Extended Use Combination Comprising Estrogens And Progestins

• US 20080234240A1
• Filed: 11/20/2004
• Published: 09/25/2008
• Est. Priority Date: 11/26/2003
• Status: Abandoned Application

• Current Assignee: Bayer Schering Pharma AG (Bayer AG)
• Original Assignee: Schering Ag (Merck & Co., Inc.)
• Inventors: Endrikat, Jan, Schurmann, Rolf, Düsterberg, Bernd
• Application Number:
  US10/584,045
• Publication Number:
  US 20080234240A1
• 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 31/566 having an oxo group in position 17, e.g. estrone
• CPC Class Codes: A61K 31/567 substituted in position 17 alpha, e.g. mestranol, norethandrolone
• CPC Class Codes: A61K 31/569 substituted in position 17 alpha, e.g. ethisterone
• 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: A61K 31/585 containing lactone rings, e.g. oxandrolone, bufalin
• 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
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A pharmaceutical preparation to obtain a continuous hormonal treatment over a desired period of time longer than 21-28 days comprising a first composition containing at least one estrogen and/or at least one progestin in a predetermined amount to be administered in the first 21-28 days and a second composition which contains at least one estrogen and/or at least one progestin in a predetermined amount higher than the amount of the first composition and comprises a mono or multiphase sequence of pharmaceutical dosages.

Claims

1. A pharmaceutical preparation to obtain a continuous hormonal treatment over a desired period of time longer than 21-28 days comprising a first composition containing at least one estrogen and/or at least one progestin in a predetermined amount to be administered in the first 21-28 days and a second composition characterised in that it contains at least one estrogen and/or at least one progestin in a predetermined amount higher than the amount of the first composition and comprises a mono or multiphase sequence of pharmaceutical dosages.

2. A pharmaceutical preparation according to claim 1 characterised in that it comprises pharmaceutical dosages for the administration over a total time of 56, 84, 112, 140, or 168 days.

3. A pharmaceutical preparation according to claim 1 characterised in that the second composition comprises a one phase sequence of pharmaceutical dosages.

4. A pharmaceutical preparation according to claim 1 characterised in that the second composition comprises a two phase sequence of pharmaceutical dosages.

5. A pharmaceutical preparation according to claim 3 characterised in that the pharmaceutical dosage of at least one estrogen of the second composition is higher than the amount contained in the first composition.

6. A pharmaceutical preparation according to claim 3 characterised in that the pharmaceutical dosage of at least one progestin of the second composition is higher than the amount contained in the first composition.

7. A pharmaceutical preparation according to claim 4 characterised in that the pharmaceutical dosage of at least one estrogen and/or at least one progestin of the second composition are higher than the amount contained in the first composition.

8. A pharmaceutical preparation according to claim 1 characterised in that the at least one estrogen is selected from the group consisting of following synthetic estrogens:

ethinylestradiol, mestranol, quinestranol, or a precursors capable of liberating such an synthetic estrogen and/or from the group of the following biogenic estrogens;

estradiol, estrone, estran, estriol, estetrol, conjugated equine estrogens, precursors capable of liberating such a biogenic estrogen.

9. A pharmaceutical preparation according to claim 8 characterised in that the at least one estrogen is ethinylestradiol and/or estradiol.

10. A pharmaceutical preparation according to claim 1 characterised in that the daily hormone units of estrogen preferably contain ethinylestradiol in an amount of 0.005-50 mg, most preferably in an amount of 0.005-0.030 mg and/or the estradiol in an amount of to 0.1-5.0 mg.

