Strontium-apatite-cement-preparations, cements formed therefrom, and uses thereof

• US 20050142211A1
• Filed: 12/06/2004
• Published: 06/30/2005
• Est. Priority Date: 06/07/2002
• Status: Active Grant

• Current Assignee: Kyphon SARL (Medtronic Plc)
• Original Assignee: Kyphon Incorporated
• Inventors: Wenz, Robert
• Granted Patent: US 7,273,523 B2
• Time in Patent Office: Days
• US Class Current: 424/603
• 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: 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: C04B 14/26 Carbonates
• CPC Class Codes: C04B 2111/00836 for medical or dental applications
• CPC Class Codes: C04B 28/344 the phosphate binder being present in the starting composition solely as one or more phosphates

Abstract

Calcium-strontium-hydroxyphosphate (strontium-apatite-) cement preparations are described, comprising a powder mixture, which contains molar quantities of the components calcium (Ca), strontium (Sr) and phosphate (P) in the mixture in the ranges 1.00<Ca/P≦1.50 and 0<Sr/P<1.5, together with an alkali salt or an ammonium salt of phosphoric acid, and with water and/or an aqueous solution. The powder mixture particularly contains, as the Ca-component, Ca₃(PO₄)₂ (TCP), and as the Sr-component SrHPO₄ and/or Sr₃(PO₄)₂ and optionally additional SrCO₃. As the aqueous mixing solution for the formation of the strontium-apatite cement, an aqueous solution of an alkali salt or an ammonium salt of the phosphoric acid is suitable.

Claims

1. A composition comprising:

a) a water-combinable combination of calcium, strontium and phosphate, wherein a molar ratio of calcium to phosphate is about 1 to about 1.5, and a molar ratio of strontium to phosphate is not greater than about 1.5; and

b) a salt of phosphoric acid, wherein said composition does not contain magnesium ions or contains no more than trace amounts of magnesium ions.

2. The composition of claim 1, wherein said phosphate is orthophosphate.

3. The composition of claim 2, wherein said calcium, strontium and orthophosphate comprise a powder mixture.

4. The composition of claim 2, wherein said phosphoric acid is orthophosphoric acid.

5. The composition of claim 4, wherein said salt is selected from the group consisting of an alkali salt and an ammonium salt.

6. The composition of claim 5, wherein the alkali salt of the orthophosphoric acid comprises at least one of sodium—

(Na—

) and potassium—

(K—

) salt.

7. The composition of claim 6, wherein the alkali salt of the orthophosphoric acid is selected from the group consisting of a primary potassium salt, a secondary potassium salt, a primary sodium salt, a secondary sodium salt, and combinations of said potassium and sodium salts.

8. The composition of claim 5, wherein the alkali or ammonium salt of the orthophosphoric acid is present in an aqueous solution.

9. The composition of claim 1, wherein said trace amounts of magnesium ions are of insufficient quantity to substantially inhibit the formation of a strontium-apatite structure.

10. The composition of claim 1, further comprising an aqueous solution having a pH value in the range of about 5 to about 12.

11. The composition of claim 1, wherein the strontium is present in a powder mixture as strontium phosphate or strontium hydrogenphosphate, or a mixture thereof.

12. The composition of claim 11, wherein the strontium phosphate, the strontium hydrogenphosphate, or the mixture thereof is present in said powder mixture in an amount of more than about 10 wt.-% to about 60 wt.-%.

13. The composition of claim 11, wherein the powder mixture additionally contains strontium carbonate.

14. The composition of claim 3, wherein the powder mixture comprises Ca₃(PO₄)₂ (TCP) and at least one of SrHPO₄ and Sr₃(PO₄)₂.

15. The composition of claim 14, wherein the powder mixture further comprises at least one of NaH₂PO₄, Na₂HPO₄, KH₂PO₄, K₂HPO₄, SrCO₃ and combinations of Na—

and K-salts of orthophosphoric acid.

27. A method for augmenting bone, comprising delivering a preparation according to claim 1 to a bone site.

16. A strontium-apatite cement composition, comprising a powder mixture component and an aqueous component, wherein the powder mixture component contains:

Ca₃(PO₄)₂ (TCP),

SrHPO₄ and/or Sr₃(PO₄)₂, and

SrCO₃; and

wherein the aqueous component contains a solution of an alkali salt or an ammonium salt of orthophosphoric acid.

17. The strontium-apatite cement composition of claim 16, wherein the aqueous component comprises a solution of (NH₄)₂HPO₄.

18. The strontium-apatite cement composition of claim 16, wherein the aqueous component comprises a solution of primary and/or secondary Na—

and/or K-salts of the orthophosphoric acid.

19. The strontium-apatite cement composition of claim 16, wherein the aqueous component is selected from the group consisting of a solution of the primary salt NaH₂PO₄ and/or KH₂PO₄;

a solution of the secondary salt K₂HPO₄ and/or Na₂HPO₄; and

a solution of a mixture of the primary salt KH₂PO₄ and/or NaH₂PO₄ with the secondary salt K₂HPO₄ and/or Na₂HPO₄.

20. The strontium-apatite cement composition of claim 16, wherein the powder mixture additionally contains NaH₂PO₄ and/or Na₂HPO₄;

KH₂PO₄ and/or K₂HPO₄;

or combinations of Na— and

K-salts of said orthophosphoric acid.

21. The strontium-apatite cement composition of claim 16, wherein SrHPO₄ and/or Sr₃(PO₄)₂ is present in the powder mixture component in an amount in the range from about 10 wt.-% to about 60 wt.-%.

22. The strontium-apatite cement composition of claim 16, wherein SrCO₃ in the powder mixture component is present in an amount in the range from about 0.01 wt.-% to about 10 wt.-%.

23. A composition according to claim 16, wherein at least one of the powder component and the aqueous component contains a pharmacologically and/or biologically active substance.

24. A composition according to claim 23, wherein the pharmacologically and/or biologically active substance is selected from the group consisting of an antibiotic, a cytostatic agent, an analgetic agent, a disinfectant, a growth factor, a protein and a biopolymer.

25. A composition according to claim 23, wherein the pharmacologically and/or biologically active substance is selected from the group consisting of gentamicin, tobramycin, clindamycin, vancomycin, a substance of the TGF-β

-series and a substance of the BMPs series.

26. A composition according to claim 16, wherein the powder mixture component additionally contains a substance in the form of granular particles, which dissolves in the aqueous component.

28. A method for augmenting bone, comprising delivering a preparation according to claim 16 to a bone site.

29. A process for preparing a strontium-apatite cement, comprising the steps of:

mixing a powder mixture component and an aqueous component, as set forth in claim 16 to produce a paste; and

allowing the paste to harden during formation of strontium-apatite as reaction product to produce said strontium-apatite cement.

30. The process according to claim 29, wherein said paste is filled into a mold to produce defined molded bodies.

31. The process according to claim 29, wherein an injectable liquid is formed after the mixing and before the hardening of the paste.