of protecting wood, wood products or wood-plastic composites against infestation and/or destruction by microorganisms, the method comprising contacting the wood, wood products or wood-plastic composites with the mixture as claimed in claim 1. 14. The method as claimed in claim 13, wherein the contacting comprises brushing, dipping, drenching, vacuum impregnating, pressure treatment, and combinations thereof. 15. A wood, woodbase material or wood-plastic composite comprising the biocidal mixture as claimed in claim 1. 16. The biocidal mixture as claimed in claim 1, wherein:
the penflufen-containing polymer particles comprise at least one styrene polymer, styrene copolymer, acrylic polymer or acrylic copolymer; the copper compounds comprise water-soluble inorganic copper compounds; the alkanolamines comprise C1-C8 monoalkylmonoamines, C1-C8 monoalkyldiamines, or secondary C1-C8 dialkylamines substituted by one or two hydroxyl groups. 17. The biocidal mixture as claimed in claim 16, wherein:
the amount of penflufen, based on the total amount of the penflufen-containing polymer particles, is 0.1% by weight to 30% by weight; the molar ratio of alkanolamines to penflufen is 600:1 to 8:1; and the molar amount of copper compounds, based on the molar amount of penflufen in the penflufen-containing polymer particles, is 150:1 to 2:1. 18. The biocidal mixture as claimed in claim 17, wherein:
the amount of penflufen, based on the total amount of the penflufen-containing polymer particles, is 0.5% by weight to 15% by weight; the molar ratio of alkanolamines to penflufen is 360:1 to 40:1; and the molar amount of copper compounds, based on the molar amount of penflufen in the penflufen-containing polymer particles, is 90:1 to 10:1. 19. The biocidal mixture as claimed in claim 18, wherein:
the penflufen-containing polymer particles comprise at least one polyalkyl acrylate, polyalkyl methacrylates, or copolymers of alkyl acrylates and alkyl methacrylates; the copper compounds comprise copper sulfate, copper acetate, copper carbonate, copper hydroxide, copper borate, copper fluoride, copper oxide, copper chloride, copper hydroxide carbonate, or mixtures of these compounds; and the alkanolamines comprise isopropanolamine, 1,1- and 1,2-diaminoethanol, aminoethylethanolamine, diethanolamine, triethanolamine, methylethanolamine, monoethanolamine, or mixtures of these compounds. | The invention relates to biocidal mixtures comprising penflufen-containing polymer particles, copper compounds and specific alkanolamines and to the use thereof for protecting wood and wood products, and also to wood preservatives comprising biocidal mixtures and optionally further active ingredients.1. A biocidal mixture comprising:
penflufen-containing polymer particles, at least one alkanolamine selected from the group consisting of monoalkylmonoamines, monoalkyldiamines, dialkylamines and trialkylamines, substituted by one, two or three hydroxyl groups, and at least one copper compound or copper complexes of the alkanolamine. 2. The biocidal mixture as claimed in claim 1, wherein the penflufen-containing polymer particles comprise at least one styrene polymer, styrene copolymer, acrylic polymer or acrylic copolymer. 3. The biocidal mixture as claimed in claim 1, wherein the penflufen-containing polymer particles comprise at least one polyalkyl acrylate, polyalkyl methacrylates, or copolymers of alkyl acrylates and alkyl methacrylates. 4. The biocidal mixture as claimed in claim 1, wherein the penflufen-containing polymer particles are produced by radical oil-in-water emulsion polymerization wherein at least one ethylenically unsaturated monomer is polymerized in the presence of penflufen or its salts and acid addition compounds and in the presence of a radical initiator. 5. The biocidal mixture as claimed in claim 4, wherein the ethylenically unsaturated monomers are styrene, divinylbenzene, C1-C20 alkyl acrylates, C1-C18 alkyl methacrylates, or mixtures of these monomers. 6. The biocidal mixture as claimed in claim 1, wherein the copper compounds comprise water-soluble inorganic copper compounds. 7. The biocidal mixture as claimed in claim 1, wherein the copper compounds comprise copper sulfate, copper acetate, copper carbonate, copper hydroxide, copper borate, copper fluoride, copper oxide, copper chloride, copper hydroxide carbonate, or mixtures of these compounds. 8. The biocidal mixture as claimed in claim 1, wherein the alkanolamines comprise C1-C8 monoalkylmonoamines, C1-C8 monoalkyldiamines, or secondary C1-C8 dialkylamines substituted by one or two hydroxyl groups. 9. The biocidal mixture as claimed in claim 1, wherein the alkanolamines comprise isopropanolamine, 1,1- and 1,2-diaminoethanol, aminoethylethanolamine, diethanolamine, triethanolamine, methylethanolamine, monoethanolamine, or mixtures of these compounds. 10. The biocidal mixture as claimed in claim 1, wherein the molar amount of copper compounds used, based on the molar amount of penflufen in the penflufen-containing polymer particles, is 90:1 to 10:1. 11. The biocidal mixture as claimed in claim 1, wherein the amount of penflufen, based on the total amount of the penflufen-containing polymer particles, is 0.5% by weight to 15% by weight. 12. A wood preservative comprising biocidal mixtures as claimed in claim 1 and at least one solvent or diluent, and also optionally thickeners, optionally defoamers, optionally in-container preservatives, and optionally further biocides. 13. A method of protecting wood, wood products or wood-plastic composites against infestation and/or destruction by microorganisms, the method comprising contacting the wood, wood products or wood-plastic composites with the mixture as claimed in claim 1. 14. The method as claimed in claim 13, wherein the contacting comprises brushing, dipping, drenching, vacuum impregnating, pressure treatment, and combinations thereof. 15. A wood, woodbase material or wood-plastic composite comprising the biocidal mixture as claimed in claim 1. 16. The biocidal mixture as claimed in claim 1, wherein:
the penflufen-containing polymer particles comprise at least one styrene polymer, styrene copolymer, acrylic polymer or acrylic copolymer; the copper compounds comprise water-soluble inorganic copper compounds; the alkanolamines comprise C1-C8 monoalkylmonoamines, C1-C8 monoalkyldiamines, or secondary C1-C8 dialkylamines substituted by one or two hydroxyl groups. 17. The biocidal mixture as claimed in claim 16, wherein:
the amount of penflufen, based on the total amount of the penflufen-containing polymer particles, is 0.1% by weight to 30% by weight; the molar ratio of alkanolamines to penflufen is 600:1 to 8:1; and the molar amount of copper compounds, based on the molar amount of penflufen in the penflufen-containing polymer particles, is 150:1 to 2:1. 18. The biocidal mixture as claimed in claim 17, wherein:
the amount of penflufen, based on the total amount of the penflufen-containing polymer particles, is 0.5% by weight to 15% by weight; the molar ratio of alkanolamines to penflufen is 360:1 to 40:1; and the molar amount of copper compounds, based on the molar amount of penflufen in the penflufen-containing polymer particles, is 90:1 to 10:1. 19. The biocidal mixture as claimed in claim 18, wherein:
the penflufen-containing polymer particles comprise at least one polyalkyl acrylate, polyalkyl methacrylates, or copolymers of alkyl acrylates and alkyl methacrylates; the copper compounds comprise copper sulfate, copper acetate, copper carbonate, copper hydroxide, copper borate, copper fluoride, copper oxide, copper chloride, copper hydroxide carbonate, or mixtures of these compounds; and the alkanolamines comprise isopropanolamine, 1,1- and 1,2-diaminoethanol, aminoethylethanolamine, diethanolamine, triethanolamine, methylethanolamine, monoethanolamine, or mixtures of these compounds. | 1,600 |
1,393 | 15,339,990 | 1,627 | Antifibrinolytic agents/drugs are applied to the concussive area of a patient's brain to counter the activation of a fibrinolytic process in the concussive area. Various techniques are described for administering the antifibrinolytic agent. | 1. In a method of treating concussions, the improvement being the administration of an antifibrinolytic agent to the concussive area of the patient's brain to counter the activation of a fibrinolytic process in the concussive area. 2. The method of claim 1 wherein the antifibrinolytic agent is administered to the brain via systemic administration. 3. The method of claim 1 wherein the affected concussed area is determined, and then the antifibrinolytic agent is administered to the area. 4. The method of claim 3 wherein the antifibrinolytic agent is directly administered into the area by use of a device selected from the group consisting of catheters, irrigation, needle injection and elution. 5. The method of claim 3 wherein a pharmacologic preparation containing the antifibrinolytic agent is made available to the area to provide a controlled release of the antifibrinolytic agent. 6. The method of claim 3 wherein there is a physically activated release of the antifibrinolytic agent to the area. 7. The method of claim 3 wherein there is a time release of the antifibrinolytic agent to the area. 8. The method of claim 3 wherein the antifibrinolytic agent is delivered by a technique consisting of systemically and/or percutaneously to preplanned clinical targets. 9. The method of claim 1 wherein the antifibrinolytic agent is topically applied into the area. 10. The method of claim 1 wherein the antifibrinolytic is applied by being implanted to affect the area. 11. The method of claim 1 wherein the antifibrinolytic agent is placed into the area by a device selected from the group consisting of needle injection/aspiration cannula, drug ports and depots, and micro catheters. 12. The method of claim 1 wherein the antifibrinolytic agent is attached to molecules and strategies that are designed to attach themselves to concussed affected tissue. 13. The method of claim 1 wherein the antifibrinolytic agent is administered during open surgical procedures. 14. The method of claim 1 wherein the antifibrinolytic agent is applied by a plan optimized via surgical/target planning systems and accurately delivered via a technique consisting of image guided surgical navigation systems, real time imaging, stereotactic headframes, trajectory guides, and endovascular micro catheters. 15. The method of claim 1 wherein the antifibrinolytic agent is administered using techniques that identify affected tissue. 16. The method of claim 15 wherein the affected tissue is identified by visualizing the affected tissue. 17. The method of claim 1 wherein the antifibrinolytic agent is administered using techniques which place objects into the body via needles/cannulas before the needle/cannula functions. 18. The method of claim 1 wherein the antifibrinolytic agent is administered using techniques which place objects into the body via needles/cannulas after the needle/cannula functions. 19. The method of claim 1 wherein the antifibrinolytic agent is administered using techniques which place implants into the body via needles/cannulas. 20. The method of claim 1 wherein the antifibrinolytic agent is directly injected into the area. | Antifibrinolytic agents/drugs are applied to the concussive area of a patient's brain to counter the activation of a fibrinolytic process in the concussive area. Various techniques are described for administering the antifibrinolytic agent.1. In a method of treating concussions, the improvement being the administration of an antifibrinolytic agent to the concussive area of the patient's brain to counter the activation of a fibrinolytic process in the concussive area. 2. The method of claim 1 wherein the antifibrinolytic agent is administered to the brain via systemic administration. 3. The method of claim 1 wherein the affected concussed area is determined, and then the antifibrinolytic agent is administered to the area. 4. The method of claim 3 wherein the antifibrinolytic agent is directly administered into the area by use of a device selected from the group consisting of catheters, irrigation, needle injection and elution. 