Methods and compositions for treating urinary incontinence using enantiomerically enriched (R,R)-glycopyrrolate

• US 6,204,285 B1
• Filed: 12/29/1998
• Issued: 03/20/2001
• Est. Priority Date: 07/01/1996
• Status: Expired due to Fees

• Current Assignee: Sepracor Incorporated
• Original Assignee: Sepracor Incorporated
• Inventors: Fabiano, Vincent L., McCullough, John R.
• Primary Examiner(s): MOEZIE, FATEMEH T
• Application Number:
  US09/214,168
• Time in Patent Office: 812 Days
• Field of Search: 514/424, 548/556
• US Class Current: 514/424
• 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

Abstract

A method for treating urinary incontinence, such as incontinence resulting from bladder detrusor muscle instability, using enantiomerically enriched (R, R)-glycopyrrolate. The method comprises administering a therapeutically effective amount of enantiomerically enriched (R, R)-glycopyrrolate, or a pharmaceutically acceptable salt thereof, substantially free of the (S, S)-glycopyrrolate enantiomer. Pharmaceutical compositions for the treament of urinary incontinence comprising enantiomerically enriched (R, R)-glycopyrrolate, or a pharmaceutically acceptable salt thereof, and an acceptable carrier are also disclosed.

Claims

1. A method for treating urinary incontinence, comprising administering to a subject in need thereof a therapeutically effective amount of enantiomerically enriched (R,R)-glycopyrrolate (3-[(cyclopentylhydroxyphenylacetyl)oxy]-1,1-dimethylpyrrolidinium bromide), or a pharmaceutically acceptable salt thereof.

2. The method as recited in claim 1, wherein the enantiomerically enriched (R,R)-glycopyrrolate, or a pharmaceutically acceptable salt thereof, is administered as a pharmaceutical composition comprising said enantiomerically enriched (R,R)-glycopyrrolate, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

3. The method as recited in claim 2, wherein said pharmaceutical composition is administered by oral, parenteral, transdermal, rectal, or vaginal administration.

4. The method as recited in claim 2, wherein said pharmaceutical composition is administered by injection or intravesical perfusion.

5. The method as recited in claim 1, wherein a daily amount of (R,R)-glycopyrrolate administered in the preparation is about 0.25 mg to about 500 mg.

6. The method as recited in claim 5, wherein the daily amount of (R,R)-glycopyrrolate administered in the preparation is about 1 mg to about 100 mg.

7. The method as recited in claim 2, wherein (R,R)-glycopyrrolate comprises greater than 50% by weight of the total glycopyrrolate in said pharmaceutical composition.

8. The method as recited in claim 7, wherein (R,R)-glycopyrrolate comprises at least 80% by weight of the total glycopyrrolate in said pharmaceutical composition.

9. The method as recited in claim 1, wherein (R,R)-glycopyrrolate is administered as a pharmaceutical composition comprising substantially enantiomerically enriched (R,R)-glycopyrrolate, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

10. The method as recited in claim 9, wherein (R,R)-glycopyrrolate comprises at least 85% by weight of the total glycopyrrolate in said pharmaceutical composition.

11. The method as recited in claim 10, wherein (R,R)-glycopyrrolate comprises at least 99% by weight of the total glycopyrrolate in said pharmaceutical composition.

12. The method as recited in claim 1, wherein the subject is treated for stress incontinence, urge incontinence, post-prostectomy incontinence, or enuresis.

13. A method for treating bladder detrusor muscle instability, said method comprising administering to a subject in need thereof a therapeutically effective amount of enantiomerically enriched (R,R)-glycopyrrolate, or a pharmaceutically acceptable salt thereof.

14. The method as recited in claim 13, wherein said enantiomerically enriched (R,R)-glycopyrrolate, or a pharmaceutically acceptable salt thereof, is substantially free of (S,S)-glycopyrrolate.

15. A pharmaceutical composition, comprising enantiomerically enriched (R,R)-glycopyrrolate, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

16. The pharmaceutical composition as recited in claim 15, wherein (R,R)-glycopyrrolate comprises greater than 50% by weight of the total glycopyrrolate in said pharmaceutical composition.

17. The pharmaceutical composition as recited in claim 16, wherein (R,R)-glycopyrrolate comprises at least 80% by weight of the total glycopyrrolate in said pharmaceutical composition.

18. The pharmaceutical composition as recited in claim 15, wherein the amount of (R,R)-glycopyrrolate present in said pharmaceutical composition is about 0.25 mg to about 500 mg.

19. The pharmaceutical composition as recited in claim 18, wherein the amount of (R,R)-glycopyrrolate present in said pharmaceutical composition is from about 1 mg to about 100 mg.

20. The pharmaceutical composition as recited in claim 15, wherein enantiomerically enriched (R,R)-glycopyrrolate comprises from about 1% to about 99% of the total pharmaceutical composition.

