Claims for Patent: 11,084,788

Summary for Patent: 11,084,788

Title:	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.
Inventor(s):	Nicholas S. Bodor, John J. Koleng, David Angulo
Assignee:	Bodor Laboratories Inc
Application Number:	US17/116,501
Patent Claims:	1. An anhydrous topical gel 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) at least one gelling or viscosity-controlling ingredient comprising hydroxypropyl cellulose; (d) citric acid; (e) hexylene glycol; and (f) optionally, at least one additional carrier or excipient; wherein the anhydrous topical gel composition comprises from about 1% w/v or w/w to about 25% w/v or w/w of the compound of formula (2), and wherein the anhydrous topical gel composition has greater storage stability compared to a composition comprising an aqueous solvent or aqueous buffer. 2. The anhydrous topical gel composition of claim 1, wherein said anhydrous topical gel composition further comprises at least one additional carrier or excipient. 3. The anhydrous topical gel 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. 4. The anhydrous topical gel composition of claim 1, wherein the anhydrous topical gel composition comprises the compound of formula (2) at a concentration of from about 1% w/v or w/w to about 20% w/v or w/w. 5. The anhydrous topical gel composition of claim 1, wherein the anhydrous topical gel composition comprises the compound of formula (2) at a concentration of from about 2% w/v or w/w to about 10% w/v or w/w. 6. The anhydrous topical gel composition of claim 1, wherein the anhydrous topical gel composition is 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. 7. The anhydrous topical gel composition of claim 1, wherein the anhydrous topical gel composition is 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. 8. The anhydrous topical gel 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. 9. The anhydrous topical gel composition of claim 1, wherein the anhydrous topical composition further comprises a 6% silicone gum blend in dimethicone. 10. The anhydrous topical gel composition of claim 1, wherein the anhydrous topical gel composition is administered in a dose of from about 0.5 ml to about 2.0 ml. 11. A method of treating hyperhidrosis in a subject, said method comprising topically administering an anhydrous topical gel composition 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, wherein said anhydrous topical gel composition comprises: (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) at least one gelling or viscosity-controlling ingredient comprising hydroxypropyl cellulose; (d) citric acid; (e) hexylene glycol; and (d) optionally, at least one additional carrier or excipient; wherein the anhydrous topical gel composition comprises from about 1% to about 25% of the compound of formula (2), and wherein the anhydrous topical gel composition has greater storage stability compared to a composition comprising an aqueous solvent or aqueous buffer, and wherein the anhydrous topical gel composition is administered by application to an anatomic area selected from a hand palm area, a foot plantar area, a groin area, an axilla area, and a facial area of the subject. 12. The method of claim 11, wherein said anhydrous topical gel composition comprises at least one additional carrier or excipient. 13. The method of claim 11, 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. 14. The method of claim 11, wherein the anhydrous topical gel composition comprises the compound of formula (2) at a concentration of from about 1% w/v or w/w to about 20% w/v or w/w. 15. The method of claim 11, wherein the anhydrous topical gel composition comprises the compound of formula (2) at a concentration of from about 2% w/v or w/w to about 10% w/v or w/w. 16. The method of claim 11, wherein the anhydrous topical gel composition is 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. 17. The method of claim 11, wherein the anhydrous topical gel composition is 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. 18. The method of claim 11, wherein the anhydrous topical composition further comprises a 6% silicone gum blend in dimethicone. 19. The method of claim 11, wherein the anhydrous topical gel composition is administered in -a dose of from about 0.5 ml to about 2.0 ml.