Coated implantable medical device

• US 5,824,049 A
• Filed: 10/31/1996
• Issued: 10/20/1998
• Est. Priority Date: 06/07/1995
• Status: Expired due to Term

• Current Assignee: Cook Medical Technologies, LLC (Cook Group Incorporated)
• Original Assignee: MED Institute, Inc. (Cook Group Incorporated)
• Inventors: Bates, Brian L., Fearnot, Neal E., Kozma, Thomas G., Ragheb, Anthony O., Voorhees, William D. III
• Primary Examiner(s): Yu, Mickey
• Assistant Examiner(s): CUDDIHY, FRANCIS KEVIN
• Application Number:
  US08/741,565
• Time in Patent Office: 719 Days
• Field of Search: 623/1, 623/11, 623/12, 604/53, 604/265, 424/423, 424/426, 514/772.2, 514/772.3, 514/822, 523/112, 523/113
• US Class Current: 623/1.44
• 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 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 2300/602 Type of release, e.g. controlled, sustained, slow
• 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 31/146 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: A61L 33/022 Metal or alloys
• CPC Class Codes: A61N 5/1002 Intraluminal radiation therapy

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 layer 18 of a bioactive material posited on one surface of structure 12; and at least one porous layer 20 posited over the bioactive material layer 18 posited on one surface of structure (12) and the bioactive-material-free surface. Preferably, the structure 12 is a coronary stent. The porous layer 20 is comprised of a polymer applied preferably by vapor or plasma deposition and provides 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, merely by condensation of a monomer vapor. Also disclosed is the method of manufacture of the device 10, as well as a method of using it in medical treatments.

Claims

1. An implantable vascular device, comprising:

A. a stent structure adapted for introduction into a vascular system of a patient, the stent structure comprising a biocompatible metal;

B. at least one bioactive material posited on one surface of the structure of the stent, thereby defining a bioactive-material-free stent surface on which the at least one bioactive material is not posited; and

C. a porous layer posited over the at least one bioactive material and the bioactive-material-free surface, wherein said porous layer is at least about 5000 Å

thick and is adequate to provide for a controlled release of the at least one bioactive material through said porous layer.

2. An implantable medical device (10), comprising,

a structure (12) adapted for introduction into a patient, the structure (12) being comprised of a base material (14);

at least one layer (18) of a bioactive material posited over the structure (12); and

at least one porous layer (20) posited over the at least one bioactive layer (18), comprised of a polymer applied by vapor deposition or plasma deposition, and having for a thickness adequate to provide a controlled release of the at least one bioactive material through said at least one porous layer (20).

3. The device (10) according to claim 2, wherein the at least one porous layer (20) is one polymerized from a catalyst-free monomer vapor.

4. The device (10) according to claim 2, wherein the polymer is a polyimide, parylene, a parylene derivative, poly(ethylene oxide), poly(ethlyene glycol), poly(propylene oxide), silicone, or a polymer of methane, tetrafluoroethylene or tetramethyldisiloxane.

5. The device (10) according to claim 4, wherein the at least one porous layer (20) is about 5,000 to 250,000 Å

thick.

6. The device (10) according to claim 2, wherein the structure (12) is configured as a vascular stent.

7. The device (10) according to claim 2, wherein the structure (12) is configured as at least one of:

a catheter, a wire guide, a cannula, a stent, a vascular or other graft, a cardiac pacemaker lead or lead tip, a cardiac defibrillator lead or lead tip, a heart valve, a pacemaker or portion thereof;

an orthopedic device, appliance, implant or replacement, or portion thereof;

or a portion of any of these.

8. The device (10) according to claim 2, wherein the base material (14) is biocompatible.

9. The device (10) according to claim 8, wherein the base material (14) of the structure (12) includes at least one of:

stainless steel, tantalum, titanium, nitinol, gold, platinum, inconel, iridium, silver, tungsten, or another biocompatible metal, or alloys of any of these;

carbon or carbon fiber;

cellulose acetate, cellulose nitrate, silicone, polyethylene teraphthalate, polyurethane, polyamide, polyester, polyorthoester, polyanhydride, polyether sulfone, polycarbonate, polypropylene, high molecular weight polyethylene, polytetrafluoroethylene, or another biocompatible polymeric material, or mixtures or copolymers of these;

polylactic acid, polyglycolic acid or copolymers thereof, a polyanhydride, polycaprolactone, polyhydroxy-butyrate valerate or another biodegradable polymer, or mixtures or copolymers of these;

a protein, an extracellular matrix component, collagen, fibrin or another biologic agent;

or a mixture of any of these.

