Antifungal once-a-day product, use and formulation thereof

• US 8,303,988 B2
• Filed: 09/16/2010
• Issued: 11/06/2012
• Est. Priority Date: 10/13/2000
• Status: Expired due to Term

• Current Assignee: Shionogi Inc. (Shionogi & Co., Ltd.)
• Original Assignee: Shionogi Inc. (Shionogi & Co., Ltd.)
• Inventors: Isbister, James D., Treacy, Donald J. Jr., Wassink, Sandra E., Rudnic, Edward M.
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US12/884,050
• Publication Number:
  US 20110065718A1
• Time in Patent Office: 782 Days
• Field of Search: None
• US Class Current: 424/472
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 31/10 Antimycotics

Abstract

An antifungal product is comprised of at least three dosages forms, each of which has a different release profile, with the C_max for the antifungal product being reached in less than about twelve hours. In one embodiment, there is an immediate release dosage form, as well as two or more delayed release dosage forms, with each of the dosage forms having a different release profile, wherein each reaches a C_max at different times.

Claims

1. A once-a-day antifungal product comprising:

first, second, and third dosage forms, wherein each of said dosage forms includes at least one antifungal agent and a pharmaceutically acceptable carrier;

said first dosage form is an immediate release dosage form;

said second and third dosage forms are delayed release dosage forms;

each of said first, second, and third dosage forms initiates release of said at least one antifungal agent at different times;

Cmax in serum of the total antifungal agent released from said antifungal product is achieved in less than about 12 hours from administration; and

said once-a-day antifungal product contains the total dosage of said at least one antifungal agent for a twenty-four hour period.

2. The product of claim 1, wherein the Cmax of the total antifungal agent released from said antifungal product is reached no earlier than four hours after administration.

3. The product of claim 1, wherein the antifungal agent released from the first dosage form reaches a Cmax in serum within from about 0.5 hours to about 2 hours after administration of the product.

4. The product of claim 1, wherein the antifungal agent released from the second dosage form reaches a Cmax in serum in no more than about 4 hours after administration of the product.

5. The product of claim 1, wherein the antifungal agent released from the third dosage form reaches a Cmax in serum within 8 hours after administration of the product.

6. The product of claim 1, wherein the immediate release dosage form contains at least 20% and no more than 50% of the total dosage of antifungal agent.

7. The product of claim 1, wherein the product is an oral dosage form.

8. The product of claim 7, wherein the antifungal agent released from the second dosage form reaches a Cmax in the serum after Cmax is reached in the serum for the antifungal agent released from the first dosage form.

9. The product of claim 8, wherein the antifungal agent released from the third dosage form reaches a Cmax in the serum after Cmax is reached in the serum for the antifungal agent released from the second dosage form.

10. The product of claim 9, wherein said second dosage form initiates release of said antifungal agent before said third dosage form, wherein said second dosage form provides from 30% to 60% by weight of the total antifungal released by said second and third dosage forms, and wherein said third dosage form provides the remainder of the total antifungal agent released by said second and third dosage forms.

11. The product of claim 1 further comprising a fourth antifungal dosage form, said fourth antifungal dosage form comprising at least one antifungal agent and a pharmaceutically acceptable carrier and wherein said at least one antifungal agent released from said fourth antifungal dosage form reaches a Cmax in the serum after Cmax is achieved in the serum for antifungal agent released from each of said first, second, and third dosage forms.

12. The product of claim 11, wherein said fourth antifungal dosage form is a delayed release dosage form.

13. The product of claim 12, wherein said second dosage form initiates release of said antifungal agent before said third dosage form, wherein said third dosage form initiates release of said antifungal agent before said fourth dosage form, wherein said second dosage form provides 20% to 35% by weight of the total antifungal agent released by said second, third, and fourth dosage forms, wherein said third dosage form provides from 20% to 40% by weight of the total antifungal agent released by said second, third, and fourth dosage forms, and wherein said fourth dosage form provides the remainder of the total antifungal agent released by said second, third, and fourth dosage forms.

14. The product of claim 11, wherein the antifungal agent released from the first dosage form reaches a Cmax in serum within from about 0.5 hours to about 2 hours after administration of the product.

