Claims for Patent: 9,220,707

Summary for Patent: 9,220,707

Title:	Method of dosing and use of soft anticholinergic esters
Abstract:	A method of treating hyperhidrosis in a mammalian subject comprising: a) providing a composition comprising a pharmaceutically acceptable vehicle and from about 1.0% to about 25% of a compound having the formula: and b) topically administering the composition to skin of an area of a mammalian subject suffering from hyperhidosis, before bedtime, such that, compared to untreated, baseline conditions, sweat production is reduced by at least about 25% for at least about six (6) hours.
Inventor(s):	Nicholas S. Bodor, David Angulo
Assignee:	Bodor Laboratories Inc
Application Number:	US14/213,242
Patent Claims:	1. A method of treating hyperhidrosis in a mammalian subject, said method comprising topically administering a composition comprising a pharmaceutically acceptable vehicle and from about 1.0% to about 25% of 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 steroisomeric configuration at the 1′ and 3′ position, or being a mixture thereof; to skin of an area of a mammalian subject suffering from hyperhidosis, before bedtime, such that, compared to untreated, baseline conditions, sweat production is reduced by at least about 25% for at least about 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. 2. The method according to claim 1, having one or more of the following features: a) the subject is a human; b) sweat production is reduced by about 25% to about 99%; c) the composition is formulated as a solid or semi-solid, powder, del, cream, lotion, foam, solution, suspension or emulsion; d) sweat production is reduced from about 8 hours to about 24 hours; e) the composition is applied to skin of the subject at a superficial anatomic area selected from a hand palm area, a foot plantar area, a groin area, an axilla area or a facial area. 3. The method according to claim 1, having one or more of the following features: a) sweat production is reduced by about 30% to about 75%; b) the composition is formulated as a solid or semi-solid, powder, gel, cream, lotion, foam, solution, suspension or emulsion comprising from about 2% to about 10% of said compound; c) sweat production is reduced from about 8 hours to about 12 hours. 4. The method according to claim 1, having one or more of the following features: a) sweat production is reduced from about 45% to about 60%; b) the composition is formulated as a 5% solution of the compound in 70% ethanol. 5. The method according to claim 1 wherein sweat production is reduced by about 50%. 6. The method according to claim 1, further comprising topically administering a second dose of the composition in the morning after the subject awakens. 7. The method according to claim 1, wherein the compound is selected from the group consisting of: (i) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1- (methoxycarbionyirnethyl)-1-methylpyrrolidinium bromide; (ii) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonyimethyl)-1-methyloyrrolidinium bromide; (iii) (2R) 3-(2-cyclopentyl-2 -phenyl-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-methylpyrrolidinium bromide; (iv) (2R) 3-(2-cyclopentyl-2-phervi-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide; (v) (2R,3 ′R) 3-(2-cyclopentyl-2-phenyi-2-hydroxyacetoxy)-1-(methoxycarbonylmethyi)-1-methylpyrrolidinium bromide; (vi) (2R,3′S) 3-(2-cycle pentyl-2-phenyi-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-methylpyrrolidinium bromide; (vii) (2R,3′R) 3-(2-cyciopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide; (viii) (2R,3′5) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide; (ix) (2R,1′R,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetexy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide; (x) (2R,1′S,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide; (xi) (2R,l′R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide; (xii) (2R,1′5,3 R) 3-(2-oyolopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methyloyrrolidinium bromide; (xiii) (2R.I′R,3′S ) 3-(2-cyciopentyl-2-phenyl-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-methylpyrrolidinium bromide; (xiv) (2R,1′S, 3′S ) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-methylpyrrolidinium bromide; (xv) (2R,1′R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-methylpyrrolidinium bromide; and (xvi) (2R,1′S, 3′R ) 3-(2-cyclopentyl-2-phenyi-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-methylpyrrolidinium bromide. 8. The method according to claim 1, wherein the composition has two or more of the following features: a) the composition is formulated as a solid or semi-solid, powder, gel, cream, lotion, foam, solution, suspension or emulsion comprising from about 2% to about 10% of said compound; b) the composition comprises an about 5% solution of the compound in 70% ethanol; c) the composition comprises a compound wherein R is methyl. 9. A method of dosing a subject suffering from hyperhidrosis, said method of dosing comprising administering before bedtime a composition comprising a pharmaceutically acceptable vehicle and from about 1.0% to about 25% of 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 steroisomeric configuration at the 1′ and 3′ position, or being a mixture thereof; 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 about 25% for at least about 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. 