Use of carbon-2-modified-19-nor-vitamin d analogs to induce the formation of new bone

• US 20050203071A1
• Filed: 03/12/2003
• Published: 09/15/2005
• Est. Priority Date: 03/25/2002
• Status: Abandoned Application

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: Deluca, Hector F, Shevde, Nirupama K, Pike, J. Wesley
• Application Number:
  US10/509,065
• Publication Number:
  US 20050203071A1
• Time in Patent Office: Days
• US Class Current: 514/167
• CPC Class Codes: A61K 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• CPC Class Codes: A61K 31/593 9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 3/14 for calcium homeostasis vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04

Abstract

It has been discovered that the 2-carbon-modified derivatives of 1α,25-dihydroxyvitamin D₃ specifically stimulate osteoblasts to form new bone. The ability of the 2-carbon-modified vitamin D analogs to stimulate new bone formation suggest that these compounds can be used where synthesis of new bone is required. Thus, these compounds can be used either systemically or locally to stimulate the growth of bone transplants, to increase the rate of fracture healing and thereby reduce the time required for the healing of fractures, the stimulation of bone growth when required for replacement surgery, and also for the growth of bone to implants or other devices required to maintain the skeleton or teeth in the proper positions.

Claims

1. A method of stimulating osteoblastic-medicated growth of new bone in a mammal comprising administrating to a mammal in need thereof a therapeutically effective amount of a compound having the formula:

2. The method of claim 1 wherein the compound is administered orally.

3. The method of claim 1 wherein the compounds is administered parenterally.

4. The method of claim 1 wherein the compound is administered transdermally.

5. The method of claim 1 wherein the compound is administered topically.

6. The method of claim 1 wherein the compound is administered in an immobilized form at a site where growth of new bone is desired.

7. The method of claim 1 wherein the compound is administered in a slow release form at a site where growth of new bone is desired.

8. The method of claim 1 wherein the compound is administered in a dosage of from 0.01 μ

g to 50 μ

g per day.

9. The method of claim 1 wherein the mammal is a human.

10. The method of claim 1 wherein the compound administered is 2-methylene-19-nor-20(S)-1α

,25-dihydroxyvitamin D₃ having the formula;

11. The method of claim 1 wherein the compound administered is an acylated derivative having the formula:

12. The method of claim 11 wherein the compound is a triacetate such that Y₁, Y₂ and Y₃ and each CH₃CO—

.

13. The method of claim 11 wherein the compound as a trihexanoate such that Y₁, Y₂ and Y₃ are each CH₃(CH₂)₄CO—

.

14. The method of claim 11 wherein the compound is a trinonanoate such that Y₁, Y₂ and Y₃ are each CH₃(CH₂)₇CO—

.

15. The method of claim 11 wherein the compound is a 25-acetate such that Y₁, and Y₂ are both hydrogen and Y₃ is CH₃CO—

.

16. The method of claim 11 wherein the compound is 2-methylene-19-nor-1α

,25(OH)₂-D₃-1,3,25-triacetate.

17. The method of claim 11 wherein the compound is 2-methylene-19-nor-1α

,25(OH)₂-D₃-1,3,25-trihexanoate.

18. The method of claim 11 wherein the compound is 2-methylene-19-nor-1α

,25(OH)₂-D₃-1,3,25-trinonanoate.

19. The method of claim 11 wherein the compound is 2-methylene-19-nor-1α

,25(OH)₂-D₃-25-acetate.

20. The method of claim 1 wherein the compound administered is selected from the group consisting of:

21. The method of claim 1 wherein the compound administered is selected from the group consisting of:

22. The method of claim 1 wherein the compound administered is selected from the group consisting of:

23. The method of claim 1 wherein the compound is administered to stimulate healing of a bone fracture.

24. The method of claim 1 wherein the compound is administered to stimulate healing of a bone transplant.

25. The method of claim 1 wherein the compound is administered to stimulate solidification of an implant in bone.

26. The method of claim 1 wherein the compound is administered to stimulate osseointegration of a dental implant.

27. The method of claim 1 wherein the compound is administered to stimulate periodontal bone.

28. The method of claim 1 wherein the compound is administered following a distraction osteogenesis procedure.