BIORESORBABLE METAL STENT WITH CONTROLLED RESORPTION

• US 20110076319A1
• Filed: 01/30/2008
• Published: 03/31/2011
• Est. Priority Date: 01/30/2007
• Status: Abandoned Application

• Current Assignee: Eurocor GmbH (Opto Circuits (India) Ltd.)
• Original Assignee: Eurocor GmbH (Opto Circuits (India) Ltd.)
• Inventors: Rübben, Alexander, Orlowski, Michael
• Application Number:
  US12/524,702
• Publication Number:
  US 20110076319A1
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61L 31/022 Metals or alloys
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Embodiments herein relate to a special form of a bioresorbable metal stent with controlled resorption due to a wrap with a special polymer, thereby ensuring a controlled resorption of the wrapped endoprosthesis subsequent to its implantation into a blood vessel. The resorbable implant comprises a magnesium alloy provided with a biodegradable coating. The biodegradable coating comprises biodegradable polymers and can further include at least one pharmacologically active substance such as an antiproliferative, antimigrative, antiangiogenic, antiinflammatory, antiphlogistic, cytostatic, cytotoxic and/or antithrombotic agent, anti-restenosis agents, corticoids, sex hormones, statins, epothilones, prostacyclins and/or inductors of angiogenesis.

Claims

1. Resorbable implant, wherein the resorbable implant comprises to an extent of 40% by weight to 90% by weight of magnesium contained in a magnesium alloy and wherein the resorbable implant is covered with a biodegradable coating.

2. Resorbable implant according to claim 1, wherein the resorbable implant further contains up to 10% by weight of calcium.

3. Resorbable implant according to claim 1, wherein the resorbable implant further contains up to 10% by weight of yttrium.

4. Resorbable implant according to claim 1, wherein the magnesium alloy of the resorbable implant is composed as follows:

5. Resorbable implant according to claim 1, wherein the resorbable implant further contains at least one metal selected from the group comprising lithium, beryllium, sodium, magnesium, aluminum, potassium, calcium, scandium, titanium, vanadium, chromium, manganese, iron, cobalt, nickel, copper, zinc, gallium, yttrium, zirconium, niobium, molybdenum, technetium, ruthenium, rhodium, palladium, silver, indium, tin, lanthanum, cerium, praseodymium, neodymium, promethium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, lutetium, tantalum, tungsten, rhenium, platinum, gold, lead.

6. Resorbable implant according to claim 1, wherein the metal salt comprises at least one metal ion in the following oxidation states:

Li⁺, Be²⁺, Na⁺, Mg²⁺, K⁺, Ca²⁺, Sc³⁺, Ti²⁺, Ti⁴⁺, V²⁺, V³⁺, V⁴⁺, V⁵⁺, Cr²⁺, Cr³⁺, Cr⁴⁺, Cr⁶⁺, Mn²⁺, Mn³⁺, Mn⁴⁺, Mn⁵⁺, Mn⁶⁺, Mn⁷⁺, Fe²⁺, Fe³⁺, Co²⁺, Co³⁺, Ni²⁺, Cu⁺, Cu²⁺, Zn²⁺, Ga⁺, Ga³⁺, Al³⁺, Y³⁺, Zr²⁺, Zr⁴⁺, Nb²⁺, Nb⁴⁺, Nb⁵⁺Mo⁴⁺Mo⁶⁺, Tc²⁺, Tc³⁺, Tc⁴⁺, Tc⁵⁺, Tc⁶⁺, Tc⁷⁺, Ru³⁺, Ru⁴⁺, Ru⁶⁺, Ru⁷⁺, Ru⁸⁺, Rh³⁺, Rh⁴⁺, Pd²⁺, Pd³⁺, Ag⁺, In⁺, In³⁺, Ta⁴⁺, Ta⁵⁺, W⁴⁺, W⁶⁺, Pt²⁺, Pt³⁺, Pt⁴⁺, Pt⁵⁺, Pt⁶⁺, Au⁺, Au³⁺, Au⁵⁺, Sn²⁺, Sn⁴⁺, Pb²⁺, Pb⁴⁺, La³⁺, Ce³⁺, Ce⁴⁺, Gd³⁺, Nd³⁺, Pr³⁺, Tb³⁺, Pr³⁺, Pm³⁺, Sm³⁺, Eu²⁺, Dy³⁺, Ho³⁺, Er³⁺, Tm³⁺, Yb³⁺.

7. Resorbable implant according to claim 1, wherein the biodegradable coating is a polymer coating comprises natural, synthetic and semisynthetic polymers.