21. The pharmaceutical composition as recited in claim 20, wherein enantiomerically enriched (R,R)-glycopyrrolate comprises from about 10% to about 30% of the total pharmaceutical composition.

22. A pharmaceutical composition, comprising (R,R)-glycopyrrolate, or a pharmaceutically acceptable salt thereof, substantially free of (S,S)-glycopyrrolate, and a pharmaceutically acceptable carrier.

23. The pharmaceutical composition as recited in claim 22, wherein (R,R)-glycopyrrolate comprises at least 85% by weight of the total glycopyrrolate in said pharmaceutical composition.

24. The pharmaceutical composition as recited in claim 23, wherein (R,R)-glycopyrrolate comprises at least 99% by weight of the total glycopyrrolate in said pharmaceutical composition.

25. The pharmaceutical composition as recited in claim 22, wherein the amount of (R,R)-glycopyrrolate present in said pharmaceutical composition is about 0.25 mg to about 500 mg.

26. The pharmaceutical composition as recited in claim 25, wherein the amount of (R,R)-glycopyrrolate present in said pharmaceutical composition is from about 1 mg to about 100 mg.

27. The pharmaceutical composition as recited in claim 22, wherein (R,R)-glycopyrrolate comprises from about 1% to about 99% of the total pharmaceutical composition.

28. The pharmaceutical composition as recited in claim 27, wherein (R,R)-glycopyrrolate comprises from about 10% to about 30% of the total pharmaceutical composition.

29. A pharmaceutical unit dosage form, which comprises enantiomerically enriched (R,R)-glycopyrrolate, or a pharmaceutically acceptable salt thereof, and a pharmaceutical carrier, wherein said pharmaceutical unit dosage form is a tablet.

30. The pharmaceutical unit dosage form as recited in claim 29, wherein said enantiomerically enriched (R,R)-glycopyrrolate is present in an amount of about 0.25 mg to about 250 mg.

31. The pharmaceutical unit dosage form as recited in claim 30, wherein said enantiomerically enriched (R,R)-glycopyrrolate is present in an amount of about 1 mg to about 50 mg.

32. A pharmaceutical unit dosage form which comprises substantially enantiomerically enriched (R,R)-glycopyrrolate, or a pharmaceutically acceptable salt thereof, and a pharmaceutical carrier, wherein said pharmaceutical unit dosage form is a tablet.

33. A pharmaceutical unit dosage form, which comprises enantiomerically enriched (R,R)-glycopyrrolate, or a pharmaceutically acceptable salt thereof, and a pharmaceutical carrier, wherein said pharmaceutical unit dosage form is a soft elastic gelatin capsule.

34. The pharmaceutical unit dosage form as recited in claim 33, wherein said enantiomerically enriched (R,R)-glycopyrrolate is present in an amount of about 0.25 mg to about 250 mg.

35. The pharmaceutical unit dosage for as recited in claim 34, wherein said enantiomerically enriched (R,R)-glycopyrrolate is present in an amount of about 1 mg to about 50 mg.

36. A pharmaceutical unit dosage form which comprises substantially enantiomerically enriched (R,R)-glycopyrrolate, or a pharmaceutically acceptable salt thereof, and a pharmaceutical carrier, wherein said pharmaceutical unit dosage form is a soft elastic gelatin capsule.

37. A mixture of (R,R)-glycopyrrolate and (S,S-glycopyrrolate enantiomers, or pharmaceutically acceptable salts thereof, wherein the ratio of (R,R-glycopyrrolate to (S,S)-glycopyrrolate is greater than 1:

1.

38. A mixture of (R,R)-glycopyrrolate and (S,S)-glycopyrrolate enantiomers, or pharmaceutically acceptable salts thereof, wherein the (R,R)-glycopyrrolate enantiomer comprises at least 85% by weight of the total mixture.

39. A kit for treating urinary incontinence, wherein said kit comprises a pharmaceutical composition comprising enantiomerically enriched (R,R)-glycopyrrolate, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, and instructions for administering said composition for treating urinary incontinence while reducing or eliminating concomitant liability of adverse effect.

40. The kit as recited in claim 39, wherein said adverse effect is one or more of drowsiness, epistaxis, xerostomia, mydriasis, cycloplegia, cardiovascular tachycardia, cardiovascular palpitations, increased ocular pressure, nausea, constipation, decreased sweating, impotence, or unwanted dermal manifestations.

41. A kit for treating urinary incontinence, wherein said kit comprises a pharmaceutical composition comprising substantially enantiomerically enriched (R,R)-glycopyrrolate, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, and instructions for administering said composition for treating urinary incontinence while reducing or eliminating concomitant liability of adverse effects.

42. The kit as recited in claim 41 wherein said adverse effect is one or more of drowsiness, epistaxis, xerostomia, mydriasis, cycloplegia, cardiovascular tachycardia, cardiovascular palpitations, increased ocular pressure, nausea, constipation, decreased sweating, impotence, or unwanted dermal manifestations.