METHODS FOR PREVENTION AND TREATMENT OF CONDITIONS ARISING FROM LOCAL ESTROGEN DEFICIENCY

• US 20070238713A1
• Filed: 04/05/2007
• Published: 10/11/2007
• Est. Priority Date: 04/05/2006
• Status: Abandoned Application

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: Wyeth (Pfizer Inc.)
• Inventors: HELZNER, Eileen, GAST, Michael
• Application Number:
  US11/696,917
• Publication Number:
  US 20070238713A1
• Time in Patent Office: Days
• 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 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• 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 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 5/30 Oestrogens
• CPC Class Codes: A61P 5/34 Gestagens

Abstract

The present invention relates to methods for the prevention and treatment of conditions arising from local estrogen deficiency, such as dyspareunia, vulvar atrophy, vaginal atrophy, vaginal dryness, vulvar itching, vaginal itching, vulvar burning, vaginal burning, vulvar dystrophy, atrophic vaginitis or menopausal sexual dysfunction. In some embodiments, the methods include systemic, for example oral, administration of an estrogen, such as conjugated estrogens, and a progestagen, such as MPA, contemporaneously with local administration of an estrogen, for example conjugated estrogens. In some embodiments, the methods include the oral administration of conjugated estrogens and MPA, and the vulvar, vaginal, or vulvar and vaginal administration of conjugated estrogens, for example in a cream.

Claims

1. A method for preventing or treating a condition arising from local estrogen deficiency comprising administering systemically to a patient in need thereof:

(a) an estrogen; and

(b) a progestagen;

and contemporaneously administering locally to said patient;

(c) an estrogen.

2. The method of claim 1 wherein:

said systemically administered estrogen comprises conjugated estrogens;

said systemically administered progestagen comprises medroxyprogesterone acetate; and

said locally administered estrogen comprises conjugated estrogens.

3. A method of claim 1, wherein said systemically administered estrogen (a), said systemically administered progestagen (b), and said locally administered estrogen (c), are each independently administered in a continuous, intermittent or interrupted dosing regime, wherein:

the daily dose of said systemically administered estrogen is equivalent to a dose of from about 0.15 mg to about 2.5 mg of conjugated estrogens;

the daily dose of said systemically administered progestagen is equivalent to a dose of from about 0.25 mg to about 10 mg of medroxyprogesterone acetate, or from about 5 mg to about 500 mg of progesterone; and

the daily dose of said locally administered estrogen is equivalent to a dose of from about 0.05 mg to about 2.5 mg of conjugated estrogens.

4. A method of claim 3, wherein said estrogen (a), and said progestagen (b), are administered orally.

5. A method of claim 3, wherein said locally administered estrogen is administered in one or more cream, solution, slurry, suppository, pessary, or mechanical carrier.

6. A method of claim 3, wherein said locally administered estrogen is administered in a cream.

7. A method according to claim 3, wherein said locally administered estrogen is applied to the vagina, or to the vulva, or to both the vagina and the vulva.

8. A method of claim 3, wherein said systemically administered estrogen, and said systemically administered progestagen, are administered in a single dosage form.

9. The method of claim 3 wherein:

said systemically administered estrogen comprises conjugated estrogens;

said systemically administered progestagen comprises a progestin; and

said locally administered estrogen comprises conjugated estrogens.

10. A method of claim 3, wherein:

said systemically administered estrogen comprises conjugated estrogens;

said systemically administered progestagen comprises medroxyprogesterone acetate; and

said locally administered estrogen comprises conjugated estrogens.

11. A method of claim 3, wherein condition arising from local estrogen deficiency is selected from dyspareunia, vulvar atrophy, vaginal atrophy, vaginal dryness, vulvar itching, vaginal itching, vulvar burning, vaginal burning, vulvar dystrophy, atrophic vaginitis, menopausal sexual dysfunction, and atrophic changes of the vagina, vulva, bladder, bowel or other pelvic organs.

12. A method for preventing or treating a condition arising from local estrogen deficiency, comprising administering to a patient in need thereof an orally administered component and a locally administered component, wherein:

the orally administered component comprises;

(i) conjugated estrogens; and

(ii) medroxyprogesterone acetate;

and the locally administered component comprises;

(iii) conjugated estrogens;

wherein;

said orally administered component and said locally administered component are each independently administered in a continuous, intermittent or interrupted dosing regime, wherein;

said orally administered conjugated estrogens is administered in a dose of from about 0.15 mg to about 2.5 mg;

said orally administered medroxyprogesterone acetate is administered in a dose of from about 0.25 mg to about 10 mg; and

said locally administered conjugated estrogens is administered in a dose of from about 0.05 mg to about 2.5 mg of conjugated estrogens.

