Polymeric micelles for encapsulation of hydrophobic molecules are provided. Methods and formulations for delivering hydrophobic molecules to a host via these micelles are also provided. Methods of stabilizing liposomes or lipid based formulations by addition of polymeric micelles are also provided.

The present invention relates to new hyperbranched colloidal polymers with micellar properties. The polymers comprise a mucic acid, alkyl chains and poly(ethylene glycol). Hydrophobic molecules encapsulated within these polymeric micelles are thermodynamically stable in aqueous solutions, suspensions, dispersions, emollients, lotions, creams, salves, balms and ointments at ambient, refrigerated and elevated temperatures. Further, these polymers have been found to stabilize liposomes and other lipid based structures used routinely in these types of formulations for extended periods of time such that precipitation is prevented and optical transparency is maintained. While the polymers of the present invention can be used to encapsulate and deliver any hydrophobic molecule, these colloids are particularly useful in delivery of hydrophobic drugs via various routes and in the topical delivery of hydrophobic molecules used routinely in cosmetics, toiletries, fragrances, perfumes, skin care products and beauty aids. Such hydrophobic molecules include, but are not limited to, dyes, proteins, vitamins and fragrances.
Micelles are a class of surfactants that form organized structures, referred to as colloidal spheres, in aqueous media. The hydrophobic shell of micelles makes the entire assembly water-soluble while the lipophilic core solubilizes hydrophobic molecules. Attempts have been made to use micelles in drug delivery applications because the lipophilic core serves as a microcontainer for drugs, thereby segregating the drugs from the outer environment by the hydrophilic segments. Micelles or colloids encapsulate the drug, shielding the body from potentially toxic levels of drug while simultaneously protecting the drug from inactivating agents in the blood and lymphatic system. Thus, solubilization of water-insoluble drugs by micelles has long been investigated as a means for improving solubility for drug delivery, in particular for parenteral or oral administration, and also for ophthalmic, topical, rectal and nasal delivery (Florence, A. Techniques of Solubilization of Drugs, Ed. Yalkowsky, S. (New York: Marcel Dekker, 1981); Atwood, D. and Florence, A. T. Pharmaceutical Aspects of Solubilization, Surfactant Systems. Their Chemistry, Pharmacy and Biology, (London: Chapman Hall, 1983):293-387).
However, the formation of micelles is both temperature- and concentration-dependent. The concentration dependency is defined as the critical micelle concentration or CMC. Thus, after micelles are injected into the bloodstream, they begin to equilibrate between the micellar, colloidal structure and individual surfactant molecules. Because of the change in micellar structure and size, control over the release of drugs within the micellar microcontainer cannot be maintained for long periods. Typically drug is released over a period of hours and this release is often inconsistent over this period. Thus, the thermodynamic equilibrium between surfactant and micelles may ultimately cause serious toxicity problems due to potentially large fluctuations in drug concentrations accompanied by the breakdown in micellar structure into surfactant molecules. This dilution is particularly large after oral and intravenous administration and can cause unwanted precipitation of hydrophobic drugs.
Thus, while micelles are frequently evaluated for use as drug delivery systems, there are only a few products on the market that are considered practical. This is due to the eventual aggregation and/or precipitation of drugs resulting from equilibration of micelles back to the monomer and the solubilization capacity being too low to be of practical use.
Attempts have been made to design non-ionic surfactants such as poly(ethylene oxide) containing molecules with improved solubilization characteristics. An early approach involved the production of large micellar systems. However, despite the increased micelle size, solubilization decreased with the longer hydrophobic chains. This decrease was attributed to deleterious changes in the poly(ethylene oxide) chains nearest to the core, the main locus of solubilization for most drugs (Elworthy, P. and Patel, M. J. Pharm. Pharmacol. 1982 34:543).
Liu et al. (Polym. Preprint., 1997 38(2):582-583) report the synthesis of a single species of hyperbranched polymeric micelles for encapsulation of small hydrophobic organic molecules. This species contains no divalent amino acid moiety. Instead, this species comprises a 1,1,1-tris(hydroxyphenyl) ethane moiety and an acylated mucic acid moiety as the divalent dicarboxylic moiety. There remains a need for suitable delivery systems for the administration of hydrophobic molecules.
This need is met by the present invention. The present invention provides new hyperbranched polymer micelles that are useful for solubilizing hydrophobic molecules in water thus greatly simplifying the preparation of aqueous formulations for delivery of such molecules.
Therefore, according to one aspect of the present invention, a polymer is provided having a structure selected from:
R(xe2x80x94Oxe2x80x94R1)x and R(xe2x80x94NHxe2x80x94R1)x,
wherein R(xe2x80x94Oxe2x80x94)x is a polyol moiety and R(xe2x80x94NHxe2x80x94)x is a polyamine moiety, with x being between 2 and 10, inclusive, and each R1 independently has the structure:
wherein
xe2x80x83is a divalent amino acid moiety with R2 being a covalent bond or having from 1 to 8 carbon atoms, and y and z are between 0 and 10, inclusive, provided that y and z are not both 0;
wherein
xe2x80x83is a divalent dicarboxylic acid moiety in which R3 is an alkylene or cycloalkylene group containing from 1 to about 15 carbon atoms substituted with a total of from 1 to about 10 hydroxyl groups, with at least a portion of the hydroxyl groups being acylated with 3 to 24 carbon atom carboxylic acids; and
wherein R4 is a poly(alkylene oxide) having the structure:
R5xe2x80x94(xe2x80x94R6xe2x80x94Oxe2x80x94)axe2x80x94R6xe2x80x94Qxe2x80x94
with R5 being selected from 1 to 40 carbon atom alkyl groups, OH, xe2x80x94OR7, xe2x80x94NH2, xe2x80x94NHR7, xe2x80x94NR7R8, xe2x80x94CH2xe2x80x94OH, xe2x80x94CH2xe2x80x94OR7, xe2x80x94CH2xe2x80x94Oxe2x80x94CH2xe2x80x94R7, xe2x80x94CH2xe2x80x94NH2, xe2x80x94CH2xe2x80x94NHR7 and xe2x80x94CH2xe2x80x94NR7R8;
R6, R7 and R8 being independently selected from 2 to 40 carbon atom, straight chain or branched alkylene groups;
Q being a divalent linkage moiety; and a being between 2 and 110, inclusive;
with the proviso that when y is zero and R is a 1,1,1-tris(hydroxyphenyl) ethane moiety, the divalent dicarboxylic moiety is not an acylated mucic acid moiety.
The polymers of the present invention encapsulate a wide variety of hydrophobic molecules. The encapsulation is a physical encapsulation, and not a simple association of the hydrophobic molecule with the polymer. According to a preferred embodiment of the present invention, upon formation of the encapsulated hydrophobic molecule, the polymer is recovered and rinsed to remove any residue of non-encapsulated hydrophobic molecules.
Therefore, according to another aspect of the present invention, a hydrophobic molecule encapsulated in a polymer is provided, wherein the polymer has a structure selected from:
R(xe2x80x94Oxe2x80x94R1)x, and R(xe2x80x94NHxe2x80x94R1)x
wherein R(xe2x80x94Oxe2x80x94)x is a polyol moiety and R(xe2x80x94NHxe2x80x94)x is a polyamine moiety, with x being between 2 and 10, inclusive, and each R1 independently has the structure:
wherein
xe2x80x83is a divalent amino acid moiety with R2 being a covalent bond or having from 1 to 8 carbon atoms, and y and z are between 0 and 10, inclusive, provided that y and z are not both 0;
wherein
xe2x80x83is a divalent dicarboxylic acid moiety in which R3 is an alkylene or cycloalkylene group containing from 1 to about 15 carbon atoms substituted with a total of from 1 to about 10 hydroxyl groups, with at least a portion of the hydroxyl groups being acylated with 3 to 24 carbon atom carboxylic acids; and
wherein R4 is a poly(alkylene oxide) having the structure:
R5xe2x80x94(xe2x80x94R6xe2x80x94Oxe2x80x94)axe2x80x94R6xe2x80x94Qxe2x80x94
with R5 being selected from 1 to 40 carbon atom alkyl groups, OH, xe2x80x94OR7, xe2x80x94NH2, xe2x80x94NHR7, xe2x80x94NR7R8, xe2x80x94CH2xe2x80x94OH, xe2x80x94CH2xe2x80x94OR7, xe2x80x94CH2xe2x80x94Oxe2x80x94CH2xe2x80x94R7, xe2x80x94CH2xe2x80x94NH2, xe2x80x94CH2xe2x80x94NHR7 and xe2x80x94CH2xe2x80x94NR7R8;
R6, R7 and R8 being independently selected from 2 to 40 carbon atom, straight chain or branched alkylene groups;
Q being a divalent linkage moiety; and
a being between 2 and 110, inclusive;
with the proviso that when y is zero and R is a 1,1,1-tris(hydroxyphenyl) ethane moiety, the divalent dicarboxylic acid moiety is not a mucic acid moiety acylated with carboxylic acids having less than six carbon atoms.
The present invention incorporates the discovery that acylation with carboxylic acids of six carbon atoms or greater produces an unexpected increase in the affinity of the polymer interior for hydrophobic molecules. The polymers of the present invention meet the need for micellar encapsulants for hydrophobic molecules that are thermodynamically stable in aqueous media. In a preferred embodiment, the hydrophobic molecules encapsulated by the polymers are hydrophobic molecules with biological or pharmaceutical activity.
Furthermore, because the polymer encapsulates of the present invention are thermodynamically stable in aqueous media, the present invention also includes aqueous solutions, suspensions and dispersions of polymer encapsulated hydrophobic molecules. Again, the hydrophobic molecules preferably have biological or pharmaceutical activity.
The polymers of the present invention are ideal vehicles for the delivery of hydrophobic molecules to a host via a variety of administration routes, including, but not limited to orally, topically or intravenously. Accordingly, the present invention also includes formulations comprising a polymer of the present invention encapsulating hydrophobic molecules and an acceptable carrier or vehicle. In addition, the present invention includes methods of delivering a hydrophobic molecule to a host by administering to the host a formulation comprising a polymer of the present invention encapsulating hydrophobic molecules and an acceptable carrier or vehicle. Acceptable vehicles for the formulations include, but are not limited to, aqueous solutions, suspensions, dispersions, emollients, lotions, creams, salves, balms and ointments. The polymer encapsulated hydrophobic molecules can also be administered in a solid form by way of a tablet or capsule, for example, to be dissolved in the digestive tract, and, consequently, in the bloodstream. By xe2x80x9chostxe2x80x9d it meant to include both plants and animals including humans.
