Compliant tissue sealants

• US 5,900,245 A
• Filed: 09/23/1996
• Issued: 05/04/1999
• Est. Priority Date: 03/22/1996
• Status: Expired due to Term

• Current Assignee: Genzyme Corporation (Sanofi )
• Original Assignee: Focal PLLC
• Inventors: Lyman, Michelle D., Jarrett, Peter K., Rudowsky, Ronald S., Sawhney, Amapreet S.
• Primary Examiner(s): Nutter, Nathan M.
• Application Number:
  US08/710,689
• Time in Patent Office: 953 Days
• Field of Search: 424/426, 424/489, 424/490, 528/354, 528/361, 128/898, 525/54.1, 525/54.2, 525/408, 525/413, 525/415, 514/772.1, 514/772.3, 514/773, 514/777
• US Class Current: 424/426
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 24/0042 Materials resorbable by the body
• 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 26/0019 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: C08G 63/64 Polyesters containing both carboxylic ester groups and carbonate groups
• CPC Class Codes: C08G 63/676 in which at least one of the two components contains aliphatic unsaturation
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

An improved barrier or drug delivery system which is highly adherent to the surface to which it is applied is disclosed, along with methods for making the barrier. In the preferred embodiment, the system is compliant, in that it is capable of conforming to the three dimensional structure of a tissue surface as the tissue bends and deforms during healing processes. The barrier or drug delivery systems is formed as a polymeric coating on tissue surfaces by applied a polymerizable monomer to the surface, and then polymerizing the monomer. The polymerized compliant coating preferably is biodegradable and biocompatible, and can be designed with selected properties of compliancy and elasticity for different surgical and therapeutic applications.

Claims

1. A compliant polymeric material on a tissue surface, wherein the material is formed by

a) contacting the tissue surface with a polymerization initiator,

b) contacting the tissue surface with a solution containing a monomer and a polymerization initiator, and

c) polymerizing the photopolymerizable groups in an interfacial and bulk manner to form a compliant polymeric material.

2. The material of claim 1 wherein the compliant material is a hydrogel,

wherein the monomer is a photopolymerizable, biodegradable, water-soluble block copolymer comprising photopolymerizable groups, and

the polymerization initiator is a free radical polymerization initiator.

3. The material of claim 1 wherein the polymerized material has an elongation at rupture which is similar to or greater than the elongation of the tissue in vivo.

4. The material of claim 1 wherein the polymerized material has an elongation at rupture which is greater than about 100%.

5. The material of claim 1 wherein the polymerized material has an elastic modulus which is less than about 150 kPa.

6. The material of claim 1 wherein the material has an adherence to the surface of at least about 20 grams per square centimeter.

7. The material of claim 1 wherein the material further comprises a biologically active material.

8. The material of claim 1, wherein the normalized compliance ratio of the tissue and the material is in the range of between about 0.05 and 3.

9. The material of claim 1 wherein the material forms a sealant on a tissue surface.

10. The material of claim 1 wherein the material adheres two surfaces together, and wherein at least one of the surfaces is a tissue surface.

11. A kit for the preparation of the compliant material of claim 1, comprising one or more containers each containing one or more of a polymerizable monomer, a priming material and an initiator of polymerization.

29. The material of claim 1 wherein the monomer comprises a polyethylene glycol block with a label average molecular weight of about 8,000, about five lactide monomeric units on average and two acrylate groups.

30. The material of claim 1 wherein the monomer comprises a polyethylene glycol block with a label average molecular weight of about 35,000, about four lactide monomeric units on average and two acrylate groups.

31. The material of claim 1 wherein the monomer comprises a polyethylene glycol block with a label average molecular weight of about 8,000, one or more trimethylene carbonate monomeric units on average.

32. The material of claim 1 wherein the monomer comprises a polyethylene glycol block with a label average molecular weight of about 35,000, about 3.3 caprolactan monomeric units on average and two acrylate groups.

33. The material of claim 1 wherein the monomer comprises a polyethylene glycol block with a label average molecular weight of about 35,000, about eighteen lactide monomeric units on average and two acrylate groups.

34. The material of claim 1 wherein the monomer comprises a polyethylene glycol block with a label average molecular weight of about 35,000, about eight trimethylene carbonate monomeric units on average and two acrylate groups.

35. The material of claim 1 wherein the monomer comprises a polyethylene glycol/polypropylene glycol block, about four trimethylene carbonate monomeric units on average and two acrylate groups.

36. The material of claim 1 wherein the monomer comprises a polyethylene glycol block with a label average molecular weight of about 20,000, about eight trimethylene carbonate monomeric units on average and two acrylate groups.

37. The material of claim 1 wherein the monomer comprises one or more trimethylene carbonate monomeric units.

12. A method for forming a compliant polymeric material on a tissue surface, the method comprising

a) contacting the tissue surface with a polymerization initiator,

b) contacting the tissue surface with a solution containing a monomer and a polymerization initiator, and

c) polymerizing the material on the surface;

wherein the normalized compliance ratio of the tissue and the material is in the range of about 0.05 to about 3.

13. The method of claim 12 wherein the material further forms a sealant on the tissue surface.

14. The method of claim 13 wherein the monomer is a photopolymerizable, biodegradable, water-soluble block copolymer comprising photopolymerizable groups, and

wherein the method comprises photopolymerizing the monomer on the tissue surface in the presence of a free radical polymerization initiator.

15. The method of claim 12 wherein the polymerized material has an elongation at rupture which is similar to or greater than the elongation of the tissue in vivo.

16. The method of claim 12 wherein the polymerized material has an elongation at rupture which is greater than about 100%.

17. The method of claim 12 wherein the polymerized material has an elastic modulus which is less than about 150 kPa.

18. The method of claim 12 wherein the material has an adherence to the surface of at least about 20 grams per square centimeter.

19. The method of claim 12 wherein the material further comprises a biologically active material.

20. The method of claim 12, wherein the normalized compliance ratio of the tissue and the material is in the range of between about 0.05 and 3.

21. The method of claim 19 wherein the method comprises applying the polymerizable monomer and the biologically active material to the surface of a biological tissue and polymerizing the monomer on the tissue to form a polymeric compliant material on the surface incorporating the biologically active material, wherein the material is capable of controlled release of the biologically active material.

22. The method of claim 12 wherein the polymerizable monomer is applied to a plurality of surfaces, at least one of said surfaces being a tissue surface, and wherein the polymerization of the material on the surface causes adhering of the surfaces.

23. The method of claim 13 wherein the compliant polymeric material is formed on the surface of a lung in vivo.

24. A method for forming a compliant polymeric material on a tissue surface, the method comprising:

a) contacting the tissue surface with a polymerization initiator,

b) contacting the tissue surface with a solution containing a monomer and a polymerization initiator, and

c) polymerizing the material on the surface;

wherein one or both of the polymerization initiators is a redox system.

25. The method of claim 24 wherein the redox system comprises a peroxygen compound.

26. The method of claim 24 wherein the redox system comprises a metal ion.

27. The method of claim 26 wherein the metal ion is selected from the group consisting of ferrous ions, ferric ions, cerous ions, ceric ions, cupric ions, cuprous ions, cobaltic ions, cobaltous ions, vanadate V ions, vanadate IV ions, permanganate ions, manganic ions, and manganous ions.

28. The method of claim 26 wherein the metal ion is a lanthanide or actinide ion.