Claims
- 1. A method of inhibiting 3-Deoxyglucosone (3DG) synthesis in the skin of a mammal, said method comprising administering to said mammal an effective amount of an inhibitor of 3DG synthesis, thereby inhibiting 3DG synthesis in the skin of a mammal.
- 2. The method of claim 1, wherein said inhibitor of 3DG synthesis is administered via a route selected from the group consisting of topical, oral, rectal, vaginal, intramuscular, and intravenous.
- 3. The method of claim 2, wherein said inhibitor of 3DG synthesis is administered via a topical route.
- 4. The method of claim 1, wherein said inhibitor of 3DG synthesis is an enzyme inhibitor.
- 5. The method of claim 4, wherein said enzyme inhibitor is an inhibitor of fructosamine kinase function.
- 6. The method of claim 5, wherein said inhibitor of fructosamine kinase function inhibits amadorase.
- 7. The method of claim 5, wherein said inhibitor of fructosamine kinase function binds with fructosamine kinase.
- 8. The method of claim 7, wherein said inhibitor of fructosamine kinase function which binds with fructosamine kinase is an antibody.
- 9. The method of claim 8, wherein said fructosamine kinase is amadorase.
- 10. The method of claim 8, wherein said antibody binds with fructosamine kinase or a fragment thereof.
- 11. The method of claim 10, wherein said antibody is selected from the group consisting of a polyclonal antibody, a monoclonal antibody, a humanized antibody, a chimeric antibody, and a synthetic antibody.
- 12. A composition comprising an antibody that specifically binds with fructosamine kinase, or a fragment thereof, and a pharmaceutically-acceptable carrier.
- 13. The composition of claim 12, wherein said fructosamine kinase shares at least 30% sequence identity with the amino acid sequence of SEQ ID NO:2.
- 14. A composition comprising an isolated nucleic acid complementary to a nucleic acid encoding a fructosamine kinase, or a fragment thereof, said complementary nucleic acid being in an antisense orientation, and a pharmaceutically-acceptable carrier.
- 15. The method of claim 5, wherein said inhibitor of fructosamine kinase function is a compound comprising the formula of formula XIX:
- 16. The method of claim 15, wherein said compound comprising formula XIX is selected from the group consisting of galactitol lysine, 3-deoxy sorbitol lysine, 3-deoxy-3-fluoro-xylitol lysine, 3-deoxy-3-cyano sorbitol lysine, 3-O-methyl sorbitollysine, meglumine, sorbitol lysine and mannitol lysine.
- 17. The method of claim 16, wherein said compound is 3-O-methyl sorbitollysine.
- 18. The method of claim 1, wherein said inhibitor of 3DG synthesis inhibits 3DG accumulation in said skin.
- 19. The method of claim 1, wherein said inhibitor of 3DG synthesis inhibits induction of said 3DG synthesis.
- 20. The method of claim 1, wherein said inhibitor of 3DG synthesis inhibits a precursor of said 3DG.
- 21. The method of claim 20, wherein said precursor of 3DG is fructose-lysine.
- 22. The method of claim 1, wherein said mammal is a human.
- 23. The method of claim 1, wherein said inhibitor of 3DG synthesis inhibits transcription of a fructosamine kinase mRNA.
- 24. The method of claim 23, wherein said inhibitor inhibits transcription of a nucleic acid comprising SEQ ID NO: 1.
- 25. The method of claim 23, wherein said fructosamine kinase mRNA encodes amadorase.
- 26. The method of claim 23, wherein said inhibitor binds with a nucleic acid encoding fructosamine kinase mRNA.
- 27. The method of claim 26, wherein said inhibitor is an antisense oligonucleotide.
- 28. The method of claim 27, wherein the length of said oligonucleotide is selected from the group consisting of 5-25 nucleotides, 26-50 nucleotides, 51-100 nucleotides, and 101-200 nucleotides.
- 29. A method of inhibiting 3DG synthesis in a mammal, said method comprising administering to said mammal a 3DG synthesis inhibiting amount of an isolated nucleic acid complementary to a nucleic acid encoding a fructosamine kinase protein, or a fragment thereof, wherein said fructosamine kinase is required for said 3DG synthesis, said complementary nucleic acid being in an antisense orientation, thereby inhibiting 3DG synthesis in said mammal.
- 30. The method of claim 29, wherein said fructosamine kinase is amadorase.
- 31. The method of claim 1, wherein said inhibitor of 3DG synthesis, inhibits translation of a fructosamine kinase.
- 32. The method of claim 31, wherein said fructosamine kinase is amadorase.
- 33. The method of claim 31, wherein said inhibitor binds with fructosamine kinase mRNA.
- 34. The method of claim 33, wherein said inhibitor is an antisense oligonucleotide.
- 35. The method of claim 31, wherein said inhibitor is an isolated nucleic acid complementary to a nucleic acid encoding a fructosamine kinase protein, or a fragment thereof, said complementary nucleic acid being in an antisense orientation.
- 36. The method of claim 1, wherein said inhibitor of 3DG synthesis inhibits a nonenzymatic pathway of 3DG synthesis.
- 37. A method of identifying a compound which inhibits 3DG synthesis in the skin of a mammal, said method comprising administering a test compound to said mammal and comparing the level of 3DG in said skin of said mammal with the level of 3DG in the skin of an otherwise identical mammal not administered said test compound, wherein a lower level of 3DG in said skin of said mammal administered said test compound, compared with said level of 3DG in said skin of an otherwise mammal not administered said test compound, is an indication that said test compound inhibits 3DG synthesis in said skin of said mammal, thereby identifying a compound which inhibits 3DG synthesis in the skin of a mammal.
- 38. A compound identified by the method of claim 37.
- 39. The method of claim 37, wherein said mammal is a human.
- 40. A composition comprising a compound identified by the method of claim 1 and a pharmaceutically acceptable carrier.
- 41. A method of identifying a compound which inhibits 3DG synthesis in a cell in vitro, said method comprising administering a test compound to said cell in vitro and comparing the level of 3DG in said cell in vitro with the level of 3DG in an otherwise identical cell in vitro not administered said test compound, wherein a lower level of said 3DG in said cell in vitro administered said test compound, compared with said level of 3DG in said cell in vitro not administered said test compound, is an indication that said test compound inhibits said 3DG synthesis in said cell in vitro, thereby identifying a compound which inhibits 3DG synthesis in said cell in vitro.
- 42. A compound identified by the method of claim 41.
- 43. The method of claim 41, wherein said cell is a human cell.
- 44. A composition comprising a compound identified by the method of claim 41 and a pharmaceutically acceptable carrier.
- 45. The method of claim 41, wherein said cell in vitro is selected from the group consisting of a cell in a cell culture, an organ culture, and an isolated tissue sample.
- 46. The method of claim 45, wherein said cell in said cell culture is a skin cell.
- 47. The method of claim 45, wherein said tissue sample is a skin sample.
- 48. A method of inhibiting alpha-dicarbonyl sugar function in the skin of a mammal, said method comprising administering to said mammal an effective amount of an inhibitor of alpha-dicarbonyl sugar function, thereby inhibiting alpha-dicarbonyl sugar function in the skin of a mammal.
- 49. The method of claim 48, wherein said inhibitor of alpha-dicarbonyl sugar function inhibits protein crosslinking.
- 50. The method of claim 48, wherein said inhibitor of alpha-dicarbonyl sugar function inhibits formation of reactive oxygen species.
- 51. The method of claim 48, wherein said inhibitor of alpha-dicarbonyl sugar function inhibits apoptosis.
- 52. The method of claim 48, wherein said inhibitor of alpha-dicarbonyl sugar function inhibits mutagenicity.