In a preferred embodiment, formulations are prepared for topical administration. The present invention incorporates the discovery that the encapsulation of hydrophobic molecules by the polymers of the present invention enhances transdermal delivery of the hydrophobic molecule. In fact, absorption through the skin can be increased by a factor of up to 1000. Preferred formulations for transdermal delivery include, but are not limited to aqueous solutions, suspensions, dispersions, aqueous gels and water-in-oil or oil-in-water emulsions. The formulations can also be applied directly to the skin as a lotion, cream or salve, or a transdermal delivery device such as a transdermal patch can be employed, in which the polymer encapsulated hydrophobic molecule is retained in the active agent reservoir of the patch. In addition to hydrophobic drugs, topical formulations are particularly useful in delivery of hydrophobic molecules including, but not limited to, dyes, proteins, vitamins and fragrances, which are used routinely in cosmetics, toiletries, fragrances, perfumes, skin care products and beauty aids.
The polymer encapsulated hydrophobic molecules may be the only active molecule in the topical formulation, or the formulation may contain the hydrophobic molecules stabilized in the formulation by other means, so that the non-encapsulated hydrophobic molecule provides a xe2x80x9cburst effectxe2x80x9d upon initial delivery, followed by a sustained delivery of the polymer-encapsulated molecule.
Therefore, according to another aspect of the present application, a method for transdermal delivery to an animal in need thereof of a hydrophobic molecule having biological or pharmaceutical activity is provided. An effective amount of a topical dosage form containing the hydrophobic molecule encapsulated by the polymer of the present invention and a pharmaceutically acceptable topical carrier, is applied to the skin or mucosa of the animal. Preferred polymers according to the present invention hydrolyze into components known to be biocompatible, i.e., sugars, fatty acids, amino acids and poly(ethylene glycol). This also results in low cytotoxicity of the polymer and its hydrolysis products. The poly(alkylene oxide) units enhance the immunogenicity of the encapsulate, enabling the hydrophobic molecules to evade the body""s immune system, thereby increasing the circulation time of the hydrophobic molecule. This allows for effective treatment with reduced quantities of the hydrophobic molecule, which, together with the enhanced immunogenicity, prevents or reduces the severity and incidence of toxic side effects of the hydrophobic molecules.
The polymeric micelles have also been found to stabilize liposomes and other lipid-based structures for extended periods of time so that precipitation is prevented and the optical transparency of formulations is maintained. Therefore, another aspect of this invention relates to the use of these polymeric micelles in the stabilization of formulations comprising liposomes or other lipid based structures.
The above and other objects, features and advantages of the present invention will become clear from the following description of the preferred embodiment.
The polymers of the present invention are prepared by coupling a plurality of hydrophobic moieties to the hydroxyl groups of a polyol core. The resulting polymer is then made water-soluble by attaching a poly(alkylene oxide) to the end of each hydrophobic moiety.
Polyols that are suitable for use as the polymer core are nearly limitless. Aliphatic polyols having from 1 to 10 carbon atoms and from 1 to 10 hydroxyl groups may be used, including ethylene glycol, alkane diols, alkyl glycols, alkylidene alkyl diols, alkyl cycloalkane diols, 1,5-decalindiol, 4,8-bis(hydroxymethyl)tricyclodecane, cycloalkylidene diols, dihydroxyalkanes, trihydroxyalkanes, and the like. Cycloaliphatic polyols may also be employed, including straight chained or closed-ring sugars and sugar alcohols, such as mannitol, sorbitol, inositol, xylitol, quebrachitol, threitol, arabitol, erythritol, adonitol, dulcitol, facose, ribose, arabinose, xylose, lyxose, rhamnose, galactose, glucose, fructose, sorbose, mannose, pyranose, altrose, talose, tagitose, pyranosides, sucrose, lactose, maltose, and the like. More examples of aliphatic polyols include derivatives of glyceraldehyde, glucose, ribose, mannose, galactose, and related stereoisomers.
Aromatic polyols are preferred because of their hydrophobicity. Among the suitable aromatic polyols are 1,1,1-tris(4xe2x80x2-hydroxyphenyl) alkanes, such as 1,1,1-tris(4-hydroxyphenyl)ethane, (1,3-adamantanediyl)diphenol, 2,6-bis(hydroxyalkyl)cresols, 2,2xe2x80x2alkylene-bis(6-t-butyl-4-alkylphenols), 2,2xe2x80x2-alkylene-bis(t-butylphenols), catechol, alkylcatechols, pyrogallol, fluoroglycinol, 1,2,4-benzenetriol, resorcinol, alkylresorcinols, dialkylresorcinols, orcinol monohydrate, olivetol, hydroquinone, alkylhydroquinones, 1,1-bi-2-naphthol, phenyl hydroquinones, dihydroxynaphthalenes, 4,4xe2x80x2-(9-fluorenylidene)-diphenol, anthrarobin, dithranol, bis (hydroxyphenyl) methane biphenols, dialkylstilbesterols, bis(hydroxyphenyl)alkanes, bisphenol-A and derivatives thereof, meso-hexesterol, nordihydroguaiaretic acid, calixarenes and derivatives thereof, tannic acid, and the like.
Other core polyols that may be used include crown ether, cyclodextrins, dextrins and other carbohydrates such as starches and amylose. Alkyl groups may be straight-chained or branched, and may contain from 1 to 10 carbon atoms.
Hydrophobic moieties are coupled to two or more of the core polyol hydroxyl groups. Preferably, all of the hydroxyl groups of the core polyol are coupled to a hydrophobic moiety.
According to one embodiment of the present invention, the hydrophobic moiety is a dicarboxylic acid moiety containing from 1 to about 10 carbon atoms and substituted with from 1 to about 10 hydroxyl groups, wherein at least a portion of the hydroxyl groups are acylated with 3 to 24 carbon atom carboxylic acids. One carboxylic acid group of the dicarboxylic acid is coupled to a hydroxyl group of the core polyol by way of an ester linkage, while the other carboxylic acid group remains free for coupling to the poly(alkylene oxide). The dicarboxylic acid may be a straight chained or branched, aliphatic or cycloaliphatic, dicarboxylic acid. Suitable aliphatic dicarboxylic acids include mucic acid, malic acid, citromalic acid, alkylmalic acid, hydroxy derivatives of glutaric acid, and alkyl glutaric acids, tartaric acid, citric acid, hydroxy derivatives of furnaric acid, and the like. Alkyl groups may be straight-chained or branched and may contain from 1 to 10 carbon atoms. The cycloaliphatic dicarboxylic acids include dicarboxylic acid derivatives of sugar alcohols.
The carboxylic acids acylating the hydroxyl groups of the dicarboxylic acids preferably contain from 6 to 24 carbon atoms. Preferably, every hydroxyl group of a dicarboxylic acid is acylated with a carboxylic acid.
The polyol coupled to two or more acylated dicarboxylic acid branches forms the hydrophobic core of the polymer of the present invention. According to another embodiment of the present invention, the volume of the cavity formed by the hydrophobic core of the polymer may be increased by inserting an amino acid or peptide linkage between the core polyol and each hydrophobic moiety. That is, a linkage as small as one amino acid up to the size of an oligopeptide containing 10 amino acid residues may be attached to each core polyol hydroxyl group or polyamine amino group, with the hydrophobic moiety being coupled to the end of the amino acid or peptide opposite the core polyol hydroxyl group or polyamine amino group.
The carboxylic acid terminus of an amino acid or peptide is coupled to a hydroxyl group of the core polyol by an ester linkage or an amino group of a core polyamine by an amide linkage. A carboxylic acid group of the acylated dicarboxylic acid is then coupled to the amine terminus of the amino acid or peptide by an amide linkage. The other carboxylic acid group again remains free for coupling to a poly(alkylene oxide). The number of amino acids employed in each peptide linkage should not be so great as to render the entire polymer water-insoluble. A peptide linkage containing from 3 to 6 amino acids is preferred. Preferred amino acids include lysine, serine, threonine, cysteine, tyrosine, aspartic acid, glutamic acid and arginine. Like the other components of the polymers of the present invention, the amino acid linkages also hydrolyze to form biocompatible degradation products.
The free carboxylic acids on the end of each hydrophobic branch on the polyol core are then coupled to a poly(alkylene oxide). The poly(alkylene oxides) are preferably coupled to the free carboxylic acids by either ester or amide linkages. The alkylene oxide units contain from 2 to 4 carbon atoms and may be straight, chained or branched. Poly(ethylene glycol) (PEG) is preferred. Alkoxy-terminated poly(alkylene oxides) are preferred, with methoxy-terminated poly(alkylene oxides) being more preferred.
The poly(alkylene oxide) preferably has between about 2 and about 110 repeating units. A poly(alkylene oxide) having between about 50 and about 110 repeating units is more preferred.
The polymers of the present invention are prepared by first acylating the hydroxyl substituted dicarboxylic acid. The dicarboxylic acid is reacted with a stoichiometric excess of the appropriate acyl chloride in the presence of a catalyst, if needed, such as ZnCl2 with heating, up to the reflux temperature of the reaction mixture. Those of ordinary skill in the art will understand that the appropriate acyl chloride will have from about 2 to about 24, and preferably from about 6 to about 24, carbon atoms.
The reaction continues until substantially complete, approximately 5 hours, after which the reaction product is extracted into an ether such as diethyl ether, followed by washing of the ether fraction with water, drying and evaporation. The resulting crude product is the purified by recrystallization.
The acylated dicarboxylic acid is then coupled to a core polyol by means of a carbodiimide-mediated coupling reaction. The core polyol and a stoichiometric excess of the acylated dicarboxylic acid are dissolved in a common solvent, such as an ether, for example, diethyl ether. Carbodiimide-mediated coupling reactions are disclosed in Bodanszky, Practice of Peptide Synthesis, (Springer-Verlag, New York, 1984) at page 145. A quantity of a solution providing a molar equivalent of a carbodiimide and N,N-dimethylaminopyridine (DMAP) for each polyol hydroxyl group, dissolved in a common solvent such as methylene chloride, is added to the reaction mixture. The reaction proceeds rapidly to completion, after which the urea side-product corresponding to the carbodiimide is removed by suction filtration. The filtrate solution is then washed and dried, and the reaction solvent is then evaporated to recover the crude reaction product. The crude product is then purified, for example, by flash chromatography.
Carbodiimides suitable for use with the present invention include dicyclohexylcarbodiimide (DCC) 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, 1-alkyl-3-(3-dimethylaminopropyl)carbodiimide(alkyl=isopropyl, cyclochexyl), 1-cyclohexyl-3-(2-morpholinyl-(4-ethyl))carbodiimide, 1-cyclohexyl-3-(4-diethylaminocyclohexyl)carbodiimide, 1-cyclohexyl-3-(diethylaminoethyl)carbodiimide, 1,3-di-(4-diethyl aminocyclohexyl)carbodiimide, 1-alkyl-3-(3-morpholinyl-(4-propyl))carbodiimide (alkyl=methyl, ethyl), 1-benzyl-3-(3-dimethylamino-(N)-propyl)carbodiimide, and 1-ethyl-3-(4-azonia-4,4-dimethylpentyl)carbodiimide. In each case, the carbodiimide is used as the free base or a salt (HCl, methiodide, metho-p-toluenesulfonate, and the like). The preferred carbodiimide is DCC.
