EP1135165A1 - Endoprothese comportant en surface un principe actif sous forme de cristaux - Google Patents

Endoprothese comportant en surface un principe actif sous forme de cristaux

Info

Publication number
EP1135165A1
EP1135165A1 EP99961692A EP99961692A EP1135165A1 EP 1135165 A1 EP1135165 A1 EP 1135165A1 EP 99961692 A EP99961692 A EP 99961692A EP 99961692 A EP99961692 A EP 99961692A EP 1135165 A1 EP1135165 A1 EP 1135165A1
Authority
EP
European Patent Office
Prior art keywords
medical device
therapeutic agent
coating
polymer
crystals
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Withdrawn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
EP99961692A
Other languages
German (de)
English (en)
Inventor
Maria Palasis
Marlene Schwarz
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.)
Boston Scientific Ltd Barbados
Original Assignee
Boston Scientific Ltd Barbados
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 Boston Scientific Ltd Barbados filed Critical Boston Scientific Ltd Barbados
Publication of EP1135165A1 publication Critical patent/EP1135165A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6957—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a device or a kit, e.g. stents or microdevices
    • 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
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/08—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
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A61L29/16—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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L75/00—Compositions of polyureas or polyurethanes; Compositions of derivatives of such polymers
    • C08L75/04—Polyurethanes
    • 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
    • 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
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602—Type of release, e.g. controlled, sustained, slow
    • A61L2300/604—Biodegradation
    • 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
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606—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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/63—Crystals

