Implant for filling bone cavities and fixing bone fragments in a living body, method of producing the same, and bone implant system

• US 4,610,692 A
• Filed: 06/22/1984
• Issued: 09/09/1986
• Est. Priority Date: 02/20/1981
• Status: Expired due to Term

• Current Assignee: Mundipharma GmbH Mundipharma Strasse
• Original Assignee: Mundipharma GmbH (Germany) (Mundipharma International Limited)
• Inventors: Eitenmuller, Jurgen, Wimmer, Walter, Rackur, Helmut, Weiss, Marija
• Primary Examiner(s): McCarthy, Helen M.
• Application Number:
  US06/623,364
• Time in Patent Office: 809 Days
• Field of Search: 604/890, 604/891, 3/1.9, 3/1.91, 3/1, 128/92 G, 128/92 C, 264/44, 264/60, 424/19, 424/80, 424/150, 623/16, 623/66
• US Class Current: 424/422
• CPC Class Codes: A61F 2310/00293 containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61L 2300/202 with halogen atoms, e.g. triclosan, povidone-iodine
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/406 Antibiotics
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/12 Phosphorus-containing materials, e.g. apatite
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence

Abstract

A sintered tricalcium phosphate implant for filling bone cavities and for fixing bone fragments is provided, which comprises a discretely-shaped, porous body, at least one therapeutically-active ingredient impregnated into this porous body and distributed among the pores therein, and at least one coating of predetermined thickness of a biodegradable substance on at least a portion of this porous body, so that the time of absorption of the therapeutically-active ingredient is controlled by the thickness of the biodegradable substance. A process for producing this sintered tricalcium phosphate implant is also provided, along with an implant system for filling bone cavities and for fixing bone fragments in a living body, comprising a number of such tricalcium phosphate bone implants, with discrete coatings of biodegradable substance of predetermined thicknesses over at least some of the porous bodies constituting the tricalcium phosphate bone implants.

Claims

1. Method of producing sintered tricalcium phosphate implants for filling bone cavities and for fixing bone fragments in a living body, which comprises

mixing tricalcium phosphate with at least one substance which under heat sufficiently high to bake said tricalcium phosphate, forms a gas,

shaping the thus-formed mixture into shaped bodies thereof,

baking the shaped bodies at a temperature sufficiently high to cause gas formation from said substance, thereby forming pores in said shaped bodies,

impregnating said shaped porous bodies with a therapeutically-active ingredient, thereby distributing the same in the pores, and

coating at least a portion of one of said shaped, porous bodies having said therapeutically-active ingredient distributed therein, with a coating of a predetermined thickness of a biodegradable substance,

whereby the time of absorption of said therapeutically-active ingredient is controlled by the thickness of said biodegradable substance.

2. The method of claim 1 in which said gas-forming substance is selected from a group consisting of hydrogen peroxide, urea, sugar, ammonium bicarbonate, ammonium carbamate, calcium hydrogen phosphate, and mixtures thereof.

3. The method of claim 2 in which about 1% to about 3% by weight of hydrogen peroxide, based on the weight of said tricalcium phosphate, is mixed therewith.

4. The method of claim 2 in which about 10% to about 20% by weight of urea, based on the weight of said tricalcium phosphate, is mixed therewith.

5. The method of claim 1 in which about 3% to about 30% by weight of said gas-forming substance, based on the weight of said tricalcium phosphate, is mixed therewith.

6. The method of claim 5 in which about 10% to about 20% by weight of said gas-forming substance, based on the weight of said tricalcium phosphate, is mixed therewith.

7. The method of claim 1 in which said shaped, porous bodies are impregnated with up to about 45% by weight of said therapeutically-active ingredient, based upon the weight of said baked, porous bodies.

8. The method of claim 7 in which said therapeutically-active ingredient is selected from the group consisting of polyvinyl pyrrolidone iodine, penicillin, cycloserin, bacitracin, nystatin, amphotericin, gentamycin, novobiocin, erythromycin, momycin, streptomycin, flucloxacillin, sulfonamide and mixtures thereof.

9. The method of claim 7 in which said therapeutically-active ingredient is polyvinyl pyrrolidone iodine.

10. The method of claim 9 in which said shaped, porous bodies are impregnated with a solution or complex of polyvinyl pyrrolidone iodine having about a 10% iodine content.

11. The method of claim 1 in which said biodegradable substance is selected from at least one of polymethacrylate, polylactide, and polydextran.

