PROGESTERONE FOR THE TREATMENT OR PREVENTION OF SPONTANEOUS PRETERM BIRTH

• US 20080188829A1
• Filed: 02/01/2008
• Published: 08/07/2008
• Est. Priority Date: 02/06/2007
• Status: Active Grant

• Current Assignee: Allergan Sales LLC (Abbvie Incorporated), Columbia Laboratories, Inc. (Catalent, Inc.)
• Original Assignee: Columbia Laboratories, Inc. (Catalent, Inc.)
• Inventors: Creasy, George
• Granted Patent: US 8,828,981 B2
• Time in Patent Office: Days
• US Class Current: 604/522
• 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 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/06 Antiabortive agents; Labour repressants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system

Abstract

A method for treating or preventing spontaneous preterm birth in pregnant women and improving neonatal morbidity and mortality. The method includes administering to a pregnant woman in need thereof an effective amount of progesterone sufficient to prolong gestation by minimizing the shortening or effacing of her cervix. Treatment and prophylaxis with progesterone in pregnant women having symptoms of short cervix has been clinically shown to increase neonatal health.

Claims

1. A method for treating or preventing the onset of preterm labor and subsequent preterm birth in a pregnant woman with a short cervix comprising administering an effective amount of progesterone sufficient to prolong gestation by minimizing the shortening or effacing of the cervix.

2. The method of claim 1, wherein the progesterone is administered as a vaginal gel.

3. The method of claim 1, wherein the progesterone is administered as a vaginal suppository.

4. The method of claim 1, wherein the progesterone is administered by intramuscular injection.

5. The method of claim 1, wherein the progesterone is administered orally.

6. The method of claim 1, wherein the progesterone is administered by rectal administration.

7. The method of claim 1, wherein the progesterone comprises natural progesterone or a metabolite of progesterone.

8. The method of claim 1, wherein the progesterone comprises a synthetic progesterone selected from a group consisting of 17-alpha-hydroxyprogesterone caproate, medroxyprogesterone acetate, norethindrone, norethindrone acetate, norethindrone enanthate, desogestrel, levonorgestrel, lynestrenol, ethynodiol diacetate, norgestrel, norgestimate, norethynodrel, gestodene, drospirenone, trimegestone, levodesogestrel, gestodyne, nesterone, etonogestrel, and derivatives from 19-nor-testosterone.

9. The method of claim 1, wherein the progesterone is administered daily.

10. The method of claim 9, wherein the progesterone is administered beginning about the 18^th to 22^nd week of gestation until about the 37^th week of gestation.

11. The method of claim 9, wherein the progesterone is administered for about 14 to 19 weeks.

12. The method of claim 1, wherein the amount of progesterone that is administered is between about 45 mg and 800 mg.

13. The method of claim 1, wherein the progesterone is administered via a drug delivery system that comprises progesterone, a water-soluble, water-swellable cross-linked polycarboxylic acid polymer, and at least one adjuvant.

14. The method of claim 1, wherein the progesterone is administered to a pregnant woman whose cervix has a length greater than about 1.0 cm.

15. The method of claim 14, wherein the progesterone is administered to a pregnant woman whose cervix has a length between about 1.0 cm and 8.0 cm.

16. The method of claim 14, wherein the progesterone is administered to a pregnant woman whose cervix has a length less than or equal to about 3.0 cm.

17. The method of claim 1, wherein the progesterone comprises both natural progesterone and 17-alpha-hydroxyprogesterone.

18. The method of claim 1, wherein the progesterone is administered by a delivery device configured for insertion into the vagina.

19. The method of claim 18, wherein the delivery device comprises a cervical ring.

20. The method of claim 9, wherein the progesterone is administered beginning about the 16^th week of gestation until about the 37^th week of gestation.

21. The method of claim 9, wherein the progesterone is administered for about 21 weeks.

22. The method of claim 9, wherein the progesterone is administered beginning about the time of a positive pregnancy test until about the 37^th week of gestation.

23. The method of claim 9, wherein the progesterone is administered beginning about the 2^nd to 4^th week of gestation.

24. The method of claim 9, wherein the progesterone is administered for about 33 to 35 weeks.

25. The method of claim 9, wherein the progesterone is administered depending on the gestational age at the beginning of treatment and the date of delivery.

26. The method of claim 12, wherein the amount of progesterone that is administered is about 90 mg and the progesterone is natural progesterone administered vaginally.

27. The method of claim 1, wherein the progesterone is administered as a vaginal cream.

28. The method of claim 1, wherein the progesterone is administered as a vaginal solid dosage form.

29. A method of improving neonatal morbidity and mortality in a preterm neonate comprising:

administering to a pregnant woman symptomatic of a shortened or an effaced cervix in need thereof an effective amount of progesterone sufficient to maintain and/or delay a further shortening of cervical length or sufficient to prolong gestation.

30. The method of claim 29, wherein the progesterone is administered using one or more forms selected from the following group:

a vaginal gel, a vaginal suppository, vaginal drug delivery device, vaginal cream, and other vaginal pharmaceutical application.

31. The method of claim 29, wherein the progesterone is adapted for oral, subcutaneous, rectal, vaginal, intradermal, topical, intranasal, intramuscular, intraperitoneal, intraarticular, intraventricular, intrathecal, intravaginal, or intravenous administration.

32. The method of claim 29, wherein the progesterone comprises natural progesterone or a metabolite of progesterone.

33. The method of claim 29, wherein the progesterone comprises a synthetic progesterone selected from a group consisting of 17-alpha-hydroxyprogesterone caproate, medroxyprogesterone acetate, norethindrone, norethindrone acetate, norethindrone enanthate, desogestrel, levonorgestrel, lynestrenol, ethynodiol diacetate, norgestrel, norgestimate, norethynodrel, gestodene, drospirenone, trimegestone, levodesogestrel, gestodyne, nesterone, etonogestrel, and derivatives from 19-nor-testosterone.

34. The method of claim 29, wherein the progesterone is administered daily.

35. The method of claim 34, wherein the progesterone is administered beginning about the 18^th to 22^nd week of gestation until about the 37^th week of gestation.

36. The method of claim 34, wherein the progesterone is administered for about 14 to 19 weeks.

37. The method of claim 29, wherein the amount of progesterone that is administered is between about 45 mg and 800 mg.

38. The method of claim 29, wherein the progesterone is administered via a drug delivery system that comprises progesterone, a water-soluble, water-swellable cross-linked polycarboxylic acid polymer, and at least one adjuvant.

39. The method of claim 29, wherein the progesterone is administered to a pregnant woman whose cervix has a length greater than about 1.0 cm.

40. The method of claim 39, wherein the progesterone is administered to a pregnant woman whose cervix has a length between about 1.0 cm and 8.0 cm.

41. The method of claim 39, wherein the progesterone is administered to a pregnant woman whose cervix has a length less than or equal to about 3.0 cm.

42. The method of claim 29, wherein the progesterone comprises both natural progesterone and 17-alpha-hydroxyprogesterone.

43. The method of claim 29, wherein the progesterone is administered by a delivery device configured for insertion into the vagina.

44. The method of claim 29, wherein the progesterone is administered in combination with one or more compounds for the treatment or prophylaxis of preterm birth.

45. The method of claim 29, wherein the progesterone is administered in combination with a clinical procedure for the treatment or prophylaxis of preterm birth.