Definitions

  • the present invention relates to the localized delivery of therapeutic agents, and more particularly to the localized delivery of crystalline therapeutic agents to target locations within a body.
  • systemic administration of drug agents treats the body as a whole even though the disease to be treated may be localized.
  • systemic administration may not be desirable because the drug agents often have unwanted effects on parts of the body that are not intended to be treated, or because treatment of the diseased part of the body requires a high concentration of drug agent that may not be achievable by systemic administration.
  • U.S. Patent No. 5,304,121 which is incorporated herein by reference, discloses a method of delivering water-soluble drugs to tissue at desired locations of a body lumen wall. The method generally includes the steps of impregnating a hydrogel polymer on a balloon catheter with an aqueous drug solution, inserting the catheter into a blood vessel to a desired location, and expanding the catheter balloon against the surrounding tissue to allow the release of the drug.
  • One potential drawback to conventional localized drug administration is the uncontrolled rapidity at which the drug or drug solution is released from the delivery device. It is often desired, if not necessary, to control and/or lengthen the time period over which the drug is released. For example, it might be advantageous to lengthen the release time from seconds to minutes, or from minutes to hours, days, or even weeks. Exceptionally long release times as long as several months are often desired, for example, where the drug is released from an implanted device such as a stent. Moreover, it is often desired to control the release rate of the drug over prolonged periods of time.
  • the present invention provides a medical device for insertion into a mammalian body, wherein the medical device has a therapeutic agent applied to at least a portion of a surface thereof, and the therapeutic agent is in a crystalline form.
  • the present invention provides a method of delivering a therapeutic agent to a target location within a mammalian body.
  • the method comprises the steps of placing crystals of the therapeutic agent on at least a portion of a surface of a medical device, and delivering the medical device to the target location.
  • One advantage of the present invention is that it retards the release of therapeutic agents from a localized drug delivery system.
  • Another advantage of the present invention is that it provides for a controlled release rate of therapeutic agents from a localized drug delivery system.
  • Balloon catheter refers to a tubular instrument with a balloon or multiple balloons that can be inflated or deflated without removal after insertion into the body.
  • Biodegradable refers to a substance that can be substantially chemically degraded or decomposed by exposure to bodily tissue or fluids.
  • Biostable refers to a substance that is not substantially chemically degraded or decomposed by exposure to bodily tissue or fluids.
  • Crystal refers to a solid of regular shape and, for a given material, characteristic angles, wherein the individual atoms or molecules within the crystal take up regular positions with respect to one another.
  • Crystalstallization refers to the process whereby a material assumes a crystalline form when a vapor or liquid becomes solidified, or a solute precipitates from solution under proper conditions.
  • Drug and “therapeutic agent” are used interchangeably to refer to any substance used in the prevention, diagnosis, alleviation, treatment or cure of disease.
  • Stepsis refers to a stricture of any bodily canal.
  • Stent refers to any tubular structure used to maintain or support a bodily orifice or cavity.
  • Fig. 1 is a scanning electron microphotograph of medical device having crystals of therapeutic agent thereon.
  • Fig. 2 is a scanning electron microphotograph of medical device having a layer of therapeutic agent crystals thereon.
  • Fig. 3 is a graph showing the release profiles of paclitaxel from coated stents, for paclitaxel in both crystalline and non-crystalline form.
  • the present invention makes use of crystals of therapeutic agents to retard the release of the therapeutic agent when delivered to a target location within a mammalian body. Moreover, the release of the therapeutic agent in its crystalline form is controlled in that the therapeutic agent is released at a characteristic rate or release profile over time.
  • the present invention provides a medical device for insertion into a mammalian body, wherein the medical device has a therapeutic agent applied to at least a portion of a surface thereof, and the therapeutic agent is in the form of crystals.
  • the therapeutic agent used in the present invention includes, for example, any pharmaceutically active material that can be crystallized.
  • Such therapeutic agents may include biologically active solutes such as anti-thrombogenic agents such as heparin, heparin derivatives, urokinase, PPACK (dextrophenylalanine proline arginine chloromethylketone), rapamycin, probucol, and verapimil; angiogenic and anti-angiogenic agents; anti-proliferative agents such as enoxaprin, angiopeptin, or monoclonal antibodies capable of blocking smooth muscle cell proliferation, hirudin, and acetylsalicylic acid; anti-inflammatory agents such as dexamethasone, prednisolo ⁇ e, corticosterone, budesonide, estrogen, sulfasalazine, and mesalamine; antineoplastic/ antiproliferative/ anti-mitotic agents such as paclitaxel, 5-fluorouracil
  • Preferred therapeutic agents for use in the present invention are paclitaxel and derivatives thereof.
  • the therapeutic agent is placed on a medical device for insertion into the body to a target location.