Carbodiimide-mediated coupling reactions are also used to create an amino acid or peptide linkage between the core polyol hydroxyl groups or core polyamine amino groups and the acylated dicarboxylic acids. The coupling reaction is first performed between the core polyol or polyamine and the amino acid or peptide, after which the amino acid or peptide-branched polyol or polyamine is then reacted with the acylated dicarboxylic acid in another carbodiimide-mediated coupling reaction.
The poly(alkylene oxide) chains are then attached by reacting the substituted core polyol or polyamine with an activated poly(alkylene oxide) in another carbodiimide-mediated coupling reaction. To attach the poly(alkylene oxide) chains by way of an amide linkage, poly(alkylene oxide) amines are employed. For an ester linkage, a poly(alkylene oxide) is employed. For an anhydride linkage, a poly(alkylene oxide) carboxylic acid is employed. Other linkages represented by Q in the above formulas that are suitable for use with the present invention are well known to those skilled in the pegylation art and require no further description.
A reaction mixture of the substituted core polyol and the activated poly(alkylene oxide) in a common solvent such as methylene chloride is formed. A quantity of a solution providing a molar equivalent of carbodiimide and DMAP for each substituted hydroxyl group of the core polyol, dissolved in a common solvent such as methylene chloride, is then added to the reaction mixture. The reaction mixture is maintained at room temperature with stirring for at least 12 hours, after which it is evaporated to dryness, followed by purification, for example by recrystallization, followed by flash chromatography.
The polymers of the present invention have a number average molecular weight between about 1,000 and about 100,000 daltons, measured by Gel Permeation Chromatography relative to polystyrene standards. Molecular weights between about 2,500 and about 25,000 daltons are preferred.
The resulting polymers may be used for essentially any application in which conventional micelles are employed. Examples include drug solubilization, fragrance encapsulation, passive targeting for drug delivery, waste water treatment, enhanced capillary electrophoresis activation, and induction of protein crystallization. Alkali metal cations may also be encapsulated by the polymer to form solvent-free polymer-salt complex solid electrolytes.
Polymeric micelles, unlike conventional micelles, do not have properties that are dependent on concentration or temperature. Thus, polymeric micelles do not have a CMC. Typical micelles can only encapsulate hydrophobic moieties when above the CMC and within a specific temperature range. In contrast, the polymeric systems of the present invention are useful at concentrations typically well below that of micelles in current use. For example, effective liposome stabilization has been achieved at 10xe2x88x9210 M. Use of the polymeric micelles to encapsulate these hydrophobic molecules thus provides multiple advantages. Specifically, the polymeric micelles act as dispersing agents for hydrophobic molecules such as dyes, fragrances, proteins, vitamins and biologically active molecules thus providing a more even distribution as compared to currently available technologies such as detergents, micelles, surfactants, fatty acids, lipids, amphiphiles and colloids. The polymeric micelles also have the ability to stabilize liposomes, emulsions, solutions, suspensions, dispersions, aqueous gels, water-in-oil or oil-in-water emulsions, and microemulsions for extended periods of time at ambient, refrigerated and elevated temperatures. Further, the spherical architecture of the polymeric micelles as opposed to agents with a linear architecture such as lipids and amphiphiles, is believed to increase lubricating ability by decreasing solution viscosity. Polymeric micelles of the present invention also have the ability to encapsulate extremely hydrophobic molecules such as lidocaine and naphthalenes. Because the hydrophobic moieties are encapsulated, they become completely water-soluble thus enhancing their absorption upon topical application. Aqueous solutions of the polymeric micelle encapsulated hydrophobic molecules are transparent and do not require addition of other solubilizing agents. Finally, the polymeric micelles have been demonstrated to be non-toxic to cells such as fibroblasts and are believed to be completely biocompatible.
According to one embodiment of the present invention, hydrophobic molecules are encapsulated by dissolving the hydrophobic molecules and the polymer in a common solvent, such as methylene chloride. The solvent is then removed, for example, by rotoevaporation. The resulting solid is then washed thoroughly with a non-polar solvent such as hexane, to remove any residual non-encapsulated hydrophobic materials. The washed solid is then thoroughly dried, preferably under vacuum, to completely remove any adsorbed solvent, and to obtain the essentially pure polymer-encapsulated hydrophobic material.
According to an alternative embodiment, the polymer of the present invention is dissolved in water, and an excess quantity of the hydrophobic material is added to the aqueous solution, with stirring. After allowing the hydrophobic material sufficient contact with the aqueous polymer solution, the excess hydrophobic material is permitted to separate from the aqueous solution, after which it is removed. The polymer-encapsulated material may then be kept in this aqueous solution, or the aqueous solution may be concentrated, or the polymer encapsulate may be recovered in dry form by evaporating the water.
When the water is evaporated, the dried polymer may be subjected to non-polar solvent rinsing to remove any residual hydrophobic material and further evaporation to remove any residual adsorbed non-polar solvent.
The present invention contemplates the use of polymer-encapsulated hydrophobic molecules at concentrations as high as 1 M and greater, up to 106 M. At the same time, another advantage of the present invention is the thermodynamic stability of the polymers, which permit the formation of low concentration stable aqueous solutions of the polymer encapsulates, far below the CMCs of conventional surfactants. Stable aqueous solutions as low as 10xe2x88x9210 M have been obtained, although, at present, concentrations of 10xe2x88x928 and greater are expected to have the greatest commercial utility. The polymers of the present invention are believed to form stable aqueous encapsulate solutions below the presently available limits of detection, i.e., below 10xe2x88x9210 M.
In a preferred embodiment of the present invention, the polymers are used to solubilize hydrophobic molecules with biological or pharmaceutical activity for drug delivery.
Pharmaceutical dosage forms of polymer-encapsulated hydrophobic molecules having biological or pharmaceutical activity may be formulated using physiologically acceptable carriers, excipients, stabilizers and the like, and may be provided in sustained release or timed release formulation. Acceptable carriers, excipients and diluents for therapeutic use are well known in the pharmaceutical field, and are described, for example, in Remington""s Pharmaceutical Science (A. R. Gennaro Edit., Mack Publishing Co., 1985). Such materials are non-toxic to the recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate, acetate and other organic acid salts, antioxidants such as ascorbic acid, low molecular weight (less than about 10 residues) peptides such as polyarginine, proteins, such as serum albumin, gelatin and immunoglobulins, hydrophilic polymers such as poly(vinyl pyrrolidinone), amino acids such as glycine, glutamic acid, aspartic acid and arginine, monosaccharides, disaccharides, and other carbohydrates, including cellulose and its derivatives, glucose, mannose and dextrines, chelating agents such as EDTA, sugar alcohols such as mannitol and sorbitol, and conventional cationic and nonionic surfactants such as TWEEN, PULRONICS, and PEG.
Dosage formulations to be used for therapeutic administration must be sterile. Sterility is readily accomplished by filtration through sterile membranes, or by other conventional methods such as irradiation or treatment with gases or heat. The pH of the dosage formulations of this invention typically will be between 3 and 11, and more preferably from 5 to 9.
Hosts in need of treatment (typically mammalian) using the dosage formulations of this invention can be administered dosages that will provide optimal efficacy. The dose and method of administration will vary from subject to subject and be dependent upon such factors as the type of host being treated, and in the case of animals, its sex, weight, diet, concurrent medication, overall clinical condition, the particular hydrophobic compounds employed, the specific use for which these compounds are employed, and other factors which those skilled in the arts will recognize.
Therapeutically effective dosages may be determined by either in vitro or in vivo methods. For each particular dosage form of the present invention, individual determinations may be made to determine the optimal dosage required. The range of therapeutically effective dosages will naturally be influenced by the route of administration, the therapeutic objectives, and the condition of the host. For the various suitable routes of administration, the absorption efficiency must be individually determined for each hydrophobic compound by methods well known in pharmacology. Accordingly, it may be necessary for the therapist to titer the dosage and modify the route of administration as required to obtain the optimal therapeutic effect. The determination of effective dosage levels, that is, the dosage levels necessary to achieve the desired result, will be within the ambit of one skilled in the art.
Typically, applications of compound are commenced at lower dosage levels, with dosage levels being increased until the desired effect is achieved.
A typical dosage might range from about 0.001 mg to about 1,000 mg of hydrophobic material, per kg of patient weight. Preferred dosages range from about 0.01 mg/kg to about 100 mg/kg, and more preferably from about 0.10 mg/kg to about 20 mg/kg. Advantageously, the dosage forms of this invention may administered several times daily, and other dosage regimens may also be useful.
The dosage formulations of this invention may be prepared for storage under conditions suitable for the preservation of the biological or pharmaceutical activity of the hydrophobic material, as well as for maintaining the integrity of the polymer, and are typically suitable for storage in ambient or refrigerated temperatures. The polymer encapsulates of the present invention may be formulated for administration orally, subcutaneously, intramuscularly, intravenously, colonically, rectally, nasally or intraperitonially, employing a variety of dosage forms such as solutions, tablets, capsules, gelcaps, suppositories, implanted pellets or small cylinders, aerosols and topical formulations such as lotions, ointments, drops and dermal patches. The dosage formulations of this invention are suitable for applications where localized drug delivery is desired, as well as in situations where a systemic delivery is desired.