8. Resorbable implant according to claim 7, wherein the biodegradable coating comprises at least one of the following biodegradable substances or of mixtures of the following biodegradable substances:

polyvalerolactone, poly-ε

-decalactone, polylactonic acid, polyglycolic acid, polylactides, polyglycolides, copolymers of the polylactides and polyglycolides, poly-ε

-caprolactone, polyhydroxybutyric acid, polyhydroxybutyrates, polyhydroxyvalerates, polyhydroxybutyrate-co-valerate, poly(1,4-dioxane-2,3-one), poly(1,3-dioxane-2-one), poly-para-dioxanone, polyanhydrides, polymaleic acid anhydride, polyhydroxy methacrylates, fibrin, polycyanoacrylate, polycaprolactone dimethylacrylates, poly-β

-maleic acid, polycaprolactone butyl acrylates, multiblock polymers from oligocaprolactonediols and oligodioxanonediols, polyether ester multiblock polymers from PEG and poly(butylene terephthalate), polypivotolactones, polyglycolic acid trimethyl carbonates, polycaprolactone glycolides, poly(□

-ethyl glutamate), poly(DTH-iminocarbonate), poly(DTE-co-DT-carbonate), poly(bisphenol A-iminocarbonate), polyorthoesters, polyglycolic acid trimethyl carbonate, polytrimethyl carbonates, polyiminocarbonates, poly(N-vinyl)-pyrrolidone, polyvinyl alcohols, polyester amides, glycolized polyesters, polyphosphoesters, polyphosphazenes, poly[p-carboxyphenoxy)propane], polyhydroxy pentanoic acid, polyanhydrides, polyethylene oxide propylene oxide, soft polyurethanes, polyurethanes having amino acid residues in the backbone, polyetheresters such as polyethylene oxide, polyalkene oxalates, polyorthoesters as well as copolymers thereof, lipids, carrageenans, fibrinogen, starch, collagen, protein based polymers, polyamino acids, synthetic polyamino acids, zein, polyhydroxyalkanoates, pectic acid, actinic acid, carboxymethyl sulfate, albumin, hyaluronic acid, chitosan and derivatives thereof, heparan sulfates and derivatives thereof, heparins, chondroitin sulfate, dextran, β

-cyclodextrins, copolymers with PEG and polypropylene glycol, gum arabic, guar, gelatin, collagen N-hydroxysuccinimide, phospholipids, polyacrylic acid, polyacrylates, polymethyl methacrylate, polybutyl methacrylate, polyacrylamide, polyacrylonitriles, polyamides, polyetheramides, polyethylene amine, polyimides, polycarbonates, polycarbourethanes, polyvinyl ketones, polyvinyl halogenides, polyvinylidene halogenides, polyvinyl ethers, polyisobutylenes, polyvinyl aromatics, polyvinyl esters, polyvinyl pyrrolidones, polyoxymethylenes, polytetramethylene oxide, polyethylene, polypropylene, polytetrafluoroethylene, polyurethanes, polyether urethanes, silicone polyether urethanes, silicone polyurethanes, silicone polycarbonate urethanes, polyolefin elastomers, EPDM gums, fluorosilicones, carboxymethyl chitosans, polyaryletheretherketones, polyetheretherketones, polyethylene terephthalate, polyvalerates, carboxymethylcellulose, cellulose, rayon, rayon triacetates, cellulose nitrates, cellulose acetates, hydroxyethyl cellulose, cellulose butyrates, cellulose acetate butyrates, ethyl vinyl acetate copolymers, polysulfones, epoxy resins, ABS resins, silicones such as polysiloxanes, polydimethylsiloxanes, polyvinyl halogens and copolymers, cellulose ethers, cellulose triacetates, chitosans and copolymers and/or mixtures of the aforementioned polymers.

9. Resorbable implant according to claim 8, wherein the biodegradable coating comprises a polyester, polyurethane, parylene, amino-ppx, polylactide or a mixture of two or more of the aforementioned polymers.

10. Resorbable implant according to claim 1, wherein the coating allows for a fluid permeation.

11. Resorbable implant according to claim 1, wherein the biodegradable coating is a semipermeable membrane.

12. Resorbable implant according to claim 1, wherein the coating is provided with holes.

13. Resorbable implant according to claim 12, wherein, subsequent to the coating, the holes in the coating are created mechanically, chemically or optically by lasering.

14. Resorbable implant according to claim 1, wherein at least one pharmacologically active substance is provided on and/or in the resorbable implant.

