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.

What is claimed is: 
     
         1 . A topical composition for treating, inhibiting or ameliorating excessive sweating, said composition comprising:
 (a) a compound having the formula:   
       
         
           
           
               
               
           
         
         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; 
         (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 25% of the compound of formula (2), said composition having greater storage stability compared to a composition comprising an aqueous solvent or aqueous buffer. 
       
     
     
         2 . The composition of  claim 1 , wherein at least one gelling or viscosity-controlling ingredient is present. 
     
     
         3 . The composition of  claim 1 , wherein at least one additional carrier or excipient is present. 
     
     
         4 . The composition of  claim 2 , wherein at least one additional carrier or excipient is present. 
     
     
         5 . The composition of  claim 1 , wherein the compound of formula (2) is selected from the group consisting of:
 (i) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;   (ii) (2R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;   (iii) (2R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;   (iv) (2R,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;   (v) (2R,1′R,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;   (vi) (2R,1′S,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;   (vii) (2R,1′R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide; and   (viii) (2R,1′S,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide.   
     
     
         6 . The composition of  claim 1 , wherein the compound of formula (2) is at a concentration of from about 1% to about 20% of the composition. 
     
     
         7 . The composition of  claim 1 , wherein the compound of formula (2) is at a concentration of from about 2% to about 10%. 
     
     
         8 . The composition of  claim 1 , 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. 
     
     
         9 . The composition of  claim 1 , 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. 
     
     
         10 . The composition of  claim 1 , wherein the compound of formula (2) is (2R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide. 
     
     
         11 . The composition of  claim 5 , wherein the compound of formula (2) is from about 1% to about 20% of the composition. 
     
     
         12 . The composition of  claim 6 , wherein the compound of formula (2) is (2R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide. 
     
     
         13 . The composition of  claim 7 , wherein the compound of formula (2) is (2R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide. 
     
     
         14 . The composition of  claim 8 , wherein the compound of formula (2) is (2R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide. 
     
     
         15 . The composition of  claim 9 , wherein the compound of formula (2) is (2R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide. 
     
     
         16 . The composition of  claim 2 , wherein the gelling or viscosity-controlling ingredient is hydroxypropyl cellulose. 
     
     
         17 . The composition of  claim 2 , further comprising citric acid. 
     
     
         18 . The composition of  claim 2 , further comprising hexylene glycol. 
     
     
         19 . The composition of  claim 2 , further comprising DIMETHICONOL BLEND 20. 
     
     
         20 . The composition of  claim 16 , further comprising citric acid, hexylene glycol and DIMETHICONOL BLEND 20. 
     
     
         21 . A method of treating hyperhidrosis in a subject, said method comprising topically administering a composition as claimed in  claim 1  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. 
     
     
         22 . The method of  claim 21 , wherein the compound of formula (2) is selected from the group consisting of:
 (i) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;   (ii) (2R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;   (iii) (2R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;   (iv) (2R,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;   (v) (2R,1′R,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;   (vi) (2R,1′S,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide;   (vii) (2R,1′R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide; and   (viii) (2R,1′S,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide.   
     
     
         23 . The method of  claim 21 , wherein the compound of formula (2) is at a concentration of from about 1% to about 20% of the composition. 
     
     
         24 . The method of  claim 21 , wherein the compound of formula (2) is at a concentration of from about 2% to about 10%. 
     
     
         25 . The method of  claim 21 , wherein the compound of formula (2) is (2R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide. 
     
     
         26 . The method of  claim 21 , wherein a dose of from about 0.5 ml to about 2.0 ml is applied.