  • the medical device used in the present invention is any insertable or implantable device including, for example, stents, balloon catheters, blood clot filters, vascular grafts, stent grafts, aneurysm filling coils, intralumenal paving systems, etc., as are known in the art.
  • a preferred medical device for use with the present invention is an implantable device such as a stent, for which the present invention allows for the continued release of therapeutic agents therefrom for extended time periods of up to several months.
  • the therapeutic agent is applied to the medical device, for example, such that isolated, individual crystals 101 exist on the surface of the medical device 102.
  • the therapeutic agent is applied to the medical device such that a layer 201 of crystals exists on at least a portion of the medical device 202.
  • the crystals of the therapeutic agent are optionally placed within or over a polymer coating, which at least partially coats the medical device as described further herein.
  • the crystals of the therapeutic agent are applied to the medical device by any suitable method.
  • the crystals are formed by the following steps: i) placing a therapeutic agent, while in a non-crystalline form, into solution with a polymer in which the therapeutic agent is substantially soluble; ii) applying the solution onto at least a portion of a medical device as a coating; iii) drying the coating to form a dry coating wherein the therapeutic agent is dispersed in the polymer; iv) exposing the coated medical device to a non-solvent (i.e., a material in which the therapeutic agent is relatively insoluble); and v) allowing the therapeutic agent to diffuse out of the coating to the interface between the coating and the non-solvent, whereupon the therapeutic agent crystallizes on the surface of the coating.
  • a non-solvent i.e., a material in which the therapeutic agent is relatively insoluble
  • the non-solvent penetrates the coating such that the therapeutic agent crystallizes within the coating.
  • the polymer coating comprises any polymeric material in which the therapeutic agent is substantially soluble.
  • the polymer is, for example, hydrophilic, hydrophobic, and/or biodegradable.
  • the polymer is selected from the group consisting of polycarboxylic acids, cellulosic polymers, gelatin, polyvinylpyrrolidone, maleic anhydride polymers, polyamides, polyvinyl alcohols, polyethylene oxides, glycosaminoglycans, polysaccharides, polyesters, polyurethanes, silicones, polyorthoesters, polyanhydrides, polycarbonates, polypropylenes, polylactic acids, polyglycolic acids, polycaprolactones, polyhydroxybutyrate valerates, polyacrylamides, polyethers, and mixtures and copolymers thereof.
  • Coatings from polymer dispersions such as polyurethane dispersions (BAYHYDROL, etc.) and acrylic latex dispersions are also within the scope of the present invention.
  • a preferred polymer for use in the polymer coating of the present invention is polyurethane.
  • the crystals are formed by the following steps: i) forming a miscible solution comprising the therapeutic agent, a solvent and a non-solvent, wherein the therapeutic agent is substantially soluble in the solvent and substantially insoluble in the non- solvent, and wherein the solvent is miscible in, and more volatile than, the non-solvent; ii) applying the solution onto a medical device as a coating; and iii) allowing at least a portion of the solvent to evaporate from the coating, whereupon the therapeutic agent forms into crystals on the surface of the medical device.
  • the therapeutic agent is applied to the medical device, while in solution or otherwise, by any suitable method.
  • Preferred methods include spraying the device with the therapeutic agent or solution, and dipping the device into the therapeutic agent or solution.
  • the thickness of the therapeutic agent, together with any polymer is in the range of from 1 to about 50 microns. The thickness of such a coating is not, however, a critical feature of the present invention so long as a sufficient amount of therapeutic agent to provide a sustained or controlled release over a suitable or desired time period is provided.
  • the medical device is optionally at least partially coated with a polymer precoat for enhanced adhesion of the therapeutic agent.
  • the polymer precoat should have a low solubility for the therapeutic agent.
  • Preferred precoat materials include polycarboxylic acids, cellulosic polymers, gelatin, polyvinylpyrrolidone, maleic anhydride polymers, polyamides, polyvinyl alcohols, polyethylene oxides, glycosaminoglycans, polysaccharides, polyesters, polyurethanes, silicones, polyorthoesters, polyanhydrides, polycarbonates, polypropylenes, polylactic acids, polyglycolic acids, polycaprolactones, polyhydroxybutyrate valerates, polyacrylamides, polyethers, and mixtures and copolymers thereof.
  • the crystals of the therapeutic agent are optionally coated with a polymer topcoat for physical protection of the crystals, and/or as a barrier to premature release of the therapeutic agent, and/or to further retard or control the release rate of the therapeutic agent.
  • the topcoat may be either biodegradable or biostable. If the topcoat is biodegradable, the therapeutic agent is substantially released after the decomposition of the topcoat. If the topcoat is biostable, the therapeutic agent is substantially released by diffusion through the topcoat.
  • Preferred biodegradable materials for the topcoat include polymers such as poly(L-lactic acid), poly(DL-lactic acid), polycaprolactone, poly(hydroxy butyrate), polyglycolide, poly(dioxanone), poly(hydroxy valerate), polyorthoester; copolymers such as poly (lactide-co- glycolide), polyhydroxy(butyrate-co-valerate), polyglycolide-co-trimethylene carbonate; polyanhydrides; polyphosphoester; polyphosphoester-urethane; polyamino acids; polycyanoacrylates; biomolecules such as fibrin, fibrinogen, cellulose, starch, collagen and hyaluronic acid; and mixtures thereof.
