Calcium phosphate cements comprising a water-soluble contrast agent

• US 7,306,786 B2
• Filed: 07/28/2003
• Issued: 12/11/2007
• 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: Delaney, David, Constantz, Brent
• Primary Examiner(s): JONES, DAMERON LEVEST
• Application Number:
  US10/629,321
• Publication Number:
  US 20050023171A1
• Time in Patent Office: 1,597 Days
• Field of Search: 424/1.11, 424/1.29, 424/1.37, 424/1.61, 424/1.65, 424/9.1, 424/9.4, 424/9.41
• US Class Current: 424/9.41
• 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 mineral product, said method comprising:

(a) a setting fluid;

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

(c) a water-soluble contrast agent comprising a radio-opaque element other than calcium that is incorporated into said calcium phosphate product wherein said water-soluble contrast agent comprises a salt of a radio-opaque element;

to produce said flowable material that sets into a calcium phosphate mineral product that includes atoms of said radio-opaque element incorporated into said mineral product.

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 radio-opaque element is one that is incorporated into a calcium phosphate apatite structure of said calcium phosphate containing product.

5. The method according to claim 1 wherein said radio-opaque element is chosen from barium, oxalate, zirconium, tantalum and tungsten.

6. The method according to claim 5, wherein said radio-opaque element is barium.

7. The method according to claim 6, wherein said salt of said radio-opaque element is barium chloride.

8. The method according to claim 1, wherein said said dry reactant to setting fluid are combined in a ratio that ranges from about 0.2:

1 to 0.7;

1.

9. The method according to claim 8, wherein said flowable composition is a paste.

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

11. 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.

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

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

27. The method according to claim 1, wherein said contrast agent is present in an amount ranging from about 10 to abut 35% by weight.

13. A method of producing a paste that sets into a calcium phosphate mineral 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; and

(b) mixing said combined reactants and setting fluid to produce a paste that sets into a calcium phosphate mineral product.

14. The method according to claim 13, wherein said setting fluid comprises said water-soluble barium salt.

15. The method according to claim 13, wherein said dry reactants comprise said water-soluble barium salt.

16. The method according to claim 13, wherein said water-soluble barium salt is barium chloride.

17. The method according to claim 13, wherein said setting fluid is a solution of a soluble silicate.

18. The method according to claim 13, wherein both said setting fluid and dry reactants comprise said water-soluble barium salt.

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

20. The method according to claim 13, wherein said calcium phosphate containing product has a compressive strength ranging from about 25 to 100 MPa.

22. A kit for use in preparing a flowable composition that sets in an in vivo fluid environment into a calcium phosphate mineral product comprising calcium phosphate molecules, 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 comprising a radio-opaque element other than calcium that is incorporated into said calcium phosphate mineral product, wherein said calcium phosphate mineral product includes atoms of said radio-opaque element incorporated into said mineral product.

23. 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 comprising a radio-opaque element other than calcium that is incorporated into a calcium phosphate mineral product, wherein said water-soluble contrast agent comprises a salt of a radio-opaque element, wherein said calcium phosphate mineral product includes atoms of said radio-opaque element incorporated into said mineral product, wherein said calcium phosphate mineral product is produced upon combination of said dry reactants and setting fluid, wherein said water-soluble contrast agent is present in either said first compartment, said at least one additional compartment or in a second additional compartment.

24. The packaged calcium phosphate cement according to claim 23, wherein said removable barrier is a clip.

25. The packaged calcium phosphate cement according to claim 23, wherein said removable barrier is a frangible barrier.

26. The method according to claim 23, wherein said setting fluid is a solution of a soluble silicate.