The dosage formulations of this invention may desirably further incorporate agents to facilitate the systemic delivery of the hydrophobic material having biological or pharmaceutical activity to the desired target. The hydrophobic materials to be delivered may, in this fashion, be incorporated with antibodies, antibody fragments, growth factors, hormones, or other targeting moieties, to which the drug molecules are coupled. The present invention also contemplates the use of peptide linkages between the core polyol and the acylated dicarboxylic acids that are selected for cleavage by proteolytic enzymes, resulting in degradation of the polymer and release of the encapsulated hydrophobic material. The release of the hydrophobic material may thus be targeted by selecting a peptide sequence corresponding to a proteolytic enzyme unique to the target site, or by co-administering a proteolytic enzyme corresponding to the peptide sequence at the target site for the hydrophobic material.
However, one advantage of the polymers of the present invention is that polymer degradation is not a prerequisite for release of the hydrophobic material.
A particular class of hydrophobic molecules having biological activity that are suitable for use with the present invention are inter-cellular regulators and mediators such as interferons, growth factors, hormones, and the like. The polymers of the present invention are contemplated to be particularly effective for the efficient administration of interferons, which has proven to be problematic because of interferon""s water-insolubility. As noted above, the topical dosage forms of the present invention exhibit an unexpectedly accelerated rate of transdermal delivery attributable to the encapsulation of the hydrophobic material by the polymers of the present invention. Thus, the polymer-encapsulated hydrophobic material having biological or pharmaceutical activity may be prepared as topical dosage forms such as lotions, gels, salves, creams, balms, ointments and the like. These compositions may be in the form of aqueous solutions, or in the form of oil-in-water or water-in-oil emulsions. The formulations are essentially conventional, containing well-known additives, and are prepared using art-recognized techniques.
Topical dosage forms may also be prepared by incorporating the polymer encapsulate into the reservoir of a transdermal drug delivery device. Transdermal administration systems, or xe2x80x9cpatchesxe2x80x9d, are well-known in the art. Occlusive transdermal patches for the administration of an active agent to the skin or mucosa are described in U.S. Pat. Nos. 4,573,966; 4,597,961 and 4,839,164, the disclosures of which are incorporated herein by reference. Essentially any device capable of delivering an active agent transdermally may be employed to transdermally deliver the polymer encapsulate of the present invention.
As noted above, the polymer encapsulates are particularly well suited for efficient delivery through the dermis. By xe2x80x9cefficientxe2x80x9d it is meant that a high level of the encapsulate is evenly delivered or transported over time.
However, practically any hydrophobic therapeutic agent otherwise suitable for the practice of this invention may be employed for a variety of applications. The polymers of the present invention can also be used as thickening agents, lubricants, detergents surfactants, plasticizers and anti-fouling agents. The polymers may be used as an emulsifying, dispersing or stabilizing agent for dyes, cosmetics, pigment and pharmaceutical products. The polymers are particularly useful as an emulsifying, dispersing or stabilizing agent in the dyeing of textiles and for encapsulating dyes for cosmetics. The polymers are useful as lubricants and encapsulants for cosmetics, textiles, leathers and perfumes, and are particularly useful as a thickening agent for paints. The polymers may also be employed as an emulsifying, dispersing or stabilizing agent for components of photographic compositions and developers.
Thus, in addition to biologically or pharmaceutically active hydrophobic molecules, other hydrophobic molecules that may be encapsulated by the polymers of the present invention include insecticides, pesticides, herbicides, antiseptics, food additives, fragrances, dyes, diagnostic aids, and the like.
In a preferred embodiment, the hyperbranched polymeric micelles are used as a replacement for detergents, micelles, surfactant, fatty acids, lipids, amphiphiles, colloids and other delivery agents currently used in cosmetics, toiletries, fragrances, perfumes, skin care products and beauty aids. In this embodiment, the hyperbranched polymeric micelles are used to encapsulate hydrophobic molecules such as dyes, proteins, vitamins, biologically active molecules and fragrances which are then incorporated into aqueous solutions, suspension, dispersion, emollients, lotions, creams, salves, balms and ointment for topical delivery of these hydrophobic molecules.
Examples of hydrophobic molecules that may be encapsulated by the polymers of the present invention include, but are not limited to: abietic acid, aceglatone, acenaphthene, acenocournarol, acetohexamide, acetomeroctol, acetoxolone, acetyldigitoxins, acetylene dibromide, acetylene dichloride, acetylsalicylic acid, alantolactone, aldrin, alexitol sodium, allethrin, allylestrenol, allylsulfide, alprazolam, aluminum bis(acetylsalicylate), ambucetamide, aminochlothenoxazin, aminoglutethimide, amyl. chloride, androstenediol, anethole trithone, anilazine, anthralin, Antimycin A, aplasmomycin, arsenoacetic acid, asiaticoside, asternizole, aurodox, aurothioglycanide, 8-azaguanine, azobenzene; baicalein, Balsam Peru, Balsam Tolu, barban, baxtrobin, bendazac, bendazol, bendroflumethiazide, benomyl, benzathine, benzestrol, benzodepa, benzoxiquinone, benzphetamine, benzthiazide, benzyl benzoate, benzyl cinnamate, bibrocathol, bifenox, binapacryl, bioresmethrin, bisabolol, bisacodyl, bis(chlorophenoxy)methane, bismuth iodosubgallate, bismuth subgallate, bismuth tannate, Bisphenol A, bithionol, bornyl, bromoisovalerate, bornyl chloride, bornyl isovalerate, bornyl salicylate, brodifacoum, bromethalin, broxyquinoline, bufexamac, butamirate, butethal, buthiobate, butlated hydroxyanisole, butylated hydroxytoluene; calcium iodostearate, calcium saccharate, calcium stearate, capobenic acid, captan, carbamazepine, carbocloral, carbophenothin, carboquone, carotene, carvacrol, cephaeline, cephalin, chaulmoogric acid, chenodiol, chitin, chlordane, chlorfenac, chlorfenethol, chlorothalonil, chlorotrianisene, chlorprothixene, chlorquinaldol, chromonar, cilostazol, cinchonidine, citral, clinofibrate, clofaziminc, clofibrate, cloflucarban, clonitrate, clopidol, clorindione, cloxazolam, coroxon, corticosterone, cournachlor, coumaphos, coumithoate cresyl acetate, crimidine, crufomate, cuprobam, cyamemazine, cyclandelate, cyclarbamate cymarin, cypermethril; dapsone, defosfamide, deltamethrin, deoxycorticocosterone acetate, desoximetasone, dextromoramide, diacetazoto, dialifor, diathymosulfone, decapthon, dichlofluani, dichlorophen, dichlorphenamide, dicofol, dicryl, dicumarol, dienestrol, diethylstilbestrol, difenamizole, dihydrocodeinone enol acetate, dihydroergotamine, dihydromorphine, dihydrotachysterol, dimestrol, dimethisterone, dioxathion, diphenane, N-(1,2-diphenylethyl)nicotinamide, dipyrocetyl, disulfamide, dithianone, doxenitoin, drazoxolon, durapatite, edifenphos, emodin, enfenamic acid, erbon, ergocorninine, erythrityl tetranitrate, erythromycin stearate, estriol, ethaverine, ethisterone, ethyl biscournacetate, ethylhydrocupreine, ethyl menthane carboxamide, eugenol, euprocin, exalamide; febarbamate, fenalamide, fenbendazole, fenipentol, fenitrothion, fenofibrate, fenquizone, fenthion, feprazone, flilpin, filixic acid, floctafenine, fluanisone, flumequine, fluocortin butyl, fluoxymesterone, flurothyl, flutazolam, fumagillin, 5-furftiryl-5-isopropylbarbituric acid, fusaftmgine, glafenine, glucagon, glutethimide, glybuthiazole, griseofulvin, guaiacol carbonate, guaiacol phosphate, halcinonide, hematoporphyrin, hexachlorophene, hexestrol, hexetidine, hexobarbital, hydrochlorothiazide, hydrocodone, ibuproxam, idebenone, indomethacin, inositol niacinate, iobenzamic acid, iocetamic acid, iodipamide, iomeglamic acid, ipodate, isometheptene, isonoxin, 2-isovalerylindane-1,3-dione; josamycin, 11-ketoprogesterone, laurocapram, 3-O-lauroylpyridoxol diacetate, lidocaine, lindane, linolenic acid, liothyronine, lucensomycin, mancozeb, mandelic acid, isoamyl ester, mazindol, mebendazole, mebhydroline, mebiquine, melarsoprol, melphalan, menadione, menthyl valerate, mephenoxalone, mephentermine, mephenytoin, meprylcaine, mestanolone, mestranol, mesulfen, metergoline, methallatal, methandriol, methaqualone, methylcholanthrene, methylphenidate, 17-methyltestosterone, metipranolol, minaprine, myoral, naftalofos, naftopidil, naphthalene, 2-naphthyl lactate, 2-(2-naphthyloxy)ethanol, naphthyl salicylate, naproxen, nealbarbital, nemadectin, niclosamide, nicoclonate, nicomorphine, nifuroquine, nifuroxazide, nitracrine, nitromersol, nogalamycin, nordazepam, norethandrolone, norgestrienone;octaverine, oleandrin, oleic acid, oxazeparn, oxazolam, oxeladin, oxwthazaine, oxycodone, oxymesterone, oxyphenistan acetate, paraherquamide, parathion, pemoline, pentaerythritol tetranitrate, pentylphenol, perphenazine, phencarbamide, pheniramine, 2-phenyl-6-chlorophenol, phenthnethylbarbituric acid, phenytoin, phosalone, O-phthalylsulfathiazole, phylloquinone, picadex, pifarnine, piketopfen, piprozolin, pirozadil, plafibride, plaunotol, polaprezinc, polythiazide, probenecid, progesterone, promegestone, propanidid, propargite, propham, proquazone, protionamide, pyrimethamine, pyrimithate, pyrvinium pamoate; quercetin, quinbolone, quizalofo-ethyl, rafoxanide, rescinnamine, rociverine, ronnel; salen, scarlet red, siccanin, simazine, simetride, sobuzoxane, solan, spironolactone, squalene, stanolone, sucralfate, sulfabenz, sulfaguanole, sulfasalazine, sulfoxide, sulpiride, suxibuzone, talbutal, terguide, testosterone, tetrabromocresol, tetrandrine, thiacetazone, thiocolchicine, thioctic acid, thioquinox, thioridazine, thiram, thymyl N-isoamylcarbamate, tioxidazole, tioxolone, tocopherol, tolciclate, tolnaftate, triclosan, triflusal, triparanol; ursolic acid, valinomycin, verapamil, vinblastine, vitamin A, vitamin D, vitamin E, xenbucin, xylazine, zaltoprofen, and zearalenone.
The following non-limiting examples set forth hereinbelow illustrate certain aspects of the invention. All parts and percentages are by weight unless otherwise noted and all temperatures are in degrees Celsius. All PEGs were obtained from Shearwater Polymers (Birmingham, Ala.) and used without further purification. All other chemicals were obtained from Aldrich (Milwaukee, Wis.) and used without further purification. Analytical grade solvents were used for all the reactions. Methylene chloride, tetrahydrofuran (THF), triethylamine (TEA) and dimethylsulfoxide (DMSO) were distilled. Nuclear magnetic resonance spectroscopy (1H NMR, 13C NMR), infrared spectroscopy (IR), mass spectrometry (MS), gel permeation chromatography (GPQ and elemental analysis were used for physicochemical characterization. For differential scanning calorimetry (DSC) measurements, samples were heated under dry nitrogen gas. Data were collected at heating and cooling rates of 10xc2x0 C./minute with a two cycle minimum. For thermogravimetric analysis (TGA), samples were also heated under dry nitrogen gas. Data were collected at a heating rate of 20xc2x0 C./minute. Molecular weights were determined by GPC relative to narrow molecular weight polystyrene standards.

