Compositions of R(+) and S(−) pramipexole and methods of using the same

• US 8,445,474 B2
• Filed: 08/05/2011
• Issued: 05/21/2013
• Est. Priority Date: 05/16/2006
• Status: Active Grant

• Current Assignee: Knopp Biosciences LLC
• Original Assignee: Knopp Neurosciences Inc. (Knopp Biosciences LLC)
• Inventors: Bozik, Michael E., Petzinger, Thomas Jr., Gribkoff, Valentin
• Primary Examiner(s): SZNAIDMAN, MARCOS L
• Application Number:
  US13/204,351
• Publication Number:
  US 20110293718A1
• Time in Patent Office: 655 Days
• Field of Search: 514/183, 514/367
• US Class Current: 514/183
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/428 condensed with carbocyclic rings
• 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 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 39/06 Free radical scavengers or antioxidants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Compositions of predetermined amounts of R(+) pramipexole and S(−) pramipexole and methods of using the same, including for the treatment and prevention of Parkinson'"'"'s disease, are provided.

Claims

1. A method of treating and delaying the progression of Parkinson'"'"'s disease or the symptoms thereof comprising administering to a subject in need thereof 100 milligrams to about 3,000 milligrams of R(+) pramipexole in combination with about 0.125 mg to about 1.5 milligrams of S(−

) pramipexole, wherein said Parkinson'"'"'s disease or the symptoms thereof is treated and the progression is delayed.

2. The method of claim 1, wherein said R(+) pramipexole is from about 300 milligrams to about 1,500 milligrams.

3. The method of claim 1, wherein said R(+) pramipexole is from about 500 milligrams to about 1,000 milligrams.

4. The method of claim 1, wherein said R(+) pramipexole and said S(−

) pramipexole are administered from one to five times a day.

5. The method of claim 1, wherein said R(+) pramipexole and said S(−

) pramipexole are administered at a frequency selected from once a day, two times a day and three times a day.

6. The method of claim 1, wherein said R(+) pramipexole and said S(−

) pramipexole are administered in a single pharmaceutical composition.

7. The method of claim 6, wherein said pharmaceutical composition has a chiral purity for the R(+) enantiomer of pramipexole of 99% or greater.

8. The method of claim 1, wherein said S(−

) pramipexole is selected from 0.125 milligrams, 0.25 milligrams, 0.5 milligrams, 1.0 milligrams and 1.5 milligrams.

9. The method of claim 1, wherein said R(+) pramipexole and said S(−

) pramipexole are administered in separate pharmaceutical compositions.

10. The method of claim 1, wherein said R(+) pramipexole is administered in a unit dose.

11. The method of claim 1, wherein said S(−

) pramipexole is administered in a unit dose.

12. The method of claim 1, wherein said subject is a human.

13. The method of claim 1, wherein said R(+) pramipexole is a pharmaceutically acceptable salt thereof.

14. The method of claim 13, wherein said pharmaceutically acceptable salt is dihydrochloride.

15. The method of claim 1, wherein said S(−

) pramipexole is a pharmaceutically acceptable salt thereof.

16. The method of claim 15, wherein said pharmaceutically acceptable salt is dihydrochloride.

17. The method of claim 6 or 9, wherein each of said pharmaceutical compositions is independently selected from a tablet, a capsule and a liquid.

18. The method of claim 6 or 9, wherein each of said pharmaceutical compositions is independently suitable for administration selected from enteral administration and parenteral administration.

19. The method of claim 6 or 9, wherein each of said pharmaceutical compositions is independently suitable for administration selected from intravascular administration, subcutaneous administration, intramuscular administration, intraperitoneal administration, transdermal administration, buccal administration, ocular administration, vaginal administration, rectal administration, inhaled administration, sublingual administration, topical administration and oral administration.

20. A method of treating Parkinson'"'"'s disease or the symptoms thereof comprising administering to a subject in need thereof 100 milligrams to about 3,000 milligrams of R(+) pramipexole in combination with about 0.125 mg to about 1.5 milligrams of S(−

) pramipexole, wherein said Parkinson'"'"'s disease or the symptoms thereof is treated.

21. The method of claim 20, wherein said R(+) pramipexole is from about 300 milligrams to about 1,500 milligrams.

22. The method of claim 20, wherein said R(+) pramipexole is from about 500 milligrams to about 1,000 milligrams.

23. The method of claim 20, wherein said R(+) pramipexole and said S(−

) pramipexole are administered from one to five times a day.

24. The method of claim 20, wherein said R(+) pramipexole and said S(−

) pramipexole are administered at a frequency selected from once a day, two times a day and three times a day.

