1 α-hydroxy-2-methylene-19-nor-pregnacalciferol and its uses

• US 6,566,352 B1
• Filed: 02/18/2002
• Issued: 05/20/2003
• Est. Priority Date: 02/18/2002
• Status: Expired due to Term

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: Plum, Lori A., Clagett-Dame, Margaret, DeLuca, Hector F.
• Primary Examiner(s): QAZI, SABIHA NAIM
• Application Number:
  US10/077,916
• Time in Patent Office: 456 Days
• Field of Search: 514/167, 552/653
• US Class Current: 514/167
• CPC Class Codes: A61K 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 17/16 Emollients or protectives, e.g. against radiation
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 5/18 : of the parathyroid hormones
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07C 2601/14 : The ring being saturated
• CPC Class Codes: C07C 2602/24 : the ring system containing nine carbon atoms, e.g. perhydroindane
• CPC Class Codes: C07C 401/00 : Irradiation products of cholesterol or its derivatives; Vitamin D derivatives, 9,10-seco cyclopenta[a]phenanthrene or analogues obtained by chemical preparation without irradiation

Abstract

This invention discloses 1α-hydroxy-2-methylene-19-nor-pregnacalciferol and pharmaceutical uses therefor. This compound exhibits pronounced activity in arresting the proliferation of undifferentiated cells and inducing their differentiation to the monocyte thus evidencing use as an anti-cancer agent and for the treatment of skin diseases such as psoriasis as well as skin conditions such as wrinkles, slack skin, dry skin and insufficient sebum secretion. This compound also has little, if any, calcemic activity and therefore may be used to treat immune disorders in humans as well as renal osteodystrophy.

Claims

1. A method of treating psoriasis comprising administering to a patient with psoriasis an effective amount of 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol having the formula;

2. The method of claim 1 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered orally.

3. The method of claim 1 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered parenterally.

4. The method of claim 1 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered transdermally.

5. The method of claim 1 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered topically.

6. The method of claim 1 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered in a dosage of from about 0.01 μ

g/day to about 100 μ

g/day.

7. A method of treating a disease selected from the group consisting of leukemia, colon cancer, breast cancer or prostate cancer comprising administering to a patient with said disease an effective amount of 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol having the formula;

8. The method of claim 7 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered orally.

9. The method of claim 7 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered parenterally.

10. The method of claim 7 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered transdermally.

11. The method of claim 7 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered in a dosage of from about 0.01 g/day to about 100 μ

g/day.

12. A method of treating an autoimmune disease selected from the group consisting of multiple sclerosis, lupis, diabetes, mellitus, host versus graft reaction, and rejection of organ transplants, comprising administering to a patient with said disease an effective amount of 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol having the formula;

13. The method of claim 12 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered orally.

14. The method of claim 12 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered parenterally.

15. The method of claim 12 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered transdermally.

16. The method of claim 12 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered in a dosage of from about 0.01μ

g/day to about 100 μ

g/day.

17. A method of treating an inflammatory disease selected from the group consisting of rheumatoid arthritis, asthma, and inflammatory bowel diseases, comprising administering to a patient with said disease an effective amount of 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol having the formula;

18. The method of claim 17 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered orally.

19. The method of claim 17 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered parenterally.

20. The method of claim 17 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered transdermally.

21. The method of claim 17 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered in a dosage of from about 0.01 μ

g/day to about 100 μ

g/day.

22. 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol having the formula;

23. A method of treating a skin condition selected from the group consisting of wrinkles, lack of adequate skin firmness, lack of adequate dermal hydration and insufficient sebum secretion which comprises administering to a patient with said skin condition an effective amount of 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol having the formula;

24. The method of claim 23 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered orally.

25. The method of claim 23 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered parenterally.

26. The method of claim 23 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered transdermally.

27. The method of claim 23 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered topically.

28. The method of claim 23 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered in a dosage of from about 0.01 μ

g/day to about 100 μ

g/day.

29. A method of treating renal osteodystrophy comprising administering to a patient with renal osteodystrophy an effective amount of 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol having the formula;

30. The method of claim 29 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered orally.

31. The method of claim 29 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered parenterally.

32. The method of claim 29 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered transdermally.

33. The method of claim 29 wherein 1α

-hydroxy-2-methylene-19-nor-pregnacalciferol is administered in a dosage of from about 0.01 μ

g/day to about 100 μ

g/day.