DE202011001927U1 - Nature stent - Google Patents

Abstract

Implant, in particular stent, characterized in that it consists essentially of natural biodegradable material.

Description

The present invention relates to an implant body, in particular a stent and / or implant, which consists of natural biodegradable material.

The implantation of stents is nowadays a common surgical procedure for the treatment of stenoses. Recent studies have shown, however, that vascular constrictions do not have to be widened permanently by an endoprosthesis, in particular a stent. It is sufficient to expand the tissue temporarily by an endoprosthesis, since the tissue can regenerate in the region of vasoconstriction in the presence of a supporting prosthesis and then remains without support by, for example, a stent in the widened form. This means that after a certain period of support of the tissue by a prosthesis, the prosthesis largely loses its effect, since the regenerated tissue is again able to maintain the normal vessel diameter, so that after removal of the prosthesis no renewed vasoconstriction would occur.

Bioresorbable stent of at least 90% by weight magnesium is disclosed in the European patent EP 1 419 793 B1 disclosed. The German patent application DE 102 07 161 A1 describes stents made of magnesium alloys and zinc alloys. Bioresorbable stents made of a zinc-calcium alloy are described in German Offenlegungsschrift DE 198 56 983 A1 disclosed. Shaped bodies, implants, stents of biodegradable material and methods of making the same are well known to those skilled in the art and for example in the European patent applications EP 0 594 977 A1 and EP 1 159 347 A1 , the international patent applications WO 99/02595 and WO 00/44826 and in the manual ecological design: furniture, objects, appliances, materials, addresses ( Alastair, Fuad-Luke (2002) Handbook Ecological Design: Furniture, Objects, Equipment, Materials, Addresses; DuMont literature, Cologne, ISBN 3-8321-7005-7 ).

On the one hand, these implants / stents and premers have the disadvantage that they dissolve too quickly and also uncontrollably, and some are already disintegrated after 2 weeks. Since the draw process usually begins before the stent has grown into the vessel wall, fragments may break loose, be transported through the bloodstream and trigger a heart attack.

The object of the present invention is to provide a low-cost and easily manufactured implant / anterior body, preferably a stent, which avoids the above-mentioned disadvantage when compared to conventional implants comparable properties.

The object is achieved by an implant, preferably a stent, which according to the invention is characterized in that it is made of essentially natural biodegradable material.

The development of the implant according to the invention, preferably stents, combines the advantage of using naturally biodegradable material and the resulting lower body damage caused by inflammation, which can end up by degradation of commercially available resorbable implants, preferably stents. Thus, by using the implant according to the invention preferably stents reduces the body damage Furthermore, it is possible to introduce drugs into the material so then in the course of the absorption time or directly to the diseased z. B. Vessel is dispensed. Another advantage is the low raw material and manufacturing costs.

By naturally biodegradable material is meant in the present description and in the claims preferably compostable biopolymers and biological compounds from renewable resources, such as starch, sugar or vegetable oils and / or fossil fuels (for example, petroleum). These substances, like their degradation products, can easily be absorbed by the human or animal body.

The materials and additives used are preferably 100% naturally biodegradable. Persistent or potentially toxic intermediates of biodegradation are preferably not produced under either anaerobic or aerobic absorption conditions.

Hereinafter, an embodiment of the present invention will be explained.

The implant preferably stent according to the invention generally consists of naturally biodegradable material, preferably plastics based on polyvinyl alcohols, thermoplastics based on polycaprolactones, plant starch, biopolymers in general, cellulose, cork, production or household waste or mixtures thereof. They can be laser cut to the final product.

The term "naturally biodegradable" in the present specification and claims generally encompasses all types of disintegration into preferably non-persistent and non-toxic end-products.

The term "natural biopolymer" in the present specification and claims generally designates biodegradable polymers, preferably polysaccharides extracted from plants such as corn starch.

The term "starch" generally includes all starches of natural and plant origin, which are composed essentially of amylose and / or amylopectin. They can be obtained from various plants, such as potatoes, rice, tapioca, corn, and cereals such as rye, oats, wheat, etc. The corn starch is preferred.

