Compositions of R(+) and S(-) Pramipexole and Methods of Using the Same

• US 20080014259A1
• Filed: 05/16/2007
• Published: 01/17/2008
• 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, Petzinger, Thomas, Gribkoff, Valentin
• Granted Patent: US 8,017,598 B2
• Time in Patent Office: Days
• US Class Current: 424/457
• 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 multicomponent pharmaceutical composition comprising a first component and a second component, wherein said first component comprises R(+) pramipexole and said second component comprises S(−

) pramipexole.

2. A multicomponent pharmaceutical composition of claim 1, wherein said first component comprising R(+) pramipexole is an immediate release formulation and said second component comprising S(−

) pramipexole is an immediate release formulation.

3. A multicomponent pharmaceutical composition of claim 1, wherein said first component comprising R(+) pramipexole is an immediate release formulation and said second component comprising S(−

) pramipexole is a sustained release formulation.

4. A multicomponent pharmaceutical composition of claim 1, wherein said first component comprising R(+) pramipexole is sustained release formulation and said second component comprising S(−

) pramipexole is an immediate release formulation.

5. A multicomponent pharmaceutical composition of claim 1, wherein said first component comprising R(+) pramipexole is an sustained release formulation and said second component comprising S(−

) pramipexole is a sustained release formulation second component comprising S(−

) pramipexole is an immediate release formulation.

6. The multicomponent pharmaceutical composition of claim 1, wherein said multicomponent pharmaceutical composition is suitable for enteral administration.

7. The multicomponent pharmaceutical composition of claim 6, wherein said enteral administration is selected from oral, rectal or intranasal.

8. The multicomponent pharmaceutical composition of claim 1, wherein said multicomponent pharmaceutical composition is suitable for oral administration.

9. The multicomponent pharmaceutical composition of claim 6, wherein said multicomponent pharmaceutical composition is selected from a tablet, a capsule, and a liquid.

10. The multicomponent pharmaceutical composition of claim 1, wherein said multicomponent pharmaceutical composition is a bilayer tablet.

11. The multicomponent pharmaceutical composition of claim 1, wherein said multicomponent pharmaceutical composition is a capsule.

12. The multicomponent pharmaceutical composition of claim 1, wherein said multicomponent pharmaceutical composition is suitable for topical administration.

13. The multicomponent pharmaceutical composition of claim 1, wherein said multicomponent pharmaceutical composition is suitable for parenteral administration.

14. The multicomponent pharmaceutical composition of claim 13, wherein said parenteral administration is selected from intravascular administration, subcutaneous injection, and intramuscular administration.

15. The multicomponent pharmaceutical composition of claim 1, wherein said first component comprises a therapeutically effective amount of R(+) pramipexole and said second component comprises a therapeutically effective amount of S(−

) pramipexole.

16. The multicomponent pharmaceutical composition of claim 15, wherein said therapeutically effective amount of R(+) pramipexole is from about 100 milligrams to about 3,000 milligrams.

17. The multicomponent pharmaceutical composition of claim 15, wherein said therapeutically effective amount of R(+) pramipexole is from about 300 milligrams to about 1,500 milligrams.

18. The multicomponent pharmaceutical composition of claim 15, wherein said therapeutically effective amount of R(+) pramipexole is from about 500 milligrams to about 1,000 milligrams.

19. The multicomponent pharmaceutical composition of claim 15, wherein said therapeutically effective amount of S(−

) pramipexole is from about 0.375 milligrams to about 4.5 milligrams per day.

20. The multicomponent pharmaceutical composition of claim 1, wherein said first component comprising R(+) pramipexole is released at a first rate and said second component comprising S(−

) pramipexole is release at a second rate.

21. The multicomponent pharmaceutical composition of claim 20, wherein said first rate is faster than said second rate.

22. The multicomponent pharmaceutical composition of claim 20, wherein said first rate is slower than said second rate.

23. The multicomponent pharmaceutical composition of claim 1, wherein said first component has a chiral purity for the R(+) enantiomer of pramipexole of 80% or greater.