- 53. The method of claim 48, wherein said inhibitor of alpha-dicarbonyl sugar function inhibits formation of advanced glycation end product modified proteins.
- 54. The method of claim 48, wherein said inhibitor of alpha-dicarbonyl sugar function inhibits 3DG function.
- 55. The method of claim 48, wherein said alpha-dicarbonyl sugar is 3DG.
- 56. The method of claim 55, wherein said inhibitor inhibits formation of advanced glycation end product modified proteins.
- 57. The method of claim 55, wherein said inhibitor is arginine or a derivative or modification thereof.
- 58. The method of claim 57, wherein said inhibitor inhibits protein crosslinking.
- 59. The method of claim 55, wherein said inhibitor is administered in a pharmaceutical composition.
- 60. The method of claim 59, wherein said inhibitor comprises from about 0.0001% to about 15% by weight of said pharmaceutical composition.
- 61. The method of claim 59, wherein said inhibitor is administered as a controlled-release formulation.
- 62. The method of claim 59, wherein said pharmaceutical composition is selected from the group consisting of a lotion, a cream, a gel, a liniment, an ointment, a paste, a solution, a powder, and a suspension.
- 63. The method of claim 62, wherein said composition further comprises a moisturizer, a humectant, a demulcent, oil, water, an emulsifier, a thickener, a thinner, a surface active agent, a fragrance, a preservative, an antioxidant, a hydrotropic agent, a chelating agent, a vitamin, a mineral, a permeation enhancer, a cosmetic adjuvant, a bleaching agent, a depigmentation agent, a foaming agent, a conditioner, a viscosifier, a buffering agent, and a sunscreen.
- 64. The method of claim 55, wherein said inhibitor is administered via a route selected from the group consisting of topical, oral, intramuscular, and intravenous.
- 65. The method of claim 64, wherein said inhibitor is administered via a topical route.
- 66. The method of claim 55, wherein said inhibitor is selected from the group consisting of structural formulas I-XVII and XVIII.
- 67. The method of claim 66, wherein said structural formula is structural formula I:
- 68. The method of claim 67, wherein said compound is selected from the group consisting of N,N-dimethylimidodicarbonimidic diamide, imidodicarbonimidic diamide, N-phenylimidodicarbonimidic diamide, N-(aminoiminomethyl)-4-morpholinecarboximidamide, N-(aminoiminomethyl)-4-thiomorpholinecarboximidamide, N-(aminoiminomethyl)-4-methyl-1-piperazinecarboximidamide, N-(aminoiminomethyl)-1-piperidinecarboximidamide, N-(aminoiminomethyl)-1-pyrrolidinecarboximidamide, N-(aminoiminomethyl)-1-hexahydroazepinecarboximidamide, (aminoiminomethyl)-1-hexahydroazepinecarboximidamide, N-4-pyridylimidodicarbonimidic diamide, N,N-di-n-hexylimidodicarbonimidic diamide, N,N-di-n-pentylimidodicarbonimidic diamide, N,N-d-n-butylimidodicarbonimidic diamide, N,N-dipropylimidodicarbonimidic diamide, and N,N-diethylimidodicarbonimidic diamide.
- 69. The method of claim 66, wherein said structural formula is structural formula 1I:
- 70. The method of claim 69, wherein said compound is selected from the group consisting of 4,5-diaminopyrimidine, 4-amino-5-aminomethyl-2-methylpyrimidine, 6-(piperidino)-2,4-diaminopyrimidine 3-oxide, 4,6-diaminopyrimidine, 4,5,6-triaminopyrimidine, 4,5-diamino-6-hydroxy pyrimidine, 2,4,5-triamino-6-hydroxypyrimidine, 2,4,6-triaminopyrimidine, 4,5-diamino-2-methylpyrimidine, 4,5-diamino-2,6-dimethylpyrimidine, 4,5-diamino-2-hydroxy-pyrimidine, and 4,5-diamino-2-hydroxy-6-methylpyrimidine.
- 71. The method of claim 66, wherein said structural formula is structural formula III:
- 72. The method of claim 71, wherein said compound is selected from the group consisting of N-acetyl-2-(phenylmethylene)hydrazinecarboximidamide, 2-(phenylmethylene)hydrazinecarboximidamide, 2-(2,6-dichlorophenylmethylene) hydrazinecarboximidamide pyridoxal guanylhydrazone, pyridoxal phosphate guanylhydrazone, 2-(1-methylethylidene)hydrazinecarboximidamide, pyruvic acid guanylhydrazone, 4-acetamidobenzaldehyde guanylhydrazone, 4-acetamidobenzaldehyde N-acetylguanylhydrazone, and acetoacetic acid guanylhydrazone.
- 73. The method of claim 66, wherein said structural formula is structural formula IV:
- 74. The method of claim 73, wherein said compound is selected from the group consisting of equival n-butanehydrazonic acid hydrazide, 4-methylbenzamidrazone, N-methylbenzenecarboximidic acid hydrazide, benzenecarboximidic acid 1-methylhydrazide, 3-chlorobenzamidrazone, 4-chlorobenzamidrazone, 2-fluorobenzamidrazone, 3-fluorobenzamidrazone, 4-fluorobenzamidrazone, 2-hydroxybenzamidrazone, 3-hydroxybenzamidrazone, 4-hydroxybenzamidrazone, 2-aminobenzamidrazone, benzenecarbohydrazonic acid hydrazide, and benzenecarbohydrazonic acid 1-methylhydrazide.
- 75. The method of claim 66, wherein said structural formula is structural formula V:
- 76. The method of claim 75, wherein said compound is selected from the group consisting of 3,4-diaminopyridine, 2,3-diaminopyridine, 5-methyl-2,3-diaminopyridine, 4-methyl-2,3-diaminopyridine, 6-methyl-2,3-pyridinediamine, 4,6-dimethyl-2,3-pyridinediamine, 6-hydroxy-2,3-diaminopyridine, 6-ethoxy-2,3-diaminopyridine, 6-dimethylamino-2,3-diaminopyridine, diethyl 2-(2,3-diamino-6-pyridyl) malonate, 6 (4-methyl-1-pyperazinyl)-2,3-pyridinediamine, 6-(methylthio)-5 (trifluoromethyl)-2,3-pyridinediamine, 5-(trifluoromethyl)-2,3-pyridinediamine, 6-(2,2,2-trifluorethoxy)-5-(trifluoromethyl)-2,3-pyridinediamine, 6-chloro-5-(trifluoromethyl)-2,3-pyridinediamine, 5-methoxy-6-(methylthio)-2,3-pyridinediamine, 5-bromo-4-methyl-2,3-pyridinediamine, 5-(trifluoromethyl-2,3-pyridinediamine, 6-bromo-4-methyl-2,3-pyridinedlamine, 5-bromo-6-methyl-2,3-pyridinediamine, 6-methoxy-3,4-pyridinediamine, 2-methoxy-3,4-pyridinediamine, 5-methyl-3,4-pyridinediamine, 5-methoxy-3,4-pyridinediamine, 5-bromo-3,4-pyridinediamine, 2,3,4-pyridinetriamine, 2,3,5-pyridinetriamine, 4-methyl-2,3,6-pyridinetriamine, 4-(methylthio)-2,3,6-pyridinetriamine, 4-ethoxy-2,3,6-pyridinetriamine, 2,3,6-pyridinetriamine, 3,4,5-pyridinetriamine, 4-methoxy-2,3-pyridinediamine, 5-methoxy-2,3-pyridinediamine, and 6-methoxy-2,3-pyridinediamine.
