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Use of tyrosine kinase inhibitors for treating inflammatory diseases |
The present invention relates to a method for treating inflammatory diseases such as rheumatoid arthritis (RA), comprising administering a tyrosine kinase inhibitor to a human in need of such treatment, more particularly a non-toxic, selective and potent c-kit inhibitor. Preferably, said inhibitor is unable to promote death of IL-3 dependent cells cultured in presence of IL-3. |
1. A method for treating inflammatory diseases comprising administering a tyrosine kinase inhibitor to a mammal in need of such treatment. 2. A method according to claim 1, wherein said tyrosine kinase inhibitor is unable to promote death of IL-3 dependent cells cultured in presence of IL-3. 3. A method for treating inflammatory diseases comprising administering a c-kit inhibitor to a mammal in need of such treatment. 4. A method according to claim 3, wherein said c-kit inhibitor is a non-toxic, selective and potent c-kit inhibitor. 5. A method according to claim 4, wherein said inhibitor is selected from the group consisting of indolinones, pyrimidine derivatives, pyrrolopyrimidine derivatives, quinazoline derivatives, quinoxaline derivatives, pyrazoles derivatives, bis monocyclic, bicyclic or heterocyclic aryl compounds, vinylene-azaindole derivatives and pyridyl-quinolones derivatives, styryl compounds, styryl-substituted pyridyl compounds, seleoindoles, selenides, tricyclic polyhydroxylic compounds and benzylphosphonic acid compounds. 6. A method according to claim 4, wherein said inhibitor is selected from the group consisting of: pyrimidine derivatives, more particularly N-phenyl-2-pyrimidine-amine derivatives. indolinone derivatives, more particularly pyrrol-substituted indolinones, monocyclic, bicyclic aryl and heteroaryl compounds, and quinazoline derivatives. 7. A method according to one of claims 1 to 6, wherein said inhibitor is selected from the group consisting of N-phenyl-2-pyrimidine-amine derivatives having the formula II: Wherein R1, R2 and R3 are independently chosen from H, F, Cl, Br, I, a C1-C5 alkyl or a cyclic or heterocyclic group, especially a pyridyl group; R4, R5 and R6 are independently chosen from H, F, Cl, Br, I, a C1-C5 alkyl, especially a methyl group; and R7 is a phenyl group bearing at least one substituent, which in turn possesses at least one basic site, such as an amino function, preferably the following group: 8. A method according to claim 7, wherein said inhibitor is the 4-(4-mëhylpipërazine-1-ylmëthyl)-N-[4-mëthyl-3-(4-pyridine-3-yl)pyrimidine-2 ylamino)phënyl]-benzamide. 9. A method according to one of claims 3 to 8, wherein said c-kit inhibitor is unable to promote death of IL-3 dependent cells cultured in presence of IL-3. 10. A method according to one of claims 3 to 9, wherein said c-kit inhibitor is an inhibitor of activated c-kit. 11. A method according to claim 10, wherein said activated c-kit inhibitor is capable of inhibiting SCF-activated c-kit. 12. A method according to claim 10, wherein said inhibitor is capable of inhibiting constitutively activated-mutant c-kit. 13. A method for treating inflammatory diseases comprising administering to a mammal in need of such treatment a compound that is a selective, potent and non toxic inhibitor of activated c-kit obtainable by a screening method which comprises: a) bringing into contact (i) activated c-kit and (ii) at least one compound to be tested; under conditions allowing the components (i) and (ii) to form a complex, b) selecting compounds that inhibit activated c-kit, c) testing and selecting a subset of compounds identified in step b), which are unable to promote death of IL-3 dependent cells cultured in presence of IL-3. 14. A method according to claim 13, wherein the screening method further comprises the step consisting of testing and selecting a subset of compounds identified in step b) that are inhibitors of mutant activated c-kit, which are also capable of inhibiting SCF-activated c-kit wild. 15. A method according to claim 13, wherein activated c-kit is SCF-activated c-kit wild in step a). 16. A method according to one of claims 13 to 15, wherein putative inhibitors are tested at a concentration above 10 μM in step a). 17. A method according to one of claims 13 to 16, wherein IL-3 is preferably present in the culture media of IL-3 dependent cells at a concentration comprised between 0.5 and 10 ng/ml, preferably between 1 to 5 ng/ml. 18. A method according to claim 17, wherein IL-3 dependent cells are selected from the group consisting of mast cells, transfected mast cells, BaF3, and IC-2. 19. A method according to one of claims 13 to 17, wherein the extent to which component (ii) inhibits activated c-kit is measured in vitro or in vivo. 20. A method according to one of claims 13 to 17, further comprising the step consisting of testing and selecting compounds capable of inhibiting c-kit wild at concentration below 1 μM. 21. A method according to claim 20, wherein the testing is performed in vitro or in vivo. 22. A method according to one of claims 13 to 21, wherein the inhibition of mutant-activated c-kit and/or c-kit wild is measured using standard biochemical techniques such as immunoprecipitation and western blot. 23. A method according to one of claims 13 to 22, wherein the amount of c-kit phosphorylation is measured. 24. A method according to one of claims 13 to 23, wherein identified and selected compounds are potent, selective and non-toxic c-kit wild inhibitors. 25. A method for treating inflammatory diseases comprising administering to a mammal in need of such treatment a c-kit inhibitor obtainable by a screening method comprising: a) performing a proliferation assay with cells expressing a mutant c-kit (for example in the transphosphorylase domain), which mutant is a permanent activated c-kit, with a plurality of test compounds to identify a subset of candidate compounds targeting activated c-kit, each having an IC50<10 μM, by measuring the extent of cell death, b) performing a proliferation assay with cells expressing c-kit wild said subset of candidate compounds identified in step (a), said cells being IL-3 dependent cells cultured in presence of IL-3, to identify a subset of candidate compounds targeting specifically c-kit, c) performing a proliferation assay with cells expressing c-kit, with the subset of compounds identified in step b) and selecting a subset of candidate compounds targeting c-kit wild, each having an IC50<10 μM, preferably an IC50<1 μM, by measuring the extent of cell death. 26. A method according to claim 25, wherein the extent of cell death is measured by 3H thymidine incorporation, the trypan blue exclusion method or flow cytometry with propidium iodide. 27. A method according to one of claims 1 to 26 for preventing, delaying the onset and/or treating inflammatory diseases in human. 28. A method according to one of claims 1 to 26 for preventing, delaying the onset and/or treating an inflammatory disease selected from the group consisting of rheumatoid arthritis, conjunctivitis, rheumatoid spondylitis, osteoarthritis, gouty arthritis, polyarthritis, and other arthritic conditions as well as pain associated with these inflammatory diseases. 29. Use of a c-kit inhibitor to manufacture a medicament for treating inflammatory diseases. 30. A composition suitable for oral administration comprising a tyrosine kinase inhibitor, more particularly a c-kit inhibitor for the treatment of inflammatory disorders such as rheumatoid arthritis, conjunctivitis, rheumatoid spondylitis, osteoarthritis, gouty arthritis, polyarthritis, and other arthritic conditions as well as pain associated with these inflammatory diseases. 31. A composition suitable for topical, intranasal, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, intraventricular, transdernal, subcutaneous, intraperitoneal, enteral, sublingual, or rectal administration comprising a tyrosine kinase inhibitor, more particularly a c-kit inhibitor for the treatment of inflammatory disorders such as rheumatoid arthritis, conjunctivitis, rheumatoid spondylitis, osteoarthritis, gouty arthritis, polyarthritis, and other arthritic conditions as well as pain associated with these inflammatory diseases. |
Method for identifying compounds that specifically deplete mast cells |
The present invention relates to a screening method allowing the identification and selection of compounds capable of depleting mast cells, wherein said compounds do not show significant toxicity for other hematopeitic cells that are not mast cells or related cell or cell lines, such as SCF independent expanded human normal CD34+ cells. |
1. A method for identifying compounds capable of depleting mast cells, wherein said compounds are non-toxic for other hematopoeitic cells that are not mast cells or related cells or cell lines or derived cell lines thereof, such as SCF independent expanded human normal CD34+ cells, comprising the steps consisting of: a) culturing mast cells in vitro in a suitable culture medium b) adding to said culture medium at least one candidate compound to be tested and incubating said cells for a prolonged period of time. c) measuring the extent to which said compounds promote mast cells death or disrupt, interfere with, or inhibit mast cells growth, and selecting compounds for which mast cells depletion is observed, d) identifying a subset of compounds selected in step c) that are unable to promote significant death of a cell chosen from other hematopoeitic cells that are not mast cells or related cells or cell lines or derived cell lines thereof, such as SCF independent expanded human normal CD34+ cells. 2. A method for identifying compounds capable of depleting mast cells, wherein said compounds are non-toxic for other hematopoeitic cells that are not mast cells or related cells or cell lines or derived cell lines thereof, such as SCF independent expanded human normal CD34+ cells, comprising the step consisting of: a) providing a culture of mast cells, wherein said mast cells are selected from wild type mast cells and cell lines derived thereof, activated mutant mast cell lines, and activated wild type mast cells and cell lines derived thereof, b) contacting the culture of said cells with at least one candidate compound under conditions allowing growth and/or survival of mast cells, measuring the level of cell death in the presence of the candidate compound; and comparing the level of cell death in the presence of the candidate compound to the level of cell death in the absence of the candidate compound, wherein an increase in the level of cell death in the presence of the candidate compound is indicative of the mast cells depletion ability of the candidate compound, c) providing a culture of at least one cell other than mast cells, wherein said cell is selected from hematopoeitic cells that are not mast cells or related cells or cell lines or derived cell lines thereof, such as SCF independent expanded human normal CD34+ cells, d) contacting the culture of said cells with at least one compound identified in step b) under conditions allowing growth and/or survival of the cell depicted in step c), measuring the level of cell death in the presence of said compound; and comparing the level of cell death in the presence of the compound to the level of cell death in the absence of the compound, wherein no significant increase in the level of cell death in the presence of said compound is indicative of mast cells depletion specificity of said compound versus at least another hematopoeitic cell. 3. A method according to claim 1 or 2 wherein mast cells are chosen from isolated mast cells and cell lines derived thereof, BaF3, IC-2 mouse cells, HMC-1, P815 available at ATCC under the accession number TIB-64 , 10P2 available at ATCC under the accession number CRL-2034, 10P12 available at ATCC under the accession number CRL-2036, 11P0-1 available at ATCC under the accession number CRL-2037, and cell lines derived thereof. 4. A method according to one of claims 1 to 3, wherein other hematopoeitic cells that are not mast cells or related cells or cell lines are selected from the group consisting of human T lymphocyte Jurkat cell line (ATCC N° TIB-152 and cell lines derived thereof), the human B lymphocyte Daudi or Raji cell line (ATCC N° CCL-213 and CCL-86 respectively and cell lines derived thereof), the human monocytic U 937 cell line (ATCC N° CRL-1593.2) and the human HL-60 cell line (ATCC N° CCL-240), cell lines derived thereof ATCC N° CRL-2258 and CRL-2392) and normal human CD34+ cells that are expanded in a culture medium comprising a cocktail of cytokine except SCF. 5. A method according to one of claims 1 to 4, wherein compounds capable of depleting specifically mast cells at a concentration below 10 μM, preferably below 1 μM are selected. 6. A method according to one of claims 1 to 5, wherein the compounds exhibiting Ratios E/S ranging from 1/1000 to 1/5 are selected. 7. A method according to one of claims 1 to 6, wherein the cell death assay further comprises a cell proliferation assay, a cell viability assay and/or an apoptosis assay. 8. A method according to one of claims 1 to 6, wherein the extent of cell death is measured by 3H thymidine incorporation, the trypan blue exclusion method, using propidium iodide or by the 51Cr-release assay. 9. A method according to one of claims 1 to 6, wherein the extent of cell death is determined by a test of intracellular esterase activity, and a test of plasma membrane integrity, preferably using fluorescent calcein and ethidium homodimer-1. 10. A method according to one of claims 1 to 6, wherein the extent of cell death is determined by discriminating between living and dead cells using DiOC18 and propidium iodide. 11. A method according to one of claims 1 to 10, wherein the extent of cell death is measured by fluorometric assays of cell viability and cytotoxicity using a fluorescence microscope, a fluorometer, a fluorescence microplate reader or a flow cytometer. 12. A method according to one of claims 1 to 11, wherein the mast cells that are IL-3 dependent cells are cultured in a culture media comprising IL-3 at a concentration comprised between 0.5 and 10 ng/ml, preferably between 1 to 5 ng/ml. 13. A method according to one of claims 1 to 12, wherein compounds to be tested are selected from inhibitors of tyrosine kinases, such as Akt, c-Cb1, CRKL, Doc, p125 Fak, Fyn, Grap, Jak2, Lyn, MAPK, MATK, P13-K, PLC-γ, Raf1, Ras, SHP-1, SHP2 (Syp), Tec, Vav and Flt-3. 14. A screening method according to one of claims 1 to 12, wherein said compounds are selected from the group consisting of indolinone, pyrimidine derivatives, pyrrolopyrimidine derivatives, quinazoline derivatives, quinoxaline derivatives, pyrazoles derivatives, bis monocyclic, bicyclic or heterocyclic aryl compounds, vinylene-azaindole derivatives and pyridyl-quinolones derivatives, styryl compounds, styryl-substituted pyridyl compounds, seleoindoles, selenides, tricyclic polyhydroxylic compounds and benzylphosphonic acid compounds. 15. A compound obtainable by the method according to one of claims 1 to 12, wherein said compound is capable of depleting mast cells and has no significant toxicity for other hematopoietic cells, preferably compounds having an E/S ratio ranging 1/1000 to 1/5. 16. Use of a compound according to claim 15 to manufacture a medicament. 17. A method for treating a disease selected from autoimmune diseases, allergic diseases, bone loss, tumor angiogenesis, inflammatory diseases, inflammatory bowvel diseases (IBD), interstitial cystitis, mastocytosis, infections diseases, and CNS disorders comprising administering a compound obtainable from a method according to one of claims 1 to 14 to a mammal in need of such treatment. 18. A method for promoting hair growth and hair color revival comprising administering a compound obtainable from a method according to one or claims 1 to 14 to a human need of such treatment. 19. A method according to claim 17 for treating multiple sclerosis, psoriasis, intestine inflammatory disease, ulcerative colitis, Crohn's disease, rheumatoid arthritis and polyarthritis, local and systemic scleroderma, systemic lupus erythematosus, discoid lupus erythematosus, cutaneous lupus, dermatomyositis, polymyositis, Sjogren's syndrome, nodular panarteritis, autoimmune enteropathy, proliferative glomerulonephritis, vasculitis, active chronic hepatitis and chronic fatigue syndrome. 20. A method according to claim 17 for treating graft-versus-host disease or graft rejection in any organ transplantation including kidney, pancreas, liver, heart, lung and bone marrow. 21. A method according to claim 17 for treating subepidermal blistering disorders such as aphthous ulcers, and several bullous diseases such as pemphigus, bullous pemphigoid and cicatricial pemphigoid. 22. A method according to claim 21 comprising further administering at least one antibiotic, preferably selected from dapsone, azatlioprine, erythromycin, propionylerythromycin, neomycin, gentomycin, tobramycin and mechlocycline. 23. A method according to claim 17 for treating asthma, allergic rhinitis, allergic sinusitis, anaphylactic syndrome, urticaria, angloedema, atopic dermatitis, allergic contact dermatitis, erythema nodosum, erythema multiforme, cutaneous necrotizing venulitis, insect bite skin inflammation and blood sucking parasitic infestation. 24. A method according to claim 17 for treating skin allergic disorders such as urticaria, atopic dermatitis, allergic contact dermatitis, erythema nodosum, erythema multiforme, cutaneous necrotizing venulitis, insect bite skin inflammation and blood sucking parasitic infestation especially in dogs and cats. 25. A method according to one of claims 23 and 24 wherein the compound is administered with aerosolized formulations to target areas of a patient's respiratory tract, intranasal or topical formulation. 26. A method according to claim 17 for treating tumor angiogenesis in human. 27. A method according to claim 17 for treating skin disorders in human associated with mastocytosis, notably cutaneous mastocytosis including urticaria pigmentosa, diffuse cutaneous mastocytosis, solitary mastocytoma and bullous, erythrodermic and teleangiectatic mastocytosis. 28. A method according to claim 17 for treating category IV mastocytosis including mast cell leukemia. |
Solder composition |
A solder composition containing a lead-free SnZn alloy and a solder flux that contains at least an epoxy resin and an organic carboxylic acid. The organic carboxylic acid is dispersed in the solder composition as a solid at room temperature, and has a molecular weight of from 100 to 200 g/mol. |
1-11. (cancelled). 12. A solder composition, comprising: a lead-free SnZn alloy, and a solder flux, the solid flux including at least an epoxy resin and an organic carboxylic acid, wherein the organic carboxylic acid is dispersed in the solder composition as a solid at room temperature (25° C.). 13. The solder composition according to claim 12, wherein the epoxy resin is selected from a group consisting of bisphenol A-type epoxy resin, bisphenol F-type epoxy resin, novolak-type epoxy resin, alicyclic epoxy resin, and their mixtures. 14. The solder composition according to claim 12, wherein the organic carboxylic acid is selected from a group consisting of saturated aliphatic dicarboxylic acid, unsaturated aliphatic dicarboxylic acid, cycloaliphatic dicarboxylic acid, amino group-containing carboxylic acid, hydroxyl group-containing carboxylic acid, heterocyclic dicarboxylic acid, and their mixtures. 15. The solder composition according to claim 12, wherein the organic carboxylic acid has a melting point of from 130 to 220° C. 16. The solder composition according to claim 12, wherein the flux further contains an alcohol. 17. The solder composition according to claim 15, wherein the alcohol is a polyalcohol. 18. The solder composition according to claim 12, wherein the total content of the epoxy resin and the organic carboxylic acid in the flux is from 70 to 100% by mass of the flux, the content of the alcohol therein is from 0 to 30% by mass, and the epoxy resin and the organic carboxylic acid are preferably so formulated in the flux that the carboxylic acid is from 0.8 to 2.0 equivalents relative to 1.0 equivalent of the epoxy resin therein. 19. A solder composition, comprising: a lead-free SnZn alloy, and a solder flux that includes at least an epoxy resin and an organic carboxylic acid, wherein the organic carboxylic acid has a molecular weight in the range of from 100 to 200 g/mol. 20. The solder composition according to claim 19, wherein the epoxy resin is selected from a group consisting of bisphenol A-type epoxy resin, bisphenol F-type epoxy resin, novolak-type epoxy resin, alicyclic epoxy resin, and their mixtures. 21. The solder composition according to claim 19, wherein the organic carboxylic acid is selected from a group consisting of saturated aliphatic dicarboxylic acid, unsaturated aliphatic dicarboxylic acid, cycloaliphatic dicarboxylic acid, amino group-containing carboxylic acid, hydroxyl group-containing carboxylic acid, heterocyclic dicarboxylic acid, and their mixtures. 22. The solder composition according to claim 19, wherein the organic carboxylic acid has a melting point of from 130 to 220° C. 23. The solder composition according to claim 19, wherein the flux further contains an alcohol. 24. The solder composition according to claim 23, wherein the alcohol is a polyalcohol. 25. The solder composition according to claim 19, wherein the total content of the epoxy resin and the organic carboxylic acid in the flux is from 70 to 100% by mass of the flux, the content of the alcohol therein is from 0 to 30% by mass, and the epoxy resin and the organic carboxylic acid are preferably so formulated in the flux that the carboxylic acid is from 0.8 to 2.0 equivalents relative to 1.0 equivalent of the epoxy resin therein. 26. The solder composition as claimed in claim 19, wherein the organic carboxylic acid is dispersed in the solder composition as a solid at room temperature (25° C.). 27. A solder composition comprising: a lead-free SnZn alloy, a solder flux that includes at least an epoxy resin and an organic carboxylic acid, and microcapsules encapsulating the organic carboxylic acid with a film selected from a group consisting of epoxy resin, polyimide resin, polycarbonate resin, polyamide resin, polyester resin, polyurea resin, polyolefin resin, and polysulfone resin. 28. The solder composition according to claim 27, wherein the epoxy resin is selected from a group consisting of bisphenol A-type epoxy resin, bisphenol F-type epoxy resin, novolak-type epoxy resin, alicyclic epoxy resin, and their mixtures. 29. The solder composition according to claim 27, wherein the organic carboxylic acid is selected from a group consisting of saturated aliphatic dicarboxylic acid, unsaturated aliphatic dicarboxylic acid, cycloaliphatic dicarboxylic acid, amino group-containing carboxylic acid, hydroxyl group-containing carboxylic acid, heterocyclic dicarboxylic acid, and their mixtures. 30. The solder composition according to claim 27, wherein the organic carboxylic acid has a melting point of from 130 to 220° C. 31. The solder composition according to claim 27, wherein the flux further contains an alcohol. 32. The solder composition according to claim 31, wherein the alcohol is a polyalcohol. 33. The solder composition according to claim 27, wherein the total content of the epoxy resin and the organic carboxylic acid in the flux is from 70 to 100% by mass of the flux, the content of the alcohol therein is from 0 to 30% by mass, and the epoxy resin and the organic carboxylic acid are preferably so formulated in the flux that the carboxylic acid is from 0.8 to 2.0 equivalents relative to 1.0 equivalent of the epoxy resin therein. 34. A solder composition comprising: a lead-free SnZn alloy, a solder flux that includes at least an epoxy resin and an organic carboxylic acid, and microcapsules encapsulating the SnZn alloy with a film selected from a group consisting of epoxy resin, polyimide resin, polycarbonate resin, polyamide resin, polyester resin, polyurea resin, polyolefin resin, and polysulfone resin. 35. The solder composition according to claim 34, wherein the epoxy resin is selected from a group consisting of bisphenol A-type epoxy resin, bisphenol F-type epoxy resin, novolak-type epoxy resin, alicyclic epoxy resin, and their mixtures. 36. The solder composition according to claim 34, wherein the organic carboxylic acid is selected from a group consisting of saturated aliphatic dicarboxylic acid, unsaturated aliphatic dicarboxylic acid, cycloaliphatic dicarboxylic acid, amino group-containing carboxylic acid, hydroxyl group-containing carboxylic acid, heterocyclic dicarboxylic acid, and their mixtures. 37. The solder composition according to claim 34, wherein the organic carboxylic acid has a melting point of from 130 to 220° C. 38. The solder composition according to claim 34, wherein the flux further contains an alcohol. 39. The solder composition according to claim 38, wherein the alcohol is a polyalcohol. 40. The solder composition according to claim 34, wherein the total content of the epoxy resin and the organic carboxylic acid in the flux is from 70 to 100% by mass of the flux, the content of the alcohol therein is from 0 to 30% by mass, and the epoxy resin and the organic carboxylic acid are preferably so formulated in the flux that the carboxylic acid is from 0.8 to 2.0 equivalents relative to 1.0 equivalent of the epoxy resin therein. |