13. A method of claim 12, wherein:

said orally administered conjugated estrogens is administered in a dose of about 0.45 mg; and

said orally administered medroxyprogesterone acetate is administered in a dose of about 1.5 mg.

14. A method of claim 13, wherein said locally administered conjugated estrogens is administered in a dose of about 0.3 mg.

15. A method of claim 14, wherein said locally administered conjugated estrogens is administered in a dose of about 0.45 mg.

16. A method of claim 12, wherein said locally administered conjugated estrogens is administered in a dose of about 0.3 mg.

17. A method of claim 12, wherein said locally administered conjugated estrogens is administered in a dose of about 0.45 mg.

18. A method of claim 12, wherein:

said orally administered conjugated estrogens is administered in a dose of about 0.625 mg; and

said orally administered medroxyprogesterone acetate is administered in a dose of about 2.5 mg.

19. A method of claim 18, wherein said locally administered conjugated estrogens is administered in a dose of about 0.3 mg.

20. A method of claim 18, wherein said locally administered conjugated estrogens is administered in a dose of about 0.45 mg.

21. A method of claim 12, wherein condition arising from local estrogen deficiency is selected from dyspareunia, vulvar atrophy, vaginal atrophy, vaginal dryness, vulvar itching, vaginal itching, vulvar burning, vaginal burning, vulvar dystrophy, atrophic vaginitis, menopausal sexual dysfunction, and atrophic changes of the vagina, vulva, bladder, bowel or other pelvic organs.

22. A method according to claim 12, wherein said locally administered component is applied to the vagina, or to the vulva, or to both the vagina and the vulva.

23. A method of claim 12, wherein said locally administered component is administered in a cream, in a solution, in a slurry, in a suppository, by pessary, via intrauterine device, or in a mechanical carrier.

24. A method of claim 12, wherein said locally administered component is administered in a cream.

25. A method of claim 12, wherein said orally administered conjugated estrogens and said orally administered medroxyprogesterone acetate are administered in a single dosage form.

26. A method according to claim 12, wherein said orally administered component, and said locally administered component, are each administered in a daily dosing regime.

27. A method according to claim 12, wherein said orally administered component is administered in a daily dosing regime, and said locally administered component is administered in an intermittent or interrupted dosing regime.

28. A method of claim 27, wherein said intermittent dosing regime comprises alternate days, every third day, every fourth day, every fifth day, every sixth day or weekly.

29. A method according to claim 12, wherein said orally administered component is administered in an interrupted or intermittent dosing regime, and said locally administered component is administered in a daily dosing regime.

30. A method of claim 29, wherein said intermittent dosing regime comprises alternate days, every third day, every fourth day, every fifth day, every sixth day or weekly.

31. A method according to claim 12, wherein said orally administered component, and said locally administered component, are each administered in an intermittent or interrupted dosing regime.

32. A method of claim 31, wherein each of said intermittent dosing regimes independently comprise alternate days, every third day, every fourth day, every fifth day, every sixth day or weekly.

33. A method according to claim 12, wherein:

said locally administered conjugated estrogens is administered in a cream that is applied to the vagina, or to the vulva, or to both the vagina and the vulva; and

said orally administered conjugated estrogens, and said orally administered medroxyprogesterone acetate, are administered in a single dosage form.

34. A method according to claim 33, wherein said orally administered component, and said locally administered component, are each administered in a daily dosing regime.

35. A method according to claim 33, wherein said orally administered component is administered in a daily dosing regime, and said locally administered component is administered in an intermittent or interrupted dosing regime.

36. A method of claim 35, wherein said intermittent dosing regime comprises alternate days, every third day, every fourth day, every fifth day, every sixth day or weekly.

37. A method according to claim 33, wherein said orally administered component is administered in an interrupted or intermittent dosing regime, and said locally administered component is administered in a daily dosing regime.

38. A method of claim 37, wherein said intermittent dosing regime comprises alternate days, every third day, every fourth day, every fifth day, every sixth day or weekly.

39. A method according to claim 33, wherein said orally administered component, and said locally administered component, are each administered in an intermittent or interrupted dosing regime.

40. A method of claim 39, wherein each of said intermittent dosing regimes independently comprise alternate days, every third day, every fourth day, every fifth day, every sixth day or weekly.