  • polymers such as poly(L-lactic acid), poly(DL-lactic acid), polycaprolactone, poly(hydroxy butyrate), polyglycolide, poly(dioxanone), poly(hydroxy valerate), polyorthoester; copolymers such as poly (lactide
  • Preferred biostable materials for the topcoat include polymers such as polyurethane, silicones, polyesters, polyolefins, polyamides, polycaprolactam, polyimide, polyvinyl chloride, polyvinyl methyl ether, polyvinyl alcohol, acrylic polymers and copolymers, polyacrylonitrile, polystyrene copolymers of vinyl monomers with olefins (such as styrene acrylonitrile copolymers, ethylene methyl methacrylate copolymers, ethylene vinyl acetate), polyethers, rayons, cellulosics (such as cellulose acetate, cellulose nitrate, cellulose propionate, etc.), parylene and derivatives thereof; and mixtures and copolymers thereof.
  • polymers such as polyurethane, silicones, polyesters, polyolefins, polyamides, polycaprolactam, polyimide, polyvinyl chloride, polyvinyl methyl ether,
  • the precoat and topcoat materials are applied by any suitable method such as, for example, spraying, dipping, and vapor deposition such as plasma deposition, physical vapor deposition, chemical vapor deposition, ion bombardment, ion-beam sputter deposition, ion-beam assisted deposition, and sputtering.
  • spraying dipping
  • vapor deposition such as plasma deposition, physical vapor deposition, chemical vapor deposition, ion bombardment, ion-beam sputter deposition, ion-beam assisted deposition, and sputtering.
  • Example 1 Formation of Paclitaxel Crystals from Coated Stents by Exposure to a Non-solvent Paclitaxel (TAXOL ® ) was placed into solution by mixing about 0.19 milligrams of polyurethane, about 0.10 milligrams reagent paclitaxel, and about 27.15 milligrams of 99.9% ACS HPLC-grade chloroform stabilized with ethanol. The mixture was mixed with a magnetic stirrer for about one hour to form a solution consisting of about 1.0% solids and having a polyurethane-to-paclitaxel ratio of about 65-to-35.
  • TAXOL ® Non-solvent Paclitaxel
  • the paclitaxel solution was sprayed onto 9 millimeter NIR ® (Medinol, Tel Aviv, Israel) stents with a Badger Air Brush model 350 sprayer at a pressure of about 19 psi for about 1 minute. The distance between the stents and the spray nozzle was about 2.5 inches. A uniform coating of approximately 13 microns was obtained. The coating was dried for about 30 minutes at about 65°C to remove solvent, followed by thorough drying for about 3 hours at 70°C under vacuum.
  • 9 millimeter NIR ® Medinol, Tel Aviv, Israel
  • Paclitaxel crystals were formed on some of the stents by exposure to about 5 milliliters of distilled water for about 1.5 days while stirring at room temperature. The stents were thereafter removed from water and air dried. Scanning electron microscopy was used to confirm the presence of paclitaxel crystals on the surface of the coated stents. The crystals were up to approximately 200 microns in length.
  • Stents coated with paclitaxel in both crystalline and non- crystalline form were made in accordance with Example 1.
  • the in-vitro release of paclitaxel from these stents was measured as a function of time. As shown in Fig. 3, the paclitaxel in crystalline form was released at a slower rate than the paclitaxel dispersed in the polyurethane coating on the coated stents.
  • Topcoats are applied to the coated stents described in Example 1.
  • the topcoats comprise either poly(lactide-co-caprolactone) in solution with 99.9% ACS HPLC-grade chloroform stabilized with ethanol, or polyvinyl alcohol in solution with deionized water.
  • Topcoat solutions are applied to coated stents by spraying with a Badger Air Brush model 350 sprayer at a pressure of about 19 psi for about 10 seconds.
  • the distance between the stents and the spray nozzle is about 2.5 inches.
  • a uniform coating of approximately 1 to 2 microns is obtained.
  • Paclitaxel is placed in solution with acetonitrile, a solvent. Water, a non-solvent, is added in an amount that does not result in precipitation of the paclitaxel from the acetonitrile / water mixture.
  • the mixture of paclitaxel, acetonitrile and water is sprayed onto a NIR ® (Medinol, Tel Aviv, Israel) stent with a Badger Air Brush model 350 sprayer at a pressure of about 19 psi for about 1 minute.
  • the distance between the stents and the spray nozzle is about 2.5 inches.
  • a uniform coating of approximately 13 microns is obtained. As the acetonitrile evaporates from the coating, paclitaxel crystals form.
  • the present invention provides for the controlled, localized delivery of therapeutic agents to target locations within a mammalian body.
  • the invention makes use of crystals of such therapeutic agents to retard and/or control the rate of release.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Surgery (AREA)
  • Vascular Medicine (AREA)
  • Organic Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Materials For Medical Uses (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un dispositif médical destiné à être inséré dans un corps de mammifère, le dispositif médical contenant sur sa surface un agent thérapeutique sous forme cristalline. L'invention concerne aussi une méthode d'administration d'un agent thérapeutique à un emplacement cible situé dans le corps d'un mammifère. Cette méthode consiste à placer des cristaux de l'agent thérapeutique sur un dispositif médical et à amener ce dispositif à l'emplacement cible.
EP99961692A 1998-12-03 1999-11-17 Endoprothese comportant en surface un principe actif sous forme de cristaux Withdrawn EP1135165A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US20425598A 1998-12-03 1998-12-03
US204255 1998-12-03
PCT/US1999/027279 WO2000032238A1 (fr) 1998-12-03 1999-11-17 Endoprothese comportant en surface un principe actif sous forme de cristaux