<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of the Invention The present invention relates to a lead-free solder composition which does not require flux removal and which undergoes few changes with time in its printability and solderability. 2. Background Art Most conventional flux for solder comprises rosin or rosin-modified resin with an activator such as organic acid or halide added thereto. Rosin is the main component of flux, and when it is diluted with solvent to have a suitable viscosity, it may improve the printability of solder that comprises it. As adhesive, in addition, rosin acts to temporarily fix electronic parts to a printed circuit substrate to prevent them from dropping or shifting. Rosin contains an active ingredient of abietic acid, and even the acid alone may be effective in some degree for solderability. Rosin that may be used in cream solder flux includes, for example, natural rosin, polymerized rosin, disproportionated rosin, hydrogenated rosin, maleic acid-modified rosin. However, rosin-based flux that contains such rosin remains as a residue on printed circuit boards after using the flux to mount electronic parts, and, in many cases, the residue has caused substrate corrosion and migration. In addition, when the printed circuit board with the residue remaining thereon is encapsulated with resin (e.g., silicone gel, epoxy resin), the residue may cause curing failure in resin encapsulation and may therefore have some negative influence on the resin's adhesiveness to and insulation from backboard. To remove the residue, the soldered board is generally washed with a flon substitute or organic solvent. At present, however, the washing agent is limited owing to environmental problems with flon and VOC. An epoxy flux is a type of flux that does not cause substrate corrosion and migration and does not cause curing failure in resin encapsulation, even though its residue is not removed through washing. The epoxy flux mainly comprises an epoxy resin, a carboxylic acid, an amine and a thixotropic agent. When parts are mounted on a printed circuit board by the use of cream solder that contains an epoxy flux comprising such components, the solder is so planned that the conductor surface may be activated by the carboxylic acid in the stage of reflow-soldering. At the same time, the epoxy resin may react with the carboxylic acid to cure, and its curing may be finished when the reflowed solder has adhered to the parts. After the solder has reflowed, the cured epoxy resin remains as a flux residue. Compared with the residue from ordinary rosin-based flux, the cured epoxy resin residue does not interfere with the adhesiveness of encapsulation resin to printed circuit boards even though it is not removed after soldering. Moreover, the parts-soldered board may be directly encapsulated with resin and its insulation is good (See JP-A 2000-216300). On the other hand, an SnPb alloy is generally employed as a solder alloy to be mixed with flux. The SnPb alloy serves well for soldering, and the melting point of its eutectic composition (63Sn37Pb) is 183 E C (low), and its soldering temperature is not higher than 250 E C. Accordingly, it does not cause thermal damage to electronic parts not resistant to heat. However, solder not containing lead, that is, lead-free solder, is currently desired because of the current environmental problems caused by lead. The alloy for lead-free solder includes Sn-based SnAg alloy and SnSb alloy. Of SnAg alloys, the composition having the lowest melting point is a eutectic composition of Sn3.5Ag with a melting point of 221 E C. The soldering temperature of the solder alloy having this composition is from 260 to 280 E C and is considered to be high. When soldering is effected at such a temperature, electronic parts not resistant to heat may be thermally damaged, whereby their function may deteriorate or they may break. Among SnSb alloys, the composition having the lowest melting point is Sn5Sb, and its melting point is 235 E C on the solid phase line thereof and is 240 E C on the liquid phase line thereof, both considered to be high. Therefore, its soldering temperature is from 280 to 300 E C and is much higher than that of the Sn3.5Ag alloy. For the same reason, electronic parts not resistant to heat may be thermally damaged with this alloy. Recently, lead-free SnZn alloy solder has become much noticed in the art, of which the melting point is lower than that of SnAg alloy and SnSb alloy. Of the SnZn alloy, for example, the eutectic composition is Sn9Zn, and its melting point is 199 E C, which is near the melting point of SnPb eutectic solder. The soldering temperature of the SnZn alloy is lower than that of SnAg alloy and SnSb alloy, and the SnZn alloy may reduce thermal damage to electronic parts not resistant to heat. However, when cream solder of lead-free SnZn alloy is prepared using conventional rosin-based flux, its printability and solderability may be almost the same as those of conventional cream solder immediately after its preparation. However, for example, when stored at room temperature for a while, the viscosity of the cream solder increases and its printability worsens and, in addition, its solderability also worsens. Further with the lapse of time, the viscosity of the SnZn-based cream solder increases more, and, as a result, the solder completely loses its printability. In that condition, even though a solvent is added to it to lower its viscosity and the thus-diluted solder is used for printing, the SnZn alloy powder therein can no longer melt and will be useless for soldering. On the other hand, even when an SnZn alloy-based cream solder composition is produced using an epoxy flux so that flux residue removal may be omitted, it still has the same problems as those of rosin flux-containing solder with respect to viscosity, the printability and the solderability thereof. |
<SOH> OBJECT AND SUMMARY OF THE INVENTION <EOH>An object of the present invention is to solve the above-mentioned problems and to provide a solder composition that contains an epoxy flux and a lead-free SnZn alloy. The solder composition undergoes few changes with time in its viscosity, printability and solderability, not requiring flux removal. The printability and the solderability of the cream solder composition that contains a lead-free SnZn alloy and an epoxy flux change with time because the Zn component of the SnZn alloy is highly reactive. The Zn component may therefore react with the component of the epoxy flux, essentially with the organic carboxylic acid in the flux with the lapse of time. As a result, when the reactivity of Zn with the organic carboxylic acid in the solder composition is suppressed, the above-mentioned problem may be solved. The invention is based on this finding. Specifically, the first embodiment of the invention is a solder composition containing a lead-free SnZn alloy and a solder flux that contains at least an epoxy resin and an organic carboxylic acid. In this embodiment, the organic carboxylic acid is dispersed in the solder composition as a solid at room temperature (25 E C). The second embodiment of the invention also is a solder composition containing a lead-free SnZn alloy and a solder flux that contains at least an epoxy resin and an organic carboxylic acid. In this embodiment, the organic carboxylic acid has a molecular weight of from 100 to 200 g/mol. Preferably, the organic carboxylic acid of this embodiment is dispersed in the solder composition as a solid at room temperature (25 E C). The third embodiment of the invention likewise is a solder composition containing a lead-free SnZn alloy and a solder flux that contains at least an epoxy resin and an organic carboxylic acid. In the embodiment, the organic carboxylic acid is in microcapsules that are encapsulated with a film selected from a group consisting of epoxy resin, polyimide resin, polycarbonate resin, polyamide resin, polyester resin, polyurea resin, polyolefin resin, and polysulfone resin. The fourth embodiment of the invention also is a solder composition containing a lead-free SnZn alloy and a solder flux that contains at least an epoxy resin and an organic carboxylic acid. The SnZn alloy of this embodiment is in microcapsules that are encapsulated with a film selected from a group consisting of epoxy resin, polyimide resin, polycarbonate resin, polyamide resin, polyester resin, polyurea resin, polyolefin resin, and polysulfone resin. In the solder composition of the invention, the epoxy resin preferably is selected from a group consisting of bisphenol A-type epoxy resin, bisphenol F-type epoxy resin, novolak-type epoxy resin, alicyclic epoxy resin, and their mixtures. Also, preferably the solder composition of the invention contains an alcohol. The alcohol preferably is a polyalcohol. In the solder composition of the invention, the organic carboxylic acid preferably is selected from a group consisting of saturated aliphatic dicarboxylic acid, unsaturated aliphatic dicarboxylic acid, cycloaliphatic dicarboxylic acid, amino group-containing carboxylic acid, hydroxyl group-containing carboxylic acid, heterocyclic dicarboxylic acid, and their mixtures. The organic carboxylic acid preferably has a melting point of from 130 to 220 E C. The total content of the epoxy resin and the organic carboxylic acid in the flux preferably is from 70 to 100% by mass of the flux. The content of the alcohol therein preferably is from 0 to 30% by mass. The epoxy resin and the organic carboxylic acid preferably are so formulated in the flux that the carboxyl group is from 0.8 to 2.0 equivalents relative to 1.0 equivalent of the epoxy group therein. Since the solder composition of the invention contains a lead-free SnZn alloy, its melting point is lower than that of other lead-free Sn-containing alloys such as SnAg and SnSb. As a result, it may reduce thermal damage of electronic parts that are not resistant to heat in reflow soldering with it. In addition, since it contains an epoxy flux, it is free from problems of substrate corrosion and migration, and does not cause curing failure in resin encapsulation. It does not require flux removal. Further, the solder composition of the invention is specifically designed so that Zn in the SnZn does not react with the organic carboxylic acid component in the flux to cause changes with time in the viscosity, the printability and the solderability of the composition. Therefore, even when stored for a long period of time after prepared, the solder composition still has long-lasting good solderability, that does not undergo such changes with time. detailed-description description="Detailed Description" end="lead"? |
Device and method for recording parameters of a golf game |
A hand held device (1) for recording scores of a golf game played by one or more players comprises a VDU (3) which selectively displays reference fairways (30) graphically which permits a player to enter the position of the location of a ball after each shot on the VDU (3) by positioning a cursor at a position (41) on the green (31) or the reference fairway (30) displayed on the VDU (3), which substantially corresponds to the position of the ball on the fairway or green being played. The position of the ball after each shot until the ball is holed is entered on the screen through the cursor. A microprocessor (2) reads the position of the cursor and stores a graphical representation of the progress (37) of the ball along the screen to the hole (29). The microprocessor (2) stores the graphical representation of the reference fairway (30) with the positions (41) of the ball entered through the cursor in a RAM (5) and computes the number of shots to the hole (29). This is repeated for each hole played in a game of golf and a score card for each player is displayed on the VDU (3) at the end of the game. The device (1) may be used by a number of players playing a game of golf, and respective score cards are generated for each player and displayed on the VDU. Graphical representations of each player's performance on each fairway can be reviewed after the game. |
1-82. (Canceled) without prejudice or disclaimer 83. A device for recording parameters of a golf game, characterised in that the device comprises a display means (3) for displaying graphically a representation of a reference fairway (30), a means for indicating on the reference fairway (30) a position (41) indicative of a location taken up by a ball after a shot, a reading means (2) for reading the indicated position (41), and a computing means (2) responsive to the reading means reading an input which indicates that a ball has been holed for summing the number of indicated positions (41) indicated on the reference fairway (30) for determining the number of shots from a tee to a hole, and a first storing means (5) for storing the determined number of shots from the tee to the hole. 84. A device as claimed in claim 83 characterised in that a second storing means (6) is provided for storing graphical representations of a plurality of reference fairways (30), the pars of the holes of which are different, and preferably, the graphical representations of the respective reference fairways (30) differ depending on the par of the hole, and advantageously, the means (3) for displaying the graphical representation of one of the reference fairways (30) is provided for selectively displaying a selected one of the reference fairways (30), and preferably, the display means (3) displays a graphical representation of respective selected ones of the reference fairways (30) for each of a number of holes to be played in the golf game. 85. A device as claimed in claim 83 characterised in that the computing means (2) computes the score of a round of golf, and the first storing means (5) stores the score of a round of golf, and preferably, the first storing means (5) stores the graphical representation of each reference fairway (30) displayed for the respective holes with the indicated positions (41) on the respective graphical representations of the reference fairways for each hole played, and preferably, the graphical representation of each reference fairway (30) comprises a representation of a rough location, and advantageously, the graphical representation of each reference fairway (30) comprises an out of bounds location, and preferably, the graphical representation of each reference fairway (30) comprises a sand bunker location, and preferably, at least some of the reference fairways (30) comprise a water hazard location. 86. A device as claimed in claim 83 characterised in that the reading means (2) reads the type of location in which the location taken up by the ball after a shot is indicated on the selected reference fairway (30), and preferably, the reading means (2) determines from the indicated position (41) the type of location in which the ball is indicated as being located after a shot, and advantageously, the reading means (2) determines from the indicated position (41) the lie of the ball to the left or right of a line joining the tee to the hole, and preferably, the graphical representation of each reference fairway (30) indicates an area between a green and the tee which is within a predetermined distance from the green, and the reading means (2) reads the indicated position (41) for determining if the indicated location of the ball is within the predetermined area. 87. A device as claimed in claim 84 characterised in that the second storing means (6) stores a graphical representation of at least one reference green (31) independently of the reference fairways, and preferably, the second storing means (6) stores a plurality of graphical representations of reference greens (31), and the respective reference greens (31) are stored in the second storing means (6) cross-referenced with corresponding reference fairways (30), and advantageously, the display means (3) selectively displays a graphical representation of a reference green (31) corresponding to each reference fairway (30) displayed, and preferably, the display means (3) displays a reference green (31) independently of each reference fairway (30), and advantageously, the display means (3) displays a reference green (31) corresponding to a reference fairway (30) independently of the reference fairway (30), and preferably, the graphical representation of each reference green (31) is provided with a plurality of bands (45) of predetermined radial distance from and extending around a hole on the reference green (31) for defining predetermined distances from the hole, and advantageously, the means for indicating the position indicative of a location taken up by a ball is provided for indicating the position relative to the hole taken up by the ball on the selected reference green (31), and preferably, the means for indicating the position indicative of a location taken up by a ball after a shot on the selected one of the selected reference fairway (30) or the selected reference green (31) is provided by a cursor, and preferably, the visual display means comprises a touch sensitive screen, and advantageously, the means for indicating the position indicative of a location taken up by a ball after a shot on the selected one of the selected reference fairway (30) or the selected reference green (31) is provided by a means for reading the position on the screen on which the screen is externally touched. 88. A device as claimed in claim 83 characterised in that a first input means is provided for inputting a message indicating a lost ball, and preferably, a second input means is provided for inputting a message indicating a penalty, and advantageously, a third input means is provided for indicating that the position taken up by a ball after a shot is within a water hazard, and preferably, the computing means is responsive to the first, second and third input means for computing the score of a round of golf. 89. A device as claimed in claim 83 characterised in that a data input means is provided for facilitating selective inputting of particulars of any one of the following characteristics of a player about to play a golf game, and of the golf course on which the golf game is to be played, namely, the handicap of the player, parameters of the course, particulars of the tees being played, course conditions on the day the game is being played, weather conditions on the day the game is being played, and condition of the player on the day the game is being played. 90. A device as claimed in claim 89 characterised in that the data input means permits inputting of the number of holes in the golf course, the yardage of each hole, the par of each hole and the index of each hole, and preferably, the first storing means (5) stores data inputted through the data input means, and advantageously, the computing means (2) computes the score for each hole less the handicap of the player. 91. A device as claimed in claim 83 characterised in that the computing means (2) compares the player's score for each hole against the par and/or index of the hole, and preferably, an output means is provided for outputting the score for each hole played and the score for the round played, and preferably, the output means facilitates outputting the score of the front nine holes and the back nine holes separately of each other, and advantageously, the output means interfaces with the display means for displaying the respective scores on the display means, and preferably, the scores are displayed on the display means in tabular form. 92. A device as claimed in claim 83 characterised in that the computing means (2) is adapted for selecting the holes of each of the holes played on a particular golf course over a number of games on which the player achieved the best hole scores, and displaying the scores of the selected ones of the holes in tabular form as a “dream game”, and preferably, the computing means (2) is adapted for selecting the holes of each of the holes played on a particular golf course over a number of games on which the player achieved the worst hole scores, and displaying the scores of the selected ones of the holes in tabular form as a “nightmare game”. 93. A device as claimed in claim 83 characterised in that the device is a hand held device, and preferably, the device comprises an interface means for interfacing the device with an external computer for downloading data in respect of each game to the external computer. 94. A method for recording parameters of a golf game, characterised in that the method comprises the steps of displaying a graphical representation of a reference fairway (30) on a visual display means (3), indicating on the reference fairway (30) a position (41) indicative of a location taken up by a ball after a shot, reading the indicated position (41) by a reading means (2), summing the number of indicated positions (41) indicated on the reference fairway (30) for determining the number of shots from a tee to a hole in a computing means (2), and storing the determined number of shots from the tee to the hole in a first storing means (5). 95. A method as claimed in claim 94 characterised in that the graphical representation of each reference fairway (30) displayed for the respective holes with the indicated positions (41) on the respective graphical representations of the reference fairways for each hole played is stored in the first storing means (5), and preferably, a second storing means (6) is provided for storing graphical representations of a plurality of reference fairways (30), the pars of the holes of which are different, and preferably, the graphical representations of the respective reference fairways (30) differ depending on the par of the hole, and advantageously, the means (3) for displaying the graphical representation of one of the reference fairways (30) is provided for selectively displaying a selected one of the reference fairways (30), and preferably, the display means (3) displays a graphical representation of respective selected ones of the reference fairways (30) for each of a number of holes to be played in the golf game. 96. A method as claimed in claim 94 characterised in that the score of a round of golf is computed in the computing means (2), and the first storing means (5) stores the score of a round of golf, and preferably, the graphical representation of each reference fairway (30) comprises a representation of a rough location, and preferably, the graphical representation of each reference fairway (30) comprises an out of bounds location, and advantageously, the graphical representation of each reference fairway (30) comprises a sand bunker location, and preferably, at least some of the reference fairways (30) comprise a water hazard location. 97. A method as claimed in claim 94 characterised in that the reading means (2) reads the type of location in which the location taken up by the ball after a shot is indicated on the selected reference fairway (30), and preferably, the reading means (2) determines from the indicated position (41) the type of location in which the ball is indicated as being located after a shot, and advantageously, the reading means (2) determines from the indicated position (41) the lie of the ball to the left or right of a line joining the tee to the hole, and preferably, the graphical representation of each reference fairway (30) indicates an area between a green and the tee which is within a predetermined distance from the green, and the reading means (2) reads the indicated position (41) for determining if the indicated location of the ball is within the predetermined area. 98. A method as claimed in claim 95 characterised in that the second storing means (6) stores a graphical representation of at least one reference green (31) independently of the reference fairways, and preferably, the second storing means (6) stores a plurality of graphical representations of reference greens (31), and the respective reference greens (31) are stored in the second storing means (6) cross-referenced with corresponding reference fairways (30), and advantageously, the display means (3) selectively displays a graphical representation of a reference green (31) corresponding to each reference fairway (30) displayed, and preferably, the display means (3) displays a reference green (31) independently of each reference fairway (30), and advantageously, the display means (3) displays a reference green (31) corresponding to a reference fairway (30) independently of the reference fairway (30), and preferably, the graphical representation of each reference green (31) is provided with a plurality of bands (45) of predetermined radial distance from and extending around a hole on the reference green (31) for defining predetermined distances from the hole. 99. A method as claimed in claim 98 characterised in that the means for indicating the position indicative of a location taken up by a ball is provided for indicating the position relative to the hole taken up by the ball on the selected reference green (31), and preferably, the means for indicating the position indicative of a location taken up by a ball after a shot on the selected one of the selected reference fairway (30) or the selected reference green (31) is provided by a cursor. 100. A method as claimed in claim 98 characterised in that the visual display means comprises a touch sensitive screen, and preferably, the means for indicating the position indicative of a location taken up by a ball after a shot on the selected one of the selected reference fairway (30) or the selected reference green (31) is provided by a means for reading the position on the screen on which the screen is externally touched, and advantageously, a first input means is provided for inputting a message indicating a lost ball, and preferably, a second input means is provided for inputting a message indicating a penalty, and advantageously, a third input means is provided for indicating that the position taken up by a ball after a shot is within a water hazard, and preferably, the computing means is responsive to the first, second and third input means for computing the score of a round of golf. 101. A method as claimed in claim 94 characterised in that a data input means is provided for facilitating selective inputting of particulars of any one of the following characteristics of a player about to play a golf game, and of the golf course on which the golf game is to be played, namely, the handicap of the player, parameters of the course, particulars of the tees being played, course conditions on the day the game is being played, weather conditions on the day the game is being played, and condition of the player on the day the game is being played. 102. A method as claimed in claim 101 characterised in that the data input means permits inputting of the number of holes in the golf course, the yardage of each hole, the par of each hole and the index of each hole, and preferably, the first storing means (5) stores data inputted through the data input means. 103. A method as claimed in claim 101 characterised in that the computing means (2) computes the score for each hole less the handicap of the player, and preferably, the computing means (2) compares the player's score for each hole against the par and/or index of the hole, and advantageously, an output means is provided for outputting the score for each hole played and the score for the round played, and preferably, the output means facilitates outputting the score of the front nine holes and the back nine holes separately of each other, and advantageously, the output means interfaces with the display means for displaying the respective scores on the display means, and preferably, the scores are displayed on the display means in tabular form. 104. A method as claimed in claim 94 characterised in that the computing means (2) is adapted for selecting the holes of each of the holes played on a particular golf course over a number of games on which the player achieved the best hole scores, and displaying the scores of the selected ones of the holes in tabular form as a “dream game”, and preferably, the computing means (2) is adapted for selecting the holes of each of the holes played on a particular golf course over a number of games on which the player achieved the worst hole scores, and displaying the scores of the selected ones of the holes in tabular form as a “nightmare game”. |
