Bone substitution material and a method of its manufacture

• US 6,214,368 B1
• Filed: 05/20/1996
• Issued: 04/10/2001
• Est. Priority Date: 05/19/1995
• Status: Expired due to Term

• Current Assignee: Etex Corporation (Zimmer Biomet Holdings, Inc.)
• Original Assignee: Etex Corporation (Zimmer Biomet Holdings, Inc.)
• Inventors: Rey, Christian, Aiolova, Maria, Lee, Dosuk D.
• Primary Examiner(s): Levy, Neil S.
• Application Number:
  US08/650,764
• Time in Patent Office: 1,786 Days
• Field of Search: 424/602, 424/603, 424/57, 424/423, 424/426, 424/484, 523/218, 523/219, 428/404, 428/403, 623/16, 106/690, 106/691, 106/696, 433/180, 423/308, 423/311
• US Class Current: 424/423
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/30756 Cartilage endoprostheses A61F2/3603 takes precedence
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30762 Means for culturing cartilage
• CPC Class Codes: A61F 2002/4648 Means for culturing bone graft
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2310/00293 containing a phosphorus-containing compound, e.g. apatite
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61L 24/02 containing inorganic materials
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• 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 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/425 of phosphorus containing material, e.g. apatite
• CPC Class Codes: C01B 25/16 Oxyacids of phosphorus; Salts thereof peroxyacids or salts thereof C01B15/00
• CPC Class Codes: C01B 25/32 Phosphates of magnesium, calcium, strontium, or barium
• CPC Class Codes: C01B 25/321 Methods for converting an alkaline earth metal ortho-phosphate into another ortho-phosphate by reaction, e.g. of phosphate rock with phosphoric acid C01B25/322
• CPC Class Codes: C01B 25/325 Preparation by double decomposition
• CPC Class Codes: C04B 2111/00836 for medical or dental applications
• CPC Class Codes: C04B 28/344 the phosphate binder being present in the starting composition solely as one or more phosphates
• CPC Class Codes: Y10S 977/70 : Nanostructure
• CPC Class Codes: Y10S 977/775 : Nanosized powder or flake, e.g. nanosized catalyst
• CPC Class Codes: Y10S 977/776 : Ceramic powder or flake
• CPC Class Codes: Y10S 977/779 : Possessing nanosized particles, powders, flakes, or clusters other than simple atomic impurity doping
• CPC Class Codes: Y10S 977/833 : Thermal property of nanomaterial, e.g. thermally conducting/insulating or exhibiting peltier or seebeck effect
• CPC Class Codes: Y10S 977/896 : Chemical synthesis, e.g. chemical bonding or breaking
• CPC Class Codes: Y10S 977/90 : having step or means utilizing mechanical or thermal property, e.g. pressure, heat
• CPC Class Codes: Y10S 977/915 : Therapeutic or pharmaceutical composition
• CPC Class Codes: Y10S 977/926 : Topical chemical, e.g. cosmetic or sunscreen

Abstract

The present invention provides a novel process for converting a standard inert amorphous calcium phosphate precipitate into highly reactive amorphous solids. The amorphous solids can be used to react with other calcium phosphate solids to form a poorly-crystalline synthetic hydroxyapatite that provides both bioactivity and structural integrity. This novel amorphous material can be reacted with other calcium phosphates at or below 37° C. to form a bone-like material consisting of poorly crystalline hydroxyapatite.

Claims

1. A formable paste, suitable for use as a bone substitution material, comprising:

a powder comprising a first calcium phosphate material having at least 90% amorphous character and an acidic second calcium phosphate material, the powder having a calcium to phosphorous molar ratio in the range of about 1.2 to 1.68; and

a fluid in an amount to provide a formable or injectable consistency, said paste remaining injectable or formable for a time greater than about 60 minutes at about 22°

C. and hardenable within about 30 minutes at about 37°

C., said paste suitable for use as a bone substitute material.

2. The past of claim 1, wherein the mixture is injectable and formable at about 4°

C. for a time up to about 12 hours.

3. The past of claim 1, wherein said paste converts into a poorly crystalline hydroxyapatite having the X-ray diffraction pattern of naturally occurring bone within five hours.

4. The paste of claim 1, wherein said paste converts into a poorly crystalline hydroxyapatite having the X-ray diffraction pattern of naturally occurring bone within seventy five minutes.

5. The paste of claim 1, wherein the paste is hardenable within about 10 to 30 minutes at about 37°

C.

6. The paste of claim 1, wherein the material comprises a promoter selected to convert the calcium phosphate into a hydroxyapatitic calcium phosphate.

7. The paste of claim 1, wherein the fluid is selected from the group consisting of water, a physiologically acceptable pH-buffered solution, saline solution, serum and tissue culture medium.

8. The paste of claim 1, wherein the mixture comprises a second calcium phosphate powder which is amorphous or microcrystalline.

9. The paste of claim 1, wherein the second calcium phosphate powders selected from the group consisting of dicalcium phosphate dihydrate, calcium metaphosphate, heptacalcium phosphate, poorly crystalline hydroxyapatite, calcium pyrophosphates, octacalcium phosphate, and tricalcium phosphates.

10. The paste of claim 1 or 8, further comprising additional calcium sources.

11. The paste of claim 1 or 8, further comprising additional phosphate sources.

20. The paste of claim 1, wherein the second calcium phosphate material is an acidic calcium phosphate having a pH between 5 and 7.

12. A method of promoting bone growth, comprising:

providing a paste, said paste comprising a calcium phosphate powder, said powder comprising a first calcium phosphate material having at least 90% amorphous character and an acidic second calcium phoshate material the powder having a calcium to phosphorous molar ratio in the range of about 1.2 to 1.68, and a fluid in an amount which provides a formable or injectable consistency, said paste remaining injectable or formable for a time greater than about 60 minutes at about 22°

C.;

applying the paste to a site requiring bone growth; and

allowing the paste to harden at the site within about 30 minutes.

13. The method of claim 12, further comprising:

addition of a bone regenerative protein or an antibiotic to the mixture prior to application.

14. The method of claim 12, wherein the fluid is selected from the group consisting of water, a physiologically acceptable pH-buffered solution, saline solution, serum and tissue culture medium.

15. The method of claims 12, wherein the paste is formed into the use shape outside the body.

16. The method paste of claim 12, wherein said paste converts into a poorly crystalline hydroxyapatite having the X-ray diffraction pattern of naturally occurring bone within five hours.

17. The method of claim 12, wherein said paste converts into a poorly crystalline hydroxyapatite having the X-ray diffraction pattern of naturally occurring bone within seventy five minutes.

18. The method of claim 12, wherein the paste is hardenable within about 10 to 30 minutes at about 37°

C.

19. The method of claim 12, wherein the second calcium phosphate is selected from the group consisting of dicalcium phosphate dihydrate, calcium metaphosphate, heptacalcium phosphate, poorly crystalline hydroxyapatite, calcium pyrophosphates, octacalcium phosphate, and tricalcium phosphates.

21. The method of claim 12, wherein the second calcium phosphate material is an acidic calcium phosphate having a pH between 5 and 7.