End-capped polymers and compositions containing such compounds

• US 7,205,337 B2
• Filed: 06/19/2003
• Issued: 04/17/2007
• Est. Priority Date: 12/21/2001
• Status: Expired due to Term

• Current Assignee: Isotis Orthobiologics, Inc. (Orthofix Medical Inc.)
• Original Assignee: Isotis Orthobiologics, Inc. (Orthofix Medical Inc.)
• Inventors: Kay, John F., Eisch, John J.
• Primary Examiner(s): Woodward; Michael P.
• Assistant Examiner(s): Silverman; Eric E.
• Application Number:
  US10/600,130
• Publication Number:
  US 20040076677A1
• Time in Patent Office: 1,398 Days
• Field of Search: None
• US Class Current: 514/772.1
• CPC Class Codes: C08G 2650/04 End-capping
• CPC Class Codes: C08G 2650/58 Ethylene oxide or propylene oxide copolymers, e.g. pluronics
• CPC Class Codes: C08G 65/32 Polymers modified by chemical after-treatment
• CPC Class Codes: C08G 65/322 containing hydrogen
• CPC Class Codes: C08G 65/323 containing halogens
• CPC Class Codes: C08G 65/328 containing other elements
• CPC Class Codes: C08G 65/337 containing other elements organic compounds containing halogens only as halides of a carboxyl group C08G65/332
• CPC Class Codes: C08L 2666/26 Natural polymers, natural resins or derivatives thereof according to C08L1/00 - C08L5/00, C08L89/00, C08L93/00, C08L97/00 or C08L99/00
• CPC Class Codes: C08L 71/02 Polyalkylene oxides

Abstract

End-capped polymers, methods for making those end-capped polymers, compositions containing those end-capped polymers, and methods for using those compositions are disclosed. One of the disclosed end-capped copolymers has the formula (I):

and may be combined with natural or synthetic bone minerals, bone tissue, collagen tissue, bone protein or combinations or derivatives of those materials to form a tissue repair composition.

Claims

1. A composition comprising:

(i) a soluble product extracted from demineralized bone and (ii) a carrier comprising a polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymer wherein both terminal hydroxyl groups in the triblock copolymer have been replaced with terminal methoxy groups and wherein the polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymer is derived from a dilithium salt of a dihydroxy starting material, and wherein the compound has no hydroxyl groups.

2. The composition according to claim 1, wherein the carrier further comprises a solvent.

3. The composition according to claim 2, wherein the solvent is water.

4. The composition according to claim 3, wherein the carrier comprises about 25% to about 30% weight of the compound according to formula (I) and about 75% to about 70% weight water.

5. The composition according to claim 1, wherein the degree of polymerization of the polyoxyproplylene block is about 101 and the degree of polymerization of both polyoxyethylene blocks is about 56″

therefor.

6. The composition according to claim 4, wherein the carrier exhibits reverse phase behavior.

7. The composition according to claim 1, wherein the soluble product is about 20% to about 80% weight of the composition and the carrier is about 80% to 20% weight of the composition.

8. The composition according to claim 7, wherein the soluble product is about 60% weight of the composition and the carrier is about 40% weight of the composition.

9. The composition according to claim 1, further comprising an insoluble product extracted from demineralized bone.

10. The composition according to claim 9, wherein the soluble product is about 1% to about 80% weight of the composition, the carrier is about 10% to about 40% weight of the composition, and the insoluble product is about 20% to about 50% weight of the composition.

11. The composition according to claim 10, wherein the soluble product is about 30% to about 40% weight of the composition, the carrier is about 26% to about 28% weight of the composition, and the insoluble product is about 30% weight of the composition.

12. The composition according to claim 9, further comprising demineralized bone.

13. The composition according to claim 12, wherein the demineralized bone is in the form of a powder.

14. The composition according to claim 13, wherein the soluble product is about 1% to about 20% weight of the composition, the carrier is about 10% to about 40% weight of the composition, the insoluble product is about 0.1% to about 15% weight of the composition, and the demineralized bone powder is about 10% to about 40% weight of the composition.

15. The composition according to claim 14, wherein the soluble product is about 3% to about 5% weight of the composition, the carrier is about 26% to about 28% weight of the composition, the insoluble product is about 6% to about 9% weight of the composition, and the demineralized bone powder is about 23% to about 27% weight of the composition.