Hyperbranched polymeric micelles for encapsulation and delivery of hydrophobic molecules

Rutgers, The State University of New Jersey


A device for determining tension in or on a line, including a housing mountable to a surface, an idler and a traveler sheave rotatably mounted on the housing, and a scale operatively engaged with the traveler sheave. A block and slot are provided on the housing. A spring disposed between the block and a portion of the housing is compressed when the block moves in a first direction and is released when the block moves in a second direction. The traveler sheave and an indicator are mounted on the block and move in unison therewith. The sheaves are aligned along the same plane and the block moves in a plane substantially parallel to the plane in which the sheaves are disposed. Markings are provided on the housing and the indicator aligns with one of these markings to indicate the tension applied to the line.

1. Technical Field
This invention relates generally to sporting equipment. More particularly, this invention relates to fishing tackle. Specifically, the invention is directed to a line tensioner which preferably is mounted on a fishing rod and is selectively engageable with the fishing line extending outwardly from a reel on the rod; and which tensioner includes sheaves through which the line is reeved and a scale that indicates tension in the line.
2. Background Information
One of the most important steps a fisherman can take before going fishing is to check the strike drag on his fishing line so as to be able to apply enough line pressure to set the hook while ensuring there is less line pressure than the line-rated tensile strength. When a fish is hooked and starts to swim away, a length of line will unspool from the reel. In order to tire the fish out, the fisherman needs to have some drag on the line to make it harder for the fish to pull line off the reel. Drag is a type of braking force applied to the reel which counteracts the reel's rotation and therefore resists the unspooling of fishing line therefrom or allows line to be pulled from the reel, adjusted to not overstress line tensile strength. The fisherman can preset the amount of strike drag that will be applied to the fishing line, i.e., the drag applied to the line at the moment the fish strikes and starts to run with the bait. If the drag setting is too high, the line will barely unspool off the reel. This puts the line in danger of breaking when the fish runs. If the drag setting is too low, it will be too easy for the fish to unspool fishing line off the reel and the fish will be unlikely to tire easily.
Fishermen have typically set the strike drag on the line in one of two ways. The first way is relatively imprecise and unrepeatable in that it is set by touch or feel. What is meant by this is that the fisherman will pull a length of line off the reel and will personally sense if the line is unspooling too easily or if it is too difficult to remove the line. If the fishing line is unspooling too easily, the fisherman will change the drag setting to make it more difficult to remove line from the reel. If the line is not unspooling easily enough, the fisherman will change the drag setting to make it easier to remove the line from the reel. The problem with this methodology is that the fisherman could set the drag incorrectly and then, when a fish takes the bait and runs, the force brought to bear on the line might exceed the line's breaking strain and the line will snap. The breaking strain on a line is the force required to snap a line that is under tension. All lines have their breaking strain or tensile strength printed on their packaging. The fisherman will select a line based on its diameter and/or breaking strain and which corresponds generally to the typical weight of fish that they are trying to catch.
The second method for setting strike drag is to secure the free end of the fishing line to a spring balance. One such type of spring balance would be a scale that is typically used to weigh fish by suspending them from a hook provided on the scale. The end of the fishing line is tied into a loop and is engaged with the hook on the spring balance. If the fisherman has to do this procedure alone, he or she will secure hold the rod in one hand and will pull down on the spring balance (which is connected to the fishing line) to the point that the ratchet on the reel starts to slip. This point is easily determined as it is the moment at which the ratchet starts to make a sound (caused by the reel brake starting to slip) when the line is pulled down by the spring balance. At that point, the fisherman will look at the reading on the scale and determine if it is an acceptable measurement relative to the breaking strain on the line. The reading on the scale is desirably less than or equal to the breaking strain of the line. (If a second person is assisting the fisherman, then the fisherman will hold the rod and the assistant will pull down on the fishing line and take a reading on the spring balance.) A typical desirable relationship between the breaking strain and the force applied by pulling down on the fishing line is about 20-30% of the breaking strain. So, for instance, if the fishing line breaking strain is 30 lb, then a measurement on the spring balance of from about 6 lbs to about 9 lbs when the reel is full of fishing line would be a suitable strike drag setting. If the line has a 30 lb breaking strain and the reading on the spring balance is around 2 lbs, for example, then the fisherman knows he or she needs to increase the drag setting. If the reading on the spring balance is around 15 lbs, for example, then the drag setting on the reel will be reduced.
While this second method enables the fisherman to preset the drag to a desired degree, the methods described above have to be done prior to heading out to fish and they still require time and effort to be expended to achieve the correct drag setting. There is therefore still a need in the art for an improved device and method for setting the strike drag or tension on a fishing line which enables a fisherman to do so quickly and in a repeatable manner and at any time, without undue experimentation and time expenditure.

Line tensioner and method of operation of the same


An ammonia generating device is delimited by an outer casing that includes a main reservoir and a secondary reservoir. The main reservoir is capable of reloading with ammonia the body in the secondary reservoir. A heater is capable of heating the bodies in each reservoir. A connector connects the main reservoir to the secondary reservoir. The heater comprises first and second heating devices respectively installed inside the main reservoir and the secondary reservoir and operating independently. The main reservoir is thermally decoupled from the secondary reservoir to generate a temperature gradient between both reservoirs.

Document DE 10 2009 047 338 describes such an ammonia generating device including a reservoir separated into two portions to form a first central reservoir connected to the exhaust line of an automobile vehicle by controlled means for releasing the ammonia, here a metering valve, and a second reservoir. The first central reservoir has a size clearly smaller than that of the second reservoir. Each reservoir includes a different ammonia storage element, each element allowing release of the reducing agent following a desorption reaction. The first central reservoir is completely positioned inside the second reservoir and is connected to the latter through a switching valve, such as an anti-return valve.
Further, a heat generating element is positioned inside the first central reservoir.
The first central reservoir and the second reservoir are thermally connected to each other, so that when the heat generating element is activated, heat is also imparted to the second reservoir.
This ammonia generating device has the goal of allowing sufficient supply of reducing agent, regardless of the operating state of the vehicle, while limiting the energy required for releasing the reducing agent contained in the storage elements present in the first central reservoir and the second reservoir respectively.
Such an ammonia generating device is, however, complex to apply and may have uncertain operation notably when the heat produced by the heat generating element is insufficient for allowing the desorption reaction in the second reservoir, for example, when the vehicle covers a low mileage and when the duration for powering up the heat generating element is insufficient.


Systems and methods for providing multi-pass rendering of three-dimensional objects. A rendering pipeline that includes (N) physical texture units and one or more associated buffers emulates a rendering pipeline containing more texture units (M) than are physically present (N). Multiple rendering passes are performed for each pixel. During each texture pass only N sets of texture coordinates are passed to the texture units. The number of passes required through the pipeline to emulate M texture units is M/N, rounded up to the next integer. The N texture units of the rendering pipeline perform look-ups on a given pass for the corresponding N texture maps. The texture values obtained during the texture passes are blended by texture blenders to provide composite texture values. In successive passes, the buffers are used for temporary data and the most current composite texture values. The process is repeated until all desired texture maps are applied.

