Coated implantable medical device

• US 20070168012A1
• Filed: 11/27/2006
• Published: 07/19/2007
• Est. Priority Date: 06/07/1995
• Status: Active Grant

• 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, Kozma, Thomas, Fearnot, Neal, Ragheb, Anthony, Voorhees, William
• Granted Patent: US 7,862,605 B2
• Time in Patent Office: Days
• US Class Current: 623/1.110
• 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 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

Methods of making coated implantable medical devices are provided. The methods include positioning a first layer comprising a bioactive on at least a portion of a structure, and positioning at least one porous layer over the first layer. The at least one porous layer has a thickness adequate to provide a controlled release of the bioactive.

Claims

1-26. -26. (canceled)

27. An implantable medical device, comprising:

a structure configured as a stent graft comprising;

an expandable stent in combination with a graft formed of a base material sized and shaped for introduction into a vascular system of a patient, the graft having at least one surface;

a coating layer comprising a first polymer posited between the at least one surface of the graft and at least one bioactive layer;

the at least one bioactive layer comprising a bioactive agent posited over the at least one surface of the graft and under a porous layer;

the porous layer comprising a second polymer posited over the bioactive agent and controlling the release of the bioactive agent, the first polymer and the second polymer being the same or different.

28. The medical device of claim 27, where the graft is configured as a flexible sleeve at least partially covering the expandable stent.

29. The medical device of claim 28, where the flexible sleeve is substantially imperforate and comprises polytetrafluoroethylene.

30. The implantable medical device of claim 27, where the surface is an exterior surface of the medical device positioned to contact the wall of a body vessel upon implantation of the medical device.

31. The implantable medical device of claim 30, where the bioactive layer comprises 1 to 4 mg of bioactive per cm² of gross surface area of the graft.

32. The implantable medical device of claim 27, where the bioactive layer is about 5,000 to 250,000 angstroms thick.

33. The implantable medical device of claim 27, where the coating layer is about 50,000 to 500,000 angstroms thick.

34. The implantable medical device of claim 27, where the stent graft releases the bioactive at a rate of 0.1 to 0.5 mg/cm² of the bioactive agent per day from the bioactive layer through the porous layer upon implantation of the medical device within a body vessel.

35. The implantable medical device of claim 27, where the first polymer comprises a material selected from the group consisting of:

silane, polyimide, poly(ethylene oxide), poly(ethylene glycol), poly(propylene oxide), silicone, polytetrafluoroethylene, polytetramethyldisiloxane, parylene and a polymer of methane and parylene.

36. The medical device of claim 27, where the bioactive material comprises one or more materials selected from the group consisting of:

heparin, hirudin, hirulog, argatroban, D-phenylalanyl-L-poly-L-arginyl chloromethyl ketone, urokinase, streptokinase, aspirin, ticlopdine, colchicine, cytochalasin, methotrexate, dexamethasone, cyclosporin, trapidal, angiopeptin, dopamine, bromocriptine mesylate, pergolide mesylate, silver, captopril, enalapril, ascorbic acid, alphatocopherol, superoxide dismutase, deferoxamine, and a 21-aminosteroid (lasaroid).

37. The medical device of claim 27, wherein the bioactive comprises one or more materials selected from the group consisting of:

a thrombin inhibitor, an antithrombogenic agent, a tissue plasminogen activator, a thrombolytic agent, a fibrinolytic agent, a vasospasm inhibitor, a calcium channel blocker, a nitrate, a nitric oxide promoter, a vasodilator, an antimicrobial agent, an antibiotic agent, a glycoprotein IIb/IIIa inhibitor, an inhibitor of surface glycoprotein receptors, an antiplatelet agent, an antimitotic agent, a microtubule inhibitor agent, a retinoid, an antisecretory agent, an actin inhibitor, a remodeling inhibitor, a deoxyribonucleic acid, an antisense nucleotide, an antiproliferative agent, an anti-cancer chemotherapeutic agent, an anti-inflammatory steroid, a non-steroidal anti-inflammatory agent, an immunosuppressive agent, a PDGF antagonist agent, a growth hormone antagonist agent, an anti-growth factor antibody, a growth factor, a growth factor antagonist, a dopamine agonist agent, a radiotherapeutic agent, a radiopaque agent, a peptide, a protein, an enzyme, an extracellular matrix component, an angiotensin converting enzyme (ACE) inhibitor, a free radical scavenger agent, an iron chelator agent, an antioxidant agent, and a radiolabelled agent.

38. The implantable medical device of claim 27, where the bioactive agent is selected from the group consisting of:

antiplatelet agent, antithrombogenic agent, fibrinolytic agent, antimicrobial agent, antisecratory agent, antiproliferative agent, chemotherapeutic agent, anti-inflammatory agent, immunosuppressive agent, radiotherapeutic agent, radiopaque agent, antiviral agent, and a photodynamic therapy agent.