10. The method according to claim 9, having one or more of the following features: a) the subject is a human; b) sweat production is reduced by about 25% to about 99%; c) the composition is formulated as a solid or semi-solid, powder, gel, cream, lotion, foam, solution, suspension or emulsion; d) sweat production is reduced from about 8 hours to about 24 hours; e) the composition is applied to skin of the subject at a superficial anatomic area selected from a hand palm area, a foot plantar area, a groin area, an axilla area or a facial area. 11. The method according to claim 9, having one or more of the following features: a) sweat production is reduced by about 30% to about 75%; b) the composition is formulated as a solid or semi-solid, powder, gel, cream, lotion, foam, solution, suspension or emulsion comprising from about 2% to about 10% of said compound; c) sweat production is reduced from about 8 hours to about 12 hours. 12. The method according to claim 9, having one or more of the following features: a) sweat production is reduced from about 45% to about 60%; b) the composition is formulated as a 5% solution of the compound in 70% ethanol. 13. The method according to claim 9, wherein sweat production is reduced by about 50%. 14. The method according to claim 9, further comprising topically administering a second dose of the composition in the morning after the subject awakens. 15. The method according to claim 9, wherein the compound is selected from the group consisting of: (i) 3-(2-cyclopentyl-2-phenyi-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-methylpyrrolidinium bromide; (ii) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide; (iii) (2R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(methoxycarbohylmethyl)-1-methylpyrrolidiniurn bromide; (iv) (2R) 3-(2-cyclopentyl-2-phenyi-2-hydroxyacetoxy)-1-(ethoxycarbonyirriethyl)-1-methylpyrrolidinium bromide; (v) (2R, 3′R) 3-(2-cyclopentyl-2-phenyi-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-rnethylpyrrolidinium bromide; (vi) (2R,3′S) 3-(2-cyclopentyl-2-phanyl-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-rnethylpyrroiidinium bromide; (vii) (2R,3′R) 3-(2-cyclobentyl-2-phertyl-2-hydroxyacetoxy)-1-(ethoxycarbohylmethyl)-1-rnethylpyrrolidinium bromide; (viii) (2R,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide; (ix) (2R,1′R,3′S) 3-(2-cyclopentyl-2-phenyi-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide; (x) (2R,1′S,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-rnethyloyrrolidinium bromide; (xi) (2R,1′R,3′R) 3-(2-cyclobentyl-2-phenyi-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methyloyrrolidinium bromide; (xii) (2R,1S,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methyloyrrolidinium bromide; (xiii) (2R,1′R,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(methoxycarbonyirhethyl)-1-methylpyrrolidini2m bromide; (xiv) (2R,1′S,3′S) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(methoxycarbonylrnethyl)-1-methylpyrrolidinium bromide; (xv) (2R,1′R,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-rnethyipyrrolidinium bromide; and (xvi) (2R,1′S,3′R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-methylbyrrolidinium bromide. 16. The method according to claim 9, wherein the composition has two or more of the following features: a) the composition is formuiated as a soiid or semi-solid, powder, gel, cream, lotion, foam, solution, suspension or emulsion comprising from about 2% to about 10% of said compound; b) the composition comprises an about 5% solution of the compound in 70% ethanol; c) the composition comprises a compound wherein R is methyl. 17. The method according to claim 2, wherein R in the compound is methyl. 18. The method according to claim 2, wherein R in the compound is ethyl. 19. The method according to claim 3, wherein R in the compound is methyl. 20. The method according to claim 3, wherein R in the compound is ethyl. 21. The method according to claim 10, wherein R in the compound is methyl. 22. The method according to claim 10, wherein R in the compound is ethyl. 23. The method according to claim 11, wherein R in the compound is methyl. 24. The method according to claim 11, wherein R in the compound is ethyl. 25. The method according to claim 1, wherein the composition comprises isopropyl alcohol or ethanol alone as a solvent for the compound, or as a co-solvent with water. 26. The method according to claim 25, wherein the solvent for the compound is ethanol alone. 27. The method according to claim 25, wherein R in the compound is methyl. 28. The method according to claim 25, wherein R in the compound is ethyl. 29. The method according to claim 26, wherein R in the compound is methyl. 30. The method according to claim 26, wherein R in the compound is ethyl. 31. The method according to claim 9, wherein the composition comprises isopropyl alcohol or ethanol alone as a solvent for the compound, or as a co-solvent with water. 32. The method according to claim 31, wherein the solvent for the compound is ethanol alone. 33. The method according to claim 31, wherein R in the compound is methyl. 34. The method according to claim 31, wherein R in the compound is ethyl. 35. The method according to claim 32, wherein R in the compound is methyl. 36. The method according to claim 32, wherein R in the compound is ethyl.