Combination compound for contraception based on natural estrogen

• US 6,133,251 A
• Filed: 10/25/1996
• Issued: 10/17/2000
• Est. Priority Date: 10/28/1995
• Status: Expired due to Term

• Current Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Original Assignee: Jenapharm GmbH & Co. KG (Bayer AG)
• Inventors: Dittgen, Michael, Fricke, Sabine, Oettel, Michael, Hoffmann, Herbert, Moore, Claudia, Ostertag, Monika
• Primary Examiner(s): MOEZIE, MINNA FAY
• Application Number:
  US08/738,314
• Time in Patent Office: 1,453 Days
• Field of Search: 514/182, 514/170, 514/178, 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
• 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 5/30 Oestrogens
• CPC Class Codes: A61P 5/34 Gestagens

Abstract

The combination preparation for contraception includes a first stage of 2 to 4 first stage daily dosage portions, a second stage of two groups of second stage daily dosage portions, a third stage of 2 to 4 third stage daily dosage portions and an additional stage of 2 to 4 additional stage daily dosage portions. The first stage daily dosage portion is an effective amount of natural estrogen, the second stage daily dosage portion is an effective amount of a combination of natural estrogen and natural or synthetic gestogen, the third stage daily dosage portion is another effective amount of natural estrogen and an additional stage daily dosage portion consists of a placebo. The first group of the second stage consists of 3 to 5 daily dosage portions and the second group, 13 to 17 daily dosage portions. More of the gestogen is included in the effective amount in the second group of the second stage than in the first group. The effective amount of the natural estrogen is constant in both the first and third stages, but smaller in the third stage than in the first stage.

Claims

1. A combination preparation for contraception comprising a first stage consisting of from 2 to 4 first stage daily dosage portions, a second stage consisting of two groups of second stage daily dosage portions, a third stage consisting of from 2 to 4 third stage daily dosage portions and an additional stage consisting of from 2 to 4 additional stage daily dosage portions;

wherein said first stage daily dosage portions each consist of an effective amount of at least one natural estrogen, said second stage daily dosage portions of said first group and said second group each consist of an effective amount of a combination of said at least one natural estrogen and at least one natural or synthetic gestogen, said third stage daily dosage portions each consist of an effective amount of said at least one natural estrogen and said additional stage daily dosage portions each consist of a pharmaceutically acceptable placebo;

wherein said first group of said second stage consists of 3 to 5 of said second stage daily dosage portions, said second group of said second stage consists of 13 to 17 of said second stage daily dosage portions and said second stage daily dosage portions each include more of said at least one synthetic or natural gestogen in said second group than in said first group;

wherein said effective amount of said at least one natural estrogen is constant in said first stage and also constant in said third stage but said effective amount in said third stage is smaller than said effective amount in said first stage; and

wherein said at least one natural estrogen is selected from the group consisting of estradiol, conjugated equine estradiol and estradiol compounds that are metabolized to form estradiol when taken into the body.

2. The combination preparation as defined in claim 1, wherein said second stage daily dosage portions each include from 1.5 to 3 times more of said at least one synthetic or natural gestogen in said second group than in said first group of said second stage.

3. The combination preparation as defined in claim 1, wherein said at least one natural or synthetic gestogen is dienogest and said at least one natural estrogen is said estradiol.

4. A combination preparation for contraception comprising

a first stage consisting of from 2 to 4 first stage daily dosage portions, a second stage consisting of two groups of second stage daily dosage portions, a third stage consisting of from 2 to 4 third stage daily dosage portions and an additional stage consisting of from 2 to 4 additional stage daily dosage portions;

wherein said first stage daily dosage portions each consist of an effective amount of at least one natural estrogen, said second stage daily dosage portions of said first group and said second group each consist of an effective amount of a combination of said at least one natural estrogen and at least one natural or synthetic gestogen, said third stage daily dosage portions each consist of an effective amount of said at least one natural estrogen and said additional stage daily dosage portions each consist of a pharmaceutically acceptable placebo;