16. The composition according to claim 1, further comprising bone chips.

17. The composition according to claim 16, wherein the bone chips are about 1% to about 20% weight of the composition.

18. The composition according to claim 9, further comprising bone chips.

19. The composition according to claim 18, wherein the bone chips are about 1% to about 20% weight of the composition.

20. The composition of claim 9, further comprising at least one of hydroxylapatite, tricalcium phosphate, biphasic calcium phosphate or calcium sulfate.

21. The composition according to claim 12, further comprising at least one of hydroxylapatite, tricalcium phosphate, biphasic calcium phosphate or calcium sulfate.

22. The composition according to claim 21, wherein the at least one of hydroxylapatite, tricalcium phosphate, biphasic calcium phosphate or calcium sulfate is about 15% to about 30% weight of the composition.

23. The composition according to claim 16, further comprising at least one of hydroxylapatite, tricalcium phosphate, biphasic calcium phosphate or calcium sulfate.

24. The composition according to claim 18, further comprising at least one of hydroxylapatite, tricalcium phosphate, biphasic calcium phosphate or calcium sulfate.

37. A method of treating tissue comprising applying a composition of claim 1 to a tissue.

38. The method of claim 37, wherein the tissue is a bone defect site.

25. A composition comprising (i) at least one material of demineralized bone powder, bone chips, insoluble product, hydroxylapatite, tricalcium phosphate, biphasic calcium phosphate, or calcium sulfate, wherein the material is coated by a soluble product extracted from demineralized bone and (ii) a carrier comprising a polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymer wherein both terminal hydroxyl groups in the triblock copolymer have been replaced with terminal methoxy groups.

26. The composition according to claim 25, wherein the at least one coated material of demineralized bone powder, bone chips, insoluble product, hydroxylapatite, tricalcium phosphate, biphasic calcium phosphate, or calcium sulfate is about 30% to about 70% weight of the composition, the soluble product is about 5% to about 20% weight of the composition and the carrier is about 10% to about 40% weight of the composition.

27. The composition according to claim 25, wherein the composition comprises hydroxylapatite.

28. The composition according to claim 27, wherein the hydroxylapatite has been treated with a poreformer.

29. The composition according to claim 27, wherein the hydroxylapatite is derived from bone.

30. The composition according to claim 27, wherein the hydroxylapatite has been treated with a binder.

31. The composition according to claims 25, wherein the composition comprises a combination of hydroxylapatite and tricalcium phosphate.

32. The composition according to claim 31, wherein the hydroxylapatite is about 60% to about 80% weight of the combination and the tricalcium phosphate is about 20% to about 40% of the combination.

33. The composition according to claim 25, wherein the particle size of the demineralized bone powder and the insoluble product is between about 10 to about 1,000 microns.

34. The composition according to claim 33, wherein the particle size of the demineralized bone powder and the insoluble product is between about 125 to about 500 microns.

35. The composition according to claim 25, wherein the particle size of the bone chips, hydroxylapatite, tricalcium phosphate, biphasic calcium phosphate, and calcium sulfate is between about 100 to about 7,000 microns.

36. The composition according to claim 35, wherein the particle size of the bone chips, hydroxylapatite, tricalcium phosphate, biphasic calcium phosphate, and calcium sulfate is between about 1,000 to about 4,000 microns.

39. A method of treating tissue comprising applying a composition of claim 25 to a tissue.

40. The method of claim 39, wherein the tissue is a bone defect site.

41. A composition comprising:

(i) an osteogenic agent and (ii) a carrier comprising a polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymer wherein both terminal hydroxyl groups in the triblock copolymer have been replaced with terminal methoxy groups and wherein the polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymer is derived from a dilithium salt of a dihydroxy starting material, and wherein the compound has no hydroxyl groups.

42. The composition according to claim 41, wherein the carrier further comprises a solvent.

43. The composition according to claim 42, wherein the solvent is water.

44. The composition according to claim 43, wherein the carrier comprises about 25% to about 30% weight of the compound according to formula (I) and about 75% to about 70% weight water.

45. The composition according to claim 41, wherein a is about 101 and b is about 56.

46. The composition according to claim 43, wherein the carrier exhibits reverse phase behavior.

47. The composition of claim 41, wherein the osteogenic agent is a protein.

48. The composition of claim 47, wherein the osteogenic agent is a protein that enhances the repair of a bone defect.