The term "starch" also includes starch that has been modified to reduce the acid number to the range of 3 to 6, and potato starch in which the type and concentration of cations associated with the phosphate group have been altered. Ethoxylated starches, acetate starches, cationic starches, oxidized starches, crosslinked starches, etc. may also be used to make the implant of the invention, preferably stents.

The term "cellulose" in the present specification and claims generally includes all types of plant waste, leaves, grass and woodcutting, sawdust, etc.

The term "additive" in the present specification and claims generally includes resins, binders, natural adhesives such as bone glue, gelatin, terpenes, shellac and starch, chemicals for processing the raw materials used, each of which is preferably fully biodegradable, and be used in non-toxic concentrations.

For implants, preferably stents, a distinction is made between two types, one-piece and multi-layer implants, preferably stents.

In one embodiment, the invention provides a one-piece implant, preferably a stent, which has a one-piece, homogeneous construction, wherein the material used is preferably completely biodegradable.

In a further embodiment, the present invention relates to two- or multi-layer implants, preferably stents, consisting of core and outer shells, which in turn may be composed of a plurality of superimposed layers. Specifically, both core and outer shell are made of biodegradable material. The core is usually either wound, extruded or one-piece.

In a preferred embodiment, the invention relates to an implant, preferably a stent, which as a whole is a hollow body or whose core is a hollow body.

In a particularly preferred embodiment, the hollow body is filled, for example, with cytostatic medicaments, such as, for example, paclitaxel, with individually biodegradable contents.

The implant according to the invention, preferably a stent, can be produced, for example, by conventional methods, e.g. B. extrusion and compression molding, for example, be made under high pressure and heat. The material bound, for example, using plant starch-based resins can be processed into high-strength molded articles.

In a further embodiment, the implant according to the invention, preferably a stent, is produced by an injection molding process. For the achievement of particularly high-quality implants, preferably stents, an embodiment of the implant, preferably stents made of a core with a thin shell layer, for example, of extruded plant starch, is advantageous. In this case, after production of the core, the thin cladding layer can be sprayed on and / or these can be applied by dipping the implant according to the invention, preferably stents, into a corresponding bath.

In a preferred embodiment, in the production of one-piece implants, stents are preferably the material used, which is liquid or fluid or can be handled as a liquid or fluid, injected into a designated mold and cured.

In a particularly preferred embodiment, in the production of single-layered cores, the material used, which is liquid or liquid or fluid-handled and contains a drug for preventing restenosis (eg paclitaxel), is prefabricated into a material which is biodegradable by means of an injection molding technique Implant preferably stent hollow body (outer shell) injected, and cured.

In a preferred embodiment, the implant according to the invention is preferably encased in a stent with a luminescent marking layer, which preferably contains phosphorescent substances, so-called "phosphors", and thus also makes it possible to better identify the implant, preferably a stent, also under X-ray vision. Of the The term "phosphors" here includes crystals whose lattice structure is disturbed by very little admixture of a foreign substance. Such substances include the highly calcined sulphides of the alkaline earth metals and zinc, which are mixed with small amounts of heavy metal salts. The materials absorb the light energy when exposed to visible or ultraviolet light and emit it more or less quickly as longer wavy light. In a preferred embodiment, the phosphorescent material is the non-toxic zinc salt of hydrosilicic acid, zinc sulfide (ZnS). The implant, preferably stent, can thus be implanted before implantation by means of z. B. UV light can be activated.

Preferably, the marking layer is substantially as biodegradable as the implant is preferably a stent itself. In this connection, in a further aspect, the present invention also relates to conventional implants, preferably stents, provided with such a substantially biodegradable marking layer.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• EP 1419793 B1 [0003]
• DE 10207161 A1 [0003]
• DE 19856983 A1 [0003]
• EP 0594977 A1 [0003]
• EP 1159347 A1 [0003]
• WO 99/02595 [0003]
• WO 00/44826 [0003]

Cited non-patent literature

• Alastair, Fuad-Luke (2002) Handbook Ecological Design: Furniture, Objects, Equipment, Materials, Addresses; DuMont literature, Cologne, ISBN 3-8321-7005-7 [0003]

Claims (10)

