Contraceptive methods and formulations for use therein

• US 5,211,952 A
• Filed: 04/12/1991
• Issued: 05/18/1993
• Est. Priority Date: 04/12/1991
• Status: Expired due to Term

• Current Assignee: University of Southern California
• Original Assignee: University of Southern California
• Inventors: Spicer, Darcy V., Pike, Malcolm C.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): AZPURU, CARLOS A
• Application Number:
  US07/684,612
• Time in Patent Office: 767 Days
• Field of Search: 424/422, 424/423, 424/424, 424/426, 424/430, 424/432, 424/433, 424/484, 424/485, 424/486, 424/487, 424/488, 424/489, 424/490, 424/496, 424/497, 424/498, 424/DIG. 14, 514/2, 514/12, 514/21, 514/800, 514/841, 514/842, 514/843, 530/313, 530/850, 530/853, 128/830, 128/832, 128/833
• US Class Current: 424/426
• 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 31/05 Phenols cannabinoids A61K31/658
• 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 38/09 Luteinising hormone-releasing hormone [LHRH] , i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
• CPC Class Codes: A61K 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: Y10S 424/14 Topical contraceptives and spermacides
• CPC Class Codes: Y10S 530/85 Reproductive organs or embryos
• CPC Class Codes: Y10S 530/853 Ovary; eggs; embryos

Abstract

Contraceptive devices which are effective for extended periods of time are described, in the form of means for releasing an effective amount of a gonadotropin hormone releasing hormone composition and means for releasing an effective amount of an estrogenic hormone over a first period of time, and means for releasing an effective amount of a progestogen for a second period of time, the second period of time being substantially shorter than and running simultaneously with a portion of the first period of time. The gonadotropin hormone releasing hormone composition is selected from gonadotropin hormone releasing hormone, gonadotropin hormone releasing hormone analogues, gonadotropin hormone releasing hormone agonists, gonadotropin hormone releasing hormone antagonists and mixtures thereof. Contraceptive methods employing the devices are also described.

Claims

1. A composition for use in a contraceptive delivery system comprising:

a slow-release formulation of a gonadotropin hormone releasing hormone composition which maintains serum levels of said gonadotropin hormone releasing hormone composition at a level effective to inhibit ovulation over a first period of time comprising about two months to about six months;

a slow-release formulation of an estrogenic hormone which maintains serum levels of said estrogenic hormone at a level equivalent to a serum level of estradiol of from about 25 to about 140 pg/ml over said first period of time; and

a slow-release formulation of a progestogen which maintains serum levels of said progestogen at a level equivalent to a serum level of progesterone of from about 5 to about 20 ng/ml for a second period of time comprising about 5 to about 20 days, said second period of time running simultaneously with a portion of said first period of time.

2. A contraceptive composition according to claim 1, wherein said gonadotropin hormone releasing hormone composition is selected from the group consisting of gonadotropin hormone releasing hormone, gonadotropin hormone releasing hormone analogues, gonadotropin hormone releasing hormone agonists, gonadotropin hormone releasing hormone antagonists and mixtures thereof.

3. A contraceptive composition according to claim 2, wherein said gonadotropin hormone releasing hormone composition is a gonadotropin hormone releasing hormone agonist selected from the group consisting of leuprolide acetate, goserelin, decapeptyl, buserelin, nafarelin, deslorelin, histrelin, gonadorelin, [(Imbzl)-D-His⁶ -Pro⁹ -Net]GnRH and mixtures thereof.

4. A contraceptive composition according to claim 1, wherein said estrogenic steroid is selected from the group consisting of estradiol, estradiol benzoate, estradiol cypionate, estradiol valerate, estrone, diethylstilbestrol, piperazine estrone sulfate, ethinyl estradiol, mestranol, polyestradiol phosphate, estriol, estriol hemisuccinate, quinestrol, estropipate, pinestrol, estrone potassium sulfate, equilelinin, equilelinin sulfate, estetrol and mixtures of two or more thereof.

5. A contraceptive composition according to claim 1, wherein said progestogen is selected from the group consisting of dydrogesterone, ethynodiol diacetate, hydroxyprogesterone caproate, medroxyprogesterone acetate, norethindrone, norethindrone acetate, norethynodrel, norgestrel, progesterone, megestrol acetate and mixtures of two or more thereof.

6. A contraceptive device according to claim 1, wherein said first period of time is about three months to about four months.

7. A contraceptive device according to claim 1, wherein said second period of time is about 10 days to about 15 days.

8. A contraceptive composition according to claim 1, wherein said GnRH composition, estrogenic steroid and progestogen are administered by a subcutaneous, intramuscular, vaginal or transdermal route.

10. A method according to claim 1, wherein said gonadotropin hormone releasing hormone composition is selected from the group consisting of gonadotropin hormone releasing hormone, gonadotropin hormone releasing hormone analogues, gonadotropin hormone releasing hormone agonists, gonadotropin hormone releasing hormone antagonists and mixtures thereof.

11. A method according to claim 10, wherein said gonadotropin hormone releasing hormone composition is a gonadotropin hormone releasing hormone agonist selected from the group consisting of leuprolide acetate, goserelin, decapeptyl, buserelin, nafarelin, deslorelin, histrelin, gonadorelin, [(Imbzl)-D-His⁶ -Pro⁹ -Net]GnRH and mixtures thereof.

14. A method according to claim 1, wherein said first period of time is about three months to about four months.

9. A method for preventing conception in a mammal, comprising:

administering an amount of a gonadotropin hormone releasing hormone composition effective to maintain serum levels of said gonadotropin hormone releasing hormone composition at a level effective to inhibit ovulation for a first period of time comprising about two months to about six months;

simultaneously administering an amount of an estrogenic hormone effective to maintain serum levels of said estogenic hormone at a level equivalent to a serum level of estradiol of from about 25 to about 140 pg/ml for said first period of time; and

administering an amount of a progestogen effective to maintain serum levels of said progestogen at a level equivalent to a serum level of progesterone of from about 5 to about 20 ng/ml for a second period of time comprising about 5 to about 20 days, said second period of time running simultaneously with a portion of said first period of time;

12. A method according to claim 9, wherein said estrogenic steroid is selected from the group consisting of estradiol, estradiol benzoate, estradiol cypionate, estradiol valerate, estrone, diethylstilbestrol, piperazine estrone sulfate, ethinyl estradiol, mestranol, polyestradiol phosphate, estriol, estriol hemisuccinate, quinestrol, estropipate, pinestrol, estrone potassium sulfate, equilelinin, equilelinin sulfate, estetrol and mixtures of two or more thereof.

13. A method according to claim 9, wherein said progestogen is selected from the group consisting of dydrogesterone, ethynodiol diacetate, hydroxyprogesterone caproate, medroxyprogesterone acetate, norethindrone, norethindrone acetate, norethynodrel, norgestrel, progesterone, megestrol acetate and mixtures of two or more thereof.

15. A method according to claim 9, wherein said second period of time is about 10 days to about 15 days.

16. A method according to claim 9, wherein said GnRH composition, estrogenic steroid and progestogen are administered by a subcutaneous, intramuscular, vaginal or transdermal route.