Publications (1)

Publication Number Publication Date
EP1135165A1 true EP1135165A1 (fr) 2001-09-26

Family

ID=22757217

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99961692A Withdrawn EP1135165A1 (fr) 1998-12-03 1999-11-17 Endoprothese comportant en surface un principe actif sous forme de cristaux

Country Status (4)

Country Link
EP (1) EP1135165A1 (fr)
AU (1) AU1821200A (fr)
CA (1) CA2353606A1 (fr)
WO (1) WO2000032238A1 (fr)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10668188B2 (en) 2012-10-26 2020-06-02 Urotronic, Inc. Drug coated balloon catheters for nonvascular strictures
US10806830B2 (en) 2012-10-26 2020-10-20 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US10850076B2 (en) 2012-10-26 2020-12-01 Urotronic, Inc. Balloon catheters for body lumens
US10881839B2 (en) 2012-10-26 2021-01-05 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US10888640B2 (en) 2015-04-24 2021-01-12 Urotronic, Inc. Drug coated balloon catheters for nonvascular strictures
US10898700B2 (en) 2012-10-26 2021-01-26 Urotronic, Inc. Balloon catheters for body lumens
US11504450B2 (en) 2012-10-26 2022-11-22 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US11730864B2 (en) 2015-04-24 2023-08-22 Urotronic, Inc. Drug coated balloon catheters for nonvascular strictures
US11938287B2 (en) 2012-10-26 2024-03-26 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US11957853B2 (en) 2019-02-22 2024-04-16 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US12005206B2 (en) 2020-02-21 2024-06-11 Urotronic, Inc. Drug-coated balloon catheters for body lumens

