Hormone preparation and method

• US 5,108,995 A
• Filed: 04/26/1990
• Issued: 04/28/1992
• Est. Priority Date: 09/24/1987
• Status: Expired due to Term

• Current Assignee: Jencap Research Ltd.
• Original Assignee: Jencap Research Ltd.
• Inventors: Casper, Robert F.
• Primary Examiner(s): Rose, Shep K.
• Application Number:
  US07/515,691
• Time in Patent Office: 733 Days
• Field of Search: 514/170, 514/171
• 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 is concerned with a contraceptive formulation and a method of contraception which employs a combination of estrogen and progestin and wherein a short period of relatively dominant estrogenic activity alternates with a short period of relatively dominant progestagenic activity. The invention also concerns a hormonal replacement formulation and method for use in menopausal or castrate women which employs a similar combination of estrogen and progestin.

Claims

1. A method of treating a female in need of hormone replacement therapy comprising administering to said female repeating cycles of a pharmaceutical regimen, each cycle comprising a series of from 20 to 35 consecutive daily unit doses arranged in alternating estrogen dominant phases and progestin dominant phases, each phase consisting of from one to four consecutive daily unit doses, wherein the daily unit doses of said estrogen dominant phases contain an amount of a substance exhibiting estrogen activity or an amount of a substance exhibiting estrogen activity and an amount of a substance exhibiting progestin activity, and the daily unit doses of said progestin dominant phases contain an amount of a substance exhibiting estrogen activity and an amount of a substance exhibiting estrogen activity and an amount of a substance exhibiting progestin activity, the amount of said substance exhibiting progestin activity being alternately increased in the progestin dominant phases to provide daily unit doses exhibiting progestin dominant activity and decreased in the estrogen dominant phases to provide daily unit doses exhibiting estrogen dominant activity, and wherein the amount of substance exhibiting estrogen activity per unit dose exhibits an estrogen activity equivalent to from about 0.3 to about 2.5 mg of piperazine estrone sulfate, and the amount of substance exhibiting progestin activity per unit dose ranges from 0 to an amount which exhibits a progestin activity equivalent to about 5 mg of norethindrone.

2. A method of hormone therapy according to claim 1, wherein all of said daily unit doses contain a uniform amount of said substance exhibiting estrogen activity.

3. A method of hormone therapy according to claim 1, wherein all of said daily unit doses contain said substance exhibiting progestin activity, and the amount of said substance exhibiting progestin activity is alternately increased in said progestin dominant phases to provide daily unit doses exhibiting progestin dominant activity and decreased in said estrogen dominant phases to provide daily unit doses exhibiting estrogen dominant activity.

4. A method of hormone therapy according to claim 1, wherein said substance exhibiting estrogen activity is selected from the group consisting of 17β

-estradiol and piperazine estrone sulfate, and said substance exhibiting progestin activity is selected from the group consisting of norethindrone, desogestrel, norgestimate and progesterone.

5. A method of hormone therapy according to claim 1, wherein said daily unit doses are in orally administrable form.

6. A method of hormone therapy according to claim 1, wherein said daily unit doses are in transdermally administrable form.

7. A method of hormone therapy according to claim 1, wherein said daily unit doses are in buccally administrable form.

8. A method of hormone therapy according to claim 1, comprising administering a series of consecutive daily unit doses arranged in estrogen dominant phases of two daily unit doses each alternating with progestin dominant phases of two daily unit doses each.

9. A method of hormone therapy according to claim 1, comprising administering a series of consecutive daily unit doses arranged in estrogen dominant phases of three daily unit doses each alternating with progestin dominant phases of three daily unit doses each.

10. A method of hormone therapy according to claim 1, comprising administering a series of consecutive daily unit doses arranged in estrogen dominant phases of four daily unit doses each alternating with progestin dominant phases of three daily unit doses each.

11. A method of hormone therapy according to claim 1, comprising administering a series of consecutive daily unit doses arranged in estrogen dominant phases of three daily unit doses each alternating with progestin dominant phases of four daily unit doses each.

12. A method of hormone therapy according to claim 1, wherein the daily unit doses of said estrogen dominant phases are free of substance exhibiting progestin activity.

13. A method of hormone therapy according to claim 12, wherein each estrogen dominant phase consists of three orally administrable daily unit doses each containing 0.75 mg piperazine estrone sulfate, and each progestin dominant phase consists of three orally administrable daily unit doses each containing 0.75 mg piperazine estrone sulfate and 0.35 mg norethindrone.

14. A method of hormone therapy according to claim 12, wherein each estrogen dominant phase consists of three transdermally administrable daily unit doses each releasing 0.1 mg 17β

-estradiol, and each progestin dominant phase consists of three transdermally administrable daily unit doses each releasing 0.1 mg 17β

-estradiol and 0.35 mg norethindrone.

15. A method of hormone therapy according to claim 12, wherein each estrogen dominant phase consists of three transdermally administrable daily unit doses each releasing 0.1 mg 17β

-estradiol and 0.15 mg norethindrone, and each progestin dominant phase consists of three transdermally administrable daily unit doses each releasing 0.1 mg 17β

-estradiol and 0.35 mg norethindrone.

16. A method according to claim 1, wherein the daily unit doses of said estrogen dominant phases contain an amount of substance exhibiting progestin activity ranging from 0 to an amount which exhibits a progestin activity equivalent to 0.5 mg norethindrone, and the daily unit doses of said progestin dominant phases contain an amount of substance exhibiting progestin activity which exhibits a progestin activity equivalent to from 0.35 to 5 mg norethindrone, the amount of substance exhibiting progestin activity being greater in said progestin dominant phases than in said estrogen dominant phases.