BONE GROWTH PARTICLES AND OSTEOINDUCTIVE COMPOSITION THEREOF

• US 20100196489A1
• Filed: 03/29/2010
• Published: 08/05/2010
• Est. Priority Date: 12/21/2006
• Status: Active Grant

• Current Assignee: Zimmer Orthobiologics, Inc. (Zimmer Biomet Holdings, Inc.)
• Original Assignee: Zimmer Orthobiologics, Inc. (Zimmer Biomet Holdings, Inc.)
• Inventors: THORNE, KEVIN J.
• Granted Patent: US 8,742,072 B2
• Time in Patent Office: Days
• US Class Current: 424/489
• 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 33/42 Phosphorus; Compounds thereof
• CPC Class Codes: A61K 35/14 Blood; Artificial blood perfluorocarbons A61K31/02; umbilical cord blood A61K35/51; haemoglobin A61K38/42
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 35/32 Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61K 38/39 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/46 with phosphorus-containing inorganic fillers
• 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: C08L 89/06 derived from leather or skin , e.g. gelatin

Abstract

A biocompatible synthetic bone growth composition comprising a fibrillar collagen component and a calcium phosphate component. The composition is formed into particles, and then formed into a unitary article that may be provided at the site of a skeletal defect. An osteoinductive component may be further added, either before or after forming the unitary article. The composition may be formulated as a paste or putty and facilitates bone growth and/or repair.

Claims

1. A bone growth composition comprising

a particulate fibrillar collagen component, and

a calcium phosphate component.

2. The composition of claim 1 wherein the collagen component comprises insoluble collagen.

3. The composition of claim 2 wherein the collagen component comprises crosslinked collagen.

4. The composition of claim 3 wherein the collagen comprises dehydrothermally crosslinked collagen.

5. The composition of claim 2 wherein the collagen component comprises porous particles.

6. The composition of claim 5 wherein the total open pore volume within the particle ranges from about 50 percent to about 90 percent.

7. The composition of claim 5 wherein the pore diameter of the porous particles ranges from about 125 to about 300 microns.

8. The composition of claim 5 wherein the size of the particles ranges from about 100 to about 840 microns.

9. The composition of claim 1 wherein the collagen component exceeds 20 dry weight percent.

10. The composition of claim 1 wherein the collagen component comprises uncross-linked collagen.

11. The composition of claim 1 wherein the collagen component comprises bovine dermal collagen.

12. The composition of claim 1 wherein the collagen component comprises Type I collagen.

13. The composition of claim 1 wherein the calcium phosphate component comprises an acidic calcium phosphate.

14. The composition of claim 13 wherein the acidic calcium phosphate is selected from the group consisting of monocalcium phosphate [Ca(H₂PO₄)₂],], calcium hydrogen phosphate [CaHPO₄], calcium pyrophosphate [2CaO.P₂O₅], and combinations thereof.

15. The composition of claim 14 wherein the acidic calcium phosphate is calcium hydrogen phosphate [CaHPO₄].

16. The composition of claim 1 wherein the calcium phosphate component exceeds 30 dry weight percent.

17. The composition of claim 1 further comprising an osteoinductive component.

18. The composition of claim 17 wherein the osteoinductive component comprises a substance selected from the group consisting of a purified bone growth factor, a recombinant bone growth factor, a bone marrow component, a blood component, demineralized bone and autologous bone.

19. The composition of claim 17 wherein the osteoinductive component comprises bone marrow aspirate.

20. The composition of claim 1 further comprising a liquid.

21. The composition of claim 20 wherein the liquid exceeds 25 volume percent.

22. The composition of claim 20 wherein the composition has a pH between about pH 5 to about pH 7.4.

23. A process for producing a bone growth composition comprising

combining a fibrillar collagen component with a calcium phosphate component to produce a mineralized collagen component, and

creating particles of the mineralized collagen component.

24. The process of claim 23 wherein creation of the particles includes grinding, milling, chopping or molding.

25. The process of claim 23 wherein creation of the particles includes milling.

26. The process of claim 23 wherein the mineralized collagen component comprises the form of a gel prior to creating the particles.

27. The process of claim 23 wherein the mineralized collagen component comprises the form of a sponge prior to creating the particles.

28. The process of claim 27 wherein the sponge is crosslinked.

29. The process of claim 23 comprising including the particles in a kit.

30. The process of claim 29 wherein the kit includes a device for mixing the particles with a fluid.

31. The process of claim 29 wherein the kit includes a receptacle for mixing the particles with a fluid.

32. The process of claim 23 comprising adding an osteoinductive component to the composition.

33. The process of claim 32 wherein the osteoinductive component is added after the particles are formed.

34. The process of claim 23 comprising sizing the particles.

35. The process of claim 34 wherein the size of the particles is selected by sieving.

36. The process of claim 23 wherein creation of the mineralized collagen component comprises preparing a collagen gel.

37. The process of claim 36 wherein the collagen gel comprises an acidic calcium phosphate.

38. The process of claim 37 wherein the acidic calcium phosphate is selected from the group consisting of monocalcium phosphate [Ca(H₂PO₄)₂], calcium phosphate dibasic [CaHPO₄], calcium pyrophosphate [2CaO.P₂O₅], and combinations thereof.

39. The process of claim 38 wherein the acidic calcium phosphate comprises calcium phosphate dibasic [CaHPO₄].

40. The process of claim 36 further comprising lyophilizing the mineralized collagen component.

41. The process of claim 36 further comprising crosslinking the collagen of the mineralized collagen component.

42. The process of claim 41 wherein collagen is dehydrothermally crosslinked.

43. A method of facilitating bone growth in a patient comprising

adding an osteoinductive component to a particulate mineralized collagen component, and

implanting the composition in the patient.

44. The method of claim 43 wherein particles of the mineralized collagen component are formed prior to addition of the osteoinductive component.

45. The method of claim 43 wherein the osteoinductive component comprises a substance selected from the group consisting of a purified bone growth factor, a recombinant bone growth factor, a bone marrow component, a blood component, demineralized bone and autologous bone.

46. The method of claim 45 wherein the osteoinductive component comprises bone marrow aspirate.

47. The method of claim 43 comprising including a liquid in the composition.

48. The method of claim 47 wherein the liquid exceeds 25 volume percent of the composition.

49. The method of claim 43 wherein implanting comprises extruding the composition from a syringe into a skeletal defect.

50. The method of claim 43 comprising molding the composition.