Support |
A support (1) for mounting on a door (7) from which a coat, jacket or the like can be suspended, comprises an anchor member (2) for securing to the door, and a support member (3) which is pivotally carried on a pivot pin (6). The pivot pin (6) is carried in pivot mounting brackets (5) of the anchor member (2), and the support member (3) is pivotal about the pivot pin (6) from an inoperative position parallel to the door to an operative position extending outwardly of the door (7) for facilitating suspending a coat, or jacket therefrom. An upwardly facing abutment surface (15) of the support member (3) engages a downwardly facing abutment surface (16) of the anchor member (2) at for supporting the support member (3) in the operative position. A magnet (17) in the anchor member (2) retains the support member (3) in the inoperative position. Alternatively, a torsion spring wound on the pivot pin (6) and co-operating with the support member (3) and the anchor member (2) urges and retains the support member (3) in the inoperative position. |
1-43. (Canceled) 44. A support for supporting an article, the support comprising an anchor member (2,91) for securing the support to an upstanding member (7), and a support member (3,30,40,50,60,70,81,82,83,90) for supporting the article thereon, the support member (3) being connected to the anchor member (2), characterised in that the support member (3) is moveable relative to the anchor member (2) between an inoperative position with the support member (3) lying relatively closely to the upstanding member (7) to which the anchor member (2) is secured, and an operative position whereby the support member (3) projects outwardly from the upstanding member (7) for supporting the article thereon. 45. A support as claimed in claim 44 characterised in that the support member (3) is moveable in a generally downwardly direction from the inoperative position to the operative position. 46. A support as claimed in claim 44 characterised in that the support member (3) is pivotally connected to the anchor member (2) about a pivot axis (13), and is pivotal between the respective operative and inoperative positions about the pivot axis (13), and preferably, the support member (3) extends transversely from the pivot axis (13) and terminates in a support means (3) for supporting the article. 47. A support as claimed in claim 44 characterised in that a limit means (15,16,97,99) is provided for preventing further movement of the support member (3) when it has moved into the operative position, and advantageously, the limit means (15,16,97,99) supports the support member (3) in the operative position. 48. A support as claimed in claim 47 characterised in that the limit means (15,16,97,99) comprises a pair of engageable abutment means, one of the abutment means being provided on the anchor member (2) and the other abutment means being provided on the support member (3) and being engageable with each other when the support member (3) is in the operative position, and preferably, the abutment means on the anchor member (2) is provided on a downwardly facing surface of the anchor member (2), and the abutment means on the support member (3) is provided on an upwardly facing surface of the support member (3) so that as the support member (3) is moving from the inoperative position to the operative position, the respective abutment means engage each other when the support member (3) moves into the operative position. 49. A support as claimed in claim 48 characterised in that the abutment means on the support member (3) is located on the support member (3) relative to the pivot axis (13) on an opposite side of the pivot axis (13) to that on which the support means is located, or alternatively, the abutment means on the anchor member (2) is provided on an upwardly facing surface of the anchor member (2), and the abutment means on the support member (3) is provided on a downwardly facing surface of the support member (3), and preferably, the abutment means on the support member (3) is located on the support member (3) intermediate the pivot axis (13) and the support means. 50. A support as claimed in claim 47 characterised in that the limit means (15,16,97,99) supports the support member (3) in the operative position with the support member (3) extending outwardly from the upstanding member. 51. A support as claimed in claim 47 characterised in that the limit means (15,16,97,99) supports the support member (3) in the operative position with the support member (3) extending outwardly from the upstanding member at an angle greater than zero to the horizontal, with the support member (3) inclining downwardly towards the upstanding member, and preferably, the support member (3) is supported by the limit means (15,16,97,99) in the operative position inclined at an angle to the horizontal in the range up to 10° from the horizontal, and advantageously, the support member (3) is supported by the limit means (15,16,97,99) in the operative position inclined at an angle to the horizontal in the range up to 5° from the horizontal, and preferably, the support member (3) is supported by the limit means (15,16,97,99) in the operative position inclined at an angle to the horizontal of approximately 1° from the horizontal. 52. A support as claimed in claim 44 characterised in that a retaining means (17,101,102,112) is provided for retaining the support member (3) in the inoperative position, and advantageously, the retaining means (17,101,102,112) comprises a resilient urging means (112) for resiliently urging the support member (3) from the operative position into the inoperative position, and for retaining the support member (3) in the inoperative position, and preferably, the urging strength of the resilient urging means is such as to permit the support member (3) to be urged from the inoperative to the operative position and to be retained in the operative position by the weight of the article being supported thereon, and advantageously, the resilient urging means comprises a spring (112). 53. A support as claimed in claim 52 characterised in that the urging means comprises a torsion spring (112) co-axially located with the pivot axis (13). 54. A support as claimed in claim 52 characterised in that the retaining means (17,101,102,112) comprises a pair of interengageable complementary formations (101,102), one (102) of the said formations being formed on the support member (3), and the other (101) on the anchor member (2) so that when the support member (3) is in the inoperative position the interengageable complementary formations releasably engage each other for retaining the support member (3) in the inoperative position, and preferably, the interengageable complementary formations engage each other with a snap-fit action. 55. A support as claimed in claim 52 characterised in that the retaining means comprises a permanent magnet (17) located on one of the anchor member (2) and the support member (3) for co-operating with the other member for retaining the support member (3) in the inoperative position, and preferably, the permanent magnet (17) is located in the anchor member (2) and co-operates with a magnetic member in the support member (3), and advantageously, the support member (3) is of a magnetic material for co-operating with the permanent magnet (17) for retaining the support member (3) in the inoperative position. 56. A support as claimed in claim 44 characterised in that the anchor member (2) comprises a base member (4) for securing to the upstanding member, and preferably, at least one pivot mounting bracket (5,92) is carried on the base member (4) for pivotally carrying the support member (3), and advantageously, a pivot pin (16) is carried by the pivot mounting bracket (5,92) for pivotally engaging the support member (3), the pivot pin (6) defining the pivot axis (13) about which the support member (3) is pivotal. 57. A support as claimed in claim 56 characterised in that a pair of spaced apart pivot mounting brackets (5,92) are provided for accommodating the support member (3) therebetween, and preferably, the pivot pin extends between the respective pivot mounting brackets (5,92) for pivotally engaging the support member (3). 58. A support as claimed in claim 44 characterised in that the support means comprises at least one hook (1,30) extending from the support member (3) for supporting clothing or other articles suspended therefrom, and advantageously, a plurality of hooks (1,30) are provided. 59. A support as claimed in claim 44 characterised in that the support means comprises a support ring (32,41) located at the end of the support member (3), and preferably, the support ring (32,41) is adapted for receiving one or more coat hangers with clothing suspended therefrom, or alternatively, the support ring (32,41) is adapted for receiving a container therein and supporting the container within the support ring (32,41). 60. A support as claimed in claim 44 characterised in that the support means comprises a platform (51,61,71) for forming a shelf for supporting an article thereon. 61. A support as claimed in claim 44 characterised in that a mounting means is provided for mounting and securing the anchor member (2) to the upstanding member, and preferably, the mounting means comprises a releasable mounting means, and advantageously, the mounting means comprises a mounting bracket (5,92), and preferably, the mounting bracket (5,92) is adapted for engaging over the top of a door (7,95) or a window. 62. An upstanding member comprising the support as claimed in claim 44 secured thereto. 63. A door comprising the support as claimed in claim 44 secured thereto. |
Information delivery server, recording medium, and information delivery method |
The objective of the present invention is to provide an information distribution server which can distribute individual information for distribution, according to the position of a person who is visiting. The present invention includes: a device for obtaining the ID of a person who is visiting, which is provided within a work area, and which obtains an ID of the person who is visiting, which is information for discriminating the person who is visiting, and appends a position ID which has been set to itself to the ID of the person who is visiting which has been obtained, and dispatches it; a signal destination information database which, in the information distribution system which includes the information distribution server which is connected to the device for obtaining the ID of a person who is visiting, establishes a correspondence between signal destination information which specifies a portable terminal which is to become the object of distribution of contents, and the ID of the person who is visiting, and stores it; a signal reception means which receives as position information the ID of the person who is visiting and the position ID which are dispatched from the device for obtaining the ID of a person who is visiting; and a means which reads out contents reads out contents [sic] from a contents database which correspond to the position ID which is included in the position information which the signal reception means receives, and dispatches the contents which have been read out to the signal destination information which corresponds to the ID of the person who is visiting which is included in the position information. |
1. An information distribution server which is used in an information distribution system which comprises a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is information for discriminating the person who is visiting, and appends a position ID which is set to itself to the ID of the person who is visiting which has been obtained and dispatches it, and the information distribution server which is connected to said device for obtaining the ID of a person who is visiting, characterized by comprising: a contents database which stores contents in correspondence to position ID; a signal destination information database which establishes a correspondence between signal destination information, which is information for specifying a portable terminal which is to become the object of distribution of said contents, and said ID of the person who is visiting, and stores it as registration information; a signal reception means which receives as position information said ID of the person who is visiting and said position ID which are dispatched from said device for obtaining the ID of a person who is visiting; a contents reading out means which reads out contents from said contents database which correspond to the position ID which is included in said position information which said signal reception means receives; and a distribution means which reads out from a signal destination information database signal destination information which corresponds to said ID of the person who is visiting which is included in said position information, and dispatches said contents which have been read out by said contents reading out means based upon said signal destination information which has been read out. 2. An information distribution server in an information distribution system which comprises a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is information for discriminating the person who is visiting, and appends a position ID which is set to itself to the ID of the person who is visiting which has been obtained and dispatches it, a signal reception device which is provided within one or a plurality of enterprises for receiving contents and outputting them, and the information distribution server which distributes said contents, characterized by comprising: a contents database which stores contents in correspondence to position ID; a signal destination information database which establishes a correspondence between signal destination information, which is information for specifying said signal reception device which is to become the object of distribution of said contents, and said position ID, and stores it; a signal reception means which receives as position information said ID of the person who is visiting and said position ID which are dispatched from said device for obtaining the ID of a person who is visiting; a contents reading out means which reads out contents from said contents database which correspond to the position ID which is included in said position information which said signal reception means receives; and a distribution means which reads out from a signal destination information database signal destination information which corresponds to said position ID which is included in said position information, and dispatches said contents which have been read out by said contents reading out means based upon said signal destination information which has been read out. 3. An information distribution server in an information distribution system which comprises a portable terminal which is carried by a person who is visiting, a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is said information for discriminating the person who is visiting, and appends a position ID which is set to itself to the ID of the person who is visiting which has been obtained and dispatches it, a signal reception device which is provided within one or a plurality of enterprises and which receives contents and outputs them, and the information distribution server which distributes said contents, characterized by comprising: a contents database which stores, in correspondence to said position ID, contents for use by a signal reception device, for dispatch to said signal reception device, and contents for use by a portable terminal, for dispatch to said portable terminal, which have relevance relative to said contents for use by a signal reception device; a signal destination information database which, along with establishing a correspondence between signal destination information of a signal reception device, which is information for specifying said signal reception device which is to become the object of distribution of said contents, and said position ID, and storing it, also establishes a correspondence between signal destination information of a portable terminal, which is information for specifying said portable terminal which is to become the object of distribution of said contents, and said ID of the person who is visiting, and stores it; a signal reception means which receives as position information said ID of the person who is visiting and said position ID which are dispatched from said device for obtaining the ID of a person who is visiting; and a means for reading out contents, which reads out from said contents database contents for use by a signal reception device and contents for use by a portable terminal which correspond to the position ID which is included in said position information which said signal reception means receives; and a distribution means which, along with reading out from a signal destination information database signal destination information of a signal reception device which corresponds to said position ID which is included in said position information, and dispatching said contents for use by a signal reception device which have been read out by said contents reading out means based upon said signal destination information of said signal reception device which has been read out, also reads out from a signal destination information database signal destination information of a portable terminal which corresponds to said ID of the person who is visiting which is included in said position information, and dispatches said contents for use by a portable terminal which have been read out by said contents reading out means based upon said signal destination information of said portable terminal which has been read out. 4. An information distribution server as described in any one of claim 1 through claim 3, characterized in that: category information which specifies a category of the person who is visiting and is carrying said portable terminal is set in said ID of the person who is visiting; distribution category information is further set in advance in said contents which designates a category of the object of distribution; and said distribution means, when distributing said contents, distributes information for distribution to the portable terminal for which has been set signal destination information for which category information is set which corresponds to the distribution category information which has been set in said information for distribution. 5. An information distribution server which is used in an information distribution system which comprises a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is information for discriminating the person who is visiting, and the information distribution server which is connected to said device for obtaining the ID of a person who is visiting, characterized by comprising: a contents database which stores contents for which distribution category information which designates a category of the object for distribution has been set in advance; a signal destination information database which establishes a correspondence between signal destination information, which is information for specifying a portable terminal which is carried by the person who is visiting and is to become the object of distribution of said contents, category information which specifies a category of the person who is visiting and is carrying said portable terminal, and said ID of the person who is visiting, and stores it; a signal reception means which, if a recording medium upon which said ID of the person who is visiting is stored is approached by said person who is visiting to within a region in which reading in by said device for obtaining the ID of a person who is visiting is possible, receives from said device for obtaining the ID of a person who is visiting the ID of the person who is visiting which is obtained by said device for obtaining the ID of a person who is visiting; a contents reading out means which reads out signal destination information and category information which correspond to the ID of the person who is visiting which is received by said signal reception means, and reads out contents from said contents database in which distribution category information has been set which corresponds to the category information which has been read out; and a distribution means which dispatches said contents which have been read out to the portable terminal for which said signal destination information which has been read out is set. 6. An information distribution server as described in any one of claims 1-3 and 5, characterized by comprising: a user profile database which stores position information which said signal reception means receives; and a management console means which receives information which indicates that a specified service within a facility has been utilized, and an ID of a person who is visiting and has utilized said service, via said signal reception means as utilization information, and stores said utilization information in a user profile database in correspondence to position information, based upon said ID of the person who is visiting; and in that said management console means further, when it has received position information, detects from said user profile database whether or not a service is already being utilized, based upon said position information which it has received, and, if a service is already being utilized, performs control so as not to dispatch said contents. 7. An information distribution server in an information distribution system in which are provided a plurality of said devices for obtaining the ID of a person who is visiting, and an information distribution server which distributes contents, characterized in that: said information distribution server is the information distribution server of any one of claims 1-3 and 5; and said contents reading out means reads out contents from said contents database which correspond to a history of position information which is stored in said user profile database, based upon an action rule for determining contents to be distributed according to a profile of position information. 8. An information distribution server as described in claim 7, characterized in that: in the position information which is dispatched from the device for obtaining the ID of a person who is visiting, there is included time instant information which indicates the time instant at which said ID of the person who is visiting has been obtained; and said contents reading out means reads out contents from said contents database corresponding to a history of position information which is stored in said user profile database, based upon an action rule for determining contents to be distributed according to a history of position information and the present time instant, or an action rule for determining contents to be distributed according to the passage of time from a time instant that an ID of a person who is visiting has been registered until the present time instant, and said position information. 9. An information distribution server as described in any one of claims 1-3, 5 and 7-8, characterized in that said contents is information for performing guiding within a facility. 10. An information distribution server as described in any one of claims 1-3, 5 and 7-8, characterized in that said contents is information which can be transferred electronically. 11. An information distribution server as described in claim 10, characterized in that said information which can be transferred electronically includes at least one of amusement information, a moving image, a game, a program, an electronic coupon, and a ticket. 12. A recording medium which is used in an information distribution system as described in claims 1-3, 5 and 7-8, and upon which is stored the ID of a person who is visiting, characterized in that: said recording medium provides the ID of the person who is visiting to said device for obtaining the ID of a person who is visiting. 