5. The method of claim 3 wherein a pharmacologic preparation containing the antifibrinolytic agent is made available to the area to provide a controlled release of the antifibrinolytic agent. 6. The method of claim 3 wherein there is a physically activated release of the antifibrinolytic agent to the area. 7. The method of claim 3 wherein there is a time release of the antifibrinolytic agent to the area. 8. The method of claim 3 wherein the antifibrinolytic agent is delivered by a technique consisting of systemically and/or percutaneously to preplanned clinical targets. 9. The method of claim 1 wherein the antifibrinolytic agent is topically applied into the area. 10. The method of claim 1 wherein the antifibrinolytic is applied by being implanted to affect the area. 11. The method of claim 1 wherein the antifibrinolytic agent is placed into the area by a device selected from the group consisting of needle injection/aspiration cannula, drug ports and depots, and micro catheters. 12. The method of claim 1 wherein the antifibrinolytic agent is attached to molecules and strategies that are designed to attach themselves to concussed affected tissue. 13. The method of claim 1 wherein the antifibrinolytic agent is administered during open surgical procedures. 14. The method of claim 1 wherein the antifibrinolytic agent is applied by a plan optimized via surgical/target planning systems and accurately delivered via a technique consisting of image guided surgical navigation systems, real time imaging, stereotactic headframes, trajectory guides, and endovascular micro catheters. 15. The method of claim 1 wherein the antifibrinolytic agent is administered using techniques that identify affected tissue. 16. The method of claim 15 wherein the affected tissue is identified by visualizing the affected tissue. 17. The method of claim 1 wherein the antifibrinolytic agent is administered using techniques which place objects into the body via needles/cannulas before the needle/cannula functions. 18. The method of claim 1 wherein the antifibrinolytic agent is administered using techniques which place objects into the body via needles/cannulas after the needle/cannula functions. 19. The method of claim 1 wherein the antifibrinolytic agent is administered using techniques which place implants into the body via needles/cannulas. 20. The method of claim 1 wherein the antifibrinolytic agent is directly injected into the area. | 1,600 |
1,394 | 14,388,057 | 1,634 | A method for generating an image of a region of interest in a biological sample comprising the steps of: generating a first image including the region of interest of the biological sample having undergone a first protocol but not a second protocol; and generating a second image including the region of interest of the biological sample after having undergone a second protocol; wherein the region of interest is smaller than said sample. Also provided is a method of analyzing a biological sample, comprising providing an image of the biological sample according to the method for generating an image of a region of interest in a biological sample, and analyzing the biological sample from the image. Further provided are system and kit that comprise the means for executing the novel methods. | 1. A method of generating an image of a region of interest in a biological sample comprising the steps of:
1) generating a first image including said region of interest of said biological sample having undergone a first protocol but not a second protocol; and 2) generating a second image including said region of interest of said biological sample after having undergone a second protocol;
wherein said region of interest is smaller than said sample and wherein the second protocol includes immonufluorescence detection of a target protein or fluorescence detection of at least one target nucleic acid sequence by hybridizing a probe with the target nucleic acid sequence. 2. The method of claim 1, wherein the region of interest is selected by comparing the first image of the biological sample to pre-determined criterion. 3. The method of claim 1, wherein the first protocol includes immonufluorescence detection of a target protein. 4. The method of claim 3, wherein the immonufluorescence detection includes physically binding an antibody with the target protein. 5. The method of claim 4, wherein said antibody is labeled with a fluorophore. 6. (canceled) 7. The method of claim 3, wherein the first protocol further includes immonufluorescence detection of at least one additional protein that provides morphological information. 8-11. (canceled) 12. The method of claim 1, wherein said hybridizing reaction is selected from the group consisting of FISH, IQ-FISH, in-situ PCR, rolling circle amplification and primed in situ labeling. 13-16. (canceled) 17. The method of claim 1, wherein the first or the second protocol comprises staining the sample with a fluorescent marker that provides morphological information. 18. (canceled) 19. The method of claim 17, wherein said fluorescent marker stains the nucleus of a cell. 20. The method of claim 1, wherein the first or the second protocol comprises detecting autofluorescense of the biological sample. 21. The method of claim 1, wherein the first and second images are fluorescent images. 22. The method of claim 21, wherein generating the first image and/or generating the second image comprises generating a brightfield type image that resembles a brightfield stain, wherein said brightfield type images resemble a simulated H&E image or a simulated DAB image. 23-24. (canceled) 25. The method of claim 1, further comprising generating a composite image that includes at least the regions of interest from each of the first and the second images. 26. The method of claim 25, wherein generating of the composite image comprises registering locations of selected signals obtained during the generation of the first image with locations of selected signals obtained during the generation of the second image. 27. The method of claim 25, wherein the locations of selected signals are from within the region of interest. 28. A method of analyzing a biological sample, comprising providing an image of the biological sample according to claim 1, and analyzing the biological sample from the image. 29-31. (canceled) 32. A method of generating an image of a biological sample, comprising the steps of:
1) generating a first image of said biological sample after a first protocol and before a second protocol is performed on said biological sample; and 2) Imaging a region of interest of said sample after the second protocol has been performed on the region of interest of said biological sample, said region of interest being smaller than said sample. 33. A method of imaging a biological sample, comprising the steps of
1) generating a first image of said biological sample after performing a first protocol but prior to performing a second protocol thereon; and 2) generating a second image of a region of interest of said sample after performing said second protocol on said region of interest, wherein said region of interest is smaller than said sample. 34. The method of claim 1, wherein said second image covers a smaller area of said biological sample compared to an area covered by said first image. | A method for generating an image of a region of interest in a biological sample comprising the steps of: generating a first image including the region of interest of the biological sample having undergone a first protocol but not a second protocol; and generating a second image including the region of interest of the biological sample after having undergone a second protocol; wherein the region of interest is smaller than said sample. Also provided is a method of analyzing a biological sample, comprising providing an image of the biological sample according to the method for generating an image of a region of interest in a biological sample, and analyzing the biological sample from the image. Further provided are system and kit that comprise the means for executing the novel methods.1. A method of generating an image of a region of interest in a biological sample comprising the steps of:
1) generating a first image including said region of interest of said biological sample having undergone a first protocol but not a second protocol; and 2) generating a second image including said region of interest of said biological sample after having undergone a second protocol;
wherein said region of interest is smaller than said sample and wherein the second protocol includes immonufluorescence detection of a target protein or fluorescence detection of at least one target nucleic acid sequence by hybridizing a probe with the target nucleic acid sequence. 2. The method of claim 1, wherein the region of interest is selected by comparing the first image of the biological sample to pre-determined criterion. 3. The method of claim 1, wherein the first protocol includes immonufluorescence detection of a target protein. 4. The method of claim 3, wherein the immonufluorescence detection includes physically binding an antibody with the target protein. 5. The method of claim 4, wherein said antibody is labeled with a fluorophore. 6. (canceled) 7. The method of claim 3, wherein the first protocol further includes immonufluorescence detection of at least one additional protein that provides morphological information. 8-11. (canceled) 12. The method of claim 1, wherein said hybridizing reaction is selected from the group consisting of FISH, IQ-FISH, in-situ PCR, rolling circle amplification and primed in situ labeling. 13-16. (canceled) 17. The method of claim 1, wherein the first or the second protocol comprises staining the sample with a fluorescent marker that provides morphological information. 18. (canceled) 19. The method of claim 17, wherein said fluorescent marker stains the nucleus of a cell. 20. The method of claim 1, wherein the first or the second protocol comprises detecting autofluorescense of the biological sample. 21. The method of claim 1, wherein the first and second images are fluorescent images. 22. The method of claim 21, wherein generating the first image and/or generating the second image comprises generating a brightfield type image that resembles a brightfield stain, wherein said brightfield type images resemble a simulated H&E image or a simulated DAB image. 23-24. (canceled) 25. The method of claim 1, further comprising generating a composite image that includes at least the regions of interest from each of the first and the second images. 26. The method of claim 25, wherein generating of the composite image comprises registering locations of selected signals obtained during the generation of the first image with locations of selected signals obtained during the generation of the second image. 27. The method of claim 25, wherein the locations of selected signals are from within the region of interest. 28. A method of analyzing a biological sample, comprising providing an image of the biological sample according to claim 1, and analyzing the biological sample from the image. 29-31. (canceled) 32. A method of generating an image of a biological sample, comprising the steps of:
1) generating a first image of said biological sample after a first protocol and before a second protocol is performed on said biological sample; and 2) Imaging a region of interest of said sample after the second protocol has been performed on the region of interest of said biological sample, said region of interest being smaller than said sample. 33. A method of imaging a biological sample, comprising the steps of
1) generating a first image of said biological sample after performing a first protocol but prior to performing a second protocol thereon; and 2) generating a second image of a region of interest of said sample after performing said second protocol on said region of interest, wherein said region of interest is smaller than said sample. 34. The method of claim 1, wherein said second image covers a smaller area of said biological sample compared to an area covered by said first image. | 1,600 |