- 77. The method of claim 66, wherein said structural formula is structural formula VI:
- 78. The method of claim 77, wherein said compound is selected from the group consisting of 1-amino-2-[2-(2-hydroxyethyl) hydrazino]-2-imidazoline, 1-amino-[2-(2-hydroxyethyl) hydrazino]-2-imidazoline, 1-amino-2-(2-hydroxyethylamino)-2-imidazoline, 1-(2-hydroxyethyl)-2-hydrazino-1,4,5,6-tetrahydropyrimidine, 1-(2-hydroxyethyl) 2-hydrazino-2-imidazoline, 1-amino-2-([2-(4-morpholino)ethyl]amino)imidazoline, ([2-(4-morpholino)ethyl]amino)imidazoline, 1-amino-2-([3-(4-morpholino) propyl]amino)imidazoline, 1-amino-2-([3-(4-methylpiperazin-1-yl)propyl]-amino)imidazoline; 1-amino-2-([3-(dimethylamino)propyl]amino)imidazoline, 1-amino-2-[(3-ethoxypropyl)amino] imidazoline, 1-amino-2-([3-(1-imidazolyl)propyl]amino)imidazoline, 1-amino-2-(2-methoxyethylamino)-2-imidazoline, (2-methoxyethylamino)-2-imidazoline, 1-amino-2-(3-isopropoxypropylamino)-2-imidazoline, 1-amino-2-(3-methylthiopropylamino)-2-imidazoline, 1-amino-2 [3-(1-piperidino)propylamino)imidazoline, 1-amino-2-[2,2-dimethyl-3-(dimethylamino) propylamino]-2-imidazoline, and 1-amino-2-(neopentylamino)-2-imidazoline.
- 79. The method of claim 66, wherein said structural formula is structural formula VII:
- 80. The method of claim 79, wherein said compound is selected from the group consisting of 3,4-diamino-5-methyl-1,2,4-triazole, 3,5-dimethyl-4H-1,2,4-triazol-4-amine, 4-triazol-4-amine, 4-triazol-4-amine, 4-triazol-4-amine, 2,4-triazole-3,4-diamine, 5-(1-ethylpropyl)-4H-1,2,4-triazole-3,4-diamine, 5-isopropyl-4H-1,2,4-triazole-3,4-diamine, 5-cyclohexyl-4H-1,2,4-triazole-3,4-diamine, 5-methyl-4H-1,2,4-triazole-3,4-diamine, 5-phenyl-4H-1,2,4-triazole-3,4-diamine, 5-propyl-4H-1,2,4-triazole-3,4-diamine, and 5-cyclohexyl-4H-1,2,4-triazole-3,4-diamine.
- 81. The method of claim 66, wherein said structural formula is structural formula VIII:
- 82. The method of claim 81, wherein said compound is selected from the group consisting of 2-guanidinoberizimidazole, 1,2-diaminobenzimidazole, 1,2-diaminobenzimidazole hydrochloride, 5-bromo-2-guanidinobenzimidazole, 5-methoxy-2-guanidinobenzimidazole, 5-methylbenzimidazole-1,2-diamine, 5-chlorobenzimidazole-1,2-diamine, and 2,5-diaminobenzimidazole.
- 83. The method of claim 66, wherein said structural formula is structural formula IX:
- 84. The method of claim 83, wherein said compound is selected from the group consisting of lysine, 2,3-diaminosuccinic acid, and cysteine.
- 85. The method of claim 66, wherein said compound is a compound comprising the formula of said structural formula X:
- 86. The method of claim 85, wherein said compound is selected from the group consisting of 1,2-diamino-4-phenyl[1H]imidazole, 1,2-diaminoimidazole, 1-(2,3-diaminopropyl)imidazole trihydrochloride, 4-(4-bromophenyl)imidazole-1,2-diamine, 4-(4-chlorophenyl)imidazole-1,2-diamine, 4-(4-hexylphenyl)imidazole-1,2-diamine, 4-(4-methoxyphenyl)imidazole-1,2-diamine, 4-phenyl-5-propylimidazole-1,2-diamine, 1,2-diamino-4-methylimidazole, 1,2-diamino-4,5-dimethylimidazole, and 1,2-diamino-4-methyl-5-acetylimidazole.
- 87. The method of claim 66, wherein said structural formula is structural formula XI:
- 88. The method of claim 87, wherein said compound is selected from the group consisting of 4-(cyclohexylamino-carbonyl)-o-phenylene diamine hydrochloride, 3,4-diaminobenzhydrazide, 4-(n-butylamino-carbonyl)-o-phenylene-diamine dihydrochloride, 4-(ethylamino-carbonyl)-o-phenylene-diamine dihydrochloride, 4-carbamoyl-o-phenylene diamine hydrochloride, 4-(morpholino-carbonyl)-o-phenylene-diamine hydrochloride, 4-[(4-morpholino)hydrazino-carbonyl]-o-phenylenediamine, 4-(1-piperidinylamino-carbonyl)-o-phenylenediamine dihydrochloride, 2,4-diamino-3-hydroxybenzoic acid, 4,5-diamino-2-hydroxybenzoic acid, 3,4-diaminobenzamide, 3,4-diaminobenzhydrazide, 3,4-diamino-N,N-bis(1-methylethyl)benzamide, 3,4-diamino-N,N-diethylbenzamide, 3,4-diamino-N,N-dipropylbenzamide, 3,4-diamino-N-(2-furanylmethyl)benzamide, 3,4-diamino-N-(2-methylpropyl)benzamide, 3,4-diamino-N-(5-methyl-2-thiazolyl)benzamide, 3,4-diamino-N-(6-methoxy-2-benzothiazolyl)benzamide, 3,4-diamino-N-(6-methoxy-8-quinolinyl)benzamide, 3,4-diamino-N-(6-methyl-2-pyridinyl)benzamide, 3,4-diamino-N-(1H-benzimidazol-2-yl)benzamide, 3,4-diamino-N-(2-pyridinyl)benzamide, 3,4-diamino-N-(2-thiazolyl)benzamide, 3,4-diamino-N-(4-pyridinyl)benzamide, 3,4-diamino-N-[9H-pyrido(3,4-b)indol-6-yl]benzamide, 3,4-diamino-N-butylbenzamide, 3,4-diamino-N-cyclohexylbenzamide, 3,4-diamino-N-cyclopentylbenzamide, 3,4-diamino-N-decylbenzamide, 3,4-diamino-N-dodecylbenzamide, 3,4-diamino-N-methylbenzamide, 3,4-diamino-N-octylbenzamide, 3,4-diamino-N-pentylbenzamide, 3,4-diamino-N-phenylbenzamide, 4-(diethylamino-carbonyl)-o-phenylene