Coated implantable medical device

• US 7,410,665 B2
• Filed: 06/17/2004
• Issued: 08/12/2008
• Est. Priority Date: 06/07/1995
• Status: Expired due to Fees

• Current Assignee: Cook Medical Technologies, LLC (Cook Group Incorporated)
• Original Assignee: Cook Incorporated (Cook Group Incorporated), MED Institute, Inc. (Cook Group Incorporated)
• Inventors: Bates, Brian L., Fearnot, Neal E., Kozma, Thomas G., Ragheb, Anthony O., Voorhees, William D. III, Gershlick, Anthony H.
• Primary Examiner(s): CAMERON, ERMA C
• Application Number:
  US10/870,079
• Publication Number:
  US 20040243225A1
• Time in Patent Office: 1,517 Days
• Field of Search: 427/2.24, 427/2.25
• US Class Current: 427/2.24
• CPC Class Codes: A61F 2/0077 Special surfaces of prostheses, e.g. for improving ingrowth A61F2/30767 takes precedence
• CPC Class Codes: A61F 2/02 Prostheses implantable into the body closure means for urethra or rectum or for artificial body openings therefor A61F2/0004
• CPC Class Codes: A61F 2/06 Blood vessels
• 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 2/91 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 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• 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 2420/08 Coatings comprising 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: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• 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 method of making a coated implantable medical device, comprising the steps of:

providing a structure adapted for introduction into a human or veterinary patient, the structure being composed of a base material forming a surface;

positioning a coating layer over the surface;

applying a bioactive material comprising a peptide over the surface of the structure by dipping at least a portion of the coating layer positioned over the surface in a fluid mixture comprising the bioactive material; and

positioning at least one porous layer over the bioactive material and the coating layer, the porous layer controlling the release of the bioactive material from the medical device.

2. The method of claim 1, wherein porous layer has a thickness of about 5,000 to 250,000 Angstroms.

3. The method of claim 1, wherein coating layer has a thickness of about 50,000 to 500,000 Angstroms.

4. The method of claim 1, wherein the total amount of bioactive material applied is about 0.1 to 4 mg/cm² of the surface.

5. The method of claim 1, wherein the bioactive material comprises an antibody.

6. The method of claim 1, wherein the coating layer consists essentially of phosphatidylcholine.

7. The method of claim 1, wherein the structure is configured as a vascular stent comprising a biocompatible metal base material;

the coating layer comprises phosphatidylcholine and has a thickness of about 50,000 to 500,000 Angstroms;

the bioactive material comprises an antibody and the total amount of bioactive applied is about 0.1 to 4 mg/cm² of the surface; and

the porous layer has a thickness of about 5,000 to 250,000 Angstroms.

8. The method of claim 1, where the coated implantable medical device contains at least about 0.01 micrograms of the bioactive material per mm² of the surface;

the total amount of the bioactive material applied to the medical device is about 0.1 to 4 mg/cm² of the surface of the coated implantable medical device; and

the coated medical device releases at least half of the bioactive material after perfusion for about 10 days in 1% bovine serum albumin (BSA) in phosphate buffered saline (PBS) at about 10 ml/minute.

9. A method of making a coated implantable medical device, comprising the steps of:

providing a vascular stent adapted for introduction into a blood vessel of a human or veterinary patient, the vascular stent being composed of a base material forming a surface comprising a biocompatible metal;

positioning a coating layer over the surface;

applying a bioactive material comprising an antibody over at least a portion of the structure by dipping at least a portion of the coating layer positioned over the surface in a fluid mixture comprising the bioactive material; and

positioning a porous layer over the bioactive material and the coating layer, the porous layer having a thickness effective to provide a controlled release of the bioactive material through the porous layer.

10. The method of claim 9, further comprising the step of positioning a porous layer comprising phosphatidylcholine over the bioactive material and the coating layer;

and the total amount of bioactive material applied to the medical device is about 0.1 to 4 mg/cm² of the surface of the coated implantable medical device.