1,395 | 13,387,971 | 1,627 | The present invention relates to biodegradable polyethylene glycol based water-insoluble hydrogels comprising backbone moieties which are interconnected by hydrolytically degradable bonds, the backbone moieties further comprising reactive functional groups, wherein the water-insoluble hydrogel is further characterized in that the ratio between the time period for the complete degradation of the hydrogel by hydrolysis of the degradable bonds into water-soluble degradation products comprising one or more backbone moieties and the time period for the release of the first 10 mol-% of water-soluble degradation products comprising one or more backbone moieties based on the total amount of backbone moieties in the hydrogel is greater than 1 and equal to or less than 2. The invention further relates to conjugates of such hydrogels with ligands or ligating groups, prodrugs and pharmaceutical compositions as well as their use in a medicament. | 1-73. (canceled) 74. Biodegradable poly(ethylene glycol) based water-insoluble hydrogel comprising backbone moieties which are interconnected by hydrolytically degradable bonds, the backbone moieties further comprising reactive functional groups, wherein the water-insoluble hydrogel is further characterized in that the ratio between the time period for the complete degradation of the hydrogel by hydrolysis of the degradable bonds into water-soluble degradation products comprising one or more backbone moieties and the time period for the release of the first 10 mol-% of water-soluble degradation products comprising one or more backbone moieties based on the total amount of backbone moieties in the hydrogel is greater than 1 and equal to or less than 2. 75. Hydrogel of claim 74, wherein the hydrolytically degradable bonds are selected from the group consisting of aconityls, acetals, carboxylic anhydrides, esters, imines, hydrazones, maleamic acid amides, ortho esters, phosphamides, phosphoesters, phosphosilyl esters, silyl esters, sulfonic esters, aromatic carbamates and combinations thereof. 76. Hydrogel of claim 74, wherein the reactive functional groups are selected from the group consisting of carboxylic acid and activated derivatives, amino, maleimide, thiol, sulfonic acid and derivatives, carbonate and derivatives, carbamate and derivatives, hydroxyl, aldehyde, ketone, hydrazine, isocyanate, isothiocyanate, phosphoric acid and derivatives, phosphonic acid and derivatives, haloacetyl, alkyl halides, acryloyl and other alpha-beta unsaturated michael acceptors, arylating agents like aryl fluorides, hydroxylamine, disulfides like pyridyl disulfide, vinyl sulfone, vinyl ketone, diazoalkanes, diazoacetyl compounds, oxirane, and aziridine. 77. Hydrogel of claim 74, wherein the backbone moiety has a molecular weight in the range of from 1 kDa to 20 kDa. 78. Hydrogel of claim 74, wherein the backbone moieties are linked together through crosslinker moieties, each crosslinker moiety being terminated by at least two of the hydrolytically degradable bonds. 79. Hydrogel of claim 78, wherein the crosslinker moieties have a molecular weight in the range of from 0.5 kDa to 5 kDa. 80. Hydrogel of claim 78, wherein each crosslinker moiety is PEG based. 81. Hydrogel of claim 74, wherein each backbone moiety comprises in sum at least 16 interconnected biodegradable and reactive functional groups. 82. Hydrogel of claim 81, wherein the backbone moiety has a quarternary carbon of formula
C(A-Hyp)4, wherein each A is independently a poly(ethylene glycol) based polymeric chain terminally attached to the quarternary carbon by a permanent covalent bond and the distal end of the polymeric chain is covalently bound to a dendritic moiety Hyp, each dendritic moiety Hyp having at least four functional groups representing the interconnected and reactive functional groups. 83. Conjugate comprising a hydrogel of claim 74, characterized by being composed of backbone moieties interconnected by hydrolytically degradable bonds and additionally carrying spacer molecules or blocking groups. 84. Conjugate comprising a hydrogel of claim 74, characterized by being composed of backbone moieties interconnected by hydrolytically degradable bonds and additionally carrying permanent linkages to ligands or chelating groups. 85. Carrier-linked prodrug comprising a hydrogel of claim 74 as carrier, wherein a number of permanent linkages of the backbone moieties exist with a transient prodrug linker L to which a biologically active moiety D is covalently attached. 86. The carrier-linked prodrug of claim 85, wherein a linkage between D and L is a carbamate, carbonate, amide or ester linkage. 87. The carrier-linked prodrug of claim 85, wherein the transient prodrug linker L comprises a moiety L1, which is substituted with a moiety L2 and wherein L2 is bound to a carrier group Z, which is the hydrogel of claim 74. 88. The carrier-linked prodrug of claim 86, wherein L2 is attached to Z via a terminal group having the following structure
wherein the dashed lines indicate the attachment to L2 and Z, respectively. 89. Pharmaceutical composition comprising a prodrug of claim 85 or a pharmaceutical salt thereof together with a pharmaceutically acceptable excipient. 90. Method of treating, controlling, delaying or preventing in a mammalian patient in need of the treatment of one or more conditions comprising administering to said patient a therapeutically effective amount of a prodrug of claim 85 or a pharmaceutical composition of claim 89 or a pharmaceutically acceptable salt thereof. 91. Biodegradable poly(ethylene glycol) based water-insoluble hydrogel comprising backbone moieties which are interconnected by hydrolytically degradable bonds, the backbone moieties are characterized by having a molecular weight in the range of from 1 kDa to 20 kDa and having the structure C*-(A-Hyp)x, wherein
C* is a branching core, A is a poly(ethylene glycol) based polymeric chain, Hyp is a hyperbranched dendritic moiety, x is an integer of from 3 to 16; and wherein the hyperbranched dendritic moiety further comprises reactive functional groups and interconnected functional groups. 92. Biodegradable hydrogel of claim 91, wherein the backbone moieties are linked together through crosslinker moieties, each crosslinker moiety being terminated by at least two of the hydrolytically degradable bonds. 93. Biodegradable hydrogel of claim 92, wherein the crosslinker moieties have a molecular weight in the range of from 0.5 kDa to 5 kDa and wherein each crosslinker moiety is PEG based. 94. Biodegradable hydrogel of claim 91, wherein each backbone moiety comprises in sum at least 16 interconnected biodegradable and reactive functional groups. 95. Biodegradable hydrogel of claim 94, wherein the backbone moiety has a quarternary carbon of formula
C(A-Hyp)4, wherein each A is independently a poly(ethylene glycol) based polymeric chain terminally attached to the quarternary carbon by a permanent covalent bond and the distal end of the polymeric chain is covalently bound to a dendritic moiety Hyp, each dendritic moiety Hyp having at least four functional groups representing the interconnected and reactive functional groups. 96. The biodegradable hydrogel of claim 95, wherein the backbone moieties comprise a branching core of the following formula:
wherein the dashed line indicates attachment to the remainder of the backbone moiety. 97. The biodegradable hydrogel of claim 96, wherein the backbone moieties comprise a structure of the following formula:
wherein n is an integer of from 5 to 50 and the dashed line indicates attachment to the rest of the molecule. 98. The biodegradable hydrogel of claim 96, wherein the backbone moiety comprises a hyperbranched moiety Hyp of the following formula:
wherein the dashed lines indicate attachment to the rest of the molecule and carbon atoms marked with asterisks indicate S-configuration. 99. The biodegradable hydrogel of claim 96, wherein the backbone moieties comprise at least one spacer of the following formula:
wherein one of the dashed lines indicates attachment to the hyperbranched moiety Hyp and the second dashed line indicates attachment to the rest of the molecule; and
wherein m is an integer of from 2 to 4. 100. The biodegradable hydrogel of claim 96, wherein the backbone moieties comprise at least one spacer of the following formula:
wherein the dashed line marked with the asterisk indicates the bond between the hydrogel and the N of the thiosuccinimide group of claim 90,
wherein the other dashed line indicates attachment to Hyp, and
wherein p is an integer of from 0 to 10. 101. The biodegradable hydrogel of claim 96, wherein the backbone moieties are linked together through crosslinker moieties comprising the following structure
wherein
q is an integer from 3 to 100; 102. Conjugate comprising a hydrogel of claim 91, wherein the hydrogel is composed of backbone moieties interconnected by hydrolytically degradable bonds and additionally carrying permanent linkages to spacer molecules or blocking groups or combinations thereof. 103. Conjugate comprising a hydrogel of claim 91, wherein the hydrogel is composed of backbone moieties interconnected by hydrolytically degradable bonds and additionally carrying permanent linkages to ligands or chelating groups. 104. Carrier-linked prodrug comprising a biodegradable hydrogel of claim 91 as carrier, wherein a number of permanent linkages of the backbone moieties exist each with a transient prodrug linker L to which a biologically active moiety D is covalently attached. 105. The carrier-linked prodrug of claim 104, wherein the transient linkage between D and L is a carbamate, carbonate, amide or ester linkage. 106. The carrier-linked prodrug of claim 104, wherein the transient prodrug linker L comprises a moiety L1, which is substituted with a moiety L2 and wherein L2 is bound to a carrier group Z, which is the hydrogel of claim 74. 107. The carrier-linked prodrug of claim 106, wherein L2 is attached to Z via a terminal group having the following structure
wherein the dashed lines indicate the attachment to L2 and Z, respectively. 108. A process for the preparation of a hydrogel comprising the step of
(a) reacting a backbone reagent having the formula
wherein n is an integer from 3 to 100;
with a crosslinker reagent of the following formula
wherein
q is an integer from 3 to 100;
each m independently is an integer of from 2 to 4;