diamine, 4-(tert-butylamino-carbonyl)-o-phenylene diamine, 4-isobutylamino-carbonyl)-o-phenylene diamine, 4-(neopentylamino-carbonyl)-o-phenylene diamine, 4-(dipropylamino-carbonyl)-o-phenylene diamine, 4-(n-hexylamino-carbonyl)-o-phenylene diamine, 4-(n-decylamino-carbonyl)-o-phenylene diamine, 4-(n-dodecylamino-carbonyl)-o-phenylene diamine, 4-(1-hexadecylamino-carbonyl)-o-phenylene diamine, 4-(octadecylamino-carbonyl)-o-phenylene diamine, 4-(hydroxylamino-carbonyl)-o-phenylene diamine, 4-(2-hydroxyethylamino-carbonyl)-o-phenylene, 4-[(2-hydroxyethylamino)ethylamino-carbonyl]-o-phenylene diamine, 4-[(2-hydroxyethyloxy)ethylamino-carbonyl]-o-phenylene diamine, 4-(6-hydroxyhexylamino-carbonyl)-o-phenylene diamine, 4-(3-ethoxypropylamino-carbonyl)-o-phenylene diamine, 4-(3-isopropoxypropylamino-carbonyl)-o-phenylene diamine, 4-(3-dimethylaminopropylamino-carbonyl)-o-phenylene diamine, 4-[4-(2-aminoethyl)morpholino-carbonyl]-o-phenylene diamine, 4-[4-(3-aminopropyl) morpholino-carbonyl]-o-phenylene diamine, 4-N-(3-aminopropyl)pyrrolidino-carbonyl]-o-phenylene diamine, 4-[3-(N-piperidino)propylamino-carbonyl]-o-phenylene diamine, 4-[3-(4-methylpiperazinyl)propylamino-carbonyl]-o-phenylene diamine, 4-(3-imidazoylpropylamino-carbonyl)-o-phenylene diamine, 4-(3-phenylpropylamino-carbonyl)-o-phenylenediamine, 4-[2-(N,N-diethylamino) ethylamino-carbonyl]-o-phenylene diamine, 4-(imidazolylamino-carbonyl)-o-phenylene diamine, 4-(pyrrolidinyl-carbonyl)-o-phenylene diamine, 4-(piperidino-carbonyl)-o-phenylene diamine, 4-(1-methylpiperazinyl-carbonyl)-o-phenylene diamine, 4-(2,6-dimethylmorpholino-carbonyl)-o-phenylenediamine, 4-(pyrrolidin-1-ylamino-carbonyl)-o-phenylene diamine, 4-(homopiperidin-1-ylamino-carbonyl)-o-phenylene diamine, 4-(4-methylpiperazine-1-ylamino-carbonyl)-o-phenylene diamine; 4-(1,2,4-triazol-1-ylamino-carbonyl)-o-phenylene diamine, 4-(guanidinyl-carbonyl)-o-phenylene diamine, 4-(guanidinylamino-carbonyl)-o-phenylene diamine, 4-aminoguanidinylamino-carbonyl)-o-phenylene diamine, 4-(diaminoguanidinylamino-carbonyl)-o-phenylene diamine, 3,4-aminosalicylic acid 4-guanidinobenzoic acid, 3,4-diaminobenzohydroxamic acid, 3,4,5-triaminobenzoic acid, 2,3-diamino-5-fluoro-benzoic acid, and 3,4-diaminobenzoic acid.
- 89. The method of claim 66, wherein said structural formula is structural formula XII:
- 90. The method of claim 89, wherein said compound is selected from the group consisting of 3,4-diaminopyrazole, 3,4-diamino-5-hydroxypyrazole, 3,4-diamino-5-methylpyrazole, 3,4-diamino-5-methoxypyrazole, 3,4-diamino-5-phenylpyrazole, 1-methyl-3-hydroxy-4,5-diaminopyrazole, 1-(2-hydroxyethyl)-3-hydroxy-4,5-diaminopyrazole, 1-(2-hydroxyethyl)-3-phenyl-4,5-diaminopyrazole, 1-(2-hydroxyethyl)-3-methyl-4,5-diaminopyrazole, 1-(2-hydroxyethyl)-4,5-diaminopyrazole, 1-(2-hydroxypropyl)-3-hydroxy-4,5-diaminopyrazole, 3-amino-5-hydroxypyrazole, and 1-(2-hydroxy-2-methylpropyl)-3-hydroxy-4,5-diaminopyrazole.
- 91. The method of claim 66, wherein said structural formula is structural formula XIII:
- 92. The method of claim 66, wherein said structural formula is structural formula XIV:
- 93. The method of claim 92, wherein said compound is selected from the group consisting of 2-(2-hydroxy-2-methylpropyl)hydrazinecarboximidic hydrazide, N-(4-morpholino)hydrazinecarboximidamide, 1-methyl-N-(4-morpholino)hydrazinecarboximidamide, 1-methyl-N-(4-piperidino)hydrazinecarboximidamide, 1-(N-hexahydroazepino)hydrazinecarboximidamide, N,N-dimethylcarbonimidic dihydrazide, 1-methylcarbonimidic dihydrazide, 2-(2-hydroxy-2-methylpropyl) carbohydrazonic dihydrazide, and N-ethylcarbonimidic dihydrazide.
- 94. The method of claim 66, wherein said structural formula is structural formula V:
- 95. The method of claim 94, wherein said compound is selected from the group consisting of methylglyoxal bis-(2-hydrazino-benzoic acid)hydrazone, methylglyoxal bis-(dimethyl-2-hydrazinobenzoate)hydrazone, methylglyoxal bis-(phenylhydrazine)hydrazone, methyl glyoxal bis-(dimethyl-2-hydrazinobenzoate)hydrazone, methylglyoxal bis-(4-hydrazinobenzoic acid)hydrazone, methylglyoxal bis-(dimethyl-4-hydrazinobenzoate)hydrazone, methylglyoxal bis-(2-pyridyl)hydrazone, methylglyoxal bis-(diethyleneglycol methylether-2-hydrazinobenzoate)hydrazone, methylglyoxal bis-[1-(2,3-dihydroxypropane)-2-hydrazinebenzoatehydrazone, methyl glyoxal bis-[1-(2-hydroxyethane)-2-hydrazinobenzoate]hydrazone, methylglyoxal bis-[(1-hydroxymethyl-1-acetoxy))-2-hydrazino-2-benzoate]hydrazone, methylglyoxal bis-[(4-nitrophenyl)-2-hydrazinobenzoate]hydrazone, methylglyoxal bis-[(4-methylpyridyl)-2-hydrazinobenzoate]hydrazone, methylglyoxal bis-(triethylene glycol 2-hydrazinobenzoate)hydrazone, and methylglyoxal bis-(2-hydroxyethylphosphate-2-hydrazinebenzoate)hydrazone.
