Topical compositions for treatment of skin conditions

Abstract

The invention provides a topical formulation adapted for treatment of a skin condition comprising (i) at least one retinoid; and (ii) salicylic acid or an ester, amide, salt, or solvate thereof. The invention also includes a kit for treatment of skin conditions comprising a retinoid and salicylic acid, as well as a method of treating skin conditions utilizing the inventive formulation and kit.

1 . A topical formulation adapted for treatment of a skin condition, the formulation comprising:
 (i) at least one retinoid; and   (ii) salicylic acid or an ester, amide, salt, or solvate thereof.   
     
     
         2 . The topical formulation of  claim 1 , wherein the retinoid has either of the following structures: 
       
         
           
           
               
               
           
         
       
       wherein R is: 
       
         
           
           
               
               
           
         
         X is —H, —F, —Cl, —Br, —I, —OH, —OR, —OR′ 
       
       
         
           
           
               
               
           
         
         —NO 2 , —NH 2 , —NHR′, or —NR′ 2 ; 
         n is a number from 1 to 5; 
         R′ is H or any of the lower alkyls ranging from C 1  to C 6 ; 
         wherein R″ is 
       
       
         
           
           
               
               
           
         
         or R′; 
         R′″ is the hydrocarbon backbone of fatty acids; 
         R″″ is R′ or the hydrocarbon backbone of fatty acids; 
         R′″″ is the lower alkyls ranging from C 1  to C 6 ; and further, 
         where the are two or more R′, R″, R′″, R″″, or R′″″ groups attached to the same carbon, 
         each R′, R″, R′″, R″″, or R′″″ group may be the same as or different from the other R′, R″, R′″, R″″, or R′″″ groups attached to that carbon. 
       
     
     
         3 . The topical formulation of  claim 2 , wherein the retinoid is 13-trans retinoic 1-hydroxy-3,3-dimethyl-2-butanone ester or 2-(13-cis-retinoyloxy)-4′-methoxyacetophenone. 
     
     
         4 . The topical formulation of  claim 2 , wherein the retinoid is selected from the group consisting of 1-(13-cis-retinoyloxy)-2-propanone, 1-(13-cis-retinoyloxy)-3-decanoyloxy-2-propanone, 1,3-bis-(13-cis-retinoyloxy)-2-propanone, 2-(13-cis-retinoyloxy)-acetophenone, 13-cis-retinoyloxy methyl 2,2-dimethyl propanoate, 2-(13-cis-retinoyloxy)-n-methyl-acetamide, 1-(13-cis-retinoyloxy)-3-hydroxy-2-propanone, 1-(13-cis-retinoyloxy)-2,3-dioleoylpropanone, succinimdyl 13-cis-retinoate, 1-(13-cis-retinoyloxy)methyl phenyl ketone, 1-(13-cis-retinoyloxy)-2,3-dioleoylpropane, 1-(all-trans-retinoyloxy)-2-propanone, and 2-(all-trans-retinoyloxy)-4′-methoxyacetophenone. 
     
     
         5 . The topical formulation of  claim 1 , wherein the retinoid has either of the following structures: 
       
         
           
           
               
               
           
         
       
       wherein R is: 
       
         
           
           
               
               
           
         
       
       wherein X is —H, —F, —Cl, —Br, —I, —OH, —OR, —OR′ 
       
         
           
           
               
               
           
         
         —NO 2 , —NH 2 , —NHR′, or —NR′ 2 ; 
         wherein n is a number from 1 to 5; 
         wherein R′ is H or any of the lower alkyls ranging from C 1  to C 6 ; 
         wherein R″ is 
       
       
         
           
           
               
               
           
         
         or R′; 
         wherein R′″ is the hydrocarbon backbone of fatty acids; 
         wherein R″″ is R″ or the hydrocarbon backbone of fatty acids; 
         wherein R′″″ is the lower alkyls ranging from C 1  to C 6 ; and further, 
         where the are two or more R′, R″, R′″, R″″, or R′″″ groups attached to the same carbon, 
         each R′, R″, R′″, R″″, or R′″″ group may be the same as or different from the other R′, R″, R′″, R″″, or R′″″ groups attached to that carbon. 
       
     
     
         6 . The topical formulation of  claim 5 , wherein the retinoid is pinacoyl 9-cis-retinoate. 
     
