Modified green tea polyphenol formulations

Abstract

Modified green tea polyphenols and methods of their use are provided. One aspect provides compounds and compositions containing green tea polyphenols with one on more ester-linked fatty acids.

1 . A topical formulation comprising a modified green tea polyphenol and an excipient suitable for topical administration,
 wherein the modified green tea polyphenol comprises (−)-epicatechin, (−)-epigallocatechin, (−)-epicatechin-3-gallate, (−)-epigallocatechin-3-gallate, or an enantiomer, isomer, or epimer thereof, substituted with one or more C 1 -C 30  hydrocarbon chains.   
     
     
         2 . The formulation of  claim 1 , wherein the one or more C 1 -C 30  hydrocarbon chains are linked to the green tea polyphenol by ester groups. 
     
     
         3 . The formulation of  claim 2 , wherein the one or more hydrocarbon chains are C 15  or C 17  hydrocarbon chains. 
     
     
         4 . The formulation of  claim 1 , wherein the modified green tea polyphenol comprises a compound defined by Formula I: 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , R 3 , R 4 , R 5 , are each independently H, OH, 
       
       
         
           
           
               
               
           
         
         wherein R 7  is a linear, branched or cyclic, saturated or unsaturated, substituted or unsubstituted C 1 -C 30  group, wherein if R 7  is cyclic, R 7  is a C 3 -C 30  group; 
         R 6  is O; and 
         wherein at least one of R 1 , R 2 , R 3 , R 4 , or R 5  is 
       
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or prodrug thereof. 
       
     
     
         5 . The formulation of  claim 4 , wherein at least two of R 1 , R 2 , R 3 , R 4 , R 5  are independently 
       
         
           
           
               
               
           
         
       
     
     
         6 . The formulation of  claim 4 , wherein at least three of R 1 , R 2 , R 3 , R 4 , R 5  are independently 
       
         
           
           
               
               
           
         
       
     
     
         7 . The formulation of  claim 4 , wherein at least four of R 1 , R 2 , R 3 , R 4 , R 5  are independently 
       
         
           
           
               
               
           
         
       
     
     
         8 . The formulation of  claim 4 , wherein R 7  is a C 15  or a C 17  group, 
     
     
         9 . The formulation of  claim 1 , wherein the modified green tea polyphenol comprises a compound defined by Formula II: 
       
         
           
           
               
               
           
         
         wherein R 1 , R 2 , R 3 , R 4 , R 7 , R 8 , R 9 , and R 10  are each independently H, OH, 
       
       
         
           
           
               
               
           
         
         R 11  is a linear, branched, or cyclic, saturated or unsaturated, substituted or unsubstituted C 1 -C 30  group, wherein if R 11  is cyclic, R 11  is a C 3 -C 30  group; 
         R 5  is independently O, —NR 12 R 13  or S, wherein R 12  and R 13  are independently hydrogen, or a linear, branched, or cyclic, saturated or unsaturated, substituted or unsubstituted C 1 -C 30  group, wherein if R 12  and/or R 13  are cyclic, R 12  and/or R 13 are  C 3 -C 30  groups; 
         R 6  is O; and 
         wherein at least one of R 1 , R 2 , R 3 , R 4 , R 7 , R 8 , R 9 , or R 10  are independently 
       
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or prodrug thereof. 
       
     
     
         10 . The formulation of  claim 9 , wherein at least two of R 1 , R 2 , R 3 , R 4 , R 7 , R 8 , R 9 , or R 10  are independently 
       
         
           
           
               
               
           
         
       
     
     
         11 . The formulation of  claim 9 , wherein at least three of R 1 , R 2 , R 3 , R 4 , R 7 , R 8 , R 9 , or R 10  are independently 
       
         
           
           
               
               
           
         
       
     
     
         12 . The formulation of  claim 9 , wherein at least four of R 1 , R 2 , R 3 , R 4 , R 7 , R 8 , R 9 , or R 10  are independently 
       
         
           
           
               
               
           
         
       
     
     
         13 . The formulation of  claim 9 , wherein R 11  is a C is  group. 
     
     
         14 . The formulation of  claim 9 , wherein R 11  is a C 17  group. 
     
     
         15 . The formulation of  claim 1 , wherein the excipient is selected from the group consisting of surfactants, emulsifiers, emulsion stabilizers, emollients, buffers, solvents, oils, detergents, waxes, and preservatives. 
     
     
         16 . The formulation of  claim 15 , further comprising an additional bioactive ingredient. 
     
     
         17 . The formulation of  claim 16 , wherein the additional bioactive ingredient is selected from the group consisting of vitamins, anti-psoriasis agents, anti-fungal agents, anti-bacterial agents, skin protectants, salicylic acid, coal tar, zinc pyrithione, selenium sulfide, and combinations thereof. 
     
     
         18 . The formulation of  claim 15 , wherein the formulation is a bar soap, liquid soap, shampoo, conditioner, body wash, lotion, oil, spray, emulsion, foam, cream, gel, milk, balm, lip balm, powder, pencil, or stick. 
     
     
         19 . A method of treating a dermatological condition comprising contacting skin with an effective amount of the composition defined by  claim 1  to reduce inflammation or hyperproliferation of keratinocytes. 
     
     
         20 . The method of  claim 19 , wherein the dermatological condition is dermatitis selected from the group consisting of cercarial dermatitis, dermatitis herpetiformis, atopic dermatitis, seborrhoeic dermatitis, and contact dermatitis.