Coated implantable medical device

• US 7,550,005 B2
• Filed: 08/14/2002
• Issued: 06/23/2009
• Est. Priority Date: 06/07/1995
• Status: Expired due to Fees

• Current Assignee: Cook Medical Incorporated (Cook Group Incorporated)
• Original Assignee: Cook Incorporated (Cook Group Incorporated)
• Inventors: Bates, Brian L., Fearnot, Neal E., Kozma, Thomas G., Ragheb, Anthony O., Voorhees, William D. III
• Primary Examiner(s): PREBILIC, PAUL B
• Application Number:
  US10/218,305
• Publication Number:
  US 20030028243A1
• Time in Patent Office: 2,505 Days
• Field of Search: 623/1.42, 623/1.43, 623/1.15
• US Class Current: 623/1.15
• CPC Class Codes: A61F 2/24 Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61F 2/885 comprising a coil including a plurality of spiral or helical sections with alternate directions around a central axis
• CPC Class Codes: A61F 2/91 made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
• CPC Class Codes: A61F 2210/0076 multilayered, e.g. laminated structures
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• CPC Class Codes: A61K 51/1282 Devices used in vivo and carrying the radioactive therapeutic or diagnostic agent, therapeutic or in vivo diagnostic kits, stents
• CPC Class Codes: A61L 2300/256 Antibodies, e.g. immunoglobulins, vaccines
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 27/306 Other specific inorganic materials not covered by A61L27/303 - A61L27/32
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/106 Inorganic materials other than carbon
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/088 Other specific inorganic materials not covered by A61L31/084 or A61L31/086
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61L 33/022 : Metal or alloys
• CPC Class Codes: A61N 5/1002 : Intraluminal radiation therapy
• CPC Class Codes: C08L 65/04 : Polyxylenes

Abstract

A coated implantable medical device 10 includes a structure 12 adapted for introduction into the vascular system, esophagus, trachea, colon, biliary tract, or urinary tract; at least one coating layer 16 posited on one surface of the structure; and at least one layer 18 of a bioactive material posited on at least a portion of the coating layer 16, wherein the coating layer 16 provides for the controlled release of the bioactive material from the coating layer. In addition, at least one porous layer 20 can be posited over the bioactive material layer 18, wherein the porous layer includes a polymer and provides for the controlled release of the bioactive material therethrough. Preferably, the structure 12 is a coronary stent. The porous layer 20 includes a polymer applied preferably by vapor or plasma deposition and provides for a controlled release of the bioactive material. It is particularly preferred that the polymer is a polyamide, parylene or a parylene derivative, which is deposited without solvents, heat or catalysts, and merely by condensation of a monomer vapor.

Claims

1. A stent comprising:

a plurality of metal arms;

a first arm of the plurality of metal arms, the first arm having a first surface facing in a first direction, and a second surface facing in a second direction generally opposite to the first direction,

a first hole or well formed in the metal of the first arm, the first hole or well having an opening defined in the first surface of the first arm,

a layer within the first hole or well, wherein the layer within the first hole or well comprises a therapeutic agent and extends completely across and at least partially fills the first hole or well,

at least a second hole or well formed in the metal of the first arm, with the second hole or well having an opening defined in the first surface of the arm,

a layer within the second hole or well, wherein the layer within the second hole or well comprises the therapeutic agent and extends completely across and at least partially fills the second hole or well,

a segment of the first arm between the first hole or well and the second hole or well, and

at least portions of the first surface and of the second surface on the segment that are free from any layer that comprises the therapeutic agent.

2. The stent of claim 1, wherein the first hole or well is a hole, and the second hole or well is a hole.

3. The stent of claim 1, wherein the first hole or well is a well, and the second hole or well is a well.

4. The stent of claim 1, wherein the therapeutic agent is an immunosuppressive agent.

5. The stent of claim 1, wherein the therapeutic agent is an antiproliferative agent.

6. The stent of claim 1, wherein the first hole or well and the second hole or well are cut into the metal so as to have substantially the same size and shape.

7. The stent of claim 4, wherein the immunosuppressive agent is cyclosporin.

8. The stent of claim 1, also comprising porous layer material posited over the layer within the first hole or well and over the layer within the second hole or well.

