Rapid-hardening calcium phosphate cement compositions

• US 20050074415A1
• Filed: 09/15/2004
• Published: 04/07/2005
• Est. Priority Date: 01/24/2001
• Status: Active Grant

• Current Assignee: ADA Foundation
• Original Assignee: ADA Foundation
• Inventors: Takagi, Shozo, Chow, Laurence C.
• Granted Patent: US 7,294,187 B2
• Time in Patent Office: Days
• US Class Current: 424/49
• 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 6/858 Calcium sulfates, e.g, gypsum
• 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 6/898 Polysaccharides
• CPC Class Codes: A61L 24/02 containing inorganic materials
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: C04B 14/28 of calcium
• CPC Class Codes: C04B 20/008 Micro- or nanosized fillers, e.g. micronised fillers with particle size smaller than that of the hydraulic binder colloidal silica C04B14/062 ; silica fume C04B18/146
• CPC Class Codes: C04B 2103/10 Accelerators; Activators
• CPC Class Codes: C04B 2103/42 Pore formers
• CPC Class Codes: C04B 2103/445 Gelling agents
• CPC Class Codes: C04B 2111/00836 for medical or dental applications
• CPC Class Codes: C04B 22/064 of the alkaline-earth metals
• CPC Class Codes: C04B 22/085 containing nitrogen in the anion, e.g. nitrites
• CPC Class Codes: C04B 22/122 Acids
• CPC Class Codes: C04B 22/143 Calcium-sulfate
• CPC Class Codes: C04B 24/003 : Phosphorus-containing compounds
• CPC Class Codes: C04B 24/04 : Carboxylic acids; Salts, anhydrides or esters thereof
• CPC Class Codes: C04B 24/06 : containing hydroxy groups
• CPC Class Codes: C04B 24/38 : Polysaccharides or derivatives thereof C04B24/243 takes precedence
• CPC Class Codes: C04B 24/383 : Cellulose or derivatives thereof
• CPC Class Codes: C04B 28/34 : containing cold phosphate binders
• CPC Class Codes: C04B 28/344 : the phosphate binder being present in the starting composition solely as one or more phosphates
• CPC Class Codes: C04B 28/346 : the phosphate binder being present in the starting composition as a mixture of free acid and one or more phosphates
• CPC Class Codes: C04B 38/02 : by adding chemical blowing agents
• CPC Class Codes: C04B 40/0028 : Aspects relating to the mixing step of the mortar preparation
• CPC Class Codes: C04B 40/0082 : making use of a rise in temperature, e.g. caused by an exothermic reaction
• CPC Class Codes: C04B 40/0259 : Hardening promoted by a rise in pressure C04B40/024 takes precedence
• CPC Class Codes: C08L 1/284 : with hydroxylated hydrocarbon radicals
• CPC Class Codes: C08L 1/286 : substituted with acid radicals, e.g. carboxymethyl cellulose [CMC] C08L1/282 takes precedence
• CPC Class Codes: C08L 5/04 : Alginic acid; Derivatives thereof
• CPC Class Codes: C08L 5/08 : Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

A bone or dental implant material in the form of a paste includes a mixture of calcium phosphate and/or calcium-containing powders and a solution that is (1) an acidic calcium phosphate solution saturated with respect to one or more calcium phosphate compounds, (2) a concentrated acid solution, or (3) salt solutions with a cationic component other than calcium. The paste is stable, resistant to washout and will form hydroxyapatite and harden relatively rapidly to a cement.

Claims

1. A composition of matter for dental restoration and bone implants and restoration comprising:

a powdered calcium compound including one or more calcium phosphate salts selected from the group consisting of monocalcium phosphate monohydrate, monocalcium phosphate anhydrous, dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, octacalcium phosphate, α

-tricalcium phosphate, P-tricalcium phosphate, amorphous calcium phosphate, hydroxyapatite, tetracalcium phosphate and combinations thereof; and

an acidic calcium phosphate solution saturated with respect to monocalcium phosphate monohydrate, monocalcium phosphate anhydrous or combinations thereof.

2. The composition of claim 1 wherein the powdered calcium compound includes one or more calcium salts selected from the group consisting of calcium oxide, calcium hydroxide, calcium carbonate, calcium glycerophosphate, calcium gluconate, calcium sulfate, calcium lactate and combinations thereof.

3. The composition of claim 1 including one or more additives selected from the group consisting of medicaments, filler materials, crystal adjustors, viscosity modifiers, gelling agents, pore forming agents, resorbable and nonresorbable fibers and meshes, osteoinductive factors, bone morphogenic proteins, and other proteins.

4. The composition of claim 3, wherein the one or more additives is a gelling agent selected from the group consisting of hydroxypropyl methyl cellulose, carboxymethyl cellulose, chitosan, chitosan derivatives, collagen, gum, gelatin, and alginate, and combinations thereof.

5. The composition of claim 3, wherein the one or more additives is a filler material.

6. The composition of claim 3, wherein the one or more additives is a pore forming agent.

7. The composition of claim 1, wherein the pH of the acidic composition is initially less than about 1.9.

14. The composition of claim 1, wherein the pH of the acidic composition is initially between about 1.9 to about 4.3.

28. A method of repairing bone and tooth defects comprising:

(a) preparing the composition of any one of claims 1, 8, 15 and 22; and

(b) filling the defect with the composition prior to hardening of the composition.

