Composition for an injectable bone mineral substitute material

• US 7,417,077 B2
• Filed: 07/16/2001
• Issued: 08/26/2008
• Est. Priority Date: 07/17/2000
• Status: Expired due to Fees

• Current Assignee: BONE Support NYA AB
• Original Assignee: Bone Support AB (BONESUPPORT HOLDING AB)
• Inventors: Lidgren, Lars, Nilsson, Malin
• Primary Examiner(s): Yoon; Tae H
• Application Number:
  US10/333,026
• Publication Number:
  US 20040048947A1
• Time in Patent Office: 2,598 Days
• Field of Search: 523/115, 523/116, 424/602
• US Class Current: 523/115
• CPC Class Codes: A61L 24/0063 Phosphorus containing materials, e.g. apatite
• CPC Class Codes: A61L 24/02 containing inorganic materials
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/425 of phosphorus containing material, e.g. apatite
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system

Abstract

The invention refers to an injectable composition for a bone mineral substitute material, which comprises a dry powder mixed with an aqueous liquid. The powder comprises a first reaction component comprising a calcium sulphate hemihydrate with the capability of being hardened to calcium sulphate dihydrate when reacting with said aqueous liquid; a second reaction component, which comprise a calcium phosphate with the capability of being hardened to a calcium phosphate cement when reacting with said aqueous liquid; and at least one accelerator for the reaction of said first and/or second reaction component with said aqueous liquid. A method of producing an injectable bone mineral substitute material is also provided, wherein the composition is mixed in a closed mixing and delivery system for delivery.

Claims

1. A composition for a bone mineral substitute material comprising a dry powder, the dry powder comprising a first setting reaction component, which is a calcium sulphate hemihydrate;

a second setting reaction component, which is a calcium phosphate; and

at least one particulate accelerator for the setting reaction of both the first and the second setting reaction components, wherein the at least one accelerator for the reaction of the first setting reaction component is particulate calcium sulphate dihydrate, and the at least one accelerator for the reaction of the second setting reaction component is hardened particulate calcium phosphate cement.

2. The composition of claim 1, wherein the calcium sulphate hemihydrate is an α

-calcium sulphate hemihydrate.

3. The composition of claim 1, wherein the calcium phosphate is a tricalcium phosphate.

4. The composition of claim 1, wherein the particulate calcium phosphate cement has a Ca/P ratio between 1.5 and 2.

5. The composition of claim 1, wherein the particulate calcium phosphate cement is hydroxylapatite (HA), tricalcium phosphate (TCP), or a mixture thereof.

6. The composition of claim 5, wherein the hydroxylapatite is precipitated hydroxylapatite (PHA).

7. The composition of claim 1, wherein the particulate calcium phosphate cement has a particle size which is less than 20 μ

m.

8. The composition of claim 7, wherein the particulate calcium phosphate cement has a particle size which is less than 10 μ

m.

9. The composition of claim 1, wherein the particulate calcium phosphate cement comprises 0.1 wt % to 10 wt % of the calcium phosphate.

10. The composition of claim 9, wherein the particulate calcium phosphate cement comprises 0.5 wt % to 5 wt % of the calcium phosphate.

11. The composition of claim 1, wherein at least one of the calcium sulfate hemihydrate or the calcium phosphate reaction component is in particulate form with a particle size of 1 μ

m to 100 μ

m.

12. The composition of claim 11, wherein the particle size is 1 μ

m to 10 μ

m.

13. The composition of claim 3, wherein the tricalcium phosphate is α

-tricalcium phosphate.

14. The composition claim 1, wherein the particulate calcium sulphate dihydrate is α

-calcium sulphate dihydrate.

15. The composition of claim 14, wherein the particulate calcium sulphate dihydrate has a particle size less than 1 mm.

16. The composition of claim 15, wherein the particulate calcium sulphate dihydrate has a particle size less than 150 μ

m.

17. The composition of claim 16, wherein the particulate calcium sulphate dihydrate has a particle size less than 50 μ

m.

18. The composition of claim 1, wherein the particulate calcium sulphate dihydrate comprises 0.1 wt % to 10 wt % of the first reaction component.

19. The composition of claim 18, wherein the particulate calcium sulphate dihydrate comprises 0.1 wt % to 2 wt % of the first reaction component.

