Graduated estrogen contraceptive

• US 20050107351A1
• Filed: 11/12/2004
• Published: 05/19/2005
• Est. Priority Date: 11/14/2003
• Status: Active Grant

• Current Assignee: Allergan Therapeutics LLC (Abbvie Incorporated)
• Original Assignee: Warner Chilcott Company LLC (Abbvie Incorporated)
• Inventors: Boissonneault, Roger M.
• Granted Patent: US 8,124,595 B2
• Time in Patent Office: Days
• US Class Current: 514/170
• 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 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/567 substituted in position 17 alpha, e.g. mestranol, norethandrolone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 15/18 Feminine contraceptives
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/24 of the sex hormones
• CPC Class Codes: A61P 5/30 Oestrogens
• CPC Class Codes: A61P 7/06 Antianaemics

Abstract

A multiphasic estrogenic/progestogenic contraceptive regimen that provides for the reduction or elimination of estrogen in the initial phase is disclosed. Also described is a contraceptive kit that may be used to practice the method of the invention.

Claims

1. A method of contraception comprising the steps of sequentially administering to a female of child bearing age:

(a) a composition I containing a progestogen in an amount equivalent to about 0.3 to about 1.5 mg norethindrone acetate and an estrogen in an amount equivalent to about 0 to less than about 10 mcg of ethinyl estradiol for about 5 to about 9 days;

(b) a composition II containing a progestogen in an amount equivalent to about 0.3 to about 1.5 mg of norethindrone acetate and an estrogen in an amount equivalent to about 10 to about 50 mcg of ethinyl estradiol for about 5 to about 9 days; and

(c) a composition III containing a progestogen in an amount equivalent to about 0.3 to about 1.5 mg of norethindrone acetate and an estrogen in an amount equivalent to about 10 to about 50 mcg of ethinyl estradiol for about 8 to about 12 days, wherein the sequential administration of compositions I, II and In is repeated after a period of about 1 to about 4 days has elapsed after the completion of the administration of composition III.

2. The method according to claim 1, wherein composition I contains an estrogen in an amount equivalent to about 0 to about 5 mcg of ethinyl estradiol.

3. The method according to claim 1, further comprising the step of administering on a daily basis a composition IV containing ferrous fumarate between the completion of the administration of composition III and beginning the repeated sequential administration of compositions I, II and III.

4. The method according to claim 1, further comprising the step of administering on a daily basis a composition IV which is a placebo between the completion of the administration of composition III and beginning the repeated sequential administration of compositions I, II and III.

5. The method according to claim 1, wherein composition I is substantially free of estrogen.

6. The method according to claim 1, wherein the amount of estrogen in Composition III is greater than the amount of estrogen in composition II by at least an amount equivalent to 5 mcg of ethinyl estradiol.

7. The method according to claim 1, wherein the progestogen in each composition is norethindrone acetate.

8. The method according to claim 1, wherein the estrogen in each composition is ethinyl estradiol.

9. The method according to claim 8, wherein composition I contains an amount of ethinyl estradiol from about 0.5 to about 5 mcg.

10. The method according to claim 9, wherein composition I contains about 5 mcg of ethinyl estradiol.

11. The method according to claim 8, wherein composition I is substantially free of ethinyl estradiol.

12. The method according to claim 8, wherein the amount of ethinyl estradiol in composition III is at least 5 mcg greater than the amount of ethinyl estradiol in composition II.

13. The method according to claim 8, wherein composition I contains about 0 to about 5 mcg of ethinyl estradiol and the amount of ethinyl estradiol in composition III is at least 5 mcg greater than the amount of ethinyl estradiol in composition II.

14. The method according to claim 13, further comprising administering on a daily basis a composition IV which contains ferrous fumarate or is a placebo for about 1 to 4 days.

15. The method according to claim 14, wherein the sequential administration of compositions I, II, III and IV is repeated upon completion of the administration of composition IV.

16. The method according to claim 14, wherein the daily administration of compositions I, II, III and IV is for a 19 to 34 day period.

17. The method according to claim 16, wherein the daily administration of compositions I, II, III and IV is for a 28 day period.

18. The method according to anyone of claims 1 to 6, wherein each of compositions I, II and III contain a progestogen in an amount equivalent to about 0.5 to about 1.5 mg of norethindrone acetate.

19. The method according to anyone of claims 7 to 17, wherein each of compositions I, II and III contain norethindrone acetate in an amount from about 0.5 to about 1.5 mg.

20. The method according to claim 17, wherein composition I contains about 1.0 mg of norethindrone acetate and is administered for about 7 days, composition II contains about 1.0 mg of norethindrone acetate and is administered for about 7 days, composition III contains about 1.0 mg of norethindrone acetate and is administered for about 10 days, and composition IV contains about 75 mg of ferrous fumarate and is administered for about 4 days.