12. The method of claim 1 comprising the additional step of mixing at least one fluoride compound selected from at least one of alkaline metal fluorides and alkali earth fluorides, with said tricalcium phosphate prior to baking.

13. The method of claim 12 in which said fluoride compound is selected from the group consisting of CaF₂, NaF, MgF₂, and mixtures thereof.

14. The method of claim 1 in which the thus-formed mixture is formed into a plurality of bodies each having its own discrete shape and dimensions, which are subsequently baked to form said discretely-shaped, porous bodies.

15. The method of claim 1 wherein said biodegradable substance is coated to have a predetermined thickness from about 4 microns to about 30 microns on said porous bodies.

16. The method of claim 15 wherein said bidegradable substance is coated to have a predetermined thickness of about 8 microns to about 20 microns on said porous bodies.

30. A sintered tricalcium phosphate implant for filling bone cavities and for fixing bone fragments in a living body, prepared by the method according to claim 1.

17. A sintered tricalcium phosphate implant for filling bone cavities and for fixing bone fragments in a living body, comprising

a discretely-shaped, baked porous body of tricalcium phosphate,

at least one therapeutically-active ingredient impregnated into said porous body and distributed among the pores therein, and

at least one coating of predetermined thickness of a biodegradable substance on at least a portion of said porous body impregnated with said therapeutically-active ingredient,

whereby the time of absorption of said therapeutically-active ingredient is controlled by the thickness of said biodegradable substance.

18. The implant of claim 17 wherein said discretely-shaped porous body of tricalcium phosphate, is formed by

mixing the same with at least one substance which under heat sufficiently high to bake said tricalcium phosphate, forms a gas;

and

baking said shaped body at a temperature sufficiently high to cause gas formation from said substance, thereby forming a discretely-shaped, porous body of tricalcium phosphate.

19. The implant of claim 18, wherein said gas-forming substance is selected from the group consisting of hydrogen peroxide, urea, sugar, ammonium bicarbonate, ammonium carbamate, calcium hydrogen phosphate, and mixtures thereof.

20. The implant of claim 19 wherein about 1% to about 3% by weight of hydrogen peroxide, based on the weight of said tricalcium phosphate, is mixed therewith.

21. The implant of claim 19 wherein about 10% to about 20% by weight of urea, based on the weight of said tricalcium phosphate, is mixed therewith.

22. The implant of claim 17, in which said therapeutically-active ingredient is selected from the group consisting of polyvinyl pyrrolidone iodine, penicillin, cycloserin, bacitracin, nystatin, amphotericin, gentamycin, novobiocin, erythromycin, momycin, streptomycin, flucloxacillin, sulfonamide and mixtures thereof.

23. The implant of claim 17, in which said biodegradable substance is selected from at least one of polymethacrylate, polylactide, and polydextran.

24. The implant of claim 22, in which said shape, porous body is impregnated with up to about 45% by weight of said therapeutically-active ingredient, based upon the weight of said baked, porous body.

25. The implant of claim 24, wherein said therapeutically-active ingredient is polyvinyl pyrrolidone iodine.

26. The implant of claim 17, in which said discretely-shaped, porous body of tricalcium phosphate additonally comprises at least one fluoride compound selected from at least one of alkali metal fluorides and alkaline earth fluorides.

27. The implant of claim 26, in which said fluoride compound is selected from the group consisting of CaF₂, NaF, MgF₂, and mixtures thereof.

28. The implant of claim 17 wherein the thickness of said biodegradable substance is from about 4 microns to about 30 microns.

29. The implant of claim 28 wherein the thickness of said biodegradable substance is from about 8 microns to about 20 microns.

31. An implant system for filling bone cavities and for fixing bone fragments in a living body, said system comprising

discretely-shaped, porous bodies of tricalcium phosphate,

at least one therapeutically-active ingredient impregnated into said porous bodies and distributed among the pores therein, and

at least one coating of predetermined thickness of a biodegradable substance on at least a portion of one of said porous bodies impregnated with said therapeutically-active ingredient,

whereby the time of absorption of said therapeutically-active ingredient is controlled by the thickness of said biodegradable substance.

32. The system of claim 31 wherein at least one porous body is coated with said biodegradable substance having a thickness of about 8 microns, at least one other porous body is coated with biodegradable substance having a thickness of about 20 microns, and at least a third porous body remains uncoated.

33. A method for filling bone cavities and for fixing bone fragments after fractures, which comprises employing an implant system according to claim 31.