     
         7 . The topical formulation of  claim 5 , wherein the retinoid is selected from the group consisting of 1-(9-cis-retinoyloxy)-2-propanone, 1-(9-cis-retinoyloxy)-3-decanoyloxy-2-propanone, 1,3-bis-(9-cis-retinoyloxy)-2-propanone, 2-(9-cis-retinoyloxy)-acetophenone, 9-cis-retinoyloxy methyl 2,2-dimethyl propanoate, 2-(9-cis-retinoyloxy)-n-methyl-acetamide, 1-(9-cis-retinoyloxy)-3-hydroxy-2-propanone, 1-(9-cis-retinoyloxy)-2,3-dioleoylpropanone, and succinimidyl 9-cis-retinoate. 
     
     
         8 . The topical formulation of  claim 1 , wherein the retinoid is selected from the group consisting of 13-trans retinoic 1-hydroxy-3,3-dimethyl-2-butanone ester, 2-(13-cis-retinoyloxy)-4′-methoxyacetophenone, and pinacoyl 9-cis-retinoate, and the salicylic acid is in the form of an alkali metal salt. 
     
     
         9 . The topical formulation of  claim 1 , wherein the retinoid is derived from 13-cis-retinoic acid, 13-trans retinoic acid, or 9-cis-retinoic acid, and wherein the retinoid is characterized by an absence of skin irritation, mutagenicity, and teratogenicity. 
     
     
         10 . A kit for treatment of a skin condition, the kit comprising (i) at least one retinoid in a topical formulation; (ii) salicylic acid or an ester, amide, salt, or solvate thereof in a topical formulation; and (iii) instructions for usage of the kit to treat a skin condition. 
     
     
         11 . The kit of  claim 10 , wherein the retinoid component and the salicylic acid component are formulated in a single topical formulation. 
     
     
         12 . The kit of  claim 10 , wherein the retinoid component and the salicylic acid component are formulated in separate topical formulations. 
     
     
         13 . The kit of  claim 10 , wherein the retinoid has either of the following structures: 
       
         
           
           
               
               
           
         
       
       wherein R is: 
       
         
           
           
               
               
           
         
         X is —H, —F, —Cl, —Br, —I, —OH, —OR, —OR′ 
       
       
         
           
           
               
               
           
         
         —NO 2 , —NH 2 , —NHR′, or —NR′ 2 ; 
         n is a number from 1 to 5; 
         R′ is H or any of the lower alkyls ranging from C 1  to C 6 ; 
         wherein R″ is 
       
       
         
           
           
               
               
           
         
         or R′; 
         R′″ is the hydrocarbon backbone of fatty acids; 
         R″″ is R′ or the hydrocarbon backbone of fatty acids; 
         R′″″ is the lower alkyls ranging from C 1  to C 6 ; and further, 
         where the are two or more R′, R″, R′″, R″″, or R′″″ groups attached to the same carbon, 
         each R′, R″, R′″, R″″, or R′″″ group may be the same as or different from the other R′, R″, R′″, R″″, or R′″″ groups attached to that carbon. 
       
     
     
         14 . The kit of  claim 13 , wherein the retinoid is 13-trans retinoic 1-hydroxy-3,3-dimethyl-2-butanone ester or 2-(13-cis-retinoyloxy)-4′-methoxyacetophenone. 
     
     
         15 . The kit of  claim 13 , wherein the retinoid is selected from the group consisting of 1-(13-cis-retinoyloxy)-2-propanone, 1-(13-cis-retinoyloxy)-3-decanoyloxy-2-propanone, 1,3-bis-(13-cis-retinoyloxy)-2-propanone, 2-(13-cis-retinoyloxy)-acetophenone, 13-cis-retinoyloxy methyl 2,2-dimethyl propanoate, 2-(13-cis-retinoyloxy)-n-methyl-acetamide, 1-(13-cis-retinoyloxy)-3-hydroxy-2-propanone, 1-(13-cis-retinoyloxy)-2,3-dioleoylpropanone, succinimdyl 13-cis-retinoate, 1-(13-cis-retinoyloxy)methyl phenyl ketone, 1-(13-cis-retinoyloxy)-2,3-dioleoylpropane, 1-(all-trans-retinoyloxy)-2-propanone, and 2-(all-trans-retinoyloxy)-4′-methoxyacetophenone. 
     