Implant, in particular stent, characterized in that it consists essentially of natural biodegradable material. Implant, in particular stent according to claim 1, characterized in that cytostatics preferably paclitaxel is included. Implant preferably stent according to claim 1 and 2, characterized in that the degradation products are ecologically and medically safe. Implant preferably stent according to claim 1 to 3, characterized in that the material is a biodegradable material based on biopolymers, plant starch and cellulose or mixtures thereof. Implant preferably stent according to claim 1 to 4, characterized in that the degradation process by exposure, in particular blood, water and / or microorganisms is accelerated. Implant preferably stent according to claim 1 to 5, characterized in that it is coated with a marking layer. Implant preferably stent according to claim 6, characterized in that the layer fluoresces. Implant preferably stent, characterized in that it is covered with a layer consisting of biodegradable material as defined in claim 6 or 7. Implant preferably stent according to claim 1 to 8, wherein it is at least one pharmacologically active substance selected from the group and in the implant preferably stent is integrated, comprising: abciximab, acemetacin, acetylvismion B, aclarubicin, ademetionin, adriamycin, aescin, Afromoson, Akagerin, aldesleukin, amidorone, aminoglutethemide, amsacrine, anakinra, anastrozole, anemonin, anopterin, antifungals, 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, bombrestatin, boswellic acids and their derivatives, bruceanols A, B and C, bryophyllin A, busulfan, antithrombin, bivalirudin, cadherins, camptothecin, capecitabine, o-carbamoylphenoxyacetic acid , Carboplatin, carmustine, celecoxib, cepharantin, cerivastatin, CETP inhibitors, Chl orambucil, chloroquine phosphate, cictoxin, ciprofloxacin, cisplatin, cladribine, clarithromycin, colchicine, concanamycin, coumadin, C-type natriuretic peptides (CNP), cudraisoflavone A, curcumin, cyclophosphamide, cyclosporin A, cytarabine, dacarbazine, daclizumab, dactinomycin, dapsone, daunorubicin , Diclofenac, 1,11-dimethoxycanthin-6-one, docetaxel, doxorubicin, dunaimycin, epirubicin, epothilones A and B, erythromycin, estramustine, etoboside, everolimus, filgrastim, fluroblastin, fluvastatin, fludarabine, fludarabine 5'-dihydrogen phosphate, fluorouracil , Folinycin, fosfestrol, gemcitabine, ghalacinoside, ginkgol, ginkgolic acid, glycoside 1a, 4-hydroxyoxycyclophosphamide, idarubicin, ifosfamide, josamycin, lapachol, lomustine, lovastatin, melphalan, midecamycin, mitoxantrone, nimustine, pitavastatin, pravastatin, procarbazine, mitomycin, methotrexate, Mercaptopurine, Thioguanine, Oxaliplatin, Irinotecan, Topotecan, Hydroxycarbamide, Miltefosine, Pentostatin, Pegasparase, Exemestane, Letrozole, Formestan, SMC-Prol iferation inhibitor 2w, mitoxanthrone, mycophenolate mofetil, c-myc antisense, b-myc antisense, β-lapachone, podophyllotoxin, podophyllic acid 2-ethylhydrazide, molgramostim (rhuGM-CSF), peginterferon α-2b, lanograstim (r HuG-CSF), macrogol, selectin (cytokine antagonist), cytokine inhibitors, COX-2 inhibitor, NFkB, angiopeptin, monoclonal antibodies that inhibit muscle cell proliferation, bFGF antagonists, probucol, prostaglandins, 1-hydroxy-11-methoxycanthin-6 on, scopolectin, NO donors such as pentaerythrityl tetranitrate and syndnoeimines, S-nitrosated derivatives, tamoxifen, staurosporine, β-estradiol, α-estradiol, estriol, estrone, ethinylestradiol, medroxyprogesterone, estradiol cypionates, estradiol benzoates, tranilast, camebakaurin and other terpenoids known in the art Cancer therapy, verapamil, tyrosine kinase inhibitors (tyrphostins), paclitaxel and its derivatives such as 6-α-hydroxy-paclitaxel, taxoters, carbon suboxide (MCS) and