Self-setting calcium phosphate cements and methods for preparing and using them

• US 5,997,624 A
• Filed: 04/16/1998
• Issued: 12/07/1999
• Est. Priority Date: 09/24/1993
• Status: Expired due to Term

• Current Assignee: ADA Foundation
• Original Assignee: American Dental Association Health Foundation
• Inventors: Takagi, Shozo, Chow, Laurence C.
• Primary Examiner(s): MARCANTONI, PAUL D
• Application Number:
  US09/061,577
• Time in Patent Office: 600 Days
• Field of Search: 106/35, 106/690, 106/691, 106/792, 423/308, 423/309, 423/311
• US Class Current: 106/35
• CPC Class Codes: A61F 2310/00293 containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61K 6/54 Filling; Sealing
• CPC Class Codes: A61K 6/69 Medicaments
• CPC Class Codes: A61K 6/838 Phosphorus compounds, e.g. apatite
• CPC Class Codes: A61K 6/864 Phosphate cements apatite A61K6/838
• CPC Class Codes: A61K 6/873 Carbonates
• CPC Class Codes: A61K 6/876 Calcium oxide
• CPC Class Codes: A61K 6/891 Compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 24/02 containing inorganic materials
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: C08L 89/00 Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00

Abstract

The invention includes methods and compositions relating to calcium phosphate cements, which self-harden substantially to hydroxyapatite at ambient temperature when in contact with an aqueous medium. More specifically the cements comprise a combination of one or more sparingly soluble calcium phosphates other than tetracalcium phosphate with an aqueous solution adjusted with a base to maintain a pH of about 12.5 or above and having sufficient dissolved phosphate salt to yield a solution mixture with phosphate concentration equal to or greater than about 0.2 mol/L.

Claims

1. A calcium phosphate-containing composition, which self-hardens to hydroxyapatite as the predominant product at ambient temperature, comprising a calcium phosphate salt that is substantially free of tetracalcium phosphate, an additional source of slightly soluble calcium and an aqueous solution having a pH of about 12.5 or above.

3. A calcium phosphate tissue substitute precursor having as a calcium phosphate component the composition of claim 1.

5. A calcium phosphate bone cement which self-hardens at ambient temperature and is resorbable when implanted in contact with living bone comprising the composition of claim 1.

7. A biological implant comprised of the cement of claim 5 inserted into contact with living tissue.

9. A method of bonding living tissue comprising the step of inserting the tissue substitute precursor of claim 3 into the tissue to form a bridging agent between the tissue to be bonded.

11. A method of augmenting living tissue comprising the step of inserting the tissue substitute precursor of claim 3 into contact with the living tissue.

13. A method for repairing bony defects comprising the step of filling the defect with the tissue substitute precursor of claim 3.

18. A calcium phosphate-containing composition according to claim 1, wherein the additional source of slightly soluble calcium is selected from the group consisting of calcium carbonate, calcium oxide and calcium hydroxide.

2. A calcium phosphate-containing composition, which self-hardens to hydroxyapatite as the predominant product at ambient temperature, comprising a calcium phosphate salt that is substantially free of tetracalcium phosphate, an additional source of slightly soluble calcium and an aqueous solution having a concentration of phosphate of about 0.2 mol/L or above, in the absence of solid crystalline phosphoric acid.

4. A calcium phosphate tissue substitute precursor having as a calcium phosphate component the composition of claim 2.

6. A calcium phosphate bone cement which self-hardens at ambient temperature and is resorbable when implanted in contact with living bone comprising the composition of claim 2.

8. A biological implant comprised of the cement of claim 6 inserted into contact with living tissue.

10. A method of bonding living tissue comprising the step of inserting the tissue substitute precursor of claim 4 into the tissue to form a bridging agent between the tissue to be bonded.

12. A method of augmenting living tissue comprising the step of inserting the tissue substitute precursor of claim 4 into contact with the living tissue.

14. A method for repairing bony defects comprising the step of filling the defect with the tissue substitute precursor of claim 4.

19. A calcium phosphate-containing composition according to claim 2, wherein the additional source of slightly soluble calcium is selected from the group consisting of calcium carbonate, calcium oxide and calcium hydroxide.

15. A kit for preparing a calcium phosphate-containing composition comprising (1) a calcium phosphate salt which is substantially free of tetracalcium phosphate, (2) an additional source of slightly soluble calcium and (3) an aqueous solution having a pH of about 12.5 or above.

20. A kit according to claim 15, wherein the additional source of slightly soluble calcium is selected from the group consisting of calcium carbonate, calcium oxide and calcium hydroxide.

16. A kit for preparing a calcium phosphate-containing composition comprising (1) a calcium phosphate salt that is substantially free of tetracalcium phosphate, (2) an additional source of slightly soluble calcium, and (3) an aqueous solution having a phosphate concentration of about 0.2 mol/L or above, in the absence of solid crystalline phosphoric acid.

21. A kit according to claim 16, wherein the additional source of slightly soluble calcium is selected from the group consisting of calcium carbonate, calcium oxide and calcium hydroxide.

17. An implant constructed in vitro for reconstruction of bone or dental tissue comprising a mixture of (1) a calcium phosphate salt that is substantially free of tetracalcium phosphate, (2) an additional source of slightly soluble calcium, and an aqueous solution having a pH of about 12.5 or above, and having a high phosphate concentration, in the absence of solid crystalline phosphoric acid whereby the mixture self-hardens to hydroxyapatite as the predominant product at ambient temperature and can be shaped as desired.

22. An implant according to claim 17, wherein the additional source of slightly soluble calcium is selected from the group consisting of calcium carbonate, calcium oxide and calcium hydroxide.