15. The product of claim 11, wherein the antifungal agent released from the second dosage form reaches a Cmax in serum in no more than about 4 hours after administration of the product.

16. The product of claim 11, wherein the antifungal agent released from the third dosage form reaches a Cmax in serum within 8 hours after administration of the product.

17. A process for treating a fungal infection in a host comprising:

administering to a host the antifungal product of claim 1 once-a-day.

18. A process for treating a fungal infection in a host comprising:

administering to a host the antifungal product of claim 2 once-a-day.

19. A process for treating a fungal infection in a host comprising:

administering to a host the antifungal product of claim 3 once-a-day.

20. A process for treating a fungal infection in a host comprising:

administering to a host the antifungal product of claim 4 once-a-day.

21. A process for treating a fungal infection in a host comprising:

administering to a host the antifungal product of claim 5 once-a-day.

22. A process for treating a fungal infection in a host comprising:

administering to a host the antifungal product of claim 6 once-a-day.

23. A process for treating a fungal infection in a host comprising:

administering to a host the antifungal product of claim 7 once-a-day.

24. A process for treating a fungal infection in a host comprising:

administering to a host the antifungal product of claim 8 once-a-day.

25. A process for treating a fungal infection in a host comprising:

administering to a host the antifungal product of claim 9 once-a-day.

26. A process for treating a fungal infection in a host comprising:

administering to a host the antifungal product of claim 10 once-a-day.

27. A process for treating a fungal infection in a host comprising:

administering to a host the antifungal product of claim 11 once-a-day.

28. A process for treating a fungal infection in a host comprising:

administering to a host the antifungal product of claim 12 once-a-day.

29. A process for treating a fungal infection in a host comprising:

administering to a host the antifungal product of claim 13 once-a-day.

30. A process for treating a fungal infection in a host comprising:

administering to a host the antifungal product of claim 14 once-a-day.

31. A process for treating a fungal infection in a host comprising:

administering to a host the antifungal product of claim 15 once-a-day.

32. A process for treating a fungal infection in a host comprising:

administering to a host the antifungal product of claim 16 once-a-day.

33. The product of claim 11, wherein the Cmax of the total antifungal agent released from said antifungal product is reached no earlier than four hours after administration.

34. The product of claim 11, wherein the product is an oral dosage form.

35. The product of claim 34, wherein the antifungal agent released from the second dosage form reaches a Cmax in serum after Cmax is reached for the antifungal agent released from the first dosage form.

36. The product of claim 35, wherein the antifungal agent released from the third dosage form reaches a Cmax in serum after Cmax is reached for the antifungal agent released from the second dosage form.

37. A process for treating fungal infection in a host comprising administering to a host the antifungal product of claim 33 once-a-day.

38. A process for treating a fungal infection in a host comprising administering to a host the antifungal product of claim 34 once-a-day.

39. A process for treating a fungal infection in a host comprising administering to a host the antifungal product of claim 35 once-a-day.

40. A process for treating a fungal infection in a host comprising administering to a host the antifungal product of claim 36 once-a-day.

43. The product of claim 1, wherein each of said dosage forms includes only one antifungal agent.

44. The product of claim 43, wherein each of said dosage forms has the same antifungal agent.

41. A once-a-day antifungal product for oral administration comprising:

first, second, and third dosage forms, wherein each of said dosage forms includes at least one antifungal agent and a pharmaceutically acceptable carrier;

said first dosage form is an immediate release dosage form;

said second and third dosage forms are delayed release dosage forms;

each of said first, second and third dosage forms initiates release of said at least one antifungal agent at different times;

Cmax in serum of the total antifungal agent released from said antifungal product is achieved in less than about 12 hours from administration; and

said once-a-day antifungal product contains the total dosage of said at least one antifungal agent for a twenty-four hour period.

42. A process for treating a fungal infection in a host comprising administering to a host the antifungal product of claim 41 once-a-day.

45. The product of claim 41, wherein the Cmax of the total antifungal agent released from said antifungal product is reached no earlier than 4 hours after administration.