1. The Field of the Invention
The present invention relates to systems and methods for providing multi-pass rendering of three-dimensional graphics. More specifically, the present invention is directed to systems and methods for utilizing one or more texture units and a plurality of associated frame buffers in a rendering pipeline to perform multiple rendering passes, to support the use and storage of extra temporary data, and to blend data from multiple texture maps that is applied to a polygon so as to model a three-dimensional object.
2. Background and Related Art
Adding realism to computer graphics involves rendering an object that has three-dimensional characteristics on a two-dimensional display device. Such three-dimensional characteristics include shadows and variations in color and shade of the object. For each desired three-dimensional characteristic, a specific texture map is applied to a frame of polygons in order to render the object. When multiple characteristics are desired, the corresponding texture maps are blended. Therefore, the blending and applying of various corresponding texture maps renders the object as having the desired three-dimensional characteristics, such as any desired color, pattern, appearance, etc.
A conventional technique for applying multiple texture maps to render a three-dimensional image includes utilizing a single texture unit and a single frame buffer. As multiple passes are performed, the frame buffer is used as the temporary data storage between passes. While such a technique adequately applies light or shadow maps on opaque objects, the conventional technique cannot be adequately utilized for transparent objects since temporary data and current destination pixel data cannot co-exist under the conventional technique.
Another technique for applying multiple texture maps to render a three-dimensional image uses a rendering pipeline that includes a texture unit for every texture map that is applied. The texture units are placed in series within the rendering pipeline, which assembles one or more polygons to represent an object having three-dimensional characteristics and applies multiple texture maps to the assembled polygon. Many effects are only renderable if one or more temporary pieces of data are allowed to exist between texture units of a pipeline. Thus, under this conventional technique, an additional piece of temporary data is passed between the texture units of the rendering pipeline and is fully consumed by the end of the pipeline.
By way of example, FIG. 1 illustrates a conventional rendering pipeline that includes vertex unit 10, setup unit 11, edge walk unit 12, span walk unit 13, z-buffer 14, texture units 15, destination blender 18, and frame buffer 19. In the rendering pipeline, vertex unit 10 assembles data describing the values at each vertex of a polygon. The data includes three-dimensional coordinates, which represent each of the polygons that together model a three-dimensional object, and texture coordinates, the values for which are determined later in the pipeline through a series of texture units. Vertex unit 10 provides the assembled data to setup unit 11, which generates parametric function coefficients for an interpolation of intermediary points between the three-dimensional coordinates. Edge walk unit 12 receives the output of setup unit 11 and determines the starting pixel and the value of the starting pixel for each horizontal row of pixels lying within the bounds of the polygon. Span walk unit 13 then determines the values for all of the pixels for each horizontal row within the polygon. The values determined by edge walk unit 12 and span walk unit 13 are provided to z-buffer 14, which determines whether the pixels are occluded or visible, so that only currently visible pixels are drawn.
A set of texture coordinates representing the various layers of textures that are to be applied to the generated polygons are passed through a series of texture units 15. The number of texture units in series corresponds to the number of texture layers that are to be applied. In the example of FIG. 1, five texture layers are applied to the generated polygons. Other conventional rendering pipelines may include any number of texture units in series to apply the corresponding number of texture maps.
In FIG. 1, each texture unit 15 receives a series of texture coordinate sets for each pixel, performs a texture map look up to obtain the values of the coordinate sets related to a texture map, and performs a blending operation that may include blending the obtained values with values from one or more previous texture maps. Temporary data is passed between the texture units 15 and is fully consumed by the end of the rendering pipeline.
Therefore, with reference to the series of texture units 15 of FIG. 1, texture unit 15a receives a series of texture coordinate sets from z-buffer 14 for each pixel. An example of a series of texture coordinate sets for a given pixel is (u0,v0), (u1,v1), (u2,v2), (u3,v3), and (u4,v4), where (u0,v0) is the texture coordinate set for the first texture map, (u1,v1) is the texture coordinate set for the second texture map, (u2,v2) is the texture coordinate set for the third texture map, (u3,v3) is the texture coordinate set for the fourth texture map, and (u4,v4) is the texture coordinate set for the fifth texture map. Because the texture units are in series, the full complement of texture coordinate sets, which, in this example include (u0,v0), (u1,v1), (u2,v2), (u3,v3), and (u4, v4), are transmitted from z-buffer 14 to texture unit 15a. In this manner, each of the texture units 15a–15e can select the texture coordinate set it needs to perform a texture map look up operation.
The following example illustrates the conventional technique that is currently performed for each pixel. Texture unit 15a takes the texture coordinate set (u0,v0) corresponding to the first texture map and performs a look up at texture cache 16a to obtain the texture values for the pixel. Texture blender 17a performs a blending operation to apply the texture values to the pixel corresponding to the first texture map.
Texture unit 15b receives the series of texture coordinate sets for the pixel from texture unit 15a. The texture coordinate set (u1,v1), which corresponds to the second texture map, is selected by texture unit 15b and a look up is performed at texture cache 16b to obtain the texture values for the pixel. Texture blender 17b then performs a blending operation, which includes blending the texture values corresponding to texture coordinates (u0,v0) and (u1,v1), to apply the texture values to the pixel corresponding to the first and second texture maps.
Texture unit 15c receives from texture unit 15b the series of texture coordinate sets for the pixel. The texture coordinate set (u2,v2), which corresponds to the third texture map, is selected by texture unit 15c and a look up is performed at texture cache 16c to obtain the texture values for the pixel. Texture blender 17c performs a blending operation, which includes blending the texture values corresponding to texture coordinates (u0,v0), (u1,v1) and (u2,v2), to apply the texture values to the pixel corresponding to the first, second and third texture maps.
Texture unit 15d receives the series of texture coordinate sets for the pixel from texture unit 15c. The texture coordinate set (u3,v3), which corresponds to the fourth texture map, is selected by texture unit 15d and a look up is performed at texture cache 16d to obtain the texture values for the pixel. Texture blender 17d performs a blending operation, which includes blending the texture values corresponding to texture coordinates (u0,v0), (u1,v1), (u2,v2) and (u3,v3), to apply the texture values to the pixel corresponding to the first, second, third, and fourth texture maps.
Texture unit 15e receives the series of texture coordinate sets for the pixel from texture unit 15d. The texture coordinate set (u4,v4), which corresponds to the fifth texture map, is selected by texture unit 15e and a look up is performed at texture cache 16e to obtain the texture values for the pixel. Texture blender 17e performs a blending operation, which includes blending the texture values corresponding to texture coordinates (u0,v0), (u1,v1), (u2,v2), (u3,v3) and (u4,v4), to apply the texture values to the pixel corresponding to the first, second, third, and fourth texture maps.
The process explained above is performed for each of the pixels and the composite texture values, which are the blended texture values for each pixel corresponding to texture coordinates (u0,v0), (u1,v1), (u2,v2), (u3,v3) and (u4,v4). After texturing, the pixels are optionally modified by the destination blender 18, which applies optional fog blending, iterated specular blending, and/or alpha blending to the pixels that are then mapped to a frame buffer 19. Once the completed values for all of the pixels are mapped to frame buffer 19, the display device is refreshed with the rendered image.
Another conventional technique for applying multiple texture maps to render a three-dimensional image utilizes a rendering pipeline, such as the rendering pipeline illustrated in FIG. 1, and an extra piece of temporary data that only exists between texture stages. However, with this technique it is possible for the regular multi-texturing type of temporary data to concurrently exist between texture stages since previous texture stages could have other texture lookup proceeding. As such, there are up to two pieces of temporary inter-texture stage data and one piece of destination pixel data in the frame buffer.
Due to significant and sometimes prohibitive amounts of computing resources that are required, including a high demand for memory, conventional rendering techniques are limited to typically two or three texture units rather than the maximum number of eight. As such, the conventional techniques only allow for three stages of multi-texturing and the conventional techniques are limited to one pass through the rendering pipeline unless no extra temporary data is required after each pass, the pixels are opaque, and there is no pixel discarding occurring during each texture stage (e.g. color keying).

This patent is subject to a terminal disclaimer.

Applying multiple texture maps to objects in three-dimensional imaging processes


A tape guide device comprising a pipe-shaped guide member for guiding a tape, an ultrasonic vibrator for vibrating the guide member by standing waves, and a support member for holding the guide member, wherein one end of the ultrasonic vibrator is kept free while the other end thereof is attached fixedly to a vibrational loop on the peripheral surface of the guide member, and vibrational nodes of the guide member are held by the support member, hence stabilizing the characteristic of standing-wave vibration.

1. Field of the Invention
The present invention relates to a tape guide device adapted for use in a video tape recorder or the like and, more particularly, to a device where ultrasonic vibration is utilized to reduce the friction in contact with a tape.
2. Description of the Prior Art
There are known conventional tape guide devices inclusive of an example filed by the present applicant and disclosed in Japanese Patent Application No. Hei 1 (1989)-53287. As shown in FIG. 11, such known tape guide device 1 comprises a mount member 8, a pair of support shafts 7 fixed therein, a guide member 2 which is held by fore ends of the support shafts fitted into lateral portions thereof and serves to guide a tape wound therearound over a predetermined angle, and a laminated piezoelectric element 3 serving as an ultrasonic vibrator and bonded at one end to the guide member 2 while being bonded at the other end to the mount member 8. The guide member 2 is vibrated by standing waves from the laminated piezoelectric element 3 so as to diminish the resistance that is caused by agglutination derived from the intermolecular attraction and the interatomic attraction on the contact surfaces of the tape and the guide member 2 and also by thrust and upturn of the irregularities on such contact surfaces, hence reducing the frictional force.
FIG. 12 shows another conventional tape guide device proposed by the present applicant and disclosed in Japanese Patent Application No. Hei 1 (1989)-58449. The tape guide device of FIG. 12 is structurally similar to the aforementioned conventional example with the exception that a recess 2a is formed in a portion of the guide member 2, and both ends of the laminated piezoelectric element 3 are anchored firmly in such recess 2a.
However, in the former conventional example of FIG. 11, the respective thermal expansion coefficients of the support shaft 7 and the laminated piezoelectric element 3 are mutually different, so that there arises a problem of lowering the positional precision relative to the guide member 2. Furthermore, since one end of the laminated piezoelectric element 3 is fixedly attached to the guide member 2 as mentioned, the standing-wave frequency characteristic is harmfully affected by the vibrations of the mount member 8 and the support shafts 7 to be thereby complicated, hence rendering the resonance control difficult and lowering the vibration efficiency.
In addition, as the standing waves generated in the guide member 2 are affected by the mount member 8 and the support shafts 7, the partial standing waves thus affected are distorted to consequently fail in attaining complete reduction of the friction to the tape. Besides the above, the friction of the guide member is rendered partially nonuniform to eventually bring about a failure in stabilizing the motion of the tape.
Meanwhile in the latter conventional example of FIG. 12 where a recess 2a is formed in a portion of the guide member 2, both ends of the laminated piezoelectric element 3 are anchored firmly in such recess 2a, so that the harmful influence of vibration to other members can be reduced. However, since the guide member 2 is formed into an uncommon shape, it is extremely difficult to derive the resonance characteristic of the guide member 2, and the waveform of the standing waves is complicated similarly to the foregoing conventional example, hence raising the same problem. In addition, there also exist other problems inclusive of increased production cost that results from requirements of high precision relative to the component parts and the assembling with the process of cutting the recess 2a and so forth.
Furthermore, thermal expansion of the laminated piezoelectric element 3 is caused by the heat generated during the operation and therefore the surface secured to the recess 2a is pressed to consequently distort the guide member 2, hence failing in complete reduction of the friction while inducing harmful influence on the motion of the tape.

Tape guide device having vibrator with free end portion


A heat trap assembly for a hot water tank includes a heat trap insert and a sealing member retained by the heat trap insert. The heat trap insert includes a seat having an opening that is dimensioned to be covered by the sealing member when no water is flowing through the assembly. The heat trap insert also includes a plurality of fingers to retain the sealing member when water is flowing through the heat trap assembly.