wherein said first group of said second stage consists of 3 to 5 of said second stage daily dosage portions, said second group of said second stage consists of 13 to 17 of said second stage daily dosage portions and said second stage daily dosage portions each include more of said at least one synthetic or natural gestogen in said second group than in said first group;

wherein said effective amount of said at least one natural estrogen is constant in said first stage and also constant in said third stage but said effective amount in said third stage is smaller than said effective amount in said first stage; and

wherein said at least one natural estrogen is selected from the group consisting of estradiol, conjugated equine estradiol and estradiol valerate and said at least one natural or synthetic gestogen is selected from the group consisting of progesterone, desogestrel, gestoden, levonorgestrel, medroxyprogesterone acetate, chlormadinone acetate and dienogest.

5. A method of contraception, said method comprising the steps of:

a) administering from 2 to 4 first stage daily dosage portions each consisting of an effective amount of at least one natural estrogen in a first stage of the method;

b) after step a), administering a first group of 3 to 5 second stage daily dosage portions each consisting of a first effective amount of a combination of said at least one natural estrogen and at least one natural or synthetic gestogen in a second stage of the method;

c) after step b), administering a second group of 13 to 17 second stage daily dosage portions each consisting of a second effective amount of said combination of said at least one natural estrogen and said at least one natural or synthetic gestogen in the second stage of the method;

d) after step c), administering from 2 to 4 third stage daily dosage portions each consisting of an effective amount of said at least one natural estrogen in a third stage; and

e) after step d), administering in an additional stage consisting of from 2 to 4 additional stage daily dosage portions each consisting of a pharmaceutically acceptable placebo;

wherein said second effective amount of said combination in said second group of said second stage includes more of said at least one synthetic or natural gestogen than said first effective amount of said combination in said first group;

wherein said effective amount of said at least one natural estrogen is constant in said first stage and also constant in said third stage, but said effective amount of said at least one natural estrogen is smaller in said third stage than in said first stage; and

wherein said at least one natural estrogen is selected from the group consisting of estradiol, conjugated equine estradiol and estradiol compounds that are metabolized to form estradiol when taken into the body.

6. The method as defined in claim 5, wherein said at least one natural or synthetic gestogen is dienogest and said at least one natural estrogen is said estradiol.

7. A method of contraception, said method comprising the steps of:

a) administering from 2 to 4 first stage daily dosage portions each consisting of an effective amount of at least one natural estrogen in a first stage of the method;

b) after step a), administering a first group of 3 to 5 second stage daily dosage portions each consisting of a first effective amount of a combination of said at least one natural estrogen and at least one natural or synthetic gestogen in a second stage of the method;

c) after step b), administering a second group of 13 to 17 second stage daily dosage portions each consisting of a second effective amount of said combination of said at least one natural estrogen and said at least one natural or synthetic gestogen in the second stage of the method;

d) after step c), administering from 2 to 4 third stage daily dosage portions each consisting of an effective amount of said at least one natural estrogen in a third stage; and

e) after step d), administering in an additional stage consisting of from 2 to 4 additional stage daily dosage portions each consisting of a pharmaceutically acceptable placebo;

wherein said second effective amount of said combination in said second group of said second stage includes more of said at least one synthetic or natural gestogen than said first effective amount of said combination in said first group;

wherein said effective amount of said at least one natural estrogen is constant in said first stage and also constant in said third stage, but said effective amount of said at least one natural estrogen is smaller in said third stage than in said first stage; and

wherein said at least one natural estrogen is selected from the group consisting of estradiol, conjugated equine estradiol and estradiol valerate and said at least one natural or synthetic gestogen is selected from the group consisting of progesterone, desogestrel, gestoden, levonorgestrel, medroxyprogesterone acetate, chlormadinone acetate and dienogest.