ePTFE covering for endovascular prostheses and method of manufacture

• US 20030060871A1
• Filed: 09/25/2001
• Published: 03/27/2003
• Est. Priority Date: 09/25/2001
• Status: Active Grant

• Current Assignee: Lifeshield Sciences LLC (Acacia Research Corporation)
• Original Assignee: Scimed Life Systems Incorporated (Boston Scientific Corporation)
• Inventors: Hill, Jason Peter, Tseng, David, Sogard, David John
• Granted Patent: US 6,827,737 B2
• Time in Patent Office: Days
• US Class Current: 623/1.15
• CPC Class Codes: A61F 2/0077 Special surfaces of prostheses, e.g. for improving ingrowth A61F2/30767 takes precedence
• 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 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/048 obtained 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 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08L 27/18 Homopolymers or copolymers or tetrafluoroethene

Abstract

An implantable composite device for regulated delivery of bioactive agents to the site of implantation includes at least two zones of distinct porosities through its cross-section. One zone is of a sufficient porosity to permit regulated transport of bioactive agents associated with the device to an area of the body in need of treatment. The bioactive agent associated with the device can be either a therapeutic or diagnostic agent. In a particular embodiment of the invention, the device includes a tubular body consisting of a first luminal layer of ePTFE having a porosity sufficient to promote cell endothelization along the luminal surface; and a second polymeric layer disposed on the first layer of a porosity permitting regulated transport of the bioactive agents.

Claims

1. An implantable composite device for regulating delivery of bioactive agents associated therewith to a site of implantation of said device comprising:

(a) a luminal zone of first porosity; and

(b) a second zone of second porosity overlying said luminal zone, said second zone permitting regulated transport of said bioactive agents therethrough.

2. The composite device of claim 1 wherein said second zone has a drug embedded therein.

3. The composite device of claim 1 wherein said second zone has a drug coated thereon.

4. The composite device of claim 1 wherein said second zone includes a reservoir for containing a drug.

5. The composite device of claim 1 having a third zone of third porosity overlying said second zone.

6. The composite device of claim 5 wherein said third zone has a drug embedded therein.

7. The composite device of claim 5 wherein said third zone has a drug coated thereon.

8. The composite device of claim 5 wherein said third zone includes a reservoir formed therein for containing a drug.

9. The composite device of claim 5 further including a reservoir between said second and third zones for containing a drug.

10. The composite device of claim 1 wherein said bioactive agents are selected from the group consisting of growth factors, anti-coagulant substances, stenosis inhibitors, thrombo-resistant agents, antibiotic agents, anti-tumor agents, anti-proliferative agents, growth hormones, antiviral agents, anti-angiogenic agents, angiogenic agents, anti-mitotic agents, anti-inflammatory agents, cell cycle regulating agents, genetic agents, cholesterol-lowering agents, vasodilating agents, agents that interfere with endogenous vasoactive mechanisms, hormones, their homologs, derivatives, fragments, pharmaceutical salts and combinations thereof.

11. The composite device of claim 1 further comprising an implantable stent between said luminal and said second zones.

12. The composite device of claim 5 further comprising an implantable stent between said luminal and said second zones

13. The composite device of claim 5 further comprising an implantable stent between said second and said third zones.

14. The composite device of claim 1 wherein said device is a tubular member.

15. An implantable composite device for regulating delivery of bioactive agents associated therewith to a site of implantation of said device comprising:

(a) a first luminal layer of ePTFE having a first porosity sufficient to promote cell endothelization therealong; and

(b) a second polymeric layer disposed on said first layer, said second layer having a second porosity permitting regulated transport of said bioactive agents therethrough.

16. The composite device of claim 15, wherein said second layer has a drug embedded therein.

17. The composite device of claim 15, wherein said second layer has a drug coated thereon.

18. The composite device of claim 15, wherein said second layer includes a reservoir for containing a drug.

19. The composite device of claim 15 further comprising a third layer of ePTFE having a third porosity wherein said third layer is disposed on said second polymeric layer.

20. The composite device of claim 19, wherein said third layer has a drug embedded therein.

21. The composite device of claim 19, wherein said third layer has a drug coated thereon.

22. The composite device of claim 19, wherein said third layer includes a reservoir formed therein for containing a drug.

23. The composite device of claim 19, further including a reservoir between said second and third zones for containing a drug.

24. The composite device of claim 15 wherein said device is a tubular member.

25. The composite device of claim 15, wherein said second layer comprises ePTFE having pores of an internodal distance from about 5 to about 10 microns.

26. The composite device of claim 25, wherein said second layer has a specific node/fibril geometry of about 5 to about 10 microns.

27. The composite device of claim 19, wherein said third layer exhibits a radial strength in excess of the radial strength of said first layer.

28. The composite device of claim 27, wherein said first layer of ePTFE has pores of an internodal distance of greater than 40 microns and said third layer of ePTFE has pores of an internodal distance of less than 40 microns.

29. The composite device of claim 15, wherein said first layer exhibits a radial strength in excess of the radial strength of said third layer.

