US20050187611A1 - Drug coating with topcoat - Google Patents

Drug coating with topcoat Download PDF

Info

Publication number
US20050187611A1
US20050187611A1 US11/116,256 US11625605A US2005187611A1 US 20050187611 A1 US20050187611 A1 US 20050187611A1 US 11625605 A US11625605 A US 11625605A US 2005187611 A1 US2005187611 A1 US 2005187611A1
Authority
US
United States
Prior art keywords
stent
medical device
polymer composition
topcoat
coating
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.)
Abandoned
Application number
US11/116,256
Inventor
Ni Ding
Michael Helmus
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 Scimed Inc
Original Assignee
Boston Scientific Scimed Inc
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=25542881&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=US20050187611(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from US08/663,518 external-priority patent/US6120536A/en
Application filed by Boston Scientific Scimed Inc filed Critical Boston Scientific Scimed Inc
Priority to US11/116,256 priority Critical patent/US20050187611A1/en
Publication of US20050187611A1 publication Critical patent/US20050187611A1/en
Assigned to SCHNEIDER (USA) INC. reassignment SCHNEIDER (USA) INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: HELMUS, MICHAEL N., DING, NI
Assigned to BOSTON SCIENTIFIC SCIMED, INC. reassignment BOSTON SCIENTIFIC SCIMED, INC. CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: SCHNEIDER (USA) INC.
Abandoned legal-status Critical Current

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L33/00Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
    • A61L33/0005Use of materials characterised by their function or physical properties
    • A61L33/0011Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/22Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/227Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L31/00Materials 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
    • A61L31/08Materials for coatings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L31/00Materials 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
    • A61L31/08Materials for coatings
    • A61L31/10Macromolecular materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L31/00Materials 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
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/141Plasticizers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L31/00Materials 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
    • A61L31/14Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16Biologically active materials, e.g. therapeutic substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2210/00Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2210/0014Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof using shape memory or superelastic materials, e.g. nitinol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2250/00Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0058Additional features; Implant or prostheses properties not otherwise provided for
    • A61F2250/0067Means for introducing or releasing pharmaceutical products into the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/23Carbohydrates
    • A61L2300/236Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404Biocides, antimicrobial agents, antiseptic agents
    • A61L2300/406Antibiotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/416Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/42Anti-thrombotic agents, anticoagulants, anti-platelet agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602Type of release, e.g. controlled, sustained, slow
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606Coatings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2300/00Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606Coatings
    • A61L2300/608Coatings having two or more layers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2420/00Materials or methods for coatings medical devices
    • A61L2420/08Coatings comprising two or more layers

Definitions

  • the present invention relates generally to providing biostable elastomeric coatings on the surfaces of implants which incorporate biologically active species having controlled release characteristics in the coating and relates particularly to providing a non-thrombogenic surface during and after timed release of the biologically active species.
  • the invention is particularly described in terms of coatings on therapeutic expandable stent prostheses for implantation in body lumens, e.g., vascular implantation.
  • stent devices In surgical or other related invasive procedures, the insertion and expansion of stent devices in blood vessels, urinary tracts or other locations difficult to otherwise access for the purpose of preventing restenosis, providing vessel or lumen wall support or reinforcement and for other therapeutic or restorative functions has become a common form of long-term treatment.
  • prostheses are applied to a location of interest utilizing a vascular catheter, or similar transluminal device, to carry the stent to the location of interest where it is thereafter released to expand or be expanded in situ.
  • These devices are generally designed as permanent implants which may become incorporated in the vascular or other tissue which they contact at implantation.
  • One type of self-expanding stent has a flexible tubular body formed of several individual flexible thread elements each of which extends in a helix configuration with the centerline of the body serving as a common axis.
  • the elements are wound in the same direction but are displaced axially relative to each other and meet, under crossing a like number of elements also so axially displaced, but having the opposite direction of winding.
  • This configuration provides a resilient braided tubular structure which assumes stable dimensions upon relaxation. Axial tension produces elongation and corresponding diameter contraction that allows the stent to be mounted on a catheter device and conveyed through the vascular system as a narrow elongated device. Once tension is relaxed in situ, the device at least substantially reverts to its original shape.
  • Prostheses of the class including a braided flexible tubular body are illustrated and described in U.S. Pat. Nos. 4,655,771 and 4,954,126 to Wallsten and U.S. Pat. No. 5,061,275 to Wallsten et al.
  • Implanted stents have been used to carry medicinal agents, such as thrombolytic agents.
  • U.S. Pat. No. 5,163,952 to Froix discloses a thermalmemoried expanding plastic stent device formulated to carry a medicinal agent in the material of the stent itself.
  • Pinchuk in U.S. Pat. No. 5,092,877, discloses a stent of a polymeric material which may have a coating associated with the delivery of drugs.
  • Other patents which are directed to devices of the class utilizing bio-degradable or bio-sorbable polymers include Tang et al., U.S. Pat. No. 4,916,193, and MacGregor, U.S. Pat. No. 4,994,071.
  • a patent to Sahatjian, U.S. Pat. No. 5,304,121 discloses a coating applied to a stent consisting of a hydrogel polymer and a preselected drug such as a cell growth inhibitors or heparin.
  • a further method of making a coated intravascular stent carrying a therapeutic material is described in Berg et al., U.S. Pat. No. 5,464,650, issued on Nov. 7, 1995 and corresponding to European Patent Application No. 0 623 354 A1 published 9 Nov. 1994.
  • a polymer coating material is dissolved in a solvent and the therapeutic material dispersed in the solvent; the solvent evaporated after application.
  • a coating containing a hydrophilic or a lipophobic drug is usually very fast initially when the coated device contacts body fluid or blood.
  • One of the methods to reduce the so called “burst effect” is to add a membrane containing porosigen over the coating layer containing the biologically active material. See e.g., U.S. Pat. No. 5,605,696 to Eury et al. and U.S. Pat. No. 5,447,724 to Helmus et al. When the porosigen elutes, a porous membrane is formed and the drug in the undercoat will release.
  • polymeric stents may have mechanical properties that are inferior to those of metal stents of like thickness and weave.
  • Metallic vascular stents braided of even relatively fine metal can provide a large amount of strength to resist inwardly directed circumferential pressure.
  • a polymer material of comparable strength requires a much thicker-walled structure or heavier, denser filament weave, which in turn, reduces the cross-sectional area available for flow through the stent and/or reduces the relative amount of open space in the weave. Also, it is usually more difficult to load and deliver polymeric stents using catheter delivery systems.
  • the coating and coating modification process of the present invention is not so limited and can be used on a wide variety of prosthetic devices.
  • the present invention also applies, for example, to the class of stents that are not self-expanding, including those which can be expanded, for instance, with a balloon; as well as polymeric stents of all kinds.
  • Other medical devices that can benefit from the present invention include blood exchanging devices, vascular access ports, central venus catheters, cardiovascular catheters, extracorpeal circuits, vascular grafts, pumps, heart valves, and cardiovascular sutures, to name a few. Regardless of detailed embodiments, applicability of the invention should not be considered limited with respect to implant design, implant location or materials of construction. Further, the present invention may be used with other types of implantable prostheses.
  • Another object of the invention is to provide a coating and process for coating a stent prostheses using a biostable hydrophobic elastomer in which biologically active species are incorporated within a coating.
  • Still another object of the present invention is to provide a multi-layer coating and process for the delivery of biologically active species in which the percentage of active material can vary from layer to layer.
  • Yet another object of the present invention is to provide a multi-layer coating and process for the delivery of biologically active species from a coating with a non-thrombogenic surface.
  • Another object of the invention is to provide a coating for the delivery of biologically active species having a top layer or topcoat which reduces the initial release of the species, in which the topcoat is substantially free of pores or porosigens and covers less than the entire surface of the undercoat.
  • the topcoat can cover less than the entire surface of the undercoat before and/or while the device is implanted.
  • a further object of the invention is to provide a multilayer coating for the delivery of biologically active species such as heparin having a fluorosilicone top layer.
  • a still further object of the invention is to provide a multi-layer coating for the delivery of biologically active species such as heparin having a surface containing immobilized polyethylene glycol (PEG).
  • biologically active species such as heparin having a surface containing immobilized polyethylene glycol (PEG).
  • the present invention provides a relatively thin layered coating of biostable elastomeric material containing an amount of biologically active material dispersed therein in combination with a non-thrombogenic surface that is useful for coating the surfaces of prostheses such as deployable stents.
  • the preferred stent to be coated is a self-expanding, open-ended tubular stent prostheses.
  • the tubular body is formed of a self expanding open braid of fine single or polyfilament metal wire which flexes without collapsing, readily axially deforms to an elongate shape for transluminal insertion via a vascular catheter and resiliently expands toward predetermined stable dimensions upon removal in situ.
  • the initial coating is preferably applied as a mixture, solution or suspension of polymeric material and finely divided biologically active species dispersed in an organic vehicle or a solution or partial solution of such species in a solvent or vehicle for the polymer and/or biologically active species.
  • the term “finally divided” means any type or size of included material from dissolved molecules through suspensions colloids and particulate mixtures.
  • the biologically active material is dispersed in a carrier material which may be the polymer, a solvent, or both.
  • the coating is preferably applied as a plurality of relatively thin layers sequentially applied in relatively rapid sequence and is preferably applied with the stent in a radially expanded state.
  • the layered coating is referred to or characterized as including an undercoat and topcoat.
  • the coating thickness ratio of the topcoat to undercoat may vary with the desired effect and/or the elution system. Typically these are of different formulations with most or all of the biologically active material being contained in the undercoat and a non-thrombogenic or biocompatible non-porous surface found in the topcoat.
  • the topcoat be substantially free of connected pores or porosigens (materials which can elute during implantation and form pores).
  • the addition of a porous membrane as a top coat will increase the coating thickness and reduce the overall drug loading.
  • the release of porosigens into the body can be undesirable since it introduces additional foreign materials into the body, which can cause the patient to have adverse reactions.
  • the topcoat should be substantially free of pores, the topcoat should cover less than the entire surface of the undercoat. Preferably, the topcoat should cover only about 10% to about 95% of the surface of the undercoat.
  • the biologically active material or drug of the undercoat is permitted to be released from the undercoat through those parts of the undercoat which are not covered by the topcoat.
  • FIG. 9 shows a surface of a prosthesis 101 covered by a coating 102 comprising an undercoat 103 and a topcoat 104 .
  • the topcoat 104 which only partially covers the undercoat 103 , leaves certain areas 106 of the undercoat, including drug particles 105 , exposed to body fluids at the implantation site. It is through these “uncovered” areas 106 of the undercoat that the drug particles 105 of the undercoat 103 are allowed to be released into the implantation site.
  • the topcoats have an average thickness equivalent to the average particle size of the drug in the undercoat.
  • the average thickness is about 1 to 7 microns and more preferable that the topcoat average thickness be about 1 to 5 microns.
  • the polymer of the topcoat may be the same as or different from the polymer of the undercoat.
  • the coating may be applied by dipping or spraying using evaporative solvent materials of relatively high vapor pressure to produce the desired viscosity and quickly establish coating layer thicknesses.
  • the preferred process is predicated on reciprocally spray coating a rotating radially expanded stent employing an air brush device.
  • the coating process enables the material to adherently conform to and cover the entire surface of the filaments of the open structure of the stent but in a manner such that the open lattice nature of the structure of the braid or other pattern is preserved in the coated device.
  • the coating is exposed to room temperature ventilation for a predetermined time (possibly one hour or more) for solvent vehicle evaporation.
  • a predetermined time possibly one hour or more
  • the polymer material is cured at room temperature or elevated temperatures. Curing is defined as the process of converting the elastomeric or polymeric material into the finished or useful state by the application of heat and/or chemical agents which induce physico-chemical changes.
  • solvent evaporation can occur at room temperature rendering the undercoat useful for controlled drug release without further curing.
  • the applicable ventilation time and temperature for cure are determined by the particular polymer involved and particular drugs used.
  • silicone or polysiloxane materials such as polydimethylsiloxane
  • Urethane prepolymers can also be utilized. Unlike the polyurethane thermoplastic elastomers, some of these materials are applied as prepolymers in the coating composition and must thereafter be heat cured.
  • the preferred silicone species have a relatively low cure temperatures and are known as a room temperature vulcanizable (RTV) materials.
  • RTV room temperature vulcanizable
  • Some polydimethylsiloxane materials can be cured, for example, by exposure to air at about 90° C. for a period of time such as 16 hours.
  • a curing step may be implemented both after application of the undercoat or a certain number of lower layers and the top layers or a single curing step used after coating is completed.
  • the coated stents may thereafter be subjected to a postcure process which includes an inert gas plasma treatment, and sterilization which may include gamma radiation, ETO treatment, electron beam or steam treatment.
  • a postcure process which includes an inert gas plasma treatment, and sterilization which may include gamma radiation, ETO treatment, electron beam or steam treatment.
  • unconstrained coated stents are placed in a reactor chamber and the system is purged with nitrogen and a vacuum applied to 20-50 mTorr. Thereafter, inert gas (argon, helium or mixture of them) is admitted to the reaction chamber for the plasma treatment.
  • inert gas argon, helium or mixture of them
  • argon (Ar) gas operating at a power range from 200 to 400 watts, a flow rate of 150-650 standard ml per minute, which is equivalent to about 100-450 mTorr, and an exposure time from 30 seconds to about 5 minutes.
  • the stents can be removed immediately after the plasma treatment or remain in the argon atmosphere for an additional period of time, typically five minutes.
  • the topcoat or surface coating may be applied in any of several ways to further control thrombolytic effects and optionally, control the release profile especially the initial very high release rate associated with the elution of heparin.
  • an outer layer of fluorosilicone (FSi) is applied to the undercoat as a topcoat.
  • the outer layer can also contain heparin.
  • polyethylene glycol (PEG) is immobilized on the surface of the coating.
  • the underlayer is subjected to inert gas plasma treatment and immediately thereafter is treated by ammonia (NH3) plasma to aminate the surface.
  • NH3 plasma ammonia
  • Amination means creating mostly imino groups and other nitro containing species on the surface. This is followed by immediate immersion into electrophilically activated polyethylene glycol (PEG) solution with a reductive agent, i.e., sodium cyanoborohydride.
  • a substantially non-porous topcoat can be produced from a topcoat composition which comprises a substantially pure polymeric material.
  • the material preferably provides biocompatibility to the implanted device during and after release of the biologically active material.
  • a number of methods can be used. For instance, by controlling the thickness of the topcoat so that it has an average thickness less than that of the diameter of certain drug particles, the undercoat will be only partly covered by the topcoat since some of drug particles will not be covered by the topcoat.
  • a partial topcoat can be formed by using a topcoat polymer which is incompatible with the undercoat polymer to generate a microphase separation in the topcoat. Furthermore, to make a topcoat which covers less than the entire surface of the undercoat or which only partially covers the undercoat, a poor solvent wash can be applied to the topcoat, to force the topcoat polymer to shrink so that the undercoat is not entirely covered.
  • the topcoat can partially or fully cover the undercoat prior to delivery or implantation of the device.
  • the topcoat materials can be selected so they have certain water permeability. When water penetrates the topcoat and into the drug particles of the undercoat, the water will swell the particles or dissolve the particles. In either situation, it creates osmotic pressure in the surrounding coating material of the undercoat. The pressure then breaks the thinnest part of the topcoat, and leave the void space in the topcoat for the drug to elute out.
  • the topcoat material has a different Young's modulus (either while it is wet or dry) than that of the undercoat material. More specifically, the Young's modulus can be higher for the topcoat material.
  • the coating undergoes compression or stretching. Topcoat materials with higher Young's modulus tend to crack and form void spaces for the drug to elute from undercoat.
  • topcoat Another way to form a topcoat is to cover the undercoat with a bioabsorbable material.
  • the topcoat can cover either the entire undercoat or only part of the undercoat before or after implantation.
  • the bioabsorbable material of the topcoat will degrade. The rate of degradation depends upon the bioabsorbable material used.
  • the topcoat is partially absorbed, the undercoat is exposed to the body fluid and the drug is released, however the burst effect will be reduced.
  • the coated and cured stents having the modified outer layer or surface optionally are subjected to a final gamma radiation sterilization nominally at 2.5-3.5 Mrad.
  • Argon (Ar) plasma treated stents enjoy full resiliency after radiation whether exposed in a constrained or non-constrained status, while constrained stents subjected to gamma sterilization without Ar plasma pretreatment lose resiliency and do not recover at a sufficient or appropriate rate where the undercoat is silicone.
  • the elastomeric materials that form the stent coating underlayers should possess certain properties.
  • the layers should be of suitable hydrophobic biostable elastomeric materials which do not degrade.
  • Surface layer or topcoat materials should minimize tissue rejection and tissue inflammation and permit encapsulation by tissue adjacent the stent implantation site. Exposed material is designed to reduce clotting tendencies in blood contacted and the surface is preferably modified accordingly.
  • underlayers of the above materials are preferably provided with a silicone or a fluorosilicone outer coating layer which should not contain imbedded bioactive material, such as heparin in order to avoid the formation of pores in the topcoat.
  • the outer coating may consist essentially of polyethylene glycol (PEG), polysaccharides, phospholipids, or combinations of the foregoing.
  • Polymers generally suitable for the undercoats or underlayers include silicones (e.g., polysiloxanes and substituted polysiloxanes), polyurethanes, thermoplastic elastomers in general, ethylene vinyl acetate copolymers, polyolefin elastomers, polyamide elastomers, and EPDM rubbers.
  • silicones e.g., polysiloxanes and substituted polysiloxanes
  • thermoplastic elastomers in general, ethylene vinyl acetate copolymers, polyolefin elastomers, polyamide elastomers, and EPDM rubbers.
  • the above-referenced materials are considered hydrophobic with respect to the contemplated environment of the invention.
  • Surface layer or topcoat materials can include the same polymer as that of the undercoat.
  • suitable polymers include without limitation fluorosilicones and polyethylene glycol (PEG), polysaccharides, phospholipids, and combinations of the foregoing.
  • agents possibly suitable for incorporation include antithrobotics, anticoagulants, antibiotics antiplatelet agents, thrombolytics, antiproliferatives, steroidal and nonsteroidal antiinflammatories, agents that inhibit hyperplasia and in particular restenosis, smooth muscle cell inhibitors, growth factors, growth factor inhibitors, cell adhesion inhibitors, cell adhesion promoters and drugs that may enhance the formation of healthy neointimal tissue, including endothelial cell regeneration.
  • the positive action may come from inhibiting particular cells (e.g., smooth muscle cells) or tissue formation (e.g., fibromuscular tissue) while encouraging different cell migration (e.g., endothelium) and tissue formation (neointimal tissue).
  • cells e.g., smooth muscle cells
  • tissue formation e.g., fibromuscular tissue
  • cell migration e.g., endothelium
  • tissue formation eointimal tissue
  • Suitable materials for fabricating the braided stent include stainless steel, tantalum, titanium alloys including nitinol (a nickel titanium, thermomemoried alloy material), and certain cobalt alloys including cobalt-chromium-nickel alloys such as Elgiloy® and Phynox®. Further details concerning the fabrication and details of other aspects of the stents themselves, may be gleaned from the above referenced U.S. Pat. Nos. 4,655,771 and 4,954,126 to Wallsten and U.S. Pat. No. 5,061,275 to Wallsten et al., which are incorporated by reference herein.
  • polymer coating materials can be coordinated with biologically active species of interest to produce desired effects when coated on stents to be implanted in accordance with the invention.
  • Loadings of therapeutic materials may vary.
  • the mechanism of incorporation of the biologically active species into the surface coating, and egress mechanism depend both on the nature of the surface coating polymer and the material to be incorporated.
  • the mechanism of release also depends on the mode of incorporation.
  • the material may elute via interparticle paths or be administered via transport or diffusion through the encapsulating material itself.
  • “elution” is defined as any process of release that involves extraction or release by direct contact of the material with bodily fluids through the interparticle paths connected with the exterior of the coating.
  • Transport or “diffusion” are defined to include a mechanism of release in which the material released traverses through another material.
  • the desired release rate profile can be tailored by varying the coating thickness, the radial distribution (layer to layer) of bioactive materials, the mixing method, the amount of bioactive material, the combination of different matrix polymer materials at different layers, and the crosslink density of the polymeric material.
  • the crosslink density is related to the amount of crosslinking which takes place and also the relative tightness of the matrix created by the particular crosslinking agent used. This, during the curing process, determines the amount of crosslinking and so the crosslink density of the polymer material. For bioactive materials released from the crosslinked matrix, such as heparin, a denser crosslink structure will result in a longer release time and reduced burst effect.
  • FIG. 1 is a schematic flow diagram illustrating the steps of the process of the invention
  • FIG. 2 represents a release profile for a multi-layer system showing the percentage of heparin released over a two-week period
  • FIG. 3 represents a release profile for a multi-layer system showing the relative release rate of heparin over a two-week period
  • FIG. 4 illustrates a profile of release kinetics for different drug loadings at similar coating thicknesses illustrating the release of heparin over a two-week period without associated means to provide a long term non-thrombogenic surface thereafter;
  • FIG. 5 illustrates drug elution kinetics at a given loading of heparin over a two-week period at different coating thicknesses without associated means to provide a long term non-thrombogenic surface thereafter;
  • FIG. 6 illustrates the release kinetics for a given undercoat and topcoat material varied according to thickness in which the percentage heparin in the undercoat and topcoats are kept constant;
  • FIG. 7 is a plot of heparin release kinetics in phosphate buffer system at pH 7.4 with and without fluorosilicone (FSi) topcoat.
  • FIG. 8 is another plot of heparin release kinetics in phosphate buffer system in which a topcoat containing fluorosilicone (FSi) only is compared with an FSi topcoat containing 16.7% imbedded heparin.
  • FSi fluorosilicone
  • FIG. 9 illustrates a surface of an implantable prosthesis covered with an undercoat, containing a biologically active material, which is partly covered by a topcoat.
  • the stent coatings incorporating biologically active materials for timed delivery in situ in a body lumen of interest are preferably sprayed in many thin layers from prepared coating solutions or suspensions.
  • the steps of the process are illustrated generally in FIG. 1 .
  • the coating solutions or suspensions are prepared at 10 as will be described later.
  • the desired amount of crosslinking agent (if any) is added to the suspension/solution as at 12 and material is then agitated or stirred to produce a homogenous coating composition at 14 which is thereafter transferred to an application container or device which may be a container for spray painting at 16 .
  • Typical exemplary preparations of coating solutions that were used for heparin and dexamethasone appear next.
  • Silicone was obtained as a polymer precursor in solvent (xylene) mixture.
  • the manufacturer crosslinker solution was added by using Pasteur P-pipet. The amount of crosslinker added was formed to effect the release rate profile. Typically, five drops of crosslinker solution were added for each five grams of silicone-xylene mixture. The solution was stirred by using the stirring rod until the suspension was homogenous and milk-like. The coating solution was then transferred into a paint jar in condition for application by air brush.
  • Silicone (35% solution as above) was weighed into a beaker on a Metler balance. The weight of dexamethasone free alcohol or acetate form was calculated by silicone weight multiplied by 0.35 and the desired percentage of dexamethasone (1 to 40%) and the required amount was then weighed.
  • the dexamethasone was weighed in a beaker on an analytical balance and half the total amount of THF was added. The solution was stirred well to ensure full dissolution of the dexamethasone. The stirred DEX-THF solution was then transferred to the silicone container. The beaker was washed with the remaining THF and this was transferred to the silicone container. The crosslinker was added by using a Pasteur pipet. Typically, five drops of crosslinker were used for five grams of silicone.
  • the application of the coating material to the stent was quite similar for all of the materials and the same for the heparin and dexamethasone suspensions prepared as in the above Examples.
  • the suspension to be applied was transferred to an application device, at 16 in FIG. 1 .
  • an application device such as a Badger Model 150, supplied with a source of pressurized air through a regulator (Norgren, 0-160 psi) was used. Once the brush hose was attached to the source of compressed air downstream of the regulator, the air was applied. The pressure was adjusted to approximately 15-25 psi and the nozzle condition checked by depressing the trigger.
  • the spray nozzle was adjusted so that the distance from the nozzle to the stent was about 2-4 inches and the composition was sprayed substantially horizontally with the brush being-directed along the stent from the distal end of the stent to the proximal end and then from the proximal end to the distal end in a sweeping motion at a speed such that one spray cycle occurred in about three stent rotations.
  • a pause of less than one minute normally about one-half minute, elapsed between layers.
  • the number of coating layers did and will vary with the particular application. For example, typical tie-layers as at 18 in FIG. 1 , for a coating level of 3-4 mg of heparin per cm 2 of projected area, 20 cycles of coating application are required and about 30 ml of solution will be consumed for a 3.5 mm diameter by 14.5 cm long stent.
  • the rotation speed of the motor can be adjusted as can the viscosity of the composition and the flow rate of the spray nozzle as desired to modify the layered structure.
  • the best results have been obtained at rotational speeds in the range of 30-50 rpm and with a spray nozzle flow rate in the range of 4-10 ml of coating composition per minute, depending on the stent size. It is contemplated that a more sophisticated, computer-controlled coating apparatus will successfully automate the process demonstrated as feasible in the laboratory.
  • the undercoat As at 18 .
  • additional upper undercoat layers which may be of the same or different composition with respect to bioactive material, the matrix. polymeric materials and crosslinking agent, for example, may be applied as the top layer as at 20 .
  • the application of the top layer follows the same coating procedure as the undercoat with the number and thickness of layers being optional. of course, the thickness of any layer can be adjusted by adjusting the speed of rotation of the stent and the spraying conditions. Generally, the total coating thickness is controlled by the number of spraying cycles or thin coats which make up the total coat.
  • the coated stent is thereafter subjected to a curing step in which the prepolymer and crosslinking agents cooperate to produce a cured polymer matrix containing the biologically active species.
  • the curing process involves evaporation of the solvent xylene, THF, etc. and the curing and crosslinking of the polymer.
  • Certain silicone materials can be cured at relatively low temperatures, (i.e., RT-50° C.) in what is known as a room temperature vulcanization (RTV) process. More typically, however, the curing process involves higher temperature curing materials and the coated stents are put into an oven at approximately 90° C. or higher for approximately 16 hours. The temperature may be raised to as high as 150° C. for dexamethasone containing coated stents. Of course, the time and temperature may vary with particular silicones, crosslinkers and biologically active species.
  • Stents coated and cured in the manner described need to be sterilized prior to packaging for future implantation.
  • gamma radiation is a preferred method particularly for heparin containing coatings; however, it has been found that stents coated and cured according to the process of the invention subjected to gamma sterilization may be too slow to recover their original posture when delivered to a vascular or other lumen site using a catheter unless a pretreatment step as at 24 is first applied to the coated, cured stent.
  • the pretreatment step involves an argon plasma treatment of the coated, cured stents in the unconstrained configuration.
  • the stents are placed in a chamber of a plasma surface treatment system such as a Plasma Science 350 (Himont/Plasma Science, Foster City, Calif.).
  • the system is equipped with a reactor chamber and RF solid-state generator operating at 13.56 mHz and from 0-500 watts power output and being equipped with a microprocessor controlled system and a complete vacuum pump package.
  • the reaction chamber contains an unimpeded work volume of 16.75 inches (42.55 cm) by 13.5 inches (34.3 cm) by 17.5 inches (44.45 cm) in depth.
  • unconstrained coated stents are placed in a reactor chamber and the system is purged with nitrogen and a vacuum applied to 20-50 mTorr. Thereafter, inert gas (argon, helium or mixture of them) is admitted to the reaction chamber for the plasma treatment.
  • inert gas argon, helium or mixture of them
  • a highly preferred method of operation consists of using argon gas, operating at a power range from 200 to 400 watts, a flow rate of 150-650 standard ml per minute, which is equivalent to 100-450 mTorr, and an exposure time from 30 seconds to about 5 minutes.
  • the stents can be removed immediately after the plasma treatment or remain in the argon atmosphere for an additional period of time, typically five minutes.
  • the stents may be exposed to gamma sterilization at 2.5-3.5 Mrad.
  • the radiation may be carried out with the stent in either the radially unconstrained status or in the radially constrained status.
  • the surface is modified prior to plasma treatment or just prior to sterilization by one of several additional processing methods of which some are described in relation to the following examples.
  • the undercoat of a stent was coated as multiple applied layers as described above thereafter and cured as described at 22 .
  • the heparin content of the undercoat was 37.5% and the coating thickness was about 30-40 ⁇ .
  • the solution was stirred very well and spray-coated on the stent at 32 using the technique of the application of the undercoat process at 18 and the coated stents were cured at 90° C. for 16 hours.
  • the coated stents are argon plasma treated prior to gamma sterilization according to the procedures described above in accordance with steps 22 - 26 .
  • FIG. 7 is a plot of heparin release kinetics in phosphate buffer system with fluorosilicone topcoat and without any topcoat.
  • the thickness of the topcoat is about 10-15 A. While it does not appear on the graph of FIG. 7 it should be noted that the release rate for the coating without FSi is initially about 25 times higher than that with FSi, i.e., during the first 2 hours. This is, of course, clearly off the scale of the graph. It is noteworthy, however, that the coating with the FSi top layer or diffusion barrier does show a depressed initial release rate combined with an enhanced elution rate after the first day and through the first week up until about the tenth day.
  • the fluorosilicone (FSi) topcoat by virtue of the high electronegativity of fluorination maintains non-thrombogenic surface qualities during and after the elusion of the biologically active heparin species.
  • the electro-negativity of the fluorosilicone topcoat may be, at least in part, responsible for the modified heparin release kinetic profile.
  • FIG. 8 compares a plot of fluorosilicone (FSi) top coating containing 16.7% imbedded heparin with one containing fluorosilicone (FSi) only.
  • An undercoating is identical to that utilized in FIG. 7 containing about 37.5% heparin to a thickness of about 30-40 microns.
  • An undercoat was coated on a stent and cured at 22 as in Example 1.
  • the stent was then treated by argon gas plasma as at 24 and ammonium gas plasma at 40 .
  • the equipment and the process of argon gas plasma treatment was as has been described above.
  • the ammonium plasma treatment was implemented immediately after the argon gas plasma treatment, to aminate the surface of the coating.
  • the ammonium flow rate was in the range of 100-700 cubic centimeter per minute (ccM) in preferably in the range of 500-600 ccM.
  • the power output of radio frequency plasma was in the range of 50-500 watts, preferably in ⁇ 200 watts.
  • the process time was in the range of 30 sec-10 min, preferably ⁇ 5 min.
  • PEG polyethylene glycol
  • electrophilically activated polyethylene glycol PEG
  • examples of electrophilically activated PEG are PEG nitrophenyl carbonates, PEG trichlorophenyl carbonates, PEG tresylate, PEG glycidyl ether, PEG isocyanate, etc., optionally with one end terminated with methoxyl group.
  • Molecular weight of PEG ranged from about 1000-6000, and is preferable about 3000. It has been observed that simple ammonium amination will not generate large quantities of primary and secondary amines on the elastomeric polymer surface (for example silicone).
  • imine >C ⁇ N—H
  • reductive agent such as NaBH 3 CN
  • the typical concentration of NaBH 3 CN is about 2 mg/ml. Since PEG and its derivatives dissolve in water and many polar and aromatic solvents, the solvent used in the coating must be a solvent for PEG but not for the drug in the undercoat to prevent the possible loss of the drug through leaching.
  • a mixed solvent of formamide and methyl ethyl ketone (MEK) or a mixed solvent of formamide and acetone are preferred solvents, (preferably at ratios of 30 formamide: 70 MEK or acetone by volume), since they will not dissolve heparin.
  • concentration of PEG, the reaction time, the reaction temperature and the pH value depend on the kind of PEG employed.
  • 5% PEG tresylate in (30-70) Formamide/MEK was used successfully.
  • the reaction time was 3 hours at room temperature. PEG was then covalently bound to the surface. Gamma radiation was then used for sterilization of this embodiment as previously described.
  • the percentage in the undercoat is nominally from about 30-50% and that of the topcoat from about 0-30% active material.
  • the coating thickness ratio of the topcoat to the undercoat varies from about 1:10 to 1:2 and is preferably in the range of from about 1:6 to 1:3.
  • topcoat which is substantially free of pores
  • materials such as porosigens, which can be removed or leached out of the topcoat should not be included in the composition used to form the topcoat.
  • One way of preparing a substantially non-porous topcoat is to apply a topcoat composition which comprises substantially pure polymeric materials. These materials preferably impart biocompatibility to the implanted device during and after the release of the biologically active material.
  • a topcoat which only partially covers the undercoat can be formed in a number of ways. Such methods include controlling the thickness of the topcoat so that it is less than the diameter of certain drug particles in the undercoat. For example, when a drug used in the undercoat has an average particle size of 5 ⁇ m, it is possible that 15% of the particles will be greater than or equal to 8 ⁇ m. At the molecular level, the surface unevenness is at least more than 5 microns. By application of a topcoat of about 5 micron or less. The uneven surface will become smooth to a certain degree. But uncovered areas will still exist, which allows water to penetrate into the undercoat, swelling the drug particle, or dissolving the drug. Due to the osmotic pressure, the drug will elute out through the uncovered areas. If the osmotic pressure is too high, cracks or voids may form in the topcoat which allows drugs to elute from the undercoat to the body.
  • a thin topcoat 104 of the coating 102 only partially covers the undercoat 103 of the coating 102 .
  • the topcoat 104 cover less than the entire surface of the undercoat 103 , parts of the undercoat 103 , including a number of drug particles 105 , are exposed to body fluids at the implantation site so that the drug 105 can be released.
  • a topcoat 104 having a thickness which is about the average particle size of the drug 105 certain larger sized drug particles 106 will not be covered by the topcoat 104 .
  • topcoat Other methods to form a partially covered topcoat include using a polymer which is incompatible to the undercoat elastomer as the biocompatible material of the topcoat. Because of the incompatibility between the materials, a microphase separation will form in the topcoat which will leave the undercoat partially uncovered. Persons skilled in the art are aware of suitable combinations of such incompatible materials.
  • Another method involves applying a poor solvent wash to the topcoat to force the biocompatible polymer to shrink and create uneven surfaces voids in the topcoat which forms a topcoat which partially covers the undercoat.
  • topcoat and undercoat materials having different Young's moduli are used.
  • a topcoat material having a higher Young's modulus compared to that of the undercoat material can be employed.
  • the topcoat material undergoes compression or stretching or other types of mechanical challenges. Since the topcoat material has a higher Young's modulus, it will tend to crack and form voids in the topcoat to allow the drug of the undercoat to elute therefrom.
  • topcoat Another method for forming the topcoat involves using a bioabsorbable material in the topcoat, which can cover the entire undercoat or only a part of the undercoat.
  • a bioabsorbable material in the topcoat, which can cover the entire undercoat or only a part of the undercoat.
  • the topcoat begins to degrade either at the surface or throughout the bulk of the topcoat. The rate of degradation depends upon the type of bioabsorbable material used. Once the topcoat has been partially absorbed, the undercoat is exposed to body tissue and the drug in the undercoat is released, but the burst release or effect is reduced.
  • Suppressing the burst effect also enables a reduction in the drug loading or in other words, allows a reduction in the coating thickness, since the physician will give a bolus injection of antiplatelet/anticoagulation drugs to the patient during the stenting process.
  • the drug imbedded in the stent can be fully used without waste. Tailoring the first day release, but maximizing second day and third day release at the thinnest possible coating configuration will reduce the acute or subacute thrombosis particularly if drugs such as heparin are incorporated.
  • FIG. 4 depicts the general effect of drug loading for coatings of similar thickness.
  • the initial elution rate increases with the drug loading as shown in FIG. 5 .
  • the release rate also increases with the thickness of the coating at the same loading but tends to be inversely proportional to the thickness of the topcoat as shown by the same drug loading and similar undercoat thickness in FIG. 6 .
  • stent coatings can be prepared using a combination of two or more drugs and the drug release sequence and rate controlled.
  • antiproliferation drugs may be combined in the undercoat and antiplatelet drugs in the topcoat.
  • the antiplatelet drugs for example, heparin, will elute first followed by antiproliferation drugs to better enable safe encapsulation of the implanted stent.
  • heparin concentration measurement were made utilizing a standard curve prepared by complexing azure A dye with dilute solutions of heparin. Sixteen standards were used to compile the standard curve in a well-known manner.
  • the stents were immersed in a phosphate buffer solution at pH 7.4 in an incubator at approximately 37° C. Periodic samplings of the solution were processed to determine the amount of heparin eluted. After each sampling, each stent was placed in heparin-free buffer solution.
  • the allowable loading of the elastomeric material with heparin may vary, in the case of silicone materials, heparin may exceed 60% of the total weight of the layer. However, the loading generally most advantageously used is in the range from about 10% to 45% of the total weight of the layer. In the case of dexamethasone, the loading may be as high as 50% or more of the total weight of the layer but is preferably in the range of about 0.4% to 45%.
  • the mechanism of incorporation of the biologically active species into a thin surface coating structure applicable to a metal stent is an important aspect of the present invention.
  • the need for relatively thick-walled polymer elution stents or any membrane overlayers associated with many prior drug elution devices is obviated, as is the need for utilizing biodegradable or reabsorbable vehicles for carrying the biologically active species.
  • the technique clearly enables long-term delivery and minimizes interference with the independent mechanical or therapeutic benefits of the stent itself.
  • Coating materials are designed with a particular coating technique, coating/drug combination and drug infusion mechanism in mind. Consideration of the particular form and mechanism of release of the biologically active species in the coating allow the technique to produce superior results. In this manner, delivery of the biologically active species from the coating structure can be tailored to accommodate a variety of applications.
  • any number of layers and combinations of loadings can be employed to achieve a desired release profile.
  • gradual grading and change in the loading of the layers can be utilized in which, for example, higher loadings are used in the inner layers.
  • layers can be used which have no drug loadings at all.
  • a pulsatile heparin release system may be achieved by a coating in which alternate layers containing heparin are sandwiched between unloaded layers of silicone or other materials for a portion of the coating.
  • each applied layer is typically from approximately 0.5 microns to 15 microns in thickness.
  • the total number of sprayed layers can vary widely, from less than 10 to more than 50 layers; commonly, 20 to 40 layers are included.
  • the total thickness of the coating can also vary widely, but can generally be, from about 10 to 200 microns.
  • the polymer of the coating may be any compatible biostable elastomeric material capable of being adhered to the stent material as a thin layer
  • hydrophobic materials are preferred because it has been found that the release of the biologically active species can generally be more predictably controlled with such materials.
  • Preferred materials include silicone rubber elastomers and biostable polyurethanes specifically.

