Calcium phosphate cements comprising a water-soluble contrast agent

• US 20050023171A1
• Filed: 07/28/2003
• Published: 02/03/2005
• Est. Priority Date: 07/28/2003
• Status: Active Grant

• Current Assignee: Colson Medical LLC (Berkshire Hathaway Incorporated)
• Original Assignee: Skeletal Kinetics, LLC (Berkshire Hathaway Incorporated)
• Inventors: Constantz, Brent, Delaney, David
• Granted Patent: US 7,306,786 B2
• Time in Patent Office: Days
• US Class Current: 206/438
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2310/00293 containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61L 24/02 containing inorganic materials
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite

Abstract

Methods are provided for producing flowable compositions, e.g. pastes, that set into calcium phosphate products and include a contrast agent. In the subject methods, dry reactants that include a calcium source and a phosphate source are combined with setting fluid and a water-soluble contrast agent, e.g., a water-soluble barium salt, and the combined reactants are mixed to produce the flowable composition. Also provided are the compositions themselves as well as kits for preparing the same. The subject methods and compositions produced thereby find use in a variety of applications, including the repair of hard tissue defects, e.g., bone defects.

Claims

1. A method of producing a flowable composition that sets into a calcium phosphate containing product, said method comprising:

combining;

(a) a setting fluid;

(b) dry reactants comprising a calcium source and a phosphate source; and

(c) a water-soluble contrast agent;

in a ratio sufficient to produce said flowable material.

2. The method according to claim 1, wherein said setting fluid comprises said water-soluble contrast agent.

3. The method according to claim 1, wherein said dry reactants comprise said water-soluble contrast agent.

4. The method according to claim 1, wherein said water-soluble contrast agent comprises a salt of a radio-opaque element.

5. The method according to claim 4, wherein said radio-opaque element has a radio-opacity that differs from calcium.

6. The method according to claim 4, wherein said radio-opaque element is one that is incorporated into a calcium phosphate apatite structure of said calcium phosphate containing product.

7. The method according to claim 4, wherein said radio-opaque element is chosen from barium, oxalate, zirconium, tantalum and tungsten.

8. The method according to claim 7, wherein said radio-opaque element is barium.

9. The method according to claim 8, wherein said salt of said radio-opaque element is barium chloride.

10. The method according to claim 1, wherein said ratio ranges from about 0.2:

1 to 0.7;

1.

11. The method according to claim 10, wherein said flowable composition is a paste.

12. The method according to claim 1, wherein said setting fluid is a solution of a soluble silicate.

13. The method according to claim 1, wherein said flowable composition sets into said calcium phosphate containing product in a period of time ranging from about 5 to 10 minutes.

14. The method according to claim 1, wherein said calcium phosphate containing product has a compressive strength ranging from about 25 to 100 MPa.

23. A flowable composition that sets into a calcium phosphate containing product, wherein said composition is produced by the method according to claim 1.

24. A method of repairing a hard tissue defect, said method comprising:

applying to the site of said defect a flowable composition that sets into a calcium phosphate containing product, wherein said composition is produced by the method according to claim 1.

15. A method of producing a paste that sets into a calcium phosphate containing product, said method comprising:

(a) combining;

(i) dry reactants comprising a calcium source and a phosphate source;

(ii) a setting fluid; and

(iii) a water-soluble barium salt;

wherein said dry reactants, setting fluid and water-soluble barium salt are combined in a ratio sufficient to provide for said paste; and

(b) mixing said combined reactants and setting fluid for a sufficient period of time to produce a paste capable of setting into a calcium phosphate containing product.

16. The method according to claim 15, wherein said setting fluid comprises said water-soluble barium salt.

17. The method according to claim 15, wherein said dry reactants comprise said water-soluble barium salt.

18. The method according to claim 15, wherein said water-soluble barium salt is barium chloride.

19. The method according to claim 15, wherein said setting fluid is a solution of a soluble silicate.

20. The method according to claim 15, wherein both said setting fluid and dry reactants comprise said water-soluble barium salt.

21. The method according to claim 15, wherein said flowable composition sets into said calcium phosphate containing product in a period of time ranging from about 5 to 10 minutes.

22. The method according to claim 15, wherein said calcium phosphate containing product has a compressive strength ranging from about 25 to 100 MPa.

25. A kit for use in a preparing a flowable composition that sets in an in vivo fluid environment into a calcium phosphate product, said kit comprising:

(a) dry reactants comprising a calcium source and a phosphate source;

(b) a setting fluid or components for producing the same; and

(c) a water-soluble contrast agent.

26. A packaged calcium phosphate cement, said packaged cement comprising:

a tubular element separated into a first compartment and at least one additional compartment by a removable barrier;

(i) dry reactants comprising a source of calcium and phosphate present in said first compartment;

(ii) a setting fluid or components thereof present in said at least one additional compartment; and

(iii) a water-soluble contrast agent present in either said first compartment, said at least one additional compartment or in a second additional compartment.

27. The packaged calcium phosphate cement according to claim 26, wherein said removable barrier is a clip.

28. The packaged calcium phosphate cement according to claim 26, wherein said removable barrier is a frangible barrier.

29. The packaged calcium phosphate cement according to claim 26, wherein said setting fluid is a solution of a soluble silicate.