15. Resorbable implant according to claim 1, wherein at least one pharmacologically active substance is provided on, in and/or underneath the biodegradable coating.

16. Resorbable implant according to claim 14, wherein the at least one pharmacologically active substance is selected from the group comprising antiproliferative, antimigrative, antiangiogenic, antiinflammatory, antiphlogistic, cytostatic, cytotoxic and/or antithrombotic agents, anti-restenosis agents, corticoids, sex hormones, statins, epothilones, prostacyclins, inductors of angiogenesis.

17. Resorbable implant according to claim 16, wherein the at least one pharmacologically active substance is selected from the group comprising:

abciximab, acemetacin, acetylvismione B, aclarubicin, ademetionine, adriamycin, aescin, afromosone, akagerine, aldesleukin, amidorone, aminoglutethimide, amsacrine, anakinra, anastrozole, anemonin, anopterine, antimycotics, antithrombotics, apocymarin, argatroban, aristolactam-AII, aristolochic acid, ascomycin, asparaginase, aspirin, atorvastatin, auranofin, azathioprine, azithromycin, baccatin, bafilomycin, basiliximab, bendamustine, benzocaine, berberine, betulin, betulinic acid, bilobol, bisparthenolidine, bleomycin, combrestatin, Boswellic acids and derivatives thereof, bruceanol A, B and C, bryophyllin A, busulfan, antithrombin, bivalirudin, cadherins, camptothecin, capecitabine, o-carbamoyl-phenoxyacetic acid, carboplatin, carmustine, celecoxib, cepharanthin, cerivastatin, CETP inhibitors, chlorambucil, chloroquine phosphate, cicutoxin, ciprofloxacin, cisplatin, cladribine, clarithromycin, colchicine, concanamycin, coumadin, C-type natriuretic peptide (CNP), cudraisoflavone A, curcumin, cyclophosphamide, ciclosporin A, cytarabine, dacarbazine, daclizumab, dactinomycin, dapsone, daunorubicin, diclofenac, 1,11-dimethoxycanthin-6-one, docetaxel, doxorubicin, daunamycin, epirubicin, epothilone A and B, erythromycin, estramustine, etoposide, everolimus, filgrastim, fluoroblastin, fluvastatin, fludarabine, fludarabine-5′

-dihydrogen phosphate, fluorouracil, folimycin, fosfestrol, gemcitabine, ghalakinoside, ginkgol, ginkgolic acid, glycoside 1a, 4-hydroxyoxy cyclophosphamide, idarubicin, ifosfamide, josamycin, lapachol, lomustine, lovastatin, melphalan, midecamycin, mitoxantrone, nimustine, pitavastatin, pravastatin, procarbazine, mitomycin, methotrexate, mercaptopurine, thioguanine, oxaliplatin, irinotecan, topotecan, hydroxycarbamide, miltefosine, pentostatin, pegaspargase, exemestane, letrozole, formestane, inhibitor-2□

of smc proliferation, mycophenolate mofetil, c-myc antisense, b-myc antisense, β

-lapachone, podophyllotoxin, podophyllic acid 2-ethyl hydrazide, molgramostim (rhuGM-CSF), peginterferon α

-2b, lenograstim (r-HuG-CSF), macrogol, selectin (cytokine antagonist), cytokinin inhibitors, COX-2 inhibitor, NFkB, angiopeptin, monoclonal antibodies inhibiting muscle cell proliferation, bFGF antagonists, probucol, prostaglandins, 1-hydroxy-11-methoxycanthin-6-one, scopoletin, NO donors such as pentaerythritol tetranitrate and sydnonimines, S-nitroso derivatives, tamoxifen, staurosporine, β

-estradiol, α

-estradiol, estriol, estrone, ethinyl estradiol, medroxyprogesterone, estradiol cypionates, estradiol benzoates, tranilast, kamebakaurin and other terpenoids used in cancer therapy, verapamil, tyrosine kinase inhibitors (tyrphostins), paclitaxel and derivatives thereof such as 6-α

-hydroxy-paclitaxel, taxoteres, carbon suboxide (MCS) and macrocylic oligomers thereof, mofebutazone, lonazolac, lidocaine, ketoprofen, mefenamic acid, piroxicam, meloxicam, penicillamine, hydroxychloroquine, sodium aurothiomalate, oxaceprol, β