in a ratio amine/active ester of 2:1 to 1.05:1, preferably resulting in a hydrogel loading of 0.02 to 2 mmol amine per g hydrogel; and wherein the reagents are dissolved in an aprotic solvent in the presence of a suitable base. 109. Hydrogel obtainable from a process of claim 108. 110. Hydrogel of claim 74 in the shape of a coating, mesh, stent or microparticle obtainable by comminution by mechanical processes such as stirring, crushing, cutting pressing, or milling, and optionally sieving. | The present invention relates to biodegradable polyethylene glycol based water-insoluble hydrogels comprising backbone moieties which are interconnected by hydrolytically degradable bonds, the backbone moieties further comprising reactive functional groups, wherein the water-insoluble hydrogel is further characterized in that the ratio between the time period for the complete degradation of the hydrogel by hydrolysis of the degradable bonds into water-soluble degradation products comprising one or more backbone moieties and the time period for the release of the first 10 mol-% of water-soluble degradation products comprising one or more backbone moieties based on the total amount of backbone moieties in the hydrogel is greater than 1 and equal to or less than 2. The invention further relates to conjugates of such hydrogels with ligands or ligating groups, prodrugs and pharmaceutical compositions as well as their use in a medicament.1-73. (canceled) 74. Biodegradable poly(ethylene glycol) based water-insoluble hydrogel comprising backbone moieties which are interconnected by hydrolytically degradable bonds, the backbone moieties further comprising reactive functional groups, wherein the water-insoluble hydrogel is further characterized in that the ratio between the time period for the complete degradation of the hydrogel by hydrolysis of the degradable bonds into water-soluble degradation products comprising one or more backbone moieties and the time period for the release of the first 10 mol-% of water-soluble degradation products comprising one or more backbone moieties based on the total amount of backbone moieties in the hydrogel is greater than 1 and equal to or less than 2. 75. Hydrogel of claim 74, wherein the hydrolytically degradable bonds are selected from the group consisting of aconityls, acetals, carboxylic anhydrides, esters, imines, hydrazones, maleamic acid amides, ortho esters, phosphamides, phosphoesters, phosphosilyl esters, silyl esters, sulfonic esters, aromatic carbamates and combinations thereof. 76. Hydrogel of claim 74, wherein the reactive functional groups are selected from the group consisting of carboxylic acid and activated derivatives, amino, maleimide, thiol, sulfonic acid and derivatives, carbonate and derivatives, carbamate and derivatives, hydroxyl, aldehyde, ketone, hydrazine, isocyanate, isothiocyanate, phosphoric acid and derivatives, phosphonic acid and derivatives, haloacetyl, alkyl halides, acryloyl and other alpha-beta unsaturated michael acceptors, arylating agents like aryl fluorides, hydroxylamine, disulfides like pyridyl disulfide, vinyl sulfone, vinyl ketone, diazoalkanes, diazoacetyl compounds, oxirane, and aziridine. 77. Hydrogel of claim 74, wherein the backbone moiety has a molecular weight in the range of from 1 kDa to 20 kDa. 78. Hydrogel of claim 74, wherein the backbone moieties are linked together through crosslinker moieties, each crosslinker moiety being terminated by at least two of the hydrolytically degradable bonds. 79. Hydrogel of claim 78, wherein the crosslinker moieties have a molecular weight in the range of from 0.5 kDa to 5 kDa. 80. Hydrogel of claim 78, wherein each crosslinker moiety is PEG based. 81. Hydrogel of claim 74, wherein each backbone moiety comprises in sum at least 16 interconnected biodegradable and reactive functional groups. 82. Hydrogel of claim 81, wherein the backbone moiety has a quarternary carbon of formula
C(A-Hyp)4, wherein each A is independently a poly(ethylene glycol) based polymeric chain terminally attached to the quarternary carbon by a permanent covalent bond and the distal end of the polymeric chain is covalently bound to a dendritic moiety Hyp, each dendritic moiety Hyp having at least four functional groups representing the interconnected and reactive functional groups. 83. Conjugate comprising a hydrogel of claim 74, characterized by being composed of backbone moieties interconnected by hydrolytically degradable bonds and additionally carrying spacer molecules or blocking groups. 84. Conjugate comprising a hydrogel of claim 74, characterized by being composed of backbone moieties interconnected by hydrolytically degradable bonds and additionally carrying permanent linkages to ligands or chelating groups. 85. Carrier-linked prodrug comprising a hydrogel of claim 74 as carrier, wherein a number of permanent linkages of the backbone moieties exist with a transient prodrug linker L to which a biologically active moiety D is covalently attached. 86. The carrier-linked prodrug of claim 85, wherein a linkage between D and L is a carbamate, carbonate, amide or ester linkage. 87. The carrier-linked prodrug of claim 85, wherein the transient prodrug linker L comprises a moiety L1, which is substituted with a moiety L2 and wherein L2 is bound to a carrier group Z, which is the hydrogel of claim 74. 88. The carrier-linked prodrug of claim 86, wherein L2 is attached to Z via a terminal group having the following structure
wherein the dashed lines indicate the attachment to L2 and Z, respectively. 89. Pharmaceutical composition comprising a prodrug of claim 85 or a pharmaceutical salt thereof together with a pharmaceutically acceptable excipient. 90. Method of treating, controlling, delaying or preventing in a mammalian patient in need of the treatment of one or more conditions comprising administering to said patient a therapeutically effective amount of a prodrug of claim 85 or a pharmaceutical composition of claim 89 or a pharmaceutically acceptable salt thereof. 91. Biodegradable poly(ethylene glycol) based water-insoluble hydrogel comprising backbone moieties which are interconnected by hydrolytically degradable bonds, the backbone moieties are characterized by having a molecular weight in the range of from 1 kDa to 20 kDa and having the structure C*-(A-Hyp)x, wherein
C* is a branching core, A is a poly(ethylene glycol) based polymeric chain, Hyp is a hyperbranched dendritic moiety, x is an integer of from 3 to 16; and wherein the hyperbranched dendritic moiety further comprises reactive functional groups and interconnected functional groups. 92. Biodegradable hydrogel of claim 91, wherein the backbone moieties are linked together through crosslinker moieties, each crosslinker moiety being terminated by at least two of the hydrolytically degradable bonds. 93. Biodegradable hydrogel of claim 92, wherein the crosslinker moieties have a molecular weight in the range of from 0.5 kDa to 5 kDa and wherein each crosslinker moiety is PEG based. 94. Biodegradable hydrogel of claim 91, wherein each backbone moiety comprises in sum at least 16 interconnected biodegradable and reactive functional groups. 95. Biodegradable hydrogel of claim 94, wherein the backbone moiety has a quarternary carbon of formula
C(A-Hyp)4, wherein each A is independently a poly(ethylene glycol) based polymeric chain terminally attached to the quarternary carbon by a permanent covalent bond and the distal end of the polymeric chain is covalently bound to a dendritic moiety Hyp, each dendritic moiety Hyp having at least four functional groups representing the interconnected and reactive functional groups. 96. The biodegradable hydrogel of claim 95, wherein the backbone moieties comprise a branching core of the following formula:
wherein the dashed line indicates attachment to the remainder of the backbone moiety. 97. The biodegradable hydrogel of claim 96, wherein the backbone moieties comprise a structure of the following formula:
wherein n is an integer of from 5 to 50 and the dashed line indicates attachment to the rest of the molecule. 98. The biodegradable hydrogel of claim 96, wherein the backbone moiety comprises a hyperbranched moiety Hyp of the following formula:
wherein the dashed lines indicate attachment to the rest of the molecule and carbon atoms marked with asterisks indicate S-configuration. 99. The biodegradable hydrogel of claim 96, wherein the backbone moieties comprise at least one spacer of the following formula:
wherein one of the dashed lines indicates attachment to the hyperbranched moiety Hyp and the second dashed line indicates attachment to the rest of the molecule; and
wherein m is an integer of from 2 to 4. 100. The biodegradable hydrogel of claim 96, wherein the backbone moieties comprise at least one spacer of the following formula:
wherein the dashed line marked with the asterisk indicates the bond between the hydrogel and the N of the thiosuccinimide group of claim 90,
wherein the other dashed line indicates attachment to Hyp, and
wherein p is an integer of from 0 to 10. 101. The biodegradable hydrogel of claim 96, wherein the backbone moieties are linked together through crosslinker moieties comprising the following structure
wherein
q is an integer from 3 to 100; 102. Conjugate comprising a hydrogel of claim 91, wherein the hydrogel is composed of backbone moieties interconnected by hydrolytically degradable bonds and additionally carrying permanent linkages to spacer molecules or blocking groups or combinations thereof. 103. Conjugate comprising a hydrogel of claim 91, wherein the hydrogel is composed of backbone moieties interconnected by hydrolytically degradable bonds and additionally carrying permanent linkages to ligands or chelating groups. 104. Carrier-linked prodrug comprising a biodegradable hydrogel of claim 91 as carrier, wherein a number of permanent linkages of the backbone moieties exist each with a transient prodrug linker L to which a biologically active moiety D is covalently attached. 105. The carrier-linked prodrug of claim 104, wherein the transient linkage between D and L is a carbamate, carbonate, amide or ester linkage. 106. The carrier-linked prodrug of claim 104, wherein the transient prodrug linker L comprises a moiety L1, which is substituted with a moiety L2 and wherein L2 is bound to a carrier group Z, which is the hydrogel of claim 74. 107. The carrier-linked prodrug of claim 106, wherein L2 is attached to Z via a terminal group having the following structure
wherein the dashed lines indicate the attachment to L2 and Z, respectively. 108. A process for the preparation of a hydrogel comprising the step of
(a) reacting a backbone reagent having the formula
wherein n is an integer from 3 to 100;
with a crosslinker reagent of the following formula
wherein
q is an integer from 3 to 100;
each m independently is an integer of from 2 to 4;
in a ratio amine/active ester of 2:1 to 1.05:1, preferably resulting in a hydrogel loading of 0.02 to 2 mmol amine per g hydrogel; and wherein the reagents are dissolved in an aprotic solvent in the presence of a suitable base. 109. Hydrogel obtainable from a process of claim 108. 110. Hydrogel of claim 74 in the shape of a coating, mesh, stent or microparticle obtainable by comminution by mechanical processes such as stirring, crushing, cutting pressing, or milling, and optionally sieving. | 1,600 |
1,396 | 16,535,693 | 1,612 | A whitening composition, an oral care product including the whitening composition, and a method for whitening teeth are disclosed. The whitening composition may include an anhydrous component and an aqueous component. The anhydrous component may include a base gel and a chloroisocyanurate. The chloroisocyanurate may be present in the anhydrous component in an amount of from about 0.01 weight % to about 30 weight %, based on a totally weight of the anhydrous component. The anhydrous component may include water. | 1. A whitening composition, comprising:
an anhydrous component comprising a base gel and a chloroisocyanurate, wherein the chloroisocyanurate is present in the anhydrous component in an amount of from about 0.01 weight % to about 30 weight %, based on a total weight of the anhydrous component; and an aqueous component comprising water. 2. The whitening composition of claim 1, wherein the chloroisocyanurate comprises one or more of a dichloroisocyanurate, a trichloroisocyanurate, or combinations thereof. 3. The whitening composition of claim 1, wherein the chloroisocyanurate comprises an alkali metal salt of dichloroisocyanurate. 4. The whitening composition of claim 3, wherein the alkali metal salt of dichloroisocyanurate is sodium dichloroisocyanurate dihydrate. 5. The whitening composition of claim 1, wherein the base gel comprises a polysiloxane fluid. 6. The whitening composition of claim 1, wherein the base gel comprises a pressure sensitive adhesive, wherein the pressure sensitive adhesive is a polyorganosiloxane. 7. The whitening composition of claim 1, wherein the base gel comprises a thickener, wherein the thickener comprises one or more selected from the group consisting of colloidal silica, fumed silica, a cross-linked polyvinylpyrrolidone (PVP) polymer, and combinations thereof. 8. The whitening composition of claim 1, wherein the base gel comprises an adhesion enhancing agent, wherein the adhesion enhancing agent is white petrolatum. 9. The whitening composition of claim 1, wherein the aqueous component comprises a hydrophilic polymer, wherein the hydrophilic polymer comprises a carboxypolymethylene. 10. The whitening composition of claim 1, wherein the aqueous component comprises one or more selected from the group consisting of a basifying agent, a buffering agent, and combinations thereof. 11. The whitening composition of claim 1, wherein the whitening composition is substantially free of peroxides and peroxide compounds. 12. The whitening composition of claim 1, wherein a weight ratio of the anhydrous component to the aqueous component is from about 0.1:1 to about 1.5:1. 13. An oral care product, comprising:
the whitening composition of claim 1; and a dental tray defining a reservoir configured to contain said whitening composition. 14. The oral care product of claim 13, further comprising:
a first syringe defining a first chamber, wherein the anhydrous component of the whitening composition is disposed in the first chamber; and a second syringe defining a second chamber, wherein the aqueous component of the whitening composition is disposed in the second chamber. 15. The oral care product of claim 13, further comprising a dual-chamber syringe defining a first chamber and a second chamber, wherein the anhydrous component of the whitening composition is disposed in the first chamber, and wherein the aqueous component of the whitening composition is disposed in the second chamber. 16. A method for whitening teeth, comprising:
contacting the anhydrous component and the aqueous component of the whitening composition of claim 1 with one another to form a mixture; and contacting the mixture with surfaces of the teeth. 17. The method of claim 16, further comprising generating a whitening agent after contacting the anhydrous component and the aqueous component with one another, wherein the whitening agent is a hypochlorite. 18. The method of claim 16, wherein contacting the mixture with the surfaces of the teeth comprises disposing the mixture in a dental tray. 19. The method of claim 18, wherein contacting the mixture with the surfaces of the teeth further comprises disposing the dental tray about the teeth to contact the whitening agent with the surfaces of the teeth. 20. The method of claim 16, further comprising contacting the mixture with the surfaces of the teeth for at least 30 seconds. | A whitening composition, an oral care product including the whitening composition, and a method for whitening teeth are disclosed. The whitening composition may include an anhydrous component and an aqueous component. The anhydrous component may include a base gel and a chloroisocyanurate. The chloroisocyanurate may be present in the anhydrous component in an amount of from about 0.01 weight % to about 30 weight %, based on a totally weight of the anhydrous component. The anhydrous component may include water.1. A whitening composition, comprising:
an anhydrous component comprising a base gel and a chloroisocyanurate, wherein the chloroisocyanurate is present in the anhydrous component in an amount of from about 0.01 weight % to about 30 weight %, based on a total weight of the anhydrous component; and an aqueous component comprising water. 2. The whitening composition of claim 1, wherein the chloroisocyanurate comprises one or more of a dichloroisocyanurate, a trichloroisocyanurate, or combinations thereof. 3. The whitening composition of claim 1, wherein the chloroisocyanurate comprises an alkali metal salt of dichloroisocyanurate. 4. The whitening composition of claim 3, wherein the alkali metal salt of dichloroisocyanurate is sodium dichloroisocyanurate dihydrate. 5. The whitening composition of claim 1, wherein the base gel comprises a polysiloxane fluid. 6. The whitening composition of claim 1, wherein the base gel comprises a pressure sensitive adhesive, wherein the pressure sensitive adhesive is a polyorganosiloxane. 7. The whitening composition of claim 1, wherein the base gel comprises a thickener, wherein the thickener comprises one or more selected from the group consisting of colloidal silica, fumed silica, a cross-linked polyvinylpyrrolidone (PVP) polymer, and combinations thereof. 8. The whitening composition of claim 1, wherein the base gel comprises an adhesion enhancing agent, wherein the adhesion enhancing agent is white petrolatum. 9. The whitening composition of claim 1, wherein the aqueous component comprises a hydrophilic polymer, wherein the hydrophilic polymer comprises a carboxypolymethylene. 10. The whitening composition of claim 1, wherein the aqueous component comprises one or more selected from the group consisting of a basifying agent, a buffering agent, and combinations thereof. 11. The whitening composition of claim 1, wherein the whitening composition is substantially free of peroxides and peroxide compounds. 12. The whitening composition of claim 1, wherein a weight ratio of the anhydrous component to the aqueous component is from about 0.1:1 to about 1.5:1. 13. An oral care product, comprising:
the whitening composition of claim 1; and a dental tray defining a reservoir configured to contain said whitening composition. 14. The oral care product of claim 13, further comprising:
a first syringe defining a first chamber, wherein the anhydrous component of the whitening composition is disposed in the first chamber; and a second syringe defining a second chamber, wherein the aqueous component of the whitening composition is disposed in the second chamber. 15. The oral care product of claim 13, further comprising a dual-chamber syringe defining a first chamber and a second chamber, wherein the anhydrous component of the whitening composition is disposed in the first chamber, and wherein the aqueous component of the whitening composition is disposed in the second chamber. 16. A method for whitening teeth, comprising:
contacting the anhydrous component and the aqueous component of the whitening composition of claim 1 with one another to form a mixture; and contacting the mixture with surfaces of the teeth. 17. The method of claim 16, further comprising generating a whitening agent after contacting the anhydrous component and the aqueous component with one another, wherein the whitening agent is a hypochlorite. 18. The method of claim 16, wherein contacting the mixture with the surfaces of the teeth comprises disposing the mixture in a dental tray. 19. The method of claim 18, wherein contacting the mixture with the surfaces of the teeth further comprises disposing the dental tray about the teeth to contact the whitening agent with the surfaces of the teeth. 20. The method of claim 16, further comprising contacting the mixture with the surfaces of the teeth for at least 30 seconds. | 1,600 |
1,397 | 14,886,946 | 1,653 | Disclosed herein, in certain instances, are tissue grafts derived from UCAM. Further disclosed herein, in certain instances, are use for tissue grafts derived from UCAM. | 1. A method of treating a wound in an individual in need thereof, comprising: contacting a wound of the individual with an umbilical cord powder, or with an umbilical cord product from which water has not been removed. 2. The method of claim 1, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed is derived from frozen or previously-frozen umbilical cord. 3. The method of claim 1, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed comprises amniotic membrane and Wharton's jelly. 4. The method of claim 1, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed consists essentially of umbilical cord-derived amniotic membrane. 5. The method of claim 1, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed is substantially free of a vein or artery. 6. The method of claim 1, wherein the wound is an ulcer. 7. The method of claim 6, wherein the ulcer is a foot ulcer, a diabetic foot ulcer, an arterial insufficiency ulcer, a venous stasis (VS) ulcer, or an ocular ulcer. 8. The method of claim 1, wherein the wound is a burn, a laceration, an incision, an abrasion, a puncture, a penetration, necrosis, or damage to an eye. 9. The method of claim 2, wherein the umbilical cord product from which water has not been removed is a substantially-flattened sheet or tubular sheet, or is pulverized. 10. The method of claim 1, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed is cryopreserved, terminally sterilized, or a combination thereof. 11. A method for reducing inflammation, scarring, or adhesion in a tissue in need thereof, comprising: contacting the tissue with an umbilical cord powder, or with an umbilical cord product from which water has not been removed. 12. The method of claim 11, wherein the contacting occurs in vivo. 13. The method of claim 11, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed is derived from frozen or previously-frozen umbilical cord. 14. The method of claim 11, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed comprises amniotic membrane and Wharton's jelly. 15. The method of claim 11, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed consists essentially of amniotic membrane. 16. The method of claim 11, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed is substantially free of vein or artery. 17. The method of claim 11, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed is cryopreserved, terminally sterilized, or a combination thereof. 18. The method of claim 11, wherein the tissue comprises an ulcer, a burn, a laceration, an incision, an abrasion, a puncture, a penetration, necrosis, or damage an eye. 19. The method of claim 18, wherein the ulcer is a foot ulcer, a diabetic foot ulcer, an arterial insufficiency ulcer, a venous stasis (VS) ulcer, or an ocular ulcer. 20. The method of claim 11, wherein the umbilical cord product from which water has not been removed is a substantially-flattened sheet or tubular sheet, or is pulverized. | Disclosed herein, in certain instances, are tissue grafts derived from UCAM. Further disclosed herein, in certain instances, are use for tissue grafts derived from UCAM.1. A method of treating a wound in an individual in need thereof, comprising: contacting a wound of the individual with an umbilical cord powder, or with an umbilical cord product from which water has not been removed. 2. The method of claim 1, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed is derived from frozen or previously-frozen umbilical cord. 3. The method of claim 1, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed comprises amniotic membrane and Wharton's jelly. 4. The method of claim 1, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed consists essentially of umbilical cord-derived amniotic membrane. 5. The method of claim 1, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed is substantially free of a vein or artery. 6. The method of claim 1, wherein the wound is an ulcer. 7. The method of claim 6, wherein the ulcer is a foot ulcer, a diabetic foot ulcer, an arterial insufficiency ulcer, a venous stasis (VS) ulcer, or an ocular ulcer. 8. The method of claim 1, wherein the wound is a burn, a laceration, an incision, an abrasion, a puncture, a penetration, necrosis, or damage to an eye. 9. The method of claim 2, wherein the umbilical cord product from which water has not been removed is a substantially-flattened sheet or tubular sheet, or is pulverized. 10. The method of claim 1, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed is cryopreserved, terminally sterilized, or a combination thereof. 11. A method for reducing inflammation, scarring, or adhesion in a tissue in need thereof, comprising: contacting the tissue with an umbilical cord powder, or with an umbilical cord product from which water has not been removed. 12. The method of claim 11, wherein the contacting occurs in vivo. 13. The method of claim 11, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed is derived from frozen or previously-frozen umbilical cord. 14. The method of claim 11, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed comprises amniotic membrane and Wharton's jelly. 15. The method of claim 11, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed consists essentially of amniotic membrane. 16. The method of claim 11, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed is substantially free of vein or artery. 17. The method of claim 11, wherein the umbilical cord powder or the umbilical cord product from which water has not been removed is cryopreserved, terminally sterilized, or a combination thereof. 18. The method of claim 11, wherein the tissue comprises an ulcer, a burn, a laceration, an incision, an abrasion, a puncture, a penetration, necrosis, or damage an eye. 19. The method of claim 18, wherein the ulcer is a foot ulcer, a diabetic foot ulcer, an arterial insufficiency ulcer, a venous stasis (VS) ulcer, or an ocular ulcer. 20. The method of claim 11, wherein the umbilical cord product from which water has not been removed is a substantially-flattened sheet or tubular sheet, or is pulverized. | 1,600 |