Families Citing this family (58)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070032853A1 (en) 2002-03-27 2007-02-08 Hossainy Syed F 40-O-(2-hydroxy)ethyl-rapamycin coated stent
DE10191512D2 (de) 2000-04-11 2003-03-13 Univ Heidelberg Umhüllungen und Folien aus Poly-Tri-Fluor-Ethoxypolyphosphazen
AU2003267309A1 (en) 2000-11-16 2004-04-08 Microspherix Llc Flexible and/or elastic brachytherapy seed or strand
AU2001297657A1 (en) * 2000-11-16 2002-09-12 Microspherix Llc Polymeric imagable brachytherapy seed
US6746661B2 (en) 2000-11-16 2004-06-08 Microspherix Llc Brachytherapy seed
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
DE10115740A1 (de) * 2001-03-26 2002-10-02 Ulrich Speck Zubereitung für die Restenoseprophylaxe
DE02717541T1 (de) * 2001-05-07 2004-08-26 Cornell Research Foundation, Inc. Biologisch abbaubare copolymere, die an ein segment mit mehreren funktionellen gruppen gebunden sind
DE50208282D1 (de) 2001-08-17 2006-11-09 Polyzenix Gmbh Vorrichtung auf basis von nitinol mit polyphosphazenüberzug
WO2004006976A1 (fr) 2002-07-12 2004-01-22 Cook Incorporated Dispositif medical muni d'un revetement
DE10244847A1 (de) 2002-09-20 2004-04-01 Ulrich Prof. Dr. Speck Medizinische Vorrichtung zur Arzneimittelabgabe
US20050118344A1 (en) 2003-12-01 2005-06-02 Pacetti Stephen D. Temperature controlled crimping
US8551512B2 (en) 2004-03-22 2013-10-08 Advanced Cardiovascular Systems, Inc. Polyethylene glycol/poly(butylene terephthalate) copolymer coated devices including EVEROLIMUS
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
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
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
ES2691646T3 (es) 2005-07-15 2018-11-28 Micell Technologies, Inc. Revestimientos poliméricos que contienen polvo de fármaco de morfología controlada
AU2011256902B2 (en) * 2005-07-15 2015-03-12 Micell Technologies, Inc. Polymer coatings containing drug powder of controlled morphology
US20090062909A1 (en) 2005-07-15 2009-03-05 Micell Technologies, Inc. Stent with polymer coating containing amorphous rapamycin
US7842312B2 (en) 2005-12-29 2010-11-30 Cordis Corporation Polymeric compositions comprising therapeutic agents in crystalline phases, and methods of forming the same
US7919108B2 (en) * 2006-03-10 2011-04-05 Cook Incorporated Taxane coatings for implantable medical devices
US7875284B2 (en) 2006-03-10 2011-01-25 Cook Incorporated Methods of manufacturing and modifying taxane coatings for implantable medical devices
EP2944382A1 (fr) 2006-04-26 2015-11-18 Micell Technologies, Inc. Revêtements contenant plusieurs médicaments
WO2008033199A1 (fr) * 2006-09-12 2008-03-20 Boston Scientific Limited Dépôt de masque liquide pour le revêtement sélectif d'une endoprothèse vasculaire
US11426494B2 (en) 2007-01-08 2022-08-30 MT Acquisition Holdings LLC Stents having biodegradable layers
CN101711137B (zh) 2007-01-08 2014-10-22 米歇尔技术公司 具有可生物降解层的支架
DE102007003184A1 (de) * 2007-01-22 2008-07-24 Orlowski, Michael, Dr. Verfahren zur Beladung von strukturierten Oberflächen
US8802184B2 (en) 2007-05-30 2014-08-12 Abbott Cardiovascular Systems Inc. Medical devices containing biobeneficial particles
US9192697B2 (en) 2007-07-03 2015-11-24 Hemoteq Ag Balloon catheter for treating stenosis of body passages and for preventing threatening restenosis
US8679519B2 (en) * 2007-10-23 2014-03-25 Abbott Cardiovascular Systems Inc. Coating designs for the tailored release of dual drugs from polymeric coatings
