Skin Lightening Compositions

Abstract

Compositions and methods for lightening and/or depigmenting skin are provided, the compositions comprising compounds having the structure: wherein: R 1 and R 2 are same or different and are each selected from the group consisting of hydrogen, alkyl, carbomethoxy, carboethoxy, alkoxy, and alkanoyl, any of which may be halogen-substituted, and halogen; R 6 is selected from the group consisting of hydrogen, methyl, and ethyl; and R 3 , R 4 and R 5 are the same or different and are each selected from the group consisting of hydrogen, methyl, methoxy, ethoxy, methoxyethoxy, ethoxyethoxy, propoxy, propoxymethoxy, and the like, any of which may be halogen-substituted; or having the structure: wherein: R 2 is hydrogen, lower alkyl or hydroxy lower alkyl; R 3 is lower alkyl, —CH 2 CN, hydroxy lower alkyl, —NO, —CH 2 N═C or (wherein R 6 and R 7 are independently selected from the group consisting of hydrogen and lower alkyl) or hydrogen provided R 2 is not hydrogen; R 4 is Z-T-W wherein Z represents —O—, —NH— or a single bond; T represents a straight- or branched-chain lower-alkylene group; when Z is a single bond, T also represents an ethenylene or a propenylene group wherein the unsaturated carbon is at the single bond; when Z is —O—, T also represents an allylene group wherein the saturated carbon is at the oxygen; and W represents hydrogen, when T is allylene and Z is —O—, and Ar, wherein Ar is selected from thienyl, pyridinyl, furanyl, phenyl and substituted phenyl wherein there are one or more substituents on the phenyl independently selected from halogen or lower alkyl; and R 5 is hydrogen, halogen or lower alkyl; or pharmaceutically-, cosmetically- and dermatologically-acceptable salts, solvates, and bioprecursors, and stereoisomers and enantiomers of these compounds, free from or mixed with other enantiomers or stereoisomers; and such compounds in compositions with a pharmaceutically-, cosmetically- or dermatologically-acceptable carrier thereof comprising a safe and effective amount of the skin lightening or depigmenting compound.

What is claimed is: 
     
         1 . A topically applicable composition for lightening or depigmenting skin, comprising in the range of from about 0.00005% to about 0.5% of at least one compound selected from the group consisting of omeprazole (5- or 6-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole); esomeprazole (S-5-methoxy-2-{(4-methoxy-3,5dimethylpyridin-2-yl)methylsufinyl]-3H-benzoimidazole); lansoprazole (2-{[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl-1H-benzo(d)imidazole); pantoprazole (RS-6-(difluoromethoxy))-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]-1H-benzo(d)imidazole); rabeprazole (pariprazole) (2-([4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl)-1H-benzo(d)imidazole); leminoprazole (2-((o-(isobutylmethylamino)benzyl)sulfinyl)benzimidazole); timoprazole (2-(pyridine-2-ylmethylsulfinyl)-1H-benzimidazole); and sulfides and sodium salts thereof; and
 a cosmetic ingredient which is a further skin lightening compound, a sunscreen, or a combination thereof;   formulated into a topically applicable, cosmetically or dermatologically acceptable vehicle, carrier or diluent therefor.   
     
     
         2 . The topically applicable composition for lightening or depigmenting skin according to  claim 1 , comprising at least one sulfide of at least one compound selected from the group consisting of omeprazole (5- or 6-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole); esomeprazole (S-5-methoxy-2-{(4-methoxy-3,5dimethylpyridin-2-yl)methylsufinyl]-3H-benzoimidazole); lansoprazole (2-{[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl-1H-benzo(d)imidazole); pantoprazole (RS-6-(difluoromethoxy))-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]-1H-benzo(d)imidazole); rabeprazole (pariprazole) (2-([4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl)-1H-benzo(d)imidazole); leminoprazole (2-((o-(isobutylmethylamino)benzyl)sulfinyl)benzimidazole); and timoprazole (2-(pyridine-2-ylmethylsulfinyl)-1H-benzimidazole). 
     
     
         3 . The topically applicable composition for lightening or depigmenting skin according to  claim 2 , comprising a sulfide of omeprazole (5- or 6-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole). 
     
     
         4 . The topically applicable composition for lightening or depigmenting skin according to  claim 1 , which is in the form of an anhydrous composition, an aqueous-based solution, a suspension, a dispersion, a lotion, a serum, an essence, an emulsion, a milk, a cream, a gel, a paste, an ointment, a spray, a stick, a mousse, an aerosol or microcapsules. 
     
     
         5 . A method of lightening or depigmenting the skin, comprising topically applying to skin in need of such treatment a topically applicable composition comprising in the range of from about 0.00005% to about 0.5% of at least one compound selected from the group consisting of esomeprazole (S-5-methoxy-2-{(4-methoxy-3,5dimethylpyridin-2-yl)methylsufinyl]-3H-benzoimidazole); lansoprazole (2-{[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl-1H-benzo(d)imidazole); pantoprazole (RS-6-(difluoromethoxy))-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]-1H-benzo(d)imidazole); rabeprazole (pariprazole), (2-([4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl)-1H-benzo(d)imidazole); leminoprazole (2-((o-(isobutylmethylamino)benzyl)sulfinyl)benzimidazole); timoprazole (2-(pyridine-2-ylmethylsulfinyl)-1H-benzimidazole); and sulfides and sodium salts thereof; and
 a cosmetic ingredient which is a further skin lightening compound, a sunscreen, or a combination thereof;   formulated into a topically applicable, cosmetically or dermatologically acceptable vehicle, carrier or diluent therefor.   
     
     
         6 . The method of lightening or depigmenting the skin according to  claim 5 , wherein the topically applicable composition comprises at least one sulfide of at least one compound selected from the group consisting of omeprazole (5- or 6-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole); esomeprazole (S-5-methoxy-2-{(4-methoxy-3,5dimethylpyridin-2-yl)methylsufinyl]-3H-benzoimidazole); lansoprazole (2-{[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl-1H-benzo(d)imidazole); pantoprazole (RS-6-(difluoromethoxy))-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]-1H-benzo(d)imidazole); rabeprazole (pariprazole) (2-([4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl)-1H-benzo(d)imidazole); leminoprazole (2-((o-(isobutylmethylamino)benzyl)sulfinyl)benzimidazole); and timoprazole (2-(pyridine-2-ylmethylsulfinyl)-1H-benzimidazole). 
     
     
         7 . The method of lightening or depigmenting the skin according to  claim 5 , wherein the topically applicable composition comprises a sulfide of omeprazole (5- or 6-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole). 
     
     
         8 . The method of lightening or depigmenting the skin according to  claim 5 , wherein the topically applicable composition is in the form of an anhydrous composition, an aqueous-based solution, a suspension, a dispersion, a lotion, a serum, an essence, an emulsion, a milk, a cream, a gel, a paste, an ointment, a spray, a stick, a mousse, an aerosol or microcapsules.