30. The composite device of claim 29, wherein said first layer of ePTFE has pores of an internodal distance of less than 40 microns and said third layer of ePTFE has pores of an internodal distance of greater than 40 microns.

31. The composite device of claim 15, further comprising an implantable prosthetic stent between said first and said second layers.

32. The composite device of claim 19, further comprising an implantable prosthetic stent between said first and said second layers.

33. The composite device of claim 19, further comprising an implantable prosthetic stent between said second and said third layers.

34. The composite device of claim 15, wherein said second layer is selected from the group consisting of synthetic polymer, natural polymer or a combination thereof.

35. The composite device of claim 34, wherein said synthetic polymer is selected from the group consisting of ePTFE, polyurethanes, polyacrylamides, polyvinyl alcohols, polyphosphate esters, polyethersulfone, polyorthoesters, polyesters, siloxane polymers, silicones, polyvinylpyrrolidone, polyvinyl ethers, polyethers, polycarbonate, polyalkylenes, polyamides, polyanhydrides, polyethylene oxides, polyvinyl aromatics, polyhydroxybutyrate valerate, polyhydroxybutyrate-co-hydroxyvalerate, polyacrylic acid and derivatives and mixtures thereof.

36. The composite device of claim 34, wherein said natural polymer is selected from the group consisting of fibrin, elastin, celluloses, collagen, gelatin, vitronectin, fibronectin, laminin, reconstituted basement membrane matrices, starches, dextrans, alginates, hyaluronic acid, polylactic acid, polyglycolic acid, polypeptides, glycosaminoglycans, their derivatives and mixtures thereof.

37. The composite device of claim 34, wherein said natural polymer and said synthetic polymer are biostable or bioabsorbable polymers.

38. The composite device of claim 15, wherein said bioactive agents are selected from the group consisting of growth factors, anti-coagulant substances, stenosis inhibitors, thrombo-resistant agents, antibiotic agents, anti-tumor agents, anti-proliferative agents, growth hormones, antiviral agents, anti-angiogenic agents, angiogenic agents, anti-mitotic agents, anti-inflammatory agents, cell cycle regulating agents, genetic agents, cholesterol-lowering agents, vasodilating agents, agents that interfere with endogenous vasoactive mechanisms, hormones, their homologs, derivatives, fragments, pharmaceutical salts and combinations thereof.

39. An implantable composite device for regulating delivery of bioactive agents associated therewith to a site of implantation of said device comprising:

(a) a first luminal layer of ePTFE having pores of an internodal distance of greater than 40 microns; and

(b) a second layer of ePTFE disposed on said first layer, said second layer having pores of an internodal distance from about 5 to about 10 microns and a specific node/fibril geometry of about 5 to about 10 microns, the second layer permitting regulated transport of natural or synthetic bioactive agents therethrough.

40. The implantable composite device of claim 39, further comprising a third layer of ePTFE disposed on said second layer, said third layer having pores of an internodal distance of less than 40 microns.

41. The implantable composite device of claim 39, wherein said second layer further includes a natural polymer selected from the group consisting of fibrin, elastin, celluloses, collagen, gelatin, vitronectin, fibronectin, laminin, reconstituted basement membrane matrices, starches, dextrans, alginates, hyaluronic acid, polylactic acid, polyglycolic acid, polypeptides, glycosaminoglycans, their derivatives and mixtures thereof.

42. The implantable composite device of claim 39, wherein said bioactive agents are selected from the group consisting of growth factors, anti-coagulant substances, stenosis inhibitors, thrombo-resistant agents, antibiotic agents, anti-tumor agents, anti-proliferative agents, growth hormones, antiviral agents, anti-angiogenic agents, angiogenic agents, anti-mitotic agents, anti-inflammatory agents, cell cycle regulating agents, genetic agents, cholesterol-lowering agents, vasodilating agents, agents that interfere with endogenous vasoactive mechanisms, hormones, their homologs, derivatives, fragments, pharmaceutical salts and combinations thereof.

43. The composite device of claim 39 further comprising an implantable prosthetic stent between said first and said second layers.

44. The composite device of claim 40 further comprising an implantable prosthetic stent between said second and said third layers.

45. The composite device of claim 40 further comprising an implantable prosthetic stent between said first and said second layers.

46. An implantable composite device for regulating delivery of bioactive agents to a site of implantation of said device comprising:

(a) a first layer of ePTFE having pores of an internodal distance of less than 40 microns; and

(b) a second layer of ePTFE disposed on said first layer, said second layer having pores of an internodal distance from about 5 to about 10 microns and a specific node/fibril geometry of about 5 to about 10 microns, the second layer permitting regulated transport of natural or synthetic bioactive agents therethrough.

47. The implantable composite device of claim 46, further comprising a third layer of ePTFE disposed on said second layer, said third layer having pores of an internodal distance of greater than 40 microns.

48. The implantable composite device of claim 46, wherein said second layer further includes a natural polymer selected from the group consisting of fibrin, elastin, celluloses, collagen, gelatin, vitronectin, fibronectin, laminin, reconstituted basement membrane matrices, starches, dextrans, alginates, hyaluronic acid, polylactic acid, polyglycolic acid, polypeptides, glycosaminoglycans, their derivatives and mixtures thereof.