EP2271294B1 (fr) 2008-04-17 2018-03-28 Micell Technologies, Inc. Stents à couches bioabsorbables
CA2728668A1 (fr) 2008-06-25 2009-12-30 Boston Scientific Scimed, Inc. Dispositifs medicaux renfermant des agents therapeutiques
US9510856B2 (en) 2008-07-17 2016-12-06 Micell Technologies, Inc. Drug delivery medical device
AU2009270849B2 (en) 2008-07-17 2013-11-21 Micell Technologies, Inc. Drug delivery medical device
US8500687B2 (en) 2008-09-25 2013-08-06 Abbott Cardiovascular Systems Inc. Stent delivery system having a fibrous matrix covering with improved stent retention
IT1394522B1 (it) * 2009-01-09 2012-07-05 Invatec Technology Ct Gmbh Dispositivo medicale con rilascio di farmaco
US20120231037A1 (en) 2009-02-02 2012-09-13 Yissum Research Development Companyof the Hebrew U Crystalline drug-containing coatings
WO2010120552A2 (fr) 2009-04-01 2010-10-21 Micell Technologies, Inc. Endoprothèses enduites
WO2010121187A2 (fr) 2009-04-17 2010-10-21 Micell Techologies, Inc. Endoprothèses vasculaires ayant une élution contrôlée
EP3064230B1 (fr) 2009-07-10 2019-04-10 Boston Scientific Scimed, Inc. Utilisation de nanocristaux pour un ballonnet de distribution de médicament
WO2011008393A2 (fr) * 2009-07-17 2011-01-20 Boston Scientific Scimed, Inc. Nucléation de ballons d’administration de médicament pour fournir une taille et une densité des cristaux améliorées
EP2501431B1 (fr) 2009-11-19 2020-01-08 Wellinq Medical B.V. Cathéter médical à ballonet extensible, libérant une composition et de profil étroit
US11369498B2 (en) 2010-02-02 2022-06-28 MT Acquisition Holdings LLC Stent and stent delivery system with improved deliverability
US10232092B2 (en) 2010-04-22 2019-03-19 Micell Technologies, Inc. Stents and other devices having extracellular matrix coating
CA2805631C (fr) 2010-07-16 2018-07-31 Micell Technologies, Inc. Dispositif medical d'administration de medicament
US8889211B2 (en) 2010-09-02 2014-11-18 Boston Scientific Scimed, Inc. Coating process for drug delivery balloons using heat-induced rewrap memory
CA2841360A1 (fr) 2011-07-15 2013-01-24 Micell Technologies, Inc. Dispositif medical d'administration de medicament
US9056152B2 (en) 2011-08-25 2015-06-16 Boston Scientific Scimed, Inc. Medical device with crystalline drug coating
US10188772B2 (en) 2011-10-18 2019-01-29 Micell Technologies, Inc. Drug delivery medical device
US11039943B2 (en) 2013-03-12 2021-06-22 Micell Technologies, Inc. Bioabsorbable biomedical implants
JP2016519965A (ja) 2013-05-15 2016-07-11 マイセル・テクノロジーズ，インコーポレイテッド 生体吸収性バイオメディカルインプラント
DE102013014821A1 (de) * 2013-09-10 2015-03-12 Alexander Rübben Gefäßendoprothesenbeschichtung
DE102013110294B4 (de) 2013-09-18 2016-07-07 Innora Gmbh Limus-Depot-Formulierung auf Ballonkathetern
US20150196489A1 (en) * 2013-12-18 2015-07-16 Massachusetts Institute Of Technology Polymer matrices for controlling crystallization
WO2015181826A1 (fr) 2014-05-27 2015-12-03 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Revêtement cristallin et libération d'agents bioactifs
US9655998B2 (en) 2014-08-07 2017-05-23 Cook Medical Technologies Llc Encapsulated drug compositions and methods of use thereof
US11241520B2 (en) 2014-08-07 2022-02-08 Cook Medical Technologies Llc Compositions and devices incorporating water-insoluble therapeutic agents and methods of the use thereof
US9180226B1 (en) 2014-08-07 2015-11-10 Cook Medical Technologies Llc Compositions and devices incorporating water-insoluble therapeutic agents and methods of the use thereof