29. A calcium phosphate bone cement that self-hardens at ambient temperature and is resorbable when implanted in contact with living bone comprising the composition of any one of claims 1, 8, 15 and 22.

8. A composition of matter for dental restoration and bone implants and restoration comprising:

a powdered calcium compound including one or more calcium phosphate salts selected from the group consisting of monocalcium phosphate monohydrate, monocalcium phosphate anhydrous, dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, octacalcium phosphate, α

-tricalcium phosphate, β

-tricalcium phosphate, amorphous calcium phosphate, hydroxyapatite, tetracalcium phosphate and combinations thereof; and

an acidic calcium phosphate solution saturated with respect to dicalcium phosphate dihydrate, dicalcium phosphate anhydrous and combinations thereof.

9. The composition of claim 8 wherein the powdered calcium compound includes one or more calcium salts selected from the group consisting of calcium oxide, calcium hydroxide, calcium carbonate, calcium glycerophosphate, calcium gluconate, calcium sulfate, calcium lactate and combinations thereof.

10. The composition of claim 8 including one or more additives selected from the group consisting of medicaments, filler materials, crystal adjustors, viscosity modifiers, gelling agents, pore forming agents, resorbable and nonresorbable fibers and meshes, osteoinductive factors, bone morphogenic proteins, and other proteins.

11. The composition of claim 10, wherein the one or more additives is a gelling agent selected from the group consisting of hydroxypropyl methyl cellulose, carboxymethyl cellulose, chitosan, chitosan derivatives, collagen, gum, gelatin, and alginate, and combinations thereof.

12. The composition of claim 10, wherein the one or more additives is a filler material.

13. The composition of claim 10, wherein the one or more additives is a pore forming agent.

15. A composition of matter for dental restoration and bone implants and restoration comprising:

a powdered calcium compound including one or more calcium phosphate salts selected from the group consisting of monocalcium phosphate monohydrate, monocalcium phosphate anhydrous, dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, octacalcium phosphate, α

-tricalcium phosphate, β

-tricalcium phosphate, amorphous calcium phosphate, hydroxyapatite, tetracalcium phosphate and combinations thereof; and

a concentrated acid solution.

17. The composition of claim 15 wherein the powdered calcium compound includes one or more calcium salts selected from the group consisting of calcium oxide, calcium hydroxide, calcium carbonate, calcium glycerophosphate, calcium gluconate, calcium sulfate, calcium lactate and combinations thereof.

18. The composition of claim 15 including one or more additives selected from the group consisting of medicaments, filler materials, crystal adjustors, viscosity modifiers, gelling agents, pore forming agents, resorbable and nonresorbable fibers and meshes, osteoinductive factors, bone morphogenic proteins, and other proteins.

19. The composition of claim 18, wherein the one or more additives is a gelling agent selected from the group consisting of hydroxypropyl methyl cellulose, carboxymethyl cellulose, chitosan, chitosan derivatives, collagen, gum, gelatin, and alginate, and combinations thereof.

20. The composition of claim 18, wherein the one or more additives is a filler material.

21. The composition of claim 18, wherein the one or more additives is a pore forming agent.

16. The composition of claim 16, wherein the concentrated acid solution is selected from the group consisting of hydrochloric acid, nitric acid, phosphoric acid, acetic acid, glycerolphosphoric acid, and combinations thereof.

22. A composition of matter for dental restoration and bone implants and restoration comprising:

a powdered calcium compound including one or more calcium phosphate salts selected from the group consisting of monocalcium phosphate monohydrate, monocalcium phosphate anhydrous, dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, octacalcium phosphate, α

-tricalcium phosphate, β

-tricalcium phosphate, amorphous calcium phosphate, hydroxyapatite, tetracalcium phosphate and combinations thereof; and

a solution of a salt where the cationic component(s) is not calcium and one or more of the anionic component(s) form (i) strong calcium complexes in the solution or (ii) insoluble salts with calcium.

23. The composition of claim 22 wherein the powdered calcium compound includes one or more calcium salts selected from the group consisting of calcium oxide, calcium hydroxide, calcium carbonate, calcium glycerophosphate, calcium gluconate, calcium sulfate, calcium lactate and combinations thereof.

24. The composition of claim 22 including one or more additives selected from the group consisting of medicaments, filler materials, crystal adjustors, viscosity modifiers, gelling agents, pore forming agents, resorbable and nonresorbable fibers and meshes, osteoinductive factors, bone morphogenic proteins, and other proteins.

25. The composition of claim 24, wherein the one or more additives is a gelling agent selected from the group consisting of hydroxypropyl methyl cellulose, carboxymethyl cellulose, chitosan, chitosan derivatives, collagen, gum, gelatin, and alginate, and combinations thereof.

26. The composition of claim 24, wherein the one or more additives is a filler material.

27. The composition of claim 24, wherein the one or more additives is a pore forming agent.