Glycopyrrolate salts

• US 10,548,875 B2
• Filed: 12/28/2018
• Issued: 02/04/2020
• Est. Priority Date: 02/28/2013
• Status: Active Grant

• Current Assignee: Journey Medical Corp. (Fortress Biotech, Inc.)
• Original Assignee: Dermira, Inc.
• Inventors: Statler, John Allan, Shaw, Anthony Adrian, Imbert, Delphine Caroline, Nelson, Jennifer Leigh, Andres, Patricia, McQueen, Lisa Lynn, Boerrigter, Stephan Xander Mattheus, Selbo, Jon Gordon, Andres, Mark Christopher
• Primary Examiner(s): Jackson, Shawquia
• Application Number:
  US16/235,120
• Publication Number:
  US 20190133999A1
• Time in Patent Office: 403 Days
• 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 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• 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: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 207/12 Oxygen or sulfur atoms

Abstract

Salts of glycopyrrolate, including solid forms and formulations such as topicals thereof, are disclosed. Methods of making glycopyrrolate salts, including formulations such as topicals thereof, and methods of treating hyperhidrosis with salts of glycopyrrolate, and formulations such as topicals thereof, are disclosed.

Claims

1. A racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate.

2. An absorbent pad comprising a pharmaceutically acceptable solution comprising a racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and at least one pharmaceutically acceptable additive.

3. The absorbent pad of claim 2, wherein one pharmaceutically acceptable additive is ethanol.

4. The absorbent pad of claim 2, wherein the weight percent of said racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate in said pharmaceutically acceptable solution is between 1% and 6%;

and the pH of said pharmaceutically acceptable solution is between 3.5 and 5.5.

5. The absorbent pad of claim 2, wherein the absorbent pad comprises polypropylene.

6. The absorbent pad of claim 2, wherein the absorbent pad is nonwoven 100% polypropylene.

7. The absorbent pad of claim 2, wherein the absorbent pad is sealed in a pouch.

8. The absorbent pad of claim 7, wherein the pouch is a laminate containing aluminum foil as a layer.

9. A pharmaceutically acceptable solution comprising a racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and at least one pharmaceutically acceptable additive.

10. The pharmaceutically acceptable solution of claim 9, wherein one pharmaceutically acceptable additive is ethanol.

11. The pharmaceutically acceptable solution of claim 9, wherein the weight percent of said racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate is between 1% and 6%;

and the pH of said pharmaceutically acceptable solution is between 3.5 and 5.5.

12. A method of treating hyperhidrosis comprising topically administering a therapeutically effective amount of a pharmaceutically acceptable solution of a racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate to the skin of a mammal.

13. The method of claim 12, wherein said mammal is human.

14. The method of claim 13, wherein said pharmaceutically acceptable solution is applied to the axilla.

15. The method of claim 13, wherein said pharmaceutically acceptable solution is applied to the hands.

16. The method of claim 13, wherein said pharmaceutically acceptable solution is applied to the feet.

17. The method of claim 13, wherein said pharmaceutically acceptable solution is applied to the groin, face, back, or abdomen.

18. The method of claim 12, where the administration is with an absorbent pad comprising an absorbed pharmaceutically acceptable solution of a racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate.

19. The method of claim 14, where the administration is with an absorbent pad comprising an absorbed pharmaceutically acceptable solution of a racemic mixture of (R)-3-((S)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate and (S)-3-((R)-2-cyclopentyl-2-hydroxy-2-phenylacetoxy)-1,1-dimethylpyrrolidinium 4-methylbenzenesulfonate.

20. The method of claim 12, wherein one pharmaceutically acceptable additive is ethanol.

21. The method of claim 14, wherein one pharmaceutically acceptable additive is ethanol.

22. The method of claim 18, wherein one pharmaceutically acceptable additive is ethanol.

23. The method of claim 22, wherein the pharmaceutically acceptable solution comprises between about 57 and 59.5% by weight dehydrated ethanol.

24. The method of claim 22, wherein the pH of said pharmaceutically acceptable solution is between about 4.0 and about 5.0.

25. The method of claim 22, wherein the pH of said pharmaceutically acceptable solution is between about 4.0 and about 4.7.

26. The method of claim 22, wherein the pH of said pharmaceutically acceptable solution is between about 4.1 and about 4.6.

27. The method of claim 22, wherein said pharmaceutically acceptable solution is clear and colorless or pale yellow at a pH of between about 4.0 and about 5.0 at 25°

C.