Biomaterial composition and method for preparing same

• US 6,001,394 A
• Filed: 04/13/1998
• Issued: 12/14/1999
• Est. Priority Date: 08/07/1995
• Status: Expired due to Term

• Current Assignee: Centre National De La Recherche Scientifique
• Original Assignee: Centre National De La Recherche Scientifique
• Inventors: Daculsi, Guy, Weiss, Pierre, Dupraz, Anne, Lapkowski, Mieczyslam
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Benston, Jr., William E.
• Application Number:
  US09/011,215
• Time in Patent Office: 610 Days
• Field of Search: 424/423, 424/426, 424/489, 424/494
• US Class Current: 424/489
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61L 27/46 with phosphorus-containing inorganic fillers
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: C08L 1/28 Alkyl ethers
• CPC Class Codes: C08L 3/02 Starch; Degradation products thereof, e.g. dextrin
• CPC Class Codes: C08L 5/14 Hemicellulose; Derivatives thereof

Abstract

A biomaterial composition for the resorption/substitution of organic supporting tissues, including 20-75 wt. % of an inorganic phase consisting of particles that include either hydroxyapatite (A) optionally mixed with tricalcium phosphate β (B), or calcium-titaniumphosphate (Ca(Ti)₄ (PO₄)₆) (C), and 80-25 wt. % of a liquid phase including an aqueous solution of a water-soluble biocompatible polymer that is cross-linkable under the effect of the pH of the medium. The composition is sterilizable, injectable and curable in biological media to form a biomaterial for replacing supporting tissues.

Claims

1. A composition for a biomaterial for resorption/substitution of supporting organic tissues, comprising:

20 to 75% by weight of an inorganic phase consisting of particles including either hydroxyapatite (A), optionally mixed with β

tricalcium phosphate (B), or calcium titanium phosphate (Ca(Ti)₄ (PO₄)₆) (C), and

80 to 25% by weight of a liquid phase including an aqueous solution of a water-soluble, biocompatible polymer self-crosslinkable under the effect of the pH of the medium.

2. The composition according to claim 1, wherein said inorganic phase comprises a mixture of hydroxyapatite (A) and of β

tricalcium phosphate (B) in an A/B weight ratio of 80/20 to 30/70.

3. The composition according to claim 1, wherein said inorganic phase comprises a mixture of hydroxyapatite (A) and of β

tricalcium phosphate (B) in an A/B weight ratio of approximately 60/40.

4. The composition according to claim 1, wherein said inorganic phase consists of a powder whose particle size when the composition is prepared is between 80 and 200 μ

m in diameter.

5. The composition according to claim 1, wherein said polymer self-crosslinks forming covalent bonds under the effect of the pH.

6. The composition according to claim 1, wherein said polymer contains side groups of alkali metal or ammonium silanolate or silanolate precursor.

7. The composition according to claim 1, wherein said polymer contains side groups of alkali metal or ammonium silanolate or silanolate precursor, the side groups representing from 1 to 5% of the total dry weight of the said polymer.

8. The composition according to claim 1, wherein said polymer is derived from a polymer selected from the group consisting of cellulose, a nonionic cellulose ether, guar and starch.

9. The composition according to claim 1, wherein said polymer is derived from a polymer selected from the group consisting of cellulose, a nonionic cellulose ether, guar and starch, and said polymer results from the etherification of cellulose or of a derivative thereof with a compound of formula (1) XSi(OZ)₃ where X denotes a halogen atom or a hydrocarbon group containing an epoxy functional group, and Z is selected from the group consisting of a hydrogen atom, an alkali metal and an alkyl group.

10. The composition according to claim 1, wherein the concentration of said self-crosslinkable polymer in the liquid phase is from 1 to 5% by weight.

11. The composition according to claim 1, which is sterile.

14. A kit for the preparation of a composition according to claim 1, which is sterilized, comprising:

a sterile inorganic phase consisting of particles including either hydroxyapatite (A), optionally mixed with β

tricalcium phosphate (B), or calcium titanium phosphate (Ca(Ti)₄ (PO₄)₆) (C), and

a sterile liquid phase comprising an aqueous solution of a water-soluble, biocompatible polymer self-crosslinkable under the effect of the pH of the medium, which are intended to be mixed extemporaneously under sterile atmosphere before implanting of the composition.

12. A method for the preparation of a composition for a biomaterial for resorption/substitution of supporting organic tissues, comprising:

20 to 75% by weight of an inorganic phase consisting of particles including either hydroxyapatite (A), optionally mixed with β

tricalcium phosphate (B), or calcium titanium phosphate (Ca(Ti)₄ (PO₄)₆) (C), and

80 to 25% by weight of a liquid phase including an aqueous solution of a water-soluble, biocompatible polymer self-crosslinkable under the effect of the pH of the medium, comprising the following steps;

preparing a liquid phase by dissolving said polymer in an aqueous solvent,

mixing said inorganic phase with said liquid phase, and

sterilizing the mixture thus obtained.

13. The method according to claim 12, wherein the sterilization is performed in an autoclave at a temperature of 121 or 130°

C.