Estrogen-gestagen combination preparations and uses thereof

• US 20040266745A1
• Filed: 03/26/2004
• Published: 12/30/2004
• Est. Priority Date: 09/29/2001
• Status: Abandoned Application

• Current Assignee: Solvay Pharmaceuticals GmbH (Abbvie Incorporated)
• Original Assignee: Solvay Pharmaceuticals GmbH (Abbvie Incorporated)
• Inventors: Hachmeister, Bernd, Rogoll, Jutta, Schwanitz, Diethard
• Application Number:
  US10/809,802
• Publication Number:
  US 20040266745A1
• Time in Patent Office: Days
• US Class Current: 514/182
• 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: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 5/30 Oestrogens
• CPC Class Codes: A61P 5/34 Gestagens

Abstract

Estragen/gestagen combination preparations useful in hormone replacement therapy to treat, for example, menopausal or climacteric complaints, and method of use thereof.

Claims

1. A method of treating or inhibiting menopausal symptoms in a woman when a menstrual cycle is no longer desired, said method comprising orally administering to said woman over a period of at least 28 days uninterrupted alternating daily dosage units of an estrogen active ingredient and combined daily dosage units of a combination of estrogen active ingredient and a gestagen active ingredient.

2. A method according to claim 1, wherein said woman is a woman with an intact uterus.

3. An orally administrable pharmaceutical preparation for treating or inhibiting menopausal symptoms in a woman when a menstrual cycle is no longer desired, said pharmaceutical preparation containing 14 separate daily dosage units or an integral multiple thereof of an estrogen active ingredient and a corresponding number of combined daily dosage units of a combination of estrogen active ingredient with a gestagen active ingredient, said daily dosage units facilitating daily alternating uninterrupted administration of daily dosage units of the estrogen active ingredient and the combined daily dosage units of the combination of estrogen active ingredient and gestagen active ingredient over a period of at least 28 days.

4. An orally administrable pharmaceutical preparation according to claim 3, wherein said pharmaceutical preparation contains 14 daily dosage units of an estrogen active ingredient and 14 combined daily dosage units of a combination of estrogen active ingredient and a gestagen active ingredient for a 28-day cycle.

5. An orally administrable pharmaceutical preparation according to claim 3, wherein said pharmaceutical preparation contains 42 daily dosage units of the estrogen active ingredient and a corresponding number of combination daily dosage units containing a combination of estrogen active ingredient with a gestagen active ingredient, whereby alternating daily doses of said estrogen active ingredient and daily combination doses of a combination of estrogen active ingredient and a gestagen active ingredient can be administered over a 12 week period of time.

6. An orally administrable pharmaceutical preparation according to claim 3, wherein said estrogen active ingredient is selected from the group consisting of estradiol, 17β

-estradiol, estradiol valerate, natural conjugated estrogens including those of equine origin, estrone, estropipate (piperazine estrone sulfate), ethinyl estradiol, mestranol and quinestranol.

7. An orally administrable pharmaceutical preparation according to claim 6, wherein said estrogen active ingredient is natural conjugated equine estrogens.

8. An orally administrable pharmaceutical preparation according to claim 3, wherein said gestagen active ingredient is selected from the group consisting of levonorgestrel, dl-norgestrel, norethindrone (norethistrone), norethindrone (norethistrone) acetate, ethynodiol diacetate, dydrogesterone, medroxyprogesterone acetate, norethynodrel, allylestrenol, lynoestrenol, quingestanol acetate, medrogestone, norgestrienone, dimethisterone, ethisterone, cyproterone acetate, chlormadinone acetate, megestrole acetate, gestoden, desogestrel, trimegestone, dienogest, drosperinone and nomegestrole acetate.

9. An orally administrable pharmaceutical preparation according to claim 8, wherein said gestagen active ingredient is selected from the group consisting of dydrogesterone, medroxyprogesterone acetate, norethistrone acetate, trimegestone, dienogest, drosperinone and medrogestone.

10. An orally administrable pharmaceutical preparation according to claim 9, wherein said gestagen active agent is medrogestone.

