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 .- 13 . (canceled) 
     
     
         14 . A topical composition, said composition comprising the following ingredients:
 (a) a compound having the formula:   
       
         
           
           
               
               
           
         
       
       wherein R is methyl or ethyl, said compound having the R stereoisomeric configuration at the 2 position and the R, S or RS stereoisomeric configuration at the 1′ and 3′ positions, or being a mixture thereof;
 (b) anhydrous ethanol present in an amount sufficient to act as a non-aqueous solvent for the compound of formula (2); 
 (c) optionally, at least one gelling or viscosity-controlling ingredient; and 
 (d) optionally, at least one additional carrier or excipient; 
 provided that said topical composition is anhydrous and comprises from about 1% to about 20% w/w of the compound of formula (2), said composition having greater storage stability compared to a composition comprising an aqueous solvent or aqueous buffer. 
 
     
     
         15 . The composition of  claim 14 , comprising at least about 70% w/w anhydrous ethanol. 
     
     
         16 . The composition of  claim 14 , comprising from about 70% to about 99.99% w/w anhydrous ethanol. 
     
     
         17 . The composition of  claim 14 , wherein at least one gelling or viscosity-controlling ingredient is present. 
     
     
         18 . The composition of  claim 14 , wherein at least one additional carrier or excipient is present. 
     
     
         19 . The composition of  claim 17 , wherein at least one additional carrier or excipient is present. 
     
     
         20 . The composition of  claim 14 , wherein the compound of formula (2) is selected from the group consisting of:
 (a) (2R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;   (b) (2R,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;   (c) (2R,1′R,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;   (d) (2R,1′S,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;   (e) (2R,1′R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;   (f) (2R,1′S,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;   (g) (2R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-methyl-1-methoxycarbonylmethylpyrrolidinium bromide;   (h) (2R,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-methyl-1-methoxycarbonylmethylpyrrolidinium bromide;   (i) (2R,1′R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-methyl-1-methoxycarbonylmethylpyrrolidinium bromide;   (j) (2R,1′R,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-methyl-1-methoxycarbonylmethylpyrrolidinium bromide;   (k) (2R,1′S,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-methyl-1-methoxycarbonylmethylpyrrolidinium bromide; and   (l) (2R,1′S,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-methyl-1-methoxycarbonylmethylpyrrolidinium bromide.   
     
     
         21 . The composition of  claim 14 , wherein the compound of formula (2) is at a concentration of from about 2% w/w to about 10% w/w of the composition. 
     
     
         22 . The composition of  claim 14 , packaged into a multiple dose container that meters a dose of from about 0.5 ml to about 1.0 ml of the composition for each application. 
     
     
         23 . The composition of  claim 14 , packaged into a single or unit dose container that delivers a single or unit dose of about 0.5 ml to about 1.0 ml of the composition for each application. 
     
     
         24 . The composition of  claim 14 , wherein the compound of formula (2) is (2R, 3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide. 
     
     
         25 . The composition of  claim 17 , wherein the gelling or viscosity-controlling ingredient is hydroxypropyl cellulose. 
     
     
         26 . The composition of  claim 25 , further comprising citric acid. 
     
     
         27 . The composition of  claim 25 , further comprising hexylene glycol. 
     
     
         28 . The composition of  claim 25 , further comprising a 6% silicone gum blend in dimethicone. 
     
     
         29 . The composition of  claim 25 , further comprising citric acid, hexylene glycol and a 6% silicone gum blend in dimethicone. 
     
     
         30 . A method of treating hyperhidrosis in a subject, said method comprising topically administering a composition as claimed in  claim 14  to skin of an area of a subject suffering from hyperhidrosis, before bedtime, such that, compared to untreated, baseline conditions, sweat production is reduced by at least 25% for at least six (6) hours; and such that sweat production is reduced by an amount substantially equivalent to an amount that sweat production is reduced as compared to untreated, baseline conditions, following administration of a composition comprising the same concentration of glycopyrrolate, and with an improved safety profile compared to topical glycopyrrolate. 
     
     
         31 . A method of treating hyperhidrosis in a subject, said method comprising topically administering a composition as claimed in  claim 14  to skin of an area of a subject suffering from hyperhidrosis, such that, compared to untreated, baseline conditions, sweat production is reduced by at least 25% for at least six (6) hours; and such that sweat production is reduced by an amount substantially equivalent to an amount that sweat production is reduced as compared to untreated, baseline conditions, following administration of a composition comprising the same concentration of glycopyrrolate, and with an improved safety profile compared to topical glycopyrrolate.