9. The stent of claim 8, wherein the porous layer material comprises parylene or a parylene derivative.

10. The stent of claim 8, wherein the porous layer material comprises a bioabsorbable polymer.

11. The device of claim 10, wherein the bioabsorbable polymer is selected from the group consisting of poly(L-lactic acid), polycaprolactone, poly(lactide-co-glycolide), poly(hydroxybutyrate), poly (hydroxybutyrate-co-valerate), polydioxanone, polyorthoester, polyanhydride, poly(glycolic acid), poly(D,L-lactic acid), poly(glycolic acid-co-trimethylene carbonate), polyphosphoester, polyphosphoester urethane, poly(amino acids), cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), copoly(ether-esters), polyalkylene oxalates, and polyphosphazenes.

12. The device of claim 11, wherein the bioabsorbable polymer is poly(L-lactic acid) or poly(D,L-lactic acid).

13. The device of claim 11, wherein the bioabsorbable polymer is poly(lactideco-glycolide).

14. The stent of claim 8, wherein the porous layer material comprises a biostable polymer.

15. The stent of claim 10, wherein the first hole or well is a hole, and the second hole or well is a hole.

16. A medical device, comprising:

(a) a metal vascular stent having at least a first metal arm;

(b) at least a first aperture in the metal of the arm at a first position, and at least a second aperture in the metal of the arm at a second position, the first position spaced from the second position along a length of the arm;

(c) the first aperture containing a layer comprising a therapeutic agent and extending completely across and at least partially filling the first aperture, and the second aperture containing a layer comprising the therapeutic agent and extending completely across and at least partially filling the second aperture;

(d) first surface portions of a first side of the arm between the first position and the second position, and second surface portions of a second side of the arm between the first position and the second position;

(e) the first surface portions of the first side of the arm and the second surface portions of the second side of the arm free from any layer comprising the therapeutic agent and;

(f) the first aperture having an opening in the first side of the arm, and the second aperture having an opening in the first side of the arm.

17. The device of claim 16, wherein the metal vascular stent is a coronary stent.

18. The device of claim 16, wherein the therapeutic agent is an immunosuppressive agent.

19. The device of claim 16, wherein the therapeutic agent is an antiproliferative agent.

20. The device of claim 16, wherein the first aperture and second aperture are cut into the metal so as to have substantially the same size and shape.

21. The device of claim 16, also comprising porous layer material posited over the layer contained in the first aperture and over the layer contained in the second aperture.

22. The device of claim 21, wherein the porous layer material comprises a bioabsorbable polymer.

23. The device of claim 22, wherein the bioabsorbable polymer is selected from the group consisting of poly(L-lactic acid), polycaprolactone, poly(lactide-co-glycolide), poly(hydroxybutyrate), poly (hydroxybutyrate-co-valerate), polydioxanone, polyorthoester, polyanhydride, poly(glycolic acid), poly(D,L-lactic acid), poly(glycolic acid-co-trimethylene carbonate), polyphosphoester, polyphosphoester urethane, poly(amino acids), cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), copoly(ether-esters), polyalkylene oxalates, and polyphosphazenes.

24. The device of claim 23, wherein the bioabsorbable polymer is poly(L-lactic acid) or poly(D,L-lactic acid).

25. The device of claim 23, wherein the bioabsorbable polymer is poly(lactide-co-glycolide).

26. The device of claim 21, wherein the porous layer material comprises a biostable polymer.

27. The device of claim 16, wherein the apertures are holes.

28. The device of claim 18, wherein the apertures are holes.

29. The device of claim 19, wherein the apertures are holes.

30. The device of claim 16, wherein the apertures are wells.

31. The device of claim 18, wherein the apertures are wells.

32. The device of claim 19, wherein the apertures are wells.

33. A stent comprising:

a plurality of metal arms;

a first hole or well formed in the metal of at least a first arm of the plurality of metal arms;

a layer within the first hole or well, wherein the layer within the first hole or well comprises a therapeutic agent and extends completely across and at least partially fills the first hole or well;

at least a second hole or well formed in the metal of the first arm;

a layer within the second hole or well, wherein the layer within the second hole or well comprises the therapeutic agent and extends completely across and at least partially fills the second hole or well;

a segment of the first arm between the first hole or well and the second hole or well, the segment having a first surface and a second surface opposite the first surface;

at least portions of the first surface and of the second surface of the segment that are free from any layer that comprises the therapeutic agent; and

porous layer material posited over the layer within the first hole or well and over the layer within the second hole or well.