13. A recording medium as described in claim 12, characterized in that said recording medium is an RFID tag. 14. An information distribution method for an information distribution system which comprises a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is information for discriminating the person who is visiting, and appends a position ID which is set to itself to the ID of the person who is visiting which has been obtained and dispatches it, and the information distribution server which is connected to said device for obtaining the ID of a person who is visiting, characterized in that: said ID of the person who is visiting and said position ID which are dispatched from said device for obtaining the ID of a person who is visiting are received as position information; contents, which correspond to the position ID which is included in said position information which is received, are read out from a contents database in which contents are stored in correspondence to position ID; and signal destination information which corresponds to said ID of the person who is visiting which is included in said position information is read out from a signal destination information database, and said contents which have been read out are dispatched to the signal destination information which has been read out. 15. An information distribution method for an information distribution system which comprises a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is information for discriminating the person who is visiting, and appends a position ID which is set to itself to the ID of the person who is visiting which has been obtained and dispatches it, a signal reception device which is provided within one or a plurality of enterprises and which receives contents and outputs them, and the information distribution server which distributes said contents, characterized in that: said ID of the person who is visiting and said position ID which are dispatched from said device for obtaining the ID of a person who is visiting are received as position information and a history of position information is created; contents, which correspond to said history of position information which has been created, are read out from a contents database, based upon an action rule for determining contents which are to be distributed according to a profile of said position information; and signal destination information, which corresponds to said ID of the person who is visiting which is included in said position information, is read out from a signal destination information database which stores signal destination information, which is information for specifying said signal reception device, and the contents which have been read out are dispatched to the signal destination information which has been read out. 16. A recording medium which can be read in by a computer, on which is recorded an information distribution program for an information distribution system which comprises a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is information for discriminating the person who is visiting, and appends a position ID which is set to itself to the ID of the person who is visiting which has been obtained and dispatches it, and an information distribution server which is connected to said device for obtaining the ID of a person who is visiting, for causing a computer to execute: a receiving step of receiving said ID of the person who is visiting and said position ID which are dispatched from said device for obtaining the ID of a person who is visiting as position information; a step of reading out contents, which correspond to the position ID which is included in said position information which has been received, from a contents database; and a step of reading out signal destination information which corresponds to said ID of the person who is visiting which is included in said position information from a signal destination information database, and dispatching said contents which have been read out to the signal destination information which has been read out. 17. A recording medium on which is recorded an information distribution program for an information distribution system which comprises a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is information for discriminating the person who is visiting, and appends a position ID which is set to itself to the ID of the person who is visiting which has been obtained and dispatches it, a signal reception device which is provided within one or a plurality of enterprises and which receives contents and outputs them, and an information distribution server which distributes said contents, for causing a computer to execute: a step of receiving said ID of the person who is visiting and said position ID which are dispatched from said device for obtaining the ID of a person who is visiting as position information, and of creating a history of position information; a step of reading out contents, which correspond to said history of position information which has been created, from a contents database, based upon an action rule for determining contents which are to be distributed according to a history of said position information; and a step of reading out signal destination information, which corresponds to said ID of the person who is visiting which is included in said position information, from a signal destination information database, and of dispatching the contents which have been read out to the signal destination information which has been read out. 18. An information distribution program for an information distribution system which comprises a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is information for discriminating the person who is visiting, and appends a position ID which is set to itself to the ID of the person who is visiting which has been obtained and dispatches it, and an information distribution server which is connected to said device for obtaining the ID of a person who is visiting, for causing a computer to execute: a receiving step of receiving said ID of the person who is visiting and said position ID which are dispatched from said device for obtaining the ID of a person who is visiting as position information; a step of reading out contents, which correspond to the position ID which is included in said position information which has been received, from a contents database; and a step of reading out signal destination information which corresponds to said ID of the person who is visiting which is included in said position information from a signal destination information database, and dispatching said contents which have been read out to the signal destination information which has been read out. 19. An information distribution program for an information distribution system which comprises a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is information for discriminating the person who is visiting, and appends a position ID which is set to itself to the ID of the person who is visiting which has been obtained and dispatches it, a signal reception device which is provided within one or a plurality of enterprises and which receives contents and outputs them, and an information distribution server which distributes said contents, for causing a computer to execute: a step of receiving said ID of the person who is visiting and said position ID which are dispatched from said device for obtaining the ID of a person who is visiting as position information, and of creating a history of position information; a step of reading out contents, which correspond to said history of position information which has been created, from a contents database, based upon an action rule for determining contents which are to be distributed according to a history of said position information; and a step of reading out signal destination information, which corresponds to said ID of the person who is visiting which is included in said position information, from a signal destination information database, and of dispatching the contents which have been read out to the signal destination information which has been read out. |
<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of the Invention This invention is one which relates to an information distribution system which distributes information according to the positions of persons who visit an enterprise. 2. Description of the Related Art For a compound business facility in which a plurality of enterprises such as restaurants, cinemas, goods sales outlets and the like are collected together, it is known to perform guiding to each enterprise within the compound business facility for persons who visit. This guiding is performed, for example, by distributing paper handouts or pamphlets, by posting signs, or the like. Persons who visit this compound business facility take advantage of these guides or distributed materials or the like for roaming the compound business facility according to their own desires, to purchase goods, and to receive services. However, with the above-described method of guidance, the guide information is presented to all the persons who visit within the facility, and it has been difficult to present individualized information to the persons who visit. Furthermore, if posting of signs is utilized, the persons who visit have only been able, in the same place, to obtain information with the same contents. The present invention has been conceived of in the light of this type of circumstance, and its objective is to provide an information distribution server, which can distribute individualized information for distribution according to the positions of persons who are visiting. Furthermore, another objective of the present invention is to provide an information distribution system, which is able to distribute information for distribution according to the history of the path which persons who visit have pursued. |
<SOH> SUMMARY OF THE INVENTION <EOH>In order to implement the above described objectives, the present invention is an information distribution server which is used in an information distribution system which comprises a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is information for discriminating the person who is visiting, and appends a position ID which is set to itself to the ID of the person who is visiting which has been obtained and dispatches it, and the information distribution server which is connected to said device for obtaining the ID of a person who is visiting, characterized by comprising: a contents database which stores contents in correspondence to position ID; a signal destination information database which establishes a correspondence between signal destination information, which is information for specifying a portable terminal which is to become the object of distribution of said contents, and said ID of the person who is visiting, and stores it as registration information; a signal reception means which receives as position information said ID of the person who is visiting and said position ID which are dispatched from said device for obtaining the ID of a person who is visiting; a contents reading out means which reads out contents from said contents database which correspond to the position ID which is included in said position information which said signal reception means receives; and a distribution means which reads out from a signal destination information database signal destination information which corresponds to said ID of the person who is visiting which is included in said position information, and dispatches said contents which have been read out by said contents reading out means based upon said signal destination information which has been read out. Furthermore, the present invention is an information distribution server in an information distribution system which comprises a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is information for discriminating the person who is visiting, and appends a position ID which is set to itself to the ID of the person who is visiting which has been obtained and dispatches it, a signal reception device which is provided within one or a plurality of enterprises and receives contents and outputs them, and the information distribution server which distributes said contents, characterized by comprising: a contents database which stores contents in correspondence to position ID; a signal destination information database which establishes a correspondence between signal destination information, which is information for specifying said signal reception device which is to become the object of distribution of said contents, and said position ID, and stores it; a signal reception means which receives as position information said ID of the person who is visiting and said position ID which are dispatched from said device for obtaining the ID of a person who is visiting; a contents reading out means which reads out contents from said contents database which correspond to the position ID which is included in said position information which said signal reception means receives; and a distribution means which reads out from said signal destination information database signal destination information which corresponds to said position ID which is included in said position information, and dispatches said contents which have been read out by said contents reading out means based upon said signal destination information which has been read out. Furthermore, the present invention is an information distribution server in an information distribution system which comprises a portable terminal which is carried by a person who is visiting, a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is said information for discriminating the person who is visiting, and appends a position ID which is set to itself to the ID of the person who is visiting which has been obtained and dispatches it, a signal reception device which is provided within one or a plurality of enterprises and which receives contents and outputs them, and the information distribution server which distributes said contents, characterized by comprising: a contents database which stores, in correspondence to said position ID, contents for use by a signal reception device, for dispatch to said signal reception device, and contents for use by a portable terminal, for dispatch to said portable terminal, which have relevance relative to said contents for use by a signal reception device; a signal destination information database which, along with establishing a correspondence between signal destination information of a signal reception device, which is information for specifying said signal reception device which is to become the object of distribution of said contents, and said position ID, and storing it, also establishes a correspondence between signal destination information of a portable terminal, which is information for specifying said portable terminal which is to become the object of distribution of said contents, and said ID of the person who is visiting, and stores it; a signal reception means which receives as position information said ID of the person who is visiting and said position ID which are dispatched from said device for obtaining the ID of a person who is visiting; and a means for reading out contents, which reads out from said contents database contents for use by a signal reception device and contents for use by a portable terminal which correspond to the position ID which is included in said position information which said signal reception means receives; and a distribution means which, along with reading out from a signal destination information database signal destination information of a signal reception device which corresponds to said position ID which is included in said position information, and dispatching said contents for use by a signal reception device which have been read out by said contents reading out means based upon said signal destination information of said signal reception device which has been read out, also reads out from a signal destination information database signal destination information of a portable terminal which corresponds to said ID of the person who is visiting which is included in said position information, and dispatches said contents for use by a portable terminal which have been read out by said contents reading out means based upon said signal destination information of said. portable terminal which has been read out. Furthermore, according to the present invention, the above described information distribution server is characterized in that: category information which specifies a category of the person who is visiting and is carrying said portable terminal is set in said ID of the person who is visiting; distribution category information is further set in advance in said contents which designates a category of the object of distribution; and said distribution means, when distributing said contents, distributes information for distribution to the portable terminal for which has been set signal destination information for which category information is set which corresponds to the distribution category information which has been set in said information for distribution. Further, the present invention is an information distribution server which is used in an information distribution system which comprises a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is information for discriminating the person who is visiting, and the information distribution server which is connected to said device for obtaining the ID of a person who is visiting, characterized by comprising: a contents database which stores contents for which distribution category information which designates a category of the object for distribution has been set in advance; a signal destination information database which establishes a correspondence between signal destination information, which is information for specifying a portable terminal which is carried by the person who is visiting and is to become the object of distribution of said contents, category information which specifies a category of the person who is visiting and is carrying said portable terminal, and said ID of the person who is visiting, and stores it; a signal reception means which, if a recording medium upon which said ID of the person who is visiting is stored is approached by said person who is visiting to within a region in which reading in by said device for obtaining the ID of a person who is visiting is possible, receives from said device for obtaining the ID of a person who is visiting the ID of the person who is visiting which is obtained by said device for obtaining the ID of a person who is visiting; a contents reading out means which reads out signal destination information and category information which correspond to the ID of the person who is visiting which is received by said signal reception means, and reads out contents from said contents database in which distribution category information has been set which corresponds to the category information which has been read out; and a distribution means which dispatches said contents which have been read out to the portable terminal for which said signal destination information which has been read out is set. Furthermore, according to the present invention, the above described information distribution server is characterized by comprising: a user profile database which stores position information which said signal reception means receives; and a management console means which receives information which indicates that a specified service within a facility has been utilized, and an ID of a person who is visiting and has utilized said service, via said signal reception means as utilization information, and stores said utilization information in a user profile database in correspondence to position information, based upon said ID of the person who is visiting; and in that said management console means further, when it has received position information, detects from said user profile database whether or not a service is already being utilized, based upon said position information which it has received, and, if a service is already being utilized, performs control so as not to dispatch said contents. Furthermore, the present invention is an information distribution server in an information distribution system in which are provided a plurality of said devices for obtaining the ID of a person who is visiting, and an information distribution server which distributes contents, characterized in that: said information distribution server is the information distribution server of any one of claim 1 through claim 6 ; and said contents reading out means reads out contents from said contents database which correspond to a history of position information which is stored in said user profile database, based upon an action rule for determining contents to be distributed according to a profile of position information. Furthermore, according to the present invention, the above described information distribution server is characterized in that: in the position information which is dispatched from the device for obtaining the ID of a person who is visiting, there is included time instant information which indicates the time instant at which said ID of the person who is visiting has been obtained; and said contents reading out means reads out contents from said contents database corresponding to a history of position information which is stored in said user profile database, based upon an action rule for determining contents to be distributed according to a history of position information and the present time instant, or an action rule for determining contents to be distributed according to the passage of time from a time instant that an ID of a person who is visiting has been registered until the present time instant, and said position information. Furthermore, according to the present invention, the above described information distribution server is characterized in that said contents is information for performing guiding within a facility. Furthermore, according to the present invention, the above described information distribution server is characterized in that said contents is information which can be transferred electronically. Furthermore, according to the present invention, the above described information distribution server is characterized in that said information which can be transferred electronically includes at least one of amusement information, a moving image, a game, a program, an electronic coupon, and a ticket. Furthermore, the present invention is a recording medium which is used in an information distribution system as described in claim 1 through claim 11 , and upon which is stored the ID of a person who is visiting, characterized in that: said recording medium provides the ID of the person who is visiting to said device for obtaining the ID of a person who is visiting. Furthermore, the present invention is characterized in that said recording medium is an RFID tag. Furthermore, the present invention is an information distribution method for an information distribution system which comprises a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is information for discriminating the person who is visiting, and appends a position ID which is set to itself to the ID of the person who is visiting which has been obtained and dispatches it, and the information distribution server which is connected to said device for obtaining the ID of a person who is visiting, characterized in that: said ID of the person who is visiting and said position ID which are dispatched from said device for obtaining the ID of a person who is visiting are received as position information; contents, which correspond to the position ID which is included in said position information which is received, are read out from a contents database in which contents are stored in correspondence to position ID; and signal destination information which corresponds to said ID of the person who is visiting which is included in said position information is read out from a signal destination information database, and said contents which have been read out are dispatched to the signal destination information which has been read out. Furthermore, the present invention is an information distribution method for an information distribution system which comprises a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is information for discriminating the person who is visiting, and appends a position ID which is set to itself to the ID of the person who is visiting which has been obtained and dispatches it, a signal reception device which is provided within one or a plurality of enterprises and which receives contents and outputs them, and the information distribution server which distributes said contents, characterized in that: said ID of the person who is visiting and said position ID which are dispatched from said device for obtaining the ID of a person who is visiting are received as position information and a history of position information is created; contents, which correspond to said history of position information which has been created, are read out from a contents database, based upon an action rule for determining contents which are to be distributed according to a profile of said position information; and signal destination information, which corresponds to said ID of the person who is visiting which is included in said position information, is read out from a signal destination information database which stores signal destination information, which is information for specifying said signal reception device, and the contents which have been read out are dispatched to the signal destination information which has been read out. Furthermore, the present invention is a recording medium which can be read in by a computer, on which is recorded an information distribution program for an information distribution system which comprises a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is information for discriminating the person who is visiting, and appends a position ID which is set to itself to the ID of the person who is visiting which has been obtained and dispatches it, and an information distribution server which is connected to said device for obtaining the ID of a person who is visiting, for causing a computer to execute: a receiving step of receiving said ID of the person who is visiting and said position ID which are dispatched from said device for obtaining the ID of a person who is visiting as position information; a step of reading out contents, which correspond to the position ID which is included in said position information which has been