20. The composition of claim 1, wherein the calcium sulfate hemihydrate comprises 2 wt % to 80 wt % of the dry powder.

21. The composition of claim 20, wherein the calcium sulfate hemihydrate comprises 10 wt % to 30 wt % of the dry powder.

22. The composition of claim 1, wherein the calcium phosphate reaction component comprises 10 wt % to 98 wt % of the dry powder.

23. The composition of claim 22, wherein the calcium phosphate reaction component comprises 70 wt % to 90 wt % of the dry powder.

24. The composition of claim 1, further comprising a biologically active substance.

25. The composition of claim 24, wherein the biologically active substance comprises a growth factor, an anti-cancer substance, an antibiotic, and an antioxidant, and mixtures thereof.

38. A kit for use in preparing a composition for a bone mineral substitute material, said kit comprising:

(1) the composition according to claim 1; and

(2) optionally an aqueous liquid.

39. The composition of claim 1, wherein the composition further comprises an aqueous liquid.

40. The composition of claim 39, wherein the aqueous liquid comprises between 0.1 ml and 2 ml per gram of the dry powder.

41. The composition of claim 40, wherein the aqueous liquid comprises between 0.5 ml and 1 ml per gram of the dry powder.

42. The composition according to claim 39, wherein the aqueous liquid comprises distilled water or a balanced salt solution.

43. The composition of claim 39, wherein the composition is contacted with the aqueous liquid and is capable of being hardened in a body fluid in vivo to a bi-phasic cement implant that with time obtains a porous structure for bone ingrowth.

26. A composition for a bone mineral substitute material comprising a dry powder, the dry powder comprising

a first setting reaction component, which is a calcium sulphate hemihydrate;

a second setting reaction component, which is a calcium phosphate;

at least one accelerator for the setting reaction of the first or second setting reaction component, or both the first and the second setting reaction components, wherein the at least one accelerator is chosen from at least one accelerator for the reaction of the first setting reaction component, wherein the accelerator is particulate calcium sulphate dihydrate, and the at least one accelerator for the reaction of the second setting reaction component, wherein the accelerator is hardened particulate calcium phosphate cement; and

a biologically compatible oil to improve the injectability of the composition.

27. The composition of claim 26, wherein the calcium sulphate hemihydrate is an α

-calcium sulphate hemihydrate.

28. The composition according to claim 26, wherein the calcium phosphate is a tricalcium phosphate.

29. The composition according to claim 26, wherein the biologically compatible oil is vitamin E.

30. The composition according to claim 26, wherein the biologically compatible oil comprises 0.1 wt % to 5 wt % of the composition.

31. The composition according to claim 30, wherein the biologically compatible oil comprises 0.5 wt % to 2 wt % of the composition.

32. A composition for a bone mineral substitute material comprising

a dry powder, the dry powder comprising a first setting reaction component, which is a calcium sulphate hemihydrate;

a second setting reaction component, which is a calcium phosphate;

at least one accelerator for the setting reaction of the first or the second setting reaction component, or both the first and the second setting reaction components, wherein the at least one accelerator is chosen from at least one accelerator for the reaction of the first setting reaction component, the accelerator being a particulate calcium sulphate dihydrate, and at least one accelerator for the reaction of the second setting reaction component, the accelerator being a hardened particulate calcium phosphate cement; and

a pH reducing component to improve the injectability of the composition.

33. The composition of claim 32, wherein the calcium sulphate hemihydrate is an α

-calcium sulphate hemihydrate.

34. The composition of claim 32, wherein the calcium phosphate is a tricalcium phosphate.

35. The composition of claim 32, wherein the pH reducing component is ascorbic acid or citric acid.

36. The composition of claim 32, wherein the pH reducing component comprises 0.1 wt % to 5 wt % of the composition.

37. The composition of claim 36, wherein the pH reducing component comprises 0.5 wt % to 2 wt % of the composition.

44. A composition for a bone mineral substitute material comprising a dry powder, the dry powder comprising a first setting reaction component, which is a calcium sulphate hemihydrate;

a second setting reaction component, which is a calcium phosphate; and

at least one particulate accelerator for the setting reaction of both the first and the second setting reaction components, wherein the at least one accelerator for the reaction of the first setting reaction component is particulate calcium sulphate dihydrate, and the at least one accelerator for the reaction of the second setting reaction component is hardened particulate calcium phosphate cement, wherein the calcium sulphate dihydrate comprises 0.1 wt % to 10 wt % of the first reaction component.

45. A composition for a bone mineral substitute material according to claim 44, wherein the calcium sulphate dihydrate comprises 0.1 wt % to 2 wt % of the first reaction component.