34. The stent of claim 33, wherein the porous layer material comprises parylene or a parylene derivative.

35. The stent of claim 33, wherein the porous layer material comprises a bioabsorbable polymer.

36. The device of claim 35, wherein the bioabsorbable polymer is selected from the group consisting of poly(L-lactic acid), polycaprolactone, poly(lactide-co-glycolide), poly(hydroxybutyrate), poly (hydroxybutyrate-co-valerate), polydioxanone, polyorthoester. polyanhydride, poly(glycolic acid), poly(D,L-lactic acid), poly(glycolic acid-co-trimethylene carbonate), polyphosphoester, polyphosphoester urethane, poly(amino acids), cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), copoly(ether-esters), polyalkylene oxalates, and polyphosphazenes.

37. The device of claim 36, wherein the bioabsorbable polymer is poly(L-lactic acid) or poly(D,L-lactic acid).

38. The device of claim 36, wherein the bioabsorbable polymer is poly(lactide-co-glycolide).

39. The stent of claim 33, wherein the porous layer material comprises a biostable polymer.

40. The stent of claim 35, wherein the first hole or well is a hole, and the second hole or well is a hole.

41. A medical device, comprising:

a metal vascular stent having at least a first metal arm;

at least a first aperture in the metal of the arm at a first position, and at least a second aperture in the metal of the arm at a second position, the first position spaced from the second position along a length of the arm;

the first aperture containing a layer comprising a therapeutic agent and extending completely across and at least partially filling the first aperture, and the second aperture containing a layer comprising the therapeutic agent and extending completely across and at least partially filling the second aperture;

first surface portions of a first side of the arm between the first position and the second position, and second surface portions of a second side of the arm between the first position and the second position;

the first surface portions and the second surface portions free from any layer comprising the therapeutic agent; and

porous layer material posited over the layer contained in the first aperture and over the layer contained in the second aperture.

42. The device of claim 41, wherein the porous layer material comprises a bioabsorbable polymer.

43. The device of claim 42, wherein the bioabsorbable polymer is selected from the group consisting of poly(L-lactic acid), polycaprolactone, poly(lactide-co-glycolide), poly(hydroxybutyrate), poly (hydroxybutyrate-co-valerate), polydioxanone, polyorthoester, polyanhydride, poly(glycolic acid), poly(D,L-lactic acid), poly(glycolic acid-co-trimethylene carbonate), polyphosphoester, polyphosphoester urethane, poly(amino acids), cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), copoly(ether-esters), polyalkylene oxalates, and polyphosphazenes.

44. The device of claim 43, wherein the bioabsorbable polymer is poly(L-lactic acid) or poly(D,L-lactic acid).

45. The device of claim 43, wherein the bioabsorbable polymer is poly(lactide-co-glycolide).

46. The device of claim 41, wherein the porous layer material comprises a biostable polymer.

47. A medical device, comprising:

a metal vascular stent having at least a first metal arm;

at least a first aperture in the metal of the arm at a first position, and at least a second aperture in the metal of the arm at a second position, the first position spaced from the second position along a length of the arm;

the first aperture containing a layer comprising a therapeutic agent and extending completely across and at least partially filling the first aperture;

first surface portions of a first side of the arm between the first position and the second position, and second surface portions of a second side of the arm between the first position and the second position;

the first surface portions and the second surface portions free from any layer comprising the therapeutic agent; and

porous layer material posited over the layer contained in the first aperture.

48. The device of claim 47, wherein the porous layer material comprises a bioabsorbable polymer.

49. The device of claim 48, wherein the bioabsorbable polymer is selected from the group consisting of poly(L-lactic acid), polycaprolactone, poly(lactide-co-glycolide), poly(hydroxybutyrate), poly (hydroxybutyrate-co--valerate), polydioxanone, polyorthoester, polyanhydride, poly(glycolic acid), poly(D,L-lactic acid), poly(glycolic acid-co-trimethylene carbonate), polyphosphoester, polyphosphoester urethane, poly(amino acids), cyanoacrylates, poly(trimethylene carbonate) poly(iminocarbonate), copoly(ether-esters), polyalkylene oxalates, and polyphosphazenes.

50. The device of claim 49, wherein the bioabsorbable polymer is poly(L-lactic acid) or poly(D,L-lactic acid).

51. The device of claim 49, wherein the bioabsorbable polymer is poly(lactide-co-glycolide).

52. The device of claim 47, wherein the porous layer material comprises a biostable polymer.