- 96. The method of claim 66, wherein said structural formula is structural formula XVI:
- 97. The method of claim 96, wherein said compound is selected from the group consisting of methyl glyoxal bis(guanylhydrazone), methyl glyoxal bis(2-hydrazino-2-imidazoline-hydrazone), terephthaldicarboxaldehyde bis(2-hydrazino-2-imidazoline hydrazone), terephaldicarboxaldehyde bis(guanylhydrazone), phenylglyoxal bis(2-hydrazino-2-imidazoline hydrazone), furylglyoxal bis(2-hydrazino-2-imidazoline hydrazone), methyl glyoxal bis (1-(2-hydroxyethyl)-2-hydrazino-2-imidazoline hydrazone), methyl glyoxal bis (1-(2-hydroxyethyl)-2-hydrazino-1,4,5,6-tetrahydropyrimidine hydrazone), phenyl glyoxal bis (guanylhydrazone), phenyl glyoxal bis (1-(2-hydroxyethyl)-2-hydrazino-2-imidazoline hydrazone), furyl glyoxal bis (1-(2-hydroxyethyl)-2-hydrazino-2-imidazoline hydrazone), phenyl glyoxal bis (1-(2-hydroxyethyl)-2-hydrazino-1,4,5,6-tetrahydropyrimidine hydrazone), furyl glyoxal bis (1-(2-hydroxyethyl)-2-hydrazino-1,4,5,6-tetrahydropyrimidine hydrazone), 2,3-butanedione bis (2-hydrazino-2-imidazoline hydrazone), 1,4-cyclohexanedione bis(2-hydrazino-2-imidazoline hydrazone), o-phthalic dicarboxaldehyde bis(2-hyd carboximidamide hydrazone), furylglyoxal bis(guanyl hydrazone)dihydrochloride dihydrate, 2,3-pentanedione bis(2-tetrahydropyrimidine)hydrazone dihydrobromide, 1,2-cyclohexanedione bis(2-tetrahydropyrimidine)hydrazone dihydrobromide, 2,3-hexanedione bis(2-tetrahydropyrimidine)hydrazone dihydrobromide, 1,3-diacetyl bis(2-tetrahydropyrimidine)hydrazone dihydrobromide, 2,3-butanedione bis(2-tetrahydropyrimidine)hydrazone dihydrobromide, 2,6-diacetylpyridine-bis-(2-hydrazino-2-imidazoline hydrazone)dihydrobromide; 2,6-diacetylpyridine-bis-(guanyl hydrazone)dihydrochloride, 2,6-pyridine dicarboxaldehyde-bis-(2-hydrazino-2-imidazoline hydrazone)dihydrobromide trihydrate), 2,6-pyridine dicarboxaldehyde-bis (guanyl hydrazone)dihydrochloride,; 1,4-diacetyl benzene-bis-(2-hydrazino-2-imidazoline hydrazone)dihydrobromide dihydrate, 1,3-diacetyl benzene-bis-(2-hydrazino-2-imidazoline)hydrazone dihydrobromide, 1,3-diacetyl benzene-bis (guanyl)-hydrazone dihydrochloride, isophthalaldehyde-bis-(2-hydrazino-2-imidazoline) hydrazone dihydrobromide, isophthalaldehyde-bis-(guanyl)hydrazone dihydrochloride, 2,6-diacetylaniline bis-(guanyl)hydrazone dihydrochloride, 2,6-diacetyl aniline bis-(2-hydrazino-2-imidazoline)hydrazone dihydrobromide, 2,5-diacetylthiophene bis(guanyl)hydrazone dihydrochloride, 2,5-diacetylthiophene bis-(2-hydrazino-2-imidazoline)hydrazone dihydrobromide, 1,4-cyclohexanedione bis(2-tetrahydropyrimidine)hydrazone dihydrobromide, 3,4-hexanedione bis(2-tetrahydropyrimidine)hydrazone dihydrobromide, methylglyoxal-bis-(4-amino-3-hydrazino-1,2,4-triazole)hydrazone dihydrochloride, methylglyoxal-bis-(4-amino-3-hydrazino-5-methyl-1,2,4-triazole)hydrazone dihydrochloride, 2,3-pentanedione-bis-(2-hydrazino-3-imidazoline)hydrazone dihydrobromide, 2,3-hexanedione-bis-(2-hydrazino-2-imidazoline)hydrazone dihydrobromide, 3-ethyl-2,4-pentane dione-bis-(2-hydrazino-2-imidazoline)hydrazone dihydrobromide, methylglyoxal-bis-(4-amino-3-hydrazino-5-ethyl-1,2,4-triazole)hydrazone dihydrochloride, methylglyoxal-bis-(4-amino-3-hydrazino-5-isopropyl-1,2,4-triazole)hydrazone dihydrochloride, methyl glyoxal-bis-(4-amino-3-hydrazino-5-cyclopropyl-1,2,4-triazole)hydrazone dihydrochlorimethylglyoxal-bis-(4-amino-3-hydrazino-5-cyclobutyl-1,2,4-triazole) hydrazone dihydrochloride, 1,3-cyclohexanedione-bis-(2-hydrazino-2-imidazoline) hydrazone dihydrobromide, 6-dimethylpyridine bis(guanyl)hydrazone dihydrochloride, 3,5-diacetyl-1,4-dihydro-2,6-dimethylpyridine bis-(2-hydrazino-2-imidazoline hydrazone dihydrobromide, bicyclo-(3,3,1)nonane-3,7-dione bis-(2-hydrazino-2-imidazoline)hydrazone dihydrobromide, and cis-bicyclo-(3,3,1)octane-3,7-dione bis-(2-hydrazino-2-imidazoline)hydrazone dihydrobromide.
- 98. The method of claim 66, wherein said structural formula is structural formula XVII:
- 99. The method of claim 98, wherein said compound is selected from the group consisting of 3-aminothiazolium mesitylenesulfonate, 3-amino-4,5-dimethylaminothiazolium mesitylenesulfonate, 2,3-diaminothiazolinium mesitylenesulfonate, 3-(2-methoxy-2-oxoethyl)-thiazolium bromide, 3-(2-methoxy-2-oxoethyl)-4,5-dimethylthiazolium bromide, 3-(2-methoxy-2-oxoethyl)-4-methylthiazolium bromide, 3-(2-phenyl-2-oxoethyl)-4-methylthizolium bromide, 3-(2-phenyl-2-oxoethyl)-4,5-dimethylthiazolium bromide, 3-amino-4-methylthiazolium mesitylenesulfonate, 3-(2-methoxy-2-oxoethyl)-5-methylthiazolium bromide, 3-(3-(2-phenyl-2-oxoethyl)-5-methylthiazolium bromide, 3-[2-(4′-bromophenyl)-2-oxoethyl] thiazolium bromide, 3-[2-(4′-bromophenyl)-2-oxoethyl]-4-methylthiazolium bromide, 3-[2-(4′-bromophenyl)-2-oxoethyl]-5-methylthiazolium bromide, 3-[2-(4′-bromophenyl)-2-oxoethyl]-4,5-dimethylthiazolium bromide, 3-(2-methoxy-2-oxoethyl)-4-methyl-5-(2-hydroxyethyl) thiazolium bromide, 3-(2-phenyl-2-oxoethyl)-4-methyl-5-(2-hydroxyethyl) thiazolium bromide, 3-[2-(4′-bromophenyl)-2-oxoethyl]-4-methyl-5-(2-hydroxyethyl) thiazolium bromide, 3,4-dimethyl-5-(2-hydroxyethyl) thiazolium iodide, 3-ethyl-5-(2-hydroxyethyl)-4-methylthiazolium bromide, 3-benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chloride, 3-(2-methoxy-2-oxoethyl)benzothiazolium bromide, 3-(2-phenyl-2-oxoethyl)benzothiazolium bromide, 3-[2-(4′bromophenyl)-2-oxoethyl] benzothiazolium bromide, 3-(carboxymethyl) benzothiazolium bromide, 2,3-(diamino) benzothiazolium mesitylenesulfonate, 3-(2-amino-2-oxoethyl) thiazolium bromide, 3-(2-amino-2-oxoethyl)-4-methylthiazolium bromide, 3-(2-amino-2-oxoethyl)-5-methylthiazolium bromide, 3-(2-amino-2-oxoethyl) 4,5-dimethylthiazolium bromide, 3-(2-amino-2-oxoethyl)benzothiazolium bromide, 3-(2-amino-2-oxoethyl) 4-methyl-5-(2-hydroxyethyl)thiazolium bromide, 3-amino-5-(2-hydroxyethyl)-4-methylthiazolium mesitylenesulfonate, 3-(2-methyl-2-oxoethyl)thiazolium chloride, 3-amino-4-methyl-5-(2-acetoxyethyl)thiazolium mesitylenesulfonate, 3-(2-phenyl-2-oxoethyl)thiazolium bromide, 3-(2-methoxy-2-oxoethyl)-4-methyl-5-(2-acetoxyethyl) thiazoliumbromide, 3-(2-amino-2-oxoethyl)-4-methyl-5-(2-acetoxyethyl)thiazolium bromide, 2-amino-3-(2-methoxy-2-oxoethyl) thiazolium bromide, 2-amino-3-(2-methoxy-2-oxoethyl) benzothiazolium bromide, 2-amino-3-(2-amino-2-oxoethyl)thiazolium bromide, 2-amino-3-(2-amino-2-oxoethyl)benzothiazolium bromide, 3-[2-(4′-methoxyphenyl)-2-oxoethyl]-thiazolinium bromide, 3-[2-(2′,4′-dimethoxyphenyl)-2-oxoethyl]-thiazolinium bromide, 3-[2-(4′-fluorophenyl)-2-oxoethyl]-thiazolinium bromide, 3-[2-(2′,4′-difluorophenyl)-2-oxoethyl]-thiazolinium bromide, 3-[2-(4′-diethylaminophenyl)-2-oxoethyl]-thiazolinium bromide, 3-propargyl-thiazolinium bromide, 3-propargyl-4-methylthiazolinium bromide, 3-propargyl-5-methylthiazolinium bromide, 3-propargyl-4,5-dimethylthiazolinium bromide, and 3-propargyl-4-methyl-5-(2-hydroxyethyl)-thiazolinium bromide.