1,398 | 15,586,652 | 1,618 | A composition includes a therapeutically effective pharmaceutical dosage form including a plurality of individual particulates. The individual particulates respectively have: a core including an active ingredient combination of an L-carnitine and a nootropic substance and a release controlling polymer over the core that substantially prevents release of the active ingredients in stomach acid and permits release of the active ingredients in an intestinal pH environment. The composition may be used to treat conditions associated with a reduction of the amount of L-carnitine in the body and/or cognitive impairment. | 1. A composition comprising a therapeutically effective pharmaceutical dosage form including a plurality of individual particulates, the individual particulates respectively having:
a core including an active ingredient combination of an L-carnitine and a nootropic substance; and a release controlling polymer over the core that substantially prevents release of the active ingredient combination in stomach acid and permits release of the active ingredient combination an intestinal pH environment. 2. The composition of claim 1, wherein the L-carnitine is within an interior solid portion of the core and the nootropic substance is within a coating over the interior solid portion of the core. 3. The composition of claim 1, wherein the core includes a solid interior portion and the L-carnitine and nootropic substance are in the solid interior portion of the core. 4. The composition of claim 1, wherein the L-carnitine is selected from at least one of L-carnitine, acetyl L-carnitine, and propionyl L-carnitine. 5. The composition of claim 1, wherein the nootropic substance is selected from at least one of L-serine and citicoline. 6. The composition of claim 1, wherein an average diameter of the individual particulates is 0.1 to 3 mm. 7. The composition of claim 1, wherein the therapeutically effective pharmaceutical dosage form includes 300 mg to 800 mg of the L-carnitine and 25 mg to 300 mg of the nootropic substance. 8. The composition of claim 1, wherein the therapeutically effective pharmaceutical dosage form includes 400 mg to 600 mg of the L-carnitine and 200 mg to 250 mg of the nootropic substance. 9. The composition of claim 1, wherein the L-carnitine is in an amount that is at least two times greater than the nootropic substance. 10. The composition of claim 1, wherein the individual particulates respectively include by % w/w of the particulate: 35% to 65% w/w of the L-carnitine and 15% to 30% w/w of the nootropic substance. 11. The composition of claim 1, wherein the individual particulates respectively include by % w/w of the particulate: 45% to 55% w/w of the L-carnitine and 20% to 30% w/w of the nootropic substance. 12. The composition of claim 1, wherein:
the individual particulates respectively include by %w/w of the particulate: 35% to 65% w/w of the L-carnitine and 15% to 30% w/w of the nootropic substance; the therapeutically effective pharmaceutical dosage form includes 300 mg to 800 mg of the L-carnitine and 25 mg to 300 mg of the nootropic substance; an average diameter of the individual particulates is 0.1 to 3 mm; and the nootropic substance is selected from at least one of L-serine and citicoline. 13. A composition comprising a therapeutically effective pharmaceutical dosage form including a plurality of individual particulates, the individual particulates respectively having by % w/w of the particulate:
a solid core including 35% to 65% w/w of an L-carnitine; 1% to 20% w/w of a subcoating over the solid core; 15% to 30% w/w of a nootropic substance that is within the solid core or within the subcoating; and an enteric coating over the subcoating. 14. The composition of claim 13, wherein the core includes a solid interior portion and the L-carnitine and nootropic substance are in the solid interior portion of the core. 15. The composition of claim 13, wherein the L-carnitine is selected from at least one of L-carnitine, acetyl L-carnitine, and propionyl L-carnitine. 16. The composition of claim 13, wherein an average diameter of the individual particulates is 0.1 mm to 3 mm. 17. The composition of claim 13, wherein the nootropic substance is selected from at least one of L-serine and citicoline. 18. The composition of claim 13, wherein the individual particulates respectively include by % w/w of the particulate: 45% to 55% w/w of the L-carnitine and 20% to 30% w/w of the nootropic substance. 19. The composition of claim 13, wherein the L-carnitine is in an amount that is at least two times greater than the nootropic substance. 20. The composition of claim 13, wherein therapeutically effective pharmaceutical dosage form includes 300 mg to 800 mg of the L-carnitine and 25 mg to 300 mg of the nootropic substance. 21. The composition of claim 13, wherein:
an average diameter of the individual particulates is 0.1 mm to 3 mm; the nootropic substance is selected from at least one of L-serine and citicoline; the individual particulates respectively include by % w/w of the particulate: 45% to 55% w/w of the L-carnitine and 20% to 30% w/w of the nootropic substance; and therapeutically effective pharmaceutical dosage form includes 300 mg to 800 mg of the L-carnitine and 25 mg to 300 mg of the nootropic substance. 22. A method of treating a physiological condition associated with cognitive impairment, the method comprising:
administering to a patient in need thereof a therapeutically effective pharmaceutical dosage form including a plurality of individual particulates, the individual particulates respectively having:
a core including an active ingredient combination of an L-carnitine and a nootropic substance; and
a release controlling polymer over the core that substantially prevents release of the active ingredient combination in stomach acid and permits release of the active ingredient combination in an intestinal pH environment. 23. The method of claim 22, wherein administering the therapeutically effective pharmaceutical dosage form to the patient comprises administering at least one capsule containing the plurality of individual particulates therein. 24. The method of claim 22, wherein the L-carnitine is within an interior solid portion of the core and the nootropic substance is within a coating over the interior solid portion of the core. 25. The method of claim 22, wherein the core includes a solid interior portion and the L-carnitine and nootropic substance are in the solid interior portion of the core. 26. The method of claim 22, wherein the L-carnitine is selected from at least one of L-carnitine, acetyl L-carnitine, and propionyl L-carnitine. 27. The method of claim 22, wherein the nootropic substance is selected from at least one of L-serine and citicoline. 28. The method of claim 22, wherein an average diameter of the individual particulates is 0.1 to 3 mm. 29. The method of claim 22, wherein the therapeutically effective pharmaceutical dosage form includes 300 mg to 800 mg of the L-carnitine and 25 mg to 300 mg of the nootropic substance. 30. The method of claim 22, wherein the therapeutically effective pharmaceutical dosage form includes 400 mg to 600 mg of the L-carnitine and 200 mg to 250 mg of the nootropic substance. 31. The method of claim 22, wherein the L-carnitine is in an amount that is at least two times greater than the nootropic substance. 32. The method of claim 22, wherein the individual particulates respectively include by % w/w of the particulate: 35% to 65% w/w of the L-carnitine and 15% to 30% w/w of the nootropic substance. 33. The method of claim 22, wherein the individual particulates respectively include by % w/w of the particulate: 45% to 55% w/w of the L-carnitine and 20% to 30% w/w of the nootropic substance. 34. The method of claim 22, wherein:
the individual particulates respectively include by % w/w of the particulate: 35% to 65% w/w of the L-carnitine and 15% to 30% w/w of the nootropic substance; the therapeutically effective pharmaceutical dosage form includes 300 mg to 800 mg of the L-carnitine and 25 mg to 300 mg of the nootropic substance; an average diameter of the individual particulates is 0.1 to 3 mm; and the nootropic substance is selected from at least one of L-serine and citicoline. | A composition includes a therapeutically effective pharmaceutical dosage form including a plurality of individual particulates. The individual particulates respectively have: a core including an active ingredient combination of an L-carnitine and a nootropic substance and a release controlling polymer over the core that substantially prevents release of the active ingredients in stomach acid and permits release of the active ingredients in an intestinal pH environment. The composition may be used to treat conditions associated with a reduction of the amount of L-carnitine in the body and/or cognitive impairment.1. A composition comprising a therapeutically effective pharmaceutical dosage form including a plurality of individual particulates, the individual particulates respectively having:
a core including an active ingredient combination of an L-carnitine and a nootropic substance; and a release controlling polymer over the core that substantially prevents release of the active ingredient combination in stomach acid and permits release of the active ingredient combination an intestinal pH environment. 2. The composition of claim 1, wherein the L-carnitine is within an interior solid portion of the core and the nootropic substance is within a coating over the interior solid portion of the core. 3. The composition of claim 1, wherein the core includes a solid interior portion and the L-carnitine and nootropic substance are in the solid interior portion of the core. 4. The composition of claim 1, wherein the L-carnitine is selected from at least one of L-carnitine, acetyl L-carnitine, and propionyl L-carnitine. 5. The composition of claim 1, wherein the nootropic substance is selected from at least one of L-serine and citicoline. 6. The composition of claim 1, wherein an average diameter of the individual particulates is 0.1 to 3 mm. 7. The composition of claim 1, wherein the therapeutically effective pharmaceutical dosage form includes 300 mg to 800 mg of the L-carnitine and 25 mg to 300 mg of the nootropic substance. 8. The composition of claim 1, wherein the therapeutically effective pharmaceutical dosage form includes 400 mg to 600 mg of the L-carnitine and 200 mg to 250 mg of the nootropic substance. 9. The composition of claim 1, wherein the L-carnitine is in an amount that is at least two times greater than the nootropic substance. 10. The composition of claim 1, wherein the individual particulates respectively include by % w/w of the particulate: 35% to 65% w/w of the L-carnitine and 15% to 30% w/w of the nootropic substance. 11. The composition of claim 1, wherein the individual particulates respectively include by % w/w of the particulate: 45% to 55% w/w of the L-carnitine and 20% to 30% w/w of the nootropic substance. 12. The composition of claim 1, wherein:
the individual particulates respectively include by %w/w of the particulate: 35% to 65% w/w of the L-carnitine and 15% to 30% w/w of the nootropic substance; the therapeutically effective pharmaceutical dosage form includes 300 mg to 800 mg of the L-carnitine and 25 mg to 300 mg of the nootropic substance; an average diameter of the individual particulates is 0.1 to 3 mm; and the nootropic substance is selected from at least one of L-serine and citicoline. 13. A composition comprising a therapeutically effective pharmaceutical dosage form including a plurality of individual particulates, the individual particulates respectively having by % w/w of the particulate:
a solid core including 35% to 65% w/w of an L-carnitine; 1% to 20% w/w of a subcoating over the solid core; 15% to 30% w/w of a nootropic substance that is within the solid core or within the subcoating; and an enteric coating over the subcoating. 14. The composition of claim 13, wherein the core includes a solid interior portion and the L-carnitine and nootropic substance are in the solid interior portion of the core. 15. The composition of claim 13, wherein the L-carnitine is selected from at least one of L-carnitine, acetyl L-carnitine, and propionyl L-carnitine. 16. The composition of claim 13, wherein an average diameter of the individual particulates is 0.1 mm to 3 mm. 17. The composition of claim 13, wherein the nootropic substance is selected from at least one of L-serine and citicoline. 18. The composition of claim 13, wherein the individual particulates respectively include by % w/w of the particulate: 45% to 55% w/w of the L-carnitine and 20% to 30% w/w of the nootropic substance. 19. The composition of claim 13, wherein the L-carnitine is in an amount that is at least two times greater than the nootropic substance. 20. The composition of claim 13, wherein therapeutically effective pharmaceutical dosage form includes 300 mg to 800 mg of the L-carnitine and 25 mg to 300 mg of the nootropic substance. 21. The composition of claim 13, wherein:
an average diameter of the individual particulates is 0.1 mm to 3 mm; the nootropic substance is selected from at least one of L-serine and citicoline; the individual particulates respectively include by % w/w of the particulate: 45% to 55% w/w of the L-carnitine and 20% to 30% w/w of the nootropic substance; and therapeutically effective pharmaceutical dosage form includes 300 mg to 800 mg of the L-carnitine and 25 mg to 300 mg of the nootropic substance. 22. A method of treating a physiological condition associated with cognitive impairment, the method comprising:
administering to a patient in need thereof a therapeutically effective pharmaceutical dosage form including a plurality of individual particulates, the individual particulates respectively having:
a core including an active ingredient combination of an L-carnitine and a nootropic substance; and
a release controlling polymer over the core that substantially prevents release of the active ingredient combination in stomach acid and permits release of the active ingredient combination in an intestinal pH environment. 23. The method of claim 22, wherein administering the therapeutically effective pharmaceutical dosage form to the patient comprises administering at least one capsule containing the plurality of individual particulates therein. 24. The method of claim 22, wherein the L-carnitine is within an interior solid portion of the core and the nootropic substance is within a coating over the interior solid portion of the core. 25. The method of claim 22, wherein the core includes a solid interior portion and the L-carnitine and nootropic substance are in the solid interior portion of the core. 26. The method of claim 22, wherein the L-carnitine is selected from at least one of L-carnitine, acetyl L-carnitine, and propionyl L-carnitine. 27. The method of claim 22, wherein the nootropic substance is selected from at least one of L-serine and citicoline. 28. The method of claim 22, wherein an average diameter of the individual particulates is 0.1 to 3 mm. 29. The method of claim 22, wherein the therapeutically effective pharmaceutical dosage form includes 300 mg to 800 mg of the L-carnitine and 25 mg to 300 mg of the nootropic substance. 30. The method of claim 22, wherein the therapeutically effective pharmaceutical dosage form includes 400 mg to 600 mg of the L-carnitine and 200 mg to 250 mg of the nootropic substance. 31. The method of claim 22, wherein the L-carnitine is in an amount that is at least two times greater than the nootropic substance. 32. The method of claim 22, wherein the individual particulates respectively include by % w/w of the particulate: 35% to 65% w/w of the L-carnitine and 15% to 30% w/w of the nootropic substance. 33. The method of claim 22, wherein the individual particulates respectively include by % w/w of the particulate: 45% to 55% w/w of the L-carnitine and 20% to 30% w/w of the nootropic substance. 34. The method of claim 22, wherein:
the individual particulates respectively include by % w/w of the particulate: 35% to 65% w/w of the L-carnitine and 15% to 30% w/w of the nootropic substance; the therapeutically effective pharmaceutical dosage form includes 300 mg to 800 mg of the L-carnitine and 25 mg to 300 mg of the nootropic substance; an average diameter of the individual particulates is 0.1 to 3 mm; and the nootropic substance is selected from at least one of L-serine and citicoline. | 1,600 |
1,399 | 15,550,763 | 1,623 | An injectable device, comprising a hyaluronic acid-based composition, useful for long lasting facial sculpting and correction of facial features, for example, for augmenting and shaping the profile, including for example, the chin, jawline or the nose, in a human being is provided. Methods of treatment are also provided. | 1. A sterile composition, implantable subdermally or supraperiostially into the chin area, jawline or nose of a patient in need thereof, the composition comprising a crosslinked hyaluronic acid (HA) crosslinked with 1,4-butanediol diglycidyl ether (BDDE);
wherein a HA concentration of the composition is greater than 20 mg/g; wherein the HA used for crosslinking is made with a mixture of low molecular weight hyaluronic acid and high molecular weight hyaluronic acid; wherein the HA used for crosslinking is a mixture containing at least 50% by weight of low molecular weight HA, based on a total weight of the HA; wherein the composition has an elastic modulus between about 500 Pa and about 900 Pa at 5 Hz; wherein the composition has a cohesivity above 60 gmf; and wherein the composition exhibits an extrusion force between about 4N and about 15N at 13 mm/min using a 1 mL COC syringe and a 27G×13 mm needle. 2. The composition of claim 1, wherein the HA concentration is at least about 22.5 mg/g. 3. The composition of claim 1, wherein the HA concentration is about 25 mg/g. 4. The composition of claim 1, wherein the HA concentration is about 27.5 mg/g. 5. The composition of claim 1, wherein the HA used for crosslinking is a mixture containing at least 70% by weight of low molecular weight HA based on the total weight of the HA. 6. The composition of claim 1, wherein the HA used for crosslinking is a mixture containing about 90% by weight of low molecular weight HA and about 10% by weight of high molecular weight HA, based on the total weight of the HA. 7. The composition of claim 1, wherein the cohesivity is between about 60 gmf and about 200 gmf. 8. The composition of claim 1, wherein the cohesivity is between about 60 gmf and about 100 gmf. 9. The composition of claim 1, wherein the extrusion force is between about 7N and about 12N at 13 mm/min using a 1 mL COC syringe and a 27G×13 mm needle. 10. The composition of claim 1, wherein the extrusion force is between about 8N and about 10N at 13 mm/min using a 1 mL COC syringe and a 27G×13 mm needle. 11. The composition of claim 1, wherein the composition further includes an anesthetic agent. 12. The composition of claim 1, wherein the composition further includes lidocaine hydrochloride. 13. The composition of claim 1, wherein the composition further includes about 0.3% by weight lidocaine hydrochloride, based on the total weight of the composition. 14. The composition of claim 1, wherein the HA has a degree of crosslinking of between about 4% and about 10%. 15. The composition of claim 1, wherein the HA has a degree of crosslinking of about 4%. 16. The composition of claim 1, wherein the HA has a degree of crosslinking of about 6%. 17. The composition of claim 1, wherein the HA has a degree of crosslinking of about 8%. 18. The composition of claim 1, wherein the HA has a degree of crosslinking of about 10% or about 6.5%. 19. The composition of claim 1, wherein the composition comprises about 25 mg of crosslinked HA and 3 mg of lidocaine in a phosphate buffer pH 7.2 q.s. 1 mL, and wherein the crosslinked HA has a degree of crosslinking of about 6.5%. 20. A method for correcting chin retrusion in a patient comprising:
supraperiostally administering into at least one treatment area of the face of the patient, an effective amount of a composition comprising BDDE-crosslinked hyaluronic acid (HA), the HA having a degree of crosslinking of about 6.5%, and having a HA concentration of greater than 20 mg/g, wherein the HA used for crosslinking is a mixture containing at least 50% by weight of low molecular weight HA, based on a total weight of the HA; the treatment area being selected from the group consisting of the pogonion, the mentum, the left pre-jowl sulcus, the right pre-jowl sulcus, and the sublabial crease. 21. The method of claim 20 wherein, prior to the administering, the patient has a G-Sn-Pog angle of less than about 165° based on calculations of facial angle derived from digital images of the patient. 22. The method of claim 20, wherein the administering results in the patient having an increased G-Sn-Pog angle. 23. The method of claim 20, wherein the patient has an increased G-Sn-Pog angle for a period of time in the range of about 9 months to about 24 months after the step of administering. 24. The method of claim 20, wherein the patient has an increased G-Sn-Pog angle for at least about 6 months after the step of administering. 25. The method of claim 20, wherein the patient has an increased G-Sn-Pog angle for at least about 9 months after the step of administering. 26. The method of claim 20, wherein the patient has an increased G-Sn-Pog angle for at least about 12 months after the step of administering. 27. The method of claim 20, wherein the patient has an increased G-Sn-Pog angle for at least about 18 months after the step of administering. 28. The method of claim 20, wherein the patient has a G-Sn-Pog angle of about 169° or greater after the step of administering. 29. The method of claim 20, wherein:
the HA concentration of the composition is about 25 mg/g, wherein the HA used for crosslinking the composition is made with about 90% by weight of low molecular weight hyaluronic acid and about 10% by weight of high molecular weight hyaluronic acid, based on the total weight of the HA; wherein the composition has an elastic modulus comprised between about 500 Pa and about 800 Pa at 5 Hz; wherein the composition has a cohesivity between about 60 gmf and 100 gmf; and wherein the composition has an extrusion force between about 8N and about 10N at 13 mm/min using a 1 mL COC syringe and a 27G×13 mm needle. 30. A method of creating or restoring volume to the chin or jaw of a patient, the method comprising injecting a sterile composition, subdermally or supraperiostially, into the chin area or jawline of the patient in need thereof, the composition comprising a crosslinked hyaluronic acid (HA) crosslinked with 1,4-butanediol diglycidyl ether (BDDE) and wherein the HA used for crosslinking is a mixture containing at least 50% by weight of low molecular weight HA, based on a total weight of the HA;
