Bioerodable polymeric adhesives for tissue repair

• US 20020034533A1
• Filed: 09/19/2001
• Published: 03/21/2002
• Est. Priority Date: 04/16/1996
• Status: Active Grant

• Current Assignee: Depuy Products Incorporated (Johnson & Johnson)
• Original Assignee: Dale R. Peterson, Deng Z. David, Todd P. Glancy
• Inventors: Glancy, Todd P., Peterson, Dale R., Deng, Z. David
• Granted Patent: US 6,733,787 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61K 9/204 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 24/0073 with a macromolecular matrix
• CPC Class Codes: A61L 24/0084 containing fillers of phosphorus-containing inorganic compounds, e.g. apatite
• CPC Class Codes: A61L 24/046 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043 takes precedence
• CPC Class Codes: A61L 27/04 Metals or alloys
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/46 with phosphorus-containing inorganic fillers
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: Y10S 528/931 Physical treatment of natural rubber or natural rubber containing material or chemical treatment of non-rubber portion thereof, e.g. extraction of rubber from milk weed

Abstract

Methods for tissue repair are provided employing a matrix comprising a biocompatible, bioerodable polymer, said polymer comprising a thermoplastic lactide-containing terpolymer of monomer units derived from lactic acid, glycolic acid, and either caprolactone or valerolactone, which has a water solubility of about 0.01 to about 500 mg/mL at about 25° C. and adhesive strength of about 600 to about 150,000 Pa and applying the matrix to a tissue defect. The matrix or adhesive can further comprise a filler or a bioactive agent, or both.

Claims

1. A method for repairing bone having a defect comprising the steps of

obtaining a matrix for tissue repair comprising a biocompatible, bioerodable polymer, wherein the polymer has a water solubility of about 0.01 to about 500 mg/mL at about 25°

C. and an adhesive strength of about 600 to about 150,000 Pa so that the matrix is tissue adherent, and

applying the matrix to the defect.

2. The method of claim 1 wherein the polymer has a glass transition temperature of less than 0°

C.

3. The method of claim 1 wherein the matrix further comprises a filler.

4. The method of claim 1 wherein the matrix further comprises a bioactive agent.

5. A method for repairing cartilage comprising the steps of obtaining a matrix for tissue repair comprising a biocompatible, bioerodable polymer, wherein the polymer has a water solubility of about 0.01 to about 500 mg/mL at about 25°

C. and an adhesive strength of about 600 to about 150,000 Pa so that the matrix is tissue adherent, and

applying the matrix to the cartilage.

6. The method of claim 5 wherein the polymer has a glass transition temperature of less than 0°

C.

7. The method of claim 5 wherein the matrix further comprises a filler.

8. The method of claim 5 wherein the matrix further comprises a bioactive agent.

9. A method for repairing a tissue having a defect comprising the steps of

obtaining a matrix for tissue repair, said matrix comprising a thermoplastic terpolymer selected from the group consisting of poly(lactide/glycolide/caprolactone) and poly(lactide/glycolide/valerolactone), said terpolymer having an average molecular weight of 1,000 to 3,000, exhibiting an adhesive strength of about 600 to about 150,000 Pa and having a water solubility of 0.01 to about 500 mg/ml at about 25°

C., and

applying the matrix to the defect.

10. The method of claim 9 wherein the tissue is selected from the group consisting of bone and cartilage.

11. The method of claim 9 wherein the terpolymer is poly(lactide/glycolide/caprolactone).

12. The method of claim 11 wherein the terpolymer comprises about 35-45% lactide, about 35-45% glycolide, and about 10 to about 30% caprolactone.

13. The method of claim 12 wherein the terpolymer has a glass transition temperature of less than 0°

C.

14. The method of claim 9 wherein the matrix further comprises a filler.

15. The method of claim 14 wherein the filler is selected from the group consisting of bone chips, tricalcium phosphate, hydroxylapatite, small intestine submucosa, bioglass granules, synthetic polymers, calcium carbonate, calcium sulfate and collagen.

16. The method of claim 9 wherein the matrix further comprises a bioactive agent.

17. The method of claim 16 wherein the bioactive agent is a growth factor.

18. The method of claim 17 wherein the growth factor is selected from the group consisting of a fibroblast growth factor, a transforming growth factor, a bone morphogenetic protein, an epidermal growth factor, a platelet-derived growth factor or an insulin-like growth factor.

19. The method of claim 9 wherein the matrix is provided as a moldable putty.

20. In the method of repairing tissue using a bioerodable implant matrix, the improvement comprising using a matrix to repair the defect, wherein the matrix comprises a biocompatible, bioerodable polymer, wherein the polymer has a water solubility of about 0.01 to about 500 mg/mL at about 25°

C. and an adhesive strength of about 600 to about 150,000 Pa so that the matrix is tissue adherent.

21. The method of claim 20 wherein the tissue is selected from the group consisting of bone, joint, and cartilage.

22. An implantable article of manufacture for use in the release of a bioactive agent into a physiological environment, said article comprising a matrix,

said matrix comprising

a biocompatible, bioerodable polymer, wherein the polymer has a water solubility of about 0.01 to about 500 mg/mL at about 25°

C. and an adhesive strength of about 600 to about 150,000 Pa so that the matrix is tissue adherent, and

a bioactive agent.

23. The article of claim 22 wherein the bioactive agent is a growth factor.

24. The article of claim 22 wherein the polymer is poly(lactide/glycolide/caprolactide).