Silver implantable medical device

• US 5,873,904 A
• Filed: 02/24/1997
• Issued: 02/23/1999
• Est. Priority Date: 06/07/1995
• Status: Expired due to Term

• Current Assignee: Cook Medical Incorporated (Cook Group Incorporated)
• Original Assignee: Cook Incorporated (Cook Group Incorporated), MED Institute, Inc. (Cook Group Incorporated)
• Inventors: Roberts, Joseph W., Bates, Brian L., Fearnot, Neal E., Kozma, Thomas G., Ragheb, Anthony O., Voorhees, William D. III, Osborne, Thomas A.
• Primary Examiner(s): Yu, Mickey
• Assistant Examiner(s): CUDDIHY, FRANCIS KEVIN
• Application Number:
  US08/803,843
• Time in Patent Office: 729 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: 623/1.13
• 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 silver implantable medical device 29 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. Also included is a layer or impregnation of silver 45. 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. Silver is included as a base material, coating or included in a carrier, drug, medicant material utilized with the implantable stent.

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 posited on at least one surface of the structure (12);

at least one porous layer (20) posited over the layer (18) of bioactive material and composed of a polymer to provide for a controlled release of the bioactive material therethrough; and

an antiproliferative agent selected from the group consisting of elemental silver, silver alloys, silver ions and other silver containing materials and included in or on at least one of said base material, said bioactive material, and said polymer.

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 polymer is selected from the group consisting of a polyamide, polymers of parylene or derivatives thereof, poly(ethylene oxide), poly(ethylene glycol), poly(propylene oxide), silicone based polymers, polymers of methane, tetrafluoroethylene or tetramethyldisiloxane or a polymer derived from photopolymerizeable monomers.

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

.

5. The device (10) according to claim 1, further comprising at least one additional coating layer (16) between the structure (12) and the at least one bioactive material layer (18).

6. The device (10) according to claim 5, wherein the at least one additional coating layer (16) is less porous than the at least one porous layer (20).

7. The device (10) according to claim 6, wherein the polymer is selected from the group consisting of polyamide, polymers of parylene or derivatives thereof, or a polymer derived from photopolymerizable monomers of bisphenol A diglycidyl ether and acrylic acid or methacrylic acid, and the at least one additional coating layer (16) is about 50,000 to 500,000 Å

thick.

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

9. The device (10) according to claim 1, wherein the structure (12) is configured as at least one of:

a stent, a vascular or other graft, a vascular or other graft in combination with a stent, heart valve, an orthopedic device, appliance, implant or replacement, or portion thereof;

or a portion of any of these.

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

11. The device (10) according to claim 10, 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 thereof;

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 thereof.

12. The device (10) according to claim 1, wherein the bioactive material includes at least one of:

heparin, covalent 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, ticlopidine, a glycoprotein IIb/IIIa inhibitor or another inhibitor of surface glycoprotein receptors, or another antiplatelet agent;

colchicine or another antimitotic, or another microtubule inhibitor, dimethyl sulfoxide (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;

tamoxifen citrate, Taxol®

or derivatives thereof, or other anti-cancer chemotherapeutic agents;

dexamethasone, dexamethasone sodium phosphate, dexamethasone acetate or another dexamethasone derivative, or another anti-inflammatory steroid or non-steroidal anti-inflammatory agent;

cyclosporin or another immunosuppressive agent;

trapidal (a PDGF antagonist), angiogenin, angiopeptin (a growth hormone antagonist), a growth factor or 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, alpha tocopherol, superoxide dismutase, deferoxamine, a 21-amino steroid (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;

estrogen or another sex hormone;

AZT or other antipolymerases;

acyclovir, famciclovir, rimantadine hydrochloride, ganciclovir sodium or other antiviral agents;

5-aminolevulinic acid, meta-tetrahydroxyphenylchlorin, hexadecafluoro zinc phthalocyanine, tetramethyl hematoporphyrin, rhodamine 123 or other photodynamic therapy agents;

an IgG2 Kappa antibody against Pseudomonas aeruginosa exotoxin A and reactive with A431 epidermoid carcinoma cells, monoclonal antibody against the noradrenergic enzyme dopamine beta-hydroxylase conjugated to saporin or other antibody targeted therapy agents;

gene therapy agents; and

enalapril and other prodrugs, or a mixture of any of these.

