Topical Antiviral Formulations

Abstract

The present invention relates to formulations of nucleotide reverse transcriptase inhibitors (N(t)RTIs), preferably [2-(6-Amino-purin-9-yl)-1-methyl-ethoxymethyl]-phosphonic acid (tenofovir, PMPA), or a physiologically functional derivative thereof, suitable for topical application and their use in the prevention of HIV infections.

1 . A method for the prevention of the symptoms or effects of an HIV infection in an infected animal which comprises administering to said animal a prophylactically effective amount of a topical formulation comprising an effective amount of an NRTI in combination with a pharmaceutically acceptable vehicle.  
     
     
         2 . A method according to  claim 1  wherein the NRTI comprises [2-(6-Amino-purin-9-yl)-1-methyl-ethoxymethyl]-phosphonic acid diisopropoxycarbonyloxymethyl ester (tenofovir) or a physiologically functional derivative thereof.  
     
     
         3 . The method according to  claim 2  wherein the formulation comprises from about 0.2 to about 2 weight percent tenofovir.  
     
     
         4 . The method according to  claim 1  wherein the NRTI comprises a physiologically functional derivative of tenofovir which has the structure:  
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are independently selected from H, C 1 -C 6  alkyl, C 1 -C 6  substituted alkyl, C 6 -C 20  aryl, C 6 -C 20  substituted aryl, C 6 -C 20  arylalkyl, C 6 -C 20  substituted arylalkyl, acyloxymethyl esters —CH 2 OC═O)R and acyloxymethyl carbonates —CH 2 OC(═O)OR 9  where R 9  is C 1 -C 6  alkyl, C 1 -C 6  substituted alkyl, C 6 -C 20  aryl or C 6 -C 20  substituted aryl;  
         R 3  is H C 1 -C 6  alkyl, C 1 -C 6  substituted alkyl, or CH 2 OR 8  where R 8  is C 1 -C 6  alkyl, C 1 -C 6  hydroxyalkyl or C 1 -C 6  haloalkyl;  
         R 4  and R 5  are independently selected from H, NH 2 , NHR and NR 2  where R is C 1 -C 6  alkyl; and  
         R 6  and R 7  are independently selected from H and C 1 -C 6  alkyl.  
       
     
     
         5 . A pharmaceutical formulation comprising an NRTI and a pharmaceutically acceptable medium suitable for topical application.  
     
     
         6 . A pharmaceutical formulation comprising [2-(6-Amino-purin-9-yl)-1-methyl-ethoxymethyl]-phosphonic acid diisopropoxycarbonyloxymethyl ester (tenofovir) or a physiologically functional derivative thereof and a pharmaceutically acceptable medium suitable for topical application.  
     
     
         7 . The formulation according to  claim 5  wherein the NRTI comprises a physiologically functional derivative of tenofovir which has the structure:  
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are independently selected from H, C 1 -C 6  alkyl, C 1 -C 6  substituted alkyl, C 6 -C 20  aryl, C 6 -C 20  substituted aryl, C 6 -C 20  arylalkyl, C 6 -C 20  substituted arylalkyl, acyloxymethyl esters —CH 2 OC(═O)R and acyloxymethyl carbonates —CH 2 OC(═O)OR 9  where R 9  is C 1 -C 6  alkyl, C 1 -C 6  substituted alkyl, C 6 -C 20  aryl or C 6 -C 20  substituted aryl;  
         R 3  is H, C 1 -C 6  alkyl, C 1 -C 6  substituted alkyl, or CH 2 OR 8  where R 8  is C 1 -C 6  alkyl, C 1 -C 6  hydroxyalkyl or C 1 -C 6  haloalkyl;  
         R 4  and R 5  are independently selected from H, NH 2 , NHR and NR 2  where R is C 1 -C 6  alkyl; and  
         R 6  and R 7  are independently selected from H and C 1 -C 6  alkyl.  
       
     
     
         8 . A gel formulation of  claims 5  to  7 .  
     
     
         9 . A cream formulation of  claims 5  to  7 .  
     
     
         10 . A foam formulation of  claims 5  to  7 .  
     
     
         11 . A suppository formulation of  claims 5  to  7 .  
     
     
         12 . A condom coated with a formulation of  claims 5  to  7 .