11. The method of claim 10, wherein

the coating layer comprises phosphatidylcholine and has a thickness of about 50,000 to 500,000 Angstroms;

the bioactive material comprises a GP IIb/IIIa antibody and the total amount of bioactive applied to the medical device is at least about 0.01 micrograms of the antibody per mm² of the surface; and

the porous layer comprises phosphatidylcholine, and has a thickness of about 5,000 to 250,000 Angstroms.

12. A method of making a coated implantable medical device, comprising the steps of:

providing a structure adapted for introduction into a human or veterinary patient, the structure being composed of a base material forming a surface;

positioning a coating layer over the surface; and

applying a bioactive material comprising a peptide over at least a portion of the structure by contacting a fluid mixture comprising the bioactive material with at least a portion of the coating layer positioned over the surface;

positioning at least one porous layer comprising phosphatidylcholine over the bioactive material, the porous layer providing for a controlled release of the bioactive material through the porous layer.

13. A method of controlling the release of a bioactive material from an implantable medical device having a structure composed of a base material forming a surface and being adapted for introduction into a human or veterinary patient, the method comprising the steps of:

positioning a coating layer of an adsorbent or absorbent material over the surface;

attaching a bioactive material comprising a peptide to the coating layer by dipping at least a portion of the coating layer positioned over the surface in a fluid mixture comprising the bioactive material; and

positioning at least one porous layer over the bioactive material and the coating layer to form a coated medical device, the porous layer controlling the release of the bioactive material from the coated medical device.

14. The method of claim 13, where the bioactive material comprises an antibody and the coated medical device releases at least half of the bioactive material after perfusion for about 10 days in 1% bovine serum albumin (BSA) in phosphate buffered saline (PBS) at about 10 ml/minute.

15. The method of claim 14, where the porous layer comprises phosphatidylcholine.

16. The method of claim 15, where the coating layer has a thickness of about 50 to 500,000 Angstroms.

17. The method of claim 13, wherein the bioactive material comprises a protein.

18. The method of claim 13, wherein the bioactive material comprises an antibody.

19. The method of claim 13, wherein the bioactive material comprises a GP IIb/IIIa antibody.

20. The method of claim 13, wherein the coating layer comprises phosphatidylcholine.

21. The method of claim 13, wherein the base material comprises one or more materials selected from the group consisting of:

stainless steel, tantalum, titanium, nitinol, gold, platinum, a biocompatible metal alloy, iridium, silver, tungsten, carbon, carbon fiber, cellulose acetate, cellulose nitrate, silicone, polyethylene teraphthalate, polyurethane, polyamide, polyester, polyorthoester, polyanhydride, polyether sulfone, polycarbonate, polypropylene, polyethylene, polytetrafluoroethylene, polylactic acid, polyglycolic acid, a polyanhydride, polycaprolactone, polyhydroxybutyrate valerate extracellular matrix, collagen, and fibrin.

22. The method of claim 13, wherein the medical device is configured as a vascular stent.

23. The method of claim 13, wherein the medical device is configured as a vascular stent;

the porous layer comprises phosphatidylcholine; and

the coating layer comprises phosphatidylcholine;

the bioactive material comprises a material selected from the group consisting of;

a protein and an antibody; and

the base material comprises one or more materials selected from the group consisting of;

stainless steel, tantalum, titanium, nitinol, gold, platinum, a biocompatible metal alloy, iridium, silver, tungsten, carbon, carbon fiber, cellulose acetate, cellulose nitrate, silicone, polyethylene teraphthalate, polyurethane, polyamide, polyester, polyorthoester, polyanhydride, polyether sulfone, polycarbonate, polypropylene, polyethylene, polytetrafluoroethylene, polylactic acid, polyglycolic acid, a polyanhydride, polycaprolactone, polyhydroxybutyrate valerate extracellular matrix, collagen, and fibrin.