Methods for using medical devices having nanoporous layers

• US 20060193888A1
• Filed: 02/10/2006
• Published: 08/31/2006
• Est. Priority Date: 11/13/2002
• Status: Active Grant

• Current Assignee: Medtronic Vascular, Inc. (Medtronic Plc), University of Virginia Patent Foundation (University of Virginia)
• Original Assignee: Medtronic Vascular, Inc. (Medtronic Plc)
• Inventors: Wamhoff, Brian R., Spradlin, Joshua, Owens, Gary K., Hudson, Matthew S., Lye, Whye-Kei, Looi, Kareen
• Granted Patent: US 8,449,602 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61F 2/07 Stent-grafts
• CPC Class Codes: A61F 2/91 made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
• CPC Class Codes: A61F 2/915 with bands having a meander structure, adjacent bands being connected to each other
• CPC Class Codes: A61F 2002/91541 Adjacent bands are arranged out of phase
• CPC Class Codes: A61F 2210/0076 multilayered, e.g. laminated structures
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2400/12 Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
• CPC Class Codes: A61L 31/022 Metals or alloys
• 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 31/18 Materials at least partially X-ray or laser opaque
• CPC Class Codes: A61N 1/05 for implantation or insertion into the body, e.g. heart electrode A61N1/06 takes precedence

Abstract

The present invention relates generally to medical devices with therapy eluting components and methods for making same. More specifically, the invention relates to implantable medical devices having at least one porous layer, and methods for making such devices, and loading such devices with therapeutic agents. A mixture or alloy is placed on the surface of a medical device, then one component of the mixture or alloy is generally removed without generally removing the other components of the mixture or alloy. In some embodiments, a porous layer is adapted for bonding non-metallic coating, including drug eluting polymeric coatings. A porous layer may have a random pore structure or an oriented or directional grain porous structure. One embodiment of the invention relates to medical devices, including vascular stents, having at least one porous layer adapted to resist stenosis or cellular proliferation without requiring elution of therapeutic agents. The invention also includes methods, devices, and specifications for loading of drugs and other therapeutic agents into nanoporous coatings.

Claims

1. A method for treating a mammal, comprising:

providing an implantable device comprising a porous surface with an outer surface, an interstitial space, a tortuosity factor of greater than about 1.1, an average thickness of less than 10 microns and a peak-valley surface roughness of less than about 2 microns; and

implanting the implantable device into a location in the body.

2. The method for treating a mammal as in claim 1, wherein the location in the body is a blood vessel.

3. The method for treating a mammal as in claim 1, wherein the location in the body is a portion of the gastrointestinal tract.

4. The method for treating a mammal as in claim 1, wherein the location in the body is a portion of the genitourinary tract.

5. The method for treating a mammal as in claim 1, wherein the location in the body is at least partially in a bone.

6. The method for treating a mammal as in claim 1, wherein the location in the body is at least partially subcutaneous.

7. The method for treating a mammal as in claim 1, wherein the implantable device further comprises a therapeutic agent occupying at least a portion of the interstitial space.

8. The method for treating a mammal as in claim 7, further comprising eluting the therapeutic agent.

9. The method for treating a mammal as in claim 7, wherein the therapeutic agent is selected from a group consisting of:

actinomycin-D, batimistat, c-myc antisense, dexamethasone, paclitaxel, taxanes, sirolimus, tacrolimus and everolimus, unfractionated heparin, low-molecular weight heparin, enoxaprin, bivalirudin, tyrosine kinase inhibitors, Gleevec, wortmannin, PDGF inhibitors, AG1295, rho kinase inhibitors, Y27632, calcium channel blockers, arnlodipine, nifedipine, and ACE inhibitors, synthetic polysaccharides, ticlopinin, dipyridamole, clopidogrel, fondaparinux, streptokinase, urokinase, r-urokinase, r-prourokinase, rt-PA, APSAC, TNK-rt-PA, reteplase, alteplase, monteplase, lanoplase, pamiteplase, staphylokinase, abciximab, tirofiban, orbofiban, xemilofiban, sibrafiban, roxifiban, ABT-578, CC1-779, biolimus-A9, temsirolimus, anti-CD34 antibodies, mycophenolic acid, Vitamin E, omega-3 fatty acids, tempamine, and docetaxel, an agent for altering cytochrome P450 function, cyclosporine, an azole antifungal agent, itraconazole, ketoconazole, a macrolide antibiotic, clarithromycin, erythromycin, troleandomycin, an non-nucleoside reverse transcriptase inhibitor, delavirdine, a protease inhibitor, indinavir, ritonavir, saquinavir, ritonavir, grapefruit juice extract, mifepristone, nefazodone, an anti-restenosis agent, an anti-thrombogenic agent, an antibiotic, an anti-platelet agent, an anti-clotting agent, an anti-inflammatory agent, an anti-neoplastic agent, a chelating agent, penicillamine, triethylene tetramine dihydrochloride, EDTA, DMSA (succimer), deferoxamine mesylate, a radiocontrast agent, a radio-isotope, a prodrug, antibody fragments, antibodies, live cells, therapeutic drug delivery microspheres or microbeads, gene therapy agents, viral vectors and plasmid DNA vectors.

