Combination contraceptive

• US 6,225,297 B1
• Filed: 11/01/1996
• Issued: 05/01/2001
• Est. Priority Date: 12/22/1993
• Status: Expired due to Term

• Current Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Original Assignee: Schering Akitiengesellschaft
• Inventors: Chwalisz, Kristof, Stockemann, Klaus
• Primary Examiner(s): Raymond, Richard L.
• Application Number:
  US08/666,592
• Time in Patent Office: 1,642 Days
• Field of Search: 514/170, 514/171, 514/179, 514/178, 514/180, 514/843
• 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

Abstract

This invention relates to a combination product that consists of individual dosage units of a competitive progesterone antagonist and, in addition, sequentially provided individual dosage units of a compound with gestagenic action, as well as its use for the production of contraceptives based on the inhibition of implantation (receptivity inhibition).

Claims

1. A product that contains in combination individual dosage units of a competitive progesterone antagonist and individual dosage units of a gestagen useful for its sequential, oral administration, in which the amount of the competitive progesterone antagonist in each of its individual dosage units is non-ovulation-inhibiting and non-abortion-inducing.

2. The product according to claim 1, in which the amount of the competitive progesterone antagonist in each of its individual dosage units is effective for once-daily to once-weekly administration.

3. The product according to claim 2, in which the amount of the competitive progesterone antagonist in each of its individual dosage units is effective for once-daily administration.

4. The product according to claim 2, in which the amount of the competitive progesterone antagonist in each of its individual dosage units is effective for once-weekly administration.

5. The product according to claim 1, in which the amount of the gestagen in each of its individual dosage units is effective for daily administration on successive days.

6. The product according to claim 1, in which the gestagen is distributed in 2 to 12 dosage units.

7. The product according to claim 6, in which the dosage units are arrayed according to a sequential schedule for their administration, so that the gestagen units are to be administered sequentially starting on day 18 or later after the first dosage unit of the competitive progesterone antagonist is to be administered.

8. The product according to claim 7, in which the dosage units are arrayed so that the gestagen units are to be administered starting on day 21 or 22 after the first dosage unit of the competitive progesterone antagonist is to be administered.

9. The product according to claim 1, in which the competitive progesterone antagonist dosage units contain at least one compound selected from the group consisting of

11β

-((4-N,N-dimethylamino)-phenyl)-17β

-hydroxy-17α

-propinyl-4,9(10)-estradien-3-one,

11β

-((4-N,N-dimethylamino)-phenyl)-17β

-hydroxy-18-methyl-17α

-propinyl-4,9(10)-estradien-3-one,

11β

-((4-N,N-dimethylamino)-phenyl)-17α

β

-hydroxy-17aα

-propinyl-D-homo-4,9(10), 16-estratien-3-one,

11β

-p-methoxyphenyl-17β

-hydroxy-17α

-ethinyl-4,9(10)-estradien-3-one,

11β

-(4-acetylphenyl)-17β

-hydroxy-17α

-(prop-1-inyl)-4,9(10)-estradien-3-one,

11β

-((4-dimethylamino)phenyl)-17α

-hydroxy-17β

-(3-hydroxypropyl)-13α

-methyl-4,9(10)-gonadien-3-one,

11β

,19-(4-acetylphenyl)-17β

-hydroxy-17α

-(3-hydroxyprop-1(Z)-enyl)-4,9 (10)-estradien-3-one,

11β

,19-(4-(cyanophenyl)-17β

-hydroxy-17α

-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one, and

11β

,19-(4-(3-pyridinyl)-o-phenylene)-17β

-hydroxy-17a-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one.

10. The product according to claim 1, in which the amount of the competitive progesterone antagonist in each individual dosage unit is 0.1 to 50 mg of 11β

-((4-dimethylamino)phenyl)-17α

-hydroxy-17β

-(3-hydroxypropyl)-13α

-methyl-4,9(10)-gonadien-3-one, 0.1-5.0 mg of 11β

-((4-N,N-dimethylamino)-phenyl)-17β

-hydroxy-17α

-propinyl-4,9(10)-estradien-3-one or a biologically equivalent amount of another competitive progesterone antagonist.

