Implantable medical devices with antimicrobial and biodegradable matrices

• US 20050283224A1
• Filed: 06/22/2004
• Published: 12/22/2005
• Est. Priority Date: 06/22/2004
• Status: Active Grant

• Current Assignee: Lifeshield Sciences LLC (Acacia Research Corporation)
• Original Assignee: Scimed Life Systems Incorporated (Boston Scientific Corporation)
• Inventors: King, Tamarah L.
• Granted Patent: US 7,794,490 B2
• Time in Patent Office: Days
• US Class Current: 623/1.13
• CPC Class Codes: A61F 2/06 Blood vessels
• CPC Class Codes: A61F 2/07 Stent-grafts
• CPC Class Codes: A61F 2002/072 Encapsulated stents, e.g. wire or whole stent embedded in lining
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body

Abstract

A composite vascular graft is provided, which incorporates bioactive agents that can be controllably delivered to the implantation site to deliver therapeutic materials and/or to reduce infection of the implant. The vascular graft of the present invention includes a luminal layer of ePTFE; and a biodegradable polymer layer including a bioactive agent, such as an antimicrobial agent. The biodegradable polymer layer is posited on the external surface of the luminal ePTFE layer. The graft also includes a fabric layer, which is posited on the external surface of the biodegradable layer. The graft is particularly useful as an arterial-venous graft for hemodialysis procedures.

Claims

1. A vascular graft comprising:

a luminal layer of ePTFE;

a biodegradable polymer layer comprising a bioactive agent, said biodegradable layer being posited on the external surface of said luminal layer; and

a fabric layer posited on the external surface of said biodegradable layer.

2. The vascular graft of claim 1, wherein the bioactive agent is an antimicrobial agent.

3. The vascular graft of claim 1, wherein the antimicrobial agent is an antiseptic agent selected from the group consisting of a silver agent, chlorhexidine, triclosan, iodine, benzalkonium chloride, and combinations thereof.

4. The vascular graft of claim 1, wherein said fabric is of sufficient porosity to allow tissue ingrowth.

5. The vascular graft of claim 4, wherein said fabric porosity is from about 5,000 to about 17,000 on the Wesolowski scale.

6. The vascular graft of claim 1, wherein said ePTFE has an internodal distance of about 70 to about 90 microns.

7. The vascular graft of claim 6, wherein said internodal distance of about 70 to about 90 microns allows for cellular communication between blood and perigraft tissue.

8. The vascular graft of claim 1, wherein said biodegradable layer is comprised of a natural, modified natural or synthetic polymer.

9. The vascular graft of claim 8, wherein said polymer is selected from the group consisting of fibrin, collagen, elastin, celluloses, gelatin, vitronectin, fibronectin, laminin, reconstituted basement membrane matrices, starches, dextrans, alginates, hyaluronic acid, poly(lactic acid), poly(glycolic acid), polypeptides, glycosaminoglycans, their derivatives and mixtures thereof.

10. The vascular graft of claim 8, wherein said polymer is selected from the group consisting of polydioxanones, polyoxalates, poly(α

-esters), polyanhydrides, polyacetates, polycaprolactones, poly(orthoesters), polyamino acids, polyamides and mixtures and copolymers thereof.

11. The vascular graft of claim 8, wherein said polymer is selected from the group consisting of stereopolymers of L- and D-lactic acid, copolymers of bis(p-carboxyphenoxy) propane acid and sebacic acid, sebacic acid copolymers, copolymers of caprolactone, poly(lactic acid)/poly(glycolic acid)/polyethyleneglycol copolymers, copolymers of polyurethane and (poly(lactic acid), copolymers of polyurethane and poly(lactic acid), copolymers of α

-amino acids, copolymers of α

-amino acids and caproic acid, copolymers of α

-benzyl glutamate and polyethylene glycol, copolymers of succinate and poly(glycols), polyphosphazene, polyhydroxy-alkanoates and mixtures thereof.

12. The vascular graft of claim 8, wherein said biodegradable layer is comprised of a synthetic hydrogel polymer.

13. The vascular graft of claim 1, wherein said bioactive agent is controllably released from said biodegradable layer to the site of implantation of said graft by hydrolysis of chemical bonds in said biodegradable polymer.

14. The vascular graft of claim 3, wherein said silver agent comprises silver ions.

15. The vascular graft of claim 3, wherein said silver agent is selected from the group consisting of silver acetate, silver benzoate, silver carbonate, silver iodate, silver iodide, silver lactate, silver laurate, silver nitrite, silver oxide, silver palmitate, silver protein, silver sulfadiazine and combinations thereof.

16. The vascular graft of claim 1, wherein said fabric layer is formed from synthetic yarns selected from the group consisting of polyesters, PET polyesters, polypropylenes, polyethylenes, polyurethanes, polytetrafluoroethylenes and combinations thereof.

17. The vascular graft of claim 1, wherein said fabric layer comprises a textile construction selected from the group consisting of weaves, knits, braids, filament windings, spun fibers and combinations thereof.