- 100. The method of claim 66, wherein said structural formula is structural formula XVIII:
- 101. The method of claim 55, wherein said compound which inhibits 3DG function, stimulates detoxification of 3DG.
- 102. The method of claim 55, wherein said compound which inhibits 3DG function in the skin of a mammal binds with 3DG.
- 103. The method of claim 102, wherein said compound which binds with 3DG is an antibody directed against 3DG.
- 104. The method of claim 103, wherein said antibody is selected from the group consisting of a polyclonal antibody, a monoclonal antibody, a humanized antibody, a chimeric antibody, and a synthetic antibody.
- 105. The method of claim 55, wherein said inhibitor of 3DG function stimulates clearance of 3DG from skin.
- 106. The method of claim 105, wherein said clearance occurs via the bloodstream.
- 107. The method of claim 105, wherein said clearance occurs via urine.
- 108. The method of claim 105, wherein said clearance occurs via sweat.
- 109. The method of claim 105, wherein said clearance occurs via exfoliation.
- 110. A composition comprising an inhibitor of 3DG function in the skin and a pharmaceutically acceptable carrier.
- 111. A method of stimulating detoxification of alpha-dicarbonyl sugars in the skin of a mammal, said method comprising administering to said mammal an effective amount of a stimulator of detoxification of alpha-dicarbonyl sugars in the skin of a mammal, thereby stimulating detoxification of alpha-dicarbonyl sugars in the skin of a mammal.
- 112. The method of claim 111, wherein said detoxification occurs using an enzymatic detoxification pathway.
- 113. The method of claim 112, wherein said enzymatic detoxification pathway is an aldehyde reductase detoxification pathway.
- 114. A method of stimulating detoxification of 3DG in the skin of a mammal, said method comprising administering to said mammal an effective amount of a stimulator of detoxification of 3DG in the skin of a mammal, thereby stimulating detoxification of 3DG in the skin of a mammal.
- 115. The method of claim 114, wherein said detoxification occurs using an enzymatic detoxification pathway.
- 116. The method of claim 115, wherein said enzymatic detoxification pathway is an aldehyde reductase detoxification pathway.
- 117. The method of claim 116, wherein said stimulator stimulates aldehyde reductase activity.
- 118. The method of claim 115, wherein said enzymatic detoxification pathway is an oxoaldehyde dehydrogenase pathway.
- 119. The method of claim 118, wherein said stimulator stimulates oxoaldehyde dehydrogenase activity.
- 120. The method of claim 114, wherein said detoxification of 3DG in the skin of a mammal is stimulated by a compound which detoxifies 3DG pharmacologically via formation of rapidly excreted derivatives.
- 121. The method of claim 120, wherein said compound binds with 3DG.
- 122. The method of claim 114, wherein said detoxification comprises clearance of 3DG from skin.
- 123. The method of claim 122, wherein said clearance of 3DG from skin occurs via sweat.
- 124. The method of claim 122, wherein said clearance of 3DG from skin occurs via the blood stream.
- 125. The method of claim 122, wherein said clearance of 3DG from skin occurs via urine.
- 126. A method of identifying a compound which inhibits alpha-dicarbonyl sugar function in the skin of a mammal, said method comprising administering a test compound to said mammal and comparing the level of alpha-dicarbonyl sugar function in said skin of a mammal administered said test compound with the level of alpha-dicarbonyl sugar function in the skin of an otherwise identical mammal not administered said test compound, wherein a lower level of said alpha-dicarbonyl sugar function in said skin of a mammal administered said test compound, compared with the level of alpha-dicarbonyl sugar function in the skin of said otherwise identical mammal not administered said test compound, is an indication that said test compound inhibits alpha-dicarbonyl sugar function in said skin of a mammal, thereby identifying a compound which inhibits alpha-dicarbonyl sugar function in the skin of a mammal.
- 127. A compound identified by the method of claim 126.
- 128. A method of identifying a compound which inhibits alpha-dicarbonyl sugar function in the skin of a mammal, said method comprising administering a test compound to said mammal and comparing the level of alpha-dicarbonyl sugar function in said skin of said mammal administered said test compound with the level of alpha-dicarbonyl sugar function in said skin of said mammal before said test compound was administered, wherein a lower level of said alpha-dicarbonyl sugar function in said skin of a mammal administered said test compound, compared with the level of alpha-dicarbonyl sugar function in said skin of said mammal before said test compound was administered, is an indication that said test compound inhibits alpha-dicarbonyl sugar function in said skin of said mammal, thereby identifying a compound which inhibits alpha-dicarbonyl sugar function in the skin of a mammal.
- 129. A method of identifying a compound which inhibits 3DG function in the skin of a mammal, said method comprising administering a test compound to said mammal and comparing the level of 3DG function in said skin of a mammal administered said test compound with the level of 3DG function in the skin of an otherwise identical mammal not administered said test compound, wherein a lower level of said 3DG function in said skin of a mammal administered said test compound, compared with the level of 3DG function in the skin of an otherwise identical mammal not administered said test compound, is an indication that said test compound inhibits 3DG function in said skin of a mammal, thereby identifying a compound which inhibits 3DG function in the skin of a mammal.
- 130. A compound identified by the method of claim 129.
- 131. The method of claim 129, wherein said mammal is a human.
- 132. The method of claim 129, wherein said compound inhibits advanced glycation end product modified protein formation.
- 133. The method of claim 129, wherein said compound inhibits a function selected from the group consisting of protein crosslinking, apoptosis, formation of reactive oxygen species, and mutagenesis.
- 134. The method of claim 129, wherein said compound stimulates 3DG detoxification.
- 135. The method of claim 129, wherein said compound stimulates 3DG clearance.
- 136. A method of identifying a compound which inhibits 3DG function in the skin of a mammal, said method comprising administering a test compound to said mammal and comparing the level of 3DG function in said skin of said mammal administered said test compound with the level of 3DG function in said skin of said mammal before said test compound was administered, wherein a lower level of said 3DG function in said skin of a mammal administered said test compound, compared with the level of 3DG function in said skin of said mammal before said test compound was administered, is an indication that said test compound inhibits 3DG function in said skin of said mammal, thereby identifying a compound which inhibits 3DG function in the skin of a mammal.
- 137. A method of treating an alpha-dicarbonyl sugar associated skin disease or disorder in a mammal, said method comprising, administering to said mammal an alpha-dicarbonyl sugar inhibiting amount of a compound which inhibits said alpha-dicarbonyl sugar associated skin disease or disorder, thereby treating an alpha-dicarbonyl sugar associated skin disease or disorder of a mammal.
- 138. The method of claim 137, wherein said alpha-dicarbonyl sugar associated skin disease or disorder comprises a disease or disorder associated with a function selected from the group consisting of protein crosslinking, apoptosis, mutagenesis, and formation of reactive oxygen species.
- 139. The method of claim 137, wherein said alpha-dicarbonyl sugar associated skin disease or disorder comprises a disease or disorder associated with advanced glycation end product modified protein formation.
