3-Deoxyglucosone And Skin

Abstract

The invention relates to a method of removing 3-deoxyglucosone and other alpha-dicarbonyl sugars from skin. The invention further relates to methods of inhibiting production and function of 3-deoxyglucosone and other alpha-dicarbonyl sugars in skin. The invention also relates to methods of treating 3-deoxyglucosone and other alpha-dicarbonyl sugars associated diseases and disorders of skin.

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 - 14 . (canceled) 
     
     
         15 . The method of  claim 5 , wherein said inhibitor of fructosamine kinase function is a compound comprising the formula of formula XIX: 
       
         
           
           
               
               
           
         
         a. wherein X is —NR′—, —S(O)—, —S(O) 2 —, or —O—, R′ being selected from the group consisting of H, linear or branched chain alkyl group (C 1 -C 4 ), CH 2 (CHOR 2 ) n CH 2 OR 2  where n=1-5 and R 2  is H, alkyl (C 1 -C 4 ) or an unsubstituted or substituted aryl group (C 6 -C 10 ) or araalkyl group (C 7 -C 10 ), CH(CH 2 OR 2 )(CHOR 2 ) n CH 2 OR 2  where n=1-4 and R 2  is H, alkyl (C 1 -C 4 ) or an unsubstituted or substituted aryl group (C 6 -C 10 ) or araalkyl group (C 7 -C 10 ), an unsubstituted or substituted aryl group (C 6 -C 10 ), and an unsubstituted or substituted aralkyl group (C 7 -C 10 ); 
         b. R is a substituent selected from the group consisting of H, an amino acid residue, a polyaminoacid residue, a peptide chain, a linear or branched chain aliphatic group (C 1 -C 8 ), which is unsubstituted or substituted with at least one nitrogen- or oxygen-containing substituent, a linear or branched chain aliphatic group (C 1 -C 8 ), which is unsubstituted or substituted with at least one nitrogen- or oxygen-containing substituent and interrupted by at least one —O—, —NH—, or —NR″— moiety; 
         c. R″ being linear or branched chain alkyl group (C 1 -C 6 ) and an unsubstituted or substituted aryl group (C 6 -C 10 ) or aralkyl group (C 7 -C 10 ), with the proviso that when X represents —NR′—, R and R′, together with the nitrogen atom to which they are attached, may also represent a substituted or unsubstituted heterocyclic ring having from 5 to 7 ring atoms, with at least one of nitrogen and oxygen being the only heteroatoms in said ring, said aryl group (C 6 -C 10 ) or aralkyl group (C 7 -C 10 ) and said heterocyclic ring substituents being selected from the group consisting of H, alkyl (C 1 -C 6 ), halogen, CF 3 , CN, NO 2  and —O-alkyl (C 1 -C 6 ); R 1  is a polyol moiety having 1 to 4 linear carbon atoms, Y is a hydroxymethylene moiety —CHOH—; 
         d. Z is selected from the group consisting of —H, —O-alkyl (C 1 -C 6 ), -halogen, —CF 3 , —CN, —COOH, and —SO 3 H 2 , and optionally —OH; and 
         e. the isomers and pharmaceutically acceptable salts of said compound, except that X—R in the above formula does not represent hydroxyl or thiol. 
       
     
     
         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 - 21 . (canceled) 
     
     
         22 . The method of  claim 1 , wherein said mammal is a human. 
     
     
         23 - 136 . (canceled) 
     
     
         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 - 139 . (canceled) 
     
     
         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 . (canceled) 
     
     
         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 - 144 . (canceled) 
     
     
         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 . (canceled) 
     
     
         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: 
       
         
           
           
               
               
           
         
         a. wherein X is —NR′—, —S(O)—, —S(O) 2 —, or —O—, R′ being selected from the group consisting of H, and linear or branched chain alkyl group (C 1 -C 4 ) and an unsubstituted or substituted aryl group (C 6 -C 10 ) or aralkyl group (C 7 -C 10 ); 
         b. R is a substituent selected from the group consisting of H, an amino acid residue, a polyaminoacid residue, a peptide chain, a linear or branched chain aliphatic group (C 1 -C 8 ), which is unsubstituted or substituted with at least one nitrogen- or oxygen-containing substituent, a linear or branched chain aliphatic group (C 1 -C 8 ), which is unsubstituted or substituted with at least one nitrogen- or oxygen-containing substituent and interrupted by at least one —O—, —NH—, or —NR″— moiety; 
         c. R″ being linear or branched chain alkyl group (C 1 -C 6 ) and an unsubstituted or substituted aryl group (C 6 -C 10 ) or aralkyl group (C 7 -C 10 ), with the proviso that when X represents —NR′—, R and R′, together with the nitrogen atom to which they are attached, may also represent a substituted or unsubstituted heterocyclic ring having from 5 to 7 ring atoms, with at least one of nitrogen and oxygen being the only heteroatoms in said ring, said aryl group (C 6 -C 10 ) or aralkyl group (C 7 -C 10 ) and said heterocyclic ring substituents being selected from the group consisting of H, alkyl (C 1 -C 6 ), halogen, CF 3 , CN, NO 2  and —O-alkyl (C 1 -C 6 ); R 1  is a polyol moiety having 1 to 4 linear carbon atoms, Y is a hydroxymethylene moiety —CHOH—; 
         d. Z is selected from the group consisting of —H, —O-alkyl (C 1 -C 6 ), -halogen, —CF 3 , —CN, —COOH, and —SO 3 H 2 , and optionally —OH; and 
         e. the isomers and pharmaceutically acceptable salts of said compound, except that X—R in the above formula does not represent hydroxyl or thiol. 
       
     
     
         152 . The method of  claim 151 , wherein said compound is 3-O-methyl sorbitollysine. 
     
     
         153 - 158 . (canceled) 
     
     
         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 - 163 . (canceled) 
     
     
         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 - 216 . (canceled)