18. The vascular graft of claim 1, further comprising an implantable stent between said luminal ePTFE layer and said biodegradable polymer layer.

19. A vascular graft comprising:

a luminal layer of ePTFE having an internodal distance of about 70 to about 90 microns;

a biodegradable polymer layer comprising an antimicrobial agent, said biodegradable layer being posited on the external surface of said luminal layer; and

a fabric layer posited on the external surface of said biodegradable layer, said fabric layer being of sufficient porosity to allow tissue ingrowth to replace the biodegradable polymer layer upon hydrolysis thereof.

20. The vascular graft of claim 19, wherein the antimicrobial agent is a silver agent.

21. The vascular graft of claim 19, wherein said fabric layer has a porosity of about 5,000 to about 17,000 on the Wesolowski scale.

22. The vascular graft of claim 19, wherein said biodegradable layer is comprised of a natural, modified natural or synthetic polymer.

23. The vascular graft of claim 22, wherein said polymer is selected from the group consisting of fibrin, collagen, elastin, celluloses, gelatin, vitronectin, fibronectin, laminin, reconstituted basement membrane matrices, starches, dextrans, alginates, hyaluronic acid, poly(lactic acid), poly(glycolic acid), polypeptides, glycosaminoglycans, their derivatives and mixtures thereof.

24. The vascular graft of claim 22, wherein said polymer is selected from the group consisting of polydioxanoes, polyoxalates, poly(α

-esters), polyanhydrides, polyacetates, polycaprolactones, poly(orthoesters), polyamino acids, polyamides and mixtures and copolymers thereof.

25. The vascular graft of claim 22, wherein said polymer is selected from the group consisting of stereopolymers of L- and D-lactic acid, copolymers of bis(p-carboxyphenoxy) propane acid and sebacic acid, sebacic acid copolymers, copolymers of caprolactone, poly(lactic acid)/poly(glycolic acid)/polyethyleneglycol copolymers, copolymers of polyurethane and (poly(lactic acid), copolymers of polyurethane and poly(lactic acid), copolymers of α

-amino acids, copolymers of α

-amino acids and caproic acid, copolymers of α

-benzyl glutamate and polyethylene glycol, copolymers of succinate and poly(glycols), polyphosphazene, polyhydroxy-alkanoates and mixtures thereof.

26. The vascular graft of claim 22, wherein said biodegradable layer is comprised of a synthetic hydrogel polymer.

27. The vascular graft of claim 19, wherein said fabric layer is formed of synthetic yarns selected from the group consisting of polyesters, PET polyesters, polypropylenes, polyethylenes, polyurethanes, polytetrafluoroethylenes and combinations thereof.

28. The vascular graft of claim 19, wherein said fabric layer comprises a knit textile construction.

29. The vascular graft of claim 20, wherein said silver agent is selected from the group consisting of silver acetate, silver benzoate, silver carbonate, silver iodate, silver iodide, silver lactate, silver laurate, silver nitrite, silver oxide, silver palmitate, silver protein, silver sulfadiazine and combinations thereof.

30. A method of making a vascular graft for controllable delivery of a bioactive agent associated therewith to a site of implantation of said graft, said method comprising:

providing a luminal layer of ePTFE;

positing a biodegradable polymer layer comprising a bioactive agent on the external side of said luminal layer; and

positing a fabric layer on the external surface of said biodegradable layer.

31. The method of claim 30, wherein the bioactive agent is an antimicrobial agent.

32. The method of claim 30, wherein said biodegradable polymer layer is applied as a coating to said luminal layer of ePTFE.

33. The method of claim 32, further comprising the step of incorporating said bioactive agent into said coating.

34. The method of claim 30, further comprising the step of crosslinking said biodegradable polymer layer after the positing of said fabric layer so as to bond said luminal, biodegradable and fabric layers together.

35. The method of claim 34, wherein said crosslinking is via microwave or chemical crosslinking.

36. The method of claim 30, wherein said ePTFE has an internodal distance of about 70 to about 90 microns.

37. The method of claim 30, wherein said biodegradable layer is comprised of a synthetic hydrogel polymer.

38. The method of claim 30, wherein said bioactive agent is controllably released from said biodegradable layer to the site of implantation of said graft by hydrolysis of chemical bonds in the biodegradable polymer.

39. The method of claim 38, wherein said fabric layer is of a porosity to allow sufficient tissue ingrowth to replace said biodegradable polymer following said hydrolysis.

40. The method of claim 30 wherein said bioactive agent in said biodegradable layer is a silver ion.

41. The method of claim 30, wherein said fabric layer is formed of synthetic polyester yarns.

42. The method of claim 30, wherein said fabric layer comprises a textile construction selected from the group consisting of weaves, knits, braids, filament windings, spun fibers and combinations thereof.

43. The method of claim 30 further comprising interposing an implantable prosthetic stent between said luminal and said biodegradable layers.