Formulation for soft anticholinergic analogs

Abstract

Topical formulations comprising soft glycopyrrolates are useful for treating excessive sweating conditions in subjects, such as humans suffering from hyperhidrosis. Preferably, at least one soft anticholinergic agent is provided in an effective amount or concentration in an anhydrous formulation that can inhibit excessive perspiration resulting from a condition such as hyperhidrosis.

1 . An anhydrous topical composition for reduction or amelioration of excessive sweating, said composition comprising:
 a) one or more soft glycopyrrolate analogue as an active ingredient, having the formula:   
       
         
           
           
               
               
           
         
       
       wherein R is methyl or ethyl; and
 b) one or more non-aqueous pharmaceutically acceptable solvents, 
 
       said composition comprising at least about 0.1% to about 30% of the glycopyrrolate analogue and having greater storage stability compared to a composition comprising an aqueous solvent or aqueous buffer. 
     
     
         2 . The anhydrous topical composition of  claim 1 , wherein said compound is: 
       
         
           
           
               
               
           
         
       
       wherein R is methyl or ethyl; 
     
     
         3 . The composition of  claim 1 , wherein R is ethyl. 
     
     
         4 . The composition of  claim 1  wherein R is methyl. 
     
     
         5 . The composition of  claim 1  wherein the compound has a stereoisomeric configuration at the 2 position and the 1′ and 3′ positions selected from R, S and RS, or a mixture thereof. 
     
     
         6 . The composition of  claim 2  wherein the compound has R-stereoisomeric configuration at the 2 position, and stereoisomeric configuration at the 1′ and 3′ positions selected from R, S and RS, or a mixture thereof. 
     
     
         7 . The composition of  claim 1  wherein the compound is selected from the group consisting of:
 (i) 3-[2-cyclopentylphenylhydroxyacetoxy]-1′-methyl-1′-methoxycarbonylmethyl-pyrrolidinium bromide; 
 (ii) 3-[2-cyclopentylphenylhydroxyacetoxy]-1′-methyl-1′-ethoxycarbonylmethyl-pyrrolidinium bromide; 
 (iii) 3-[2(R)-cyclopentylphenylhydroxyacetoxy]-1′-methyl-1′-methoxycarbonylmethyl-pyrrolidinium bromide; 
 (iv) 3-[2(R)-cyclopentylphenylhydroxyacetoxy]-1′-methyl-1′-ethoxycarbonylmethyl-pyrrolidinium bromide; 
 (v) 3′(R)-[2(R)-cyclopentylphenylhydroxyacetoxy]-1′-methyl-1′-methoxycarbonylmethyl-pyrrolidinium bromide; 
 (vi) 3′(S)-[2(R)-cyclopentylphenylhydroxyacetoxy]-1′-methyl-1′-methoxycarbonylmethyl-pyrrolidinium bromide; 
 (vii) 3′(R)-[2(R)-cyclopentylphenylhydroxyacetoxy]-1′-methyl-1′-ethoxycarbonylmethyl-pyrrolidinium bromide; 
 (viii) 3′(S)-[2(R)-cyclopentylphenylhydroxyacetoxy]-1′-methyl-1′-ethoxycarbonylmethyl-pyrrolidinium bromide; 
 (ix) 1′(R)-3′(R)-[2(R)-cyclopentylphenylhydroxyacetoxy]-1′-methyl-1′-ethoxycarbonylmethyl-pyrrolidinium bromide; 
 (x) 1′(R)-3′(S)-[2(R)-cyclopentylphenylhydroxyacetoxy]-1′-methyl-1′-ethoxycarbonylmethyl-pyrrolidinium bromide; 
 (xi) 1′(S)-3′(R)-[2(R)-cyclopentylphenylhydroxyacetoxy]-1′-methyl-1′-ethoxycarbonylmethyl-pyrrolidinium bromide; 
 (xii) 1′(S)-3′(R)-[2(R)-cyclopentylphenylhydroxyacetoxy]-1′-methyl-1′-ethoxycarbonylmethyl-pyrrolidinium bromide; 
 (xiii) 1′(R)-3′(R)-[2(R)-cyclopentylphenylhydroxyacetoxy]-1′-methyl-1′-methoxycarbonylmethyl-pyrrolidinium bromide; 
 (xiv) 1′(R)-3′(S)-[2(R)-cyclopentylphenylhydroxyacetoxy]-1′-methyl-1′-methoxycarbonylmethyl-pyrrolidinium bromide; 
 (xv) 1′(S)-3′(R)-[2(R)-cyclopentylphenylhydroxyacetoxy]-1′-methyl-1′-methoxycarbonylmethyl-pyrrolidinium bromide; and 
 (xvi) 1′(S)-3′(R)-[2(R)-cyclopentylphenylhydroxyacetoxy]-1′-methyl-1′-methoxycarbonylmethyl-pyrrolidinium bromide. 
 
     
     
         8 . (canceled) 
     
     
         9 . The composition of  claim 1  packaged into a multiple dose container that meters a dose of about 0.5 to about 2.0 ml of the composition for each application. 
     
     
         10 . The composition of  claim 1  packaged into a single or unit dose container that delivers a single or unit dose of about 0.5 to about 2.0 ml of the composition for application. 
     
     
         11 . The composition of  claim 1  wherein the non-aqueous solvent is ethanol. 
     
     
         12 . The composition of  claim 1  further comprising an antiperspirant. 
     
     
         13 . The composition of  claim 12  wherein the antiperspirant is an aluminum salt.