Method of dosing and use of soft anticholinergic esters

• US 9,492,429 B2
• Filed: 11/13/2015
• Issued: 11/15/2016
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Bodor Laboratories, Inc.
• Original Assignee: Bodor Laboratories, Inc.
• Inventors: Bodor, Nicholas S., Angulo, David
• Primary Examiner(s): Weddington, Kevin E
• Application Number:
  US14/941,183
• Publication Number:
  US 20160067214A1
• Time in Patent Office: 368 Days
• Field of Search: 424/65, 514/424, 514/947
• US Class Current: 1/1
• CPC Class Codes: A61K 31/14 Quaternary ammonium compounds, e.g. edrophonium, choline betaines A61K31/205
• CPC Class Codes: A61K 31/205 Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/4015 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 8/416 Quaternary ammonium compounds A61K8/35 takes precedence
• CPC Class Codes: A61K 8/4913 having five membered rings, e.g. pyrrolidone carboxylic acid
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61Q 15/00 Anti-perspirants or body deodorants deodorisation of air A61L9/00

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.

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:

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, 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.

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 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.

15. The method according to claim 1, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

16. The method according to claim 1, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

17. The method according to claim 2, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

18. The method according to claim 2, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

19. The method according to claim 3, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

20. The method according to claim 3, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

27. 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.

28. The method according to claim 27, wherein the solvent for the compound is ethanol alone.

29. The method according to claim 27, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

30. The method according to claim 27, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

31. The method according to claim 28, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

32. The method according to claim 28, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

8. 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:

9. The method according to claim 8, 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.

10. The method according to claim 8, 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.

11. The method according to claim 8, 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.

12. The method according to claim 8, wherein sweat production is reduced by about 50%.

13. The method according to claim 8, further comprising topically administering a second dose of the composition in the morning after the subject awakens.

14. The method according to claim 8, 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.

21. The method according to claim 8, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

22. The method according to claim 8, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

23. The method according to claim 9, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

24. The method according to claim 9, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

25. The method according to claim 10, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

26. The method according to claim 10, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

33. The method according to claim 8, wherein the composition comprises isopropyl alcohol or ethanol alone as a solvent for the compound, or as a co-solvent with water.

34. The method according to claim 33, wherein the solvent for the compound is ethanol alone.

35. The method according to claim 33, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

36. The method according to claim 33, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

37. The method according to claim 34, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(methoxycarbonylmethyl)-1-methylpyrrolidinium bromide.

38. The method according to claim 34, wherein the compound is (2R,3′

R) 3-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1-(ethoxycarbonylmethyl)-1-methylpyrrolidinium bromide.