- 140. The method of claim 137, wherein said disease or disorder is selected from the group consisting of skin cancer, psoriasis, skin aging, skin wrinkling, hyperkeratosis, hyperplasia, acanthosis, papillomatosis, dermatosis, rhinophyma, scleroderma, and rosacea.
- 141. The method of claim 139, wherein said disease or disorder is selected from the group consisting of skin cancer, psoriasis, skin aging, skin wrinkling, hyperkeratosis, hyperplasia, acanthosis, papillomatosis, dermatosis, rhinophyma, and rosacea.
- 142. A method of treating a 3DG associated skin disease or disorder in a mammal, said method comprising, administering to said mammal a 3DG inhibiting amount of a compound which inhibits said 3DG associated skin disease or disorder, thereby treating a 3DG associated skin disease or disorder in a mammal.
- 143. The method of claim 142, wherein said 3DG associated skin disease or disorder comprises a disease or disorder associated with a function selected from the group consisting of protein crosslinking, apoptosis, mutagenesis, and formation of reactive oxygen species.
- 144. The method of claim 142, wherein said 3DG associated skin disease or disorder comprises a disease or disorder associated with advanced glycation end product modified protein formation.
- 145. The method of claim 142, wherein said disease or disorder is selected from the group consisting of skin cancer, psoriasis, skin aging, skin wrinkling, hyperkeratosis, hyperplasia, acanthosis, papillomatosis, dermatosis, rhinophyma, scleroderma, and rosacea.
- 146. The method of claim 144, wherein said disease or disorder is selected from the group consisting of skin cancer, psoriasis, skin aging, skin wrinkling, hyperkeratosis, hyperplasia, acanthosis, papillomatosis, dermatosis, rhinophyma, scleroderma, and rosacea.
- 147. The method of claim 142, wherein said mammal is a human.
- 148. The method of claim 142, wherein said compound inhibits 3DG synthesis.
- 149. The method of claim 148, wherein said compound is an enzyme inhibitor.
- 150. The method of claim 149, wherein said enzyme inhibitor inhibits fructosamine kinase.
- 151. The method of claim 150, wherein said inhibitor is a compound comprising the formula of formula XIX:
- 152. The method of claim 151, wherein said compound is 3-O-methyl sorbitollysine.
- 153. The method of claim 142, wherein said compound inhibits 3DG function.
- 154. The method of claim 153, wherein said inhibitor of 3DG function is selected from the group consisting of structural formulas I-XIX and arginine.
- 155. The method of claim 153, wherein said inhibitor is arginine.
- 156. The method of claim 153, wherein said inhibitor of 3DG function binds with 3DG.
- 157. The method of claim 153, wherein said compound inhibits advanced glycation end product modified protein formation.
- 158. The method of claim 153, wherein said compound inhibits a function selected from the group consisting of protein crosslinking, apoptosis, mutagenesis, and formation of a reactive oxygen species.
- 159. The method of claim 142, wherein said compound is administered via a route selected from the group consisting of topical, oral, intramuscular, and intravenous.
- 160. The method of claim 159, wherein said compound is administered via a topical route.
- 161. The method of claim 160, wherein said compound inhibits 3DG synthesis.
- 162. The method of claim 160, wherein said compound inhibits 3DG function.
- 163. The method of claim 162, wherein said compound stimulates 3DG detoxification.
- 164. The method of claim 159, wherein said inhibitor is administered in a pharmaceutical composition.
- 165. The method of claim 164, wherein said composition is selected from the group consisting of a lotion, a cream, a gel, a liniment, an ointment, a paste, a solution, a powder, and a suspension.
- 166. The method of claim 165, wherein said composition further comprises a moisturizer, a humectant, a demulcent, oil, water, an emulsifier, a thickener, a thinner, a surface active agent, a fragrance, a preservative, an antioxidant, a hydrotropic agent, a chelating agent, a vitamin, a mineral, a permeation enhancer, a cosmetic adjuvant, a bleaching agent, a depigmentation agent, a foaming agent, a conditioner, a viscosifier, a buffering agent, and a sunscreen.
- 167. The method of claim 159, wherein said inhibitor is administered at a frequency selected from the group consisting of once a day, twice a day, three times a day, four times a day, once a week, twice a week, once a month, and twice a month.
- 168. The method of claim 159, wherein said inhibitor is administered at a dosage ranging from about 1 ng/kg/application to about 100 g/kg/application.
- 169. The method of claim 159, wherein said inhibitor is administered at a dosage ranging from about 1 ng/kg/application to about 100 mg/kg/application.
- 170. The method of claim 159, wherein said inhibitor is administered as a controlled-release formulation.
- 171. The method of claim 170, wherein said inhibitor comprises from about 0.0001% to about 15% by weight of the composition.
- 172. A kit for administering a compound which inhibits alpha-dicarbonyl sugar synthesis in the skin of a mammal, said kit comprising a compound which inhibits alpha-dicarbonyl sugar synthesis, a standard, an applicator, and an instructional material for the use thereof.
- 173. A kit for administering a compound which inhibits alpha-dicarbonyl sugar function in the skin of a mammal, said kit comprising a compound which inhibits alpha-dicarbonyl sugar function, a standard, an applicator, and an instructional material for the use thereof.
- 174. A kit for inhibiting alpha-dicarbonyl sugar associated protein crosslinking in the skin of a mammal, said kit comprising an inhibitor of said alpha-dicarbonyl sugar associated protein cross-linking, a standard, an applicator, and an instructional material for the use thereof.
- 175. A kit for treating an alpha-dicarbonyl sugar associated disease or disorder in the skin of a mammal, said kit comprising an inhibitor of said alpha-dicarbonyl sugar, a standard, an applicator, and an instructional material for the use thereof.
- 176. A kit for administering a compound which inhibits 3DG synthesis in the skin of a mammal, said kit comprising a compound which inhibits 3DG synthesis, a standard, an applicator, and an instructional material for the use thereof.
- 177. The kit of claim 176, wherein said mammal is a human.
- 178. A kit for administering a compound which inhibits 3DG function in the skin of a mammal, said kit comprising a compound which inhibits 3DG function, a standard, an applicator, and an instructional material for the use thereof.
- 179. The kit of claim 178, wherein said mammal is a human.
- 180. A kit for inhibiting 3DG associated protein crosslinking in the skin of a mammal, said kit comprising an inhibitor of said 3DG associated protein cross-linking, a standard, an applicator, and an instructional material for the use thereof.
- 181. The kit of claim 180, wherein said mammal is a human.
- 182. A kit for treating a 3DG associated disease or disorder in the skin of a mammal, said kit comprising an inhibitor of said 3DG, a standard, an applicator, and an instructional material for the use thereof.
- 183. The kit of claim 182, wherein said inhibitor inhibits 3DG synthesis.
- 184. The kit of claim 182, wherein said inhibitor inhibits 3DG function.
- 185. The kit of claim 182, wherein said inhibitor inhibits 3DG accumulation.
- 186. The kit of claim 182, wherein said inhibitor causes detoxification of 3DG.
- 187. The kit of claim 182, wherein said mammal is a human.
- 188. A method for diagnosing an alpha-dicarbonyl sugar associated wrinkling, aging, disease, or disorder of the skin in a test subject, said method comprising acquiring a biological sample from said test subject, and comparing the level of an alpha-dicarbonyl sugar associated parameter of wrinkling, aging, disease, or disorder of the skin, in said biological sample with the level of said alpha-dicarbonyl associated parameter from an otherwise identical biological sample from a control subject with no alpha-dicarbonyl sugar associated wrinkling, aging, disease, or disorder of the skin, wherein a higher level of said parameter in said test subject, compared with the level of said parameter in said biological sample from said control subject, is an indication that said test subject has an alpha-dicarbonyl sugar associated wrinkling, aging, disease, or disorder of the skin, thereby diagnosing an alpha-dicarbonyl sugar associated wrinkling, aging, disease, or disorder of the skin.