received, from a contents database; and a step of reading out signal destination information which corresponds to said ID of the person who is visiting which is included in said position information from a signal destination information database, and dispatching said contents which have been read out to the signal destination information which has been read out. Furthermore, the present invention is a recording medium on which is recorded an information distribution program for an information distribution system which comprises a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is information for discriminating the person who is visiting, and appends a position ID which is set to itself to the ID of the person who is visiting which has been obtained and dispatches it, a signal reception device which is provided within one or a plurality of enterprises and which receives contents and outputs them, and an information distribution server which distributes said contents, for causing a computer to execute: a step of receiving said ID of the person who is visiting and said position ID which are dispatched from said device for obtaining the ID of a person who is visiting as position information, and of creating a history of position information; a step of reading out contents, which correspond to said history of position information which has been created, from a contents database, based upon an action rule for determining contents which are to be distributed according to a history of said position information; and a step of reading out signal destination information, which corresponds to said ID of the person who is visiting which is included in said position information, from a signal destination information database, and of dispatching the contents which have been read out to the signal destination information which has been read out. Furthermore, the present invention is an information distribution program for an information distribution system which comprises a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is information for discriminating the person who is visiting, and appends a position ID which is set to itself to the ID of the person who is visiting which has been obtained and dispatches it, and an information distribution server which is connected to said device for obtaining the ID of a person who is visiting, for causing a computer to execute: a receiving step of receiving said ID of the person who is visiting and said position ID which are dispatched from said device for obtaining the ID of a person who is visiting as position information; a step of reading out contents, which correspond to the position ID which is included in said position information which has been received, from a contents database; and a step of reading out signal destination information which corresponds to said ID of the person who is visiting which is included in said position information from a signal destination information database, and dispatching said contents which have been read out to the signal destination information which has been read out. Furthermore, the present invention is an information distribution program for an information distribution system which comprises a device for obtaining the ID of a person who is visiting, which obtains an ID of the person who is visiting, which is information for discriminating the person who is visiting, and appends a position ID which is set to itself to the ID of the person who is visiting which has been obtained and dispatches it, a signal reception device which is provided within one or a plurality of enterprises and which receives contents and outputs them, and an information distribution server which distributes said contents, for causing a computer to execute: a step of receiving said ID of the person who is visiting and said position ID which are dispatched from said device for obtaining the ID of a person who is visiting as position information, and of creating a history of position information; a step of reading out contents, which correspond to said history of position information which has been created, from a contents database, based upon an action rule for determining contents which are to be distributed according to a history of said position information; and a step of reading out signal destination information, which corresponds to said ID of the person who is visiting which is included in said position information, from a signal destination information database, and of dispatching the contents which have been read out to the signal destination information which has been read out. |
Compensation of mismatch between quadrature paths |
An apparatus for improving signal mismatch compensation between first and second RF signals comprises: at least one switch which applies a first RF signal, present on a first pathway, and a second RF signal, present on a second pathway, to respective first and second frequency mixers, during a first time period; the mixers provide a first pair of mixed first and second RF signals. Means for reversing the at least one switch, during a subsequent time period is provided so that the first RF signal is applied to the second mixer, via the second pathway, and the second RF signal is applied to the first mixer, via the first pathway. The mixers thereby provide a second pair of mixed first and second RF signals. Monitoring monitors respective first and second pairs of mixed RF signals during an interval. The monitoring means provides time averaged values for the first and second signals in each of said first and second pairs of RF signals, so that effects of signal mismatch on the first and second RF signals are minimised in each channel, by subjecting said RF signals in each channel, for substantially the same time, to the same pathways. |
1. An apparatus for improving signal mismatch compensation, the signal mismatch occurs between first and second RF signals, the apparatus comprising: at least one switch which applies a first RF signal, present on a first pathway, and a second RF signal, present on a second pathway, to respective first and second frequency mixers, during a first time period; the mixers providing a first pair of mixed first and second RF signals; means for reversing the at least one switch, during a subsequent time period, so that the first RF signal is applied to the second mixer, via the second pathway, and the second RF signal is applied to the first mixer, via the first pathway; the mixers thereby provide a second pair of mixed first and second RF signals; monitoring means provided to monitor respective first and second pairs of mixed RF signals during an interval, said interval comprising a plurality of sequential time periods; the monitoring means providing time averaged values for the first and second signals in each of said first and second pairs of RF signals, so that effects of signal mismatch on the first and second RF signals are minimised in each channel, by subjecting said RF signals in each channel, for substantially the same time, to the same pathways. 2. An apparatus according to claim 1 wherein the first and second signals are orthogonal one to another. 3. An apparatus according to claim 2 wherein the first and second signals are encoded quadrature components of an OFDM signal. 4. An apparatus according to claim 1 wherein frequency mixing is performed at a baseband frequency substantially around 20 MHz. 5. An apparatus according to claim 4 wherein means is provided for down conversion from an intermediate to a base-band frequency. 6. An apparatus according to claim 5 wherein the down conversion is achieved by multiplication with a scale factor. 7. An apparatus according to claim 1 wherein two switches are provided, each for the respective first and second channels. 8. An apparatus according to claim 7 wherein the switches he controlled by way of a microprocessor. 9. An apparatus according to claim 8 including at least one flip-flop associated with each channel which receives either of said first or second RF signals. 10. An apparatus according to claim 1 including a frequency mismatch compensator. 11. An apparatus according to claim 10 included in an adaptive Radio Frequency (RF) filter. 12. An apparatus according to claim 1 wherein means is provided for generating a test signal digitally and sending a time domain sample of the test signal to a Digital/Analog Converter (DAC) and subsequently to an RF Transceiver in a test mode. 13. An apparatus according to claim 12 wherein means is provided to route the test signal through the I and Q paths of the transmit chain. 14. An apparatus according to claim 12 wherein means is provided to route the test signal through the I and Q paths of the receive chain. 15. An apparatus according to claim 12 wherein transmit and receive filters are combined to a single set of filters and which are capable of being used in both transmit and receive modes using multiplexers. 16. An apparatus according to claim 12 wherein transmit and receive paths are selected by multiplexers before and after the filters are switched to receive or transmit modes. 17. A method of signal mismatch compensation comprising: applying a first training signal, of known characteristics, to a circuit which includes at least one filter, receiving a filtered training signal, from the circuit, deriving a transfer function from the received filtered signal; obtaining the inverse transfer function and applying the inverse transfer function to a subsequently received signal in order to correct any signal mismatch in the subsequently received signal. 18. A method according to claim 17 wherein transmit and receive filters are combined to form a single set of filters which may be used in both transmit and receive modes, in conjunction with one or more multiplexers. 19. A method according to claim 18 wherein the transmit and receive paths are selected by multiplexers before and after the filters are switched to receive or transmit instants. 20. A method according to claim 17 or 18 wherein a test or training signal is generated digitally and a time domain sample of the test or training signal is sent to a DAC and subsequently to an RF transceiver in a test mode. 21. A method according to claim 20 wherein the test signal is routed through the I and Q paths of the transmit chain. 22. A method according to claim 20 wherein the test signal is routed through the I and Q paths of the receive chain. |
<SOH> BACKGROUND OF THE INVENTION <EOH>As greater demands are placed on RF systems, for example in WLAN's, in order to increase channel capacity by utilizing available bandwidth, corresponding demands are placed upon performance and tolerance of components used in their RF circuits. Various standards have been developed in order to increase channel capacity. HIPERLAN 2 is a Wireless Local Area Network (WLAN) protocol, based on, and incorporating, an Orthogonal Frequency Division Multiplexing (OFDM) scheme. An advantage of using an OFDM scheme for transmitting RF signals is that it is possible to transmit more data for a given channel bandwidth than was previously possible. OFDM transceivers are used in Digital Audio Broadcast (DAB); Digital Video Broadcast (DVB); Asymmetric Digital Subscriber Loop (ADSL) transmission techniques, as well as wireless broadband transmission techniques such as IEEE 802.11A; and the Japanese MMAC standard. Most systems require transmit and receive sections for bidirectional communication. DVB is an exception due to its one way communication nature. The following modulation formats may be incorporated in the HIPERLAN 2 scheme: Binary Phase Shift Keying (BPSK); Quadrature Phase Shift Keying (QPSK); and Quadrature Amplitude Modulation (16 QAM) or 64 QAM. The flexibility of use of the aforementioned modulation techniques means that data rates of between 6 to 54 Mbit/s can be transmitted. A particular advantage of the HIPERLAN 2 scheme, is that systems incorporating it may be used in offices, shops, airports or in similar environments, which were previously prone to multipath dispersion. This is because RF transmissions which use HIPERLAN 2 are reflection resistant. Typically HIPERLAN 2 operates at 5.5 GHz with multiple channels; each channel has 52 active sub-carriers within a 20 MHz bandwidth. OFDM modulation schemes require two component signals to be in phase quadrature. The two component signals are referred to as the I and Q signals. During operation, and following down conversion to a base-band signal, the base-band signal of interest has two 10 MHz side band signals, at which sub-carrier frequencies, the I and Q component signals lie. FIGS. 1 a and 1 b illustrate diagrammatically how close together the sub-carrier channels are one from another. However, because only a relatively small frequency band separates adjacent sub-carrier channels, even small changes in component characteristics can cause variations in the overall behaviour of a device to signals. These changes, which may arise as a result of thermal drift, can give rise to, for example, variations in device characteristics. This in turn can cause cross-talk interference between adjacent sub-carriers. Typically a change in overall absolute tolerance of ±16% of passive components' value, prevents a filter from achieving the required −27dB stop band performance needed in HIPERLAN 2. So as to assist in the understanding of the invention a basic description of Orthogonal Frequency Division Multiplexing (OFDM) is provided with reference to FIGS. 1 to 4 . The time domain signal transmitted to an OFDM transceiver 10 consists of a sum of (K) sinusoidal waveforms of different amplitudes A(i) and phases φ(i). At transmission of the RF signal, digital information is mapped onto the (K) sub-carrier signals or sub-carriers. These signals are then transformed into time domain signals using Inverse Fast Fourier transform (IFFT). Denoting the sampling period T, the duration of the IFFT output block is T u =NT (where N>K). A cyclic extension of length T e can be added before the block, forming a symbol of duration denoted as T p =T u +T e . The sample block is serialized and converted to an analog signal. The sub-carrier spacing is 1T u . The sub-carriers are of overlapping frequencies. However, the IFFT guarantees that data mapped on each frequency can be recovered independently from data carried on the (K-1) other sub-carriers by means of a Fast Fourier Transform (FFT) and that this has no influence on data content of other sub-carriers. This is a result of processing theory. Orthogonal Frequency Division Multiplexing exploits this principle. Hence OFDM ensures very efficient use of available bandwidth for a given data transmission speed. A time domain signal (consisting of successive symbols) is converted from digital to analog and up-converted to an RF center frequency (f c ) using appropriate frequency shifts by way of frequency mixers (not shown). The RF signal is then transmitted through an appropriate medium. Thus, the OFDM signal contains (K) sub-carriers at frequencies f c +i/T u . A received RF signal (R fc ) is translated to a base band signal; converted from analog to a digital signal; and then transformed to the frequency domain using Fast Fourier Transforms after having removed its cyclic extension. Information is recovered in the form A(i) and φ(i). This information is then demapped into its basic elements in order to recover a transmitted digital bit stream. The so-called front end 40 of a receiver down-converts a received signal (in the 5.15-5.725 GHz band) and provides base band information to the digital signal processor device. Conversion can be done in two steps, for example as in a standard heterodyne receiver which uses an appropriate intermediate frequency (IF). After the IF frequency there are two possibilities to convert the analog signal for transportation to analog-to-digital converters (ADC's) 57 and 58 . These are: analog I-Q generation (base band); and down conversion to a second, low intermediate frequency (IF). Analog I-Q generation requires mixing the IF signal using two mixers: one multiplies the signal with a sine function, thereby generating the I signal; and the other multiplies with a signal (of the same frequency) but phase shifted by 90 degrees, such as cosine function, in order to generate the Q signal. All analog treatment during and after this multiplication: such as base-band low pass filtering used for channel selectivity; mixing; amplification and analog to digital conversion; are thereafter subject to mismatch. Base-band low pass filtering is required to eliminate adjacent channels from interfering with the selected signal channel during analog-to-digital conversion. These mismatches are due to slight differences in the values and behavior of active and passive elements found in I and the Q signal paths, even though great care is taken in the design and layout of these elements in a symmetrical way during the design of the system and/or circuit. Mismatches are even more pronounced when the aforementioned effects of thermal drift are taken into account. One way of envisaging down conversion of the RF signal to base-band (I and Q signals) in the receiver, is to imagine that the original RF channel is ‘folded in half’ around the center frequency, such that the (I and Q) base-band signals have effectively half the bandwidth compared with the corresponding RF channel. In base band the original RF center frequency occurs at DC and sub-carriers that were symmetrically located to the left and right of the center frequency (in RF), following down conversion, the subcarriers effectively become superimposed onto each other, so that they occur in pairs on half the number (K/2) of sub-carrier frequencies in base-band. Only precisely matched I and Q signal generation and signal treatment throughout the processing chain, allows correct demodulation of the information to be performed by exact superimposition of sub-carriers. Any mismatch between I and Q signal paths, however small, results in cross-talk between the superimposed sub-carriers. Given the tolerances imposed, such cross-talk reduces the available bandwidth for data transmission and/or introduces unacceptable errors. It will be appreciated that the same criteria apply for transmitter signal processing, however in reverse order. The outcome of this mismatch is that the representation of A(i) and φ(i), of the various sub-carriers may not be correct and can cause decoding errors of the base-band signal. |
<SOH> SUMMARY OF THE INVENTION <EOH>According to a first aspect of the present invention there is provided an apparatus for improving signal mismatch compensation, the signal mismatch occurs between first and second RF signals, the apparatus comprising : at least one switch which applies a first RF signal, present on a first pathway, and a second RF signal, present on a second pathway, to respective first and second frequency mixers, during a first time period; the mixers providing a first pair of mixed first and second RF signals; means for reversing the at least one switch, during a subsequent time period, so that the first RF signal is applied to the second mixer, via the second pathway, and the second RF signal is applied to the first mixer, via the first pathway; the mixers thereby provide a second pair of mixed first and second RF signals; monitoring means provided to monitor respective first and second pairs of mixed RF signals during an interval, said interval comprising a plurality of sequential time periods; the monitoring means providing time averaged values for the first and second signals in each of said first and second pairs of RF signals, so that effects of signal mismatch on the first and second RF signals are minimised in each channel, by subjecting said RF signals in each channel, for substantially the same time, to the same pathways. The first and second signals are orthogonal one to another and may be encoded quadrature components of an OFDM signal. Frequency mixing is advantageously performed at a baseband frequency, typically around 20 MHz, because lower sampling rates are required for processing and processors and samplers which operate around this frequency band, tend to be relatively cheap. Down conversion from an intermediate to a base-band (prior to mixing preserves the digital data) is preferably achieved by multiplication with a scale factor. Preferably two switches are provided, each for the respective first and second channels. Switching may be controlled by way of a micro-processor and is advantageously achieved using a device which includes at least one flip-flop associated with each channel which receives either of said first or second RF signals. A signal mismatch compensator may be incorporated in an adaptive Radio Frequency (RF) filter for filtering first and second RF signals from an OFDM encoded carrier signal. An example of such an adaptive RF filter is described and claimed in the current Assignee's Patent Application, of even filing date, entitled: An Adaptive Filter. In OFDM transceivers, basically two types of analog signal transfer, can be undertaken between the analog transceiver section and the digital transceiver section. In a first method, an analog signal is transported on a low intermediate frequency (IF), for example 20 MHz. In this case each of the OFDM sub-carriers is assigned its own specific frequency. The procedure is also called Intermediate Frequency (IF) sampling. Between analog and digital transceiver sections, the procedure requires one signal path for reception (one ADC) and one signal path for transmission (one DAC). The second of these is illustrated for purposes of assisting better understanding of the invention, in FIG. 3 . In the second method the analog signal is transported in a base-band signal. In this case the OFDM center frequency is at zero Hertz (Hz) and the sub-carriers are symmetrically spaced left and right from the center. Therefore in RF terms they have to ‘share’ the same carrier frequency in base band. These two base band signals are referred to as I and Q signals. They are usually represented as direct and quadrature components of a complex signal. Both I and Q signals are required to transport the complete information. The procedure is also called base-band sampling. According to a second aspect of the invention there is provided a method of signal mismatch compensation comprising: applying a first training signal, of known characteristics, to a circuit which includes at least one filter, receiving a filtered training signal, from the circuit, deriving a transfer function from the received filtered signal; obtaining the inverse transfer function and applying the inverse transfer function to a subsequently received signal in order to correct any signal mismatch in the subsequently received signal. Transmit and receive filters may be combined to form a single set of filters which may be used in both transmit and receive modes, in conjunction with one or more multiplexers. This enables the invention to be used in both half and full-duplex modes. An advantage of this is that compensation training is performed only once and post compensation parameters for receive, as well as precompensation parameters for transmit, are the same. Transmit and receive paths are preferably selected by multiplexers before and after filters are switched to receive or transmit instants of the protocol from a base-band DSP. This second aspect of the invention requires two signal paths for reception, using two Analog to Digital Converters (ADCs); and two signal paths for transmission, using two Digital to Analog Converters (DACs), between the analog and digital transceiver sections. Since in this second aspect, RF signals are transported within half the available OFDM channel bandwidth; signals can be sampled (converted) and processed, with relatively little power consumption. Therefore under particular circumstances, and when applied to some components, (for example filters) it may be more efficient to employ the second aspect of the invention. Means may be provided for generating a test or training signal digitally and sending a time domain sample of the test or training signal to a DAC and subsequently to an RF transceiver in a test mode. This may be achieved by routing the test signal through the I and Q paths of the transmit chain, or routing the test signal through the I and Q paths of the receive chain. This digitally generated test or training signal is advantageously used to compensate frequency mismatch in filters. The aforementioned first aspect of the invention is particularly well suited for use with switches and mixers. Another advantage of the second aspect of the invention is that it has no image channel at down conversion to base-band at reception. The second method however is more difficult to implement for OFDM because it demands high quality matching between the I and Q signal paths, in order to avoid signal impairment. An OFDM transceiver with analog I/Q generation may be envisaged as comprising signal treatment blocks that are essentially down converters, I/Q generators, analog/digital converters (ADC) and digital signal processors (DSP's) for the receive path; digital/analog converters (DAC's); I/Q summation means; and up mixers, for the transmit path. The expressions Digital Signal Processor (DSP's) and base-band controller are used synonymously throughout the present Application. It will be appreciated that DSP architecture may vary from a dedicated state machine to a generic software driven processor. Preferred embodiments of the Invention will now be described, by way of example only, and with a reference to the Figures, in which: |
Screening method |