its macrocyclic oligomers, mofebutazone, Lonazola c, lidocaine, ketoprofen, mefenamic acid, piroxicam, meloxicam, penicillamine, hydroxychloroquine, sodium aurothiomalate, oxaceprol, β-sitosterol, myrtainaine, polidocanol, nonivamide, levomenthol, ellipticin, D-24851 (Calbiochem), colcemid, cytochalasin A-E, indanocine, Nocadazole, S 100 protein, bacitracin, vitronectin receptor antagonist, azelastine, guanidyl cyclase stimulator, metalloproteinase 1 and 2 tissue inhibitor, free nucleic acids, nucleic acids incorporated in virus carriers, DNA and RNA fragments, plaminogen activator inhibitor-1, plasminogen Activator inhibitor-2, antisense oligonucleotides, VEGF inhibitors, IGF-1, drugs from the group of antibiotics such as cefadroxil, cefazolin, cefaclor, cefotixine tobramycin, gentamycin, penicillins such as dicloxacillin, oxacillin, sulfonamides, metronidazole, enoxoparin, desulfated and N- reacetylated heparin, tissue plasminogen activator, GpIIb / IIIa platelet membrane receptor, Factor X _a inhibitor antibody, heparin, hirud in, r-hirudin, PPACK, protamine, prourokinase, Streptokinase, warfarin, urokinase, vasodilators such as dipyramidol, 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 tranilast, molsidomine, tepolyphenols, epicatechingallate, epigallocatechin gallate, leflunomide, etanercept, sulfasalazine, etoposide, dicloxacyllin, tetracycline, triamcinolone, Mutamycin, procainimide, retinoic acid, quinidine, disopyrimide, flecainide, propafenone, sotolol, natural and synthetic steroids such as inotodiol, maquiroside A, ghalakinoside, mansonine, strebloside, hydrocortisone, betamethasone, dexamethasone, nonsteroidal substances (NSAIDS) such as fenoporfen, ibuprofen, indomethacin , Naproxen, phenylbutazone and and antiviral agents such as acyclovir, ganciclovir and zidovudine, clotrimazole, flucytosine, griseofulvin, ketoconazole, miconazole, nystatin, terbinafine, antiprozoal agents such as chloroquine, mefloquine, quinine, and natural terpenoids such as hippocaesculin, barringtogenol-C21-lanthanum, 14-dehydroagrostistachine, Agroskerin, agrostistachin, 17-hydroxyagrostistachine, ovatodiolides, 4,7-oxycycloanisomelic acid, baccharinoids B1, B2, B3 and B7, tubeimoside, bruceantinosides C, yadanziosides N, and P, isodeoxyelephantopin, tomenphantopin A and B, coronarine A, B, C and D, ursolic acid, hyptate 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-Senecioyloxychaparrine, Taxamairin A and B, Regenilol, Triptolide, Cymarin, Hydroxyanopterin, Protoanemonin, Cheliburine chloride, sinococulin A and B, dihydronitidine, nitidine chloride, 12-beta-hydroxypregnadiene 3,20-dione, helenaline, indicin, indicin-N-oxide, lasiocarpine, inotodiol, podophyllotoxin, justicidin A and B, larreatin, malloterine, mallotochromanol, isobutyrylmallotochromanol , Maquiroside A, Marchantin A, Maytansin, Lycoridicin, Margetin, Pancratistatin, Liriodenin, Bispsrthenolidine, Oxoushinsunin, Periplocoside A, Ursolic Acid, Deoxypypsorospermine, Psycorubin, Ricin A, Sanguinarine, Manwuweizic Acid, Methylsorbifolin, Sphatheliachromes, Stizophyllin, Mansonin, Strebloside, Dihydrousambaraensin, Hydroxyusambarin , Strychnopentamine, Strychnophyllin, Usambarin, Usambarensin, Liriodenin, Oxoushinsunin, Daphnoretin, Lariciresinol, Methoxylariciresinol, Syringaresinol , Sirolimus (rapamycin), somatostatin, tacrolimus, roxithromycin, troleandomycin, simvastatin, rosuvastatin, vinblastine, vincristine, vindesine, teniposide, vinorelbine, tropfosfamide, treosulfan, tremozolomide, thiotepa, tretinoin, spiramycin, umbelliferone, desacetylvismion A, vismions A and B, Zeorin. Resorbable implant according to one of the preceding claims, wherein the natural resorbable implant is a stent for blood vessels, urinary tract, respiratory tract, biliary tract or the digestive tract.