EP1024842A2 - Implants medicaux revetus, leur procede de preparation et leur utilisation pour la prevention de restenoses - Google Patents

Implants medicaux revetus, leur procede de preparation et leur utilisation pour la prevention de restenoses

Info

Publication number
EP1024842A2
EP1024842A2 EP98952617A EP98952617A EP1024842A2 EP 1024842 A2 EP1024842 A2 EP 1024842A2 EP 98952617 A EP98952617 A EP 98952617A EP 98952617 A EP98952617 A EP 98952617A EP 1024842 A2 EP1024842 A2 EP 1024842A2
Authority
EP
European Patent Office
Prior art keywords
polymer
medical implants
stent
epothilone
active ingredient
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP98952617A
Other languages
German (de)
English (en)
Inventor
Werner Krause
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer Pharma AG
Original Assignee
Schering AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Schering AG filed Critical Schering AG
Publication of EP1024842A2 publication Critical patent/EP1024842A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
    • C09D175/00—Coating compositions based on polyureas or polyurethanes; Coating compositions based on derivatives of such polymers
    • C09D175/04—Polyurethanes
    • C09D175/08—Polyurethanes from polyethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A61L31/10—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus

Definitions

  • the invention relates to agents for the production of coated, drug-delivering medical implants, e.g. Stents, the implants prepared in this way, processes for their preparation and their use for restenosis prophylaxis.
  • coated, drug-delivering medical implants e.g. Stents
  • Implants especially stents, are state of the art (Pschyrembel, clinical dictionary 257th edition, publisher W. de Gruyter). Stents are self-expanding endoprostheses that keep the gait open
  • Enable structures in human or animal bodies e.g. vascular, esophageal, tracheal, bile duct stent. They are used as a palliative measure for narrowing due to occlusion (eg atherosclerosis) or external pressure (eg for tumors).
  • Radioactive stents are used, for example, after vascular surgery or interventional radiological interventions (eg balloon angioplasty) for prophylaxis of restenosis.
  • a stent is known from international patent application WO 94/13268, which gradually releases an active substance in the body.
  • a polymer composition is known from US Pat. No. 5,599,552 which can gel in the body. In solid form, it represents an implant that can gradually release an active ingredient.
  • the object of the present invention is therefore to provide medical implants which are better tolerated than conventional medical implants.
  • the surface of the medical implants is coated with a polymer into which at least one active ingredient based on the epothilone base, e.g. Epothilon A or B or a derivative of epothilone, as well as possibly other active substances, e.g. thrombosis-preventing substances and / or estrogens and / or corticosteroids are incorporated.
  • Epothilone and its synthesis are known from the literature (Höfle et al., Angew. Chem. 108: 1 671 -3 (1 996), Schinzer et al., Angew. Chem. 1 09: 543-4 (1997)).
  • the active substance epothilone can also be applied directly to the medical implant without a polymer.
  • the device according to the invention thus consists of the medical implant, possibly of a polymer on the surface of the implant and at least one active ingredient from the class of the epothilones.
  • the invention also relates to devices, substances, solutions and containers for the coating of implants according to the invention, for example in the form of a kit. Such kits can be used by the physician on site for the coating of selected implants.
  • the commercially available implants can be used as the base body, for the stents e.g. a Wiktor stent, a Strecker stent or a Palmaz-Schatz stent.
  • suitable polymers are polyurethanes, polylactides, mixed polylactide glycolides or other polymers described in the literature.
  • the implants according to the invention - described with the aid of stents - can be produced by way of example as follows:
  • An uncoated stent is first coated with a polymer (e.g. a polyurethane, obtainable from the reaction of an amphiphilic polyether, diphenyimethane-4-4'-diisocyanate and butanediol).
  • a polymer e.g. a polyurethane, obtainable from the reaction of an amphiphilic polyether, diphenyimethane-4-4'-diisocyanate and butanediol.
  • a solvent e.g. chloroform
  • Active ingredient epothilone
  • the same solvent for example chloroform or ethyl acetate
  • Another active ingredient can be applied to epothilone derivative.
  • active ingredients are antithrombotic drugs, e.g. Iloprost, estrogens such as ethinyl estradiol or corticoids such as Dexamethasone, Fluocortolon, Difluorcortolon or their esters.
  • An uncoated stent can first be coated with a polymer (e.g. a polyurethane, obtainable from the reaction of an amphiphilic polyether, diphenylmethane-4-4'-diisocyanate and butanediol). This polymer is modified so that it is on the surface
  • Cyclodextrin carries.
  • the polymer is dissolved in a solvent (e.g. chloroform) and the stent is immersed in the polymer solution. After the stent has been removed from the polymer solution, it is dried in a drying chamber at room temperature.
  • the "activation" of the stent now takes place by immersing the modified stent in an aqueous solution of epothilone. The active ingredient is incorporated into the cyclodextrin. The stent is now ready for use.
  • the implants according to the invention achieve the task described in the introduction.
  • the implants according to the invention are physiologically well tolerated.
  • the particular advantage of the implants according to the invention is that the physician can select a stent according to his needs on site and then activate the selected stent by the described method.
  • the few substances and solutions required for this can be delivered prepared accordingly, so that the corresponding medical practitioner only has to immerse the uncoated stent in the given order in the individual solutions.
  • the invention thus also relates to those substances, solutions and preparations (kits) and containers prepared for the method according to the invention.
  • the polymer used is polyurethane, which can be obtained as a chain extender by reacting an amphiphilic polyether, diphenylmethane-4,4'-diisocyanate and butanediol.
  • the stents are coated by immersing them in a 5% chloroform solution of the polymer. Then they are allowed to dry in a clean room drying chamber at room temperature. The average layer thickness is 20 ⁇ m.
  • Epothilon A is coated by immersing the polymer-coated stent in an aqueous solution of Epothilon A (0.5 mg / ml). After drying, the stent is ready for use.
  • the coating of the stent with the polymer and the subsequent coating with epothilone A is carried out as described in Example 1. However, the stent is now alternately immersed in a solution with the polymer and - after drying - in an aqueous solution of Epothilon A. This creates a multi-layer structure. The amount of active ingredient incorporated can be controlled via the number of epothilone-containing layers. The stent is implanted after the last drying cycle.
  • the coating is carried out as described in Example 2. However, the stent is now alternately immersed in a solution with the polymer and - each after drying - in an aqueous solution of epothilone A or lloprost or a solution of an estrogen derivative or corticoid in chloroform.
  • the order of the coating materials can be varied. This creates a multi-layer structure. The amount of active ingredient incorporated can be controlled via the number of the respective layers.
  • the stent is implanted after the last drying cycle.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Surgery (AREA)
  • Vascular Medicine (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Materials Engineering (AREA)
  • Biomedical Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Materials For Medical Uses (AREA)
  • Media Introduction/Drainage Providing Device (AREA)

