Contraceptive process and kit for female mammals, comprising a combination of gestagen and oestrogen

• US 6,995,149 B1
• Filed: 12/20/1996
• Issued: 02/07/2006
• Est. Priority Date: 12/23/1995
• Status: Expired due to Fees

• Current Assignee: Bayer Schering Pharma AG (Bayer AG)
• Original Assignee: Schering Ag (Merck & Co., Inc.)
• Inventors: Endrikat, Jan, Düsterberg, Bernd, Reilhac, Pia
• Primary Examiner(s): QAZI, SABIHA NAIM
• Application Number:
  US09/091,665
• Time in Patent Office: 3,336 Days
• Field of Search: 514/170, 514/179, 514/181, 514/182, 514/180
• 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 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/18 Feminine contraceptives

Abstract

The present invention relates to a female mammal contraceptive process consisting of the sequential administration for at least 28 days of (a) a gestagen in an ovulation-preventing dose for at least 28 days in combination with (b) a natural oestrogen for 5 to 10 days at the end of the sequential dosage of at least 28 days, and a contraception kit.

Claims

1. A method of contraception in a female mammal, comprising administering to said mammal a gestagen over a period of at least 28 days, wherein said period has a first phase and a second phase,

wherein said first phase consists essentially of administering an ovulation-inhibiting amount of a gestagen, and said second phase comprises administering an ovulation-inhibiting amount of a gestagen and a natural estrogen in an amount effective to achieve regular menstrual-like bleeding,

wherein said second phase is the last 5 to 10 days of said period and said first phase is the remainder of said period.

2. The method of claim 1, wherein said period is 28 days.

3. The method of claim 1, wherein in the second phase, the gestagen and natural estrogen are administered in combination.

4. The method of claim 1, wherein in the second phase, the gestagen and natural estrogen are administered separately.

5. The method according to claim 1, wherein the female mammal is human.

6. The method according to claim 1, wherein the gestagen is administered orally and the natural estrogen is administered transdermally.

7. The method according to claim 1, wherein the gestagen is administered transdermally and the natural estrogen is administered orally.

8. The method according to claim 1, wherein the gestagen and the natural estrogen are administered transdermally.

9. The method according to claim 1, wherein the gestagen is levonorgestrel or gestodene.

10. The method according to claim 1, wherein the gestagen is

levonorgestrel in a dose of 0.05–

0.2 mg/day, or

gestodene in a dose of 0.05–

0.15 mg/day.

11. The method according to claim 1, wherein the gestagen and natural estrogen are each independently administered locally, topically, enterally, transdermally and/or parenterally.

12. The method according to claim 1, wherein gestodene, levonorgestrel, desogestrel, 3-ketodesogestrol or a mixture thereof is administered transdermally, and estradiol is administered transdermally at a dose of 0.025–

0.25 mg of release/day.

13. The method of claim 3, wherein

during the first phase, at least 18–

23 first daily dosage units of a gestagen in an ovulation-inhibiting dose are administered, and

during the second phase, at least 5 to 10 second daily dosage units of a gestagen in an ovulation-inhibiting dose plus a natural estrogen are administered.

14. The method according to claim 13, wherein 28 daily dosage units are administered;

during the first phase, 18 to 23 of said first daily dosage units of a gestagen are administered; and

during the second phase, 5 to 10 of said second daily dosage units of a gestagen plus a natural estrogen are administered.

15. The method according to claim 13, wherein during the second phase, 10 daily dosage units of said gestagen plus estrogen are administered.

16. The method according to claim 3, wherein the gestagen in each phase, independently, is

gestodene,

progesterone,

levonorgestrel,

cyproterone acetate,

chloromadinone acetate,

drospirenone (dihydrospirorenone),

norethisterone,

norethisterone acetate,

norgestimate,

desogestrel,

3-ketodesogestrel,

dienogest,

or a mixture thereof.

17. The method according to claim 3, wherein the gestagen in each phase is, independently,

levonorgestrel in a dose of 0.1 mg/day,

gestodene in a dose of 0.075 mg/day, or

another gestagen in a bioequivalent dosage.

20. The method according to claim 1, wherein the second phase is the last 10 days of said at least 28 day period.

21. The method according to claim 1, wherein the gestagen is

gestodene,

progesterone,

levonorgestrel,

cyproterone acetate,

chloromadinone acetate,

drospirenone (dihydrospirorenone),

norethisterone,

norethisterone acetate,

norgestimate,

desogestrel,

3-ketodesogestrel,

dienogest,

or a mixture thereof.

22. The method according to claim 1, wherein the gestagen is

levonorgestrol at 0.05–

0.2 mg/day,

gestodene at 0.05–

0.15 mg/day,

or another gestagen in a bioequivalent dose.

23. The method according to claim 1, wherein the gestagen is administered orally and/or transdermally.

24. The method according to claim 1, wherein the natural estrogen is administered orally and/or transdermally.

44. A method according to claim 1, wherein the gestagen is administered orally and/the natural estrogen is administered orally.

49. A method according to claim 1, wherein there is a menstrual bleeding at the end of said period.

54. A method according to claim 1, wherein the second phase is the last 8 to 10 days of said period.

55. A method according to claim 1, wherein said period is 28–

84 days.

56. A method according to claim 1, wherein said period is 28–

56 days.

57. A method according to claim 1, wherein said method consists essentially of administering to said mammal, during said first phase, an ovulation-inhibiting amount of a gestagen, and, during said second phase, administering an ovulation-inhibiting amount of a gestagen and a natural estrogen in an amount effective to achieve regular menstrual-like bleeding.