25. The method of claim 20, wherein said R(+) pramipexole and said S(−

) pramipexole are administered in a single pharmaceutical composition.

26. The method of claim 25, wherein said pharmaceutical composition has a chiral purity for the R(+) enantiomer of pramipexole of 99% or greater.

27. The method of claim 20, wherein said S(−

) pramipexole is selected from 0.125 milligrams, 0.25 milligrams, 0.5 milligrams, 1.0 milligrams and 1.5 milligrams.

28. The method of claim 20, wherein said R(+) pramipexole and said S(−

) pramipexole are administered in separate pharmaceutical compositions.

29. The method of claim 20, wherein said R(+) pramipexole is administered in a unit dose.

30. The method of claim 20, wherein said S(−

) pramipexole is administered in a unit dose.

31. The method of claim 20, wherein said subject is a human.

32. The method of claim 20, wherein said R(+) pramipexole is a pharmaceutically acceptable salt thereof.

33. The method of claim 32, wherein said pharmaceutically acceptable salt is dihydrochloride.

34. The method of claim 20, wherein said S(−

) pramipexole is a pharmaceutically acceptable salt thereof.

35. The method of claim 34, wherein said pharmaceutically acceptable salt is dihydrochloride.

36. The method of claim 25 or 28, wherein each of said pharmaceutical compositions is independently selected from a tablet, a capsule and a liquid.

37. The method of claim 25 or 28, wherein each of said pharmaceutical compositions is independently suitable for administration selected from enteral administration and parenteral administration.

38. The method of claim 25 or 28, wherein each of said pharmaceutical compositions is independently suitable for administration selected from intravascular administration, subcutaneous administration, intramuscular administration, intraperitoneal administration, transdermal administration, buccal administration, ocular administration, vaginal administration, rectal administration, inhaled administration, sublingual administration, topical administration and oral administration.

39. A method of delaying the progression of Parkinson'"'"'s disease or the symptoms thereof comprising administering to a subject in need thereof 100 milligrams to about 3,000 milligrams of R(+) pramipexole in combination with about 0.125 mg to about 1.5 milligrams of S(−

) pramipexole, wherein the progression of Parkinson'"'"'s disease or symptoms thereof is delayed.

40. The method of claim 39, wherein said R(+) pramipexole is from about 300 milligrams to about 1,500 milligrams.

41. The method of claim 39, wherein said R(+) pramipexole is from about 500 milligrams to about 1,000 milligrams.

42. The method of claim 39, wherein said R(+) pramipexole and said S(−

) pramipexole are administered from one to five times a day.

43. The method of claim 39, wherein said R(+) pramipexole and said S(−

) pramipexole are administered at a frequency selected from once a day, two times a day and three times a day.

44. The method of claim 39, wherein said R(+) pramipexole and said S(−

) pramipexole are administered in a single pharmaceutical composition.

45. The method of claim 44, wherein said pharmaceutical composition has a chiral purity for the R(+) enantiomer of pramipexole of 99% or greater.

46. The method of claim 39, wherein said S(−

) pramipexole is selected from 0.125 milligrams, 0.25 milligrams, 0.5 milligrams, 1.0 milligrams and 1.5 milligrams.

47. The method of claim 39, wherein said R(+) pramipexole and said S(−

) pramipexole are administered in separate pharmaceutical compositions.

48. The method of claim 39, wherein said R(+) pramipexole is administered in a unit dose.

49. The method of claim 39, wherein said S(−

) pramipexole is administered in a unit dose.

50. The method of claim 39, wherein said subject is a human.

51. The method of claim 39, wherein said R(+) pramipexole is a pharmaceutically acceptable salt thereof.

52. The method of claim 51, wherein said pharmaceutically acceptable salt is dihydrochloride.

53. The method of claim 39, wherein said S(−

) pramipexole is a pharmaceutically acceptable salt thereof.

54. The method of claim 53, wherein said pharmaceutically acceptable salt is dihydrochloride.

55. The method of claim 44 or 47, wherein each of said pharmaceutical compositions is independently selected from a tablet, a capsule and a liquid.

56. The method of claim 44 or 47, wherein each of said pharmaceutical compositions is independently suitable for administration selected from enteral administration and parenteral administration.

57. The method of claim 44 or 47, wherein each of said pharmaceutical compositions is independently suitable for administration selected from intravascular administration, subcutaneous administration, intramuscular administration, intraperitoneal administration, transdermal administration, buccal administration, ocular administration, vaginal administration, rectal administration, inhaled administration, sublingual administration, topical administration and oral administration.