Hardenable ceramic hydraulic cement

• US 6,461,632 B1
• Filed: 04/18/2001
• Issued: 10/08/2002
• Est. Priority Date: 10/19/1998
• Status: Expired due to Fees

• Current Assignee: Synthes USA LLC (Johnson & Johnson)
• Original Assignee: Synthes USA LLC (Johnson & Johnson)
• Inventors: Gogolewski, Sylwester
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Bennett, Rachel M.
• Application Number:
  US09/836,267
• Time in Patent Office: 538 Days
• Field of Search: 623/16.11, 623/23.61, 623/23.72, 623/23.62, 424/423, 424/426, 424/422, 514/772.3
• US Class Current: 424/426
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/412 Tissue-regenerating or healing or proliferative agents
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/428 Vitamins, e.g. tocopherol, riboflavin
• CPC Class Codes: A61L 24/0015 Medicaments; Biocides
• CPC Class Codes: A61L 24/02 containing inorganic materials

Abstract

A method for delivering a therapeutically effective drug via a hardenable ceramic hydraulic cement composition including a first component of at least one sodium or calcium salts of inorganic and organic acids, a second component of at least one alkaline, and optionally third and fourth components including an organic carboxylic acid and pure water, respectively, wherein the cement composition is implanted in an animal or human body, hardens, and then degrades in situ after time to releases a amount of the drug into a locally targeted area.

Claims

1. A method of delivering a composition which comprises:

providing a first component comprising at least one of a calcium or sodium salt of an inorganic and/or organic acid;

providing a second component comprising sodium silicate or calcium silicate;

mixing the first and second components to form a ceramic hydraulic cement composition; and

implanting a therapeutically effective amount of the composition into an animal,

wherein the first component is different from the second component,

wherein the composition hardens in situ,

and wherein the composition degrades in situ over a period of time to release a drug to a locally targeted area.

2. The method of claim 1, wherein the inorganic and/or organic acid comprises carbonic acid, phosphoric acid, or glycerophosphoric acid.

3. The method of claim 2, wherein the calcium or sodium salt comprises at least one of hydroxyapatite, tricalcium phosphate, calcium carbonate, calcium hydrogen phosphate, disodium hydrogen phosphate, or calcium glycerophosphate.

4. The method of claim 1, wherein the first component further comprises a therapeutically active agent and the animal is human.

5. The method of claim 1, wherein the second component comprises an aqueous solution of sodium silicate or calcium silicate.

6. The method of claim 1, wherein the second component further comprises water.

7. The method of claim 6, wherein the amount of the sodium silicate or calcium silicate in the second component is from 0.01 to 10 weight percent.

8. The method of claim 1, wherein the composition further comprises a third component comprising an organic carboxylic acid.

9. The method of claim 8, wherein the third component comprises at east one of ascorbic acid, citric acid, or tartaric acid.

10. The method of claim 8, wherein the third component comprises ascorbic acid.

11. The method of claim 1, wherein the composition degrades in 10 hours to 4 months.

12. The method of claim 11, wherein the composition degrades in 10 hours to 30 days.

13. The method of claim 1, wherein the locally targeted area is a bone defect.

14. The method of claim 1, wherein the composition further comprises an osteogenic agent.

15. The method of claim 14, wherein the osteogenic agent comprises at least one of growth factors, osteocalcines, calcium binding proteins, bone morphogenetic proteins, antimicrobial agents, or vitamins.

30. The method of claim 8, wherein the first component further comprises a therapeutically active agent and the animal is human.

31. The method of claim 8, wherein the second component further comprises water, and wherein the amount of the sodium silicate or calcium silicate in the second component is from 0.01 to 10 weight percent.

32. The method of claim 8, wherein the third component comprises at least one of ascorbic acid, citric acid, or tartaric acid.

33. The method of claim 8, wherein the composition degrades in 10 hours to 4 months.

34. The method of claim 30, wherein the locally targeted area is a bone defect and wherein the therapeutically active agent comprises at least one osteogenic agent comprising growth factors, osteocalcines, calcium binding proteins, bone morphogenetic proteins, antimicrobial agents, or vitamins.

16. A ceramic hydraulic cement composition comprising:

a first component comprising at least one of a calcium or sodium salt of an inorganic and/or organic acid;

a second component comprising sodium silicate or calcium silicate; and

a third component comprising an organic carboxylic acid,

wherein the first component is different from the second component, and

wherein the composition degrades in the presence of water in 10 hours to 4 months.

17. The composition of claim 16, wherein the inorganic and/or organic acid comprises carbonic acid, phosphoric acid, or glycerophosphoric acid.

18. The composition of claim 17, wherein the calcium or sodium salt comprises at least one of hydroxyapatite, tricalcium phosphate, calcium carbonate, calcium hydrogen phosphate, disodium hydrogen phosphate, or calcium glycerophosphate.

19. The composition of claim 16, wherein the first component comprises therapeutically active agent and the animal is human.

20. The composition of claim 16, wherein the composition further comprises at least one of growth factors, osteocalcines, calcium binding proteins, bone morphogenetic proteins, antimicrobial agents, or vitamins.

21. The composition of claim 16, wherein the composition degrades in water in 10 hours to 30 days.

22. The composition of claim 16, wherein the second component comprises an aqueous solution of sodium silicate or calcium silicate.

23. The composition of claim 16, wherein the second component further comprises water.

24. The composition of claim 23, wherein the amount of the sodium silicate or calcium silicate in the second component is from 0.01 to 10 weight percent.

25. The composition of claim 16, wherein the composition further comprises a fourth component comprising pure water.

26. The composition of claim 25, wherein the third component comprises at least one of ascorbic acid, citric acid, or tartaric acid.

27. A method of delivering a composition which comprises:

providing a first component comprising at least one of a calcium or sodium salt of an inorganic and/or organic acid;

providing a second component comprising sodium silicate or calcium silicate;

providing a third component comprising an organic carboxylic acid;

mixing the first, second, and third components to form a ceramic hydraulic cement composition; and

implanting a therapeutically effective amount of the composition into an human, wherein the first the component is different from the second component,

wherein the composition hardens in situ,

and wherein the composition degrades in situ over a period of time to release a drug to a locally targeted area.

28. The method of claim 27, wherein the inorganic and/or organic acid comprises carbonic acid, phosphoric acid, or glycerophosphoric acid.

29. The method of claim 28, wherein the calcium or sodium salt comprises at least one of hydroxyapatite, tricalcium phosphate, calcium carbonate, calcium hydrogen phosphate, disodium hydrogen phosphate, or calcium glycerophosphate.