The invention describes a method wherein therapeutically useful compounds can be identified via the determination of the expression of glycoprotein antigens of the CEACAM family. These have properties that can prevent the development of hyperplastic alterations that have been identified as the precursors of neoplastic transformation and can lead to the development of a carcinoma, or restore the normalization of the tissue. In particular, the present invention relates to a method for the identification of one or more compounds that are suitable for the prevention of tumorigenesis or for the treatment of precursor stages of tumors. The selected compounds are in a position, through regulation of gene expression, to increase the apoptosis sensitivity (or lowers the apoptosis resistance) of cells of the colon mucosa, especially the precursor cells. In addition, the invention is directed towards a diagnostic method and towards the use of cells identified in accordance with the invention in pharmaceutical compounds for the prevention of tumorigenesis and the treatment of precursor stages. |
1-33. (canceled) 34. The method for the identification of compounds capable of altering the CEACAM-1 gene or gene product expression, comprising the steps incubation of a sample, that can express the CEACAM-1 gene or the CEACAM-1 gene product with one of more compounds; incubation of a second sample, that can express the CEACAM-1 gene or the CEACAM-1 gene product in the absence of the compound(s); comparison of the expression of the CEACAM-1 gene or gene product in the samples by the measurement of the rate of apoptosis. 35. A method according to claim 34, characterized in that the sample comprises cells or cell lines which are optionally altered by genetic engineering. 36. A method according to claim 34, wherein the compound increases the expression of CEACAM-1 and CEACAM-7 in its presence compared to its absence. 37. A method according to claim 34, wherein the compound increases the expression of CEACAM-1 and CEACAM-7 in its presence compared to its absence and at the same time the compound lowers the expression of CEA and/or CEACAM-6 in its presence compared to its absence. 38. A method according to claim 34, wherein the determination is at the mRNA level. 39. A method according to claim 34, wherein the determination of expression is at the protein level. 40. A method according to claim 34, characterized in that the compounds that cross-link the CEACAM molecules are identified. 41. A method according to claim 40, characterized in that the compounds are antibodies or polymers. 42. A diagnostic method for the recognition of tumor precursor cells, comprising the step of determination of the expression of one member/members of the CEACAM family in a sample. 43. A diagnostic method according to claim 42, wherein the sample is a cell homogenate or a tissue section. 44. A diagnostic method according to claim 42, characterized in that the expression of CEACAM-1, CEACAM-6, CEACAM-7 and/or CEA is determined. 45. A method according to claim 42, characterized in that the lowering of CEACAM-1 and/or CEACAM-7 expression is determined and/or that the increase in CEACAM-6 and/or CEA expression is determined. 46. A diagnostic kit comprising components for the determination of the expression of one member/members of the CEACAM family according to claim 42. 47. Pharmaceutical compositions containing one or more compounds as the effective compound for the prophylatic treatment of tumors. 48. Pharmaceutical compositions according to claim 47, wherein the tumor is a tumor of the gastrointestinal region. 49. Pharmaceutical compositions according to claim 47, wherein the tumor is a colon carcinoma. 50. Method for the prophylatic treatment of tumors comprising the administration of compounds which increases the expression of CEACAM-1 and/or CEACAM-7 in its presence compared to its absence and/or lowers the expression of CEA and/or CEACAM-6 in its presence compared to its absence. 51. The method according to claim 50, wherein the individuals have a predisposition for the development of tumors. 52. Method according to claim 51, wherein the tumor is a tumor of the gastrointestinal region. 53. Method according to claim 51, wherein the tumor is a colon carcinoma. to its absence and/or lowers the expression of CEA |
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention relates to a method for the identification of compound(s), comprising the steps: incubation of a sample, that can express one or more genes, or one or more gene products, of the CEACAM family with one or more compounds; incubation of a second sample, that can express one or more genes, or one or more gene products, of the CEACAM family in the absence of the compound(s): Comparison of the expression of the gene(s)/gene product(s) of the CEACAM family in the samples. If necessary, the identification of the compound(s) can also be achieved through a determination of the rate of apoptosis in the samples. Compounds that can directly or indirectly regulate an alteration of the expression of one or more genes, or one or more gene products, or which contribute to an increase in the rate of apoptosis of the cells, can be used in a regimen that prevents the development of early precursor lesions that can lead to carcinomas, or treats such precursor lesions. According to the invention, the expression of members of the CEACAM family is used as a parameter to identify substances that influence the expression of antigens. The determination of the rate of apoptosis ran be used in a functional sense to identify compounds that can be used for treatment of the precursor lesions. Moreover, the present invention provides a rest system and kit that enable compounds to be investigated for their capacity to regulate the dysregulation of the expression of members of the CEACAM family, for example to restore expression to the level of an unaltered cell. Furthermore, the test system allows the investigation of substances that influence the signal cascade via a member of the CEACAM family so that the rate of apoptosis is increased, That is to say, compounds can also be identified that, for example, through cross-linking of CEACAM molecules, contribute to a signal transmission that results in an increase in the rate of apoptosis. These substances can be used in pharmaceutical compositions that are used in the prophylactic treatment of tumors in the beginning of carcinogenesis. In addition, the present invention relates to a diagnostic method, comprising the determination of CEACAM expression in test samples. This method permits the identification of precursor lesions at an early stage of tumorgenesis. The invention is based on the new observations that certain molecules in the CEACAM family are important, in a manner not known to date, for the regulation of apoptosis (programmed cell death), but these molecules are unable to perform this regulation as a result of a disruption of their expression in the earliest tissue changes. It was surprisingly found that there is a direct relationship between the expression of members of the CEACAM family, such as CEACAM-1 and CEACAM-7, and the sensitivity of colon cells to apoptosis. |
Method for preparation of vesicles loaded with biological material and different uses thereof |
The present invention discloses a method for an efficient entrapment of active biological material in liposomes. The method is based on the steps of drying a suspension of liposome-forming lipids and then hydrating the dry composition obtained with an aqueous solution containing a biologically active material to be entrapped in high yield in the liposomes thus formed. The invention also concerns liposomal formulations produced by the method of the invention and their uses. |
1-53. (canceled) 54. A method for loading biological material in liposomal vesicles comprising: i) solubilizing at least one liposome-forming lipid in a solvent and freeze-drying the same to effect a dry liposome-forming lipid; ii) providing an aqueous solution of biological material; iii) hydrating the freeze-dried liposome-forming lipid with the solution of the biological material in a manner to effect loading of said biological material in liposomes formed from the liposome-forming lipid. 55. The method of claim 54, wherein said liposome-forming lipid is selected from phospholipids, lipopolymers, cationic lipids, sphingolipids a combination thereof and a combination thereof with membrane active sterols. 56. The method of claim 56, wherein said phospholipids is selected from hydrogenated, partially hydrogenated or non-hydrogenated phospholipids, all derived from a natural source, said natural source is selected from egg, yolk, milk, rice or soybeans. 57. The method of claim 54, wherein said phospholipids are fully synthetic or semi-synthetic phospholipids selected from dimyristoyl phosphatidylcholine (DMPC), dimyristoyl phosphatidylglycerols (DMPG), phosphatidylglycerols, phosphatidylinositols, phosphatidylserines, sphingomyelins, or mixture thereof 58. The method of claim 57, wherein said phospholipids comprise a mixture of DMPC and DMPG. 59. The method of claim 58, wherein said mixture of DMPC and DMPG is at a molar ratio of between 1:20 and 20:1 60. The method of claim 55, wherein said lipopolymers are PEGylated lipids. 61. The method of claim 55, wherein said sphingolipids are sphingomyelins (SPM) selected from egg-derived SPM, milk-derived SPM, N-palmitoyl-SPM, N-stearoyl-SPM, N-oleoyl-SPM (C18:1), N-nervacyl C (C24:1) SPM, N-lignoceryl SPM (C24:0), or a mixture thereof. 62. The method of claim 55, wherein said cationic lipids are monocationic lipids selected from 1,2-dimyristoyl-3-trimethylammonium propane (DMTAP), 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), 1,2-distearoyl-3-trimethylammonium propane (DSTAP), or a polycationic lipid being spermine-based N-[2-[[2,5-bis[(3-aminopropyl)amino]-1-oxopentyl]amino]ethyl]-N,N-dimethyl-2,3-bis[(1-oxo-9-octadecenyl)oxy]-1-propanaminium 1,2-dimyristoyl-3-trimethylammonium propane (DOSPA), or a cationic lipid modified with cholesterol. 63. The method of claim 54, wherein said biological material comprises biological cell structures, cell products, and natural or synthetic biopolymers and/or oligomers. 64. The method of claim 63, wherein said biological cell structures comprise cell membranes, ribosomes, or mitochondriae; and said biopolymers or oligomers are enzymes, proenzymes, cofactors, receptors, virions, or virion surface antigens, bacteria or other pathogens, their membranes, fragments and surface antigens; antigens, antibodies, complement factors, hormones, cytokines, growth factors, nucleotides, DNA, mRNA, rRNA, tRNA, iRNA, antisense DNA or antisense RNA. 65. The method of claim 64, wherein said biological material is an immunoadjuvant. 66. The method of claim 65, wherein said immunoadjuvant is an immunostimulatory oligodeoxynucleotide sequence (ISS-ODN). 67. The method of claim 64, wherein said biological material is an antigen or a mixture of antigens. 68. The method of claim 64, wherein said biological material is a peptide or peptide mixture. 69. The method of claim 64, wherein said biological material is an antisense oligonucleotide. 70. The method of claim 64, wherein said biological material is a cytokine. 71. The method of claim 64, wherein said biological material is a combination of an immunoadjuvant and at least one antigen. 72. The method of claim 54 wherein said solvent is a polar, water miscible solvent or an apolar solvent. 73. The method of claim 72, wherein said polar, water miscible solvent is tertiary-butanol. 74. The method of claim 72, wherein said apolar solvent is cyclohexane. 75. The method of claim 54, wherein said solution of biological material is a solution thereof in sterile water or in a physiologically acceptable aqueous solution selected from the group consisting of 0.9% NaCl, buffered Saline, 5% dextrose, buffered dextrose, 10% sucrose and buffered sucrose. 76. The method of claim 54 for achieving more than 60% loading of biological material in liposomes. 77. A pharmaceutical formulation comprising as active ingredient a therapeutically effective amount of liposomes loaded with a biological material and a pharmaceutically acceptable additive, the loaded liposomes being prepared by the method of claim 54. 78. The pharmaceutical formation of claim 77, wherein said liposomes are formed from liposome-forming lipids, the liposome forming lipids being selected from phospholipids, lipopolymers, cationic lipids, sphingolipids a combination thereof and a combination thereof with membrane active sterols. 79. The pharmaceutical formation of claim 78, wherein said phospholipids is selected from hydrogenated, partially hydrogenated or non-hydrogenated phospholipids, all derived from a natural source, said natural source is selected from egg, yolk, milk, rice or soybeans. 80. The pharmaceutical formation of claim 78, wherein said phospholipids are fully synthetic or semi-synthetic phospholipids selected from dimyristoyl phosphatidylcholine (DMPC), dimyristoyl phosphatidylglycerols (DMPG), phosphatidylglycerols, phosphatidylinositols, phosphatidylserines, sphingomyelins, or mixture thereof. 81. The pharmaceutical formation of claim 78, wherein said phospholipids comprise a mixture of DMPC and DMPG. 82. The pharmaceutical formation of claim 81, wherein said mixture of DMPC and DMPG is at a molar ratio of between 1:20 and 20:1 83. The pharmaceutical formation of claim 78, wherein said lipopolymers are PEGylated lipids. 84. The pharmaceutical formation of claim 78, wherein said sphingolipids are sphingomyelins (SPM) selected from egg-derived SPM, milk-derived SPM, N-palmitoyl-SPM, N-stearoyl-SPM, N-oleoyl-SPM (C18:1), N-nervacyl C (C24:1) SPM, N-lignoceryl SPM (C24:0), or a mixture thereof. 85. The pharmaceutical formation of claim 78, wherein said cationic lipids are monocationic lipids selected from 1,2-dimyristoyl-3-trimethylammonium propane (DMTAP), 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), 1,2-distearoyl-3-trimethylammonium propane (DSTAP), or a polycationic lipid being spermine-based N-[2-[[2,5-bis[(3-aminopropyl)amino]-1-oxopentyl]amino]ethyl]-N,N-dimethyl-2,3-bis[(1-oxo-9-octadecenyl)oxy]-1-propanaminium 1,2-dimyristoyl-3-trimethylammonium propane (DOSPA), or a cationic lipid modified with cholesterol. 86. The pharmaceutical formation of claim 77, wherein said biological material comprises biological cell structures, cell products, and natural or synthetic biopolymers and/or oligomers. 87. The pharmaceutical formation of claim 86, wherein said biological cell structures comprise cell membranes, ribosomes, or mitochondriae; and said biopolymers or oligomers are enzymes, proenzymes, cofactors, receptors, virions, or virion surface antigens, bacteria or other pathogens, their membranes, fragments and surface antigens; antigens, antibodies, complement factors, hormones, cytokines, growth factors, nucleotides, DNA, mRNA, rRNA, tRNA, iRNA, antisense DNA or antisense RNA. 88. The pharmaceutical formation of claim 86, wherein said biological material is an immunoadjuvant. 89. The pharmaceutical formation of claim 88, wherein said immunoadjuvant is an immunostimulatory oligodeoxynucleotide sequence (ISS-ODN). 90. The pharmaceutical formation of claim 87, wherein said biological material is an antigen or a mixture of antigens. 91. The pharmaceutical formation of claim 87, wherein said biological material is a peptide or peptide mixture. 92. The pharmaceutical formation of claim 87, wherein said biological material is an antisense oligonucleotide. 93. The pharmaceutical formation of claim 87, wherein said biological material is a cytokine. 94. The pharmaceutical formation of claim 88, wherein said biological material is a combination of an immunoadjuvant and at least one antigen. 95. The pharmaceutical formation of claim 77, comprising more than 60% of the biological material loaded in said liposomes. 96. A method for the prevention or treatment of a disease comprising administering to a subject in need a therapeutically effective amount of a pharmaceutical formulation according to claim 78. 97. The method of claim 96, wherein said liposomes are formed from a mixture of DMPC and DMPG. 98. The method of claim 97, wherein said mixture of DMPC and DMPG is at a molar ratio of between 1:20 and 20:1. 99. The method of claim 96, wherein said liposomes are formed PEGylated lipids. 100. The method of claim 96, wherein said biological material is an immunoadjuvant. 101. The method of claim 96, wherein said immunoadjuvant is an immunostimulatory oligodeoxynucleotide sequence (ISS-ODN). 102. The method of claim 96, comprising administration of said pharmaceutical formulation in combination with at least one antigen, said antigen being in a free form, or encapsulated in a liposome. 103. The method of claim 96, wherein said pharmaceutical formulation comprises at least 60% of said biological material loaded onto liposomes. 104. The method of claim 96, wherein said effective amount is a dosage of up to 2,000 mg of loaded liposomal vesicles, measured by phospholipid per kg body wt. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Several attempts have been made to use lipid vesicles formed by natural or synthetic phospholipids as vehicles for the administration of effective substances. Proposed clinical uses have included vaccine adjuvanticity, gene transfer and diagnostic imaging, but the major effort has been in the development of liposomes as non-targetable and targetable drug carriers in the treatment of malignancy, and infectious diseases such as fungal infections. Amphotericin B, an effective but toxic antifungal, was the first liposomally formulated agent to be licensed for parenteral use in Europe. Antitumor agents like adriamycin (doxorubicin) have also been incorporated into liposomes. DOXIL (liposomal doxorubicin) is the first liposomal drug approved for parenteral clinical use in the USA. Other liposomal formulations were developed as carriers for vaccines, adjuvants and biological response modifiers like cytokines and others. Liposomes are also utilized as vehicles in the field of gene transfer [Kastel P. L., and Greenstein R. J., Biotechnol. Annu. Rev. 5:197-220 (2000)]. In another application, liposomes were used for the delivery of therapeutic proteins. N. Sakuragawa et al. [Thrombosis Research 38:681-685, (1985); Clinical Hematology 29(5):655-661 (1988)] report that liposomes containing factor VIII have been prepared for oral administration to patients suffering from von Willebrand's disease. The encapsulation of factor VIII was carried out by dissolving the protein factor VIII concentrates in an aprotinin containing solution and transferred into lecithin coated flasks. After drying the flasks by rotation for 30 min under negative pressure liposomes were formed which entrapped factor VIII concentrates. The liposome dispersion was centrifuged yielding 40% of factor VIII entrapped in liposomes. Another method for entrapment of drugs in liposomes is based on a procedure referred to by the term “dehydration-re-hydration”. This is described by C. Kirby and G. Gregoriadis [Bio/Technology, November 1984, pages 979-984]. In this preparation the entrapment was increased by using additional lipid and the use of cholesterol is described as having positive influence on drug entrapment. Yet another method for loading vesicles with biological substances is described by 3.2.2 in U.S. Pat. Nos. 6,066,331 and 6,156,337. According to the method(s) described therein, liposomes loaded with biological structures, biopolymers and/or oligomers, are obtained by codying a fraction of an amphipathic material (liposome-forming lipids) in an organic solvent and a fraction of the biological structure(s), biopolymers and/or oligomers, from an aqueous medium. The present invention aims for the providence of a novel method for efficient encapsulation (>60%) of biological material, particularly those being therapeutically active, into lipid membrane vesicles (liposomes). A group of biological materials of interest according to the present invention are oligonucleotides and, especially, immunostimulatory oligodeoxy-nucleotides and their analogs (ISS-ODN or CpG motifs). Typically, ISS-ODN are short synthetic oligodeoxynucleotides (6-30 bases) usually containing an active 6-mer sequence that has the general structure of two 5′ purines, an unmethylated CpG dinucleotide, and two 3′ pyrimidines (Pu-Pu-CpG-Pyr-Pyr). Bacterial DNA and its synthetic ISS-ODN are known to be potent stimulators of both innate immunity and specific adaptive immune responses, including direct activation of monocytes/macrophages, dendritic cells, NK cells and B cells. Further, bacterial DNA and its synthetic ISS-ODN induce the production of pro-inflammatory cytokines (e.g., IL-6, IL-12, IFNs, TNFα) and up-regulate the expression of MHC I, MHC II and co-stimulatory molecules [Van Uden J., and Raz, E. in Springer Semin. Immunopathol. 22:1-9 (2000)]. In animal studies, ISS-ODNs exhibit strong Thl and mucosal adjuvanticity to a wide range of antigens [McCluskie, M. J., et al. Vaccine, 19:2657-2660 (2001)] or allergens [Horner, A. A., et al. Immunol Rev. 179:102-118 (2001)]. Furthermore, pretreatment with ISS-ODN, even without concomitant administration of the relevant antigen, was shown to afford protection (for about 2 weeks) against subsequent infection with intracellular pathogens [Klinman, D. M., Springer Semin Immunopathol. 22:173-183 (2000)], indicating activation of innate immunity. The immunostimulatory activity of ISS-ODNs requires cellular uptake by endocystosis following their binding to a cell receptor belonging to the Toll-like receptor family, TLR9. Endosomal acidification and digestion of the ODN followed by interaction with specific protein kinases results in rapid generation of reactive oxygen intermediates, leading to activation of MAPK and NF-κB pathways and subsequent is cytokine production (Chu, W., et al. Cell 103:909-918 (2000)]. In mice, doses of 50-100 μg/dose/mouse of soluble ISS-ODN, and in many cases two or more administrations are required to achieve the desired immunomodulatory effects. This relatively high dose and repeated administration, in theory, may cause adverse reactions resulting from the “cytokine storm” induced [Wagner, H., et al. Springer Semin. Immunopathol. 22:167-171 (2000)]. Liposomes can effectively entrap various drugs and biologicals, which are slowly released over an extended period of time in vivo, and are rapidly and efficiently taken up by macrophages and dendritic cells, suggesting that liposomes can serve as an efficient delivery system for biological material such as ISS-ODN-based vaccines [Alving, C R. (1997) in New generation vaccines, 2 nd ed. (Levine, M. M., Woodrow, G. C., Kaper, J. B., and Cobon, G. S., eds.), Marcel Dekker, New York, pp. 207-213; and Kedar, E. and Barenholz, Y. (1998) in The biotherapy of cancers: from immunotherapy to gene therapy (Chouaib S, ed.), INSERM, Paris, pp. 333-362]. Other groups of biological materials of interest according to the present invention are antigens (i.e., vaccines) and immunostimulatory cytokines (e.g., interleukin-2 [IL-2], granulocyte-macrophage colony-stimulating factor [GM-CSF], interferon γ [IFN-γ] It has been shown in several studies that liposomal delivery of vaccines and cytokines markedly enhance their bioactivity in animal models [Alving C. R. (1997) in New generation vaccines, 2 nd ed. (Levine, M. M., Woodrow, G. C., Kaper, J. B., and Cobon, G. S., eds.), Marcel Dekker, New York, pp. 207-213; Kedar, E. and Barenholz, Y. (1998) in The biotherapy of cancers: from immunotherapy to gene therapy (Chouaib S, ed.), INSERM, Paris, pp. 333-362; Gregoriadis, G., McCormack, B., Obrenovic, M., Saffie, R., Zadi, B. and Perrie, Y. Methods 19: 156-162 (1999)]. It should be noted, however, that in these studies, encapsulation in liposomes was carried out by various techniques which are time-consuming, and often result in a low encapsulation efficiency and low stability. |
