Medical devices having nanoporous bonding layers

• US 20060193887A1
• Filed: 02/10/2006
• Published: 08/31/2006
• Est. Priority Date: 11/13/2002
• Status: Abandoned Application

• 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
• Application Number:
  US11/352,419
• Publication Number:
  US 20060193887A1
• 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 polymer coated drug delivery stent, comprising:

a tubular metal stent body;

a porous layer on the body, wherein the pores of the porous layer have an angular component;

a tie layer which is mechanically bonded to the porous layer; and

a drug delivery layer bonded to the tie layer.

2. The polymer coated drug delivery stent of claim 1, wherein the porous layer is a nanoporous layer.

3. The polymer coated drug delivery stent of claim 2, wherein the porous layer has an average pore size of about 1 nanometer to about 1000 nanometers.

4. The polymer coated drug delivery stent of claim 1, wherein the porous layer is generally configured by the removal of at least one sacrificial material from a matrix comprising at least one sacrificial material with one or more structural materials that comprise the porous layer.

5. The polymer coated drug delivery stent of claim 1, further comprising at least one therapeutic agent in the drug delivery layer.

6. The polymer coated drug delivery stent of claim 5, 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, amlodipine, 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, CCI-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.

7. The polymer coated drug delivery stent of claim 5, further comprising at least two therapeutic agents in the drug delivery layer.

8. The polymer coated drug delivery stent of claim 7, wherein one of the at least two therapeutic agents is a cytochrome P450 inhibitor.

9. The polymer coated drug delivery stent of claim 8, wherein the cytochrome P450 inhibitor is ritonavir.

10. The polymer coated drug delivery stent of claim 1, wherein the drug delivery layer 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.

11. The polymer coated drug delivery stent of claim 10, wherein the drug delivery layer comprises poly(lactide-co-glycolide).

12. The polymer coated drug delivery stent of claim 1, wherein the drug delivery layer has a thickness of about 1 micron to about 100 microns.

13. The polymer coated drug delivery stent of claim 12, wherein the drug delivery layer has a thickness of about 2 microns to about 15 microns.

14. A method of making a drug delivery stent, comprising the steps of:

providing a stent having a porous surface, wherein the pores of the porous surface have an angular component; and

applying a drug delivery layer to the porous surface under conditions which cause a portion of the drug delivery layer to advance into the porous surface to provide a bond between the porous surface and the drug delivery layer.

15. The method of making a drug delivery stent of claim 14, wherein the porous surface is a nanoporous surface.

16. The method of making a drug delivery stent of claim 15, wherein the porous surface has an average pore size of about 1 nanometer to about 1000 nanometers.

17. The method of making a drug delivery stent of claim 14, wherein the porous surface is generally configured by the removal of at least one sacrificial material from a matrix comprising at least one sacrificial material with one or more structural materials that comprise the porous surface.

18. The method of making a drug delivery stent of claim 14, wherein the drug delivery layer comprises an eluting rate controlling material and a therapeutic agent.

19. A method of making a drug delivery stent, comprising the steps of:

providing a stent having a porous surface, wherein the pores of the porous surface have an angular component;

bonding a tie layer to the porous surface; and

bonding a drug delivery layer to the tie layer.

20. The method of making a drug delivery stent of claim 19, wherein the porous surface is a nanoporous surface.

21. The method of making a drug delivery stent of claim 20, wherein the porous surface has an average pore size of about 1 nanometer to about 1000 nanometers.

22. The method of making a drug delivery stent of claim 19, wherein the porous surface is generally configured by the removal of at least one sacrificial material from a matrix comprising at least one sacrificial material with one or more structural materials that comprise the porous surface.

23. A method of reducing the risk of delamination between a stent and a polymeric drug delivery layer during balloon expansion of the stent, comprising the steps of:

providing the stent with a porous surface, wherein the pores of the porous surface have an angular component; and

bonding the drug delivery layer to the porous surface.

24. The method of reducing the risk of delamination between a stent and a polymeric drug delivery layer during balloon expansion of the stent of claim 23, wherein the porous surface is a nanoporous surface.

25. The method of reducing the risk of delamination between a stent and a polymeric drug delivery layer during balloon expansion of the stent of claim 24, wherein the porous surface has an average pore size of about 1 nanometer to about 1000 nanometers.

26. The method of reducing the risk of delamination between a stent and a polymeric drug delivery layer during balloon expansion of the stent of claim 23, wherein the porous surface is generally configured by the removal of at least one sacrificial material from a matrix comprising at least one sacrificial material with one or more structural materials that comprise the porous surface.

27. The method of reducing the risk of delamination between a stent and a polymeric drug delivery layer during balloon expansion of the stent of claim 23, wherein the drug delivery layer is bonded directly to the porous surface.

28. The method of reducing the risk of delamination between a stent and a polymeric drug delivery layer during balloon expansion of the stent of claim 23, wherein the drug delivery layer is bonded to a tie layer which is bonded to the porous surface.

29. A method of reducing the risk of delamination between a stent and a polymeric drug delivery layer during balloon expansion of the stent, comprising the steps of:

providing a stent having a drug delivery layer;

radially dilating the stent; and

retaining the drug delivery layer on the stent by a plurality of links between the drug delivery layer and pores in the stent;

wherein the pores of the stent have an angular component.

30. The method of reducing the risk of delamination between a stent and a polymeric drug delivery layer during balloon expansion of the stent of claim 29, wherein the pores are nanopores.

31. The method of reducing the risk of delamination between a stent and a polymeric drug delivery layer during balloon expansion of the stent of claim 29, wherein the pores are angular pores.

32. The method of reducing the risk of delamination between a stent and a polymeric drug delivery layer during balloon expansion of the stent of claim 30, wherein the pores have an average pore size of about 1 nanometer to about 1000 nanometers.

33. The method of reducing the risk of delamination between a stent and a polymeric drug delivery layer during balloon expansion of the stent of claim 29, wherein the pores are generally configured by the removal of at least one sacrificial material from a matrix comprising at least one sacrificial material with one or more structural materials that comprise at least a portion of the stent.

34. A method of bonding a polymer coating to a biomedical device with nanoporous layer, comprising:

providing a polymeric coating material;

selecting a solvent to dissolve a polymeric coating material for increased penetration/wicking of polymeric materials into a nanoporous coating;

dissolving the polymeric coating material using the selected solvent; and

applying the dissolved polymeric coating material to a nanoporous surface.

35. The method of bonding a polymer coating to a biomedical device with nanoporous layer as in claim 34, wherein the nanoporous coating is a dealloyed nanoporous coating.

36. The method of bonding a polymer coating to a biomedical device with nanoporous layer as in claim 34, wherein the polymeric coating material is selected from a 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.

37. The method of bonding a polymer coating to a biomedical device with nanoporous layer as in claim 36, wherein the polymeric coating material is poly(lactide-co-glycolide).