CALCIUM-CONTAINING RESTORATION MATERIALS

• US 20100212545A1
• Filed: 05/03/2010
• Published: 08/26/2010
• 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 8,282,396 B2
• Time in Patent Office: Days
• US Class Current: 106/35
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 33/06 Aluminium, calcium or magnesium; Compounds thereof , e.g. clay
• CPC Class Codes: A61K 33/42 Phosphorus; Compounds thereof
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/46 with phosphorus-containing inorganic fillers
• CPC Class Codes: C04B 2111/00836 for medical or dental applications
• CPC Class Codes: C04B 24/02 Alcohols; Phenols; Ethers
• CPC Class Codes: C04B 24/045 Esters, e.g. lactones
• CPC Class Codes: C04B 24/06 containing hydroxy groups
• CPC Class Codes: C04B 24/14 Peptides; Proteins; Derivatives thereof
• CPC Class Codes: C04B 24/32 Polyethers, e.g. alkylphenol polyglycolether
• 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 28/344 the phosphate binder being present in the starting composition solely as one or more phosphates
• CPC Class Codes: C04B 40/065 Two or more component mortars

Abstract

A bone or dental implant material in the form of a paste includes a mixture of calcium phosphate and/or calcium-containing powders, liquid glycerol, organic acid and gelling agent. The paste is stable, resistant to washout and will harden upon exposure to water. Physical characteristics of the paste, including consistency, porosity, and hardening time, are controlled by the choice and ratio of constituents.

Claims

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

a non-toxic non-aqueous water-miscible liquid;

a powdered calcium compound selected from the group consisting of monocalcium phosphate monohydrate, monocalcium phosphate anhydrous, dicalcium phosphate anhydrous, dicalcium phosphate dehydrate, octacalcium phosphate, α

-tricalcium phosphate, β

-tricalcium phosphate, amorphous calcium phosphate, calcium deficient hydroxyapatite, non-stoichiometric hydroxyapatite, tetracalcium phosphate, CaSO₄, CaSO₄.0.5H₂O, CaSO₄.2H₂O, CaO, Ca(OH)₂, CaCO₃ and mixtures thereof; and

an organic acid for forming calcium complexes when reacted with the calcium compound in the presence of water.

2. The composition of claim 1 including a gelling agent.

3. The composition of claim 2, wherein the gelling agent is selected from the group consisting of hydroxypropyl methyl cellulose, carboxymethyl cellulose, chitosan, collagen, gum, gelatin, and alginate, and combinations thereof.

4. The composition of claim 1, wherein the organic acid is a carboxylic acid.

5. The composition of claim 4, wherein the carboxylic acid is selected from the group consisting of glycolic, citric, tartaric, malonic, malic, and maleic acids and combinations thereof.

6. The composition of claim 1, wherein the liquid is selected from the group consisting of glycerin, propylene glycol, poly(propylene glycol), poly(ethylene glycol) and mixtures thereof.

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

(a) filling the defect with the composition of any of claims 1-6; and

(b) contacting the composition with an aqueous fluid to promote hardening of the composition.

21. The method of claim 20, wherein the composition is mixed with the aqueous fluid prior to filling the defect with the composition.

22. The method of claim 20, wherein the composition is contacted with the aqueous fluid subsequent to filling the defect with the composition.

7. A paste for bone and tooth restoration comprising, in combination:

an essentially water-free mixture of calcium compound powder, a non-toxic non-aqueous water-miscible liquid and carboxylic acid.

8. The paste of claim 7 wherein the calcium compound powder comprises tetracalcium phosphate.

9. The paste of claim 8, wherein the tetracalcium phosphate has a calcium to phosphate molar ratio of between about 1.67 to about 2.

10. The paste of claim 7 wherein the calcium compound powder comprises tricalcium phosphate.

11. The paste of claim 10, wherein the tricalcium phosphate has a calcium to phosphate molar ratio of between about 1.5 to about 1.67.

12. The paste of claim 7, wherein the calcium compound powder comprises tetracalcium phosphate and dicalcium phosphate anhydrous.

13. The paste of claim 7, wherein the powder has a particle size of between about 1 to about 200 μ

m.

14. The paste of claim 13, wherein the powder has a particle size of between about 2 to about 50 μ

m.

15. The paste of claim 7, wherein non-toxic non-aqueous water-miscible liquid is selected from the group consisting of glycerin, propylene glycol, poly(propylene glycol), poly(ethylene glycol) and mixtures thereof.

16. The paste of claim 7, wherein the carboxylic acid is selected from the group consisting of glycolic, citric, tartaric, malonic, malic, and maleic acids and combinations thereof.