21. The method according to claim 20, wherein composition I contains about 5 mcg of ethinyl estradiol, composition II contains about 30 mcg of ethinyl estradiol and composition III contains about 35 mcg of ethinyl estradiol.

22. The method according to claim 21, wherein composition I is substantially free of ethinyl estradiol, composition II contains about 30 mcg of ethinyl estradiol and composition III contains about 35 mcg of ethinyl estradiol.

23. A method of contraception comprising the steps of sequentially administering to a female of child bearing age:

(a) a composition I containing about 0.3 to about 1.5 mg norethindrone acetate and about 0 to about 5 mcg of ethinyl estradiol for about 5 to about 9 days;

(b) a composition II containing about 0.3 to about 1.5 mg norethindrone acetate and about 20-40 mcg ethinyl estradiol for about 5 to about 9 days;

(c) a composition III containing about 0.3 to about 1.5 mg norethindrone acetate and about 25-50 mcg ethinyl estradiol for about 8 to about 12 days; and

(d) optionally a composition IV that contains ferrous fumurate or is a placebo for about 1 to about 4 days,

wherein the sequential administration of compositions I, II and III is repeated and the number of days between completion of the administration of composition III and beginning the repeated sequential administration of compositions I, II and III is from about 1 to about 4 days.

24. The method according to claim 23, wherein composition III contains at least 5 mcg of ethinyl estradiol more than composition II.

25. The method according to claim 24, wherein composition IV is administered on a daily basis between the completion of the administration of composition III and beginning the repeated sequential administration of compositions I, II and III.

26. The method according to anyone of claims 23 to 25, wherein each of compositions I, II and III contain about 0.5 to about 1.5 mg of norethindrone acetate.

27. A multiphase combination and contraceptive kit comprising a package containing daily dosages of:

(a) a Phase I composition containing a progestogen in an amount equivalent to about 0.3 to about 1.5 mg of norethindrone acetate and an estrogen in an amount equivalent to about 0 to about 5 mcg of ethinyl estradiol;

(b) a Phase II composition containing a progestogen in an amount equivalent to about 0.3 to about 1.5 mg of norethindrone acetate and an estrogen in an amount equivalent to about 10 to about 50 mcg of ethinyl estradiol; and

(c) a Phase III composition containing a progestogen in an amount equivalent to about 0.3 to about 1.5 mg of norethindrone acetate and an estrogen in an amount equivalent to about 10 to about 50 mcg of ethinyl estradiol, wherein the amount of estrogen in the Phase III composition is greater than the amount of estrogen in the Phase II composition by at least an amount equivalent to 5 mcg ethinyl estradiol.

28. The kit according to claim 27, wherein the kit contains about 5 to about 9 dosages of the Phase I composition;

about 5 to about 9 dosages of the Phase II composition; and

about 8 to about 12 dosages of the Phase III composition.

29. The kit according to claim 28, wherein the kit further comprises about 1 to about 4 dosages of a Phase IV composition which contains ferrous fumarate or is a placebo.

30. The kit according to claim 29, wherein the progestogen in each Phase is norethindrone acetate.

31. The kit according to claim 30, wherein the estrogen in each Phase is ethinyl estradiol.

32. The kit according to claim 31, wherein the Phase II composition contains about 20 to about 40 mcg of ethinyl estradiol and the Phase III composition contains about 25 to about 50 mcg of ethinyl estradiol.

33. The kit according to anyone of claims 27 to 29, wherein each of the Phase I, II and III compositions contains a progestogen in an amount equivalent to about 0.5 to about 1.5 mg of norethindrone acetate.

34. The kit according to anyone of claims 30 to 32, wherein each of the Phase I, II and III compositions contains norethindrone acetate in an amount from about 0.5 to about 1.5 mg.

35. The kit according to claim 32, wherein the Phase I composition contains about 1 mg of norethindrone acetate, the Phase II composition contains about 1 mg of norethindrone acetate and about 30 mcg of ethinyl estradiol, the Phase III composition contains about 1 mg of norethindrone acetate and about 35 mcg of ethinyl estradiol, and the Phase IV composition contains about 75 mg of ferrous fumarate.

36. The kit according to claim 35, wherein the kit contains about 7 dosages of the Phase I composition, about 7 dosages of the Phase II composition, about 10 dosages of the Phase III composition and about 4 dosages of the Phase IV composition.

37. The kit according to claim 35, wherein the Phase I composition contains about 5 mcg of ethinyl estradiol.

38. The kit according to claim 35, wherein the Phase I composition is substantially free of ethinyl estradiol.

39. The kit according to claim 36, wherein the Phase I composition contains about 5 mcg of ethinyl estradiol.

40. The kit according to claim 36, wherein the Phase I composition is substantially free of ethinyl estradiol.