CA2576223A1

CA2576223A1 - A moisture curable, isocyanate-functional medical adhesive and methods of tissue adhesion

Info

Publication number: CA2576223A1
Application number: CA002576223A
Authority: CA
Inventors: Eric J. Beckman; Michael Buckley; Sudha Agarwal; Jianying Zhang
Original assignee: Individual
Current assignee: University of Pittsburgh
Priority date: 2004-05-27
Filing date: 2004-05-27
Publication date: 2005-12-15
Anticipated expiration: 2024-05-27
Also published as: CN1968718A; AU2004320265A2; WO2005118011A1; ZA200609694B; AU2004320265B2; CA2576223C; RU2346704C2; NZ550970A; AU2004320265A1; MXPA06013721A; CN1968718B; EP1755693A1; RU2006144819A; JP2008500095A; IL179643A0; BRPI0418804A

Abstract

An adhesive including a mixture of isocyanate capped molecules formed by reacting multi-isocyanate functional molecules with multi-functional precursor molecules including terminal functional groups selected from the group consisting of a hydroxyl group, a primary amino group and a secondary amino group. Preferably, the functional groups are hydroxyl groups. The multi-functional precursor compounds are biocompatible. Multiamine functional precursors of the multi-isocyanate functional molecules are also biocompatible. As discussed, above, the mixture of molecules preferably has an average isocyanate functionality of at least 2.1 and, more preferably, has an average isocyanate functionality of at least 2.5. As also described above, the mixture of molecules preferably has a viscosity in the range of approximately 1 to approximately 100 centipoise. The mixture of molecules forms a crosslinked polymer network upon contact with the organic tissue in the presence of water. The crosslinked polymer network is biocompatible and biodegradable. The crosslinked polymer network degrades into degradation products including the precursor molecules and the multi-amine functional precursors.

Claims

1. A method of applying an adhesive to organic tissue, comprising the step of applying a mixture of molecules to the organic tissue, the molecules having terminal isocyanate functional groups, the mixture of molecules having an average isocyanate functionality of at least 2.1, the mixture of molecules having a viscosity in the range of approximately 1 to approximately 100 centipoise, the mixture of molecules forming a crosslinked polymer network upon contact with the organic tissue in the presence of water, the crosslinked polymer network being biocompatible and biodegradable, the crosslinked polymer network biodegrading into molecules that are biocompatible.

2. The method of Claim 1 wherein the average isocyanate functionality of the mixture of molecules is at least 2.5.

3. The method of Claim 1 wherein the mixture of molecules includes lysine tri-isocyanate or a lysine tri-isocyanate derivative.

4. The method of Claim 1 wherein the mixture of molecules includes lysine tri-isocyanate ethyl ester.

5. The method of Claim 1 wherein the mixture of molecules includes isocyanate capped molecules formed by reacting multi-isocyanate functional molecules with multi-functional precursor molecules including terminal functional groups selected from the group consisting of a hydroxyl group, a primary amino group and a secondary amino group, the multi-functional precursor compounds being biocompatible, multi-amine functional precursors of the multi-isocyanate functional molecules also being biocompatible.

6. The method of Claim 5 wherein the multi-amine functional precursors of the multi-isocyanate functional molecules are biocompatible amino acids or biocompatible derivatives of amino acids.

7. The method of Claim 5 wherein the multi-functional precursor molecules include at least one of polyethylene glycol, a polyamino acid, an aliphatic polyester, a saccharide, a polysaccharide, an aliphatic polycarbonate, a polyanhydride, a steroid, glycerol, ascorbic acid, an amino acid, or a peptide.

8. The method of Claim 7 wherein the multi-functional precursor molecules include polyethylene glycol and the multi-isocyanate functional molecules include at least one of lysine di-isocyanate ethyl ester or lysine tri-isocyanate ethyl ester.