Abstract

A coating and method for a coating an implantable device or prostheses are disclosed. The coating includes an undercoat of polymeric material containing an amount of biologically active material, particularly heparin, dispersed herein. The coating further includes a topcoat which covers less than the entire surface of the undercoat and wherein the topcoat comprises a polymeric material substantially free of pores and porosigens. The polymeric material of the topcoat can be a biostable, biocompatible material which provides long term non-thrombogenicity to the device portion during and after release of the biologically active material.

Description

    CROSS-REFERENCE TO RELATED APPLICATIONS
  • The present application is a Continuation-In-Part of co-pending application Ser. No. 08/633,518, filed Jun. 13, 1996.
  • BACKGROUND OF THE INVENTION
  • 1. Field of the Invention
  • The present invention relates generally to providing biostable elastomeric coatings on the surfaces of implants which incorporate biologically active species having controlled release characteristics in the coating and relates particularly to providing a non-thrombogenic surface during and after timed release of the biologically active species. The invention is particularly described in terms of coatings on therapeutic expandable stent prostheses for implantation in body lumens, e.g., vascular implantation.
  • 2. Related Art
  • In surgical or other related invasive procedures, the insertion and expansion of stent devices in blood vessels, urinary tracts or other locations difficult to otherwise access for the purpose of preventing restenosis, providing vessel or lumen wall support or reinforcement and for other therapeutic or restorative functions has become a common form of long-term treatment. Typically, such prostheses are applied to a location of interest utilizing a vascular catheter, or similar transluminal device, to carry the stent to the location of interest where it is thereafter released to expand or be expanded in situ. These devices are generally designed as permanent implants which may become incorporated in the vascular or other tissue which they contact at implantation.
  • One type of self-expanding stent has a flexible tubular body formed of several individual flexible thread elements each of which extends in a helix configuration with the centerline of the body serving as a common axis. The elements are wound in the same direction but are displaced axially relative to each other and meet, under crossing a like number of elements also so axially displaced, but having the opposite direction of winding. This configuration provides a resilient braided tubular structure which assumes stable dimensions upon relaxation. Axial tension produces elongation and corresponding diameter contraction that allows the stent to be mounted on a catheter device and conveyed through the vascular system as a narrow elongated device. Once tension is relaxed in situ, the device at least substantially reverts to its original shape. Prostheses of the class including a braided flexible tubular body are illustrated and described in U.S. Pat. Nos. 4,655,771 and 4,954,126 to Wallsten and U.S. Pat. No. 5,061,275 to Wallsten et al.
  • Implanted stents have been used to carry medicinal agents, such as thrombolytic agents. U.S. Pat. No. 5,163,952 to Froix discloses a thermalmemoried expanding plastic stent device formulated to carry a medicinal agent in the material of the stent itself. Pinchuk, in U.S. Pat. No. 5,092,877, discloses a stent of a polymeric material which may have a coating associated with the delivery of drugs. Other patents which are directed to devices of the class utilizing bio-degradable or bio-sorbable polymers include Tang et al., U.S. Pat. No. 4,916,193, and MacGregor, U.S. Pat. No. 4,994,071.
  • A patent to Sahatjian, U.S. Pat. No. 5,304,121, discloses a coating applied to a stent consisting of a hydrogel polymer and a preselected drug such as a cell growth inhibitors or heparin. A further method of making a coated intravascular stent carrying a therapeutic material is described in Berg et al., U.S. Pat. No. 5,464,650, issued on Nov. 7, 1995 and corresponding to European Patent Application No. 0 623 354 A1 published 9 Nov. 1994. In that disclosure, a polymer coating material is dissolved in a solvent and the therapeutic material dispersed in the solvent; the solvent evaporated after application.
  • An article by Michael N. Helmus (a co-inventor of the present invention) entitled “Medical Device Design—A Systems Approach: Central Venous Catheters”, 22nd International Society for the Advancement of Material and Process Engineering Technical Conference (1990) relates to polymer/drug/membrane systems for releasing heparin. Those polymer/drug/membrane systems require two distinct types of layers to function.
  • It has been recognized that contacting blood with the surface of a foreign body in vivo has a tendency to induce thrombogenic responses and that as the surface area of a foreign device in contact with host blood increases, the tendency for coagulation and clot forming at these surfaces also increases. This has led to the use of immobilized systemic anti-coagulant or thrombolytic agents such as heparin on blood contacting surfaces such as oxygen uptake devices to reduce this phenomenon. Such an approach is described by Winters, et al., in U.S. Pat. Nos. 5,182,317; 5,262,451 and 5,338,770 in which the amine functional groups of the active material are covalently bonded using polyethylene oxide (PEO) on a siloxane surface.
  • Another approach is described in U.S. Pat. No. 4,613,665 to Larm in which heparin is chemically covalently bound to plastic surface materials containing primary amino groups to impart a non-thrombogenic surface to the material. Other approaches for bonding heparin are described in Barbucci, et al., “Coating of commercially available materials with a new heparinizable material”, Journal of Biomedical Materials Research, Vol. 25, pp. 1259-1274 (1991); Hubbell, J. A., “Pharmacologic Modification of Materials”, Cardiovascular Pathology, Vol. 2, No. 3 (Suppl.), 121S-127S (1993); Gravlee, G. P., “Heparin-Coated Cardiopulmonary Bypass Circuits”, Journal of Cardiothoracic and Vascular Anesthesia, Vol. 8, No. 2, pp. 213-222 (1994).
  • Moreover, drug elution rates for a coating containing a hydrophilic or a lipophobic drug is usually very fast initially when the coated device contacts body fluid or blood. One of the methods to reduce the so called “burst effect” is to add a membrane containing porosigen over the coating layer containing the biologically active material. See e.g., U.S. Pat. No. 5,605,696 to Eury et al. and U.S. Pat. No. 5,447,724 to Helmus et al. When the porosigen elutes, a porous membrane is formed and the drug in the undercoat will release. Even though the method might be quite successful to control the drug release, it increases the coating thickness, reduces the effective drug loading and introduces undesirable additional foreign materials into the patient. Hence, there is a need for a coating which reduces the burst effect but is not too thick and does not require the release of porosigens into the body.
  • With regard to stents, polymeric stents, although effective, may have mechanical properties that are inferior to those of metal stents of like thickness and weave. Metallic vascular stents braided of even relatively fine metal can provide a large amount of strength to resist inwardly directed circumferential pressure. A polymer material of comparable strength requires a much thicker-walled structure or heavier, denser filament weave, which in turn, reduces the cross-sectional area available for flow through the stent and/or reduces the relative amount of open space in the weave. Also, it is usually more difficult to load and deliver polymeric stents using catheter delivery systems.
  • While certain types of stents such as braided metal stents may be preferred for some applications, the coating and coating modification process of the present invention is not so limited and can be used on a wide variety of prosthetic devices. Thus, in the case of stents, the present invention also applies, for example, to the class of stents that are not self-expanding, including those which can be expanded, for instance, with a balloon; as well as polymeric stents of all kinds. Other medical devices that can benefit from the present invention include blood exchanging devices, vascular access ports, central venus catheters, cardiovascular catheters, extracorpeal circuits, vascular grafts, pumps, heart valves, and cardiovascular sutures, to name a few. Regardless of detailed embodiments, applicability of the invention should not be considered limited with respect to implant design, implant location or materials of construction. Further, the present invention may be used with other types of implantable prostheses.
  • Accordingly, it is a primary object of the present invention to provide a coating and process for coating a stent to be used as a deployed stent prostheses, the coating being capable of effective controlled long-term delivery of biologically active materials.
  • Another object of the invention is to provide a coating and process for coating a stent prostheses using a biostable hydrophobic elastomer in which biologically active species are incorporated within a coating.
  • Still another object of the present invention is to provide a multi-layer coating and process for the delivery of biologically active species in which the percentage of active material can vary from layer to layer.
  • Yet another object of the present invention is to provide a multi-layer coating and process for the delivery of biologically active species from a coating with a non-thrombogenic surface.
  • Another object of the invention is to provide a coating for the delivery of biologically active species having a top layer or topcoat which reduces the initial release of the species, in which the topcoat is substantially free of pores or porosigens and covers less than the entire surface of the undercoat. The topcoat can cover less than the entire surface of the undercoat before and/or while the device is implanted.
  • A further object of the invention is to provide a multilayer coating for the delivery of biologically active species such as heparin having a fluorosilicone top layer.
  • A still further object of the invention is to provide a multi-layer coating for the delivery of biologically active species such as heparin having a surface containing immobilized polyethylene glycol (PEG).
  • Other objects and advantages of the present invention will become apparent to those skilled in the art upon familiarization with the specification and appended claims.
  • SUMMARY OF THE INVENTION
  • The present invention provides a relatively thin layered coating of biostable elastomeric material containing an amount of biologically active material dispersed therein in combination with a non-thrombogenic surface that is useful for coating the surfaces of prostheses such as deployable stents.
  • The preferred stent to be coated is a self-expanding, open-ended tubular stent prostheses. Although other materials, including polymer materials, can be used, in the preferred embodiment, the tubular body is formed of a self expanding open braid of fine single or polyfilament metal wire which flexes without collapsing, readily axially deforms to an elongate shape for transluminal insertion via a vascular catheter and resiliently expands toward predetermined stable dimensions upon removal in situ.
  • In the process, the initial coating is preferably applied as a mixture, solution or suspension of polymeric material and finely divided biologically active species dispersed in an organic vehicle or a solution or partial solution of such species in a solvent or vehicle for the polymer and/or biologically active species. For the purpose of this application, the term “finally divided” means any type or size of included material from dissolved molecules through suspensions colloids and particulate mixtures. The biologically active material is dispersed in a carrier material which may be the polymer, a solvent, or both. The coating is preferably applied as a plurality of relatively thin layers sequentially applied in relatively rapid sequence and is preferably applied with the stent in a radially expanded state.
  • In many applications the layered coating is referred to or characterized as including an undercoat and topcoat. The coating thickness ratio of the topcoat to undercoat may vary with the desired effect and/or the elution system. Typically these are of different formulations with most or all of the biologically active material being contained in the undercoat and a non-thrombogenic or biocompatible non-porous surface found in the topcoat.
  • It is desirable that the topcoat be substantially free of connected pores or porosigens (materials which can elute during implantation and form pores). The addition of a porous membrane as a top coat will increase the coating thickness and reduce the overall drug loading. Also, the release of porosigens into the body can be undesirable since it introduces additional foreign materials into the body, which can cause the patient to have adverse reactions.
  • Since in some embodiments the topcoat should be substantially free of pores, the topcoat should cover less than the entire surface of the undercoat. Preferably, the topcoat should cover only about 10% to about 95% of the surface of the undercoat.
  • By partially covering the surface during manufacture or inducing “breaks” in the topcoat during mounting/implanting of the coated device, the biologically active material or drug of the undercoat is permitted to be released from the undercoat through those parts of the undercoat which are not covered by the topcoat.
  • This mechanism is illustrated by FIG. 9, which shows a surface of a prosthesis 101 covered by a coating 102 comprising an undercoat 103 and a topcoat 104. The topcoat 104, which only partially covers the undercoat 103, leaves certain areas 106 of the undercoat, including drug particles 105, exposed to body fluids at the implantation site. It is through these “uncovered” areas 106 of the undercoat that the drug particles 105 of the undercoat 103 are allowed to be released into the implantation site.
  • Additionally, it is preferred that the topcoats have an average thickness equivalent to the average particle size of the drug in the undercoat. Preferably the average thickness is about 1 to 7 microns and more preferable that the topcoat average thickness be about 1 to 5 microns. Also, the polymer of the topcoat may be the same as or different from the polymer of the undercoat.
  • The coating may be applied by dipping or spraying using evaporative solvent materials of relatively high vapor pressure to produce the desired viscosity and quickly establish coating layer thicknesses. The preferred process is predicated on reciprocally spray coating a rotating radially expanded stent employing an air brush device. The coating process enables the material to adherently conform to and cover the entire surface of the filaments of the open structure of the stent but in a manner such that the open lattice nature of the structure of the braid or other pattern is preserved in the coated device.
  • The coating is exposed to room temperature ventilation for a predetermined time (possibly one hour or more) for solvent vehicle evaporation. In the case of certain undercoat materials, thereafter the polymer material is cured at room temperature or elevated temperatures. Curing is defined as the process of converting the elastomeric or polymeric material into the finished or useful state by the application of heat and/or chemical agents which induce physico-chemical changes. Where, for example, polyurethane thermoplastic elastomers are used as an undercoat material, solvent evaporation can occur at room temperature rendering the undercoat useful for controlled drug release without further curing.
  • The applicable ventilation time and temperature for cure are determined by the particular polymer involved and particular drugs used. For example, silicone or polysiloxane materials (such as polydimethylsiloxane) have been used successfully. Urethane prepolymers can also be utilized. Unlike the polyurethane thermoplastic elastomers, some of these materials are applied as prepolymers in the coating composition and must thereafter be heat cured. The preferred silicone species have a relatively low cure temperatures and are known as a room temperature vulcanizable (RTV) materials. Some polydimethylsiloxane materials can be cured, for example, by exposure to air at about 90° C. for a period of time such as 16 hours. A curing step may be implemented both after application of the undercoat or a certain number of lower layers and the top layers or a single curing step used after coating is completed.
  • The coated stents may thereafter be subjected to a postcure process which includes an inert gas plasma treatment, and sterilization which may include gamma radiation, ETO treatment, electron beam or steam treatment.
  • In the plasma treatment, unconstrained coated stents are placed in a reactor chamber and the system is purged with nitrogen and a vacuum applied to 20-50 mTorr. Thereafter, inert gas (argon, helium or mixture of them) is admitted to the reaction chamber for the plasma treatment. One method uses argon (Ar) gas, operating at a power range from 200 to 400 watts, a flow rate of 150-650 standard ml per minute, which is equivalent to about 100-450 mTorr, and an exposure time from 30 seconds to about 5 minutes. The stents can be removed immediately after the plasma treatment or remain in the argon atmosphere for an additional period of time, typically five minutes.
  • In accordance with the invention, the topcoat or surface coating may be applied in any of several ways to further control thrombolytic effects and optionally, control the release profile especially the initial very high release rate associated with the elution of heparin.
  • In one embodiment, an outer layer of fluorosilicone (FSi) is applied to the undercoat as a topcoat. The outer layer can also contain heparin. In another embodiment, polyethylene glycol (PEG) is immobilized on the surface of the coating. In this process, the underlayer is subjected to inert gas plasma treatment and immediately thereafter is treated by ammonia (NH3) plasma to aminate the surface. Amination, as used in this application, means creating mostly imino groups and other nitro containing species on the surface. This is followed by immediate immersion into electrophilically activated polyethylene glycol (PEG) solution with a reductive agent, i.e., sodium cyanoborohydride.
  • To form a topcoat which is substantially free of pores, porosigens or materials capable of eluting from the topcoat during implantation, should not be included in the composition used to form the topcoat. For example, a substantially non-porous topcoat can be produced from a topcoat composition which comprises a substantially pure polymeric material. The material preferably provides biocompatibility to the implanted device during and after release of the biologically active material.
  • To prepare a topcoat which covers less than the entire surface of the undercoat, a number of methods can be used. For instance, by controlling the thickness of the topcoat so that it has an average thickness less than that of the diameter of certain drug particles, the undercoat will be only partly covered by the topcoat since some of drug particles will not be covered by the topcoat.
  • Also, a partial topcoat can be formed by using a topcoat polymer which is incompatible with the undercoat polymer to generate a microphase separation in the topcoat. Furthermore, to make a topcoat which covers less than the entire surface of the undercoat or which only partially covers the undercoat, a poor solvent wash can be applied to the topcoat, to force the topcoat polymer to shrink so that the undercoat is not entirely covered.
  • In other embodiments the topcoat can partially or fully cover the undercoat prior to delivery or implantation of the device. The topcoat materials can be selected so they have certain water permeability. When water penetrates the topcoat and into the drug particles of the undercoat, the water will swell the particles or dissolve the particles. In either situation, it creates osmotic pressure in the surrounding coating material of the undercoat. The pressure then breaks the thinnest part of the topcoat, and leave the void space in the topcoat for the drug to elute out.
  • In another embodiment, the topcoat material has a different Young's modulus (either while it is wet or dry) than that of the undercoat material. More specifically, the Young's modulus can be higher for the topcoat material. During the mounting of the coated devices onto the delivery device or during deployment of the coated device, the coating undergoes compression or stretching. Topcoat materials with higher Young's modulus tend to crack and form void spaces for the drug to elute from undercoat.
  • Another way to form a topcoat is to cover the undercoat with a bioabsorbable material. In this embodiment, the topcoat can cover either the entire undercoat or only part of the undercoat before or after implantation. Upon contact with body fluids, the bioabsorbable material of the topcoat will degrade. The rate of degradation depends upon the bioabsorbable material used. When the topcoat is partially absorbed, the undercoat is exposed to the body fluid and the drug is released, however the burst effect will be reduced.
  • The coated and cured stents having the modified outer layer or surface optionally are subjected to a final gamma radiation sterilization nominally at 2.5-3.5 Mrad. Argon (Ar) plasma treated stents enjoy full resiliency after radiation whether exposed in a constrained or non-constrained status, while constrained stents subjected to gamma sterilization without Ar plasma pretreatment lose resiliency and do not recover at a sufficient or appropriate rate where the undercoat is silicone.
  • The elastomeric materials that form the stent coating underlayers should possess certain properties. Preferably the layers should be of suitable hydrophobic biostable elastomeric materials which do not degrade. Surface layer or topcoat materials should minimize tissue rejection and tissue inflammation and permit encapsulation by tissue adjacent the stent implantation site. Exposed material is designed to reduce clotting tendencies in blood contacted and the surface is preferably modified accordingly. Thus, underlayers of the above materials are preferably provided with a silicone or a fluorosilicone outer coating layer which should not contain imbedded bioactive material, such as heparin in order to avoid the formation of pores in the topcoat. Alternatively, the outer coating may consist essentially of polyethylene glycol (PEG), polysaccharides, phospholipids, or combinations of the foregoing.
  • Polymers generally suitable for the undercoats or underlayers include silicones (e.g., polysiloxanes and substituted polysiloxanes), polyurethanes, thermoplastic elastomers in general, ethylene vinyl acetate copolymers, polyolefin elastomers, polyamide elastomers, and EPDM rubbers. The above-referenced materials are considered hydrophobic with respect to the contemplated environment of the invention. Surface layer or topcoat materials can include the same polymer as that of the undercoat. Examples of suitable polymers include without limitation fluorosilicones and polyethylene glycol (PEG), polysaccharides, phospholipids, and combinations of the foregoing.
  • While heparin is preferred as the incorporated active material, agents possibly suitable for incorporation include antithrobotics, anticoagulants, antibiotics antiplatelet agents, thrombolytics, antiproliferatives, steroidal and nonsteroidal antiinflammatories, agents that inhibit hyperplasia and in particular restenosis, smooth muscle cell inhibitors, growth factors, growth factor inhibitors, cell adhesion inhibitors, cell adhesion promoters and drugs that may enhance the formation of healthy neointimal tissue, including endothelial cell regeneration. The positive action may come from inhibiting particular cells (e.g., smooth muscle cells) or tissue formation (e.g., fibromuscular tissue) while encouraging different cell migration (e.g., endothelium) and tissue formation (neointimal tissue).
  • Suitable materials for fabricating the braided stent include stainless steel, tantalum, titanium alloys including nitinol (a nickel titanium, thermomemoried alloy material), and certain cobalt alloys including cobalt-chromium-nickel alloys such as Elgiloy® and Phynox®. Further details concerning the fabrication and details of other aspects of the stents themselves, may be gleaned from the above referenced U.S. Pat. Nos. 4,655,771 and 4,954,126 to Wallsten and U.S. Pat. No. 5,061,275 to Wallsten et al., which are incorporated by reference herein.
  • Various combinations of polymer coating materials can be coordinated with biologically active species of interest to produce desired effects when coated on stents to be implanted in accordance with the invention. Loadings of therapeutic materials may vary. The mechanism of incorporation of the biologically active species into the surface coating, and egress mechanism depend both on the nature of the surface coating polymer and the material to be incorporated. The mechanism of release also depends on the mode of incorporation. The material may elute via interparticle paths or be administered via transport or diffusion through the encapsulating material itself.
  • For the purposes of this specification, “elution” is defined as any process of release that involves extraction or release by direct contact of the material with bodily fluids through the interparticle paths connected with the exterior of the coating. “Transport” or “diffusion” are defined to include a mechanism of release in which the material released traverses through another material.
  • The desired release rate profile can be tailored by varying the coating thickness, the radial distribution (layer to layer) of bioactive materials, the mixing method, the amount of bioactive material, the combination of different matrix polymer materials at different layers, and the crosslink density of the polymeric material. The crosslink density is related to the amount of crosslinking which takes place and also the relative tightness of the matrix created by the particular crosslinking agent used. This, during the curing process, determines the amount of crosslinking and so the crosslink density of the polymer material. For bioactive materials released from the crosslinked matrix, such as heparin, a denser crosslink structure will result in a longer release time and reduced burst effect.
