Bone graft material incorporating demineralized bone matrix and lipids

• US 6,565,884 B2
• Filed: 09/10/2001
• Issued: 05/20/2003
• Est. Priority Date: 09/10/2001
• Status: Expired due to Term

• Current Assignee: Biomet Manufacturing, LLC (Zimmer Biomet Holdings, Inc.)
• Original Assignee: Interpore Cross International LLC (Zimmer Biomet Holdings, Inc.)
• Inventors: Nimni, Marcel E.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): FUBARA, BLESSING M
• Application Number:
  US09/950,264
• Publication Number:
  US 20030049326A1
• Time in Patent Office: 617 Days
• Field of Search: 424/484, 424/423, 424/318, 424/422, 424/549, 530/350, 514/560, 514/558
• US Class Current: 424/484
• CPC Class Codes: A61K 35/32 Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane

Abstract

A demineralized bone putty composition comprises: (1) demineralized bone matrix (DBM); and (2) a lipid fraction selected from the group consisting of lecithin and a mixture of lecithin and triglycerides containing unsaturated fatty acids. The putty composition is moldable, biocompatible, slowly resorbable, and soluble in tissue fluids, and non-extrudable. The composition delivers a biologically active product to animals and humans that will enhance bone formation at sites where bone is lost, deficient, or present in suboptimal amounts. The composition can further comprise calcium, an antioxidant such as Vitamin E or Vitamin C, or a hydrophilic polymer such as methylcellulose or hydroxypropyl methylcellulose.

Claims

1. A demineralized bone putty composition comprising:

(a) demineralized bone matrix (DBM); and

(b) a lipid fraction selected from the group consisting of lecithin and a mixture of lecithin and triglycerides containing unsaturated fatty acids;

such that the putty composition is moldable, biocompatible, slowly resorbable, insoluble in tissue fluids, and non-extrudable.

2. The composition of claim 1 wherein the composition comprises from about 20% to about 80% of DBM and from about 80% to about 20% of the lipid fraction.

3. The composition of claim 2 wherein the composition comprises about 30-40% of DBM and about 60% of the lipid fraction.

4. The composition of claim 3 wherein the composition comprises about 35-40% of DBM.

5. The composition of claim 1 wherein the lipid fraction comprises lecithin.

6. The composition of claim 1 wherein the lipid fraction comprises a mixture of lecithin and triglycerides containing unsaturated fatty acids.

7. The composition of claim 6 wherein the mixture of lecithin and triglycerides containing unsaturated fatty acids is about a 1:

1 mixture.

8. The composition of claim 6 wherein the mixture of lecithin and triglycerides containing unsaturated fatty acids is about a 64:

36 mixture.

9. The composition of claim 6 wherein the unsaturated fatty acids are from corn oil.

10. The composition of claim 9 wherein the ratio of lecithin and unsaturated fatty acids from corn oil is about 20:

80.

11. The composition of claim 9 wherein the ratio of lecithin and unsaturated fatty acids from corn oil is about 40:

60.

12. The composition of claim 9 wherein the ratio of lecithin and unsaturated fatty acids from corn oil is about 35:

65.

13. The composition of claim 1 wherein the composition further comprises a calcium salt.

14. The composition of claim 13 wherein the proportion of the calcium salt is about 0.1% to about 2%.

15. The composition of claim 14 wherein the proportion of the calcium salt is from about 0.5% to about 2%.

16. The composition of claim 13 wherein the calcium salt is selected from the group consisting of CaCO₃ and Ca₃(PO₄)₂.

17. The composition of claim 16 wherein the calcium salt is CaCO₃.

18. The composition of claim 16 wherein the calcium salt is Ca₃(PO₄)₂.

19. The composition of claim 1 wherein the composition further comprises at least one antioxidant selected from the group consisting of Vitamin E and Vitamin C.

20. The composition of claim 19 wherein the antioxidant is Vitamin E.

21. The composition of claim 19 wherein the Vitamin E is tocopherol.

22. The composition of claim 20 wherein the Vitamin E comprises from about 0.01% to about 1.0% of the composition.

23. The composition of claim 22 wherein the Vitamin E comprises about 0.1% of the composition.

24. The composition of claim 19 wherein the antioxidant is Vitamin C.

25. The composition of claim 24 wherein the Vitamin C comprises from about 0.01% to about 2.0% of the composition.

26. The composition of claim 25 wherein the Vitamin C comprises from about 0.1% to about 0.5% of the composition.

27. The composition of claim 26 wherein the Vitamin C comprises about 0.2% of the composition.

28. The composition of claim 1 wherein the composition further comprises at least one ingredient selected from the group consisting of methylcellulose and hydroxypropyl methylcellulose.

29. The composition of claim 28 wherein the ingredient is methylcellulose.

30. The composition of claim 28 wherein the ingredient is hydroxypropyl methylcellulose.

31. The composition of claim 30 wherein the lipid fraction comprises a mixture of lecithin and triglycerides containing unsaturated fatty acids, the ratio of lecithin to triglycerides containing unsaturated fatty acids is about 20:

80, the composition comprises about 40% of DBM, and the composition comprises about 4.0% of hydroxypropyl methylcellulose.

32. The composition of claim 1 wherein the lipid fraction is sterilized by radiation.

33. The composition of claim 1 wherein the phospholipids are liquid at room temperature.

34. The composition of claim 1 wherein the phospholipids are solid at room temperature.

35. The composition of claim 1 wherein the DBM is human DBM.

36. The composition of claim 1 wherein the DBM is rat DBM.

37. The composition of claim 1 wherein the DBM is DBM isolated from an animal species selected from the group consisting of cow, horse, pig, dog, cat, and sheep, or another socially or economically important animal species.

38. The composition of claim 1 wherein the DBM is delipidated.

39. The composition of claim 38 wherein the delipidation is performed by treatment with a mixture of chloroform and methanol.

40. The composition of claim 1 wherein the lipid fraction further contains a long-chain saturated fatty acid.

41. The composition of claim 40 wherein the long-chain saturated fatty acid is palmitic acid.