40. The implantable medical device of claim 27, where the second polymer comprises at least one material selected from the group consisting of:

parylene, poly(n-butyl-acrylate), poly(n-butyl methacrylate), poly 2-ethylhexyl acrylate, poly lauryl-acrylate, poly 2-hydroxy-propyl acrylate, polyvinyl chloride, polyvinyl methyl ether, polyvinylidene fluoride, polyvinylidene chloride, polyacrylonitrile, polystyrene, polyvinyl acetate, ethylenemethyl methacrylate copolymers, acrylonitrile-styrene copolymers, ethylene glycol diacrylate, ethylene glycol dimethacrylate, trimethylopropane triacrylate, trimethylopropane trimethacrylate, pentaerythritol tetraacrylate, pentaerythritol tetramethacrylate, 1,6-hexanediol dimethacrylate, diethyleneglycol dimethacrylate, N-methylol methacrylamide butyl ether, N-vinyl pyrrolidone, vinyl oleate, polyvinyl chloride, polyvinylidene fluoride, Acrylonitrile Butadiene Styrene Resin, poly(hexamethylene adipamide), rayon, rayon-triacetate, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, carboxymethyl cellulose, poly(L-lactic acid), polycaprolactone, poly(lactide-co-caprolactone), poly(lactide-co-glycolide), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), poly(glycolic acid), poly(D,L-lactic acid), poly(glycolic acid-co-trimethylene carbonate), poly(trimethylene carbonate), poly(ethylene oxide), poly(D-lactic acid), fibrin, fibrinogen, cellulose, starch, collagen, phosphatidylcholine, and hyaluronic acid.

41. The implantable medical device of claim 27, where the expandable stent comprises at least one material selected from the group consisting of:

stainless steel, tantalum, titanium, nitinol, gold, platinum, inconel, iridium, silver, tungsten, carbon, carbon fiber, cellulose acetate, cellulose nitrate, silicone, polyethylene teraphthalate, polyurethane, polyamide, polyester, polyorthoester, polyanhydride, polyether sulfone, polycarbonate, polypropylene, polyethylene, polylactic acid, polyglycolic acid, polycaprolactone, and polyhydroxybutyrate valerate.

42. The medical device of claim 28, where the base material comprises a flexible biostable polymer, the sleeve having an exterior surface and a lumen surface defining a lumen;

the coating layer comprising a biostable polymer posited on the exterior surface and having a thickness of about 50,000 to 500,000 angstroms.

43. The medical device of claim 42, where the bioactive layer comprises 1 to 4 mg of bioactive per cm² of gross surface area of the graft, and the bioactive layer has a thickness of about 5,000 to 250,000 angstroms.

44. The medical device of claim 43, where the stent releases the bioactive at a rate of 0.1 to 0.5 mg/cm² of the bioactive agent per day from the bioactive layer through the porous layer upon implantation of the medical device within a body vessel.

45. A method of delivering a bioactive material to a body vessel comprising the steps of:

a. providing a structure configured as a stent graft comprising;

an expandable stent in combination with a graft formed of a base material sized and shaped for introduction into a vascular system of a patient, the graft having at least one surface;

the stent graft shaped for introduction into a vascular system of a patient, the graft having a vessel surface and a lumen surface;

b. depositing a coating layer having a thickness of about 50 to 500,000 angstroms on the vascular surface of the graft, the coating layer consisting of one or more materials selected from the group consisting of;

silane, polyimide, poly(ethylene oxide), poly(ethylene glycol), poly(propylene oxide), silicone, polytetrafluoroethylene, polytetramethyldisiloxane, parylene and a polymer of methane;

c. depositing a bioactive layer having a thickness of about 5,000 to about 250,000 angstroms over the coating layer, the bioactive layer comprising 1 to 4 mg of bioactive per cm² of gross surface area of the graft;

d. depositing a porous layer over the bioactive layer, the porous layer comprising a biostable polymer and having a thickness of about 5,000 to 250,000 angstroms, to form a coated stent graft;

e. inserting the coated stent graft into a body vessel using a catheter; and

f. deploying the coated stent graft within a body vessel by placing the vessel surface of the expandable stent in contact with at least a portion of the body vessel.

46. A method of treating a human or veterinary patient, comprising implanting a coated stent graft at a point of treatment within the vascular system of a human or veterinary patient, the coated stent graft comprising:

a. an expandable stent in combination with a graft formed of a base material sized and shaped for introduction into a vascular system of a patient, the graft having at least one surface;

b. a coating layer comprising a first polymer posited between the at least one surface of the graft and at least one bioactive layer;

c. the at least one bioactive layer comprising a bioactive agent posited over the at least one surface of the graft and under a porous layer;

d. the porous layer comprising a second polymer posited over the bioactive agent and controlling the release of the bioactive agent, the first polymer and the second polymer being the same or different.