  • It will also be appreciated that an unmedicated silicone thin top layer provides some advantage and additional control over drug elution.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • In the drawings, wherein like numerals designate like parts throughout the same:
  • FIG. 1 is a schematic flow diagram illustrating the steps of the process of the invention;
  • FIG. 2 represents a release profile for a multi-layer system showing the percentage of heparin released over a two-week period;
  • FIG. 3 represents a release profile for a multi-layer system showing the relative release rate of heparin over a two-week period;
  • FIG. 4 illustrates a profile of release kinetics for different drug loadings at similar coating thicknesses illustrating the release of heparin over a two-week period without associated means to provide a long term non-thrombogenic surface thereafter;
  • FIG. 5 illustrates drug elution kinetics at a given loading of heparin over a two-week period at different coating thicknesses without associated means to provide a long term non-thrombogenic surface thereafter;
  • FIG. 6 illustrates the release kinetics for a given undercoat and topcoat material varied according to thickness in which the percentage heparin in the undercoat and topcoats are kept constant;
  • FIG. 7 is a plot of heparin release kinetics in phosphate buffer system at pH 7.4 with and without fluorosilicone (FSi) topcoat; and
  • FIG. 8 is another plot of heparin release kinetics in phosphate buffer system in which a topcoat containing fluorosilicone (FSi) only is compared with an FSi topcoat containing 16.7% imbedded heparin.
  • FIG. 9 illustrates a surface of an implantable prosthesis covered with an undercoat, containing a biologically active material, which is partly covered by a topcoat.
  • DETAILED DESCRIPTION
  • According to the present invention, the stent coatings incorporating biologically active materials for timed delivery in situ in a body lumen of interest are preferably sprayed in many thin layers from prepared coating solutions or suspensions. The steps of the process are illustrated generally in FIG. 1. The coating solutions or suspensions are prepared at 10 as will be described later. The desired amount of crosslinking agent (if any) is added to the suspension/solution as at 12 and material is then agitated or stirred to produce a homogenous coating composition at 14 which is thereafter transferred to an application container or device which may be a container for spray painting at 16. Typical exemplary preparations of coating solutions that were used for heparin and dexamethasone appear next.
  • General Preparation of Heparin Undercoating Composition
  • Silicone was obtained as a polymer precursor in solvent (xylene) mixture. For example, a 35% solid silicone weight content in xylene was procured from Applied Silicone, Part #40,000. First, the silicone-xylene mixture was weighed. The solid silicone content was determined according to the vendor's analysis. Precalculated amounts of finely divided heparin (2-6 microns) were added into the silicone, then tetrahydrofuran (THF) HPCL grade (Aldrich or EM) was added. For a 37.5% heparin coating, having 35% solids, Wsilicone=5 g and Whep=5×0.35×0.375/(0.625)=1.05 g were used. The amount of THF needed (44 ml) in the coating solution was calculated by using the equation Wsilicone solid/VTHF=0.04 for a 37.5% heparin coating solution. Finally, the manufacturer crosslinker solution was added by using Pasteur P-pipet. The amount of crosslinker added was formed to effect the release rate profile. Typically, five drops of crosslinker solution were added for each five grams of silicone-xylene mixture. The solution was stirred by using the stirring rod until the suspension was homogenous and milk-like. The coating solution was then transferred into a paint jar in condition for application by air brush.
  • General Preparation of Dexamethasone Undercoating Composition
  • Silicone (35% solution as above) was weighed into a beaker on a Metler balance. The weight of dexamethasone free alcohol or acetate form was calculated by silicone weight multiplied by 0.35 and the desired percentage of dexamethasone (1 to 40%) and the required amount was then weighed. Example: Wsilicone=5 g; for a 10% dexamethasone coating, Wdex=5×0.35×0.1/0.9=0.194 g and THF needed in the coating solution and Wsilicone solid/VTHF=0.06 for a 10% dexamethasone coating solution. Example: Wsilicone=5 g; VTHF=5×0.35/0.06≈29 ml. The dexamethasone was weighed in a beaker on an analytical balance and half the total amount of THF was added. The solution was stirred well to ensure full dissolution of the dexamethasone. The stirred DEX-THF solution was then transferred to the silicone container. The beaker was washed with the remaining THF and this was transferred to the silicone container. The crosslinker was added by using a Pasteur pipet. Typically, five drops of crosslinker were used for five grams of silicone.
  • The application of the coating material to the stent was quite similar for all of the materials and the same for the heparin and dexamethasone suspensions prepared as in the above Examples. The suspension to be applied was transferred to an application device, at 16 in FIG. 1. Typically a paint jar attached to an air brush, such as a Badger Model 150, supplied with a source of pressurized air through a regulator (Norgren, 0-160 psi) was used. Once the brush hose was attached to the source of compressed air downstream of the regulator, the air was applied. The pressure was adjusted to approximately 15-25 psi and the nozzle condition checked by depressing the trigger.
  • To secure the stent for spraying and rotating fixtures were utilized successfully in the laboratory. Both ends of the relaxed stent were fastened to the fixture by two resilient retainers, commonly alligator clips, with the distance between the clips adjusted so that the stent remained in a relaxed, unstretched condition. The rotor was then energized and the spin speed adjusted to the desired coating speed, nominally about 40 rpm.
  • With the stent rotating in a substantially horizontal plane, the spray nozzle was adjusted so that the distance from the nozzle to the stent was about 2-4 inches and the composition was sprayed substantially horizontally with the brush being-directed along the stent from the distal end of the stent to the proximal end and then from the proximal end to the distal end in a sweeping motion at a speed such that one spray cycle occurred in about three stent rotations. Typically a pause of less than one minute, normally about one-half minute, elapsed between layers. Of course, the number of coating layers did and will vary with the particular application. For example, typical tie-layers as at 18 in FIG. 1, for a coating level of 3-4 mg of heparin per cm2 of projected area, 20 cycles of coating application are required and about 30 ml of solution will be consumed for a 3.5 mm diameter by 14.5 cm long stent.
  • The rotation speed of the motor, of course, can be adjusted as can the viscosity of the composition and the flow rate of the spray nozzle as desired to modify the layered structure. Generally, with the above mixes, the best results have been obtained at rotational speeds in the range of 30-50 rpm and with a spray nozzle flow rate in the range of 4-10 ml of coating composition per minute, depending on the stent size. It is contemplated that a more sophisticated, computer-controlled coating apparatus will successfully automate the process demonstrated as feasible in the laboratory.
  • Several applied layers make up what is called the undercoat as at 18. In one process, additional upper undercoat layers, which may be of the same or different composition with respect to bioactive material, the matrix. polymeric materials and crosslinking agent, for example, may be applied as the top layer as at 20. The application of the top layer follows the same coating procedure as the undercoat with the number and thickness of layers being optional. of course, the thickness of any layer can be adjusted by adjusting the speed of rotation of the stent and the spraying conditions. Generally, the total coating thickness is controlled by the number of spraying cycles or thin coats which make up the total coat.
  • As shown at 22 in FIG. 1, the coated stent is thereafter subjected to a curing step in which the prepolymer and crosslinking agents cooperate to produce a cured polymer matrix containing the biologically active species. The curing process involves evaporation of the solvent xylene, THF, etc. and the curing and crosslinking of the polymer. Certain silicone materials can be cured at relatively low temperatures, (i.e., RT-50° C.) in what is known as a room temperature vulcanization (RTV) process. More typically, however, the curing process involves higher temperature curing materials and the coated stents are put into an oven at approximately 90° C. or higher for approximately 16 hours. The temperature may be raised to as high as 150° C. for dexamethasone containing coated stents. Of course, the time and temperature may vary with particular silicones, crosslinkers and biologically active species.
  • Stents coated and cured in the manner described need to be sterilized prior to packaging for future implantation. For sterilization, gamma radiation is a preferred method particularly for heparin containing coatings; however, it has been found that stents coated and cured according to the process of the invention subjected to gamma sterilization may be too slow to recover their original posture when delivered to a vascular or other lumen site using a catheter unless a pretreatment step as at 24 is first applied to the coated, cured stent.
  • The pretreatment step involves an argon plasma treatment of the coated, cured stents in the unconstrained configuration. In accordance with this procedure, the stents are placed in a chamber of a plasma surface treatment system such as a Plasma Science 350 (Himont/Plasma Science, Foster City, Calif.). The system is equipped with a reactor chamber and RF solid-state generator operating at 13.56 mHz and from 0-500 watts power output and being equipped with a microprocessor controlled system and a complete vacuum pump package. The reaction chamber contains an unimpeded work volume of 16.75 inches (42.55 cm) by 13.5 inches (34.3 cm) by 17.5 inches (44.45 cm) in depth.
  • In the plasma process, unconstrained coated stents are placed in a reactor chamber and the system is purged with nitrogen and a vacuum applied to 20-50 mTorr. Thereafter, inert gas (argon, helium or mixture of them) is admitted to the reaction chamber for the plasma treatment. A highly preferred method of operation consists of using argon gas, operating at a power range from 200 to 400 watts, a flow rate of 150-650 standard ml per minute, which is equivalent to 100-450 mTorr, and an exposure time from 30 seconds to about 5 minutes. The stents can be removed immediately after the plasma treatment or remain in the argon atmosphere for an additional period of time, typically five minutes.
  • After this, as shown at 26, the stents may be exposed to gamma sterilization at 2.5-3.5 Mrad. The radiation may be carried out with the stent in either the radially unconstrained status or in the radially constrained status.
  • Preferably, however, the surface is modified prior to plasma treatment or just prior to sterilization by one of several additional processing methods of which some are described in relation to the following examples.
  • EXAMPLE 1 Fluorosilicone Surface Treatment of Eluting Heparin Coating
  • The undercoat of a stent was coated as multiple applied layers as described above thereafter and cured as described at 22. The heparin content of the undercoat was 37.5% and the coating thickness was about 30-40μ. Fluorosilicone (FSi) spray solution was prepared at 30 from a fluorosilicone suspension (Applied Silicone #40032) by weighing an amount of fluorosilicone suspension and adding tetrahydrofuran (THF) according to the relation equation of VTHF=1.2× the weight of fluorosilicone suspension. The solution was stirred very well and spray-coated on the stent at 32 using the technique of the application of the undercoat process at 18 and the coated stents were cured at 90° C. for 16 hours. The coated stents are argon plasma treated prior to gamma sterilization according to the procedures described above in accordance with steps 22-26.
  • FIG. 7 is a plot of heparin release kinetics in phosphate buffer system with fluorosilicone topcoat and without any topcoat. The thickness of the topcoat is about 10-15 A. While it does not appear on the graph of FIG. 7 it should be noted that the release rate for the coating without FSi is initially about 25 times higher than that with FSi, i.e., during the first 2 hours. This is, of course, clearly off the scale of the graph. It is noteworthy, however, that the coating with the FSi top layer or diffusion barrier does show a depressed initial release rate combined with an enhanced elution rate after the first day and through the first week up until about the tenth day. In addition, the fluorosilicone (FSi) topcoat, by virtue of the high electronegativity of fluorination maintains non-thrombogenic surface qualities during and after the elusion of the biologically active heparin species. In addition, because of the negative charges off the heparin itself, the electro-negativity of the fluorosilicone topcoat may be, at least in part, responsible for the modified heparin release kinetic profile.
  • FIG. 8 compares a plot of fluorosilicone (FSi) top coating containing 16.7% imbedded heparin with one containing fluorosilicone (FSi) only. An undercoating is identical to that utilized in FIG. 7 containing about 37.5% heparin to a thickness of about 30-40 microns. These elution kinetics are quite comparable with the heparin-free FSi top layer greatly reducing the initial burst of heparin release and otherwise the heparin in the FSi top layer imparts a slightly greater release over the period of the test.
  • EXAMPLE 2 Immobilization of Polyethylene Glycol (PEG) on Drug Eluting Undercoat
  • An undercoat was coated on a stent and cured at 22 as in Example 1. The stent was then treated by argon gas plasma as at 24 and ammonium gas plasma at 40. The equipment and the process of argon gas plasma treatment was as has been described above. The ammonium plasma treatment was implemented immediately after the argon gas plasma treatment, to aminate the surface of the coating. The ammonium flow rate was in the range of 100-700 cubic centimeter per minute (ccM) in preferably in the range of 500-600 ccM. The power output of radio frequency plasma was in the range of 50-500 watts, preferably in ˜200 watts. The process time was in the range of 30 sec-10 min, preferably ˜5 min.
  • Immediately after amination, the stents were immersed into electrophilically activated polyethylene glycol (PEG) solution it 42. PEG is known to be an inhibitor of protein absorption. Examples of electrophilically activated PEG are PEG nitrophenyl carbonates, PEG trichlorophenyl carbonates, PEG tresylate, PEG glycidyl ether, PEG isocyanate, etc., optionally with one end terminated with methoxyl group. Molecular weight of PEG ranged from about 1000-6000, and is preferable about 3000. It has been observed that simple ammonium amination will not generate large quantities of primary and secondary amines on the elastomeric polymer surface (for example silicone). Instead, imine (>C═N—H), and other more oxidative nitro containing groups will dominate the surface. It is generally necessary to add reductive agent, such as NaBH3CN into the reaction media so that the functional group on PEG can react with imine and possibly other nitro-containing species on the surface, and therefore immobilize PEG onto the surface. The typical concentration of NaBH3CN is about 2 mg/ml. Since PEG and its derivatives dissolve in water and many polar and aromatic solvents, the solvent used in the coating must be a solvent for PEG but not for the drug in the undercoat to prevent the possible loss of the drug through leaching. In the case of eluting-heparin coating, a mixed solvent of formamide and methyl ethyl ketone (MEK) or a mixed solvent of formamide and acetone are preferred solvents, (preferably at ratios of 30 formamide: 70 MEK or acetone by volume), since they will not dissolve heparin. The concentration of PEG, the reaction time, the reaction temperature and the pH value depend on the kind of PEG employed. In the case of eluting heparin coating, 5% PEG tresylate in (30-70) Formamide/MEK was used successfully. The reaction time was 3 hours at room temperature. PEG was then covalently bound to the surface. Gamma radiation was then used for sterilization of this embodiment as previously described.
  • With respect to the anticoagulant material heparin, the percentage in the undercoat is nominally from about 30-50% and that of the topcoat from about 0-30% active material. The coating thickness ratio of the topcoat to the undercoat varies from about 1:10 to 1:2 and is preferably in the range of from about 1:6 to 1:3.
  • To produce a topcoat which is substantially free of pores, materials such as porosigens, which can be removed or leached out of the topcoat should not be included in the composition used to form the topcoat. One way of preparing a substantially non-porous topcoat is to apply a topcoat composition which comprises substantially pure polymeric materials. These materials preferably impart biocompatibility to the implanted device during and after the release of the biologically active material.
  • A topcoat which only partially covers the undercoat can be formed in a number of ways. Such methods include controlling the thickness of the topcoat so that it is less than the diameter of certain drug particles in the undercoat. For example, when a drug used in the undercoat has an average particle size of 5 μm, it is possible that 15% of the particles will be greater than or equal to 8 μm. At the molecular level, the surface unevenness is at least more than 5 microns. By application of a topcoat of about 5 micron or less. The uneven surface will become smooth to a certain degree. But uncovered areas will still exist, which allows water to penetrate into the undercoat, swelling the drug particle, or dissolving the drug. Due to the osmotic pressure, the drug will elute out through the uncovered areas. If the osmotic pressure is too high, cracks or voids may form in the topcoat which allows drugs to elute from the undercoat to the body.
  • As illustrated in FIG. 9, in a coating 102 which covers a surface of a prosthesis 101, a thin topcoat 104 of the coating 102 only partially covers the undercoat 103 of the coating 102. By having the topcoat 104 cover less than the entire surface of the undercoat 103, parts of the undercoat 103, including a number of drug particles 105, are exposed to body fluids at the implantation site so that the drug 105 can be released. By using a topcoat 104 having a thickness which is about the average particle size of the drug 105, certain larger sized drug particles 106 will not be covered by the topcoat 104.
  • Other methods to form a partially covered topcoat include using a polymer which is incompatible to the undercoat elastomer as the biocompatible material of the topcoat. Because of the incompatibility between the materials, a microphase separation will form in the topcoat which will leave the undercoat partially uncovered. Persons skilled in the art are aware of suitable combinations of such incompatible materials.
  • Another method involves applying a poor solvent wash to the topcoat to force the biocompatible polymer to shrink and create uneven surfaces voids in the topcoat which forms a topcoat which partially covers the undercoat.
  • In yet another method of making a topcoat which partly or fully covers the undercoat, topcoat and undercoat materials having different Young's moduli (either before or after they have cured) are used. For instance, a topcoat material having a higher Young's modulus compared to that of the undercoat material can be employed. When the coated device is mounted on the delivery device or during deployment of the coated device, the topcoat undergoes compression or stretching or other types of mechanical challenges. Since the topcoat material has a higher Young's modulus, it will tend to crack and form voids in the topcoat to allow the drug of the undercoat to elute therefrom.
  • Another method for forming the topcoat involves using a bioabsorbable material in the topcoat, which can cover the entire undercoat or only a part of the undercoat. When the coated device comes into contact with body fluid, the topcoat begins to degrade either at the surface or throughout the bulk of the topcoat. The rate of degradation depends upon the type of bioabsorbable material used. Once the topcoat has been partially absorbed, the undercoat is exposed to body tissue and the drug in the undercoat is released, but the burst release or effect is reduced.
  • Suppressing the burst effect also enables a reduction in the drug loading or in other words, allows a reduction in the coating thickness, since the physician will give a bolus injection of antiplatelet/anticoagulation drugs to the patient during the stenting process. As a result, the drug imbedded in the stent can be fully used without waste. Tailoring the first day release, but maximizing second day and third day release at the thinnest possible coating configuration will reduce the acute or subacute thrombosis particularly if drugs such as heparin are incorporated.
  • FIG. 4 depicts the general effect of drug loading for coatings of similar thickness. The initial elution rate increases with the drug loading as shown in FIG. 5. The release rate also increases with the thickness of the coating at the same loading but tends to be inversely proportional to the thickness of the topcoat as shown by the same drug loading and similar undercoat thickness in FIG. 6.
  • What is apparent from the data gathered to date, however, is that the process of the present invention enables the drug elution kinetics to be controlled in a manner desired to meet the needs of the particular stent application. In a similar manner, stent coatings can be prepared using a combination of two or more drugs and the drug release sequence and rate controlled. For example, antiproliferation drugs may be combined in the undercoat and antiplatelet drugs in the topcoat. In this manner, the antiplatelet drugs, for example, heparin, will elute first followed by antiproliferation drugs to better enable safe encapsulation of the implanted stent.
  • The heparin concentration measurement were made utilizing a standard curve prepared by complexing azure A dye with dilute solutions of heparin. Sixteen standards were used to compile the standard curve in a well-known manner.
  • For the elution test, the stents were immersed in a phosphate buffer solution at pH 7.4 in an incubator at approximately 37° C. Periodic samplings of the solution were processed to determine the amount of heparin eluted. After each sampling, each stent was placed in heparin-free buffer solution.
  • As stated above, while the allowable loading of the elastomeric material with heparin may vary, in the case of silicone materials, heparin may exceed 60% of the total weight of the layer. However, the loading generally most advantageously used is in the range from about 10% to 45% of the total weight of the layer. In the case of dexamethasone, the loading may be as high as 50% or more of the total weight of the layer but is preferably in the range of about 0.4% to 45%.
  • It will be appreciated that the mechanism of incorporation of the biologically active species into a thin surface coating structure applicable to a metal stent is an important aspect of the present invention. The need for relatively thick-walled polymer elution stents or any membrane overlayers associated with many prior drug elution devices is obviated, as is the need for utilizing biodegradable or reabsorbable vehicles for carrying the biologically active species. The technique clearly enables long-term delivery and minimizes interference with the independent mechanical or therapeutic benefits of the stent itself.
  • Coating materials are designed with a particular coating technique, coating/drug combination and drug infusion mechanism in mind. Consideration of the particular form and mechanism of release of the biologically active species in the coating allow the technique to produce superior results. In this manner, delivery of the biologically active species from the coating structure can be tailored to accommodate a variety of applications.
  • Whereas the above examples depict coatings having two different drug loadings or percentages of biologically active material to be released, this is by no means limiting with respect to the invention and it is contemplated that any number of layers and combinations of loadings can be employed to achieve a desired release profile. For example, gradual grading and change in the loading of the layers can be utilized in which, for example, higher loadings are used in the inner layers. Also layers can be used which have no drug loadings at all. For example, a pulsatile heparin release system may be achieved by a coating in which alternate layers containing heparin are sandwiched between unloaded layers of silicone or other materials for a portion of the coating. In other words, the invention allows untold numbers of combinations which result in a great deal of flexibility with respect to controlling the release of biologically active materials with regard to an implanted stent. Each applied layer is typically from approximately 0.5 microns to 15 microns in thickness. The total number of sprayed layers, of course, can vary widely, from less than 10 to more than 50 layers; commonly, 20 to 40 layers are included. The total thickness of the coating can also vary widely, but can generally be, from about 10 to 200 microns.
  • Whereas the polymer of the coating may be any compatible biostable elastomeric material capable of being adhered to the stent material as a thin layer, hydrophobic materials are preferred because it has been found that the release of the biologically active species can generally be more predictably controlled with such materials. Preferred materials include silicone rubber elastomers and biostable polyurethanes specifically.
  • This invention has been described herein in considerable detail in order to comply with the Patent Statutes and to provide those skilled in the art with the information needed to apply the novel principles and to construct and use embodiments of the example as required. However, it is to be understood that the invention can be carried out by specifically different devices and that various modifications can be accomplished without departing from the scope of the invention itself.