13. The device (10) according to claim 1, wherein the structure (12) has a gross surface area, and wherein the at least one layer (18) of bioactive material contains about 0.01 to about 4 mg of the bioactive material per cm² of the gross surface area of the structure (12).

14. The device (10) according to claim 1, wherein the structure (12) includes different surfaces, and wherein different bioactive materials are posited on the different surfaces of the structure (12).

15. The device (10) according to claim 1, wherein the layer (18) of bioactive material is posited on one surface of the structure (12) and thereby defines a bioactive-material-free surface of the structure (12) different from the one surface of the structure (12), the porous layer (20) is posited over the layer (18) of bioactive material on the one surface of the structure (12) and over the bioactive-material-free surface of the structure (12), and a second bioactive material is posited on the porous layer (20) and forms an outermost layer for the device (10).

16. The device (10) according to claim 15, wherein a different and third bioactive material is posited on the bioactive-material-free surface of the structure (12), the porous layer (20) being posited over the first-mentioned bioactive material and the third bioactive material;

and wherein the second bioactive material forming the outermost layer for the device (10) is covalent heparin bound to the porous layer (20).

17. The device (10) according to claim 1, wherein the structure (12) includes a plurality of different surfaces, and wherein the device (10) comprises either a single bioactive material on one of the different surfaces of the structure (12), or a plurality of different bioactive materials on the different surfaces of the structure (12) with the porous layer (20) over said bioactive material or materials so that a second of the plurality of bioactive materials forms an outermost layer of the device (10) over the porous layer (12).

18. The device (10) according to claim 1, wherein the structure (12) has a plurality of different surfaces, and wherein individual ones of a plurality of layers of different bioactive materials are posited on the different surfaces of the structure (12) with the provisos that (a) the same bioactive material is not posited on different surfaces of the structure (12) within the same individual one of the plurality of different layers of bioactive materials, and (b) either a porous layer or a bioactive material layer may form an outermost layer for the device (10).

19. The device according to claim 5, wherein a highly pure elemental silver layer having a uniform thickness is posited on the at least one porous layer (20).

20. The device according to claim 1, wherein the polymer composing the at least one porous layer (20) forms a matrix having highly pure elemental silver, silver ions or a combination thereof impregnated therein.

21. The device according to claim 1, wherein said device is a balloon expandable vascular stent.

22. The device according to claim 1, wherein said device is a self-expanding vascular stent.

23. The device (10) according to claim 6, wherein the at least one additional coating layer (16) is composed of the same polymer as the at least one porous layer (20).

24. The device (10) according to claim 6, wherein the at least one additional coating layer (16) is composed of a different polymer than the at least one porous layer (20).

25. 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 posited on at least one surface of the structure (12);

at least one porous layer (20) posited over the layer (18) of bioactive material and composed of a polymer to provide for a controlled release of the bioactive material therethrough;

an antiproliferative agent selected from the group consisting of elemental silver, silver alloys, silver ions and other silver containing materials and included in or on at least one of said base material, said bioactive material, and said polymer; and

at least one additional coating layer (16) between the structure (12) and the at least one bioactive material layer (18);

wherein the at least one additional coating layer (16) is less porous than the at least one porous layer (20).

26. The device (10) according to claim 25, wherein the polymer is selected from the group consisting of polyamide, polymers of parylene or derivatives thereof, or a polymer derived from photopolymerizable monomers of bisphenol A diglycidyl ether and acrylic acid or methacrylic acid, and the at least one additional coating layer (16) is about 50,000 to 500,000 Å

thick.

27. The device (10) according to claim 25, wherein the at least one additional coating layer (16) is composed of the same polymer as the at least one porous layer (20).

28. The device (10) according to claim 25, wherein the at least one additional coating layer (16) is composed of a different polymer than the at least one porous layer (20).