Compositions and methods for skin care

Abstract

Compositions and methods are for disclosed for treating a skin condition that results from reactive oxygen species production in skin of a subject, including applying a topical formulation that contains a lipophilic cation-mitochondrially targeted antioxidant compound and that delivers a therapeutically effective amount of the antioxidant compound to skin fibroblasts and keratinocytes.

What is claimed is: 
     
         1 . A method of treating a skin condition that results from reactive oxygen species production in skin of a subject, the method comprising:
 applying to the skin a topical formulation that comprises
 (a) an antioxidant compound which comprises
 (i) a lipophilic cationic moiety linked by a linking moiety to an antioxidant moiety, and 
 (ii) an anionic complement for said cationic moiety, and 
 
 (b) a pharmaceutical excipient or carrier for topical use, 
   wherein the formulation delivers a therapeutically effective amount of the antioxidant compound to skin fibroblasts and keratinocytes and the cationic moiety is capable of mitochondrially targeting the antioxidant moiety, and   wherein the anionic complement is a pharmaceutically acceptable anion that is not a halogen ion or a nitrate anion and is not nucleophilic and does not exhibit reactivity against the antioxidant moiety, the cationic moiety or the linking moiety, and thereby treating the skin condition that results from reactive oxygen species production in skin.   
     
     
         2 . The method of  claim 1  wherein the antioxidant moiety comprises at least one antioxidant moiety that is selected from the group consisting of:
 (i) a quinone or a quinol, 
 (ii) vitamin E or a vitamin E derivative, 
 (iii) ascorbic acid or an ascorbic acid derivative, 
 (iv) alpha-lipoic acid or a derivative thereof, 
 (v) a chain breaking antioxidant, 
 (vi) a derivatized fullerene, 
 (vii) a spin trap, 
 (viii) an antioxidant moiety that is selected from the group consisting of butylated hydroxyanisole, butylated hydroxytoluene, 5,5-dimethylpyrroline-N-oxide, tert-butylnitrosobenzene, tert-nitrosobenzene and α-phenyl-tert-butylnitrone, and 
 (ix) N-acetyl cysteine. 
 
     
     
         3 . The method of  claim 1  wherein the topical formulation further comprises retinoic acid. 
     
     
         4 . The method of  claim 1  wherein the antioxidant compound is capable of altering (i) a detectable indicator of reactive oxygen species in a human skin fibroblast, and (ii) a detectable indicator of reactive oxygen species in a human skin keratinocyte. 
     
     
         5 . The method of  claim 1  wherein the lipophilic cationic moiety is a triphenylphosphonium cation. 
     
     
         6 . The method of  claim 1  wherein the pharmaceutically acceptable anion is an alkyl sulfonate. 
     
     
         7 . The method of  claim 1  wherein the pharmaceutically acceptable anion is selected from the group consisting of methanesulfonate, p-toluenesulfonate, ethanesulfonate, benzenesulfonate and 2-naphthalenesulfonate. 
     
     
         8 . The method of  claim 1  wherein the pharmaceutically acceptable anion is methanesulfonate. 
     
     
         9 . The method of  claim 1  wherein the antioxidant compound has the formula I: 
       
         
           
           
               
               
           
         
         or its quinol form, wherein R 1 , R 2 , and R 3  are the same or different and are selected from C 1  to C 5  alkyl and H, and wherein n is an integer from 2 to 20, and wherein Z is the anionic complement. 
       
     
     
         10 . The method of  claim 9  wherein Z is selected from the group consisting of an alkyl sulfonate, an aryl sulfonate and nitrate. 
     
     
         11 . The method of  claim 9  wherein C of (C) n  is saturated. 
     
     
         12 . The method of  claim 1  wherein the antioxidant compound has the formula: 
       
         
           
           
               
               
           
         
         or its quinol form, wherein Z is the anionic complement. 
       
     
     
         13 . The method of  claim 1  wherein the antioxidant compound has the formula: 
       
         
           
           
               
               
           
         
         or its quinol form. 
       
     
     
         14 . The method of  claim 1  wherein the pharmaceutical excipient or carrier comprises cyclodextrin. 
     
     
         15 . The method of  claim 14  wherein the antioxidant compound and cyclodextrin are present at a compound-to-cyclodextrin molar ratio of (i) from about 5:1 to about 1:5, (ii) from about 4:1 to about 1:4, (iii) from about 2:1 to about 1:2, (iv) about 1:1, (v) about 1:2, or (vi) from about 10:1 to about 1:10. 
     
     
         16 . The method of  claim 14  wherein the cyclodextrin is β-cyclodextrin. 
     