Claims (20)

1-50. (canceled)
51. A medical device comprising:
a metallic intravascular stent comprising an open lattice sidewall structure and designed for permanent implantation into a blood vessel of a patient;
a first quantity of a first polymer composition applied to at least a portion of said stent and conforming to said open lattice sidewall structure so as to preserve the open lattice sidewall structure of said stent, wherein said first polymer composition comprises a first biostable polymer and a biologically active material; and
a second quantity of a second polymer composition applied to at least a portion of said first quantity and conforming to said stent so as to preserve the open lattice sidewall structure of said stent, wherein said second polymer composition comprises a second biostable polymer that is different from said first biostable polymer, and wherein said second polymer composition is non-thrombogenic and substantially free of the biologically active material or other elutable material,
wherein when in use, the biologically active material is released from the stent to the blood vessel at a first rate that is different from a second rate, wherein the second rate is the rate of release of the same biologically active material from the stent had the second quantity of the second polymer composition not been applied to the first quantity of the first polymer composition.
52. The medical device of claim 51, wherein the metallic intravascular stent is a stainless steel intravascular stent.
53. The medical device of claim 51, wherein the first quantity of first polymer composition is different from the second quantity of second polymer composition.
54. The medical device of claim 51, wherein the first biostable polymer comprises a hydrophobic elastomeric material, an ethylene vinyl acetate copolymer material, or a mixture thereof.
55. The medical device of claim 51, wherein the biologically active material is an antithrobotic agent, anticoagulant, antibiotic, antiplatelet agent, thrombolytic agent, antiproliferative agent, steroidal antiinflammatory agent, nonsteroidal antiinflammatory agent, agent that inhibits hyperplasia, smooth muscle cell inhibitor, growth factor, growth factor inhibitor, cell adhesion inhibitor, cell adhesion promoter, drug that enhances the formation of healthy neointimal tissue, or a mixture thereof.
56. The medical device of claim 51, wherein the biologically active material is an antibiotic.
57. The medical device of claim 51, wherein the biologically active material inhibits smooth muscle cell.
58. The medical device of claim 51, wherein the biologically active material inhibits restenosis.
59. The medical device of claim 51, wherein the second biostable polymer remains non-thrombogenic during and after release of the biologically active material.
60. The medical device of claim 51, wherein the stent releases the biologically active material over a period of time.
61. A method of treating restenosis comprising implanting the medical device of claim 51 into the blood vessel of the patient.
62. A medical device comprising:
a metallic intravascular stent comprising an open lattice sidewall structure and designed for permanent implantation into a blood vessel of a patient;
a first quantity of a first polymer composition applied to at least a portion of said stent and conforming to said open lattice sidewall structure so as to preserve the open lattice sidewall structure of said stent, wherein said first polymer composition comprises an ethylene vinyl acetate copolymer material and an antibiotic; and
a second quantity of a second polymer composition applied to at least a portion of said first quantity and conforming to said stent so as to preserve the open lattice sidewall structure of said stent, wherein said second polymer composition comprises a second biostable polymer that is different from the ethylene vinyl acetate copolymer material of said first polymer composition, and wherein said second polymer composition is non-thrombogenic and substantially free of the antibiotic of the first polymer composition or other elutable material,
wherein when in use, the antibiotic is released from the stent to the blood vessel at a first rate that is different from a second rate, wherein the second rate is the rate of release of the same antibiotic from the stent had the second quantity of the second polymer composition not been applied to the first quantity of the first polymer composition.
63. The medical device of claim 62, wherein the metallic intravascular stent is a stainless steel intravascular stent.
64. The medical device of claim 62, wherein the first quantity of first polymer composition is different from the second quantity of second polymer composition.
65. The medical device of claim 62, wherein the antibiotic inhibits smooth muscle cell.
66. The medical device of claim 62, wherein the antibiotic inhibits restenosis.
67. The medical device of claim 62, wherein the second biostable polymer remains non-thrombogenic during and after release of the antibiotic.
68. The medical device of claim 62, wherein the stent releases the antibiotic over a period of time.
69. A method of treating restenosis comprising implanting the medical device of claim 62 into the blood vessel of the patient.
US11/116,256 1995-04-19 2005-04-27 Drug coating with topcoat Abandoned US20050187611A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US11/116,256 US20050187611A1 (en) 1995-04-19 2005-04-27 Drug coating with topcoat

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US42488495A 1995-04-19 1995-04-19
US52627395A 1995-09-11 1995-09-11
US08/663,518 US6120536A (en) 1995-04-19 1996-06-13 Medical devices with long term non-thrombogenic coatings
US08/996,410 US6099562A (en) 1996-06-13 1997-12-22 Drug coating with topcoat
US09/573,506 US6284305B1 (en) 1996-06-13 2000-05-18 Drug coating with topcoat
US09/942,716 US6620194B2 (en) 1995-04-19 2001-08-30 Drug coating with topcoat
US10/603,115 US20040049265A1 (en) 1995-04-19 2003-06-24 Drug coating with topcoat
US11/116,256 US20050187611A1 (en) 1995-04-19 2005-04-27 Drug coating with topcoat

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US10/603,115 Continuation US20040049265A1 (en) 1995-04-19 2003-06-24 Drug coating with topcoat

Publications (1)

Publication Number Publication Date
US20050187611A1 true US20050187611A1 (en) 2005-08-25

Family

ID=25542881

Family Applications (6)

Application Number Title Priority Date Filing Date
US08/996,410 Expired - Lifetime US6099562A (en) 1995-04-19 1997-12-22 Drug coating with topcoat
US09/573,506 Expired - Fee Related US6284305B1 (en) 1995-04-19 2000-05-18 Drug coating with topcoat
US09/942,716 Expired - Fee Related US6620194B2 (en) 1995-04-19 2001-08-30 Drug coating with topcoat
US10/603,115 Abandoned US20040049265A1 (en) 1995-04-19 2003-06-24 Drug coating with topcoat
US11/116,256 Abandoned US20050187611A1 (en) 1995-04-19 2005-04-27 Drug coating with topcoat
US11/116,052 Abandoned US20050208200A1 (en) 1995-04-19 2005-04-27 Drug coating with topcoat

Family Applications Before (4)

Application Number Title Priority Date Filing Date
US08/996,410 Expired - Lifetime US6099562A (en) 1995-04-19 1997-12-22 Drug coating with topcoat
US09/573,506 Expired - Fee Related US6284305B1 (en) 1995-04-19 2000-05-18 Drug coating with topcoat
US09/942,716 Expired - Fee Related US6620194B2 (en) 1995-04-19 2001-08-30 Drug coating with topcoat
US10/603,115 Abandoned US20040049265A1 (en) 1995-04-19 2003-06-24 Drug coating with topcoat

Family Applications After (1)

Application Number Title Priority Date Filing Date
US11/116,052 Abandoned US20050208200A1 (en) 1995-04-19 2005-04-27 Drug coating with topcoat

Country Status (4)

Country Link
US (6) US6099562A (en)
EP (2) EP1980278A3 (en)
JP (1) JP3556837B2 (en)
DE (1) DE69839869D1 (en)

Cited By (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030099682A1 (en) * 1998-11-20 2003-05-29 Francis Moussy Apparatus and method for control of tissue/implant interactions
US20050131532A1 (en) * 2000-12-22 2005-06-16 Avantec Vascular Corporation Apparatus and methods for controlled substance delivery from implanted prostheses
WO2008017814A1 (en) 2006-08-09 2008-02-14 Sinclair Pharmaceuticals Limited Prevention and treatment of microbial infection
US20080058922A1 (en) * 2006-08-31 2008-03-06 Cardiac Pacemakers, Inc. Methods and devices employing vap-1 inhibitors
US20080057027A1 (en) * 2006-08-31 2008-03-06 Cardiac Pacemakers, Inc Methods and devices to regulate stem cell homing
US20080057053A1 (en) * 2006-08-31 2008-03-06 Cardiac Pacemakers, Inc Bispecific antibodies and agents to enhance stem cell homing
US20100028403A1 (en) * 2008-07-31 2010-02-04 Boston Scientific Scimed, Inc. Medical devices for therapeutic agent delivery
US7815675B2 (en) 1996-11-04 2010-10-19 Boston Scientific Scimed, Inc. Stent with protruding branch portion for bifurcated vessels
US7833266B2 (en) 2007-11-28 2010-11-16 Boston Scientific Scimed, Inc. Bifurcated stent with drug wells for specific ostial, carina, and side branch treatment
US7842082B2 (en) 2006-11-16 2010-11-30 Boston Scientific Scimed, Inc. Bifurcated stent
US7951191B2 (en) 2006-10-10 2011-05-31 Boston Scientific Scimed, Inc. Bifurcated stent with entire circumferential petal
US7951192B2 (en) 2001-09-24 2011-05-31 Boston Scientific Scimed, Inc. Stent with protruding branch portion for bifurcated vessels
US7955382B2 (en) 2006-09-15 2011-06-07 Boston Scientific Scimed, Inc. Endoprosthesis with adjustable surface features
US7959669B2 (en) 2007-09-12 2011-06-14 Boston Scientific Scimed, Inc. Bifurcated stent with open ended side branch support
US7985252B2 (en) 2008-07-30 2011-07-26 Boston Scientific Scimed, Inc. Bioerodible endoprosthesis
US7998192B2 (en) 2008-05-09 2011-08-16 Boston Scientific Scimed, Inc. Endoprostheses
US8002821B2 (en) 2006-09-18 2011-08-23 Boston Scientific Scimed, Inc. Bioerodible metallic ENDOPROSTHESES
US8016878B2 (en) 2005-12-22 2011-09-13 Boston Scientific Scimed, Inc. Bifurcation stent pattern
US8048150B2 (en) 2006-04-12 2011-11-01 Boston Scientific Scimed, Inc. Endoprosthesis having a fiber meshwork disposed thereon
US8052743B2 (en) 2006-08-02 2011-11-08 Boston Scientific Scimed, Inc. Endoprosthesis with three-dimensional disintegration control
US8052745B2 (en) 2007-09-13 2011-11-08 Boston Scientific Scimed, Inc. Endoprosthesis
US8052744B2 (en) 2006-09-15 2011-11-08 Boston Scientific Scimed, Inc. Medical devices and methods of making the same
US8057534B2 (en) 2006-09-15 2011-11-15 Boston Scientific Scimed, Inc. Bioerodible endoprostheses and methods of making the same
US8080055B2 (en) 2006-12-28 2011-12-20 Boston Scientific Scimed, Inc. Bioerodible endoprostheses and methods of making the same
US8089029B2 (en) 2006-02-01 2012-01-03 Boston Scientific Scimed, Inc. Bioabsorbable metal medical device and method of manufacture
US8128689B2 (en) 2006-09-15 2012-03-06 Boston Scientific Scimed, Inc. Bioerodible endoprosthesis with biostable inorganic layers
US8133553B2 (en) 2007-06-18 2012-03-13 Zimmer, Inc. Process for forming a ceramic layer
US8147539B2 (en) 2006-12-20 2012-04-03 Boston Scientific Scimed, Inc. Stent with a coating for delivering a therapeutic agent
US8236048B2 (en) 2000-05-12 2012-08-07 Cordis Corporation Drug/drug delivery systems for the prevention and treatment of vascular disease
US8236046B2 (en) 2008-06-10 2012-08-07 Boston Scientific Scimed, Inc. Bioerodible endoprosthesis
US8267992B2 (en) 2009-03-02 2012-09-18 Boston Scientific Scimed, Inc. Self-buffering medical implants
US8277501B2 (en) 2007-12-21 2012-10-02 Boston Scientific Scimed, Inc. Bi-stable bifurcated stent petal geometry
US8303609B2 (en) 2000-09-29 2012-11-06 Cordis Corporation Coated medical devices
US8303643B2 (en) 2001-06-27 2012-11-06 Remon Medical Technologies Ltd. Method and device for electrochemical formation of therapeutic species in vivo
US8309521B2 (en) 2007-06-19 2012-11-13 Zimmer, Inc. Spacer with a coating thereon for use with an implant device
US8382824B2 (en) 2008-10-03 2013-02-26 Boston Scientific Scimed, Inc. Medical implant having NANO-crystal grains with barrier layers of metal nitrides or fluorides
US8449901B2 (en) 2003-03-28 2013-05-28 Innovational Holdings, Llc Implantable medical device with beneficial agent concentration gradient
US8602290B2 (en) 2007-10-10 2013-12-10 Zimmer, Inc. Method for bonding a tantalum structure to a cobalt-alloy substrate
US8668732B2 (en) 2010-03-23 2014-03-11 Boston Scientific Scimed, Inc. Surface treated bioerodible metal endoprostheses
US8808726B2 (en) 2006-09-15 2014-08-19 Boston Scientific Scimed. Inc. Bioerodible endoprostheses and methods of making the same
US8840660B2 (en) 2006-01-05 2014-09-23 Boston Scientific Scimed, Inc. Bioerodible endoprostheses and methods of making the same
US8932340B2 (en) 2008-05-29 2015-01-13 Boston Scientific Scimed, Inc. Bifurcated stent and delivery system

Families Citing this family (862)

