Pharmaceutical composition for use in hormone replacement therapy

• US 8,048,869 B2
• Filed: 05/17/2002
• Issued: 11/01/2011
• Est. Priority Date: 05/18/2001
• Status: Active Grant

• Current Assignee: Estetra SPRL
• Original Assignee: Pantarhei Bioscience B.V.
• Inventors: Bunschoten, Evert Johannes, Holinka, Christian Franz, Coelingh Bennink, Herman Jan Tijmen
• Primary Examiner(s): HUI, SAN MING R
• Application Number:
  US10/478,262
• Publication Number:
  US 20040198671A1
• Time in Patent Office: 3,455 Days
• Field of Search: 514/182, 514/171
• US Class Current: 514/171
• 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 31/00 Medicinal preparations containing organic active ingredients
• 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 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61P 5/30 Oestrogens

Abstract

One aspect of the invention is concerned with a method of hormone replacement therapy, which method comprises administering to a person in need of such a therapy an effective amount of an estrogenic component selected from the group consisting of: substances represented by the formula

in which formula R₁, R₂, R₃, R₄ independently are a hydrogen atom, a hydroxyl group or an alokxy group with 1-5 carbon atoms; each of R₅, R₆, R₇ is a hydroxyl group; and no more than 3 of R₁, R₂, R₃, R₄ are hydrogen atoms; precursors capable of liberating a substance according to the aforementioned formula when used in the present method, and mixtures thereof; said composition containing virtually no progestogen or anti-progestin.

Another aspect of the invention relates to a drug delivery system for enteral or parenteral administration that contains at least 1 μg of the aforementioned estrogenic component and virtually no progestogen or anti-progestin.

Claims

1. A method of hormone replacement therapy, comprising administering to a person in need of such a therapy an effective amount of an estrogenic component selected from the group consisting of:

substances represented by the following formula

2. The method according to claim 1, wherein the method comprises administering the estrogenic component in an effective amount to treat symptoms of or reduce the risk of developing hypoestrogenism that are selected from the group consisting of osteoporosis, arteriosclerosis, climacteric symptoms.

3. The method according to claim 2, wherein at least 2 of the groups R₁, R₂, R₃ and R₄ represent a hydrogen atom.

4. The method according to claim 2, wherein 3 of the groups R₁, R₂, R₃ and R₄ represent a hydrogen atom.

5. The method according to claim 2, wherein groups R₁, R₂ and R₄ represent hydrogen atoms.

6. The method according to claim 1, wherein the hormone replacement therapy is administered to treat (peri-)menopausal disorders, post-menopausal disorders, and/or hypoestrogenism resulting from hypogonadism, castration, primary ovarian failure, gonadotropin-releasing hormone analogue treatment or cancer treatment.

7. The method according to claim 1, wherein the method comprises daily administration of at least 0.001 mg of the estrogenic component.

8. The method according to claim 1, wherein the method comprises oral, transdermal, intranasal, intravaginal, rectal, pulmonary, buccal, subcutaneous or intra-uterine administration of the estrogenic component.

9. The method according to claim 8, wherein the method comprises oral or transdermal administration of the estrogenic component.

10. The method according to claim 9, wherein the method comprises oral administration of the estrogenic component.

11. The method according to claim 1, wherein the composition contains virtually no an antisense oligonucleotide that is complementary to a nucleotide sequence for follicle stimulating hormone receptor.

12. The method according to claim 1, wherein the estrogenic component is administered in an amount effective to achieve a blood serum concentration of at least 1 nanogram per liter.

13. The method according to claim 1, wherein the estrogenic component is administered in an amount effective to achieve a blood serum concentration of at least 10 nanograms per liter.

14. The method according to claim 1, wherein the estrogenic component is administered in an amount of at least 1 μ

g per kg of bodyweight per day.

15. The method according to claim 1, wherein the estrogenic component is administered in an amount of at least 5 μ

g per kg of bodyweight per day.

16. The method according to claim 1, wherein the method comprises administering the estrogenic component for a period of at least 1 month.

17. The method according to claim 1, wherein the method comprises administering the estrogenic compound for a period of at least 3 months.

18. The method according to claim 1, wherein the composition contains no progestogen or anti-progestogen.

19. The method according to claim 1, wherein the method is administered to individuals who have not been oophorectomized, or in whom the risk of endometrial stimulation by estrogenic compositions is not minimized or absent.

20. The method according to claim 1, wherein the method does not employ a slow release formulation.

21. A drug delivery system for enteral or parenteral administration containing the estrogenic component as defined in claim 1, said drug delivery system being selected from the group consisting of solid oral dosage units, semi-solid oral dosage units, patches, gels, tapes, creams, tablets, suppoitories and pessaries, wherein the system contains at least 1 μ

g of the estrogenic component and virtually no progestogen, anti-progestogen or gonadotropin releaing hormone.

22. The drug delivery system according to claim 21, wherein the drug delivery system is a solid or semi-solid oral dosage unit.

23. The method according to claim 2, wherein the effective amount is to treat symptoms of hypoestrogenism.

24. A method of hormone replacement therapy, comprising orally administering to a person in need of such a therapy an effective amount of an estrogenic component selected from the group consisting of:

substances represented by the following formula

25. The method according to claim 24, wherein the method comprises administering the estrogenic component in an effective amount to treat symptoms of or reduce the risk of developing hypoestrogenism that are selected from the group consisting of osteoporosis, arteriosclerosis and climacteric symptoms.

26. The method according to claim 25, wherein at least 2 of the groups R₁, R₂, R₃ and R₄ represent a hydrogen atom.

27. The method according to claim 25, wherein 3 of the groups R₁, R₂, R₃ and R₄ represent a hydrogen atom.

28. The method according to claim 25, wherein groups R₁, R₂ and R₄ represent hydrogen atoms.

29. The method according to claim 24, wherein the hormone replacement therapy is administered to treat (peri-)menopausal disorders, post-menopausal disorders, and/or hypoestrogenism resulting from hypogonadism, castration, primary ovarian failure, gonadotropin-releasing hormone analogue treatment or cancer treatment.

30. The method according to claim 24, wherein the method comprises daily administration of at least 0.001 mg of the estrogenic component.

31. The method according to claim 24, wherein the composition contains virtually no gonadotropin hormone releasing hormone analogue or luteinizing hormone releasing hormone or an antisense oligonucleotide that is complementary to the nucleotide sequence of the follicle stimulating hormone receptor.

32. The method according to claim 24, wherein the estrogenic component is administered in an amount effective to achieve a blood serum concentration of at least 1 nanogram per liter.

33. The method according to claim 24, wherein the estrogenic component is administered in an amount effective to achieve a blood serum concentration of at least 10 nanograms per liter.

34. The method according to claim 24, wherein the estrogenic component is administered in an amount of at least 1 μ

g per kg of bodyweight per day.

35. The method according to claim 24, wherein the estrogenic component is administered in an amount of at least 5 μ

g per kg of bodyweight per day.

36. The method according to claim 24, wherein the method comprises administering the estrogenic component for a period of at least 1 month.

37. The method according to claim 24, wherein the method comprises administering the estrogenic compound for a period of at least 3 months.

38. The method according to claim 24, wherein the composition contains no progestogen or anti-progestogen.

39. The method according to claim 24, wherein the method is administered to individuals who have not been oophorectomized, or in whom the risk of endometrial stimulation by estrogenic compositions is not minimized or absent.

40. The method according to claim 24, wherein the method does not employ a slow release formulation.