- 189. The method of claim 188, wherein said alpha-dicarbonyl sugar is 3DG.
- 190. The method of claim 188, wherein said parameter is selected from the group consisting of 3DG, protein crosslinking, advanced glycation end product modified proteins, 3DF, fructosamine kinase/amadorase levels, fructosamine kinase/amadorase activity, and fructosamine kinase/amadorase mRNA.
- 191. The method of claim 188, wherein said biological sample is selected from the group consisting of skin, tissue, urine, saliva, blood, plasma, and sweat.
- 192. A method for diagnosing an alpha-dicarbonyl sugar associated wrinkling, aging, disease, or disorder of the skin in a subject, said method comprising acquiring a test sample of wrinkling, aging, disease or disorder affected skin from said subject, comparing the level of an alpha-dicarbonyl sugar parameter associated with a wrinkling, aging, disease, or disorder of the skin in said test sample of affected skin with the level of said alpha-dicarbonyl associated parameter from a sample of unaffected skin from said subject, wherein a higher level of said parameter in said test sample of affected skin, compared with the level of said parameter in said sample of unaffected skin, is an indication that said test sample of affected skin has an alpha-dicarbonyl sugar associated wrinkling, aging, disease, or disorder of the skin, thereby diagnosing an alpha-dicarbonyl sugar associated wrinkling, aging, disease, or disorder of the skin.
- 193. A method of inhibiting a function of an alpha-dicarbonyl sugar in the skin of a mammal, said method comprising administering to said mammal a pharmaceutical composition comprising an effective amount of said α-amino-β,β-mercapto-β,β-dimethyl-ethane or a modification or derivative thereof, thereby inhibiting the function of an alpha-dicarbonyl sugar in a mammal.
- 194. The method of claim 193, wherein said alpha-dicarbonyl sugar is 3DG.
- 195. The method of claim 193, wherein said α-amino-β,β-mercapto-β,β-dimethyl-ethane derivative or a modification or derivative thereof is selected from the group consisting of D-penicillamine, L-penicillamine, and D,L-penicillamine.
- 196. The method of claim 193, wherein said function is selected from the group consisting of protein crosslinking, formation of reactive oxygen species, lipid peroxidation, formation of advanced glycation end product modified proteins, mutagenicity, induction of DNA photodamage, and induction of apoptosis.
- 197. The method of claim 193, wherein said mammal is a human.
- 198. The method of claim 193, wherein said α-amino-β,β-mercapto-β,β-dimethyl-ethane or a modification or derivative thereof is administered as a controlled-release formulation.
- 199. The method of claim 193, wherein said pharmaceutical composition is selected from the group consisting of a lotion, a cream, a gel, a liniment, an ointment, a paste, a solution, a powder, and a suspension.
- 200. The method of claim 199, wherein said composition further comprises a moisturizer, a humectant, a demulcent, oil, water, an emulsifier, a thickener, a thinner, a surface active agent, a fragrance, a preservative, an antioxidant, a hydrotropic agent, a chelating agent, a vitamin, a mineral, a permeation enhancer, a cosmetic adjuvant, a bleaching agent, a depigmentation agent, a foaming agent, a conditioner, a viscosifier, a buffering agent, and a sunscreen.
- 201. The method of claim 193, wherein said α-amino-β,β-mercapto-β,β-dimethyl-ethane or a modification or derivative thereof is administered via a route selected from the group consisting of topical, oral, intramuscular, and intravenous.
- 202. The method of claim 201, wherein said α-amino-β,β-mercapto-β,β-dimethyl-ethane or a modification or derivative thereof is administered via a topical route.
- 203. The method of claim 193, wherein said α-amino-β,β-mercapto-β,β-dimethyl-ethane or a modification or derivative thereof comprises the structural formula of D-penicillamine:
- 204. A method of treating an alpha-dicarbonyl sugar associated skin disease or disorder in a mammal, said method comprising administering to said mammal an alpha-dicarbonyl sugar inhibiting amount of an α-amino-β,β-mercapto-β,β-dimethyl-ethane or a modification or derivative thereof, thereby treating an alpha-dicarbonyl sugar associated skin disease or disorder of a mammal.
- 205. A kit for treating an alpha-dicarbonyl sugar associated disease or disorder in the skin of a mammal, said kit comprising an effective amount of an α-amino-β,β-mercapto-β,β-dimethyl-ethane or a modification or derivative thereof, a standard, an applicator, and an instructional material for the use thereof.
- 206. A method for diagnosing an alpha-dicarbonyl sugar associated aging, disease, or disorder of the gums in a test subject, said method comprising acquiring a biological sample from said test subject, and comparing the level of an alpha-dicarbonyl sugar associated parameter of aging, disease, or disorder of the gums, in said biological sample with the level of said alpha-dicarbonyl associated parameter from an otherwise identical biological sample from a control subject with no alpha-dicarbonyl sugar associated aging, disease, or disorder of the gums, wherein a higher level of said parameter in said test subject, compared with the level of said parameter in said biological sample from said control subject, is an indication that said test subject has an alpha-dicarbonyl sugar associated aging, disease, or disorder of the gums, thereby diagnosing an alpha-dicarbonyl sugar associated aging, disease, or disorder of the gums.
- 207. The method of claim 206, wherein said alpha-dicarbonyl sugar is 3DG.
- 208. The method of claim 206, wherein said parameter is selected from the group consisting of 3DG, protein crosslinking, advanced glycation end product modified proteins, 3DF, fructosamine kinase/amadorase levels, fructosamine kinase/amadorase activity, and fructosamine kinase/amadorase mRNA.
- 209. The method of claim 206, wherein said biological sample is selected from the group consisting of skin, tissue, urine, saliva, blood, plasma, and sweat.
- 210. A method of treating an alpha-dicarbonyl sugar associated gum disease or disorder in a mammal, said method comprising administering to said mammal a pharmaceutical composition comprising an alpha-dicarbonyl sugar inhibiting amount of a compound which inhibits said alpha-dicarbonyl sugar associated gum disease or disorder, thereby treating an alpha-dicarbonyl sugar associated gum disease or disorder.
- 211. The method of claim 210, wherein said alpha-dicarbonyl sugar associated gum disease or disorder is selected from the group consisting of gingivitis and receding gums.
- 212. The method of claim 210, wherein said alpha-dicarbonyl sugar is 3DG.
- 213. The method of claim 210, wherein said compound is selected from the group consisting of the structural formulas I-XVIII and XIX.
- 214. The method of claim 210, wherein said compound is selected from the group consisting of arginine or a modification or derivative thereof, and an α-amino-β,β-mercapto-β,β-dimethyl-ethane or a modification or derivative thereof.
- 215. The method of claim 210, wherein said pharmaceutical composition is selected from the group consisting of a paste, a gel, a toothpaste, a mouthwash, a solution, an oral rinse, a suspension, an ointment, a cream, and a coating.
- 216. The method of claim 210, wherein said mammal is a human.
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application No. 60/373,103 filed on Apr. 17, 2002 and to a U.S. Provisional Application No. 60/392,530 filed on Jun. 27, 2002.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT
[0002] This invention was supported in part using funds from the U.S. Government (NIH Grant No. R21 DK55079) and the U.S. Government may therefore have certain rights in the invention.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60392530 |
Jun 2002 |
US |
|
60373103 |
Apr 2002 |
US |