Progesterone Antagonist and Selective Progesterone Modulator in the Treatment of Excessive Uterine Bleeding

• US 20100190758A1
• Filed: 04/18/2008
• Published: 07/29/2010
• Est. Priority Date: 04/20/2007
• Status: Active Grant

• Current Assignee: PregLem SA (Chemical Works of Gedeon Richter Plc)
• Original Assignee: PregLem SA (Chemical Works of Gedeon Richter Plc)
• Inventors: Loumaye, Ernest, Fauser, Bartholomeus C.J.M.
• Granted Patent: US 8,569,274 B2
• Time in Patent Office: Days
• US Class Current: 514/171
• CPC Class Codes: A61K 31/567 substituted in position 17 alpha, e.g. mestranol, norethandrolone
• 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 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/36 Antigestagens
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents

Abstract

Progesterone antagonists and SPRM are useful to prepare a medication for the treatment or the prophylaxis of excessive uterine bleeding in women with spontaneous or iatrogenic coagulation disorders such as thrombopenia, coagulation factor deficiency or anti-coagulant therapy. Treatment will last from 1 day to 180 days.

Claims

1. A method of treating and/or preventing excessive uterine bleeding resulting from a coagulation disorder comprising administering a therapeutically effective amount of a progesterone antagonist, a selective progesterone receptor modulator (SPRM), or an active metabolite thereof, or a combination of two or more of said progesterone antagonists, SPRMs, or active metabolites, to a woman in need thereof.

2. The method of claim 1, wherein the coagulation disorder is selected from the group consisting of hemophilia, von Willebrand'"'"'s disease, hepatic function impairment, thrombocytopenia, leukemia, disseminated intravascular coagulation, bone marrow aplasia or inadequate anticoagulation treatment.

3. The method of claim 1, wherein the progesterone antagonist or SPRM is selected from the group consisting of CDB-2914, mifepristone, asoprisnil, CDB-4124, onapristone, org33628, tanaproget, tanaproget-combo, WAY 166989, NSP 989, NSP-combo, 11 beta-((4-N,N-Dimethylamino)-phenyl-17 beta-hydroxy-17 alpha-propinyl-4,9(10)-estradien-3-one-(RU-38486), 11 beta-((4-N,N-dimethylamino)-phenyl)-17 beta-hydroxy-18-methyl-17 alpha-propinyl-4,9(10)-estradien-3-one, 11 beta-((4-N,N-dimethylamino)-phenyl)-17 alpha beta-hydroxy-17a alpha-propinyl-D-homo-4,9(10),16-estratien-3-one, 11 beta-p-methoxyphenyl-17 beta-hydroxy-17 alpha-ethinyl-4,9(10)-estradien-3-one, 11 beta-(4-acetylphenyl)-17 beta-hydroxy-17 alpha-(prop-1-inyl)-4,9(10)estradien-3-one, 11 beta-(4-dimethylaminophenyl)-17 alpha-hydroxy-17 beta-(3-hydroxy-propyl)-13 alpha-methyl-4,9-gonadien-3-one, (Z)-11 beta[4-(dimethylamino)phenyl]-17beta-hydroxy-17alpha-(3-hydroxy-1-propenyl)-estr-4-en-3-one-5, 11 beta,19-(4-acetylphenyl)-17 beta-hydroxy-17 alpha-(3-hydroxyprop-1-(Z)-enyl)-4,9(10)-estradien-3-one, 11 beta, 19-(4-cyanophenyl)-17 beta-hydroxy-17 alpha-(3-hydroxyprop-1-(Z)-enyl)-4-androsten-3-one, 11 beta, 19-(4-(3-pyridinyl)-o-phenylene)-17 beta-hydroxy-17 alpha-(3-hydroxyprop-1-(Z)-enyl)-4-androsten-3-one, 17alpha-acetoxy-21-methoxy-11beta-[4-N,N-dimethylaminophenyl]-19-norpregna-4,9-diene-3,20-dione (CDB 4124), an active metabolite of any of said progesterone antagonists or SPRMs, and a combination of two or more of said progesterone antagonists, SPRMs, or active metabolites.

4. The method of claim 3, wherein said active metabolite of asoprisnil is selected from the group consisting of J912, and J956 and a combination thereof.

5. The method of claim 3, wherein said active metabolite of CDB-4124 is CDB-4453.

6. The method of claim 3, wherein said active metabolite of CDB-2914 is selected from the group consisting of CBD-3877, CDB-3963, CDB-3236, CDB-4183, and a combination of two or more of said metabolites.

7. The method of claim 1, wherein said administration is over a period of 1 to 180 days.

8. The method of claim 1, wherein said administration is during bleeding peaks or during menstruation.

9. The method of claim 1, wherein said administration is daily, every other day, once a week or once every month.

10. The method of claim 1, wherein said administration is a one-time administration.

11. The method of claim 1, wherein said progesterone antagonist, a SPRM, or an active metabolite thereof is administered at a daily dose between 0.1 to 1000 mg.

12. The method of claim 11, wherein the SPRM is CDB-2914, or an active metabolite thereof, and is administered at a daily dose between 5 to 15 mg.

13. The method of claim 1, wherein said progesterone antagonist, a SPRM or active metabolite thereof is administered with an oestrogen, either simultaneously or sequentially.

27. The method of claim 1, wherein said progesterone antagonist, SPRM, or active metabolite thereof is administered by vaginal, rectal, subcutaneous, intravenous, intradermal, intramuscular, intraperitoneal, intra-uterine, intranasal, transdermal, or buccal routes or via an implanted device.

14-26. -26. (canceled)

28. A kit for treating and/or preventing excessive uterine bleeding resulting from a coagulation disorder comprising a therapeutically effective amount of a progesterone antagonist, a SPRM, Of an active metabolite thereof, or a combination of two or more progesterone antagonists, SPRMs, or of said active metabolites, optionally with reagents and/or instructions for use.