Abstract

L'invention concerne des agents pour la préparation d'implants médicaux revêtus libérant des principes actifs, par exemple des extenseurs, les implants ainsi préparés, leur procédé de préparation et leur utilisation pour la prévention de resténoses.
EP98952617A 1997-09-29 1998-09-24 Implants medicaux revetus, leur procede de preparation et leur utilisation pour la prevention de restenoses Withdrawn EP1024842A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19744135A DE19744135C1 (de) 1997-09-29 1997-09-29 Beschichtete medizinische Implantate, Verfahren zu ihrer Herstellung und ihre Verwendung zur Restenoseprophylaxe
DE19744135 1997-09-29
PCT/EP1998/006019 WO1999016416A2 (fr) 1997-09-29 1998-09-24 Implants medicaux revetus, leur procede de preparation et leur utilisation pour la prevention de restenoses

Publications (1)

Publication Number Publication Date
EP1024842A2 true EP1024842A2 (fr) 2000-08-09

Family

ID=7844759

Family Applications (1)

Application Number Title Priority Date Filing Date
EP98952617A Withdrawn EP1024842A2 (fr) 1997-09-29 1998-09-24 Implants medicaux revetus, leur procede de preparation et leur utilisation pour la prevention de restenoses

Country Status (5)

Country Link
EP (1) EP1024842A2 (fr)
JP (1) JP2001517543A (fr)
AU (1) AU1025199A (fr)
DE (1) DE19744135C1 (fr)
WO (1) WO1999016416A2 (fr)