49. The implantable composite device of claim 46, wherein said bioactive agents are selected from the group consisting of growth factors, anti-coagulant substances, stenosis inhibitors, thrombo-resistant agents, antibiotic agents, anti-tumor agents, anti-proliferative agents, growth hormones, antiviral agents, anti-angiogenic agents, angiogenic agents, anti-mitotic agents, anti-inflammatory agents, cell cycle regulating agents, genetic agents, cholesterol-lowering agents, vasodilating agents, agents that interfere with endogenous vasoactive mechanisms, hormones, their homologs, derivatives, fragments, pharmaceutical salts and combinations thereof.

50. The composite device of claim 46 further comprising an implantable prosthetic stent between said first and said second layers.

51. The composite device of claim 47 further comprising an implantable prosthetic stent between said second and said third layers.

52. The composite device of claim 47 further comprising an implantable prosthetic stent between said first and said second layers.

53. A method of making an implantable composite device for regulating delivery of bioactive agents associated therewith to a site of implantation of said device, said method comprising:

providing a first luminal layer of ePTFE material of a first porosity; and

disposing a second layer of a natural or synthetic polymeric material of a second porosity onto said first layer, said second layer permitting regulated transport of said bioactive agents therethrough.

54. The method of claim 53, further comprising disposing a third layer of ePTFE material of a third porosity onto said second layer.

55. The method of claim 53, further comprising interposing an implantable prosthetic stent between said first and said second layers.

56. The method of claim 54, further comprising interposing an implantable prosthetic stent between said second and said third layers.

57. The method of claim 54, further comprising interposing an implantable prosthetic stent between said first and said second layers.

58. The method of claim 53, wherein said second layer has a drug embedded therein.

59. The method of claim 53, wherein said second layer has a drug coated thereon.

60. The method of claim 53, wherein said second layer includes a reservoir for containing a drug.

61. The method of claim 54, wherein said third layer has a drug embedded therein.

62. The method of claim 54, wherein said third layer has a drug coated thereon.

63. The method of claim 54, wherein said third layer includes a reservoir formed therein for coating a drug.

64. The method of claim 54, wherein said device includes a reservoir between said second and third zones for containing a drug.

65. The method of claim 53, wherein said second layer comprises ePTFE having pores of an internodal distance from about 5 to about 10 microns.

66. The method of claim 65, wherein said second layer has a specific node/fibril geometry of about 5 to about 10 microns.

67. The method of claim 54, wherein said third layer exhibits a radial strength in excess of the radial strength of said first layer.

68. The method of claim 67, wherein said first luminal layer of ePTFE has pores of an internodal distance of greater than 40 microns and said third layer of ePTFE has pores of an internodal distance of less than 40 microns.

69. The method of claim 54, wherein said first layer exhibits a radial strength in excess of the radial strength of said third layer.

70. The method of claim 69, wherein said first luminal layer of ePTFE has pores of an internodal distance of less than 40 microns and said third layer of ePTFE has pores of an internodal distance of greater than 40 microns

71. The method of claim 53, wherein said second layer is selected from the group consisting of synthetic polymer, natural polymer or a combination thereof.

72. The method of claim 71, wherein said synthetic polymer is selected from the group consisting of ePTFE, polyurethane, polyacrylamide, polyvinyl alcohol, polyphosphate ester, polyhydroxybutyrate valerate, polyhydroxybutyrate-co-hydroxyvalerate, polyacrylic acid, polyethersulfone, polyorthoesters, polyesters, siloxane polymers, silicones, polyvinylpyrrolidone, polyvinyl ethers, polyethers, polycarbonate, polyalkylenes, polyamides, polyanhydrides, polyethylene oxides, polyvinyl aromatics, polyhydroxybutyrate valerate, polyhydroxybutyrate-cohydroxyvalerate, polyacrylic acid and derivatives and mixtures thereof.

73. The method of claim 71, wherein said natural polymer is selected from the group consisting of fibrin, elastin, celluloses, collagen, gelatin, vitronectin, fibronectin, laminin, reconstituted basement membrane matrices, starches, dextrans, alginates, hyaluronic acid, polylactic acid, polyglycolic acid, polypeptides, glycosaminoglycans, their derivatives and mixtures thereof.

74. The method of claim 71, wherein said natural polymer and said synthetic polymer are biostable or bioabsorbable polymers.

75. The method of claim 53, wherein said bioactive agents are selected from the group consisting of growth factors, anti-coagulant substances, stenosis inhibitors, thrombo-resistant agents, antibiotic agents, anti-tumor agents, anti-proliferative agents, growth hormones, antiviral agents, anti-angiogenic agents, angiogenic agents, anti-mitotic agents, anti-inflammatory agents, cell cycle regulating agents, genetic agents, cholesterol-lowering agents, vasodilating agents, agents that interfere with endogenous vasoactive mechanisms, hormones, their homologs, derivatives, fragments, pharmaceutical salts and combinations thereof.