Coated implantable medical device

• US 5,609,629 A
• Filed: 06/07/1995
• Issued: 03/11/1997
• Est. Priority Date: 06/07/1995
• Status: Expired due to Term

• Current Assignee: Cook Medical Incorporated (Cook Group Incorporated)
• Original Assignee: MED Institute, Inc. (Cook Group Incorporated)
• Inventors: Voorhees, William D., Fearnot, Neal E., Kozma, Thomas G., Ragheb, Anthony O.
• Primary Examiner(s): Weiss, John G.
• Assistant Examiner(s): CUDDIHY, FRANCIS KEVIN
• Application Number:
  US08/484,532
• Time in Patent Office: 643 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: 623/1.42
• 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 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• 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 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 29/146 Porous materials, e.g. foams or sponges
• 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
• CPC Class Codes: C08L 27/18 Homopolymers or copolymers or tetrafluoroethene
• CPC Class Codes: C08L 65/04 Polyxylenes
• CPC Class Codes: C08L 71/00 Compositions of polyethers obtained by reactions forming an ether link in the main chain of polyacetals C08L59/00; of epoxy resins C08L63/00; of polythioether-ethers C08L81/02; of polyether-sulfones C08L81/06; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 77/00 : Compositions of polyamides obtained by reactions forming a carboxylic amide link in the main chain of polyhydrazides C08L79/06; of polyamideimides or polyamide acids C08L79/08; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 83/04 : Polysiloxanes

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 positioned over the structure 12; and at least one porous layer 20 positioned over the bioactive material layer 18. Preferably, the structure 12 is a coronary stent, and the bioactive material is at least one of heparin, dexamethasone or a dexamethasone derivative. The device 10 includes layers 18 and 22 of heparin and dexamethasone, the layer 22 of dexamethasone being positioned above the layer 18 of heparin. The layers of bioactive material also can be individual materials or a combination of different materials. Unexpectedly, the more soluble heparin markedly promotes the release of the less soluble dexamethasone above it. The porous layer 20 is composed of a polymer applied by vapor or plasma deposition and provides a controlled release of the bioactive material. It is particularly preferred that the polymer is a polyimide, parylene or a parylene derivative, which is deposited without solvents, heat or catalysts, merely by condensation of a monomer vapor.

Claims

1. An implantable medical device (10) comprising:

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

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

at least one porous layer (20) positioned over the bioactive material (18), composed of a polymer applied by vapored deposition or plasma deposition, and being of a thickness adequate to provide a controlled release of the bioactive material; and

at least one additional coating layer (16) applied to the base material (14) and being less porous than, but composed of the same polymer as, at least one porous layer (20).

2. The device (10) according to claim 1, wherein the at least one porous layer (20) is one polymerized from a catalyst-free monomer vapor.

3. The device (10) according to claim 1, wherein the thickness of the at least one porous layer (20) is about 5,000 to 250,000 Å

.

4. The device (10) according to claim 1, wherein the polymer is polyimide, parylene or a parylene derivative, and the at least one additional coating layer (16) is about 50,000 to 500,000 Å

thick.

5. The device (10) according to claim 1, wherein the structure (12) is configured as a vascular stent.

6. The device (10) according to claim 1, 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 suture, or a needle;

an angioplasty device or portion thereof;

a pacemaker or portion thereof;

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

or a portion of any of these.

7. The device (10) according to claim 1, wherein the base material (14) is biocompatible.

8. The device (10) according to claim 1, 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.

9. The device (10) according to claim 1, 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 remodelling 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 non-steroidal 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.

10. The device (10) according to claim 1, 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).

11. The device (10) according to claim 1, comprising at least two layers (18 and 22) of different bioactive materials positioned over the structure (12).

12. The device (10) according to claim 11, 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.

13. The device (10) according to claim 11, wherein the at least two different bioactive materials have different solubilities, and the layer (22) containing the less soluble bioactive material is positioned above the layer (18) containing the more soluble bioactive material.

14. The device (10) according to claim 13, 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.

15. The device (10) according to claim 1, further comprising a connector (26) securing the at least one porous layer (20) to the base material (14) of the structure (12).

16. An implantable medical device (10) comprising:

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

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

at least one porous layer (20) positioned over the bioactive material (18), composed of a polymer applied by vapored deposition or plasma deposition, and being of a thickness adequate to provide a controlled release of the bioactive material; and

wherein said device (10) comprises an additional layer of a different bioactive material (22) positioned over the structure (12).

17. The device (10) according to claim 16, 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.

18. The device (10) according to claim 16, wherein the at least two different bioactive materials have different solubilities, and the layer (22) containing the less soluble bioactive material is positioned above the layer (18) containing the more soluble bioactive material.

19. The device (10) according to claim 16, 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.