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6515009B1 (en) * 1991-09-27 2003-02-04 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
NZ511762A (en) * 1993-07-19 2003-09-26 Univ British Columbia Anti-angiogenic compositions and methods of use
ATE278397T1 (de) * 1997-03-31 2004-10-15 Boston Scient Ltd Verwendung von cytoskelettinhibitoren zur vorbeugung der restenose

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0032238A1 *

Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11471655B2 (en) 2012-10-26 2022-10-18 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US10881839B2 (en) 2012-10-26 2021-01-05 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US10668188B2 (en) 2012-10-26 2020-06-02 Urotronic, Inc. Drug coated balloon catheters for nonvascular strictures
US10850076B2 (en) 2012-10-26 2020-12-01 Urotronic, Inc. Balloon catheters for body lumens
US11938287B2 (en) 2012-10-26 2024-03-26 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US11925729B2 (en) 2012-10-26 2024-03-12 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US10898700B2 (en) 2012-10-26 2021-01-26 Urotronic, Inc. Balloon catheters for body lumens
US11504450B2 (en) 2012-10-26 2022-11-22 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US10994103B2 (en) 2012-10-26 2021-05-04 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US10994104B2 (en) 2012-10-26 2021-05-04 Urotronic, Inc. Balloon catheters for body lumens
US11439801B2 (en) 2012-10-26 2022-09-13 Urotronic, Inc. Balloon catheters for body lumens
US11471656B2 (en) 2012-10-26 2022-10-18 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US10806830B2 (en) 2012-10-26 2020-10-20 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US10675386B2 (en) 2012-10-26 2020-06-09 Urotronic, Inc. Drug coated balloon catheters for nonvascular strictures
US10987451B2 (en) 2012-10-26 2021-04-27 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US11648338B2 (en) 2012-10-26 2023-05-16 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US11648337B2 (en) 2012-10-26 2023-05-16 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US11826533B2 (en) 2012-10-26 2023-11-28 Urotronic, Inc. Balloon catheters for body lumens
US11826532B2 (en) 2012-10-26 2023-11-28 Urotronic, Inc. Balloon catheters for body lumens
US11730864B2 (en) 2015-04-24 2023-08-22 Urotronic, Inc. Drug coated balloon catheters for nonvascular strictures
US11904072B2 (en) 2015-04-24 2024-02-20 Urotronic, Inc. Drug coated balloon catheters for nonvascular strictures
US10888640B2 (en) 2015-04-24 2021-01-12 Urotronic, Inc. Drug coated balloon catheters for nonvascular strictures
US11484628B2 (en) 2015-04-24 2022-11-01 Urotronic, Inc. Drug coated balloon catheters for nonvascular strictures
US11957853B2 (en) 2019-02-22 2024-04-16 Urotronic, Inc. Drug-coated balloon catheters for body lumens
US12005206B2 (en) 2020-02-21 2024-06-11 Urotronic, Inc. Drug-coated balloon catheters for body lumens

Also Published As

Publication number Publication date
AU1821200A (en) 2000-06-19
CA2353606A1 (fr) 2000-06-08
WO2000032238A1 (fr) 2000-06-08
WO2000032238A9 (fr) 2000-12-07

Similar Documents

Publication Publication Date Title
EP1135165A1 (fr) Endoprothese comportant en surface un principe actif sous forme de cristaux
US8551446B2 (en) Poly(vinyl acetal) coatings for implantable medical devices
EP2682138B1 (fr) Produits médicaux améliorés avec revêtement médicamenteux et leur fabrication
US7396539B1 (en) Stent coatings with engineered drug release rate
EP1214108B1 (fr) Prothese poreuse et procede de depot de substances dans les pores
US6287628B1 (en) Porous prosthesis and a method of depositing substances into the pores
US6379381B1 (en) Porous prosthesis and a method of depositing substances into the pores
US6818247B1 (en) Ethylene vinyl alcohol-dimethyl acetamide composition and a method of coating a stent
US7901703B2 (en) Polycationic peptides for cardiovascular therapy
CN101795719B (zh) 药物缓释性支架
US7335391B1 (en) Method for coating implantable devices
US8257729B2 (en) Implants with membrane diffusion-controlled release of active ingredient
US20030088307A1 (en) Potent coatings for stents
US20040022853A1 (en) Polymer-based, sustained release drug delivery system
US20090136556A1 (en) System And Method For Coating Implantable Devices
CA2298543A1 (fr) Mise en charge et liberation de medicaments insolubles dans l'eau
KR20040005936A (ko) 공동약물을 함유하는 서방 약물 전달 시스템
US7824729B2 (en) Methods for coating an implantable device
CA2395199A1 (fr) Revetement biocompatible
WO2004000383A2 (fr) Revetements a base de polyacrylates pour dispositifs medicaux implantables
US20060216327A1 (en) Multilayer coating for releasing biologically-active agents and method of making

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20010618

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

AX Request for extension of the european patent

Free format text: AL PAYMENT 20010618;LT PAYMENT 20010618;LV PAYMENT 20010618;MK PAYMENT 20010618;RO PAYMENT 20010618;SI PAYMENT 20010618

17Q First examination report despatched

Effective date: 20031121

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20040402