24. The multicomponent pharmaceutical composition of claim 1, wherein said first component has a chiral purity for the R(+) enantiomer of pramipexole of 90% or greater.

25. The multicomponent pharmaceutical composition of claim 1, wherein said first component has a chiral purity for the R(+) enantiomer of pramipexole of 95% or greater.

26. The multicomponent pharmaceutical composition of claim 1, wherein said first component has a chiral purity for the R(+) enantiomer of pramipexole of 99% or greater.

27. The multicomponent pharmaceutical composition of claim 1, wherein said first component has a chiral purity for the R(+) enantiomer of pramipexole of 100%.

28. The multicomponent pharmaceutical composition of claim 1, wherein said first component has a chiral purity for the S(−

) enantiomer of pramipexole of 80% or greater.

29. The multicomponent pharmaceutical composition of claim 1, wherein said first component has a chiral purity for the S(−

) enantiomer of pramipexole of 90% or greater.

30. The multicomponent pharmaceutical composition of claim 1, wherein said first component has a chiral purity for the S(−

) enantiomer of pramipexole of 95% or greater.

31. The multicomponent pharmaceutical composition of claim 1, wherein said first component has a chiral purity for the S(−

) enantiomer of pramipexole of 99% or greater.

32. The multicomponent pharmaceutical composition of claim 1, wherein said first component has a chiral purity for the S(−

) enantiomer of pramipexole of 100%.

33. A sustained release pharmaceutical composition comprising S(−

) pramipexole and R(+) pramipexole in a sustained release matrix.

34. The sustained release pharmaceutical composition of claim 33, wherein said R(+) pramipexole is in a first sustained release matrix and said S(−

) pramipexole is in a second sustained release matrix.

35. The sustained release pharmaceutical composition of claim 33, wherein said sustained release pharmaceutical composition is suitable for enteral administration.

36. The sustained release pharmaceutical composition of claim 35, wherein said enteral administration is selected from oral, rectal or intranasal.

37. The sustained release pharmaceutical composition of claim 33, wherein said sustained release pharmaceutical composition is suitable of oral administration.

38. The sustained release pharmaceutical composition of claim 37, wherein said sustained release pharmaceutical composition is selected from a tablet, a capsule, and a liquid.

39. The sustained release pharmaceutical composition of claim 33, wherein said sustained release pharmaceutical composition is a bilayer tablet.

40. The sustained release pharmaceutical composition of claim 33, wherein said sustained release pharmaceutical composition is a capsule.

41. The sustained release pharmaceutical composition of claim 33, wherein said sustained release pharmaceutical composition is suitable for parenteral administration.

42. The sustained release pharmaceutical composition of claim 41, wherein said parenteral administration is selected from intravascular administration, subcutaneous injection, and intramuscular administration.

43. The sustained release pharmaceutical composition of claim 33, wherein said sustained release pharmaceutical composition comprises a therapeutically effective amount of R(+) pramipexole.

44. The sustained release pharmaceutical composition of claim 43, wherein said therapeutically effective anout of R(+) pramipexole is from about 100 milligrams to about 3,000 milligrams.

45. The sustained release pharmaceutical composition of claim 43, wherein said therapeutically effective amount of R(+) pramipexole is from about 300 milligrams to about 1,500 milligrams.

46. The sustained release pharmaceutical composition of claim 43, wherein said therapeutically effective amount of R(+) pramipexole is from about 500 milligrams to about 1,000 milligrams.

47. The sustained release pharmaceutical composition of claim 33, wherein said sustained release pharmaceutical composition comprises a therapeutically effective amount of S(−

) pramipexole.

48. The sustained release pharmaceutical composition of claim 47, wherein said therapeutically effective amount of S(−

) pramipexole is from about 0.375 milligrams to about 4.5 milligrams per day.

49. The sustained release pharmaceutical composition of claim 34, wherein said first sustained release matrix is different from said second sustained release matrix.

50. The sustained release pharmaceutical composition of claim 34, wherein said R(+) pramipexole is released at a first rate and said S(−

) pramipexole is release at a second rate.