10. The device (10) according to claim 2, wherein the bioactive material includes at least one of:

heparin or another thrombin inhibitor, hirudin, hirulog, argatroban, D-phenylalanyl-L-poly-L-arginyl chloromethyl ketone, or another antithrombogenic agent, or mixtures thereof;

urokinase, streptokinase, a tissue plasminogen activator, or another thrombolytic agent, or mixtures thereof;

a fibrinolytic agent;

a vasospasm inhibitor;

a calcium channel blocker, a nitrate, nitric oxide, a nitric oxide promoter or another vasodilator;

an antimicrobial agent or antibiotic;

aspirin, ticlopdine, a glycoprotein IIb/IIIa inhibitor or another inhibitor of surface glycoprotein receptors, or another antiplatelet agent;

colchicine or another antimitotic, or another microtubule inhibitor, dimethylsulfoxide (DMSO), a retinoid or another antisecretory agent;

cytochalasin or another actin inhibitor;

or a remodeling inhibitor;

deoxyribonucleic acid, an antisense nucleotide or another agent for molecular genetic intervention;

methotrexate or another antimetabolite or antiproliferative agent;

an anti-cancer chemotherapeutic agent;

dexamethasone, dexamethasone sodium phosphate, dexamethasone acetate or another dexamethasone derivative, or another anti-inflammatory steroid or nonsteroidal antiinflammatory agent;

cyclosporin or another immunosuppressive agent;

trapidal (a PDGF antagonist), angiopeptin (a growth hormone antagonist), an anti-growth factor antibody, or another growth factor antagonist;

dopamine, bromocriptine mesylate, pergolide mesylate or another dopamine agonist;

⁶⁰ Co, ¹⁹² Ir, ³² P, ¹¹¹ In, ⁹⁰ Y, ^99m Tc or another radiotherapeutic agent;

iodine-containing compounds, barium-containing compounds, gold, tantalum, platinum, tungsten or another heavy metal functioning as a radiopaque agent;

a peptide, a protein, an enzyme, an extracellular matrix component, a cellular component or another biologic agent;

captopril, enalapril or another angiotensin converting enzyme (ACE) inhibitor;

ascorbic acid, alphatocopherol, superoxide dismutase, deferoxamine, a 21-aminosteroid (lasaroid) or another free radical scavenger, iron chelator or antioxidant;

a ¹⁴ C-, ³ H-, ¹³¹ I-, ³² P- or ³⁶ S-radiolabelled form or other radiolabelled form of any of the foregoing;

or a mixture of any of these.

11. The device (10) according to claim 2, wherein the structure (12) has a gross surface area, and wherein the at least one layer (18) of bioactive material contains about 1 to 4 mg of the bioactive material per cm² of the gross surface area of the structure (12).

12. The device (10) according to claim 2, comprising at least two layers (18 and 22) of different bioactive materials posited over the structure (12).

13. The device (10) according to claim 12, further comprising an additional porous layer (24) of the polymer between each of the at least two layers (18 and 22) of different bioactive materials.

14. The device (10) according to claim 12, wherein the different bioactive materials in the at least two layers (18 and 22) have different solubilities, one of the different bioactive Materials being relatively less soluble and another of the different boactive materials being relatively more soluble, and wherein a first layer (18) contains the more soluble bioactive material and a second layer (22) contains the less soluble bioactive material and is posited above the first layer (18).

15. The device (10) according to claim 14, further comprising an additional porous layer (24) of the polymer between each of the at least two layers (18 and 22) of different bioactive materials.

16. The device (10) according to claim 2, further comprising a connector (26) securing the at least one porous layer (20) to the base material (14) of the structure (12).