Referring to FIG. 1, a hot water heater assembly 10 generally includes a tank 12 including a heating element (not shown), a cold water inlet pipe 14 and a hot water outlet pipe 16. As the hot water is turned on, for example the hot water spigot in a household, hot water exits through the hot water outlet pipe 16 while cold water flows through the cold water inlet 14 into the tank 12. The amount of hot water leaving the tank equals the amount of cold water replaced and heated in the tank.
Considerable heat is lost through the water inlet and outlet piping of a water heater. The heat loss is due primarily to thermal circulation and not as a result of conduction through the piping itself.
FIG. 2 displays a prior art attempt to control the heat lost through the water inlet and the water outlet piping of the water heater. A prior art cold water inlet heat trap assembly 20 includes a nipple 22, a seat 24, a cage 26, and a ball 28. The nipple 22 is received in the inlet 30 of the tank 12 and also received in the outlet 32 of the cold water inlet pipe 14. The nipple provides the housing for the heat trap assembly 20. The seat 24 is formed inside the nipple. The seat includes an opening having a diameter smaller than the diameter of the ball 28. The cage 26 is a cage-like structure that traps the ball inside the nipple as water from the inlet pipe 14 flows through the nipple 22 into the tank 12. The ball 28 has a specific gravity less than 1.0 so that when no water is flowing through the cold water inlet pipe and the nipple into the tank the ball floats up to cover the opening at the seat.
In use, the hot water is turned on somewhere in the household, or wherever the tank is located. Almost simultaneously, hot water exits the hot water tank 12 through the hot water outlet pipe 16 and cold water enters the tank 12 through cold water inlet pipe 14. As cold water flows through the nipple 22, the water dislodges the ball 28 from the seat 24 and the ball moves toward the cage 26. The cage 26 catches the ball and retains the ball inside the nipple. The cage has openings to allow the water to flow around the ball and enter the tank 12. When the hot water is turned off, the ball 28 floats upwardly back towards and into engagement with the seat 24 trapping heat below it.
A similar hot water heat trap assembly 40 is provided on the hot water outlet pipe 16. The heat trap assembly 40 includes a nipple 42, a seat 44, a cage 46, and a ball 48. The nipple 42 is received in the inlet 50 of the hot water outlet pipe 16 and in the outlet 52 of the tank 12. The seat 44 and the cage 46 are of the same or similar construction of the seat 24 and the cage 26 of the cold water heat trap assembly 20. In the hot water heat trap assembly 40, the seat 44 and the cage 46 are disposed on opposite ends of the heat trap assembly as compared to the cold water heat trap assembly 20. The ball 48 of the hot water heat trap assembly 40 has a specific gravity greater than 1.0. Accordingly, when the hot water exits the tank 12 into the nipple 42, the ball 48 is dislodged from the seat 44 and retained by the cage 46. The cage has openings to allow water to pass around the ball and through the nipple. When the hot water is turned off in the household, no hot water is flowing through the nipple 42 and the hot water outlet pipe 16 so that the ball 48 sinks toward and into engagement with the seat 44 trapping heat below.
A problem with the above-mentioned energy saving device involves "chatter" of the balls 28 and 48 inside the nipples 22 and 42. Because the diameter of the nipple required to allow the ball to float freely inside the nipple and the influence of water flowing through the nipple, the balls tend to rotate at a relatively high speed. The high speed rotation of the balls allows the ball to contact the nipple and "chatter" making an audible sound that is noticeable to those standing near the water heater. To some consumers, this is considered objectionable, although it does not represent a defect in the heat trap. Accordingly, it is desirable to provide a heat trap assembly that provides the same or better energy efficiency of the prior art heat traps while also eliminating the "chatter" that accompanies such heat trap assemblies.


The packaging machine includes: a plurality of lane guides, the plurality of lane guides being spaced apart to form a plurality of lanes; a moveable conveyor belt having a first end and second end, the first end located beneath one of the plurality of lanes, the movable conveyor belt delivers the product to each of the plurality of lanes; a support device located at the plurality of lanes; and a shifting assembly attached to the plurality of lane guides. The method for packaging a case with a product includes: conveying a first plurality of the product to a first lane; supporting the first plurality of the product within the first lane; conveying a second plurality of the product to a second lane; shifting the first lane and the second lane in a first direction; and dropping the first plurality of the products into the case.

Automated packaging devices are often used in high volume production facilities to prepare products for sale and shipment. One common automated packing device is a packaging machine, which divides up the product and drops it into a box or case. The packaging machine typically consist of five sections; a product infeed section, a case feed section, a lift table section, a grid table section and an operator interface section.
The product infeed section of the packaging machine includes a conveyor belt that transfers the product from an up stream process such as filling or labeling, in a serial fashion. The conveyor belt urges the product into grid lanes that align the product into a plurality of rows. Distribution of the product between the grid lanes is accomplished using the force of the conveyor belt and the force created between the individual product items to distribute the product between fixed, stainless steel lane guides. As the product passes between the lane guides, it rests on support strips positioned below the product. At the end of each grid lane is a separation bar, which stops the first product to enter the grid lane. The product is monitored using electronic sensors as it is fed into a grid lane. When the grid lane is filled with the desired amount of product, a brake is applied to stop the serial flow of product in the conveyor belt and, thereby, prevent further product from entering the lane guides.
While the infeed section fills the grid with product, the case feed section delivers empty boxes or cases onto the lift table via a conveyor. The lift table section lifts the cases to a point beneath the grid lanes and waits for product to enter the case before descending. The lift table section is equipped with an air or oil lift table that prompts the up and down motion of the table. As the grid area is filled with product the lift table rises. Once the product is placed in the case, the lift table lowers. The case feed section then discharges the filled case, and an empty case enters the lift table. The operation will then repeat, depending on the number of products in the infeed section.
The grid section is responsible for releasing the product into the empty cases on the lift table. The grid section accomplishes the release of the product using two primary components: the support strip on which the product rests as it enters the grid area, and a grid basket, which guides the product into the case. Once the grid lanes are filled with product, the support strips are shifted to the side allowing the product to fall through the grid basket into the case or box. The support strips are then returned to their original position and the line brake is released allowing subsequent product to be moved from the product infeed into the grid.
An operator interface section controls the system and allows the operator to manage the operation of the machine. Typically, the interface is mounted on a swing boom that enables the operator to control the machine from either side to facilitate viewing of the process. This interface consists of a series of pushbuttons, which enable the operator to start, stop, or alter the performance of the machine, and locate/correct any fault conditions.
As discussed above, the line brake is applied to the infeed conveyor to prevent over filling of the lanes. The application of the brake causes the upstream product to compress together. This compression of the product is known as "line pressure". Also, as discussed above, the product infeed section divides the product into grid lanes using the force of the conveyor belt and the force created between individual product items. As the product is forced into the grid lanes, the first product to enter the grid lane is forced against the separation bar, and the subsequent products are forced against the first product and against each other. This pressure between the products in the grid lane is known as "wind up". Despite that line pressure and wind-up cause problems in the packaging operation, they are often used to help move the product in to the grid lanes. Therefore, there is a delicate balance that must be achieved to use line pressure and wind-up without causing problems in the process.
Line pressure results in two main problems in the packaging operation. The first depends on the product being packaged. If the product is made of a glass or plastic oval shape base that has a thinner wall towards the front and back of the base and a thicker wall in the center of the base, excess line pressure may cause the product to break or deform causing delays in the operation as the damaged product is removed and the line is cleared. The second problem occurs with products having irregularly shaped containers (i.e. containers not shaped as a cylinder or parallel-piped). Because the containers are irregularly shaped, contact of containers against each other may cause tipping of adjacent containers resulting in interlocking, tipping, or mispackaging of the product, which again causes delays. To overcome the problems associated with packaging irregularly shaped products, prior art devices used additional devices such as an inflatable membrane to hold the product and prevent it from tipping.
Wind-up tends to cause problems in the packaging lanes. Most cases have product dividers or partitions that protect the product during shipment. Since the product within the lane is in a wound-up state, a gap must be created between the products before they pass into the case. Prior art packaging machines used a separation bar located on the end of the lane to release the wind-up. Once the lane is filled, the separation bar moves away from the row of product, releasing the wind-up. Unfortunately, this technique does not always work well with irregularly shaped products since the wind-up may cause the products to interlock or tip within the grid lanes.
Accordingly, it is considered to be advantageous to have a packaging machine with an infeed section that is able to deliver product into the grid lanes without the problems associated with line pressure or wind-up. It is also advantageous to have a packaging machine capable of continuously filling grid lanes without the use of a line brake. It is also considered advantageous to have a packaging machine capable of continuously filling grid lanes where the products are packaged on a first-in, first-out basis. It is also considered advantageous to provide a packaging machine capable of continuously packaging cases containing variety packs.

Packaging machine including laterally movable conveyor


The present invention provides a thickening/foam-promoting agent having thickening/foam-promoting properties and a low odor, and a detergent composition containing the agent. The thickening/foam-promoting agent is composed of the following component (A):

It is necessary for a detergent composition to have various functions such as powers to emulsify and solubilize stain components such as an oil, and detergency. A detergent composition for hard surfaces (e.g. a dishwashing agent to be routinely used by humans), a cleansing compositions for the body (e.g., a shampoo or body shampoo) and the like, among others, are required to keep improving the feeling upon use, such as rich foaming, no odor of a base material during use and adequate viscosity, as opposed to other detergents for industrial use. Meanwhile, a less yield of foaming is vital to detergent compositions for industrial use.
In order to enhance a foaming property and adjust a viscosity of a detergent composition, various thickening/foam-promoting agents have been developed, and fatty acid alkanol amides or amides are generally used as a thickening/foam-promoting agents. However, these nitrogen-containing compounds give rise to a change of hue or the like over time, depending on formulation conditions. Furthermore, a fatty acid diethanol amide raises concern about the possibility that its impure nitroso compound might be a cancer-causing substance. For these reasons, a thickening/foam-promoting agent free of nitrogen is desired.
Patent Document 1 discloses, as a thickening/foam-promoting agent free from nitrogen, a (poly)ethyleneglycol alkyl ether obtained by adding 1 to 3 moles of ethylene oxide to an alcohol having 8 to 12 carbon atoms used as a starting material. However, a short chain ethylene oxide adduct containing as few as about 1 to 3 moles of ethylene oxide contains a large amount (not less than 1% by weight) of unreacted alcohols. In addition, alcohols having 8 to 12 carbon atoms carry an strongly unpleasant odor. In particular, if unreacted alcohols having 8 to 10 carbon atoms are left behind in a large amount, the feeling upon use of such a detergent composition could weaken significantly.
While the alcohols may be removed by purification, the production process becomes complicated if the amount of the remaining alcohols is not less than several % by weight, which is industrially unfavorable in view of production cost. On the other hand, it is possible to decrease the amount of unreacted alcohols by increasing the number of ethylene oxide added, but addition of ethylene oxide in a large amount results in poor foaming.
As an example thereof, Patent Document 2 discloses an alkylene oxide adduct of an aliphatic alcohol which is improved in odor by introducing propylene oxide in addition to ethylene oxide. This adduct, however, has a low foaming property when included in a detergent composition, whereby failing to provide a detergent composition having a lower odor and a favorable foaming property.
Patent Document 3 discloses an alkylene oxide adduct of a higher aliphatic alcohol in which a short chain propylene oxide is introduced. However, the document focuses only on the application as an emulsifying agent or a solubilizing agent, and makes no reference to an odor and a foaming property.
Similarly, Patent Document 4 discloses as a detergent an alkylene oxide adduct of an aliphatic alcohol in which a short chain propylene oxide is introduced. However, the document gives no description to an odor and a foaming property.
Patent Documents 5 and 6 disclose a polyoxyalkylene alkyl or alkenyl ether in which a short chain propylene oxide is introduced as a detergent for industrial application. However, these documents make reference only to cleansing of oily matters and iron powder for industrial use, and give no description to an odor and a foaming property. Nor is there any mention about a dishwashing which requires an excellent foaming property, use for the skin or use for the hair.
None of the prior art documents describes the content of a raw material alcohol.
[Patent Document 1] JP-A-2004-277685
[Patent Document 2] JP-A-2003-226892
[Patent Document 3] JP-A-2004-98054
[Patent Document 4] JP-A-2002-226891
[Patent Document 5] JP-A-Hei06-316782
[Patent Document 6] JP-A-2003-13092

