# US 7,410,665 B2 · Coated implantable medical device

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- Number: US 7,410,665 B2
- Document ID: US7410665B2
- Status: Granted
- Kind: B2
- Application number: 10/870,079
- Filed: 2004-06-17
- Published: 2004-12-02
- Granted: 2008-08-12
- Earliest claimed: 1995-06-07
- Assignees: Cook Incorporated; MED Institute, Inc.
- Inventors: Anthony O. Ragheb; Brian L. Bates; Neal E. Fearnot; Thomas G. Kozma; William D. Voorhees, III; Anthony H. Gershlick
- Web page: https://patentgrep.com/patent/US7410665B2

## CPC

- A61L 33/022: {Metal or alloys}
- A61F 2/02: Prostheses implantable into the body
- A61F 2/06: Blood vessels
- 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)
- A61F 2/91: made from perforated sheets or tubes, e.g. perforated by laser cuts or etched holes
- A61K 51/1282: {Devices used in vivo and carrying the radioactive therapeutic or diagnostic agent, therapeutic or in vivo diagnostic kits, stents}
- A61L 27/306: {Other specific inorganic materials not covered by A61L27/303 - A61L27/32}
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61L 29/085: {Macromolecular materials}
- A61L 29/106: {Inorganic materials other than carbon}
- A61L 29/16: Biologically active materials, e.g. therapeutic substances {(A61L29/048 takes precedence)}
- A61L 31/088: {Other specific inorganic materials not covered by A61L31/084 or A61L31/086}
- A61L 31/10: Macromolecular materials
- A61L 31/16: Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)}
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61F 2/0077: {Special surfaces of prostheses, e.g. for improving ingrowth (A61F2/30767 takes precedence)}
- 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}
- A61F 2210/0076: multilayered, e.g. laminated structures
- A61F 2250/0067: Means for introducing or releasing pharmaceutical products into the body
- A61F 2250/0068: the pharmaceutical product being in a reservoir
- A61L 2300/256: Antibodies, e.g. immunoglobulins, vaccines
- A61L 2300/416: Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
- A61L 2300/602: Type of release, e.g. controlled, sustained, slow
- A61L 2300/606: Coatings
- A61L 2300/608: having two or more layers
- A61L 2420/08: Coatings comprising two or more layers
- A61N 5/1002: {Intraluminal radiation therapy}
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)

## 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

### Claim 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.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

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

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 1)

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

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 1)

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.

### Claim 8 (depends on 1)

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.

### Claim 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.

### Claim 10 (depends on 9)

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.

### Claim 11 (depends on 10)

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.

### Claim 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.

### Claim 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.

### Claim 14 (depends on 13)

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.

### Claim 15 (depends on 14)

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

### Claim 16 (depends on 15)

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

### Claim 17 (depends on 13)

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

### Claim 18 (depends on 13)

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

### Claim 19 (depends on 13)

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

### Claim 20 (depends on 13)

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

### Claim 21 (depends on 13)

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.

### Claim 22 (depends on 13)

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

### Claim 23 (depends on 13)

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.