9. The method of Claim 8 wherein the multi-functional precursor molecules further include glucose.

10. The method of Claim 8 wherein the polyethylene glycol has number average molecular weight less than 10,000.

11. The metliod of Claim 8 wherein the polyethylene glycol has number average molecular weight less than 2,000.

12. The method of Claim 8 wherein the polyethylene glycol has number average molecular weight less than 1,000.

13. The method of Claim 1 wherein the mixture of molecules forms a crosslinked polymer network in less than two minutes.

14. The method of Claim 1 wherein the crosslinked polymer network biodegrades in approximately 7 to apprxomately 14 days.

15. An adhesive, comprising a mixture of isocyanate capped molecules formed by reacting multi-isocyanate functional molecules with multi-functional precursor molecules including terminal functional groups selected from the group consisting of a hydroxyl group, a primary amino group and a secondary amino group, the multi-functional precursor compounds being biocompatible, multi-amine functional precursors of the multi-isocyanate functional molecules also being biocompatible, the mixture of molecules having an average isocyanate functionality of at least 2.1, the mixture of molecules having a viscosity in the range of approximately 1 to approximately 100 centipoise, the mixture of molecules forming a crosslinked polymer network upon contact with the organic tissue in the presence of water, the crosslinked polymer network being biocompatible and biodegradable, the crosslinked polymer network degrading into degradation products including the precursor molecules and the multi-amine functional precursors.

16. The adhesive of Claim 15 wherein the average isocyanate functionality of the mixture of molecules is at least 2.5.

17. The adhesive of Claim 15 wherein the mixture of molecules includes lysine tri-isocyanate or a lysine tri-isocyanate derivative.

18. The adhesive of Claim 15 wherein the mixture of molecules includes lysine tri-isocyanate ethyl ester.

19 19. The adhesive of Claim 15 wherein the multi-amine functional precursors of the multi-isocyanate functional molecules are biocompatible amino acids or biocompatible derivatives of amino acids.

20. The adhesive of Claim 15 wherein the multi-functional precursor molecules include at least one of polyethylene glycol, a polyamino acid, an aliphatic polyester, a saccharide, a polysaccharide, an aliphatic polycarbonate, a polyanhydride, a steroid, glycerol, ascorbic acid, an amino acid, or a peptide.

21. The adhesive of Claim 20 wherein the multi-functional precursor molecules include polyethylene glycol and the multi-isocyanate functional molecules include at least one of lysine di-isocyanate ethyl ester or lysine tri-isocyanate ethyl ester.

22. The adhesive of Claim 21 wherein the multi-functional precursor molecules further include glucose.

23. The adhesive of Claim 21 wherein the polyethylene glycol has number average molecular weight less than 10,000.

24. The adhesive of Claim 21 wherein the polyethylene glycol has number average molecular weight less than 2,000.

25. The adhesive of Claim 21 wherein the polyethylene glycol has number average molecular weight less than 1,000.

26. The adhesive of Claim 21 wherein the mixture of molecules forms a crosslinked polymer network in less than two minutes.

27. The adhesive of Claim 21 wherein the crosslinked polymer network biodegrades approximately 7 to apprxomately 14 days.

28. An adhesive, comprising a mixture of isocyanate capped prepolymers formed by reacting multi-isocyanate functional molecules with multi-functional precursor molecules including terminal functional groups selected from the group consisting of a hydroxyl group, a primary amino group and a secondary amino group, the multi-functional precursor compounds being biocompatible, multi-amine functional precursors of the multi-isocyanate functional molecules also being biocompatible, at least one of the multi-functional precursors being a flexible biocompatible polymer having a number average molecular weigh of at least 50, the mixture of prepolymers having an average isocyanate functionality of at least 2.1, the mixture of prepolymer being spreadable, the mixture of prepolymers forming a crosslinked polymer network upon contact with the organic tissue in the presence of water, the crosslinked polymer network being biocompatible and biodegradable, the crosslinked polymer network degrading into degradation products including the precursor molecules and the multi-amine functional precursors.

29. The adhesive of Claim 28 wherein at least one polymeric multi-functional precursor is polyethylene glycol.

30. The adhesive of Claim 28 wherein at least one other of the multi-functional precursor is molecule having three of more hydroxyl groups.

31. The adhesive of Claim 30 wherein the at least one polymeric multi-functional precursor is a sugar.