-sitosterol, myrtecaine, polidocanol, nonivamide, levomenthol, ellipticine, D-24851 (Calbiochem), colcemid, cytochalasin A-E, indanocine, nocodazole, S 100 protein, bacitracin, vitronectin receptor antagonists, azelastine, guanidyl cyclase stimulator, tissue inhibitor of metal proteinase-1 and -2, free nucleic acids, nucleic acids incorporated into virus transmitters, DNA and RNA fragments, plasminogen activator inhibitor 1, plasminogen activator inhibitor 2, antisense oligonucleotides, VEGF inhibitors, IGF 1, active agents from the group of antibiotics such as cefadroxil, cefazolin, cefaclor, cefoxitin, tobramycin, gentamicin, penicillins such as dicloxacillin, oxacillin, sulfonamides, metronidazole, enoxaparin, desulfated and N-reacetylated heparin, tissue plasminogen activator, GpIIb/IIIa platelet membrane receptor, antibodies to factor Xa inhibitor, heparin, hirudin, r-hirudin, PPACK, protamine, prourokinase, streptokinase, warfarin, urokinase, vasodilators such as dipyramidole, trapidil, nitroprussides, PDGF antagonists such as triazolopyrimidine and seramin, ACE inhibitors such as captopril, cilazapril, lisinopril, enalapril, losartan, thioprotease inhibitors, prostacyclin, vapiprost, interferon α

, β and

γ

, histamine antagonists, serotonin blockers, apoptosis inhibitors, apoptosis regulators such as p65, NF-kB or Bcl-xL antisense oligonucleotides, halofuginone, nifedipine, tocopherol, molsidomine, tea polyphenols, epicatechin gallate, epigallocatechin gallate, leflunomide, etanercept, sulfasalazine, tetracycline, triamcinolone, mutamycin, procainimide, retinoic acid, quinidine, disopyrimide, flecamide, propafenone, sotalol, natural and synthetically obtained steroids such as inotodiol, maquiroside A, ghalakinoside, mansonine, strebloside, hydrocortisone, betamethasone, dexamethasone, non-steroidal substances (NSAIDS) such as fenoprofen, ibuprofen, indomethacin, naproxen, phenylbutazone and other antiviral agents such as acyclovir, ganciclovir and zidovudine, clotrimazole, flucytosine, griseofulvin, ketoconazole, miconazole, nystatin, terbinafine, antiprotozoal agents such as chloroquine, mefloquine, quinine, moreover natural terpenoids such as hippocaesculin, barringtogenol-C21-angelate, 14-dehydroagrostistachin, agroskerin, agrostistachin, 17-hydroxyagrostistachin, ovatodiolids, 4,7-oxycycloanisomelic acid, baccharinoids B1, B2, B3 and B7, tubeimoside, bruceantinoside C, yadanziosides N and P, isodeoxyelephantopin, tomenphantopin A and B, coronarin A, B, C and D, ursolic acid, hyptatic acid A, iso-iridogermanal, maytenfoliol, effusantin A, excisanin A and B, longikaurin B, sculponeatin C, kamebaunin, leukamenin A and B, 13,18-dehydro-6-alpha-senecioyloxychaparrin, taxamairin A and B, regenilol, triptolide, cymarin, hydroxyanopterine, protoanemonin, cheliburin chloride, sinococuline A and B, dihydronitidine, nitidine chloride, 12-β

-hydroxypregnadien-3,20-dione, helenalin, indicine, indicine-N-oxide, lasiocarpine, inotodiol, podophyllotoxin, justicidin A and B, larreatin, malloterin, mallotochromanol, isobutyrylmallotochromanol, marchantin A, maytansin, lycoridicin, margetine, pancratistatin, liriodenine, oxoushinsunine, periplocoside A, deoxypsorospermin, psychorubin, ricin A, sanguinarine, manwu wheat acid, methylsorbifolin, chromones of spathelia, stizophyllin, dihydrousambaraensine, hydroxyusambarine, strychnopentamine, strychnophylline, usambarine, usambarensine, liriodenine, daphnoretin, lariciresinol, methoxylariciresinol, syringaresinol, sirolimus (rapamycin), somatostatin, tacrolimus, roxithromycin, troleandomycin, simvastatin, rosuvastatin, vinblastine, vincristine, vindesine, teniposide, vinorelbine, trofosfamide, treosulfan, temozolomide, thiotepa, tretinoin, spiramycin, umbelliferone, desacetylvismione A, vismione A and B, zeorin.

18. Resorbable implant according to claim 1, wherein the resorbable implant is a stent for blood vessels, urinary tracts, respiratory tracts, biliary tracts or the digestive tract.