<SOH> SUMMARY OF THE INVENTION <EOH>The present invention is based on the surprising finding that step wise hydration of lipids, a priori freeze dried, with a solution containing biological material to be loaded into liposomes, results in a very effective loading (≧60%) of the material as compared to hitherto known loading methods. Thus, according to a first of its aspects, the present invention provides a method for loading biological material in liposomes, the method comprises: i) solubilizing (dissolving) at least one liposome-forming lipid in a solvent and drying the same to effect a dry liposome-forming lipid or a mixture of such lipids; ii) providing an aqueous solution of biological material or of a mixture of biological material; iii) hydrating the dry liposome-forming lipid(s) with the solution of biological material to yield liposomes loaded with said biological material. The term “liposome” as used herein includes all spheres or vesicles of amphipathic substance that may spontaneously or non-spontaneously vesiculate, for example, phospholipids which are glycerides where at least one acyl group is replaced by a complex phosphoric acid ester. The term “loading” means any kind of interaction of the biological substances to be loaded, for example, an interaction such as encapsulation, adhesion, adsorption, entrapment (either to the inner or outer wall of the vesicle or in the intraliposomal aqueous phase), or embedment in the liposome's membrane, with or without extrusion of the liposome containing the biological substances. Also as used herein, the term “liposome-forming lipid” denotes any physiologically acceptable amphipathic substance that contains groups with characteristically different properties, e.g. both hydrophilic and hydrophobic properties or a mixture of such molecules, and which upon dispersion thereof in an aqueous medium form liposomal vesicles. As will be further elaborated hereinafter, this term refers to a single amphipathic substance or to a mixture of such substances. The amphipathic substance includes, inter alia, phospholipids, sphingolipids, glycolipids, such as cerebrosides and gangliosides, PEGylated lipids, and sterols, such as cholesterol and others. The terms “dry” or “drying” refer to any manner of drying the liposome-forming lipids which results in the formation of a dry lipid cake. According to one preferred embodiment, drying is achieved by freeze drying, also referred to as lyophilizing. Alternatively, drying may be achieved by spray drying. The term “biological material” used herein refers to any compound or polymer (e.g. biopolymer) or other biological structure having a biological effect on cells or cell constituent (e.g. enzyme, receptor). The biological material may be natural or synthetic and include, inter alia, active or inactive virions, bacteria or other pathogens, and biological cell structures (e.g., subcellular organelles such as ribosomes, membrane fractions, or mitochondriae, cell products (e.g., cytokines), and natural or synthetic biopolymers and/or natural or synthetic biooligomers (i.e., peptides, carbohydrates, and nucleic acids including DNA, RNA and oligonucleotides). The term “solubilizing” which is used herein interchangeably with the term “dissolving” or “dispersing” may be achieved by a single use of the bulk aqueous medium with which said solubilization is achieved. However, this term preferably refers to step-wise addition of two or more aliquots of the said medium. The method of the invention will at times be referred to in the following description by the term “post-encapsulation”, according to which dry lipids are hydrated with an aqueous solution containing the biological material. This is as opposed to the co-encapsulation technique. “Co-encapsulation” is an encapsulation method which includes codying the liposome-forming lipids and the biological material (co-lyophilized) after which they are co-hydrated with an aqueous medium. The co-encapsulation technique is described, inter alia, in U.S. Pat. Nos. 6,156,337 and 6,066,331. One unique feature of the post encapsulation methodology disclosed herein is that it does not necessitate the freeze-dying of the biological material. As may be appreciated, there are numerous biological substances, e.g. proteins that serve as vaccine antigens, or enzymes, which are sensitive to lyophilization, leading to the deactivation of the biological substance. One example of such a sensitive vaccine is the influenza vaccine. In addition, according to the method of the present invention, the biological material does not need to be exposed to an organic solvent or detergent that may be destructive to its activity. For example, dissolution of the influenza virus hemagglutinin molecule in the presence of an organic solvent results in the dissociation of this trimeric protein into its monomers and consequently in loss of its biological activity (immunogenicity). As indicated above and will be further shown in the following Examples, the method of the present invention enables to obtain vesicles with substantially high loading rate of the biological material (at least and preferably more than 60%). This feature is advantageous since it improves efficiency of treatment or prophylaxis with the biological material loaded into the liposomes as well as it enables to reduce the dose and frequency/number of composition administrations required in order to achieve a desired therapeutic effect. Another feature of the method of the present invention is that since the lipid(s) substance(s) and the biological material are kept separately, it enables combinatorial formulations, i.e. the physician may prescribe and the pharmacist may formulate any combination of liposome-forming substance and biological agent, and upon need, the pharmacist can easily prepare the selected combination and prepare the desired formulation, according to the said simple and flexible method steps of the present invention. Yet another feature of the present invention is that the freeze-dried lipids have a long shelf-life at 4° C. or room temperature, preserving their entrapment capability for over a year (as also exemplified in the following Example 4), and that the hydration of the lipids with the solution containing the biological material to form the liposomes is very simple and requires only several minutes. Therefore, the liposomal formulation can be readily prepared before treatment, ensuring high pharmaceutical stability of the formulation and without leakage of the entrapped material from the liposomes. According to a second aspect, there is provided a combination of two compositions, including a first composition comprising dry liposome-forming lipids and a second composition comprising biological material, the combination intended for use in the preparation of a pharmaceutical composition comprising liposomal biological material. The combination of the invention may be provided in the form of a package. Accordingly, the present invention also provides a package for the preparation of a pharmaceutical composition comprising: (a) at least one composition of dry liposome-forming lipid(s); (b) at least one composition of biological material; (c) instructions for selection and use of (a) and (b) for the preparation of said pharmaceutical composition, said instructions comprising hydrating said dry liposome-forming lipid with an aqueous solution of said biological material, to yield a pharmaceutical composition comprising liposomes loaded with said biological material, and (d) instructions prescribing adminison of said pharmaceutical composition to a healthy subject or to a patient in need of said composition. According to another aspect of the invention, there is provided a pharmaceutical composition comprising as active ingredient a therapeutically lo effective amount of biological material loaded onto liposomes; the loaded liposomes being prepared by the method of the invention. The pharmaceutically “effective amount”, including also a prophylactically effective amount, for purposes herein is determined by such considerations as are known in the art. The amount of the biological material must be effective to achieve a is desired therapeutic effect. According to yet a further aspect of the invention there is provided a method for the prevention or treatment of a disease by administration to a subject in need an effective amount of the liposomes loaded with biological material according to the present invention. The terms “prevention or treatment” or “treatment” as used herein refer to administering of a therapeutic amount of the liposome-loaded biological material which is effective to ameliorate undesired symptoms associated with a disease, to prevent the manifestation of such symptoms before they occur, to slow down the progression of the disease, slow down the deterioration of symptoms, to enhance the onset of remission period, slow down the irreversible damage caused in the progressive chronic stage of the disease, to delay the onset of said progressive stage, to lessen the severity or cure the disease, to improve survival rate or more rapid recovery, to prevent the disease form occurring, or a combination of two or more of the above. In addition, the term “treatment” in the context used herein refers to prevention of a disease from occurring. The treatment (also preventative treatment) regimen and the specific formulation to be administered will depend on the type of disease to be treated and may be determined by various considerations known to those skilled in the art of medicine, e.g. the physicians. detailed-description description="Detailed Description" end="lead"? |
Rear seat lock for vehicles |
A rear seat lock, in particular for automobile vehicles, which has an electric operating system based on a motor (23) controlled from a distant position. The lock is concealed by appropriate covers that do not show any visible operating systems to the exterior. |
1. Rear seat lock, particularly for automobiles and similar, with a casing (1) in which a pawl (4) and a trigger (3) are situated and turn, connected to each other by a spring (17) and whose profiles make different contacts in order to cause the opening or closing of a bolt from the bodywork of the vehicle that becomes housed in an opening (8) in the said casing, by means of the change of position of the trigger in relation to the said opening, which is essentially characterised in that the operating system for the pawl (4) that causes the turning of the trigger (3) in order to open or close the lock, is electric and is usually controlled from a position which is distant or remote from the lock in the rear seat. 2. Rear seat lock, in accordance with claim 1, characterised in that an electric motor (23) is used, operated by means of a switch in a position accessible to the driver, and with the lock being without any visible accessories with the exception of the opening (8) for the passage of the bolt from the bodywork of the vehicle and the trigger (3). 3. Rear seat lock, particularly for automobiles and similar, in accordance with claim 1, which is characterised in that the casing (1) which is used for the seating and turning for the pawl (4) and the trigger (3) has a stepping that forms two surface areas, one upper area for the trigger and the pawl and another lower area, in which an opening (15) is created in the said stepping, through which a lower end of the pawl, which also has a stepped shape, has access to the lower surface area, and with this end having a wheel (5) that turns, supported on the profile or edge of a cam (20), mounted on an axis over the said lower surface area, and with a toothed crown wheel (19) being situated over this axis and engaged with a worm screw (27) from the electric motor (23) takeoff shaft, in that the cam, in its turning movements, pulls the pawl (4), and having two microswitches (24, 24′) connected to the said motor, one operated by the most outer end of the cam and the other by the pawl itself on its wheel reaching the said end of the cam. 4. Rear seat lock, in accordance with claim 3, characterised in that the cam (20) has a cutout (26) in which a turret (16) from the toothed crown wheel (19) moves, and in that the cam has a spring (22) secured by one of its ends to the crown wheel. 5. Rear seat lock, in accordance with claim 3, characterised in that on the lower side of the casing and at the rear of the position of the motor, crown wheel and cam, the rocker party (10) for opening the boot has a central cutout (29), in which the end of the arm (9) fixed to the pawl (4) moves. |
Method for making holograms |
A durable holographically imaged paper, plastic film or other product is produced by embossing the image into a thermoplastic coating thereon which comprises plastic pigment particles. The plastic pigment particles are preferably hollow but may be solid. The coating preferably also comprises a thermoplastic polymer or copolymer, for example a copolymer of vinyl acetate and versatic acid, an acrylic polymer, a styrene-acrylic or other acrylic copolymer, a vinyl chloride-vinyl acetate-ethylene terpolymer, a polyvinyl acetate or a polyvinyl alcohol. Preferably, the polymer or copolymer has a glass transition temperature (Tg value) in the range 20° C. to 110° C. The thermoplastic coating may also contain inorganic pigments, for example precipitated calcium carbonate (PCC), ground natural calcium carbonate, or kaolin or other clays, and/or a starch binder. Embossing is preferably carried out directly on the thermoplastic coating by means of a holographically engraved shim. |
1. A method of producing a holographically imaged product by embossing the image into a thermoplastic coating on a substrate, wherein the coating comprises plastic pigment particles. 2. A method as claimed in claim 1, wherein the coating comprises a thermoplastic polymer or copolymer in addition to said particles. 3. A method as claimed in claim 2, wherein the glass transition temperature (Tg value) of the polymer or copolymer is in the range of about 20° C. to about 110° C. 4. A method as claimed in claim 3, wherein the polymer or copolymer is a copolymer of vinyl acetate and versatic acid, an acrylic polymer, a styrene-acrylic or other acrylic copolymer, a vinyl chloride-vinyl acetate-ethylene terpolymer, a polyvinyl acetate or a polyvinyl alcohol. 5. A method as claimed in claim 1, wherein the thermoplastic coating also contains inorganic pigments, for example precipitated calcium carbonate (PCC), ground natural calcium carbonate, or kaolin or other clays. 6. A method as claimed in claim 1, wherein the thermoplastic coating contains a starch binder. 7. A method as claimed in claim 1, wherein the thermoplastic coating contains at least 5% by weight, preferably at least 10% by weight, more preferably at least 15% by weight, of plastic pigment particles on a dry weight basis. 8. A method as claimed in claim 1, wherein at least some of the plastic pigment particles are of the hollow type. 9. A method as claimed in claim 8, wherein the coating comprises 40%-60% thermoplastic (co)polymer, 25%-35% hollow plastic pigment particles, 20%-25% starch and 10%-15% precipitated calcium carbonate by weight on a dry weight basis. 10. A method as claimed in claim 1 wherein the coatweight of the thermoplastic coating is at least 2 gm−2 on a dry basis. 11. A method as claimed in claim 1, wherein embossing is carried out directly on the thermoplastic coating by means of a holographically engraved shim. 12. A method as claimed in claim 11, wherein the embossing pressure is 5×106 Pa (50 bar) or more. 13. A method as claimed in claim 11 wherein the shim is preheated, for example by conventional heating of a roll or other support on which it is mounted. 14. A method as claimed in claim 1, wherein the thermoplastic coating is pre-heated before the embossing operation. 15. A method as claimed in claim 1 wherein the substrate is paper or plastic film. 16. A method as claimed in claim 15, wherein the substrate is an optionally coated white or colored opaque or translucent woodfree paper. 17. A method as claimed in claim 15, wherein the substrate carries one or more coatings to enhance the smoothness of the thermoplastic coating or its bonding to the base substrate. 18. A holographically imaged product produced by a method as claimed in claim 1. 19. The use, in a thermoplastic coating for a sheet or other substrate, of plastic pigment particles for the purpose of enhancing the ability of the coating to accept and retain a holographic image. 20. A coated substrate adapted to be embossed with a holographic image, the coating on the substrate comprising a thermoplastic polymer or copolymer, and, in addition to said polymer or copolymer, a proportion of plastic pigment particles, and, optionally a starch binder and/or inorganic pigment(s). 21. A coated substrate as claimed in claim 20, wherein the glass transition temperature (Tg value) of the polymer or copolymer is in the range of about 20° C. to about 110° C. 22. A coated substrate as claimed in claim 21, wherein the polymer or copolymer is a copolymer of vinyl acetate and versatic acid, an acrylic polymer, a styrene-acrylic or other acrylic copolymer, a vinyl chloride-vinyl acetate-ethylene terpolymer, a polyvinyl acetate or a polyvinyl alcohol. 23. A coated substrate as claimed in claimed in claim 20, wherein the thermoplastic coating contains at least 5% by weight, preferably at least 10% by weight, more preferably at least 15% by weight, of plastic pigment particles on a dry weight basis. 24. A coated substrate as claimed in claim 20, wherein at least some of the plastic pigment particles are of the hollow type. 25. A coated substrate as claimed in claim 24, wherein the coating comprises 40%-60% thermoplastic (co)polymer, 25%-35% hollow plastic pigment particles, 20%-25% starch and 10%-15% precipitated calcium carbonate by weight on a dry weight basis. |
Method for the production of azo compounds |
The invention relates to a method for production of azo compounds. In particular the invention relates to a step-wise method for production of an azo compound, by seeding and oxidation of the corresponding hydrazoic compound. |
1. Method of manufacture of an azo compound (A) comprising a step in which an oxidizing agent is reacted (in accordance with the equation given below) with a hydrazo compound (HA), in a liquid medium, in the presence of a sufficient quantity of crystals of the corresponding azo compound (seeds): where r and r′ in (ha) and (a) can be identical or different, with each representing: a linear or branched alkyl group, preferably a C1-C6 alkyl group, possibly substituted by a hydroxy, alkoxy or carboxy group or by a halogen atom, or a cycloalkyl group preferably with 3 to 6 carbon atoms, possibly substituted by a hydroxy, alkoxy or carboxy group or by a halogen atom, or an aryl group such as phenyl or naphthyl, possibly substituted by a hydroxy, alkyl, alkoxy or carboxy group or by a halogen atom, or an aralkyl group such as benzyl or phenethyl, possibly substituted by one or more alkyl, alkoxy, hydroxy or carboxy groups, or by one or more halogen atoms; or alternatively R and R′ form, with the carbon atom to which it is (or they are) joined, a cycloalkyl radical. 2. Method as claimed in claim 1, characterized in that compound A comprises 2,2′ azobis isobutyronitrile (R═R′═CH3), 2,2′-azobis(2,4-dimethyl-valeronitrile), 2,2′-azobis(2-methylbutyronitrile), 1,1′-azobis(1-cyclohexanecarbonitrile) or 4,4′-azobis(4-cyanopentanoic acid). 3. Method as claimed in claim 1, characterized in that the oxidizing agent comprises chlorine, oxygen, hydrogen peroxide or ozone. 4. Method as claimed in claim 1, characterized in that the liquid medium is aqueous. 5. Method as claimed in claim 1, characterized in that the temperature of the reaction medium is between 15 and 25° C. 6. Method as claimed in claim 5, characterized in that the temperature of the reaction medium is between 18 and 20° C. 7. Method as claimed in claim 1, characterized in that after the oxidation step, the resulting suspension is drained then washed and dried. 8. Method as claimed in claim 1, characterized in that the crystals of compound (A) can be prepared starting from the corresponding compound HA by a conventional method of oxidation followed by n reactions, n being an integer greater than 2, in the course of which compound HA is oxidized in a liquid medium containing a proportion of the suspension resulting from the preceding reaction. 9. Method of claim 8 wherein n is an integer greater in the range from 3 to 5. 10. Method of manufacture of 2,2′-azobis(isobutyronitrile) (AIBN) starting from dihydrocitogen, characterized in that dihydrocitogen, in suspension in an aqueous medium, is oxidized with chlorine in the presence of a sufficient quantity of crystals of 2,2′-azobis(isobutyronitrile) with average grain size between 110 and 180 μm. 11. Method as claimed in claim 10 wherein said average grain size advantageously between 110 and 150 μm. 12. Method as claimed in claim 10, characterized in that the crystals of AIBN (seeds) are present at the start of the oxidation step and represent between 0.5 and 20 wt. %, relative to the reaction medium. 13. Method as claimed in claim 12, wherein the crystals of AIBN represent between 5 and 15 wt. %, relative to the reaction medium. 14. Method as claimed in claim 10, characterized in that the dihydrocitogen suspended in the aqueous medium represents between 2 and 30 wt. % relative to the reaction medium. 15. Method as claimed in claim 14, characterized in that the dihydrocitogen suspended in the aqueous medium represents between 5 and 15 wt. % relative to the reaction medium. 16. Method as claimed in claim 10, characterized in that the temperature of the reaction medium is between 15 and 25° C. 17. Method as claimed in claim 16, characterized in that the temperature of the reaction medium is between 18 and 20° C. 18. Method as claimed in claim 10, characterized in that after the oxidation step, the resulting suspension is drained then washed and dried. 19. Method as claimed in claim 10, characterized in that the crystals of compound (A) can be prepared starting from the corresponding compound HA by a conventional method of oxidation followed by n reactions, n being an integer greater than 2, in the course of which compound HA is oxidized in a liquid medium containing a proportion of the suspension resulting from the preceding reaction. 20. Method of claim 19 wherein n is an integer greater in the range from 3 to 5. |
<SOH> BACKGROUND OF THE INVENTION <EOH>Azo compounds, and notably 2,2′-azobis(isobutyronitrile), are well-known products that are used notably as a blowing agent or synthesis intermediate or initiator of polymerization reactions employing free radicals. These reactions can be reactions of bulk polymerization, solution polymerization, suspension polymerization or emulsion polymerization, and make use of a great variety of monomers, for example (meth)acrylic monomers, vinylic monomers such as acrylamide, acrylonitrile, alkyl (meth)acrylate, styrene, vinyl acetate and chloride, vinylidene chloride. The fields of application are therefore very varied and relate notably (but not exclusively) to acrylic sheets or fibers, flocculents, paints, coating resins, grafted polyols, polystyrene, PVC, PVA, PMMA. Azo compounds are generally obtained by oxidation of the corresponding hydrazo derivatives. After oxidation, the resulting suspension is drained, then dried to give a solid in the form of powder with average grain size generally between 20 and 110 μm. For example, 2,2′-azobis(isobutyronitrile) obtained by reacting the corresponding hydrazo derivative with chlorine, in an aqueous medium, is in the form of powder with average grain size of about 45 μm after drying and the grain size at 10 wt. % (d10) is about 20 μm. Now, azo compounds, in the form described above, pose many problems: they generate dust that may present a risk of explosion and/or an industrial health risk, they have poor castability and problems of lumping are often encountered during storage. The problems identified above are solved partly or completely by the invention. The invention supplies a global solution that makes it possible to increase the average grain size of an azo compound relative to that of a compound obtained by a conventional method of manufacture. The average grain size can be doubled or even trebled. |
<SOH> SUMMARY OF THE INVENTION <EOH>The invention therefore provides a method of manufacture of an azo compound (A), starting from the corresponding hydrazo compound (HA), by seeding. The method according to the invention includes a step in which an oxidizing agent is reacted with a hydrazo compound (HA), in a liquid medium, in the presence of a sufficient quantity of crystals of the corresponding azo compound (seeds). detailed-description description="Detailed Description" end="lead"? |
Use of potent, selective and non toxic c-kit inhibitors for treating mastocytosis |
The present invention relates to a method for treating mastocytosis comprising administering a tyrosine kinase inhibitor to a human in need of such treatment, more particularly a non-toxic, selective and potent c-kit inhibitor, wherein said inhibitor is unable to promote death of IL-3 dependent cells cultured in presence of IL-3. The invention also contemplates a composition for topical application comprising said inhibitor for treating category I mastocytosis. |