     
         16 . The kit of  claim 10 , wherein the retinoid has either of the following structures: 
       
         
           
           
               
               
           
         
       
       wherein R is: 
       
         
           
           
               
               
           
         
       
       wherein X is —H, —F, —Cl, —Br, —I, —OH, —OR, —OR′ 
       
         
           
           
               
               
           
         
         NO 2 , —NH 2 , —NHR′, or —NR′ 2 ; 
         wherein n is a number from 1 to 5; 
         wherein R′ is H or any of the lower alkyls ranging from C 1  to C 6 ; 
         wherein R″ is 
       
       
         
           
           
               
               
           
         
         or R′; 
         wherein R′″ is the hydrocarbon backbone of fatty acids; 
         wherein R″″ is R″ or the hydrocarbon backbone of fatty acids; 
         wherein R′″″ is the lower alkyls ranging from C 1  to C 6 ; and further, 
         where the are two or more R′, R″, R′″, R″″, or R′″″ groups attached to the same carbon, 
         each R′, R″, R′″, R″″, or R′″″ group may be the same as or different from the other R′, R″, R′″, R″″, or R′″″ groups attached to that carbon. 
       
     
     
         17 . The kit of  claim 16 , wherein the retinoid is pinacoyl 9-cis-retinoate. 
     
     
         18 . The kit of  claim 16 , wherein the retinoid is selected from the group consisting of 1-(9-cis-retinoyloxy)-2-propanone, 1-(9-cis-retinoyloxy)-3-decanoyloxy-2-propanone, 1,3-bis-(9-cis-retinoyloxy)-2-propanone, 2-(9-cis-retinoyloxy)-acetophenone, 9-cis-retinoyloxy methyl 2,2-dimethyl propanoate, 2-(9-cis-retinoyloxy)-n-methyl-acetamide, 1-(9-cis-retinoyloxy)-3-hydroxy-2-propanone, 1-(9-cis-retinoyloxy)-2,3-dioleoylpropanone, and succinimidyl 9-cis-retinoate. 
     
     
         19 . The kit of  claim 10 , wherein the retinoid is selected from the group consisting of 13-trans retinoic 1-hydroxy-3,3-dimethyl-2-butanone ester, 2-(13-cis-retinoyloxy)-4′-methoxyacetophenone, and pinacoyl 9-cis-retinoate, and the salicylic acid is in the form of an alkali metal salt. 
     
     
         20 . The kit of  claim 10 , wherein the skin condition to be treated is selected from the group consisting of acne vulgaris, cystic acne, hyper-pigmentation, hypo-pigmentation, dermal and epidermal hypoplasia and keratoses, wrinkles of the skin as an incident of aging and actinic damage, enlarged pores, ichthyoses, follicular disorders, benign epithelial tumors, perforated dematoses, and disorders of keratinization. 
     
     
         21 . A method of treating a skin condition in a subject, comprising topically administering to the subject (i) at least one retinoid, and (ii) salicylic acid or an ester, amide, salt, or solvate thereof. 
     
     
         22 . The method of  claim 21 , wherein the retinoid component and the salicylic acid component are formulated in a single topical formulation. 
     
     
         23 . The method of  claim 21 , wherein the retinoid component and the salicylic acid component are formulated in separate topical formulations. 
     
     
         24 . The method of  claim 21 , wherein the skin condition to be treated is selected from the group consisting of acne vulgaris, cystic acne, hyper-pigmentation, hypo-pigmentation, dermal and epidermal hypoplasia and keratoses, wrinkles of the skin as an incident of aging and actinic damage, enlarged pores, surface roughness, ichthyoses, follicular disorders, benign epithelial tumors, perforated dematoses, and disorders of keratinization. 
     