58. A method according to claim 57, wherein said natural estrogen is estradiol and said gestagen is

gestodene,

progesterone,

levonorgestrel,

cyproterone acetate,

chloromadinone acetate,

drospirenone (dihydrospirorenone),

norethisterone,

norethisterone acetate,

norgestimate,

desogestrel,

3-ketodesogestrel,

dienogest,

or a mixture thereof.

59. A method according to claim 57, wherein said period is 28–

84 days.

60. A method according to claim 57, wherein said period is 28–

56 days.

61. A method according to claim 58, wherein said first phase is 18–

23 days.

62. A method according to claim 58, wherein said period is 28–

84 days.

63. A method according to claim 58, wherein said period is 28–

56 days.

64. A method according to claim 58, wherein said first phase is 18–

23 days.

18. A method of contraception in a female mammal, comprising administering to said mammal a daily steroidal preparation over a period of at least 28 days, wherein

during the last 5–

10 days of said period said mammal is daily administered a gestagen in an ovulation-inhibiting dose and a natural estrogen, and

during the rest of said period said mammal is daily administered a steroidal preparation consisting essentially of a gestagen in an ovulation-inhibiting dose.

45. A method according to claim 18, wherein the gestagen is administered orally and/the natural estrogen is administered orally.

50. A method according to claim 18, wherein there is a menstrual bleeding at the end of said period.

19. A method of contraception in a female mammal, comprising administering daily to said mammal a steroidal preparation over a period of at least 28 days, wherein

during the last 5–

10 days of said period said mammal is daily administered a gestagen in an ovulation-inhibiting dose and a natural estrogen in an amount which is effective for achieving regular menstrual-like bleeding, and

during the rest of said period said mammal is daily administered a steroidal preparation consisting essentially of gestagen in an ovulation-inhibiting dose.

46. A method according to claim 19, wherein the gestagen is administered orally and/the natural estrogen is administered orally.

51. A method according to claim 19, wherein there is a menstrual bleeding at the end of said period.

25. A method of providing contraception in a female mammal comprising administering a daily steroid preparation to said female mammal for a period of 28–

84 days and said period has a first phase and a second phase, wherein the second phase is the last 5 to 10 days of said period and said first phase is the remainder of said period,

wherein during said first phase a gestagen is daily administered in an ovulation inhibiting amount without an estrogen, and during said second phase a natural estrogen and an ovulation-inhibiting amount of a gestagen and are administered daily.

26. A method according to claim 25, wherein the second phase is the last 8 to 10 days of said 28–

84 day period.

27. A method according to claim 25, wherein said period is 28 days.

28. A method according to claim 25, wherein said period is 56 days.

29. A method according to claim 25, wherein said period is 84 days.

30. A method according to claim 25, wherein the gestagen is

gestodene,

progesterone,

levonorgestrel,

cyproterone acetate,

chloromadinone acetate,

drospirenone (dihydrospirorenone),

norethisterone,

norethisterone acetate,

norgestimate,

desogestrel,

3-ketodesogestrel,

dienogest,

or a mixture thereof.

31. A method according to claim 25, wherein the gestagen is levonorgestrol which is administered at a dosage of 0.05–

0.2 mg/day or another gestagen administered at a bioequivalent dose.

32. A method according to claim 25, wherein the gestagen is gestodene which is administered at a dosage of 0.05–

0.15 mg/day or another gestagen administered at in a bioequivalent dose.

33. A method according to claim 25, wherein the gestagen is administered orally and/or transdermally.

34. A method according to claim 25, wherein the natural estrogen is administered orally and/or transdermally.

35. A method according to claim 33, wherein the natural estrogen is administered orally and/or transdermally.

36. A method according to claim 25, wherein in the second phase, the gestagen and natural estrogen are administered in combination.

37. A method according to claim 25, wherein in the second phase, the gestagen and natural estrogen are administered separately.

38. A method according to claim 25, wherein the female mammal is human.

39. A method according to claim 25, wherein the gestagen is administered transdermally and the natural estrogen is administered orally.

40. A method according to claim 25, wherein the gestagen is levonorgestrel or gestodene.

41. A method according to claim 25, wherein the gestagen is levonorgestrel in a dose of 0.05–

0.2 mg/day or gestodene in a dose of 0.05–

0.15 mg/day.

42. A method according to claim 25, wherein gestodene, levonorgestrel, desogestrel, 3-ketodesogestrol or a mixture thereof is administered transdermally, and estradiol is administered transdermally at a dose of 0.025–

0.25 mg of release/day.

47. A method according to claim 25, wherein the gestagen is administered orally and/the natural estrogen is administered orally.

52. A method according to claim 25, wherein there is a menstrual bleeding at the end of said period.

53. A method according to claim 25, wherein there is a menstrual bleeding at the end of said period.

43. A method of providing contraception in a female mammal comprising administering a daily steroid preparation to said female mammal for a period of 28–

84 days, said period having a first phase and a second phase, wherein the second phase is the last 5 to 10 days of said period and said first phase is the remainder of said period,

wherein during said first phase a gestagen is daily administered in an ovulation inhibiting amount and the daily amount of gestagen administered remains the same throughout the period, and during said second phase a natural estrogen and an ovulation-inhibiting amount of a gestagen are administered daily.

48. A method according to claim 43, wherein the gestagen is administered orally and/the natural estrogen is administered orally.