* 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
US5811447A (en) 1993-01-28 1998-09-22 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US20020091433A1 (en) * 1995-04-19 2002-07-11 Ni Ding Drug release coated stent
US6099562A (en) * 1996-06-13 2000-08-08 Schneider (Usa) Inc. Drug coating with topcoat
US6777217B1 (en) * 1996-03-26 2004-08-17 President And Fellows Of Harvard College Histone deacetylases, and uses related thereto
US7238197B2 (en) 2000-05-30 2007-07-03 Devax, Inc. Endoprosthesis deployment system for treating vascular bifurcations
US8728143B2 (en) 1996-06-06 2014-05-20 Biosensors International Group, Ltd. Endoprosthesis deployment system for treating vascular bifurcations
US7686846B2 (en) 1996-06-06 2010-03-30 Devax, Inc. Bifurcation stent and method of positioning in a body lumen
US7959664B2 (en) * 1996-12-26 2011-06-14 Medinol, Ltd. Flat process of drug coating for stents
US10028851B2 (en) 1997-04-15 2018-07-24 Advanced Cardiovascular Systems, Inc. Coatings for controlling erosion of a substrate of an implantable medical device
US6240616B1 (en) 1997-04-15 2001-06-05 Advanced Cardiovascular Systems, Inc. Method of manufacturing a medicated porous metal prosthesis
US8172897B2 (en) 1997-04-15 2012-05-08 Advanced Cardiovascular Systems, Inc. Polymer and metal composite implantable medical devices
US6776792B1 (en) * 1997-04-24 2004-08-17 Advanced Cardiovascular Systems Inc. Coated endovascular stent
US6433154B1 (en) * 1997-06-12 2002-08-13 Bristol-Myers Squibb Company Functional receptor/kinase chimera in yeast cells
US7445792B2 (en) * 2003-03-10 2008-11-04 Abbott Laboratories Medical device having a hydration inhibitor
US6890546B2 (en) 1998-09-24 2005-05-10 Abbott Laboratories Medical devices containing rapamycin analogs
US20030129215A1 (en) * 1998-09-24 2003-07-10 T-Ram, Inc. Medical devices containing rapamycin analogs
US7399480B2 (en) * 1997-09-26 2008-07-15 Abbott Laboratories Methods of administering tetrazole-containing rapamycin analogs with other therapeutic substances using medical devices
US20060198867A1 (en) * 1997-09-25 2006-09-07 Abbott Laboratories, Inc. Compositions and methods of administering rapamycin analogs using medical devices for long-term efficacy
US7357942B2 (en) * 1997-09-26 2008-04-15 Abbott Laboratories Compositions, systems, and kits for administering zotarolimus and paclitaxel to blood vessel lumens
US8057816B2 (en) * 1997-09-26 2011-11-15 Abbott Laboratories Compositions and methods of administering paclitaxel with other drugs using medical devices
US8394398B2 (en) * 1997-09-26 2013-03-12 Abbott Laboratories Methods of administering rapamycin analogs with anti-inflammatories using medical devices
US7378105B2 (en) * 1997-09-26 2008-05-27 Abbott Laboratories Drug delivery systems, kits, and methods for administering zotarolimus and paclitaxel to blood vessel lumens
US8257725B2 (en) * 1997-09-26 2012-09-04 Abbott Laboratories Delivery of highly lipophilic agents via medical devices
US8257726B2 (en) * 1997-09-26 2012-09-04 Abbott Laboratories Compositions, systems, kits, and methods of administering rapamycin analogs with paclitaxel using medical devices
US20050171478A1 (en) * 1998-01-13 2005-08-04 Selmon Matthew R. Catheter system for crossing total occlusions in vasculature
US7208010B2 (en) 2000-10-16 2007-04-24 Conor Medsystems, Inc. Expandable medical device for delivery of beneficial agent
US6241762B1 (en) 1998-03-30 2001-06-05 Conor Medsystems, Inc. Expandable medical device with ductile hinges
US7713297B2 (en) 1998-04-11 2010-05-11 Boston Scientific Scimed, Inc. Drug-releasing stent with ceramic-containing layer
US6364856B1 (en) * 1998-04-14 2002-04-02 Boston Scientific Corporation Medical device with sponge coating for controlled drug release
US20030040790A1 (en) 1998-04-15 2003-02-27 Furst Joseph G. Stent coating
US20020099438A1 (en) * 1998-04-15 2002-07-25 Furst Joseph G. Irradiated stent coating
US20070087028A1 (en) * 1998-04-16 2007-04-19 Robert Falotico Intraluminal devices for the prevention and treatment of vascular disease
US8029561B1 (en) * 2000-05-12 2011-10-04 Cordis Corporation Drug combination useful for prevention of restenosis
US20020188037A1 (en) * 1999-04-15 2002-12-12 Chudzik Stephen J. Method and system for providing bioactive agent release coating
ES2179646T3 (en) * 1998-04-27 2003-01-16 Surmodics Inc COATING THAT RELEASES A BIOACTIVE AGENT.
ATE358456T1 (en) * 1998-05-05 2007-04-15 Boston Scient Ltd STENT WITH SMOOTH ENDS
US6200477B1 (en) * 1998-05-06 2001-03-13 Alltech Associates, Inc. Continuously regenerated and integrated suppressor and detector for suppressed ion chromatography and method
US7967855B2 (en) * 1998-07-27 2011-06-28 Icon Interventional Systems, Inc. Coated medical device
US8070796B2 (en) 1998-07-27 2011-12-06 Icon Interventional Systems, Inc. Thrombosis inhibiting graft
US20060240070A1 (en) * 1998-09-24 2006-10-26 Cromack Keith R Delivery of highly lipophilic agents via medical devices
US7960405B2 (en) * 1998-09-24 2011-06-14 Abbott Laboratories Compounds and methods for treatment and prevention of diseases
US7455853B2 (en) * 1998-09-24 2008-11-25 Abbott Cardiovascular Systems Inc. Medical devices containing rapamycin analogs
US8257724B2 (en) * 1998-09-24 2012-09-04 Abbott Laboratories Delivery of highly lipophilic agents via medical devices
JP4691745B2 (en) * 1999-06-21 2011-06-01 東洋紡績株式会社 Method for coating antibacterial antithrombotic material
US6258121B1 (en) * 1999-07-02 2001-07-10 Scimed Life Systems, Inc. Stent coating
GB9920547D0 (en) * 1999-08-31 1999-11-03 Destiny Pharma Ltd Coated implant
FI19991852A (en) * 1999-09-01 2001-03-01 Yli Urpo Antti New multilayer material with a biologically active agent, and its preparation
US7807211B2 (en) 1999-09-03 2010-10-05 Advanced Cardiovascular Systems, Inc. Thermal treatment of an implantable medical device
US20040029952A1 (en) * 1999-09-03 2004-02-12 Yung-Ming Chen Ethylene vinyl alcohol composition and coating
US7682647B2 (en) * 1999-09-03 2010-03-23 Advanced Cardiovascular Systems, Inc. Thermal treatment of a drug eluting implantable medical device
US6790228B2 (en) * 1999-12-23 2004-09-14 Advanced Cardiovascular Systems, Inc. Coating for implantable devices and a method of forming the same
US6759054B2 (en) 1999-09-03 2004-07-06 Advanced Cardiovascular Systems, Inc. Ethylene vinyl alcohol composition and coating
US20070032853A1 (en) * 2002-03-27 2007-02-08 Hossainy Syed F 40-O-(2-hydroxy)ethyl-rapamycin coated stent
AU8023200A (en) * 1999-10-13 2001-04-23 Biocardia, Inc. Pulmonary vein stent and method for use
US6716242B1 (en) * 1999-10-13 2004-04-06 Peter A. Altman Pulmonary vein stent and method for use
DE19951477A1 (en) * 1999-10-26 2001-05-03 Biotronik Mess & Therapieg Stent
US6702849B1 (en) * 1999-12-13 2004-03-09 Advanced Cardiovascular Systems, Inc. Method of processing open-celled microcellular polymeric foams with controlled porosity for use as vascular grafts and stent covers
US6908624B2 (en) * 1999-12-23 2005-06-21 Advanced Cardiovascular Systems, Inc. Coating for implantable devices and a method of forming the same
WO2001049338A1 (en) * 1999-12-30 2001-07-12 Li Wei Pin Controlled delivery of therapeutic agents by insertable medical devices
US20030129724A1 (en) 2000-03-03 2003-07-10 Grozinger Christina M. Class II human histone deacetylases, and uses related thereto
US6379382B1 (en) * 2000-03-13 2002-04-30 Jun Yang Stent having cover with drug delivery capability
KR100860860B1 (en) * 2000-03-15 2008-09-29 오르버스네이치 메디칼 인코포레이티드 Coating that promotes endothelial cell adherence
US8088060B2 (en) 2000-03-15 2012-01-03 Orbusneich Medical, Inc. Progenitor endothelial cell capturing with a drug eluting implantable medical device
US9522217B2 (en) 2000-03-15 2016-12-20 Orbusneich Medical, Inc. Medical device with coating for capturing genetically-altered cells and methods for using same
US7875283B2 (en) 2000-04-13 2011-01-25 Advanced Cardiovascular Systems, Inc. Biodegradable polymers for use with implantable medical devices
US8109994B2 (en) 2003-01-10 2012-02-07 Abbott Cardiovascular Systems, Inc. Biodegradable drug delivery material for stent
US6527801B1 (en) 2000-04-13 2003-03-04 Advanced Cardiovascular Systems, Inc. Biodegradable drug delivery material for stent
US20050002986A1 (en) * 2000-05-12 2005-01-06 Robert Falotico Drug/drug delivery systems for the prevention and treatment of vascular disease
AU2001261625B2 (en) 2000-05-16 2006-04-06 Regents Of The University Of Minnesota High mass throughput particle generation using multiple nozzle spraying
US8252044B1 (en) 2000-11-17 2012-08-28 Advanced Bio Prosthestic Surfaces, Ltd. Device for in vivo delivery of bioactive agents and method of manufacture thereof
US7682648B1 (en) 2000-05-31 2010-03-23 Advanced Cardiovascular Systems, Inc. Methods for forming polymeric coatings on stents
US6506408B1 (en) * 2000-07-13 2003-01-14 Scimed Life Systems, Inc. Implantable or insertable therapeutic agent delivery device
US6451373B1 (en) * 2000-08-04 2002-09-17 Advanced Cardiovascular Systems, Inc. Method of forming a therapeutic coating onto a surface of an implantable prosthesis
ES2312456T3 (en) 2000-08-30 2009-03-01 Johns Hopkins University DEVICES FOR INTRAOCULAR SUPPLY OF PHARMACOS.
US6953560B1 (en) 2000-09-28 2005-10-11 Advanced Cardiovascular Systems, Inc. Barriers for polymer-coated implantable medical devices and methods for making the same
US20070276474A1 (en) * 2000-09-29 2007-11-29 Llanos Gerard H Medical Devices, Drug Coatings and Methods for Maintaining the Drug Coatings Thereon
US20060222756A1 (en) * 2000-09-29 2006-10-05 Cordis Corporation Medical devices, drug coatings and methods of maintaining the drug coatings thereon
US7261735B2 (en) * 2001-05-07 2007-08-28 Cordis Corporation Local drug delivery devices and methods for maintaining the drug coatings thereon
DK1328213T3 (en) 2000-10-16 2005-11-28 Conor Medsystems Inc Expandable medical device for delivery of a useful agent
US7807210B1 (en) 2000-10-31 2010-10-05 Advanced Cardiovascular Systems, Inc. Hemocompatible polymers on hydrophobic porous polymers
US9107605B2 (en) * 2000-11-17 2015-08-18 Advanced Bio Prosthetic Surfaces, Ltd., A Wholly Owned Subsidiary Of Palmaz Scientific, Inc. Device for in vivo delivery of bioactive agents and method of manufacture thereof
US10398830B2 (en) * 2000-11-17 2019-09-03 Vactronix Scientific, Llc Device for in vivo delivery of bioactive agents and method of manufacture thereof
DE10060443A1 (en) * 2000-11-29 2002-06-06 Biotronik Mess & Therapieg Stent, in particular in the form of a coronary stent contains at least one wall section consisting of a human or animal tissue possessing sufficient elasticity
FR2817472B1 (en) * 2000-12-06 2003-01-03 Oreal OXIDATION DYEING COMPOSITION BASED ON 1- (4-AMINOPHENYL) PYRROLIDINES SUBSTITUTED AT LEAST 2 AND 3 AND DYEING METHOD THEREOF
DE60130032D1 (en) * 2000-12-22 2007-09-27 Avantec Vascular Corp Device for delivery of therapeutic agents
US6824559B2 (en) * 2000-12-22 2004-11-30 Advanced Cardiovascular Systems, Inc. Ethylene-carboxyl copolymers as drug delivery matrices
US7018405B2 (en) 2000-12-22 2006-03-28 Avantec Vascular Corporation Intravascular delivery of methylprednisolone
US6663662B2 (en) * 2000-12-28 2003-12-16 Advanced Cardiovascular Systems, Inc. Diffusion barrier layer for implantable devices
US7504125B1 (en) 2001-04-27 2009-03-17 Advanced Cardiovascular Systems, Inc. System and method for coating implantable devices
GB0100761D0 (en) 2001-01-11 2001-02-21 Biocompatibles Ltd Drug delivery from stents
GB0100760D0 (en) 2001-01-11 2001-02-21 Biocompatibles Ltd Drug delivery from stents
DE10127011A1 (en) * 2001-06-05 2002-12-12 Jomed Gmbh Implant used for treating vascular narrowing or occlusion, especially for controlling restenosis contains FK506 in chemically bound or physically fixed form
WO2002066096A2 (en) * 2001-02-16 2002-08-29 Cordis Corporation Balloon catheter stent delivery system with ridges
WO2002065947A2 (en) 2001-02-16 2002-08-29 Abbott Laboratories Vascular Enterprises Limited Implants with fk506 for prophylaxis and treatment of restonoses
US7572270B2 (en) * 2001-02-16 2009-08-11 Cordis Corporation Balloon catheter stent delivery system with ridges
US6780424B2 (en) * 2001-03-30 2004-08-24 Charles David Claude Controlled morphologies in polymer drug for release of drugs from polymer films
US6712845B2 (en) 2001-04-24 2004-03-30 Advanced Cardiovascular Systems, Inc. Coating for a stent and a method of forming the same
US8182527B2 (en) 2001-05-07 2012-05-22 Cordis Corporation Heparin barrier coating for controlled drug release
US7244853B2 (en) 2001-05-09 2007-07-17 President And Fellows Of Harvard College Dioxanes and uses thereof
US6656506B1 (en) * 2001-05-09 2003-12-02 Advanced Cardiovascular Systems, Inc. Microparticle coated medical device
US20030166197A1 (en) * 2001-05-10 2003-09-04 Ecker Joseph R. Ethylene insensitive plants
US6685745B2 (en) * 2001-05-15 2004-02-03 Scimed Life Systems, Inc. Delivering an agent to a patient's body
US7247338B2 (en) * 2001-05-16 2007-07-24 Regents Of The University Of Minnesota Coating medical devices
US6743462B1 (en) 2001-05-31 2004-06-01 Advanced Cardiovascular Systems, Inc. Apparatus and method for coating implantable devices
US7175873B1 (en) 2001-06-27 2007-02-13 Advanced Cardiovascular Systems, Inc. Rate limiting barriers for implantable devices and methods for fabrication thereof
US6695920B1 (en) 2001-06-27 2004-02-24 Advanced Cardiovascular Systems, Inc. Mandrel for supporting a stent and a method of using the mandrel to coat a stent
US7247313B2 (en) * 2001-06-27 2007-07-24 Advanced Cardiovascular Systems, Inc. Polyacrylates coatings for implantable medical devices
US8741378B1 (en) 2001-06-27 2014-06-03 Advanced Cardiovascular Systems, Inc. Methods of coating an implantable device
US6565659B1 (en) * 2001-06-28 2003-05-20 Advanced Cardiovascular Systems, Inc. Stent mounting assembly and a method of using the same to coat a stent
EP1273314A1 (en) * 2001-07-06 2003-01-08 Terumo Kabushiki Kaisha Stent
US7246321B2 (en) * 2001-07-13 2007-07-17 Anoto Ab Editing data
US7682669B1 (en) 2001-07-30 2010-03-23 Advanced Cardiovascular Systems, Inc. Methods for covalently immobilizing anti-thrombogenic material into a coating on a medical device
US7842083B2 (en) 2001-08-20 2010-11-30 Innovational Holdings, Llc. Expandable medical device with improved spatial distribution
US6692507B2 (en) * 2001-08-23 2004-02-17 Scimed Life Systems, Inc. Impermanent biocompatible fastener
US8303651B1 (en) 2001-09-07 2012-11-06 Advanced Cardiovascular Systems, Inc. Polymeric coating for reducing the rate of release of a therapeutic substance from a stent
US20080145402A1 (en) * 2001-09-10 2008-06-19 Abbott Cardiovascular Systems Inc. Medical Devices Containing Rapamycin Analogs
US7989018B2 (en) 2001-09-17 2011-08-02 Advanced Cardiovascular Systems, Inc. Fluid treatment of a polymeric coating on an implantable medical device
US7285304B1 (en) * 2003-06-25 2007-10-23 Advanced Cardiovascular Systems, Inc. Fluid treatment of a polymeric coating on an implantable medical device
US6669980B2 (en) * 2001-09-18 2003-12-30 Scimed Life Systems, Inc. Method for spray-coating medical devices
US6863683B2 (en) 2001-09-19 2005-03-08 Abbott Laboratoris Vascular Entities Limited Cold-molding process for loading a stent onto a stent delivery system
US6908622B2 (en) * 2001-09-24 2005-06-21 Boston Scientific Scimed, Inc. Optimized dosing for drug coated stents
US6753071B1 (en) 2001-09-27 2004-06-22 Advanced Cardiovascular Systems, Inc. Rate-reducing membrane for release of an agent
US7223282B1 (en) * 2001-09-27 2007-05-29 Advanced Cardiovascular Systems, Inc. Remote activation of an implantable device
US20030065377A1 (en) 2001-09-28 2003-04-03 Davila Luis A. Coated medical devices
DE10150995A1 (en) * 2001-10-08 2003-04-10 Biotronik Mess & Therapieg Implant e.g. a stent, comprises a decomposable substance which allows contact between the cell proliferation inhibitor and the stent surroundings only after a specified time
US20030077310A1 (en) 2001-10-22 2003-04-24 Chandrashekhar Pathak Stent coatings containing HMG-CoA reductase inhibitors
US8740973B2 (en) * 2001-10-26 2014-06-03 Icon Medical Corp. Polymer biodegradable medical device
US7682387B2 (en) 2002-04-24 2010-03-23 Biosensors International Group, Ltd. Drug-delivery endovascular stent and method for treating restenosis
US20030088307A1 (en) * 2001-11-05 2003-05-08 Shulze John E. Potent coatings for stents
US6939376B2 (en) 2001-11-05 2005-09-06 Sun Biomedical, Ltd. Drug-delivery endovascular stent and method for treating restenosis
US7585516B2 (en) 2001-11-12 2009-09-08 Advanced Cardiovascular Systems, Inc. Coatings for drug delivery devices
US20030216758A1 (en) * 2001-12-28 2003-11-20 Angiotech Pharmaceuticals, Inc. Coated surgical patches
US6709514B1 (en) * 2001-12-28 2004-03-23 Advanced Cardiovascular Systems, Inc. Rotary coating apparatus for coating implantable medical devices
US7105198B2 (en) * 2002-01-14 2006-09-12 Medtronic Vascular, Inc. Method for coating stent
TW200306819A (en) 2002-01-25 2003-12-01 Vertex Pharma Indazole compounds useful as protein kinase inhibitors
US7445629B2 (en) * 2002-01-31 2008-11-04 Boston Scientific Scimed, Inc. Medical device for delivering biologically active material
US7291165B2 (en) * 2002-01-31 2007-11-06 Boston Scientific Scimed, Inc. Medical device for delivering biologically active material
US7326245B2 (en) * 2002-01-31 2008-02-05 Boston Scientific Scimed, Inc. Medical device for delivering biologically active material
US20030153972A1 (en) * 2002-02-14 2003-08-14 Michael Helmus Biodegradable implantable or insertable medical devices with controlled change of physical properties leading to biomechanical compatibility
EP1485380B1 (en) 2002-03-15 2010-05-19 Vertex Pharmaceuticals Incorporated Azolylaminoazines as inhibitors of protein kinases
US7022334B1 (en) * 2002-03-20 2006-04-04 Advanced Cardiovascular Systems, Inc. Therapeutic composition and a method of coating implantable medical devices
US7919075B1 (en) 2002-03-20 2011-04-05 Advanced Cardiovascular Systems, Inc. Coatings for implantable medical devices
US7261734B2 (en) * 2002-04-23 2007-08-28 Boston Scientific Scimed, Inc. Resorption-controllable medical implants
US20040024450A1 (en) * 2002-04-24 2004-02-05 Sun Biomedical, Ltd. Drug-delivery endovascular stent and method for treating restenosis
US7083822B2 (en) * 2002-04-26 2006-08-01 Medtronic Vascular, Inc. Overlapping coated stents
US20030204168A1 (en) * 2002-04-30 2003-10-30 Gjalt Bosma Coated vascular devices
WO2004058753A1 (en) 2002-05-06 2004-07-15 Vertex Pharmaceuticals Incorporated Thiadiazoles or oxadiazoles and their use as inhibitors of jak protein kinase
US7097850B2 (en) * 2002-06-18 2006-08-29 Surmodics, Inc. Bioactive agent release coating and controlled humidity method
US8211455B2 (en) * 2002-06-19 2012-07-03 Boston Scientific Scimed, Inc. Implantable or insertable medical devices for controlled delivery of a therapeutic agent
US7105175B2 (en) * 2002-06-19 2006-09-12 Boston Scientific Scimed, Inc. Implantable or insertable medical devices for controlled delivery of a therapeutic agent
US7939094B2 (en) * 2002-06-19 2011-05-10 Boston Scientific Scimed, Inc. Multiphase polymeric drug release region
US20030236513A1 (en) * 2002-06-19 2003-12-25 Scimed Life Systems, Inc. Implantable or insertable medical devices for controlled delivery of a therapeutic agent
US8506617B1 (en) 2002-06-21 2013-08-13 Advanced Cardiovascular Systems, Inc. Micronized peptide coated stent
AU2003279253A1 (en) * 2002-06-21 2004-01-06 Genzyme Corporation Silicone blends and composites for drug delivery
US7217426B1 (en) 2002-06-21 2007-05-15 Advanced Cardiovascular Systems, Inc. Coatings containing polycationic peptides for cardiovascular therapy
US7033602B1 (en) 2002-06-21 2006-04-25 Advanced Cardiovascular Systems, Inc. Polycationic peptide coatings and methods of coating implantable medical devices
US7056523B1 (en) 2002-06-21 2006-06-06 Advanced Cardiovascular Systems, Inc. Implantable medical devices incorporating chemically conjugated polymers and oligomers of L-arginine
US7794743B2 (en) 2002-06-21 2010-09-14 Advanced Cardiovascular Systems, Inc. Polycationic peptide coatings and methods of making the same
US7622146B2 (en) * 2002-07-18 2009-11-24 Advanced Cardiovascular Systems, Inc. Rate limiting barriers for implantable devices and methods for fabrication thereof
US7294329B1 (en) * 2002-07-18 2007-11-13 Advanced Cardiovascular Systems, Inc. Poly(vinyl acetal) coatings for implantable medical devices
US20050214343A1 (en) * 2002-07-18 2005-09-29 Patrice Tremble Medical devices comprising a protein-tyrosine kinase inhibitor to inhibit restonosis
US8016881B2 (en) 2002-07-31 2011-09-13 Icon Interventional Systems, Inc. Sutures and surgical staples for anastamoses, wound closures, and surgical closures
US20050163821A1 (en) * 2002-08-02 2005-07-28 Hsing-Wen Sung Drug-eluting Biodegradable Stent and Delivery Means
US20040024448A1 (en) 2002-08-05 2004-02-05 Chang James W. Thermoplastic fluoropolymer-coated medical devices
US8227411B2 (en) 2002-08-20 2012-07-24 BioSurface Engineering Technologies, Incle FGF growth factor analogs
US7166574B2 (en) * 2002-08-20 2007-01-23 Biosurface Engineering Technologies, Inc. Synthetic heparin-binding growth factor analogs
US7363074B1 (en) * 2002-08-20 2008-04-22 Advanced Cardiovascular Systems, Inc. Coatings comprising self-assembled molecular structures and a method of delivering a drug using the same