wherein the composition has an elastic modulus between about 500 Pa and about 800 Pa at 5 Hz; wherein the composition has a cohesivity between about 60 gmf and 100 gmf; and wherein the method adds volume to the chin or jawline of the patient for a period of time in the range of about 9 months to about 24 months after injection of the composition into the chin or jawline of the patient. 31. The method of claim 30 wherein the composition has an extrusion force between about 8N and about 10N at 13 mm/min using a 1 mL COC syringe and a 27G×13 mm needle. 32. The method of claim 30, wherein the HA has a degree of crosslinking of between about 4% and about 12%. 33. The method of claim 30, wherein the HA has a degree of crosslinking of about 6%. 34. The method of claim 30, wherein the HA has a degree of crosslinking of about 8%. 35. The method of claim 30, wherein the HA has a degree of crosslinking of about 10%. 36. The method of claim 30, wherein the HA has a degree of crosslinking of about 6.5%. 37. The method of claim 30, wherein the HA has a degree of crosslinking of about 8.5%. 38. The method of claim 30, wherein the HA has a degree of crosslinking of about 10.5%. 39. A kit, comprising the composition according to claim 1, prefilled in a single-use syringe, and at least one single-use needle. 40. A method for facial sculpturing, such as for augmenting, correcting, restoring or creating volume in the chin and jaw area, in a patient comprising:
subcutaneously and/or supraperiosteally administering into at least one treatment area of the face of the patient, an effective amount of the composition of claim 1 by injection of said composition; wherein the treatment area is selected from the group consisting of the pogonion, the mentum, the left pre-jowl sulcus, the right pre-jowl sulcus, and the sublabial (mental) crease. 41. The method of claim 40, wherein the composition is injected using a 1 mL COC syringe and a fine gauge needle between about 18G and about 40G. 42. The method of claim 40, wherein the composition is injected in an injection volume of less than 4.0 mL for a single treatment area at any treatment session. 43. The method of claim 40, wherein the composition is injected in a maximum total volume of less than about 4.0 mL for initial and possible top-up treatments combined. 44. The method of claim 40, wherein the pogonion is injected supraperiosteally using multiple small boluses, wherein the mentum is injected supraperiosteally using multiple small boluses, wherein the left and/or right pre jowl sulci is injected using a deep subcutaneous fanning technique, wherein the sublabial (mental) crease is injected using linear, retrograde or anterograde superficial subcutaneous threading. 45. The method of claim 40, further comprising massaging the treatment area of the patient's face, after administering is completed, to assure that the injected composition conforms to a contour of surrounding tissues. 46. The method of claim 40, further comprising, prior to administering said composition, disinfecting the treatment area. | An injectable device, comprising a hyaluronic acid-based composition, useful for long lasting facial sculpting and correction of facial features, for example, for augmenting and shaping the profile, including for example, the chin, jawline or the nose, in a human being is provided. Methods of treatment are also provided.1. A sterile composition, implantable subdermally or supraperiostially into the chin area, jawline or nose of a patient in need thereof, the composition comprising a crosslinked hyaluronic acid (HA) crosslinked with 1,4-butanediol diglycidyl ether (BDDE);
wherein a HA concentration of the composition is greater than 20 mg/g; wherein the HA used for crosslinking is made with a mixture of low molecular weight hyaluronic acid and high molecular weight hyaluronic acid; wherein the HA used for crosslinking is a mixture containing at least 50% by weight of low molecular weight HA, based on a total weight of the HA; wherein the composition has an elastic modulus between about 500 Pa and about 900 Pa at 5 Hz; wherein the composition has a cohesivity above 60 gmf; and wherein the composition exhibits an extrusion force between about 4N and about 15N at 13 mm/min using a 1 mL COC syringe and a 27G×13 mm needle. 2. The composition of claim 1, wherein the HA concentration is at least about 22.5 mg/g. 3. The composition of claim 1, wherein the HA concentration is about 25 mg/g. 4. The composition of claim 1, wherein the HA concentration is about 27.5 mg/g. 5. The composition of claim 1, wherein the HA used for crosslinking is a mixture containing at least 70% by weight of low molecular weight HA based on the total weight of the HA. 6. The composition of claim 1, wherein the HA used for crosslinking is a mixture containing about 90% by weight of low molecular weight HA and about 10% by weight of high molecular weight HA, based on the total weight of the HA. 7. The composition of claim 1, wherein the cohesivity is between about 60 gmf and about 200 gmf. 8. The composition of claim 1, wherein the cohesivity is between about 60 gmf and about 100 gmf. 9. The composition of claim 1, wherein the extrusion force is between about 7N and about 12N at 13 mm/min using a 1 mL COC syringe and a 27G×13 mm needle. 10. The composition of claim 1, wherein the extrusion force is between about 8N and about 10N at 13 mm/min using a 1 mL COC syringe and a 27G×13 mm needle. 11. The composition of claim 1, wherein the composition further includes an anesthetic agent. 12. The composition of claim 1, wherein the composition further includes lidocaine hydrochloride. 13. The composition of claim 1, wherein the composition further includes about 0.3% by weight lidocaine hydrochloride, based on the total weight of the composition. 14. The composition of claim 1, wherein the HA has a degree of crosslinking of between about 4% and about 10%. 15. The composition of claim 1, wherein the HA has a degree of crosslinking of about 4%. 16. The composition of claim 1, wherein the HA has a degree of crosslinking of about 6%. 17. The composition of claim 1, wherein the HA has a degree of crosslinking of about 8%. 18. The composition of claim 1, wherein the HA has a degree of crosslinking of about 10% or about 6.5%. 19. The composition of claim 1, wherein the composition comprises about 25 mg of crosslinked HA and 3 mg of lidocaine in a phosphate buffer pH 7.2 q.s. 1 mL, and wherein the crosslinked HA has a degree of crosslinking of about 6.5%. 20. A method for correcting chin retrusion in a patient comprising:
supraperiostally administering into at least one treatment area of the face of the patient, an effective amount of a composition comprising BDDE-crosslinked hyaluronic acid (HA), the HA having a degree of crosslinking of about 6.5%, and having a HA concentration of greater than 20 mg/g, wherein the HA used for crosslinking is a mixture containing at least 50% by weight of low molecular weight HA, based on a total weight of the HA; the treatment area being selected from the group consisting of the pogonion, the mentum, the left pre-jowl sulcus, the right pre-jowl sulcus, and the sublabial crease. 21. The method of claim 20 wherein, prior to the administering, the patient has a G-Sn-Pog angle of less than about 165° based on calculations of facial angle derived from digital images of the patient. 22. The method of claim 20, wherein the administering results in the patient having an increased G-Sn-Pog angle. 23. The method of claim 20, wherein the patient has an increased G-Sn-Pog angle for a period of time in the range of about 9 months to about 24 months after the step of administering. 24. The method of claim 20, wherein the patient has an increased G-Sn-Pog angle for at least about 6 months after the step of administering. 25. The method of claim 20, wherein the patient has an increased G-Sn-Pog angle for at least about 9 months after the step of administering. 26. The method of claim 20, wherein the patient has an increased G-Sn-Pog angle for at least about 12 months after the step of administering. 27. The method of claim 20, wherein the patient has an increased G-Sn-Pog angle for at least about 18 months after the step of administering. 28. The method of claim 20, wherein the patient has a G-Sn-Pog angle of about 169° or greater after the step of administering. 29. The method of claim 20, wherein:
the HA concentration of the composition is about 25 mg/g, wherein the HA used for crosslinking the composition is made with about 90% by weight of low molecular weight hyaluronic acid and about 10% by weight of high molecular weight hyaluronic acid, based on the total weight of the HA; wherein the composition has an elastic modulus comprised between about 500 Pa and about 800 Pa at 5 Hz; wherein the composition has a cohesivity between about 60 gmf and 100 gmf; and wherein the composition has an extrusion force between about 8N and about 10N at 13 mm/min using a 1 mL COC syringe and a 27G×13 mm needle. 30. A method of creating or restoring volume to the chin or jaw of a patient, the method comprising injecting a sterile composition, subdermally or supraperiostially, into the chin area or jawline of the patient in need thereof, the composition comprising a crosslinked hyaluronic acid (HA) crosslinked with 1,4-butanediol diglycidyl ether (BDDE) and wherein the HA used for crosslinking is a mixture containing at least 50% by weight of low molecular weight HA, based on a total weight of the HA;
wherein the composition has an elastic modulus between about 500 Pa and about 800 Pa at 5 Hz; wherein the composition has a cohesivity between about 60 gmf and 100 gmf; and wherein the method adds volume to the chin or jawline of the patient for a period of time in the range of about 9 months to about 24 months after injection of the composition into the chin or jawline of the patient. 31. The method of claim 30 wherein the composition has an extrusion force between about 8N and about 10N at 13 mm/min using a 1 mL COC syringe and a 27G×13 mm needle. 32. The method of claim 30, wherein the HA has a degree of crosslinking of between about 4% and about 12%. 33. The method of claim 30, wherein the HA has a degree of crosslinking of about 6%. 34. The method of claim 30, wherein the HA has a degree of crosslinking of about 8%. 35. The method of claim 30, wherein the HA has a degree of crosslinking of about 10%. 36. The method of claim 30, wherein the HA has a degree of crosslinking of about 6.5%. 37. The method of claim 30, wherein the HA has a degree of crosslinking of about 8.5%. 38. The method of claim 30, wherein the HA has a degree of crosslinking of about 10.5%. 39. A kit, comprising the composition according to claim 1, prefilled in a single-use syringe, and at least one single-use needle. 40. A method for facial sculpturing, such as for augmenting, correcting, restoring or creating volume in the chin and jaw area, in a patient comprising:
subcutaneously and/or supraperiosteally administering into at least one treatment area of the face of the patient, an effective amount of the composition of claim 1 by injection of said composition; wherein the treatment area is selected from the group consisting of the pogonion, the mentum, the left pre-jowl sulcus, the right pre-jowl sulcus, and the sublabial (mental) crease. 41. The method of claim 40, wherein the composition is injected using a 1 mL COC syringe and a fine gauge needle between about 18G and about 40G. 42. The method of claim 40, wherein the composition is injected in an injection volume of less than 4.0 mL for a single treatment area at any treatment session. 43. The method of claim 40, wherein the composition is injected in a maximum total volume of less than about 4.0 mL for initial and possible top-up treatments combined. 44. The method of claim 40, wherein the pogonion is injected supraperiosteally using multiple small boluses, wherein the mentum is injected supraperiosteally using multiple small boluses, wherein the left and/or right pre jowl sulci is injected using a deep subcutaneous fanning technique, wherein the sublabial (mental) crease is injected using linear, retrograde or anterograde superficial subcutaneous threading. 45. The method of claim 40, further comprising massaging the treatment area of the patient's face, after administering is completed, to assure that the injected composition conforms to a contour of surrounding tissues. 46. The method of claim 40, further comprising, prior to administering said composition, disinfecting the treatment area. | 1,600 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.