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DE69734362T2 (de) 1996-12-03 2006-07-20 Sloan-Kettering Institute For Cancer Research Synthese von epothilonen, zwischenprodukte dazu, analoga und verwendungen davon
US6380394B1 (en) 1996-12-13 2002-04-30 The Scripps Research Institute Epothilone analogs
JP5140220B2 (ja) 1999-05-27 2013-02-06 バイオコンパテイブルズ・ユーケイ・リミテツド 局所的な薬剤送達
ATE350077T1 (de) 2000-04-11 2007-01-15 Polyzenix Gmbh Verwendung von folien aus poly-tri-fluor- ethoxypolyphosphazenen zur umhüllung von medizinischen vorrichtungen
EP1179353A1 (fr) * 2000-08-11 2002-02-13 B. Braun Melsungen Ag Implants antithrombotiques avec un revêtement de polyphosphazène et d'un agent actif
DE10100961B4 (de) 2001-01-11 2005-08-04 Polyzenix Gmbh Körperverträglicher Werkstoff und mit diesem Werkstoff beschichtetes Substrat für die Züchtung von Zellen und künstlichen aus Zellen aufgebauten oder gewachsenen organischen Implantaten
US9080146B2 (en) 2001-01-11 2015-07-14 Celonova Biosciences, Inc. Substrates containing polyphosphazene as matrices and substrates containing polyphosphazene with a micro-structured surface
WO2003015719A1 (fr) 2001-08-17 2003-02-27 Polyzenix Gmbh Dispositif a base de nitinol comportant un revetement polyphosphate
DE10107795B4 (de) * 2001-02-13 2014-05-15 Berlex Ag Gefäßstütze mit einem Grundkörper, Verfahren zur Herstellung der Gefäßstütze, Vorrichtung zur Beschichtung der Gefäßstütze
DE50210591D1 (de) 2001-02-16 2007-09-13 Abbott Lab Vascular Entpr Ltd Implantate mit fk506 zur restenosebehandlung und -prophylaxe
EP1270026A1 (fr) * 2001-06-22 2003-01-02 Erik Andersen Stents comprenant des analogues de vitamine D pour éviter les resténoses
DE10142881A1 (de) * 2001-09-03 2003-04-03 Jomed Gmbh Implantate mit Combretastatin A-4 (CA4)
SI1483251T1 (sl) 2002-03-12 2010-03-31 Bristol Myers Squibb Co C cian epotilonski derivati
DE10231336A1 (de) * 2002-07-11 2004-01-22 Bayer Ag Stents
US7649006B2 (en) 2002-08-23 2010-01-19 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
DK1767535T3 (da) 2002-08-23 2010-04-12 Sloan Kettering Inst Cancer Syntese af epothiloner, mellemprodukter deraf, analoge og deres anvendelse
CN1723018A (zh) * 2002-12-09 2006-01-18 诺瓦提斯公司 用于治疗支架狭窄的微管稳定剂
US8318235B2 (en) 2003-01-22 2012-11-27 Cordis Corporation Method for applying drug coating to a medical device in surgeon room
US20050038504A1 (en) * 2003-01-22 2005-02-17 Harry Halleriet Kit for applying drug coating to a medical device in surgeon room
US9107850B2 (en) 2004-10-25 2015-08-18 Celonova Biosciences, Inc. Color-coded and sized loadable polymeric particles for therapeutic and/or diagnostic applications and methods of preparing and using the same
US20210299056A9 (en) 2004-10-25 2021-09-30 Varian Medical Systems, Inc. Color-Coded Polymeric Particles of Predetermined Size for Therapeutic and/or Diagnostic Applications and Related Methods
US9114162B2 (en) 2004-10-25 2015-08-25 Celonova Biosciences, Inc. Loadable polymeric particles for enhanced imaging in clinical applications and methods of preparing and using the same
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ES2378905T3 (es) 2006-10-10 2012-04-19 Celonova Biosciences, Inc. Válvula cardiaca bioprotésica con polifosfaceno
EP2065054A1 (fr) * 2007-11-29 2009-06-03 Bayer Schering Pharma Aktiengesellschaft Combinaisons comprenant une prostaglandine et leurs utilisations

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Also Published As

Publication number Publication date
AU1025199A (en) 1999-04-23
JP2001517543A (ja) 2001-10-09
WO1999016416A2 (fr) 1999-04-08
DE19744135C1 (de) 1999-03-25
WO1999016416A3 (fr) 1999-08-05

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