Abstract: (A) a compound represented by the following formula (1):R1O—(PO)n/(EO)m—R2  (1),

Abstract: wherein R1 is a linear alkyl or an alkenyl group having 8 to 10 carbon atoms, PO is a propyleneoxy group, EO is an ethyleneoxy group, an average added molar number n is a number of 1.5 to 3.0, an average added molar number m is a number of 0 to 1.0, and R2 is a hydrogen atom or a methyl group, wherein the content of an alcohol of the formula (1), when n=0, m=0 and R2 is a hydrogen atom, is not more than 3000 ppm, and the detergent composition contains the component (A) and a surfactant (B).


A PCI-E connector cover includes a first, a second cover lateral sides, a plurality of bending arms, a cover top surface and a plurality of connecting posts. The first, the second cover lateral sides and the cover top surface are adapted to cover a first, a second connector lateral sides and a connector top surface of a PCI-E connector. The bending arms are connected to the first cover lateral side and lean against a first connector concave of the PCI-E connector so as to keep an interval between the first cover lateral side and the first connector concave. The cover top surface is connected to the first, the second cover lateral sides. The connecting posts are extended from the first and the second cover lateral sides to fix to a main board. A PCI-E connector module is further provided.

Field of the Invention
The invention relates to a connector cover and a connector module, and particularly relates to a peripheral component interconnect express (PCI-E) connector cover and a PCI-E connector module.
Description of Related Art
Along with quick development of technology, performance of expansion devices in a computer host is continuously improved. Taking a display card as an example, it produces a large amount of heat during a high performance operation, and in order to improve a heat dissipation effect, the display card sold in the market is generally configured with a fan at one side thereof, so as to quickly dissipate the heat produced by chips on the display card in a convection manner. However, since a weight of such type of the display card is relatively high, when the display card is plugged to a connector on a main board, a casing of the connector is probably cracked.

PCI-E connector cover and PCI-E connector module


Methods for applying an RF field in a two-dimensional electrode structure include applying RF voltages to main electrodes and to compensation electrodes. The voltages on the compensation electrodes may be proportional to the voltages on the main electrodes so as to optimize the RF field for processes involving ion excitation, including collision-induced dissociation. Electrode structures may include main trapping electrodes, one or more compensation electrodes, one or more ion exit apertures, and a device or circuitry for applying the various desired voltages.

A linear or two-dimensional ion-processing device such as an ion trap is formed by a set of electrodes coaxially arranged about a central (z) axis of the device and elongated in the direction of the central axis. Typically, each electrode is positioned in the (x-y) plane orthogonal to the central axis at a radial distance from the central axis. The inside surfaces of the electrodes are typically hyperbolic with apices facing inwardly toward the central axis. The resulting arrangement of electrodes defines an axially elongated interior space of the device between opposing inside surfaces. In operation, ions may be introduced, trapped, stored, isolated, and subjected to various reactions in the interior space, and may be ejected from the interior space for detection. The radial excursions of ions along the x-y plane may be controlled by applying a two-dimensional RF trapping field between opposing pairs of electrodes. The axial excursions of ions, or the motion of ions along the central axis, may be controlled by applying an axial DC trapping field between the axial ends of the electrodes. Additionally, auxiliary or supplemental RF fields may be applied between an opposing pair of electrodes to increase the amplitudes of oscillation of ions of selected mass-to-charge ratios along the axis of the electrode pair and thereby increase the kinetic energies of the ions for various purposes, including ion ejection and collision-induced dissociation (CID).
Ions present in the interior space of the electrode set are responsive to, and their motions influenced by, all electric fields active within the interior space. These fields include fields applied intentionally by electrical means as in the case of the above-noted DC and RF fields, and fields inherently (mechanically) generated due to the physical/geometric features of the electrode set. The inherently generated fields may or may not be intentional and, depending on the mode of operation, may or may not be desirable or optimal. Both applied fields and inherently generated fields are governed by the configuration (profile, geometry, features, and the like) of the inside surfaces of the electrodes exposed to the interior space. Points on the inside surfaces closest to the central axis, such as the apical line of a hyperbolic electrode, have the greatest influence on an RF trapping field and thus on the ions constrained by the RF trapping field to the volume around the central axis.
In an ideal case, the physical features and geometry of the electrodes would be perfect such that no imperfections in the active fields existed to impair the desired mode of operation of the ion processing device. The electrodes would be perfect hyperbolic surfaces extending to infinity toward the asymptotes. The response of ions to the fields would be completely predictable and controllable, and the performance of the device as a mass analyzer or the like could be completely optimized. In an ideal (pure) quadrupolar RF trapping field, no higher-order multipole fields would be present and the secular frequency of oscillation of an ion in a given coordinate direction would be independent of the secular frequency of oscillation in an orthogonal direction and independent of the amplitude of the oscillation. Moreover, the strength of the ideal field would increase linearly with distance from the central axis along either the x-axis or the y-axis.
In practice, however, the electrodes include a number of different features that engender various types of symmetrical and/or asymmetrical field faults or distortions affecting the manipulation and behavior of ions. For example, most linear electrode systems employed as ion traps eject ions from the interior space in a radial (x or y) direction orthogonal to the central axis, typically through a slot formed at the apex of at least one of the electrodes. The slot is a significant source of field faults that may be considered detrimental to the ion ejection or mass scanning process. For instance, a single slot formed in one of the electrodes generates odd-ordered multipole fields such as hexapolar fields, and two slots respectively formed in two opposing electrodes generate even-ordered fields such as octopole fields. Another source of field faults stems from the necessity that electrodes have truncated (finite) shapes that may likewise generate higher-order multipole field components. Multipoles in the trapping field may produce a variety of nonlinear resonances. In a real quadrupolar RF field employed for trapping ions, such imperfections may adversely affect the ion ejection process by causing shifts in the ion ejection time that are dependent on the chemical structure of the ions. The shift in ejection time results in mass shifts in the mass spectrum that are dependent on the chemical structure of an ion and not its mass. Therefore, it would be highly advantageous to eliminate such adverse effects when using the ion trap as a mass spectrometer.
Conventional approaches for ameliorating the undesired effects of field imperfections include increasing or "stretching" the separation of two opposing electrodes and shaping the electrodes in ways that deviate from theoretically ideal parameters. It is has been observed by the present inventor, however, that while these approaches may adequately compensate for multipole components due to the truncation of the electrodes to a finite size, they do not fully compensate for multipole components caused by large holes and slots in the electrodes. Another approach is to provide shim electrodes positioned inside of the apertures of the electrodes. See U.S. Patent App. Pub. No. US 2002/0185596 A1. This technique, however, does not address and fails to appreciate the need for, and benefits obtained from, compensating for the reduction in the field strength where the ions are oscillating, such as directly on the axis of symmetry of the slot and in the interior space of an ion processing device.
Conversely, the elimination of the effects of imperfections such as nonlinear resonances may be considered disadvantageous when performing other types of ion-processing operations such as collision-induced dissociation (CID). That is, the proper utilization of field defects may be advantageous during processes such as CID. Therefore, it would also be advantageous to be able to utilize field faults to optimize processes entailing ion excitation, such as dissociation and chemical reaction, which are carried out during periods of time in which ion ejection and mass scanning are not desired or at least should be delayed. It would also be advantageous to improve the duty cycle of CID and lessen the need for precisely balancing the voltage applied to drive the CID process with the effects of damping gas. The problems associated with the conventional requirement for such precise balancing are well-recognized in the art.

Field conditions for ion excitation in linear ion processing apparatus


A drive and control system is provided for a towing vehicle pulling a towed implement, such as a tractor pulling a scraper. The drive system includes a diesel engine which drives a generator for generating electric power. A tractor axle drive motor is connected to driven wheels of the tractor through a transmission. An assist drive motor is drivingly connected to driven wheels of the scraper. A power distribution unit controls distribution of electric power from the generator to the tractor and implement assist drive motors. A control unit controls the power distribution unit as a function of an operator set power split, and other sensed parameters. A one-way clutch prevents over-speed of the assist drive motor.

A tractor pulling a scraper is an example of a towing vehicle pulling a towed implement. Earth moving scrapers are heavy and often operate in soil conditions where getting power to the ground can be a challenge. The weight carried by the scraper tires provides the potential for developing tractive power to assist the towing vehicle in moving the machine. If this additional tractive potential can be utilized, the drawbar pull needed from the tractor while loading the scraper and climbing steep grades can be reduced. The operational advantage gained by employing a tractive axle on the scraper linked to a traction control system can be substantial. First, the system will develop better traction for the overall system which will lead to faster pan fills and moving more dirt in less time. Secondly, there will be less wear on the tractor tires and drivetrain due to reduced wheel slip and drawbar load. Thirdly, this reduction in the maximum drawbar load allows ballast to be removed from the tractor and lowers the parasitic losses due to the rolling resistance of the entire tractor-scraper system. This will allow for higher transport speeds and a more productive operation while providing a fuel economy advantage during the entire cycle. Lastly, the system will increase the equipment's utilization by allowing operations in conditions where a normal tractor-scraper system would become stuck.

Drive system for vehicle pulling a towed implement