11. An orally administrable pharmaceutical preparation according to claim 3, wherein the daily dosage units of estrogen active ingredient contain a mixture of natural conjugated equine estrogens in an amount of 0.05 mg to 10 mg, and the combined daily dosage units contain the estrogen active ingredient in an amount of 0.05 mg to 10 mg, and the gestagen active ingredient in an amount of 0.05 mg to 50 mg.

12. An orally administrable pharmaceutical preparation according to claim 11, wherein the combined daily dosage units contain a mixture of natural conjugated equine estrogens as the estrogen active ingredient and medrogestone in an amount of 1 mg to 20 mg as the gestagen active ingredient.

13. An orally administrable pharmaceutical preparation according to claim 12, wherein the combined daily dosage units contain an amount of 1 mg to 10 mg or medrogestone as the gestagen active ingredient.

14. An orally administrable pharmaceutical preparation according to claim 3, wherein the daily dosage units of the estrogen active ingredient contain about 14 mg of an extract from the urine of gravid mares, standardized to 0.33 mg sodium salt of estrone 3-hydrogen sulfate and 0.17 mg sodium salt of equiline 3-hydrogen sulfate (corresponding to 0.6 mg conjugated equine estrogens), and the combined daily dosage units contain a combination of about 14 mg of an extract from the urine of gravid mares, standardized to 0.33 mg sodium salt of estrone 3-hydrogen sulfate and 0.17 mg sodium salt of equiline 3-hydrogen sulfate (corresponding to 0.6 mg conjugated estrogens) as the estrogen active ingredient and about 5 mg medrogestone as the gestagen active ingredient.

15. A packaged pharmaceutical preparation for hormone replacement therapy containing:

a packaging material in which 14 daily dosage units or an integral multiple thereof of an estrogen active ingredient and a corresponding number of combined daily dosage units containing a combination of an estrogen active ingredient with a gestagen active ingredient are accommodated separately, and the daily doses of the estrogen active ingredient and the combined daily dosage units of the estrogen active ingredient and the gestagen active ingredient are labeled or characterized to differentiate them from one another, and

a label or package insert indicating that the preparation may be administered for treating or inhibiting menopausal symptoms in women when a menstrual cycle is no longer desired, by uninterrupted alternating daily administration of the daily dosage units of the estrogen active ingredient and the combined daily dosage units of the combination of estrogen active ingredient and gestagen active ingredient over a period of at least 28 days.

16. A packaged pharmaceutical preparation according to claim 15, wherein the daily dosage unit containing the estrogen active ingredient and the daily combined daily dosage unit of estrogen active ingredient and gestagen active ingredient are visibly labeled by different colors for differentiation from one another.

17. A packaged pharmaceutical preparation according to claim 15, wherein the packaging material is a blister pack on which is printed a schedule to facilitate alternating administration of the daily dosage units of the estrogen active ingredient and the combined daily dosage unit of the estrogen active ingredient and gestagen active ingredient.

18. A packaged pharmaceutical preparation according to claim 17, wherein said schedule is printed out as a diagram of integers from 1 to 28.

19. A packaged pharmaceutical preparation according to claim 17, wherein in addition to the schedule for alternating administration of the daily dosage units of estrogen active ingredient and combined daily dosage unit of estrogen active ingredient and gestagen active ingredient, the blister pack additionally has a second cyclic schedule provided on an opposite side specifying initial administration of 14 consecutive daily dosage units of the estrogen active ingredient followed by 14 combined daily dosage units of estrogen active ingredient and gestagen active ingredient for women in whom a menstrual cycle is still desired.

20. A packaged pharmaceutical preparation according to claim 15, wherein the packaging material comprises a pill dispenser subdivided into 28 compartments in which daily dosage units of estrogen active ingredient and combination daily dosage units of estrogen active ingredient and gestagen active ingredient are accommodated in alternation and are labeled to differentiate them from one another.

21. A packaged pharmaceutical preparation according to claim 19, wherein said compartments are arranged in ring shape.