1. A method for treating mastocytosis comprising administering a tyrosine kinase inhibitor to a mammalian in need of such treatment, wherein said inhibitor is unable to promote death of IL-3 dependent cells cultured in presence of IL-3. 2. A method according to claim 1, wherein said tyrosine kinase inhibitor is a non-toxic, selective and potent c-kit inhibitor. 3. A method according to claim 2, wherein said inhibitor is selected from the group consisting of indolinones, pyrimidine derivatives, pyrrolopyrimidine derivatives, quinazoline derivatives, quinoxaline derivatives, pyrazoles derivatives, bis monocyclic, bicyclic or heterocyclic aryl compounds, vinylene-azaindole derivatives and pyridyl-quinolones derivatives, styryl compounds, styryl-substituted pyridyl compounds, seleoindoles, selenides, tricyclic polyhydroxylic compounds and benzylphosphonic acid compounds. 4. A method for treating mastocytosis comprising administering a non toxic, potent and selective c-kit inhibitor to a mammalian in need of such treatment, selected from the group consisting of: pyrimidine derivatives, more particularly N-phenyl-2-pyrimidine-amine derivatives. indolinone derivatives, more particularly pyrrol-substituted indolinones, monocyclic, bicyclic aryl and heteroaryl compounds, and quinazoline derivatives, wherein said inhibitor is unable to promote death of IL-3 dependent cells cultured in presence of IL-3. 5. A method according to claim 4, wherein said inhibitor is an inhibitor of activated c-kit selected from a constitutively activated-mutant c-kit and/or SCF-activated c-kit. 6. A method according to claim 5, wherein the activated-mutant c-kit has at least one mutation selected from mutations proximal to Y823, more particularly between amino acids 800 to 850 of SEQ ID No1 involved in c-kit autophosphorylation, notably the D816V, D816Y, D816F and D820G mutants, and a deletion in the juxtamembrane domain of c-kit, preferably between codon 573 and 579. 7. A method for treating mastocytosis comprising administering to a mammalian in need of such treatment a compound that is a selective, potent and non toxic inhibitor of activated c-kit obtainable by a screening method which comprises: a) bringing into contact (i) activated c-kit and (ii) at least one compound to be tested; under conditions allowing the components (i) and (ii) to form a complex, b) selecting compounds that inhibit activated c-kit, c) testing and selecting a subset of compounds identified in step b), which are unable to promote death of IL-3 dependent cells cultured in presence of IL-3. 8. A method according to claim 7, wherein the screening method further comprises the step consisting of testing and selecting a subset of compounds identified in step b) that are inhibitors of mutant activated c-kit, which are also capable of inhibiting SCF-activated c-kit wild. 9. A method according to claim 7, wherein activated c-kit is SCF-activated c-kit wild. 10. A method according to one of claims 7 to 9, wherein putative inhibitors are tested at a concentration above 10 μM in step a). 11. A method according to one of claims 7 to 10, wherein IL-3 is present in the culture media of IL-3 dependent cells at a concentration comprised between between 0.5 and 10 ng/ml, preferably between 1 to 5 ng/ml. 12. A method according to one of claims 7 to 11, wherein the extent to which component (ii) inhibits activated c-kit can be measured in vitro or in vivo. 13. A method according to one of claims 7 to 12 wherein, the screening method further comprises the step consisting of testing and selecting in vitro or in vivo compounds capable of inhibiting c-kit wild at concentration below 1 μM. 14. A method according to claim 13 wherein, wherein the test is performed using cells lines selected from the group consisiting of mast cells, transfected mast cells, BaF3, and IC-2. 15. A method according to claim 13 wherein, wherein the test includes the determination of the amount of c-kit phosphorylation. 16. A method for treating mastocytosis according to one of claims 7 to 12, wherein the screening comprises: a) performing a proliferation assay with cells expressing a mutant c-kit (for example in the transphosphorylase domain), which mutant is a permanent activated c-kit, with a plurality of test compounds to identify a subset of candidate compounds targeting activated c-kit, each having an IC50<10 μM, by measuring the extent of cell death, b) performing a proliferation assay with cells expressing c-kit wild said subset of candidate compounds identified in step (a), said cells being IL-3 dependent cells cultured in presence of IL-3, to identify a subset of candidate compounds targeting specifically c-kit, c) performing a proliferation assay with cells expressing c-kit, with the subset of compounds identified in step b) and selecting a subset of candidate compounds targeting c-kit wild, each having an IC50<10 μM, preferably an IC50<1 μM, by measuring the extent of cell death. 17. A method according to one of claims 1 to 16 for treating category I, II, III and IV mastocytosis in human and any symptom associated with category I, II, III and IV mastocytosis. 18. A method according to claim 17 for treating urticaria pigmentosa, diffuse cutaneous mastocytosis, solitary mastocytoma in human, bullous, erythrodermic and teleangiectatic mastocytosis. 19. A method according to claim 18, wherein the inhibitor is administered topically. 20. A method according to claim 19, wherein a dermatological composition comprising the inhibitor is applied to the skin. 21. A method according to claim 17 for treating mastocytosis with an associated hematological disorder, such as a myeloproliferative or myelodysplastic syndrome, acute leukemia, myeloproliferative disorder associated with mastocytosis, and mast cell leukemia. 22. A method according to one of claims 1 to 16 for treating dog mastocytoma. 23. A composition for topical application comprising a tyrosine kinase inhibitors, more particularly a non toxic, potent and selective c-kit inhibitor. 24. A composition according to claim 23, which is suitable for topical application. 25. A composition according to claim 24, which is in the form of a gel, paste, ointment, cream, lotion, liquid suspension aqueous, aqueous-alcoholic or, oily solutions, or dispersions of the lotion or serum type, or anhydrous or lipophilic gels, or emulsions of liquid or semi-solid consistency of the milk type, obtained by dispersing a fatty phase in an aqueous phase or vice versa, or of suspensions or emulsions of soft, semi-solid consistency of the cream or gel type, or alternatively of microemulsions, of microcapsules, of microparticles or of vesicular dispersions to the ionic and/or nonionic type. 26. A composition according to claim 25, which comprises at least one ingredient selected from hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, emollients, viscosity enhancing polymers, humectants, surfactants, preservatives, antioxidants, solvents, and fillers. 27. Use of a composition according to one of claims 23 to 26 for treating skin disorders in human associated with mastocytosis, notably cutaneous mastocytosis including urticaria pigmentosa, diffuse cutaneous mastocytosis, solitary mastocytoma and bullous, erythrodermic and teleangiectatic mastocytosis. 28. Product comprising at least one tyrosine kinase inhibitor, preferably a c-kit inhibitor, wherein said inhibitor is unable to promote death of IL-3 dependent cells cultured in presence of IL-3 and at least one compound selected from 2-Chloro-2′-desoxyadenosine and analogs thereof for a separate, sequential or simultaneous use for treating category IV mastocytosis including mast cell leukemia. 29. Product comprising at least one tyrosine kinase inhibitor, preferably a c-kit inhibitor, wherein said inhibitor is unable to promote death of IL-3 dependent cells cultured in presence of IL-3 and IFNα for a separate, sequential or simultaneous use for treating systemic forms of mastocytosis, especially category III mastocytosis. |
Method and device for the classfication and cosmetic treatment of wrinkles |
The present invention relates to a method for visuallly determining and classifying the degree of facial wrikledness of the human skin, allowing a cosmetic treatment proportional to the degree of wrinkledness observed. The present invention also relates to a device (1), similar to a slide ruler, which allows a simple and accurate identification and classifation of the degree of facial wrinkledness and the immediate association with a cosmetic treatment appropriate for the degree of wrinkledness observed. |
1. Method for the classification and cosmetic treatment of wrinkles or face wrinkling, comprising: a preliminary visual observation phase of the wrinkles or face wrinkling of an individual, subsequent visual comparison with a wrinkledness scale comprising a series of photographic images or reproductions arranged in increasing order of wrinkledness on a supporting structure, to determine the degree of wrinkledness closest to that observed for said individual, association of the degree of wrinkledness determined in the previous phases with a cosmetic product having an anti-wrinkle activity proportional to the degree of wrinkledness determined in the previous phase, application of a cosmetically effective quantity of said cosmetic product on the areas of the face subject to wrinkles. 2. The method according to claim 1, wherein said wrinkledness scale comprises six degrees of facial wrinkledness. 3. The method according to claim 2, wherein an image of a human face with initial and slight wrinkles corresponds to a first degree of wrinkledness, an image of a face with moderate and fine wrinkles corresponds to a second degree, a face with widely-spread, medium wrinkles corresponds to a third degree, a face with medium/deep wrinkles corresponds to a fourth degree, a face with abundant, deep wrinkles corresponds to a fifth degree and a face with numerous and very deep wrinkles corresponds to a sixth degree. 4. The method according to one or more of the previous claims 13, wherein said cosmetic product comprises an skin anti-wrinkle or anti-aging active principle in increasing quantities and proportional to the degree of wrinkledness observed and classified. 5. The method according to one or more of the previous claims wherein said cosmetic product is RUGASTIR. 6. The method according to claim 5, wherein the local application of RUGASTIR 2.5 is associated with the second degree of wrinkledness; the application of RUGASTIR 3.5 with the third degree of wrinkledness; the application of RUGASTIR 4.5 with the fourth degree of wrinkledness and the application of RUGASTIR 5.5 with the fifth degree of wrinkledness. 7. The method according to claim 6 wherein said RUGASTIR incorporates a biological reactor RB160 with an anti-wrinkle and anti-aging activity of the skin. 8. The method according to one or more of the previous claims comprising the local application of a cosmetically effective quantity of said cosmetic product once or several times a day. 9. A device for classifying the degree of facial wrinkledness, comprising a supporting element on which photographic images or reproductions are arranged, which portray face wrinkling or wrinkles of varying depths, each of said photographic images or reproductions being associated with a product having an anti-wrinkle or anti-aging activity of the skin appropriate for the degree of wrinkledness illustrated or reproduced. 10. The device according to claim 9, wherein said supporting element is substantially rectangular-shaped, with said photographic images or reproductions arranged side by side. 11. The device according to claim 9 or 10, comprising a sliding cursor which moves along said supporting element to determine the photograph image or reproduction which is closest to the degree of face wrinkledness of the person to be treated. 12. The device according to one or more of claims 9-11 characterized in that it is made of transparent plastic material or glass. 13. The device according to claim 9, wherein said supporting element consists of a discoidal element on which said photographic images or reproductions are circumferentially arranged and the cosmetic products associated with each of said images are radially arranged. |
Method of encoding text data to include enhanced speech data for use in a text to speech(tts)system, a method of decoding, a tts system and a mobile phone including said tts system |
A text to speech (TTS) system converts text to speech and involves determining the correct pronunciation. In addition to the correct pronunciation, many TTS systems control how the text is spoken by defining a particular speech mode. A speech mode may be defined as to at least the prosody, i.e. the speech rhythms, stresses on various words, changes in pitch, rate of speaking, changes in volume and how the text is spoken in terms of currency values, dates, times etc amongst other features. The present invention relates to a method for encoding enhanced speech data. The enhanced speech data is simple, easy to use, easy to learn, uses keyboard features already on the terminal device in which the TTS system is embedded and is independent of any of the markup languages or modifications applied when designing the TTS system in situ. Thus, the output text is customised to improve the quality of the speech and enables users to personalise their messages. The present invention thus relates to a method of encoding text data, decoding annotated text data, a TTS system and a mobile phone for implementing these. |
1. A method of encoding text data to include enhanced speech data for use in a text to speech (TTS) system, said method including: adding an identifier to the text data to enable said enhanced speech data to be identified; specifying enhanced speech data; and adding said enhanced speech data to said text data; wherein the improvement lies in that said text data comprises text and initial speech data and said enhanced speech data improves the pronunciation of said text. 2. A method of encoding text data to include enhanced speech data for use in a text to speech (TTS) system as claimed in claim 1, further comprising storing said enhanced speech data and said text data. 3. A method of encoding text data to include enhanced speech data for use in a text to speech (TTS) system as claimed in claim 1, further comprising transmitting said enhanced speech data and said text data. 4. A method of encoding text data to include enhanced speech data for use in a text to speech (TTS) system as claimed in claim 1, in which said specifying said enhanced speech data includes specifying a number of control sequences which includes specifying at least one first control sequence to be open-ended thereby enabling all text to be subject to said first control sequence and/or at least one second control sequence to be closed thereby enabling the text associated with that second control sequence to be subject to that second control sequence and/or at least one third control sequence to be either open-ended or closed. 5. A method of decoding annotated text data which includes enhanced speech data and text data for use in a text to speech (TTS) system, said method comprising: detecting an identifier in the annotated text data to enable said enhanced speech data to be identified; and separating said enhanced speech data from said text data; wherein the improvement lies in that said text data comprises text and initial speech data and said enhanced speech data improves the pronunciation of said text. 6. A method of decoding annotated text data as claimed in claim 5, further comprising: receiving said text data and storing said text data. 7. A method of decoding annotated text data as claimed in claim 5, further comprising: displaying said text. 8. A text to speech (TTS) system for implementing to a method of encoding text data to include enhanced speech data, said method including: adding an identifier to the text data to enable said enhanced speech data to be identified; specifying enhanced speech data; and adding said enhanced speech data to said text data; wherein the improvement lies in that said text data comprises text and initial speech data and said enhanced speech data improves the pronunciation of said text, and a method of decoding annotated text data which includes enhanced speech data and text data, said method comprising: detecting an identifier in the annotated text data to enable said enhanced speech data to be identified; and separating said enhanced speech data from said text data; wherein the improvement lies in that said text data comprises text and initial speech data and said enhanced speech data improves the pronunciation of said text. 9. A TTS system as claimed in claim 8, including means for adding an identifier, a speech data annotator, means for detecting an identifier and a parser for separating the enhanced speech data from the text data. 10. A TTS system as claimed in claim 9, wherein said method of encoding text data to include enhanced speech data further comprises storing said enhanced speech data and said text data, said system further comprising a memory for storing said text data and said enhanced speech data. 11. A TTS system as claimed in claim 9, wherein said method of encoding text data to include enhanced speech data further comprises transmitting said enhanced speech data and said text data, said system further comprising transmission means for transmitting said text data and said enhanced speech data. 12. A mobile telephone including a text to speech system as claimed in claim 8. |
Optical guidance system for invasive catheter placement |
Light from a small laser diode is inserted in a distal end of a catheter and passed through an optical fiber that is either included in the lumen or incorporated into the wall of an invasive catheter tube during manufacture. The light is selected to be of a wavelength that is minimally absorbed by tissue, preferably in the range from about 620 nm to 1100 nm. 780 nm is preferably used as this is where the tissue absorption is near a minimum. The light passes out the end of the fiber (at the proximal end of the catheter) and through the tissue to the outside of the patient's skin where it is measured. The light pattern is observed by night vision goggles that filter out other frequencies of light. The detected light permits location of the end of the fiber, the positional accuracy depending on the thickness of tissue between the fiber tip and the exterior of the body. The method is highly accurate for small children and for catheters within a few centimeters of the skin surface of adults. |
1-16. (canceled) 17. An optical guidance system for directing the placement of an invasive catheter within a patient, comprising: a catheter tube; an optical fiber inserted into said catheter tube so as to extend to a distal end of said catheter tube; and a light source arranged to insert light into said optical fiber whereby the inserted light passes through the optical fiber to the distal end of the catheter when the catheter is inserted in a patient, and the light emitted from the distal end of the inserted catheter passes through the patient's tissue to the outside of the patient's body, whereby the light emitted outside of the patient's body is detected to assist an operator in determining the location of the distal end of the catheter within the patient's body. 18. An optical guidance system as in claim 17, wherein the light source comprises one of an LED and a laser diode that emits light in a wavelength range of 620 nm to 1100 nm. 19. An optical guidance system as in claim 18, wherein the light source emits light at a wavelength of approximately 780 nm. 20. An optical guidance system as in claim 17, further comprising a detection device that receives the light emitted outside of the patient's body. 21. An optical guidance system as in claim 20, wherein said detection device comprises night vision goggles having an interference filter over a detection surface thereof, the interference filter effectively blocking light in wavelength ranges outside of a narrow band including a wavelength range emitted by said light source. 22. An optical guidance system as in claim 21, wherein said goggles include a micro-channel plate imager in a mini-display directly in front of one eye of the operator. 23. An optical guidance system as in claim 20, wherein said detection device comprises at least one of photodiodes, photomultipliers, avalanche photodiodes, and microchannel plates. 24. An optical guidance system as in claim 17, wherein the optical fiber is embedded in a wall of the catheter tube. 25. An optical guidance system as in claim 17, wherein the optical fiber is inserted into a lumen of the catheter tube so as to extend to the distal end of the catheter tube and the optical fiber is held in place during insertion of the catheter tube into a patient. 26. An optical guidance system as in claim 17, further comprising a second optical fiber inserted into said catheter tube and terminating at a terminating position a predetermined distance proximal to a terminating position of said optical fiber and carrying light having at least one of (1) a difference in modulation frequency with light carried by said optical fiber and (2) a difference in wavelength with light carried by said optical fiber, whereby doubling back of said catheter tube during insertion may be determined from positions of the light emitted from the respective optical fibers through the patient's tissue to the outside of the patient's body. 27. A method of determining the location of a distal end of an invasive catheter inserted into a patient, comprising the steps of: inserting into a patient an invasive catheter having an optical fiber inserted therein so as to extend to a distal end of the catheter; inserting light into the optical fiber, whereby the inserted light passes through the optical fiber to the distal end of the catheter when the catheter is inserted in a patient, and the light emitted from the distal end of the inserted catheter passes through the patient's tissue to the outside of the patient's body; detecting light at a surface of the skin of the patient that has been emitted from the distal end of the catheter and passed through the patient's skin to the skin surface; and determining the location of the distal end of the catheter from the light detected at the surface of the patient's skin. 28. A method as in claim 27, wherein the light inserting step comprises the step of inserting light in a wavelength range of 620 nm to 1100 nm into said optical fiber. 29. A method as in claim 28, wherein the light inserting step comprises the step of inserting light at a wavelength of approximately 780 nm into said optical fiber. 30. A method as in claim 27, wherein the detecting step includes the step of viewing the patient's body with night vision goggles having an interference filter over a detection surface thereof. 31. A method as in claim 30, wherein the light inserted into the optical fiber is narrowband light and the determining step includes the step of filtering light emitted by the patient through the interference filter so as to effectively block light in wavelength ranges outside of a wavelength range of the narrowband light inserted into said optical fiber. 32. A method as in claim 30, wherein the detecting step further comprises the step of providing a mini-display in front of one eye of the operator while wearing said goggles. 33. A method as in claim 27, wherein the detecting step comprises the step of detecting light emitted through the patient's skin using at least one of photodiodes, photomultipliers, avalanche photodiodes, and microchannel plates. 34. A method as in claim 27, wherein the optical fiber inserting step comprises the step of embedding the optical fiber in a wall of the catheter. 35. A method as in claim 27, wherein the optical fiber inserting step comprises the steps of inserting the optical fiber into a lumen of the catheter so as to extend to the distal end of the catheter and holding the optical fiber in place during insertion of the catheter into a patient. 36. A method as in claim 27, comprising the additional steps of inserting a second optical fiber into the catheter so that said second optical fiber terminates a predetermined distance short of said distal end of said catheter, inserting light into said second optical fiber that can be distinguished from light inserted into said optical fiber, detecting light emitted through the patient's skin from respective ends of each optical fiber, and determining whether the catheter has “doubled back” on itself during insertion based on the detected locations of light emitted through the patient's skin. |
<SOH> FIELD OF THE INVENTION <EOH>The present invention relates to an optical guidance system and a method for insertion of endotracheal tubing, nasogastric tubing, feeding tubing, epidural catheters, central venous catheters, peripherally inserted central venous catheters, chest tubes plural catheters, and similar invasive catheters and tubes. |
<SOH> SUMMARY OF THE INVENTION <EOH>Light from a small laser diode is passed through an optical fiber that is either included in the lumen or incorporated into the wall of an invasive catheter tube during manufacture. The light is selected to be of a wavelength that is minimally absorbed by tissue, preferably in the range from about 620 nm to 1100 nm. In a preferred embodiment, 780 nm is used as this is where the tissue absorption is near a minimum. The light passes out the end of the fiber (at the distal end of the catheter) and through the tissue to the outside where it is measured. The light pattern is observed by night vision goggles that filter out light in other frequency ranges. The detected light allows location of the end of the fiber, the positional accuracy depending on the thickness of tissue between the fiber tip and the exterior of the body. The method is highly accurate for small children and for catheters near the skin surface of adults but may not be applicable to catheters placed within the body cavity of some large adults. |
Safety device |
A water safety device comprises a sub-surface pressure sensing consisting of a piezo electric transducer (1) located between a sealed chamber (4) and an open chamber (2) that allows water to enter through vents (3). Changes in water pressure will result in a flexing of the piezo electric transducer providing a detectable output to the processor unit (9). The safety device also analyses surface wave motion. A ball (8) is housed within a half sphere vessel (6) that has a rough inner surface. A pimple (7) prevents the ball from remaining stationary. The half sphere vessel (6) has a lid to retain the ball within the “motion detector”. As the floating detection module rocks with the waves the ball (8) will move within the half sphere vessel (6) creating vibrations due to the rough inner surface. These vibrations are sympathy with the wave motion and are detected by the piezo electric transducer (5) located in the base of the “motion detector” within the sealed chamber (4). The piezo electric transducer (5) creates an output to the processor unit (9). The processor algorithm determines the state of alarm by constantly analysing both inputs from the two separate detectors (1,5). In this case, vibrations detected using the above-mentioned second detection method will only trigger an alarm state if a change of water pressure has also been detected by the piezo electric transducer and registered. |
1. A safety device for detecting the introduction and/or presence of a foreign body or object in or on a body of liquid, the safety device comprising first detection means for detecting a first parameter indicating the possible introduction and/or presence of a foreign body or object in or on said body of liquid, second detection means for detecting a second parameter indicating the possible introduction and/or presence of a foreign body in said body of liquid, and means for indicating the introduction and/or presence of a foreign body or object in said body of liquid only in the event that at least both said first and second parameters are detected by said first and second detection means respectively. 2. A safety device according to claim 1, wherein the first parameter comprises underwater pressure change with respect to the body of liquid. 3. A safety device according to claim 1, wherein the second parameter comprises surface motion or vibration of the liquid. 4. A safety device according to claim 1, wherein the indicating means is arranged to transmit an indicator signal (via radio wave transmission or the like) to one or more remote alarm units which emit an alarm signal (whether audible or otherwise) in response to receipt of the indicator signal to alert a third party of the possible introduction to and/or presence of a foreign body in the body of liquid. 5. A safety device according to claim 1, wherein the indicating means is arranged to emit an alarm signal locally. 6. A safety device according to claim 2, wherein the underwater pressure change is detected by one or more piezo electric transducers, or the like. 7. A safety device according to claim 3, wherein the surface motion or vibration of the liquid is detected by one or more piezo electric transducer. 8. A safety device according to claim 4, including a remote wireless receiver for receiving an alarm signal from the indicating means transmitter. 9. A safety device substantially as herein described with reference to the accompanying drawings. |
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