11. A pharmaceutical preparation according to claim 1 characterised in that the at least one progestin is selected from the group consisting of levonorgestrel, norgestimate, norethisterone, dydrogesterone, drospirenone, 3-beta-hydroxydesogestrel, 3-keto desogestrel (=etonogestrel), 17-deacetyl norgestimate, 19-norprogesterone, acetoxypregnenolone, allylestrenol, anagestone, chlormadinone acetate, cyproterone acetate, demegestone, desogestrel, dienogest, dihydrogesterone, dimethisterone, ethisterone, ethynodiol diacetate, fluorogestone acetate, gastrinon, gestodene, gestrinone, hydroxymethylprogesterone, hydroxyprogesterone, lynestrenol (=lynoestrenol), medrogestone, medroxyprogesterone acetate, megestrol, melengestrol, nomegestrol, norethindrone (=norethisterone), norethynodrel, norgestrel (includes d-norgestrel and dl norgestrel), norgestrienone, normethisterone, progesterone, quingestanol, (17alpha)-17-hydroxy-11-methylene-19-norpregna-4,15-diene-20-yn-3-one, tibolone, algestone acetophenide, nestorone, promegestone, 17-hydroxyprogesterone esters, 19-nor-17hydroxyprogesterone, 17alpha-ethinyl-testosterone, 17alpha-ethinyl-19-nor-testosterone, d-17beta-acetoxy-13beta-ethyl-17alpha-ethinyl-gon-4-en-3-one oxime, hydroxytriendione ((21S)-21-hydroxy-21-methyl-14,17ethano-19-nor-pregna-4,9,15-triene-3,20-dione), 5-{2-hydroxy-3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-trifluoromethyl-propionylamino}-phthalide and precursors thereof.

12. A pharmaceutical preparation according to claim 1 characterised in that the at least one progestin is preferably selected from the group consisting of levonorgestrel, dienogest, gestodene, drospirenone, and precursors thereof.

13. A pharmaceutical preparation according to claim 1 characterised in that the daily hormone units of at least a progestin for use during the whole extended treatment preferably contain the progestin in an amount of 0.03-0.25 mg of levonorgestrel and/or 0.5-5 mg of dienogest and/or 0.03-0.15 mg of gestodene, and/or 0.5-5 mg of drospirenone or equivalent dosages of other progestins.

14. A pharmaceutical preparation according to claim 1 characterised in that the hormone units are administered orally, parenterally, sublingually, transdermally, intravaginally, intranasally or buccally.

15. A pharmaceutical preparation according to claim 1 characterised in that the hormone units are for oral administration.

16. A pharmaceutical preparation according to claim 1 characterised in that the hormone units are daily units.

17. Use of a pharmaceutical preparation according to claim 1 for the manufacture of an agent for inhibiting ovulation in a mammal, in particular a human.

18. Use of a pharmaceutical preparation according to claim 17 characterised in that the administration of said preparation extends over a time of 56, 84, 112, 140 or 168 days.

19. Use of a pharmaceutical preparation according to claim 17 for the manufacture of an agent for diminishing symptoms related to hormonal withdrawal such as premenstrual symptoms, dysmenorrhea, endometriosis, menstrual migraine.

20. Use of a pharmaceutical preparation according to claim 17 for the manufacture of an agent for diminishing symptoms related to acne

22. Pharmaceutical package according to claim 21 characterised in that said first composition and said second composition correspond to the first and the second composition as defined in the pharmaceutical preparation according to claim 1 to 16.

21. A pharmaceutical package for an extended regimen treatment longer than 21-28 days comprising:

a first composition containing at least one estrogen and/or at least one progestin in a predetermined amount to be administered in the first 21-28 days

a second composition containing at least one estrogen and/or at least one progestin in a predetermined amount higher than the amount of the first composition to be administered in the following of the treatment and comprising a mono or multiphase sequence of pharmaceutical dosages.

23. Pharmaceutical package according to claim 21 characterised in that the first and/or the second composition are administered in daily doses.

24. Pharmaceutical package according to claim 21 characterised in that the first and/or the second composition are arranged for separate sequential administration like for example in separate blisters.

25. Pharmaceutical package according to claim 21 characterised in that the administration of the first and second composition extends over a time of 56, 84, 112, 140 or 168 days.