US7598224B2 (en) 2002-08-20 2009-10-06 Biosurface Engineering Technologies, Inc. Dual chain synthetic heparin-binding growth factor analogs
US7438925B2 (en) * 2002-08-26 2008-10-21 Biovention Holdings Ltd. Drug eluting coatings for medical implants
US20040054104A1 (en) * 2002-09-05 2004-03-18 Pacetti Stephen D. Coatings for drug delivery devices comprising modified poly(ethylene-co-vinyl alcohol)
US7732535B2 (en) * 2002-09-05 2010-06-08 Advanced Cardiovascular Systems, Inc. Coating for controlled release of drugs from implantable medical devices
AU2003218077B2 (en) * 2002-09-06 2009-10-08 Abbott Laboratories Medical device having hydration inhibitor
US7201935B1 (en) 2002-09-17 2007-04-10 Advanced Cardiovascular Systems, Inc. Plasma-generated coatings for medical devices and methods for fabricating thereof
US7438722B1 (en) 2002-09-20 2008-10-21 Advanced Cardiovascular Systems, Inc. Method for treatment of restenosis
US20040059409A1 (en) * 2002-09-24 2004-03-25 Stenzel Eric B. Method of applying coatings to a medical device
US7232573B1 (en) 2002-09-26 2007-06-19 Advanced Cardiovascular Systems, Inc. Stent coatings containing self-assembled monolayers
US8202530B2 (en) * 2002-09-27 2012-06-19 Advanced Cardiovascular Systems, Inc. Biocompatible coatings for stents
US8337937B2 (en) * 2002-09-30 2012-12-25 Abbott Cardiovascular Systems Inc. Stent spin coating method
US7404979B1 (en) * 2002-09-30 2008-07-29 Advanced Cardiovascular Systems Inc. Spin coating apparatus and a method for coating implantable devices
US7087263B2 (en) * 2002-10-09 2006-08-08 Advanced Cardiovascular Systems, Inc. Rare limiting barriers for implantable medical devices
US7794494B2 (en) 2002-10-11 2010-09-14 Boston Scientific Scimed, Inc. Implantable medical devices
US7976936B2 (en) * 2002-10-11 2011-07-12 University Of Connecticut Endoprostheses
CA2503492A1 (en) * 2002-10-25 2004-05-06 Essentia Biosystems, Inc. Implantable medical devices using zinc
US20060271168A1 (en) * 2002-10-30 2006-11-30 Klaus Kleine Degradable medical device
WO2004041789A1 (en) 2002-11-01 2004-05-21 Vertex Pharmaceuticals Incorporated Compositions useful as inhibitors of jak and other protein kinases
AU2003290675A1 (en) * 2002-11-07 2004-06-03 Abbott Laboratories Method of loading beneficial agent to a prosthesis by fluid-jet application
US20040148016A1 (en) * 2002-11-07 2004-07-29 Klein Dean A. Biocompatible medical device coatings
EP1567087B1 (en) 2002-11-08 2009-04-01 Jacques Seguin Endoprosthesis for vascular bifurcation
US7022372B1 (en) 2002-11-12 2006-04-04 Advanced Cardiovascular Systems, Inc. Compositions for coating implantable medical devices
US6896965B1 (en) 2002-11-12 2005-05-24 Advanced Cardiovascular Systems, Inc. Rate limiting barriers for implantable devices
US8034361B2 (en) * 2002-11-12 2011-10-11 Advanced Cardiovascular Systems, Inc. Stent coatings incorporating nanoparticles
US6982004B1 (en) * 2002-11-26 2006-01-03 Advanced Cardiovascular Systems, Inc. Electrostatic loading of drugs on implantable medical devices
US7491234B2 (en) 2002-12-03 2009-02-17 Boston Scientific Scimed, Inc. Medical devices for delivery of therapeutic agents
US20040111144A1 (en) * 2002-12-06 2004-06-10 Lawin Laurie R. Barriers for polymeric coatings
US7211150B1 (en) * 2002-12-09 2007-05-01 Advanced Cardiovascular Systems, Inc. Apparatus and method for coating and drying multiple stents
US7468210B1 (en) 2002-12-10 2008-12-23 Biosurface Engineering Technologies, Inc. Cross-linked heparin coatings and methods
US7758880B2 (en) * 2002-12-11 2010-07-20 Advanced Cardiovascular Systems, Inc. Biocompatible polyacrylate compositions for medical applications
US7776926B1 (en) 2002-12-11 2010-08-17 Advanced Cardiovascular Systems, Inc. Biocompatible coating for implantable medical devices
US7074276B1 (en) 2002-12-12 2006-07-11 Advanced Cardiovascular Systems, Inc. Clamp mandrel fixture and a method of using the same to minimize coating defects
US7758881B2 (en) 2004-06-30 2010-07-20 Advanced Cardiovascular Systems, Inc. Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders with an implantable medical device
US8435550B2 (en) 2002-12-16 2013-05-07 Abbot Cardiovascular Systems Inc. Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders with an implantable medical device
US20060002968A1 (en) 2004-06-30 2006-01-05 Gordon Stewart Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders
AU2003297534A1 (en) * 2002-12-24 2004-07-22 Ovion, Inc. Contraceptive device and delivery system
US7311727B2 (en) * 2003-02-05 2007-12-25 Board Of Trustees Of The University Of Arkansas Encased stent
US20040167572A1 (en) * 2003-02-20 2004-08-26 Roth Noah M. Coated medical devices
ATE485847T1 (en) * 2003-02-21 2010-11-15 Sorin Biomedica Cardio Srl METHOD FOR PRODUCING A STENT AND CORRESPONDING STENT
US7255891B1 (en) 2003-02-26 2007-08-14 Advanced Cardiovascular Systems, Inc. Method for coating implantable medical devices
US7563483B2 (en) * 2003-02-26 2009-07-21 Advanced Cardiovascular Systems Inc. Methods for fabricating a coating for implantable medical devices
US6926919B1 (en) 2003-02-26 2005-08-09 Advanced Cardiovascular Systems, Inc. Method for fabricating a coating for a medical device
US8715771B2 (en) * 2003-02-26 2014-05-06 Abbott Cardiovascular Systems Inc. Coated stent and method of making the same
US7288609B1 (en) * 2003-03-04 2007-10-30 Advanced Cardiovascular Systems, Inc. Coatings for drug delivery devices based on poly (orthoesters)
US8313759B2 (en) * 2003-03-06 2012-11-20 Boston Scientific Scimed, Inc. Implantable or insertable medical devices containing miscible polymer blends for controlled delivery of a therapeutic agent
US7527632B2 (en) * 2003-03-31 2009-05-05 Cordis Corporation Modified delivery device for coated medical devices
US7241455B2 (en) * 2003-04-08 2007-07-10 Boston Scientific Scimed, Inc. Implantable or insertable medical devices containing radiation-crosslinked polymer for controlled delivery of a therapeutic agent
US20040215315A1 (en) * 2003-04-25 2004-10-28 Jones Ryan A. Drug-eluting stent with sheath and balloon deployment assembly
US20080215137A1 (en) * 2003-04-30 2008-09-04 Boston Scientific Scimed, Inc. Therapeutic driving layer for a medical device
US20040220656A1 (en) * 2003-04-30 2004-11-04 Epstein Samuel J. Coated medical devices and methods of making the same
US8791171B2 (en) 2003-05-01 2014-07-29 Abbott Cardiovascular Systems Inc. Biodegradable coatings for implantable medical devices
US7563454B1 (en) * 2003-05-01 2009-07-21 Advanced Cardiovascular Systems, Inc. Coatings for implantable medical devices
US8246974B2 (en) 2003-05-02 2012-08-21 Surmodics, Inc. Medical devices and methods for producing the same
AU2004237774B2 (en) 2003-05-02 2009-09-10 Surmodics, Inc. Implantable controlled release bioactive agent delivery device
US7279174B2 (en) 2003-05-08 2007-10-09 Advanced Cardiovascular Systems, Inc. Stent coatings comprising hydrophilic additives
BRPI0410324A (en) * 2003-05-15 2006-05-23 Biomerix Corp implantable device, elastomeric matrix production lyophilization processes having a cross-linked structure, polymerization for cross-linked elastomeric matrix preparation and cross-linked composite elastomeric implant preparation, and method for treating an orthopedic disorder
US7323209B1 (en) 2003-05-15 2008-01-29 Advanced Cardiovascular Systems, Inc. Apparatus and method for coating stents
AU2004238026A1 (en) * 2003-05-16 2004-11-25 Cinvention Ag Medical implants comprising biocompatible coatings
US20040236416A1 (en) * 2003-05-20 2004-11-25 Robert Falotico Increased biocompatibility of implantable medical devices
EP2243781A1 (en) 2003-05-30 2010-10-27 Vertex Pharmaceuticals, Inc. Pyrazolopyridine derivatives as inhibitors of JAK and CDK2 protein kinases
JP4971580B2 (en) * 2003-06-05 2012-07-11 テルモ株式会社 Stent and method for manufacturing stent
US7905902B2 (en) * 2003-06-16 2011-03-15 Ethicon Endo-Surgery, Inc. Surgical implant with preferential corrosion zone
US7465738B2 (en) 2003-06-16 2008-12-16 Vertex Pharmaceuticals Incorporated Compounds useful as promoters of SMN2
US20050118344A1 (en) 2003-12-01 2005-06-02 Pacetti Stephen D. Temperature controlled crimping
US7645504B1 (en) 2003-06-26 2010-01-12 Advanced Cardiovascular Systems, Inc. Coatings for implantable medical devices comprising hydrophobic and hydrophilic polymers
BRPI0411924A8 (en) * 2003-06-27 2017-03-07 Ams Res Corp METHODS AND DEVICES FOR OCCLUSION OF BODY LUMEN AND/OR FOR DELIVERY OF THERAPEUTIC AGENTS
US7875285B1 (en) 2003-07-15 2011-01-25 Advanced Cardiovascular Systems, Inc. Medicated coatings for implantable medical devices having controlled rate of release
EP1648548B1 (en) * 2003-07-18 2008-06-11 Boston Scientific Limited Medical devices
US7169404B2 (en) * 2003-07-30 2007-01-30 Advanced Cardiovasular Systems, Inc. Biologically absorbable coatings for implantable devices and methods for fabricating the same
US7056591B1 (en) * 2003-07-30 2006-06-06 Advanced Cardiovascular Systems, Inc. Hydrophobic biologically absorbable coatings for drug delivery devices and methods for fabricating the same
US20050033417A1 (en) * 2003-07-31 2005-02-10 John Borges Coating for controlled release of a therapeutic agent
US7914805B2 (en) * 2003-07-31 2011-03-29 Boston Scientific Scimed, Inc. Implantable or insertable medical devices containing radiation-treated polymer for improved delivery of therapeutic agent
US7431959B1 (en) * 2003-07-31 2008-10-07 Advanced Cardiovascular Systems Inc. Method and system for irradiation of a drug eluting implantable medical device
US8870814B2 (en) * 2003-07-31 2014-10-28 Boston Scientific Scimed, Inc. Implantable or insertable medical devices containing silicone copolymer for controlled delivery of therapeutic agent
US9114199B2 (en) * 2003-07-31 2015-08-25 Boston Scientific Scimed, Inc. Implantable or insertable medical devices containing acrylic copolymer for controlled delivery of therapeutic agent
US7357940B2 (en) * 2003-07-31 2008-04-15 Boston Scientific Scimed, Inc. Implantable or insertable medical devices containing graft copolymer for controlled delivery of therapeutic agents
US7785512B1 (en) 2003-07-31 2010-08-31 Advanced Cardiovascular Systems, Inc. Method and system of controlled temperature mixing and molding of polymers with active agents for implantable medical devices
US7645474B1 (en) 2003-07-31 2010-01-12 Advanced Cardiovascular Systems, Inc. Method and system of purifying polymers for use with implantable medical devices
EP1673357A2 (en) 2003-08-08 2006-06-28 Vertex Pharmaceuticals Incorporated Heteroarylaminosulfonylphenyl derivatives for use as sodium or calcium channel blockers in the treatment of pain
CA2536253A1 (en) 2003-08-20 2005-03-03 Vertex Pharmaceuticals Incorporated Aminofurazan compounds useful as protein kinase inhibitors
US7441513B1 (en) 2003-09-26 2008-10-28 Advanced Cardiovascular Systems, Inc. Plasma-generated coating apparatus for medical devices and a method of coating deposition
US7198675B2 (en) 2003-09-30 2007-04-03 Advanced Cardiovascular Systems Stent mandrel fixture and method for selectively coating surfaces of a stent
US7318932B2 (en) * 2003-09-30 2008-01-15 Advanced Cardiovascular Systems, Inc. Coatings for drug delivery devices comprising hydrolitically stable adducts of poly(ethylene-co-vinyl alcohol) and methods for fabricating the same
WO2005039564A1 (en) * 2003-10-02 2005-05-06 Vertex Pharmaceuticals Incorporated Phthalimide compounds useful as protein kinase inhibitors
US7704544B2 (en) * 2003-10-07 2010-04-27 Advanced Cardiovascular Systems, Inc. System and method for coating a tubular implantable medical device
CN1897950A (en) * 2003-10-14 2007-01-17 惠氏公司 Fused-aryl and heteroaryl derivatives and methods of their use
US6984411B2 (en) * 2003-10-14 2006-01-10 Boston Scientific Scimed, Inc. Method for roll coating multiple stents
US7329413B1 (en) * 2003-11-06 2008-02-12 Advanced Cardiovascular Systems, Inc. Coatings for drug delivery devices having gradient of hydration and methods for fabricating thereof
EP2140865A1 (en) 2003-11-14 2010-01-06 Vertex Pharmaceuticals Incorporated Thiazoles and oxazoles useful as modulators of atp-binding cassette transporters
US7261946B2 (en) * 2003-11-14 2007-08-28 Advanced Cardiovascular Systems, Inc. Block copolymers of acrylates and methacrylates with fluoroalkenes
US9114198B2 (en) 2003-11-19 2015-08-25 Advanced Cardiovascular Systems, Inc. Biologically beneficial coatings for implantable devices containing fluorinated polymers and methods for fabricating the same
US8192752B2 (en) 2003-11-21 2012-06-05 Advanced Cardiovascular Systems, Inc. Coatings for implantable devices including biologically erodable polyesters and methods for fabricating the same
US7560492B1 (en) * 2003-11-25 2009-07-14 Advanced Cardiovascular Systems, Inc. Polysulfone block copolymers as drug-eluting coating material
US7807722B2 (en) 2003-11-26 2010-10-05 Advanced Cardiovascular Systems, Inc. Biobeneficial coating compositions and methods of making and using thereof
US20050137677A1 (en) * 2003-12-17 2005-06-23 Rush Scott L. Endovascular graft with differentiable porosity along its length
US8747881B2 (en) 2003-12-19 2014-06-10 Cordis Corporation Intraluminal medical devices in combination with therapeutic agents
US8652502B2 (en) * 2003-12-19 2014-02-18 Cordis Corporation Local vascular delivery of trichostatin A alone or in combination with sirolimus to prevent restenosis following vascular injury
US20050249776A1 (en) * 2003-12-19 2005-11-10 Chen Chao C Coated aneurysmal repair device
US7435788B2 (en) 2003-12-19 2008-10-14 Advanced Cardiovascular Systems, Inc. Biobeneficial polyamide/polyethylene glycol polymers for use with drug eluting stents
US7763077B2 (en) 2003-12-24 2010-07-27 Biomerix Corporation Repair of spinal annular defects and annulo-nucleoplasty regeneration
US8309112B2 (en) * 2003-12-24 2012-11-13 Advanced Cardiovascular Systems, Inc. Coatings for implantable medical devices comprising hydrophilic substances and methods for fabricating the same
US7303758B2 (en) 2004-01-20 2007-12-04 Cordis Corporation Local vascular delivery of mycophenolic acid in combination with rapamycin to prevent restenosis following vascular injury
US20050165480A1 (en) * 2004-01-23 2005-07-28 Maybelle Jordan Endovascular treatment devices and methods
MXPA06008606A (en) 2004-01-30 2007-04-13 Vertex Pharma Modulators of atp-binding cassette transporters.
US20080227696A1 (en) * 2005-02-22 2008-09-18 Biosurface Engineering Technologies, Inc. Single branch heparin-binding growth factor analogs
US7806924B2 (en) * 2004-02-18 2010-10-05 Cordis Corporation Implantable structures for local vascular delivery of cladribine in combination with rapamycin for restenosis
JP4895826B2 (en) * 2004-02-20 2012-03-14 バイオサーフェス エンジニアリング テクノロジーズ,インク. Bone morphogenetic protein-2 positive modulator
US20050187608A1 (en) * 2004-02-24 2005-08-25 O'hara Michael D. Radioprotective compound coating for medical devices
US8828416B2 (en) 2004-03-09 2014-09-09 Cordis Corporation Local vascular delivery of topotecan in combination with rapamycin to prevent restenosis following vascular injury
US8685431B2 (en) 2004-03-16 2014-04-01 Advanced Cardiovascular Systems, Inc. Biologically absorbable coatings for implantable devices based on copolymers having ester bonds and methods for fabricating the same
WO2005089855A1 (en) * 2004-03-19 2005-09-29 Abbott Laboratories Multiple drug delivery from a balloon and a prosthesis
US20100030183A1 (en) * 2004-03-19 2010-02-04 Toner John L Method of treating vascular disease at a bifurcated vessel using a coated balloon
US8431145B2 (en) * 2004-03-19 2013-04-30 Abbott Laboratories Multiple drug delivery from a balloon and a prosthesis
US20070027523A1 (en) * 2004-03-19 2007-02-01 Toner John L Method of treating vascular disease at a bifurcated vessel using coated balloon
US7695731B2 (en) 2004-03-22 2010-04-13 Cordis Corporation Local vascular delivery of etoposide in combination with rapamycin to prevent restenosis following vascular injury
US20050208093A1 (en) 2004-03-22 2005-09-22 Thierry Glauser Phosphoryl choline coating compositions
US8551512B2 (en) 2004-03-22 2013-10-08 Advanced Cardiovascular Systems, Inc. Polyethylene glycol/poly(butylene terephthalate) copolymer coated devices including EVEROLIMUS
US7875282B2 (en) * 2004-03-22 2011-01-25 Cordis Corporation Coated medical device for local vascular delivery of Panzem® in combination with rapamycin to prevent restenosis following vascular injury
CA2560507C (en) 2004-03-26 2011-08-16 Surmodics, Inc. Composition and method for preparing biocompatible surfaces
US7550443B2 (en) 2004-03-26 2009-06-23 Surmodics, Inc. Process and systems for biocompatible surfaces
US20050214339A1 (en) 2004-03-29 2005-09-29 Yiwen Tang Biologically degradable compositions for medical applications
US7989490B2 (en) * 2004-06-02 2011-08-02 Cordis Corporation Injectable formulations of taxanes for cad treatment
US8778014B1 (en) 2004-03-31 2014-07-15 Advanced Cardiovascular Systems, Inc. Coatings for preventing balloon damage to polymer coated stents
US8003122B2 (en) * 2004-03-31 2011-08-23 Cordis Corporation Device for local and/or regional delivery employing liquid formulations of therapeutic agents
US7846940B2 (en) * 2004-03-31 2010-12-07 Cordis Corporation Solution formulations of sirolimus and its analogs for CAD treatment
US8007737B2 (en) 2004-04-14 2011-08-30 Wyeth Use of antioxidants to prevent oxidation and reduce drug degradation in drug eluting medical devices
US20050232965A1 (en) * 2004-04-15 2005-10-20 Robert Falotico Local administration of a combination of rapamycin and 17 beta-estradiol for the treatment of vulnerable plaque
US7531556B2 (en) 2004-04-28 2009-05-12 Vertex Pharmaceuticals Incorporated Compositions useful as inhibitors of rock and other protein kinases
US20050288481A1 (en) * 2004-04-30 2005-12-29 Desnoyer Jessica R Design of poly(ester amides) for the control of agent-release from polymeric compositions
US7820732B2 (en) 2004-04-30 2010-10-26 Advanced Cardiovascular Systems, Inc. Methods for modulating thermal and mechanical properties of coatings on implantable devices
US8293890B2 (en) 2004-04-30 2012-10-23 Advanced Cardiovascular Systems, Inc. Hyaluronic acid based copolymers
SI3305776T1 (en) 2004-05-14 2020-01-31 Vertex Pharmaceuticals Incorporated Pyrrole compounds as inhibitors of erk protein kinases and pharmaceutical compositions containing these compounds
US20050255230A1 (en) * 2004-05-17 2005-11-17 Clerc Claude O Method of manufacturing a covered stent
US9561309B2 (en) 2004-05-27 2017-02-07 Advanced Cardiovascular Systems, Inc. Antifouling heparin coatings
US20050266039A1 (en) * 2004-05-27 2005-12-01 Jan Weber Coated medical device and method for making the same
US20060251795A1 (en) * 2005-05-05 2006-11-09 Boris Kobrin Controlled vapor deposition of biocompatible coatings for medical devices
US7563780B1 (en) 2004-06-18 2009-07-21 Advanced Cardiovascular Systems, Inc. Heparin prodrugs and drug delivery stents formed therefrom
WO2006002112A1 (en) * 2004-06-18 2006-01-05 Surmodics, Inc. Devices, articles, coatings, and methods for controlled active agent release
WO2006010008A1 (en) 2004-06-22 2006-01-26 Vertex Pharmaceuticals Incorporated Heterocyclic derivatives for modulation of calcium channels
EP2502912A3 (en) 2004-06-24 2013-11-06 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
RS56037B1 (en) 2004-06-24 2017-09-29 Vertex Pharma Modulators of atp-binding cassette transporters
US8354427B2 (en) 2004-06-24 2013-01-15 Vertex Pharmaceutical Incorporated Modulators of ATP-binding cassette transporters
US8568469B1 (en) 2004-06-28 2013-10-29 Advanced Cardiovascular Systems, Inc. Stent locking element and a method of securing a stent on a delivery system
US20050287184A1 (en) 2004-06-29 2005-12-29 Hossainy Syed F A Drug-delivery stent formulations for restenosis and vulnerable plaque
US8241554B1 (en) 2004-06-29 2012-08-14 Advanced Cardiovascular Systems, Inc. Method of forming a stent pattern on a tube
CA2572058A1 (en) 2004-06-30 2006-01-12 Vertex Pharmaceuticals Incorporated Azaindoles useful as inhibitors of protein kinases
US7820936B2 (en) 2004-07-02 2010-10-26 Boston Scientific Scimed, Inc. Method and apparatus for controlling and adjusting the intensity profile of a laser beam employed in a laser welder for welding polymeric and metallic components
US7731890B2 (en) 2006-06-15 2010-06-08 Advanced Cardiovascular Systems, Inc. Methods of fabricating stents with enhanced fracture toughness
US8747878B2 (en) 2006-04-28 2014-06-10 Advanced Cardiovascular Systems, Inc. Method of fabricating an implantable medical device by controlling crystalline structure
US8778256B1 (en) 2004-09-30 2014-07-15 Advanced Cardiovascular Systems, Inc. Deformation of a polymer tube in the fabrication of a medical article
US20060020330A1 (en) * 2004-07-26 2006-01-26 Bin Huang Method of fabricating an implantable medical device with biaxially oriented polymers
US8747879B2 (en) 2006-04-28 2014-06-10 Advanced Cardiovascular Systems, Inc. Method of fabricating an implantable medical device to reduce chance of late inflammatory response
US7971333B2 (en) 2006-05-30 2011-07-05 Advanced Cardiovascular Systems, Inc. Manufacturing process for polymetric stents
US20060025848A1 (en) * 2004-07-29 2006-02-02 Jan Weber Medical device having a coating layer with structural elements therein and method of making the same
US8357391B2 (en) 2004-07-30 2013-01-22 Advanced Cardiovascular Systems, Inc. Coatings for implantable devices comprising poly (hydroxy-alkanoates) and diacid linkages
