Bone growth particles and osteoinductive composition thereof

• US 8,742,072 B2
• Filed: 03/29/2010
• Issued: 06/03/2014
• 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.
• Primary Examiner(s): KAM, CHIH MIN
• Application Number:
  US12/748,999
• Publication Number:
  US 20100196489A1
• Time in Patent Office: 1,527 Days
• Field of Search: 530/356, 514/2, 514/12, 514/21.2, 424/602, 424/603, 424/489
• US Class Current: 530/356
• 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 biocompatible synthetic bone growth composition comprising a fibrillar collagen component, an acidic calcium phosphate component, and demineralized bone.

2. The composition of claim 1 wherein the fibrillar collagen component is obtained from a natural source.

3. The composition of claim 2 wherein the fibrillar collagen component is obtained from the group consisting of dermis, tendon, cartilage, or bone.

4. The composition of claim 2 wherein the fibrillar collagen component is obtained from a human source.

5. The composition of claim 1 wherein the fibrillar collagen component is synthetic.

6. The composition of claim 1 wherein the fibrillar collagen component is non-immunogenic.

7. The composition of claim 1 wherein the fibrillar collagen component is crosslinked.

8. The composition of claim 7 wherein the fibrillar collagen component is crosslinked by dehydrothermal crosslinking, UV light exposure, or chemical crosslinking.

9. The composition of claim 1 wherein the fibrillar collagen component has an in vivo lifetime of up to about twelve weeks.

10. The composition of claim 1 wherein the acidic calcium phosphate is selected from the group consisting of monocalcium phosphate [Ca(H₂PO₄)₂], calcium hydrogen phosphate [CaHPO₄], and calcium pyrophosphate [2CaO.P₂O₅].

11. The composition of claim 10 wherein the acidic calcium phosphate is calcium hydrogen phosphate [CaHPO₄].

12. The composition of claim 1 wherein the equilibrium solubility of calcium or phosphate ions is greater than that of a hydroxyapatite [3.33CaO.P₂O₅(OH)₂].

13. The composition of claim 12 wherein the equilibrium solubility of calcium or phosphate ions is at least 200 times greater than that of hydroxyapatite [3.33CaO.P₂O₅(OH)₂].

14. The composition of claim 1 wherein the demineralized bone comprises at least one osteoinductive protein.

15. The composition of claim 14 wherein the equilibrium solubility of the at least one osteoinductive protein in the presence of the acidic calcium phosphate component is greater than in the presence of an equi-molar quantity of a hydroxyapatite [3.33CaO.P₂O₅(OH)₂] in the composition.

16. The composition of claim 15 wherein the equilibrium solubility of the osteoinductive protein is at least five times greater than in the presence of an equimolar quantity of hydroxyapatite [3.33CaO.P₂O₅(OH)₂] in the composition.

17. The composition of claim 1 wherein the composition is moldable.

18. The composition of claim 1 wherein the composition is a paste.

19. The composition of claim 1 wherein the composition is a putty.

20. The composition of claim 1 wherein the composition is injectable.

21. The composition of claim 1 wherein the pH of the composition is between about 5 and about 7.

22. The composition of claim 1 comprising particles of fibrillar collagen and acidic calcium phosphate.

23. The composition of claim 22 wherein the particles comprise about 33% fibrillar collagen by weight and about 67% acidic calcium phosphate by weight.

24. The composition of claim 22 wherein the particles comprise between about 25% and about 75% fibrillar collagen by weight.