Progesterone replacement therapy

• US 5,633,011 A
• Filed: 08/04/1994
• Issued: 05/27/1997
• Est. Priority Date: 08/04/1994
• Status: Expired due to Term

• Current Assignee: Encinal Pharmaceutical Investments, LLC
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Wong, Patrick S.-L., Espinal, Steven, Dong, Liang C.
• Primary Examiner(s): JORDAN, KIMBERLY R
• Application Number:
  US08/286,125
• Time in Patent Office: 1,027 Days
• Field of Search: 514/177, 424/480, 424/451
• US Class Current: 424/451
• 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 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/2004 Excipients; Inactive ingredients
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084

Abstract

A hormone replacement composition, a hormone replacement dosage form, and a method of hormone replacement are disclosed and indicated for the management of hormone replacement therapy.

Claims

1. An article of manufacture for hormone replacement comprising a drug layer comprising 10 ng to 1200 mg of a progestin, 1 mg to 30 mg of a surfactant, 5 mg to 225 mg of an alkali carboxymethylcellulose possessing a 75,000 to 350,000 molecular weight, 0.05 mg to 20 mg of a disintegrant and 0.5 mg to 75 mg of an osmagent;

a displayment layer comprising 50 mg to 200 mg of an alkali carboxymethylcellulose of 500,000 to 1,000,000 molecular weight, 1 mg to 20 mg of a hydroxypropylmethylcellulose of 9,000 to 150,000 molecular weight, and 0.5 mg to 100 mg of an osmagent; and

wherein the drug layer and the displacement layer are encased by hydroxypropylcellulose.

2. An article of manufacture for hormone replacement therapy comprising a drug layer comprising 10 ng to 1200 mg of a progestin, 1 mg to 30 mg of a surfactant, 5 mg to 225 mg of a poly(alkylene) oxide possessing a 75,000 to 350,000 molecular weight, 0.05 mg to 20 mg of a disintegrant, and 0.5 mg to 75 mg of an osmagent;

a displacement layer comprising 50 mg to 200 mg of an alkali carboxymethylcellulose of 500,000 to 1,000,000 molecular weight, 1 mg to 20 mg of a hydroxypropylmethylcellulose of 9,000 to 150,000 molecular weight, and 0.5 mg to 100 mg of an osmagent; and

wherein the drug layer and the displacement layer are surrounded by hydroxypropylcellulose.

3. An article of manufacture for hormone replacement therapy comprising a drug layer comprising 10 ng to 1200 mg of a progestin, 1 mg to 30 mg of a surfactant, 5 mg to 225 mg of an alkali carboxymethylcellulose possessing a 75,000 to 350,000 molecular weight, 0.05 mg to 20 mg of a disintegrant and 0.5 to 25 mg of an osmagent;

a displacement layer comprising 50 mg to 200 mg of an alkali carboxymethylcellulose of 500,000 to 1,000,000 molecular weight, 1 mg to 20 mg of a hydroxypropylmethylcellulose of 9,000 to 150,000 molecular weight, and 0.5 mg to 100 mg of an osmagent; and

wherein the drug layer and the displacement layer are in a capsule in layered arrangement.

4. A method of progestin hormone replacement therapy in a patient in need of progestin hormone replacement therapy, the method comprising admitting orally into the patient a dosage form comprising 10 ng to 1200 mg of a progestin, 5 mg to 225 mg of an alkali carboxymethylcellulose possessing a 75,000 to 350,000 molecular weight, 0.05 mg to 20 mg of a disintegrant, and 1 mg to 30 mg of a surfactant, and wherein the dosage form through the cooperation of the disintegrant and the surfactant provides dissolution and availability of progestin from the dosage form for progestin hormone replacement therapy.

5. The method of progestin hormone replacement therapy in a patient according to claim 4, wherein a poly(alkylene oxide) of 75,000 to 350,000 molecular weight replaces the alkali carboxymethylcellulose.

6. The method of progestin hormone replacement therapy according to claim 4, wherein the progestin is selected from the group consisting progesterone, progestogen, medroxyprogesterone, medroxyprogesterone acetate, megestrol acetate, norethindrone, norethindrone acetate, norgestrel, hydroxyprogesterone caproate, norethisterone, norethisterone acetate, levonorgestrel, norgestimate, norethynodrel, 17-hydroxyprotesterone, 17-hydroxyprogesterone esters, 17α

-ethinyl testosterone, 17α

-ethinyl-19-nortestosterone, d-17β

-acetoxy-13β

-ethyl-17α

-ethinyl-gon-4-en-3-one oxime, d-13β

-ethyl-17α

-ethinyl-17β

-hydroxygon-4-en-3-one, 13β

, 17α

-diethyl-17β

-hydroxygon-4-en-3-one, chlormadrone acetate, dimethistrone, 17α

-ethinyl-17β

-acetoxy-19-norandrost-4-en-3-one oxime, 3-kelodesogestrel, desogestrel, gestodene, and gestodene acetate.

7. A therapeutic composition for orally administering progestin for providing a normal progestin pattern in a human, wherein the therapeutic composition is characterized by 10 ng to 1200 mg of progestin and means for administering the progestin from the therapeutic composition to the human to provide a normal progestin pattern.

8. The therapeutic composition according to claim 7, wherein the therapeutic composition orally administers progestin to replace and supplement progestin in the human.

9. The therapeutic composition according to claim 7, wherein the therapeutic composition provides a progestin pattern of 2 ng/ml to 20 ng/ml in the blood of the human.