51. The sustained release pharmaceutical composition of claim 50, wherein said first rate is faster than said second rate.

52. The sustained release pharmaceutical composition of claim 50, wherein said first rate is slower than said second rate.

53. The sustained release pharmaceutical composition of claim 33, wherein said R(+) pramipexole has a chiral purity for the R(+) enantiomer of pramipexole of 80% or greater.

54. The sustained release pharmaceutical composition of claim 33, wherein said R(+) pramipexole has a chiral purity for the R(+) enantiomer of pramipexole of 90% or greater.

55. The sustained release pharmaceutical composition of claim 33, wherein said R(+) pramipexole has a chiral purity for the R(+) enantiomer of pramipexole of 95% or greater.

56. The sustained release pharmaceutical composition of claim 33, wherein said R(+) pramipexole has a chiral purity for the R(+) enantiomer of pramipexole of 99% or greater.

57. The sustained release pharmaceutical composition of claim 33, wherein said R(+) pramipexole has a chiral purity for the R(+) enantiomer of pramipexole of 100%.

58. The sustained release pharmaceutical composition of claim 33, wherein said S(−

) pramipexole has a chiral purity for the S(−

) enantiomer of pramipexole of 80% or greater.

59. The sustained release pharmaceutical composition of claim 33, wherein said S(−

) pramipexole has a chiral purity for the S(−

) enantiomer of pramipexole of 90% or greater.

60. The sustained release pharmaceutical composition of claim 33, wherein said S(−

) pramipexole has a chiral purity for the S(−

) enantiomer of pramipexole of 95% or greater.

61. The sustained release pharmaceutical composition of claim 33, wherein said S(−

) pramipexole has a chiral purity for the S(−

) enantiomer of pramipexole of 99% or greater.

62. The sustained release pharmaceutical composition of claim 33, wherein said S(−

) pramipexole has a chiral purity for the S(−

) enantiomer of pramipexole of 100%.

63. A method treating or preventing Parkinson'"'"'s disease or the symptoms thereof comprising administering a therapeutically effective amount of R(+) pramipexole and an amount of S(−

) pramipexole.

64. The method of claim 63, wherein said therapeutically effective amount of R(+) pramipexole is from about 100 milligrams to about 3,000 milligrams.

65. The method of claim 63, wherein said therapeutically effective amount of R(+) pramipexole is from about 300 milligrams to about 1,500 milligrams.

66. The method of claim 63, wherein said therapeutically effective amount of R(+) pramipexole is from about 500 milligrams to about 1,000 milligrams.

67. The method of claim 63, wherein said amount of S(−

) pramipexole is a therapeutically effective amount.

68. The method of claim 67, wherein said therapeutically effective amount of S(−

) pramipexole is from about 0.375 milligrams to about 4.5 milligrams per day.

69. The method of claim 63, wherein said therapeutically effective amount of R(+) pramipexole and said amount of S(−

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

70. The method of claim 63, wherein said therapeutically effective amount of R(+) pramipexole and said amount of S(−

) pramipexole are administered three times a day.

71. The method of claim 63, wherein said therapeutically effective amount of R(+) pramipexole and said amount of S(−

) pramipexole are administered in a single pharmaceutical composition.

72. The method of claim 71, wherein said pharmaceutical composition has a chiral purity for the R(+) enantimoer of pramipexole of 80% or greater.

73. The method of claim 71, wherein said pharmaceutical composition has a chiral purity for the R(+) enantimoer of pramipexole of 90% or greater.

74. The method of claim 71, wherein said pharmaceutical composition has a chiral purity for the R(+) enantimoer of pramipexole of 95% or greater.

75. The method of claim 71, wherein said pharmaceutical composition has a chiral purity for the R(+) enantimoer of pramipexole of 99% or greater.

76. The method of claim 63, wherein said amount of S(−

) pramipexole is no observable adverse effect amount of S(−

) pramipexole.

77. The method of claim 76, wherein said no observable adverse effect amount of S(−

) pramipexole is 1.5 milligrams or below.