Method Of Treating Atrophic Vaginitis

• US 20070264309A1
• Filed: 01/22/2007
• Published: 11/15/2007
• Est. Priority Date: 01/20/2006
• Status: Abandoned Application

• Current Assignee: Pear Tree Pharmaceuticals, Inc. (Daré Bioscience, Inc.)
• Original Assignee: Pear Tree Pharmaceuticals, Inc. (Daré Bioscience, Inc.)
• Inventors: Chollet, Janet, Mermelstein, Fred
• Application Number:
  US11/625,675
• Publication Number:
  US 20070264309A1
• Time in Patent Office: Days
• US Class Current: 424/433
• 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 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/02 Suppositories; Bougies; Bases therefor; Ovulesapparatus for making A61J3/08; devices for introducing into the body A61M31/00
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 15/02 for disorders of the vagina

Abstract

This invention relates to a method and pharmaceutical composition useful in treating a condition responsive to hormone replacement therapy. Specifically, the invention is related to the long term treatment of symptoms associated with atrophic vaginitis. The composition contains effective amounts of an estrogen, a progesterone compound and a pharmaceutically accepted vehicle, carrier and/or diluent.

Claims

1. A pharmaceutical composition for vaginal administration to a subject in need thereof comprising a therapeutically effective amount of an estrogen compound, a therapeutically effective amount of a progesterone compound, and a therapeutically effective amount of a pharmaceutically acceptable carrier for vaginal administration, wherein the composition is useful in treatment of urogenital symptoms associated with atrophic vaginitis.

2. The pharmaceutical composition according to claim 1, wherein the composition is prepared as a vaginal suppository.

3. The pharmaceutical composition according to claim 1, wherein the estrogen compound is micronized estriol.

4. The pharmaceutical composition according to claim 1, wherein the progesterone compound is micronized progesterone.

5. The pharmaceutical composition according to claim 1, wherein the estrogen compound is micronized estriol and wherein the progesterone compound is micronized progesterone.

6. The pharmaceutical composition according to claim 3, wherein the micronized estriol is present in an amount of about 1 mg per dose.

7. The pharmaceutical composition according to claim 3, wherein the micronized estriol is present in amounts from about 0.01 mg to about 10 mg, per dose.

8. The pharmaceutical composition according to claim 7, wherein the micronized estriol is present in amounts from about 0.25 mg to about 1.0 mg, per dose.

9. The pharmaceutical composition according to claim 4, wherein the micronized progesterone is present in amounts from about 5 mg to 500 mg per dose.

10. The pharmaceutical composition according to claim 9, wherein the micronized progesterone is present in amounts from about 25 mg to 50 mg per dose.

11. The pharmaceutical composition according to claim 5, wherein the micronized estriol and micronized progesterone are present in amounts of about 1 mg:

25 mg respectively per dose.

12. The pharmaceutical composition according to claim 5, wherein the micronized estriol and micronized progesterone are present in amounts of about 1 mg:

30 mg respectively per dose.

13. The pharmaceutical composition according to claim 5, wherein the micronized estriol and micronized progesterone are present in amounts of about 1 mg:

50 mg respectively per dose.

14. The pharmaceutical composition according to claim 1 further comprising at least one constituent selected from the group consisting of additives, pharmaceutically acceptable carriers, fatty acid base, a preservative, a dye, a binder, a suspending agent, a dispersing agent, a colorant, a disintegrant, an excipient, a diluent, a lubricant, a plasticizer, oils, and mixtures thereof.

15. The pharmaceutical composition according to claim 4, wherein the micronized progesterone is given in a therapeutically effective dose to reduce concomitant liability of adverse uterine effects associated with long-term unopposed estrogen administration during menopause.

16. The pharmaceutical composition according to claim 1, wherein the composition further comprises a suspending agent.

17. The pharmaceutical composition according to claim 16, wherein the suspending agent is micronized silica gel.

18. The pharmaceutical composition according to claim 17, wherein the amount of micronized silica gel is 0.020 gm per unit dose.

19. The pharmaceutical composition of claim 1, wherein the composition further comprises a fatty acid base.

20. The pharmaceutical composition of claim 19, wherein the fatty acid base is composed of JAB base per suppository.

43. The pharmaceutical composition of claim 1 further comprising an anticholinergic agent.

21. A method of treating urogenital symptoms of atrophic vaginitis, which comprises vaginally administering a pharmaceutical composition comprising therapeutically effective amounts of an estrogen compound and a progesterone compound.

22. The method according to claim 21, wherein the estrogen is a micronized estriol.

23. The method according to claim 21, wherein the progesterone is micronized progesterone.

24. The method according to claim 21, wherein the estrogen is a micronized estriol and wherein the progesterone is micronized progesterone.

25. The method according to claim 23, wherein the therapeutically effective amount of the progesterone is effective to reduce concomitant liability of adverse uterine effects associated with long-term unopposed estrogen administration during menopause.

26. The method according to claim 21, wherein the incidence of side effects associated with antimuscarinic treatment is reduced.

27. The method according to claim 24, wherein the amount of 0.5 mg micronized estriol combined with 25 mg micronized progesterone given vaginally causes an antiproliferative effect on an endometrium

28. The method according to claim 24, wherein the estrogen and progesterone are present in a dose amounts of 1 mg micronized estriol:

50 mg micronized progesterone, wherein vaginal administration causes an antiproliferative effect on an endometrium.

29. The method according to claim 24, wherein the amount of 1 mg micronized estriol combined with 25 mg micronized progesterone given vaginally causes an antiproliferative effect on an endometrium.

30. The method according to claim 24, wherein the estrogen and progesterone are present in a dose amounts of 1 mg micronized estriol:

30 mg micronized progesterone, wherein vaginal administration causes an antiproliferative effect on an endometrium.

31. The method according to claim 21 wherein administration is continued for at least 3 months.

32. The method according to claim 31, wherein administration is continued for at least 6 months.

33. The method according to claim 32, wherein administration is continued for at least 12 months.

34. The method according to claim 33, wherein administration is continued for at least 18 months.

35. The method according to claim 34, wherein administration is continued for at least 24 months.

36. The method according to claim 24, wherein the estrogen and progesterone are present in dose amounts of 1.0 mg micronized estriol:

100 mg micronized progesterone wherein vaginal administration induces a full secretory endometrium resulting in withdrawal bleeding.

37. The method according to claim 24, wherein the estrogen and progesterone are present in dose amounts of 1 mg micronized estriol:

50 mg micronized progesterone wherein vaginal administration leaves the endometrium partially secretory resulting in very light irregular bleeding and no withdrawal bleeding.

38. The method according to claim 24, wherein the estrogen and progesterone are present in dose amounts of 1 mg micronized estriol:

30 mg micronized progesterone wherein vaginal administration leaves the endometrium partially secretory resulting in very light irregular bleeding and no withdrawal bleeding.

39. The method according to claim 24, wherein the estrogen and progesterone are present in dose amounts of 1 mg micronized estriol:

25 mg micronized progesterone wherein vaginal administration leaves the endometrium partially secretory resulting in no irregular bleeding and no withdrawal bleeding.

40. The method of claim 21, wherein the estrogen compound and progesterone compound are administered as a vaginal suppository or vaginal cream.

41. The method according to claim 21, wherein the pharmaceutical compositions in administered in therapeutically effective amounts to reduce symptoms of overactive bladder.

42. The method of claim 41, wherein the symptoms of overactive bladder include frequency, urgency, nocturia, and urge incontinence.

44. The method of claim 21, wherein the pharmaceutical composition further comprises an anticholinergic agent.