     
         25 . The method of  claim 21 , wherein the retinoid has either of the following structures: 
       
         
           
           
               
               
           
         
       
       wherein R is: 
       
         
           
           
               
               
           
         
         X is —H, —F, —Cl, —Br, —I, —OH, —OR, —OR″ 
       
       
         
           
           
               
               
           
         
         —NO 2 , —NH 2 , —NHR′, or —NR′ 2 ; 
         n is a number from 1 to 5; 
         R′ is H or any of the lower alkyls ranging from C 1  to C 6 ; 
         wherein R″ is 
       
       
         
           
           
               
               
           
         
         or R′; 
         R′″ is the hydrocarbon backbone of fatty acids; 
         R″″ is R′ or the hydrocarbon backbone of fatty acids; 
         R′″″ is the lower alkyls ranging from C 1  to C 6 ; and further, 
         where the are two or more R′, R″, R′″, R″″, or R′″″ groups attached to the same carbon, 
         each R′, R″, R′″, R″″, or R′″″ group may be the same as or different from the other R′, R″, R′″, R″″, or R′″″ groups attached to that carbon. 
       
     
     
         26 . The method of  claim 25 , wherein the retinoid is 13-trans retinoic 1-hydroxy-3,3-dimethyl-2-butanone ester or 2-(13-cis-retinoyloxy)-4′-methoxyacetophenone. 
     
     
         27 . The method of  claim 25 , wherein the retinoid is selected from the group consisting of 1-(13-cis-retinoyloxy)-2-propanone, 1-(13-cis-retinoyloxy)-3-decanoyloxy-2-propanone, 1,3-bis-(13-cis-retinoyloxy)-2-propanone, 2-(13-cis-retinoyloxy)-acetophenone, 13-cis-retinoyloxy methyl 2,2-dimethyl propanoate, 2-(13-cis-retinoyloxy)-n-methyl-acetamide, 1-(13-cis-retinoyloxy)-3-hydroxy-2-propanone, 1-(13-cis-retinoyloxy)-2,3-dioleoylpropanone, succinimdyl 13-cis-retinoate, 1-(13-cis-retinoyloxy)methyl phenyl ketone, 1-(13-cis-retinoyloxy)-2,3-dioleoylpropane, 1-(all-trans-retinoyloxy)-2-propanone, and 2-(all-trans-retinoyloxy)-4′-methoxyacetophenone. 
     
     
         28 . The method of  claim 21 , wherein the retinoid has either of the following structures: 
       
         
           
           
               
               
           
         
       
       wherein R is: 
       
         
           
           
               
               
           
         
       
       wherein X is —H, —F, —Cl, —Br, —I, —OH, —OR, —OR′ 
       
         
           
           
               
               
           
         
          —NO 2 , —NH 2 , —NHR′, or —NR 12 ; 
         wherein n is a number from 1 to 5; 
         wherein R′ is H or any of the lower alkyls ranging from C 1  to C 6 ; 
         wherein R″ is 
       
       
         
           
           
               
               
           
         
         or R′; 
         wherein R′″ is the hydrocarbon backbone of fatty acids; 
         wherein R″″ is R″ or the hydrocarbon backbone of fatty acids; 
         wherein R′″″ is the lower alkyls ranging from C 1  to C 6 ; and further, 
         where the are two or more R′, R″, R′″, R″″, or R′″″ groups attached to the same carbon, 
         each R′, R″, R′″, R″″, or R′″″ group may be the same as or different from the other R′, R″, R′″, R″″, or R′″″ groups attached to that carbon. 
       
     
     
         29 . The method of  claim 28 , wherein the retinoid is pinacoyl 9-cis-retinoate. 
     
     
         30 . The method of  claim 28 , wherein the retinoid is selected from the group consisting of 1-(9-cis-retinoyloxy)-2-propanone, 1-(9-cis-retinoyloxy)-3-decanoyloxy-2-propanone, 1,3-bis-(9-cis-retinoyloxy)-2-propanone, 2-(9-cis-retinoyloxy)-acetophenone, 9-cis-retinoyloxy methyl 2,2-dimethyl propanoate, 2-(9-cis-retinoyloxy)-n-methyl-acetamide, 1-(9-cis-retinoyloxy)-3-hydroxy-2-propanone, 1-(9-cis-retinoyloxy)-2,3-dioleoylpropanone, and succinimidyl 9-cis-retinoate. 
     
     
         31 . The method of  claim 21 , wherein the retinoid is selected from the group consisting of 13-trans retinoic 1-hydroxy-3,3-dimethyl-2-butanone ester, 2-(13-cis-retinoyloxy)-4′-methoxyacetophenone, and pinacoyl 9-cis-retinoate, and the salicylic acid is in the form of an alkali metal salt.