Composition for an injectable bone mineral substitute material

• US 20040048947A1
• Filed: 10/22/2003
• Published: 03/11/2004
• Est. Priority Date: 07/17/2000
• Status: Active Grant

• Current Assignee: BONE Support NYA AB
• Original Assignee: Bone Support AB (BONESUPPORT HOLDING AB)
• Inventors: Lidgren, Lars, Nilsson, Malin
• Granted Patent: US 7,417,077 B2
• Time in Patent Office: Days
• US Class Current: 523/116
• 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 comprsises 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 fist 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 an d delivery system for delivery.

Claims

1. An injectable composition for a bone mineral substitute material with the capability of being hardened in a body fluid in vivo, which comprises a dry powder mixed with an aqueous liquid, characterized in that said dry 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 comprises 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.

2. A composition as in any of claims 1-3, characterized in that said first and/or said second reaction component is in particulate form with a particle size of 1-100 μ

m, preferably 1-10 μ

m.

3. A composition as in claim 1, characterized in that said calcium sulphate hemihydrate is α

-calcium sulphate hemihydrate.

4. A composition as in any of claims 1-3, characterized in that said first reaction component comprises 2-80 wt %, preferably 10-30 wt % of said dry powder.

5. A composition as in claim 1, characterized in that said second reaction component is selected from the group comprising tricalcium phosphate (TCP), tetracalcium phosphate (TTCP), anhydrous dicalcium phosphate, monocalcium phosphate maonohydrate (MCPM), dicalcium phosphate dihydrate (DCPD), and octocalcium phosphate (OCP).

6. A composition as in claim 5, characterized in that said tricalcium phosphate is α

-tricalcium phosphate.

7. A composition as in any of claims 1-2 or 5-6, characterized in that said second reaction component comprises 10-98 wt %, preferably 70-90 wt % of said dry powder.

8. A composition as in claim 1, characterized in that said at least one accelerator for the reaction of said first reaction component with said aqueous liquid is particulate calcium sulphate dihydrate.

9. A composition as in claims 8, characterized in that said particulate calcium sulphate dihydrate is α

-calcium sulphate dihydrate.

10. A composition as in claim 8 or 9, characterized in that said particulate calcium sulphate dihydrate has a particle size of less than 1 mm.

11. A composition as in claim 10, characterized in that said particulate calcium sulphate dihydrate has a particle size of less than 150 μ

m, preferably less than 50 μ

m.

12. A composition as in any of claims 8-11, characterized in that said particulate calcium sulphate dihydrate comprises between 0.1 and 10 wt %, preferably between 0.1 and 2 wt % of said first reaction component.

13. A composition as in claim 1, characterized in that said at least one accelerator for the reaction of said second reaction component with said aqueous liquid is particulate calcium phosphate cement.

14. A composition as in claim 13, characterized in that said particulate calcium phosphate cement has a Ca/P ratio between 1.5 and 2.

15. A composition as in claim 13 or 14, characterized in that said particulate calcium phosphate cement is hydroxylapatite (HA), tricalcium phosphate (TCP), or a mixture thereof.

16. A composition as in claim 15, characterized in that said hydroxylapatite is precipitated hydroxylapatite (PHA).

17. A composition as in any of claims 13-16, characterized in that said particulate calcium phosphate cement has a particle size which is less than 20 μ

M, preferably less than 10 μ

m.

18. A composition as in any of claims 13-17, characterized in that said particulate calcium phosphate cement comprises between 0.1 and 10 wt %, preferably between 0.5 and 5 wt % of said second reaction component.

19. A composition as in claim 1, characterized in that said aqueous liquid comprises destilled water or a balanced salt solution.

20. A composition as in claim 1 or 19, characterized in that said at least one accelerator for the reaction of said second component with said aqueous liquid is dissolved in said aqueous liquid.

21. A composition as in claim 20, characterized in that said accelerator is disodium hydrogen phosphate (Na₂HPO₄).

22. A composition as in claim 20 or 21, characterized in that said accelerator comprises 0.1-10 wt %, preferably 1-5 wt % of said aqueous liquid.

23. A composition as in claim 1 or 19, characterized in that said aqueous liquid comprises between 0.1 and 2 ml, preferably between 0.5 and 1 ml per gram of said powder.

24. A composition as in any of claims 1-23, characterized in that up to 95%, preferably between 80 and 90%, of said calcium sulphate hemihydrate is replaced by hardened calcium sulphate dihydrate in order to improve the injectability thereof.

25. A composition as in any of claims 1-23, characterized in that it further comprises a biologically compatible oil in order to improve the injectability thereof.

26. A composition as in claim 1, characterized in that said biologically compatible oil is vitamin E.

27. A composition as in claim 26 or 27, characterized in that said biologically compatible oil comprises between 0.1 and 5 wt %, preferably between 0.5 and 2 wt %.

28. A composition as in any of claims 1-23, characterized in that it further comprises a pH reducing component in order to improve the injectability thereof.

29. A composition as in claim 28, characterized in that said a pH reducing component is ascorbic acid or citric acid.

30. A composition as in claim 28 or 97, characterized in that said pH reducing component comprises between 0.1 and 5 wt %, preferably between 0.5 and 2 wt %.

31. A composition as in claim 1, characterized in that said dry powder is sterile.

32. A composition as in claim 1, characterized in that it further comprises biologically active substances, such as growth factors and/or anti-cancer substances and/or antibiotics and/or antioxidants.

33. Method of producing an injectable bone mineral substitute material, wherein a composition as in any of claims 1-32 is mixed in a closed mixing and delivery system, preferably under conditions of subatmospheric pressure.