10. The method for treating a mammal as in claim 8, wherein the implantable device further comprises a polymeric topcoat on an outer surface of the porous surface.

11. The method for treating a mammal as in claim 10, wherein the implantable device further comprises a polymeric elution-rate controlling topcoat on the outer surface of the porous surface.

12. The method for treating a mammal as in claim 8, wherein the implantable device further comprises an eluting rate modifying topcoat on an outer surface of the porous surface.

13. The method for treating a mammal as in claim 12, wherein the eluting rate modifying topcoat comprises a material selected from the group consisting of:

polyurethanes, silicones, polyesters, polyolefins, polyisobutylene, ethylene-alphaolefin copolymers, acrylic polymers and copolymers, vinyl halide polymers and copolymers such as polyvinyl chloride, polyvinyl ethers such as polyvinyl methyl ether, polyvinylidene halides such as polyvinylidene fluoride and polyvinylidene chloride, polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics such as polystyrene, polyvinyl esters such as polyvinyl acetate;

copolymers of vinyl monomers, copolymers of vinyl monomers and olefins such as ethylene-methyl methacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins, ethylene-vinyl acetate copolymers, polyamides such as Nylon 66 and polycaprolactone, alkyd resins, polycarbonates, polyoxymethylenes, polyimides, polyethers, epoxy resins, polyurethanes, rayon-triacetate, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, carboxymethyl cellulose, collagens, chitins, polylactic acid, polyglycolic acid, and polylactic acid-polyethylene oxide copolymers, lactone-based copolyesters, polyanhydrides, polyaminoacids, polysaccharides, polyphosphazenes, poly (ether-ester) copolymers, and blends of such polymers, poly (ethylene)vinylacetate, poly(hydroxy)ethylmethylmethacrylate, polyvinal pyrrolidone;

polytetrafluoroethylene, cellulose esters, elastomeric polymers such as silicones (e.g. polysiloxanes and substituted polysiloxanes), polyurethanes, thermoplastic elastomers, ethylene vinyl acetate copolymers, polyolefin elastomers, and EPDM rubbers, EVAL, poly(hydroxyvalerate), poly(L-lactic acid), polycaprolactone, poly(lactide-co-glycolide), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polydioxanone, polyorthoesters, polyanhydride, poly(glycolic acid), poly(D,L-lactic acid), poly(glycolic acid-co-trimethylene carbonate), polyphosphoesters, polyphosphoester urethanes, poly(amino acids), cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), co-poly(ether-esters) (e.g. PEO/PLA), polyalkylene oxalates, polyphosphazenes, biomolecules (such as fibrin, fibrinogen, cellulose, starch, collagen and hyaluronic acid), polyurethanes, silicones, polyesters, polyolefins, polyisobutylene and ethylene-alphaolefin copolymers, acrylic polymers and copolymers, vinyl halide polymers and copolymers (such as polyvinyl chloride), polyvinylidene halides (such as polyvinylidene fluoride and polyvinylidene chloride), polyvinyl ethers (such as polyvinyl methyl-ether), polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics (such as polystyrene), polyvinyl esters (such as polyvinyl acetate), copolymers of vinyl monomers with each other and olefins (such as ethylene-methyl methacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins, and ethylene-vinyl acetate copolymers), polyamides (such as NYLON 66 and polycaprolactam), alkyd resins, polycarbonates, polyoxymethylenes, polyimides, polyethers, epoxy resins, polyurethanes, rayon, rayon-triacetate, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellulose nitrate, cellulose propionate, cellulose ethers, carboxymethyl cellulose, CELLOPHANE, PEG, PEG-acrylate or methacrylate, silk-elastin protein block-copolymer, and mixtures thereof.

14. The method for treating a mammal as in claim 13, wherein the eluting rate modifying topcoat comprises poly(lactide-co-glycolide).

15. The method for treating a mammal as in claim 12, wherein the eluting rate modifying topcoat has a thickness in the range of about 1 micron to about 100 microns.

16. The method for treating a mammal as in claim 15, wherein the eluting rate modifying topcoat has a thickness in the range of about 2 microns to about 15 microns.

17. The method for treating a mammal as in claim 7, wherein the implantable device further comprises a second therapeutic agent occupying at least a portion of the interstitial space.

18. The method for treating a mammal as in claim 17, wherein the second therapeutic agent is a metabolic agent.

19. The method for treating a mammal as in claim 18, wherein the metabolic agent is a cytochrome P450 inhibitor.

20. The method for treating a mammal as in claim 19, wherein the cytochrome P450 inhibitor is ritonavir.

21. A method for treating a mammal, comprising:

providing a nanoporous implantable device with a means for enhancing tissue healing; and

implanting the implantable device into a space in the body.

22. A method for treating a mammal, comprising:

providing a nanoporous implantable device with a means for reduced mechanical slippage and friction with surrounding tissue; and

implanting the implantable device into a location in the body.