17. The paste of claim 7, wherein the mass ratio of powder to liquid is in the range of 1.5 to 1 to 3 to 1.

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

(a) filling the defect with the paste of any of claims 7-17; and

(b) contacting the composition with an aqueous fluid to promote hardening of the composition.

24. The method of claim 23, wherein the paste is mixed with the aqueous fluid prior to filling the defect with the composition.

25. The method of claim 23, wherein the paste is contacted with the aqueous fluid subsequent to filling the defect with the composition.

18. A method of preparing a paste for bone and tooth restoration, the method comprising:

(a) formulating a composition comprising a non-toxic, non-aqueous, water-miscible liquid including;

(i) powder selected from the group consisting of monocalcium phosphate monohydrate, monocalcium phosphate anhydrous, dicalcium phosphate anhydrous, dicalcium phosphate dehydrate, octacalcium phosphate, α

-tricalcium phosphate, β

-tricalcium phosphate, amorphous calcium phosphate, calcium deficient hydroxyapatite, non-stoichiometric hydroxyapatite, tetracalcium phosphate, CaSO₄, CaSO₄.0.5H₂O, CaSO₄.2H₂O, CaO, Ca(OH)₂, CaCO₃ and mixtures thereof; and

(ii) an organic acid for forming calcium complexes with the calcium powder, the composition being formulated under substantially anhydrous conditions; and

(b) storing said composition under substantially anhydrous conditions.

19. The method of claim 18, further compromising mixing a gelling agent with the composition, the gelling agent effective for enhancing paste cohesiveness.

26. The method of claim 18 wherein said organic acid is selected from the group consisting of glycerin, propylene glycol, poly(propyleneglycol), polyethyleneglycol) and mixtures thereof.

27. The method of claim 18 wherein the calcium compound comprises tetracalcium phosphate and dicalcium phosphate anhydrous.

28. The method of claim 18 wherein the powder has a particle size between about 1 to 200 μ

m.

29. The method of claim 18 further including an organic acid.

30. The method of claim 29 wherein said acid comprises a carboxylic acid selected from the group consisting of glycolic, citric, tartaric, malonic, malic and maleic acid and mixtures thereof.

31. The method of claim 18 wherein the mass ratio of powder to liquid is in the range of about 1.5 to 1 to 3 to 1.

32. The method of claim 19 wherein said gelling agent is selected from the group consisting of hydroxypropyl methyl cellulose, carboxymethyl cellulose, chitosan, collagen, gum, gelatin, and alginate, and combinations thereof.

33. A method of preparing a paste for bone and tooth restoration, said method comprising the following steps:

(a) formulating a composition in the form of a non-toxic, non-aqueous, water-miscible liquid by mixing in a substantially anhydrous condition;

a powdered calcium compound in the form of selectively sized powder particles, said particle size in the range of about 1 μ

m to 50 μ

m, said particles comprising a calcium compound selected from the group consisting of monocalcium phosphate monohydrate, monocalcium phosphate anhydrous, dicalcium phosphate anhydrous, dicalcium phosphate dehydrate, octacalcium phosphate, α

-tricalcium phosphate, β

-tricalcium phosphate, amorphous calcium phosphate, calcium deficient hydroxyapatite, non-stoichiometric hydroxyapatite, tetracalcium phosphate, CaSO4, CaSO4.0.5H2O, CaSO4.2H2O, CaO, Ca(OH)2, CaCO3 and mixtures thereof;

(ii) a carboxylic acid for accelerating hardening of said composition when said composition is exposed to water at a delivery site, said acid comprising an acid selected from the group consisting of glycolic, citric, tartaric, malonic, malic, and maleic acids and combinations thereof;

(iii) a non-toxic, non-aqueous water-miscible liquid; and

(iv) a gelling agent;

said powder to liquid mass ratio is at least about 1.5, said components blended to obtain a substantially homogeneous formable anhydrous paste mixture; and

(b) storing said paste mixture under substantially anhydrous conditions.

34. The method of claim 33 wherein the gelling agent is selected from the group consisting of hydroxylmethyl, cellulose, carboxymethyl cellulose, chitosan, collagen, gum, gelatin, and alginate, and combinations thereof.

35. The method according to claim 33 wherein said miscible liquid is selected from the group consisting of propylene glycol, polypropylene glycol), poly(ethylene glycol) and mixtures thereof.

36. The method of claim 33 wherein the powder particle to liquid ratio of constituents is in the range of about 1.5 to 3.0.

37. The method of claim 33 wherein said non-toxic, non-aqueous water-miscible liquid is selected from the group consisting of propylene glycol, poly(ethylene glycol), poly(ethylene glycol) and mixtures thereof;

and

said gelling agent is selected from the group consisting of hydroxyl methyl cellulose, carboxymethyl cellulose, chitosan, collagen, gum, gelatin, alginate and combinations thereof.