     
         17 . The method of  claim 1  wherein the skin condition that results from reactive oxygen species production is characterized by alteration of either one or both of (i) a detectable indicator of reactive oxygen species in a human skin fibroblast, and (ii) a detectable indicator of reactive oxygen species in a human skin keratinocyte. 
     
     
         18 . The method of  claim 1  wherein the skin condition that results from reactive oxygen species production is selected from age-related skin damage, skin photoaging, skin wrinkling, skin scar tissue deposition, altered skin elasticity, altered skin color, altered skin texture, altered skin thickness, angioma, telangiectasia, sunburn, skin dryness, skin itchiness, neoplasia, precancerous growth, erythema, skin redness and inflammation caused by laser surgery, radiation therapy, rosaceae, a burn or sepsis. 
     
     
         19 . The method of  claim 1  wherein the skin condition that results from reactive oxygen species production comprises a skin infection that comprises at least one of a bacterial infection, a viral infection, a parasitic infection and a fungal infection. 
     
     
         20 . The method of  claim 1  wherein the skin condition that results from reactive oxygen species production comprises one or more of acne, amyloidosis, a benign skin tumor, a blister or ulcer, bullous disease, skin cancer, dermatitis, eczema, inflammation, ichthyosis, an insect bite or insect sting, keratosis pilaris, pruritis, psoriasis, a scaling disease, a rash, vitiligo and a sweat gland disorder. 
     
     
         21 . The method of  claim 1  wherein the antioxidant compound is capable of altering (i) at least one detectable indicator of reactive oxygen species in a human skin fibroblast that is selected from the group consisting of reactive oxygen species generation, matrix metalloproteinase expression and an extracellular signal-related kinase (ERK) phosphorylation state, and (ii) at least one detectable indicator of reactive oxygen species in a human skin keratinocyte that is selected from the group consisting of reactive oxygen species generation, matrix metalloproteinase expression and an extracellular signal-related kinase (ERK) phosphorylation state. 
     
     
         22 . A method of promoting topical wound healing in skin of a subject, the method comprising:
 applying to the skin a topical formulation that comprises
 (a) an antioxidant compound which comprises
 a lipophilic cationic moiety linked by a linking moiety to an antioxidant moiety, and 
 (ii) an anionic complement for said cationic moiety, and 
 
 (b) a pharmaceutical excipient or carrier for topical use, 
   wherein the formulation delivers a therapeutically effective amount of the antioxidant compound to skin fibroblasts and keratinocytes and the cationic moiety is capable of mitochondrially targeting the antioxidant moiety, and   wherein the anionic complement is a pharmaceutically acceptable anion that is not a halogen ion or a nitrate anion and is not nucleophilic and does not exhibit reactivity against the antioxidant moiety, the cationic moiety or the linking moiety, and thereby treating the skin condition that results from reactive oxygen species production in skin.   
     
     
         23 . The method of  claim 22  wherein the antioxidant moiety comprises at least one antioxidant moiety that is selected from the group consisting of:
 (i) a quinone or a quinol, 
 (ii) vitamin E or a vitamin E derivative, 
 (iii) ascorbic acid or an ascorbic acid derivative, 
 (iv) alpha-lipoic acid or a derivative thereof, 
 (v) a chain breaking antioxidant, 
 (vi) a derivatized fullerene, 
 (vii) a spin trap, 
 (viii) an antioxidant moiety that is selected from the group consisting of butylated hydroxyanisole, butylated hydroxytoluene, 5,5-dimethylpyrroline-N-oxide, tert-butylnitrosobenzene, tert-nitrosobenzene and α-phenyl-tert-butylnitrone, and 
 (ix) N-acetyl cysteine. 
 
     
     
         24 . The method of  claim 23  wherein the topical formulation further comprises retinoic acid. 
     
     
         25 . The method of  claim 23  wherein the antioxidant compound is capable of altering (i) a detectable indicator of reactive oxygen species in a human skin fibroblast, and (ii) a detectable indicator of reactive oxygen species in a human skin keratinocyte. 
     
     
         26 . The method of  claim 23  wherein the lipophilic cationic moiety is a triphenylphosphonium cation. 
     
     
         27 . The method of  claim 23  wherein the pharmaceutically acceptable anion is an alkyl sulfonate. 
     
     
         28 . The method of  claim 23  wherein the pharmaceutically acceptable anion is selected from the group consisting of methanesulfonate, p-toluenesulfonate, ethanesulfonate, benzenesulfonate and 2-naphthalenesulfonate. 
     
     
         29 . The method of  claim 23  wherein the pharmaceutically acceptable anion is methanesulfonate.