11. The product according to claim 1, in which the gestagen dosage units contain at least one of gestodene, progesterone, levonorgestrel, cyproterone acetate, chlormadinone acetate, drospirenone, norethisterone, norethisterone acetate, norgestimate, desogestrel, 3-ketodesogestrel or another artificial or natural gestagen.

12. The product according to claim 1, in which the amount of the gestagen in each individual dosage unit is 0.6-6.0 mg of levonorgestrel, 2-20 mg of cyproterone acetate, 0.3-3.0 mg of gestodene or 0.2-2.0 mg of desogestrel or an equivalent of another gestagen.

13. A method of contraception, comprising administering to a patient an effective amount of a competitive progesterone antagonist and an effective amount of a gestagen, wherein the amount of said competitive progesterone antagonist does not inhibit ovulation or induce abortion.

14. The method of claim 13, wherein said effective amounts of competitive progesterone antagonist and gestagen are administered sequentially.

15. The method of claim 13, wherein said effective amounts of competitive progesterone antagonist and gestagen are administered simultaneously.

16. The method of claim 13, wherein said competitive progesterone antagonist and said gestagen are administered orally.

17. The method of claim 13, wherein said competitive progesterone antagonist is administered daily or weekly.

18. The method of claim 13, wherein said gestagen is administered daily.

19. The method of claim 13, wherein said competitive progesterone antagonist is

11β

-((4-N,N-dimethylamino)-phenyl)-17β

-hydroxy-17α

-propinyl-4,9(10)-estradien-3-one,

11β

-((4-N,N-dimethylamino)-phenyl)-17β

-hydroxy-18-methyl-17α

-propinyl-4,9(10)-estradien-3-one,

11β

-((4-N,N-dimethylamino)-phenyl)-17α

β

-hydroxy-17aα

-propinyl-D-homo-4,9(10), 16-estratien-3-one,

11β

-p-methoxyphenyl-17β

-hydroxy-17α

-ethinyl-4,9(10)-estradien-3-one,

11β

-(4-acetylphenyl)-17β

-hydroxy-17α

-(prop-1-inyl)-4,9(10)-estradien-3-one,

11β

-((4-dimethylamino)phenyl)-17α

-hydroxy-17β

-(3-hydroxypropyl)-13α

-methyl-4,9(10)-gonadien-3-one,

11β

,19-(4-acetylphenyl)-17β

-hydroxy-17α

-(3-hydroxyprop-1(Z)-enyl)-4,9(10)-estradien-3-one,

11β

,19-(4-(cyanophenyl)-17β

-hydroxy-17α

-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one, or

11β

,19-(4-(3-pyridinyl)-o-phenylene)-17β

-hydroxy-17a-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one.

20. The method of claim 13, wherein the effective amount of said competitive progesterone antagonist is 0.1 to 50 mg of 11β

-[(4-dimethylamino)phenyl]-17α

-hydroxy-17β

-(3-hydroxypropyl)-13α

-methyl-4,9(10)-gonadien-3-one, 0.1-5.0 mg of 11β

-((4-N,N-dimethylamino)-phenyl)-17β

-hydroxy-17α

-propinyl-4,9(10)-estradien-3-one or a biologically equivalent amount of another competitive progesterone antagonist.

21. The method of claim 13, wherein said gestagen is gestodene, progesterone, levonorgestrel, cyproterone acetate, chlormadinone acetate, drospirenone, norethisterone, norethisterone acetate, norgestimate, desogestrel, 3-ketodesogestrel or another artificial or natural gestagen.

22. The method of claim 13, wherein the effective amount of said gestagen is 0.6-6.0 mg of levonorgestrel, 2-20 mg of cyproterone acetate, 0.3-3.0 mg of gestodene or 0.2-2.0 mg of desogestrel or an equivalent amount of another gestagen.

23. The method of claim 13, wherein said competitive progesterone antagonist and said gestagen are administered locally, topically, enterally, transdermally or parenterally.