Biocements having improved compressive strength

• US 6,495,156 B2
• Filed: 05/11/2001
• Issued: 12/17/2002
• Est. Priority Date: 05/12/2000
• Status: Expired due to Fees

• Current Assignee: Merck Patent GmbH (Merck & Co., Inc.)
• Original Assignee: Merck Patent GmbH (Merck & Co., Inc.)
• Inventors: Wenz, Robert, Driessens, Ferdinand
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US09/853,042
• Publication Number:
  US 20020017220A1
• Time in Patent Office: 585 Days
• Field of Search: 424/426, 623/16.11, 523/115
• US Class Current: 424/426
• CPC Class Codes: A61L 24/0015 Medicaments; Biocides
• 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 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite

Abstract

The invention describes biodegradable calcium phosphate cements, in particular mixtures of calcium phosphate-containing powders of different stoichiometric composition, the precipitated hydroxylapatite present being a cation-deficient hydroxylapatite of the formula 1, with the result that the mixtures have improved properties with regard to compressive strength.

Claims

1. A mixture of powders suitable for preparation of absorbable calcium phosphate cements comprising:

tricalcium phoshate (TCP) in which,

30 to 70% of the TCP particles have a particle size of 0.1 to 7 um and

10 to 60% of the TCP particles have a particle size of 40 to 100 um;

precipitated hydroxylapatite (PHA) wherein the PHA is a cation-deficient hydroxylapatite of the formula I

2. A mixture according to claim 1, wherein said mixture after hardening has a compressive strength of between 70-80 Mpa.

3. A mixture according to claim 1, wherein the PHA has a particle size of 0.5-10 um.

4. A mixture according to claim 3, wherein the PHA has a particle size of 0.5-5 um.

5. A mixture according to claim 1, wherein the PHA content is from 1-5% by weight, based on the total dry mass.

6. A mixture according to claim 1, wherein the PHA content is from 1.7-2.7% by weight, based on the total dry mass.

7. A mixture according to claim 1, wherein said at least one other phosphate-containing inorganic compound is selected from CaHPO₄ and carbonate-containing apatite.

8. A mixture according to claim 1, additionally comprising a setting accelerator.

9. A mixture according to claim 1, additionally comprising a pharmaceutically active ingredient.

10. A mixture according to claim 9, wherein said pharmaceutically active ingredient is an antibiotic or disinfectant.

11. A mixture according to claim 1, present in the form of an aqueous solution, suspension or paste.

12. A biodegradable implant produced from a hardened mixture according to claim 11.

13. A method of preparing biodegradable implantable synthetic bone materials comprising, hardening a mixture according to claim 1.

14. A mixture according to claim 9, wherein said pharmaceutically active ingredient is a growth factor or a prostaglandin.

15. A mixture according to claim 14, wherein said growth factor is a bone morphogenic protein, a tissue growth factor, a fibroblast growth factor, or a growth factor from the TGFβ

superfamily.

16. An absorbable calcium phosphate cement paste comprising cement powders according to claim 1, and a liquid phase.

17. A kit for the preparation of a bio-cement paste comprising a mixture of powders according to claim 1, a pharmaceutical active ingredient and a liquid phase.

18. A mixture according to claim 1, wherein said precipitated hydroxylapatite (PHA) is prepared by:

homogenously mixing CaSO4, Na₃PO4, and CaCO₃ in an aqueous solution;

dissolving at least one magnesium salt into aqueous solution;

removing resultant precipitate; and

washing with a neutral electrolyte.

19. A mixture according to claim 18, wherein said at least one magnesium salt is magnesium chloride, magnesium sulfate, magnesium nitrate or one or more of their hydrates.

20. A method of repairing bone fractures comprising applying an absorbable calcium phosphate paste according to claim 16, to a bone fracture.

21. A method of preparing a mixture of powders according to claim 1, comprising:

preparing said precipitated hydroxylapatite (PHA) by

homogenously mixing CaSO4, Na₃PO4, and CaCO₃ in an aqueous solution,

dissolving at least one magnesium salt into said aqueous solution,

removing resultant precipitate, and

washing said precipitate with a neutral electrolyte; and

combining said precipitated hydroxylapatite with said tricalcium phoshate (TCP) and said at least one other phosphate-containing inorganic compound.

22. A method according to claim 21, wherein said at least one magnesium salt is magnesium chloride, magnesium sulfate, magnesium nitrate or one or more of their hydrates.

23. A mixture of powders suitable for preparation of absorbable calcium phosphate cements comprising:

tricalcium phoshate (TCP) in which,

30 to 70% of the TCP particles have a particle size of 0.1 to 7 um and

10 to 60% of the TCP particles have a particle size of 40 to 100 um;

precipitated hydroxylapatite (PHA) wherein the PHA is a cation-deficient hydroxylapatite of the formula I Ca_8.75V(Ca)_1.25[(HPO₄)_5.5-x(CO₃)_0.5](OH)_xV(OH)_2-x in which x is 0-2; and

CaCO₃.