US7494665B1 (en) 2004-07-30 2009-02-24 Advanced Cardiovascular Systems, Inc. Polymers containing siloxane monomers
US20060041102A1 (en) * 2004-08-23 2006-02-23 Advanced Cardiovascular Systems, Inc. Implantable devices comprising biologically absorbable polymers having constant rate of degradation and methods for fabricating the same
US9283099B2 (en) 2004-08-25 2016-03-15 Advanced Cardiovascular Systems, Inc. Stent-catheter assembly with a releasable connection for stent retention
US7648727B2 (en) 2004-08-26 2010-01-19 Advanced Cardiovascular Systems, Inc. Methods for manufacturing a coated stent-balloon assembly
US7244443B2 (en) 2004-08-31 2007-07-17 Advanced Cardiovascular Systems, Inc. Polymers of fluorinated monomers and hydrophilic monomers
US20060051390A1 (en) * 2004-09-03 2006-03-09 Schwarz Marlene C Medical devices having self-forming rate-controlling barrier for drug release
US7229471B2 (en) 2004-09-10 2007-06-12 Advanced Cardiovascular Systems, Inc. Compositions containing fast-leaching plasticizers for improved performance of medical devices
US8110211B2 (en) 2004-09-22 2012-02-07 Advanced Cardiovascular Systems, Inc. Medicated coatings for implantable medical devices including polyacrylates
US7901451B2 (en) * 2004-09-24 2011-03-08 Biosensors International Group, Ltd. Drug-delivery endovascular stent and method for treating restenosis
US8173062B1 (en) 2004-09-30 2012-05-08 Advanced Cardiovascular Systems, Inc. Controlled deformation of a polymer tube in fabricating a medical article
US7875233B2 (en) 2004-09-30 2011-01-25 Advanced Cardiovascular Systems, Inc. Method of fabricating a biaxially oriented implantable medical device
US8043553B1 (en) 2004-09-30 2011-10-25 Advanced Cardiovascular Systems, Inc. Controlled deformation of a polymer tube with a restraining surface in fabricating a medical article
US8603634B2 (en) 2004-10-27 2013-12-10 Abbott Cardiovascular Systems Inc. End-capped poly(ester amide) copolymers
US7390497B2 (en) 2004-10-29 2008-06-24 Advanced Cardiovascular Systems, Inc. Poly(ester amide) filler blends for modulation of coating properties
ES2478283T3 (en) 2004-11-10 2014-07-21 Boston Scientific Scimed, Inc. Atraumatic vascular endoprosthesis with reduced deployment force
US8609123B2 (en) 2004-11-29 2013-12-17 Advanced Cardiovascular Systems, Inc. Derivatized poly(ester amide) as a biobeneficial coating
US7588642B1 (en) 2004-11-29 2009-09-15 Advanced Cardiovascular Systems, Inc. Abluminal stent coating apparatus and method using a brush assembly
US7892592B1 (en) 2004-11-30 2011-02-22 Advanced Cardiovascular Systems, Inc. Coating abluminal surfaces of stents and other implantable medical devices
US20060127443A1 (en) * 2004-12-09 2006-06-15 Helmus Michael N Medical devices having vapor deposited nanoporous coatings for controlled therapeutic agent delivery
EP1828186A1 (en) 2004-12-13 2007-09-05 Sunesis Pharmaceuticals, Inc. Pyrido pyrimidinones, dihydro pyrimido pyrimidinones and pteridinones useful as raf kinase inhibitors
US20060129225A1 (en) * 2004-12-15 2006-06-15 Kopia Gregory A Device for the delivery of a cardioprotective agent to ischemic reperfused myocardium
US7632307B2 (en) * 2004-12-16 2009-12-15 Advanced Cardiovascular Systems, Inc. Abluminal, multilayer coating constructs for drug-delivery stents
US7604818B2 (en) 2004-12-22 2009-10-20 Advanced Cardiovascular Systems, Inc. Polymers of fluorinated monomers and hydrocarbon monomers
US7419504B2 (en) 2004-12-27 2008-09-02 Advanced Cardiovascular Systems, Inc. Poly(ester amide) block copolymers
US8007775B2 (en) 2004-12-30 2011-08-30 Advanced Cardiovascular Systems, Inc. Polymers containing poly(hydroxyalkanoates) and agents for use with medical articles and methods of fabricating the same
US20060153889A1 (en) * 2005-01-10 2006-07-13 Friel Francis M Discontinuous surface coating for particles
US20060171980A1 (en) * 2005-02-01 2006-08-03 Helmus Michael N Implantable or insertable medical devices having optimal surface energy
WO2006096251A2 (en) * 2005-03-03 2006-09-14 Icon Medical Corp. Improved metal alloys for medical device
US7540995B2 (en) * 2005-03-03 2009-06-02 Icon Medical Corp. Process for forming an improved metal alloy stent
WO2006110197A2 (en) * 2005-03-03 2006-10-19 Icon Medical Corp. Polymer biodegradable medical device
US20060201601A1 (en) * 2005-03-03 2006-09-14 Icon Interventional Systems, Inc. Flexible markers
US8323333B2 (en) * 2005-03-03 2012-12-04 Icon Medical Corp. Fragile structure protective coating
US9107899B2 (en) 2005-03-03 2015-08-18 Icon Medical Corporation Metal alloys for medical devices
US20060264914A1 (en) * 2005-03-03 2006-11-23 Icon Medical Corp. Metal alloys for medical devices
US20060200048A1 (en) * 2005-03-03 2006-09-07 Icon Medical Corp. Removable sheath for device protection
US20060212106A1 (en) * 2005-03-21 2006-09-21 Jan Weber Coatings for use on medical devices
JP5744376B2 (en) 2005-03-22 2015-07-08 プレジデント アンド フェローズ オブ ハーバード カレッジ Treatment of protein degradation disorders
WO2007032777A2 (en) 2005-03-23 2007-03-22 Abbott Laboratories Compositions and methods of administering rapamycin analogs using medical devices for long-term efficacy
WO2006102359A2 (en) 2005-03-23 2006-09-28 Abbott Laboratories Delivery of highly lipophilic agents via medical devices
US20060216431A1 (en) * 2005-03-28 2006-09-28 Kerrigan Cameron K Electrostatic abluminal coating of a stent crimped on a balloon catheter
US20060224226A1 (en) * 2005-03-31 2006-10-05 Bin Huang In-vivo radial orientation of a polymeric implantable medical device
US7381048B2 (en) 2005-04-12 2008-06-03 Advanced Cardiovascular Systems, Inc. Stents with profiles for gripping a balloon catheter and molds for fabricating stents
US7795467B1 (en) 2005-04-26 2010-09-14 Advanced Cardiovascular Systems, Inc. Bioabsorbable, biobeneficial polyurethanes for use in medical devices
US8778375B2 (en) 2005-04-29 2014-07-15 Advanced Cardiovascular Systems, Inc. Amorphous poly(D,L-lactide) coating
KR20080008364A (en) * 2005-05-05 2008-01-23 헤모텍 아게 All-over coating of vessel stents
US20060257355A1 (en) * 2005-05-10 2006-11-16 Abiomed, Inc. Impregnated polymer compositions and devices using them
CA2607670A1 (en) 2005-05-10 2006-11-16 Vertex Pharmaceuticals Incorporated Bicyclic derivatives as modulators of ion channels
WO2006124744A1 (en) 2005-05-16 2006-11-23 Vertex Pharmaceuticals Incorporated Bicyclic derivatives as modulators of ion channels
US7291166B2 (en) * 2005-05-18 2007-11-06 Advanced Cardiovascular Systems, Inc. Polymeric stent patterns
ATE540948T1 (en) 2005-05-20 2012-01-15 Vertex Pharma PYRROLOPYRIDINES AS PROTEIN KINASE INHIBITORS
US7605174B2 (en) 2005-06-09 2009-10-20 Vertex Pharmaceuticals Incorporated Indane derivatives as modulators of ion channels
US7622070B2 (en) * 2005-06-20 2009-11-24 Advanced Cardiovascular Systems, Inc. Method of manufacturing an implantable polymeric medical device
US7823533B2 (en) 2005-06-30 2010-11-02 Advanced Cardiovascular Systems, Inc. Stent fixture and method for reducing coating defects
US8021676B2 (en) 2005-07-08 2011-09-20 Advanced Cardiovascular Systems, Inc. Functionalized chemically inert polymers for coatings
US7785647B2 (en) 2005-07-25 2010-08-31 Advanced Cardiovascular Systems, Inc. Methods of providing antioxidants to a drug containing product
US7735449B1 (en) 2005-07-28 2010-06-15 Advanced Cardiovascular Systems, Inc. Stent fixture having rounded support structures and method for use thereof
US7658880B2 (en) 2005-07-29 2010-02-09 Advanced Cardiovascular Systems, Inc. Polymeric stent polishing method and apparatus
US20070026042A1 (en) * 2005-07-29 2007-02-01 Narayanan Pallasssana V System for treating aneurysmal disease
KR20080047375A (en) 2005-07-29 2008-05-28 콘서트 파마슈티컬즈, 인크. Novel pharmaceutical compounds
US7297758B2 (en) * 2005-08-02 2007-11-20 Advanced Cardiovascular Systems, Inc. Method for extending shelf-life of constructs of semi-crystallizable polymers
US9101949B2 (en) 2005-08-04 2015-08-11 Eilaz Babaev Ultrasonic atomization and/or seperation system
WO2007019478A2 (en) * 2005-08-08 2007-02-15 Board Of Regents, The University Of Texas System Drug delivery from implants using self-assembled monolayers - therapeutic sams
AU2006279810B2 (en) 2005-08-11 2011-10-27 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
US20070038290A1 (en) * 2005-08-15 2007-02-15 Bin Huang Fiber reinforced composite stents
US7896539B2 (en) 2005-08-16 2011-03-01 Bacoustics, Llc Ultrasound apparatus and methods for mixing liquids and coating stents
US7476245B2 (en) * 2005-08-16 2009-01-13 Advanced Cardiovascular Systems, Inc. Polymeric stent patterns
US20070045255A1 (en) * 2005-08-23 2007-03-01 Klaus Kleine Laser induced plasma machining with an optimized process gas
US9248034B2 (en) 2005-08-23 2016-02-02 Advanced Cardiovascular Systems, Inc. Controlled disintegrating implantable medical devices
US20070045252A1 (en) * 2005-08-23 2007-03-01 Klaus Kleine Laser induced plasma machining with a process gas
US20070048350A1 (en) 2005-08-31 2007-03-01 Robert Falotico Antithrombotic coating for drug eluting medical devices
US20070141040A1 (en) * 2005-09-19 2007-06-21 Chen Leon E Protein kinase C peptide modulators of angiogenesis
ZA200802685B (en) 2005-09-30 2009-10-28 Vertex Pharma Deazapurines useful as inhibitors of janus kinases
US8784860B2 (en) * 2005-10-27 2014-07-22 Cordis Corporation Local administration of a combination of rapamycin and cilostazol for the treatment of vascular disease
US20070173787A1 (en) * 2005-11-01 2007-07-26 Huang Mark C T Thin-film nitinol based drug eluting stent
PT2404919E (en) 2005-11-08 2013-10-22 Vertex Pharma Heterocyclic compound useful as a modulator of atp-binding cassette transporters.
US20070112421A1 (en) * 2005-11-14 2007-05-17 O'brien Barry Medical device with a grooved surface
WO2008079521A2 (en) 2006-11-01 2008-07-03 Vertex Pharmaceuticals Incorporated Tricyclic heteroaryl compounds useful as inhibitors of janus kinase
US20070116736A1 (en) 2005-11-23 2007-05-24 Argentieri Dennis C Local vascular delivery of PI3 kinase inhibitors alone or in combination with sirolimus to prevent restinosis following vascular injury
US20070134288A1 (en) * 2005-12-13 2007-06-14 Edward Parsonage Anti-adhesion agents for drug coatings
US7976891B1 (en) 2005-12-16 2011-07-12 Advanced Cardiovascular Systems, Inc. Abluminal stent coating apparatus and method of using focused acoustic energy
US7867547B2 (en) 2005-12-19 2011-01-11 Advanced Cardiovascular Systems, Inc. Selectively coating luminal surfaces of stents
AU2006331608B2 (en) 2005-12-21 2012-07-05 Vertex Pharmaceuticals Incorporated Heterocyclic derivatives as modulators of ion channels
SI3219705T1 (en) 2005-12-28 2020-08-31 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions of the amorphous form of n-(2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl)-1,4-dihydro-4-oxoquinoline-3-carboxamide
US20070151961A1 (en) * 2006-01-03 2007-07-05 Klaus Kleine Fabrication of an implantable medical device with a modified laser beam
US20070156230A1 (en) * 2006-01-04 2007-07-05 Dugan Stephen R Stents with radiopaque markers
US7951185B1 (en) 2006-01-06 2011-05-31 Advanced Cardiovascular Systems, Inc. Delivery of a stent at an elevated temperature
US20070160743A1 (en) * 2006-01-09 2007-07-12 Babitt John L Method for coating biocompatible material on a substrate
CN102532133A (en) 2006-01-17 2012-07-04 沃泰克斯药物股份有限公司 Azaindoles useful as inhibitors of janus kinases
WO2007089881A2 (en) 2006-01-31 2007-08-09 Regents Of The University Of Minnesota Electrospray coating of objects
US20070179219A1 (en) * 2006-01-31 2007-08-02 Bin Huang Method of fabricating an implantable medical device using gel extrusion and charge induced orientation
JP5367692B2 (en) 2006-02-08 2013-12-11 タイレックス・インコーポレイテッド Temporary stiffening mesh prosthesis
US8591531B2 (en) 2006-02-08 2013-11-26 Tyrx, Inc. Mesh pouches for implantable medical devices
US20070190104A1 (en) * 2006-02-13 2007-08-16 Kamath Kalpana R Coating comprising an adhesive polymeric material for a medical device and method of preparing the same
WO2007095584A2 (en) 2006-02-14 2007-08-23 The President And Fellows Of Harvard College Histone Deacetylase Inhibitors
AU2007345292B2 (en) 2006-02-14 2013-10-31 Dana-Farber Cancer Institute, Inc. Bifunctional histone deacetylase inhibitors
US20070196428A1 (en) 2006-02-17 2007-08-23 Thierry Glauser Nitric oxide generating medical devices
US7718213B1 (en) 2006-02-24 2010-05-18 Ingo Werner Scheer Holding device and method for coating a substrate
US7713637B2 (en) 2006-03-03 2010-05-11 Advanced Cardiovascular Systems, Inc. Coating containing PEGylated hyaluronic acid and a PEGylated non-hyaluronic acid polymer
US8828077B2 (en) 2006-03-15 2014-09-09 Medinol Ltd. Flat process of preparing drug eluting stents
CN101454006B (en) * 2006-03-16 2012-12-26 新陈代谢解决方案开发公司 Thiazolidinedione analogues for the treatment of hypertension and for lowering lipids
EP2001470A2 (en) * 2006-03-16 2008-12-17 Metabolic Solutions Development Company Combination therapies of thiazolidinedione analogues
NZ571871A (en) 2006-03-16 2011-07-29 Metabolic Solutions Dev Co Thiazolidinedione analogues for the treatment of metabolic inflammation mediated disease
US20070224235A1 (en) 2006-03-24 2007-09-27 Barron Tenney Medical devices having nanoporous coatings for controlled therapeutic agent delivery
US8187620B2 (en) 2006-03-27 2012-05-29 Boston Scientific Scimed, Inc. Medical devices comprising a porous metal oxide or metal material and a polymer coating for delivering therapeutic agents
US8235047B2 (en) 2006-03-30 2012-08-07 Conceptus, Inc. Methods and devices for deployment into a lumen
US7964210B2 (en) 2006-03-31 2011-06-21 Abbott Cardiovascular Systems Inc. Degradable polymeric implantable medical devices with a continuous phase and discrete phase
US7927676B2 (en) * 2006-03-31 2011-04-19 Codman & Shurtleff, Inc. Plasma-treated vascular occlusion devices and methods
US10022352B2 (en) 2006-04-07 2018-07-17 Vertex Pharmaceuticals Incorporated Modulators of ATP-binding cassette transporters
CA2869945C (en) 2006-04-07 2018-01-23 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
US7645789B2 (en) * 2006-04-07 2010-01-12 Vertex Pharmaceuticals Incorporated Indole derivatives as CFTR modulators
US8841483B2 (en) 2006-04-11 2014-09-23 Vertex Pharmaceuticals Incorporated Compositions useful as inhibitors of voltage-gated sodium channels
US7879086B2 (en) * 2006-04-20 2011-02-01 Boston Scientific Scimed, Inc. Medical device having a coating comprising an adhesion promoter
PL2019657T3 (en) 2006-04-26 2015-10-30 Micell Technologies Inc Coatings containing multiple drugs
US20070254012A1 (en) * 2006-04-28 2007-11-01 Ludwig Florian N Controlled degradation and drug release in stents
US20070254003A1 (en) * 2006-05-01 2007-11-01 Pu Zhou Non-sticky coatings with therapeutic agents for medical devices
CA2654540C (en) * 2006-05-03 2017-01-17 President And Fellows Of Harvard College Histone deacetylase and tubulin deacetylase inhibitors
JP5371743B2 (en) 2006-05-04 2013-12-18 ナノビール・リミテッド・ライアビリティ・カンパニー Polyamides for treating human papillomavirus
US8304012B2 (en) 2006-05-04 2012-11-06 Advanced Cardiovascular Systems, Inc. Method for drying a stent
US7985441B1 (en) 2006-05-04 2011-07-26 Yiwen Tang Purification of polymers for coating applications
US8003156B2 (en) 2006-05-04 2011-08-23 Advanced Cardiovascular Systems, Inc. Rotatable support elements for stents
US8986713B2 (en) 2006-05-12 2015-03-24 W. L. Gore & Associates, Inc. Medical device capable of being compacted and expanded having anti-thrombin III binding activity
EP2023967B1 (en) * 2006-05-12 2017-03-22 W. L. Gore & Associates, Inc. Immobilized biologically active entities having a high degree of biological activity following mecanical manipulation or sterilization
US8021677B2 (en) 2006-05-12 2011-09-20 Gore Enterprise Holdings, Inc. Immobilized biologically active entities having a high degree of biological activity
US9114194B2 (en) 2006-05-12 2015-08-25 W. L. Gore & Associates, Inc. Immobilized biologically active entities having high biological activity following mechanical manipulation
US8496953B2 (en) 2006-05-12 2013-07-30 W. L. Gore & Associates, Inc. Immobilized biologically active entities having a high degree of biological activity following sterilization
US20080279909A1 (en) * 2006-05-12 2008-11-13 Cleek Robert L Immobilized Biologically Active Entities Having A High Degree of Biological Activity Following Sterilization
US7761968B2 (en) 2006-05-25 2010-07-27 Advanced Cardiovascular Systems, Inc. Method of crimping a polymeric stent
US7775178B2 (en) 2006-05-26 2010-08-17 Advanced Cardiovascular Systems, Inc. Stent coating apparatus and method
US8752267B2 (en) 2006-05-26 2014-06-17 Abbott Cardiovascular Systems Inc. Method of making stents with radiopaque markers
US7951194B2 (en) 2006-05-26 2011-05-31 Abbott Cardiovascular Sysetms Inc. Bioabsorbable stent with radiopaque coating
US7959940B2 (en) 2006-05-30 2011-06-14 Advanced Cardiovascular Systems, Inc. Polymer-bioceramic composite implantable medical devices
US20070282434A1 (en) * 2006-05-30 2007-12-06 Yunbing Wang Copolymer-bioceramic composite implantable medical devices
US8343530B2 (en) 2006-05-30 2013-01-01 Abbott Cardiovascular Systems Inc. Polymer-and polymer blend-bioceramic composite implantable medical devices
US7842737B2 (en) 2006-09-29 2010-11-30 Abbott Cardiovascular Systems Inc. Polymer blend-bioceramic composite implantable medical devices
US20080058916A1 (en) * 2006-05-31 2008-03-06 Bin Huang Method of fabricating polymeric self-expandable stent
US9561351B2 (en) 2006-05-31 2017-02-07 Advanced Cardiovascular Systems, Inc. Drug delivery spiral coil construct
US8568764B2 (en) 2006-05-31 2013-10-29 Advanced Cardiovascular Systems, Inc. Methods of forming coating layers for medical devices utilizing flash vaporization
US8486135B2 (en) 2006-06-01 2013-07-16 Abbott Cardiovascular Systems Inc. Implantable medical devices fabricated from branched polymers
US20070281073A1 (en) * 2006-06-01 2007-12-06 Gale David C Enhanced adhesion of drug delivery coatings on stents
US7820172B1 (en) 2006-06-01 2010-10-26 Biosurface Engineering Technologies, Inc. Laminin-derived multi-domain peptides
US8034287B2 (en) 2006-06-01 2011-10-11 Abbott Cardiovascular Systems Inc. Radiation sterilization of medical devices
US20070282433A1 (en) * 2006-06-01 2007-12-06 Limon Timothy A Stent with retention protrusions formed during crimping
US8703167B2 (en) 2006-06-05 2014-04-22 Advanced Cardiovascular Systems, Inc. Coatings for implantable medical devices for controlled release of a hydrophilic drug and a hydrophobic drug
US20080124372A1 (en) * 2006-06-06 2008-05-29 Hossainy Syed F A Morphology profiles for control of agent release rates from polymer matrices
US8778376B2 (en) 2006-06-09 2014-07-15 Advanced Cardiovascular Systems, Inc. Copolymer comprising elastin pentapeptide block and hydrophilic block, and medical device and method of treating
US20070286941A1 (en) * 2006-06-13 2007-12-13 Bin Huang Surface treatment of a polymeric stent
US8603530B2 (en) 2006-06-14 2013-12-10 Abbott Cardiovascular Systems Inc. Nanoshell therapy
US8114150B2 (en) 2006-06-14 2012-02-14 Advanced Cardiovascular Systems, Inc. RGD peptide attached to bioabsorbable stents
US8048448B2 (en) 2006-06-15 2011-11-01 Abbott Cardiovascular Systems Inc. Nanoshells for drug delivery
US8535372B1 (en) 2006-06-16 2013-09-17 Abbott Cardiovascular Systems Inc. Bioabsorbable stent with prohealing layer
US20070290412A1 (en) * 2006-06-19 2007-12-20 John Capek Fabricating a stent with selected properties in the radial and axial directions
US8333000B2 (en) 2006-06-19 2012-12-18 Advanced Cardiovascular Systems, Inc. Methods for improving stent retention on a balloon catheter
JP2009541358A (en) * 2006-06-22 2009-11-26 バイオサーフェス エンジニアリング テクノロジーズ,インク. Compositions and methods for delivering a BMP-2 amplification factor / co-activator to enhance bone formation
US8017237B2 (en) 2006-06-23 2011-09-13 Abbott Cardiovascular Systems, Inc. Nanoshells on polymers
US9072820B2 (en) 2006-06-26 2015-07-07 Advanced Cardiovascular Systems, Inc. Polymer composite stent with polymer particles
US8128688B2 (en) 2006-06-27 2012-03-06 Abbott Cardiovascular Systems Inc. Carbon coating on an implantable device
US20070299511A1 (en) * 2006-06-27 2007-12-27 Gale David C Thin stent coating
US8815275B2 (en) 2006-06-28 2014-08-26 Boston Scientific Scimed, Inc. Coatings for medical devices comprising a therapeutic agent and a metallic material
WO2008002778A2 (en) 2006-06-29 2008-01-03 Boston Scientific Limited Medical devices with selective coating
US7794776B1 (en) 2006-06-29 2010-09-14 Abbott Cardiovascular Systems Inc. Modification of polymer stents with radiation
US7740791B2 (en) 2006-06-30 2010-06-22 Advanced Cardiovascular Systems, Inc. Method of fabricating a stent with features by blow molding
US8066824B2 (en) * 2006-07-07 2011-11-29 Intezyne Technologies, Inc. Covalent modification of metal surfaces
US20080009938A1 (en) * 2006-07-07 2008-01-10 Bin Huang Stent with a radiopaque marker and method for making the same
US9028859B2 (en) 2006-07-07 2015-05-12 Advanced Cardiovascular Systems, Inc. Phase-separated block copolymer coatings for implantable medical devices
US7823263B2 (en) 2006-07-11 2010-11-02 Abbott Cardiovascular Systems Inc. Method of removing stent islands from a stent
US7998404B2 (en) 2006-07-13 2011-08-16 Advanced Cardiovascular Systems, Inc. Reduced temperature sterilization of stents
US7757543B2 (en) 2006-07-13 2010-07-20 Advanced Cardiovascular Systems, Inc. Radio frequency identification monitoring of stents
US20080014244A1 (en) * 2006-07-13 2008-01-17 Gale David C Implantable medical devices and coatings therefor comprising physically crosslinked block copolymers
WO2008008291A2 (en) * 2006-07-13 2008-01-17 Icon Medical Corp. Stent
US8685430B1 (en) 2006-07-14 2014-04-01 Abbott Cardiovascular Systems Inc. Tailored aliphatic polyesters for stent coatings
US7794495B2 (en) 2006-07-17 2010-09-14 Advanced Cardiovascular Systems, Inc. Controlled degradation of stents
US7886419B2 (en) 2006-07-18 2011-02-15 Advanced Cardiovascular Systems, Inc. Stent crimping apparatus and method
US8506984B2 (en) * 2006-07-26 2013-08-13 Cordis Corporation Therapeutic agent elution control process
US8016879B2 (en) 2006-08-01 2011-09-13 Abbott Cardiovascular Systems Inc. Drug delivery after biodegradation of the stent scaffolding
US20080091262A1 (en) * 2006-10-17 2008-04-17 Gale David C Drug delivery after biodegradation of the stent scaffolding
US20080033522A1 (en) * 2006-08-03 2008-02-07 Med Institute, Inc. Implantable Medical Device with Particulate Coating
US8703169B1 (en) 2006-08-15 2014-04-22 Abbott Cardiovascular Systems Inc. Implantable device having a coating comprising carrageenan and a biostable polymer
US9173733B1 (en) 2006-08-21 2015-11-03 Abbott Cardiovascular Systems Inc. Tracheobronchial implantable medical device and methods of use
US7638159B2 (en) * 2006-09-12 2009-12-29 Boston Scientific Scimed, Inc. Liquid masking for selective coating of a stent
US7923022B2 (en) 2006-09-13 2011-04-12 Advanced Cardiovascular Systems, Inc. Degradable polymeric implantable medical devices with continuous phase and discrete phase
JP2010503469A (en) 2006-09-14 2010-02-04 ボストン サイエンティフィック リミテッド Medical device having drug-eluting film
US7875069B2 (en) 2006-09-21 2011-01-25 Boston Scientific Scimed, Inc. Stent with support element
US20080075753A1 (en) * 2006-09-25 2008-03-27 Chappa Ralph A Multi-layered coatings and methods for controlling elution of active agents
US20080075628A1 (en) * 2006-09-27 2008-03-27 Medtronic, Inc. Sterilized minocycline and rifampin-containing medical device
US8298564B2 (en) * 2006-09-27 2012-10-30 Medtronic, Inc. Two part antimicrobial boot
US8466188B2 (en) * 2006-10-12 2013-06-18 Xenon Pharmaceuticals Inc. Use of spiro-oxindole compounds as therapeutic agents
US20080097591A1 (en) 2006-10-20 2008-04-24 Biosensors International Group Drug-delivery endovascular stent and method of use
WO2008051342A2 (en) * 2006-10-20 2008-05-02 Boston Scientific Limited Reduction of burst release from therapeutically treated medical devices
US8067055B2 (en) * 2006-10-20 2011-11-29 Biosensors International Group, Ltd. Drug-delivery endovascular stent and method of use
US20080103584A1 (en) * 2006-10-25 2008-05-01 Biosensors International Group Temporal Intraluminal Stent, Methods of Making and Using
US8563573B2 (en) 2007-11-02 2013-10-22 Vertex Pharmaceuticals Incorporated Azaindole derivatives as CFTR modulators
NZ576642A (en) 2006-11-03 2011-11-25 Vertex Pharma Azaindole derivatives as cftr modulators
US9023114B2 (en) * 2006-11-06 2015-05-05 Tyrx, Inc. Resorbable pouches for implantable medical devices
US7981150B2 (en) 2006-11-09 2011-07-19 Boston Scientific Scimed, Inc. Endoprosthesis with coatings
EP2111241B1 (en) 2006-11-16 2011-01-05 Boston Scientific Limited Stent with differential timing of abluminal and luminal release of a therapeutic agent
CA2669914C (en) 2006-11-16 2017-11-07 Kai Pharmaceuticals, Inc. Polycationic calcium modulator peptides for the treatment of hyperparathyroidism and hypercalcemic disorders
US7713541B1 (en) 2006-11-21 2010-05-11 Abbott Cardiovascular Systems Inc. Zwitterionic terpolymers, method of making and use on medical devices
US20100185146A1 (en) * 2006-12-06 2010-07-22 Laura N. Dietch Drug delivery systems
US8597673B2 (en) 2006-12-13 2013-12-03 Advanced Cardiovascular Systems, Inc. Coating of fast absorption or dissolution
US8099849B2 (en) 2006-12-13 2012-01-24 Abbott Cardiovascular Systems Inc. Optimizing fracture toughness of polymeric stent
WO2008076383A2 (en) * 2006-12-18 2008-06-26 Med Institute Inc. Stent graft with releasable therapeutic agent
TW200838517A (en) 2006-12-21 2008-10-01 Vertex Pharma Compounds useful as protein kinases inhibitors
US8431149B2 (en) 2007-03-01 2013-04-30 Boston Scientific Scimed, Inc. Coated medical devices for abluminal drug delivery
US8070797B2 (en) 2007-03-01 2011-12-06 Boston Scientific Scimed, Inc. Medical device with a porous surface for delivery of a therapeutic agent
WO2008112076A1 (en) 2007-03-07 2008-09-18 Boston Scientific Scimed, Inc. Radiopaque polymeric stent
ES2559838T3 (en) 2007-03-16 2016-02-16 Concert Pharmaceuticals, Inc. Cholesterol ester transfer protein inhibitors
US20080243228A1 (en) * 2007-03-28 2008-10-02 Yunbing Wang Implantable medical devices fabricated from block copolymers
US20080241215A1 (en) 2007-03-28 2008-10-02 Robert Falotico Local vascular delivery of probucol alone or in combination with sirolimus to treat restenosis, vulnerable plaque, aaa and stroke
US20080261926A1 (en) * 2007-04-02 2008-10-23 Liu Julie F Pharmaceutical Calcimimetics
US20080248263A1 (en) * 2007-04-02 2008-10-09 Applied Microstructures, Inc. Method of creating super-hydrophobic and-or super-hydrophilic surfaces on substrates, and articles created thereby
US8236379B2 (en) * 2007-04-02 2012-08-07 Applied Microstructures, Inc. Articles with super-hydrophobic and-or super-hydrophilic surfaces and method of formation
US8067054B2 (en) 2007-04-05 2011-11-29 Boston Scientific Scimed, Inc. Stents with ceramic drug reservoir layer and methods of making and using the same
US20080255657A1 (en) * 2007-04-09 2008-10-16 Boston Scientific Scimed, Inc. Stent with unconnected stent segments
US8262723B2 (en) 2007-04-09 2012-09-11 Abbott Cardiovascular Systems Inc. Implantable medical devices fabricated from polymer blends with star-block copolymers
WO2008128166A1 (en) * 2007-04-13 2008-10-23 Concert Pharmaceuticals Inc. Deuterated derivatives of 4-(6-fluoro-1, 2-benzisoxazol-3-yl) piperidine compounds
US7528131B2 (en) * 2007-04-19 2009-05-05 Concert Pharmaceuticals Inc. Substituted morpholinyl compounds
JP2010524653A (en) * 2007-04-25 2010-07-22 ボストン サイエンティフィック サイムド,インコーポレイテッド Medical device for therapeutic drug release and method of manufacturing the same
ES2401914T3 (en) 2007-04-25 2013-04-25 Concert Pharmaceuticals Inc. Cilostazol analogues
JP4944244B2 (en) 2007-05-01 2012-05-30 コンサート ファーマシューティカルズ インコーポレイテッド Morphinan compounds
EP2150525A1 (en) * 2007-05-01 2010-02-10 Concert Pharmaceuticals Inc. Naphthyl(ethyl) acetamides
ES2951028T3 (en) 2007-05-01 2023-10-17 Sun Pharmaceutical Ind Inc Morphin compounds
EP3632916B1 (en) 2007-05-01 2022-06-08 Concert Pharmaceuticals Inc. Morphinan compounds
WO2008141021A1 (en) * 2007-05-08 2008-11-20 Concert Pharmaceuticals, Inc. Deuterated derivatives of tetrahydrotriazolopyrazine compounds and their use as dpp-iv inhibitors
CN104447716A (en) 2007-05-09 2015-03-25 沃泰克斯药物股份有限公司 Modulators of CFTR
US8147769B1 (en) 2007-05-16 2012-04-03 Abbott Cardiovascular Systems Inc. Stent and delivery system with reduced chemical degradation
US20080293777A1 (en) * 2007-05-23 2008-11-27 Erlanson Daniel A Weight Loss Treatment
US7976915B2 (en) 2007-05-23 2011-07-12 Boston Scientific Scimed, Inc. Endoprosthesis with select ceramic morphology
US9056155B1 (en) 2007-05-29 2015-06-16 Abbott Cardiovascular Systems Inc. Coatings having an elastic primer layer
US7829008B2 (en) 2007-05-30 2010-11-09 Abbott Cardiovascular Systems Inc. Fabricating a stent from a blow molded tube
US8802184B2 (en) 2007-05-30 2014-08-12 Abbott Cardiovascular Systems Inc. Medical devices containing biobeneficial particles
US7959857B2 (en) 2007-06-01 2011-06-14 Abbott Cardiovascular Systems Inc. Radiation sterilization of medical devices
US8202528B2 (en) 2007-06-05 2012-06-19 Abbott Cardiovascular Systems Inc. Implantable medical devices with elastomeric block copolymer coatings
US8293260B2 (en) 2007-06-05 2012-10-23 Abbott Cardiovascular Systems Inc. Elastomeric copolymer coatings containing poly (tetramethyl carbonate) for implantable medical devices
US8425591B1 (en) 2007-06-11 2013-04-23 Abbott Cardiovascular Systems Inc. Methods of forming polymer-bioceramic composite medical devices with bioceramic particles
ATE447554T1 (en) 2007-06-12 2009-11-15 Concert Pharmaceuticals Inc AZAPEPTIDE DERIVATIVES AS HIV PROTEASE INHIBITORS
US8109904B1 (en) 2007-06-25 2012-02-07 Abbott Cardiovascular Systems Inc. Drug delivery medical devices
US8048441B2 (en) 2007-06-25 2011-11-01 Abbott Cardiovascular Systems, Inc. Nanobead releasing medical devices
US7901452B2 (en) 2007-06-27 2011-03-08 Abbott Cardiovascular Systems Inc. Method to fabricate a stent having selected morphology to reduce restenosis
US7955381B1 (en) 2007-06-29 2011-06-07 Advanced Cardiovascular Systems, Inc. Polymer-bioceramic composite implantable medical device with different types of bioceramic particles
WO2009006404A2 (en) 2007-06-29 2009-01-08 Sunesis Pharmaceuticals, Inc. Heterocyclic compounds useful as raf kinase inhibitors
AR067354A1 (en) 2007-06-29 2009-10-07 Sunesis Pharmaceuticals Inc USEFUL COMPOUNDS AS INHIBITORS OF RAF QUINASA
US20090011117A1 (en) * 2007-07-03 2009-01-08 Endotronix, Inc. Methods for texturing a surface of an endovascular implant
WO2009009531A2 (en) * 2007-07-09 2009-01-15 Concert Pharmaceuticals Inc. Pyrimidinecarboxamide derivatives for the treatment of hiv infections
US7942926B2 (en) 2007-07-11 2011-05-17 Boston Scientific Scimed, Inc. Endoprosthesis coating
US8002823B2 (en) 2007-07-11 2011-08-23 Boston Scientific Scimed, Inc. Endoprosthesis coating
US7780095B2 (en) 2007-07-13 2010-08-24 Bacoustics, Llc Ultrasound pumping apparatus
US7753285B2 (en) 2007-07-13 2010-07-13 Bacoustics, Llc Echoing ultrasound atomization and/or mixing system
EP2187988B1 (en) 2007-07-19 2013-08-21 Boston Scientific Limited Endoprosthesis having a non-fouling surface
US20090028785A1 (en) * 2007-07-23 2009-01-29 Boston Scientific Scimed, Inc. Medical devices with coatings for delivery of a therapeutic agent
US8815273B2 (en) 2007-07-27 2014-08-26 Boston Scientific Scimed, Inc. Drug eluting medical devices having porous layers
US7931683B2 (en) 2007-07-27 2011-04-26 Boston Scientific Scimed, Inc. Articles having ceramic coated surfaces
US8221822B2 (en) 2007-07-31 2012-07-17 Boston Scientific Scimed, Inc. Medical device coating by laser cladding
JP2010535541A (en) 2007-08-03 2010-11-25 ボストン サイエンティフィック リミテッド Coating for medical devices with large surface area
CN101855218A (en) 2007-09-13 2010-10-06 康塞特医药品有限公司 Synthesizing of deuterated catechol and benzo [d] [1,3] dioxole and derivative thereof
CA2699289C (en) 2007-09-14 2016-01-19 Metabolic Solutions Development Company Thiazolidinedione analogues for the treatment of hypertension
US8304441B2 (en) 2007-09-14 2012-11-06 Metabolic Solutions Development Company, Llc Thiazolidinedione analogues for the treatment of metabolic diseases
US20090074831A1 (en) 2007-09-18 2009-03-19 Robert Falotico LOCAL VASCULAR DELIVERY OF mTOR INHIBITORS IN COMBINATION WITH PEROXISOME PROLIFERATORS-ACTIVATED RECEPTOR STIMULATORS
KR100930167B1 (en) * 2007-09-19 2009-12-07 삼성전기주식회사 Ultra wide angle optical system
US9393137B2 (en) * 2007-09-24 2016-07-19 Boston Scientific Scimed, Inc. Method for loading a stent into a delivery system
US20110230973A1 (en) * 2007-10-10 2011-09-22 Zimmer, Inc. Method for bonding a tantalum structure to a cobalt-alloy substrate
AU2008310660A1 (en) 2007-10-11 2009-04-16 Vertex Pharmaceuticals Incorporated Heteroaryl amides useful as inhibitors of voltage-gated sodium channels
WO2009051782A1 (en) * 2007-10-18 2009-04-23 Concert Pharmaceuticals Inc. Deuterated etravirine
WO2009051780A1 (en) * 2007-10-19 2009-04-23 Micell Technologies, Inc. Drug coated stents
US7863387B2 (en) * 2007-10-25 2011-01-04 Boston Scientific Scimed, Inc. Dehydrofluorination and surface modification of fluoropolymers for drug delivery applications
US8216632B2 (en) 2007-11-02 2012-07-10 Boston Scientific Scimed, Inc. Endoprosthesis coating
US7938855B2 (en) 2007-11-02 2011-05-10 Boston Scientific Scimed, Inc. Deformable underlayer for stent
US8029554B2 (en) 2007-11-02 2011-10-04 Boston Scientific Scimed, Inc. Stent with embedded material
AU2008321137A1 (en) 2007-11-13 2009-05-22 Vertex Pharmaceuticals Incorporated 4(-3-(-2-(phenyl)morpholino)-2-oxopyrrolidin-1-yl)-n-(thiazol-2-yl)benzenesulfonamide derivati ves and related compounds as modulators of ion channels for the treatment of pain
WO2009064959A1 (en) 2007-11-16 2009-05-22 Vertex Pharmaceuticals Incorporated Isoquinoline modulators of atp-binding cassette transporters
HUE031913T2 (en) 2007-12-07 2017-08-28 Vertex Pharma Solid forms of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl) benzoic acid
US8211489B2 (en) * 2007-12-19 2012-07-03 Abbott Cardiovascular Systems, Inc. Methods for applying an application material to an implantable device
US8361538B2 (en) 2007-12-19 2013-01-29 Abbott Laboratories Methods for applying an application material to an implantable device
WO2009085913A1 (en) 2007-12-19 2009-07-09 Vertex Pharmaceuticals Incorporated PYRAZOLO [1,5-a] PYRIMIDINES USEFUL AS JAK2 INHIBITORS
US20090187256A1 (en) * 2008-01-21 2009-07-23 Zimmer, Inc. Method for forming an integral porous region in a cast implant
ES2371380T3 (en) * 2008-01-24 2011-12-30 Boston Scientific Scimed, Inc. STENT TO SUPPLY A THERAPEUTIC AGENT FROM A SIDE SURFACE OF A STENT STEM.
US20090198286A1 (en) * 2008-02-05 2009-08-06 Zimmer, Inc. Bone fracture fixation system
US9603980B2 (en) 2008-02-26 2017-03-28 CARDINAL HEALTH SWITZERLAND 515 GmbH Layer-by-layer stereocomplexed polymers as drug depot carriers or coatings in medical devices
KR20100121527A (en) 2008-02-29 2010-11-17 콘서트 파마슈티컬즈, 인크. Substituted xanthine derivatives
US8252048B2 (en) * 2008-03-19 2012-08-28 Boston Scientific Scimed, Inc. Drug eluting stent and method of making the same
US8409601B2 (en) * 2008-03-31 2013-04-02 Cordis Corporation Rapamycin coated expandable devices
US8420110B2 (en) 2008-03-31 2013-04-16 Cordis Corporation Drug coated expandable devices
SI2615085T1 (en) 2008-03-31 2015-11-30 Vertex Pharmaceuticals Incorporated Pyridyl derivatives as CFTR modulators
EP2271380B1 (en) 2008-04-22 2013-03-20 Boston Scientific Scimed, Inc. Medical devices having a coating of inorganic material
US8932346B2 (en) 2008-04-24 2015-01-13 Boston Scientific Scimed, Inc. Medical devices having inorganic particle layers
US8273404B2 (en) * 2008-05-19 2012-09-25 Cordis Corporation Extraction of solvents from drug containing polymer reservoirs
US20110160253A1 (en) * 2008-05-28 2011-06-30 Harbeson Scott L Deuterated tizanidine
US8652506B2 (en) * 2008-06-05 2014-02-18 Boston Scientific Scimed, Inc. Bio-degradable block co-polymers for controlled release
US8449603B2 (en) 2008-06-18 2013-05-28 Boston Scientific Scimed, Inc. Endoprosthesis coating
US20100016890A1 (en) * 2008-07-17 2010-01-21 Steve Tsai Spool Dip And Overcoat Process For Medical Devices
KR101708946B1 (en) * 2008-07-23 2017-02-21 다나-파버 캔서 인스티튜트 인크. Deacetylase inhibitors and uses thereof
WO2010019557A1 (en) * 2008-08-12 2010-02-18 Concert Pharmaceuticals Inc. N-phenyl-2-pyrimidineamine derivatives
EP3248978B1 (en) 2008-09-19 2019-08-07 Concert Pharmaceuticals Inc. Deuterated morphinan compounds
US8076529B2 (en) 2008-09-26 2011-12-13 Abbott Cardiovascular Systems, Inc. Expandable member formed of a fibrous matrix for intraluminal drug delivery
US8049061B2 (en) 2008-09-25 2011-11-01 Abbott Cardiovascular Systems, Inc. Expandable member formed of a fibrous matrix having hydrogel polymer for intraluminal drug delivery
US8226603B2 (en) 2008-09-25 2012-07-24 Abbott Cardiovascular Systems Inc. Expandable member having a covering formed of a fibrous matrix for intraluminal drug delivery
WO2010042471A2 (en) * 2008-10-07 2010-04-15 Boston Scientific Scimed, Inc. Medical devices for delivery of therapeutic agents to body lumens
US8293897B2 (en) 2008-10-14 2012-10-23 Ning Xi Compounds comprising a spiro-ring and methods of use
SG10201703082XA (en) 2008-10-17 2017-06-29 Xenon Pharmaceuticals Inc Spiro-oxindole compounds and their use as therapeutic agents
NZ592685A (en) 2008-10-23 2013-04-26 Vertex Pharma Modulators of cystic fibrosis transmembrane conductance regulator
DK2397158T3 (en) 2008-10-30 2016-07-25 Concert Pharmaceuticals Inc COMBINATION OF MORPHINANFORBINDELSER AND antidepressants in treating pseudobulbar affect
EP2364151A1 (en) 2008-10-30 2011-09-14 Concert Pharmaceuticals Inc. Combination of morphinan compounds and antidepressant for the treatment of pseudobulbar affect, neurological diseases, intractable and chronic pain and brain injury
AU2009311645C1 (en) 2008-11-04 2014-10-02 Acer Therapeutics Inc. CXCR4 receptor compounds
UA104876C2 (en) 2008-11-06 2014-03-25 Вертекс Фармасьютікалз Інкорпорейтед Modulators of atp-binding cassette transporters
NZ592694A (en) 2008-11-06 2013-05-31 Vertex Pharma ATP-Binding Cassette (ABC) transporters as modulators of CFTR activity
US8231980B2 (en) 2008-12-03 2012-07-31 Boston Scientific Scimed, Inc. Medical implants including iridium oxide
US20110313004A1 (en) 2008-12-04 2011-12-22 Concert Pharmaceuticals, Inc. Deuterated pyridinones
US20120040951A1 (en) 2008-12-30 2012-02-16 Claudio Chuaqui Heteroaryl compounds useful as raf kinase inhibitors
WO2010088697A2 (en) * 2009-02-02 2010-08-05 Medtronic, Inc. Antimicrobial accessory for an implantable medical device
US20110053961A1 (en) 2009-02-27 2011-03-03 Concert Pharmaceuticals, Inc. Substituted xanthine derivatives
US8071156B2 (en) 2009-03-04 2011-12-06 Boston Scientific Scimed, Inc. Endoprostheses
BRPI1009199A2 (en) 2009-03-17 2016-03-08 Concert Pharmaceuticals Inc pyrazinoisoquinoline compounds
PT2821400T (en) 2009-03-20 2018-01-03 Vertex Pharma Process for making modulators of cystic fibrosis transmembrane conductance regulator
BRPI1012549B8 (en) 2009-03-20 2021-05-25 Vertex Pharma transmembrane conductance regulator modulators in cystic fibrosis, pharmaceutical composition and kit
JP2012522589A (en) 2009-04-01 2012-09-27 ミシェル テクノロジーズ,インコーポレイテッド Covered stent
US8287937B2 (en) 2009-04-24 2012-10-16 Boston Scientific Scimed, Inc. Endoprosthese
US20100278895A1 (en) * 2009-04-30 2010-11-04 Medtronic, Inc. Antioxidants and antimicrobial accessories including antioxidants
US20110319987A1 (en) 2009-05-20 2011-12-29 Arsenal Medical Medical implant
JP5820370B2 (en) 2009-05-20 2015-11-24 アーセナル メディカル, インコーポレイテッド Medical implant
US9265633B2 (en) 2009-05-20 2016-02-23 480 Biomedical, Inc. Drug-eluting medical implants
US9309347B2 (en) 2009-05-20 2016-04-12 Biomedical, Inc. Bioresorbable thermoset polyester/urethane elastomers
US8992601B2 (en) 2009-05-20 2015-03-31 480 Biomedical, Inc. Medical implants
US8888840B2 (en) * 2009-05-20 2014-11-18 Boston Scientific Scimed, Inc. Drug eluting medical implant
RU2552993C2 (en) 2009-05-28 2015-06-10 Вертекс Фармасьютикалз Инкорпорейтед Aminopyrazol triazolothiadiazole c-met protein kinase inhibitors
US20120244122A1 (en) 2009-05-28 2012-09-27 Masse Craig E Peptides for the Treatment of HCV Infections
JP2012528188A (en) 2009-05-28 2012-11-12 バーテックス ファーマシューティカルズ インコーポレイテッド Inhibitors of c-Met protein kinase
TWI483941B (en) 2009-06-17 2015-05-11 Vertex Pharma Inhibitors of influenza viruses replication
EA021019B1 (en) 2009-06-18 2015-03-31 Концерт Фармасьютикалс, Инк. Deuterated isoindoline-1,3-dione derivatives
EP2454259A1 (en) 2009-06-23 2012-05-23 Concert Pharmaceuticals Inc. Deuterium-modified triazolo-pyridazine derivatives as gaba-a receptor modulators
AR077252A1 (en) 2009-06-29 2011-08-10 Xenon Pharmaceuticals Inc ESPIROOXINDOL COMPOUND ENANTIOMERS AND THEIR USES AS THERAPEUTIC AGENTS
WO2011006066A1 (en) 2009-07-10 2011-01-13 Ironwood Pharmaceuticals, Inc. Cb receptor agonists
LT2459208T (en) 2009-07-29 2017-02-27 Kai Pharmaceuticals, Inc. Therapeutic agents for reducing parathyroid hormone levels
WO2011019393A2 (en) 2009-08-11 2011-02-17 President And Fellows Of Harvard College Class- and isoform-specific hdac inhibitors and uses thereof
EP2475329B1 (en) 2009-09-10 2015-12-02 Boston Scientific Scimed, Inc. Endoprosthesis with filament repositioning or retrieval member and guard structure
CN102655865A (en) 2009-09-11 2012-09-05 沃泰克斯药物股份有限公司 Compositions of n-benzyl-3-(4-chlorophenyl)-2-[methyl-[2-oxo-2-(3,4,5-trimethoxyphenyl) acetyl]amino]-n-[3-(4-pyridyl)-1-[2-[4-pyridyl)ethyl]propanamide and uses thereof
US8591932B2 (en) 2009-09-17 2013-11-26 W. L. Gore & Associates, Inc. Heparin entities and methods of use
US8372133B2 (en) * 2009-10-05 2013-02-12 480 Biomedical, Inc. Polymeric implant delivery system
US10052220B2 (en) 2009-10-09 2018-08-21 Boston Scientific Scimed, Inc. Stomach bypass for the treatment of obesity
NZ622072A (en) 2009-10-14 2015-10-30 Xenon Pharmaceuticals Inc Synthetic methods for spiro-oxindole compounds
WO2011047315A1 (en) 2009-10-15 2011-04-21 Concert Pharmaceuticals, Inc. Subsitituted benzimidazoles
US20110098311A1 (en) 2009-10-22 2011-04-28 Vertex Pharmaceuticals Incorported Compositions for treatment of cystic fibrosis and other chronic diseases
CN102648182A (en) 2009-10-23 2012-08-22 沃泰克斯药物股份有限公司 Process for preparing modulators of cystic fibrosis transmembrane conductance regulator
RU2568608C2 (en) 2009-10-23 2015-11-20 Вертекс Фармасьютикалз Инкорпорейтед Solid forms of n-(4-(7-azabicyclo[2,2,1]heptan-7-yl)-2-(trifluoromethyl)phenyl)-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide
US8271873B2 (en) * 2009-10-30 2012-09-18 International Business Machines Corporation Automatically detecting layout of bidirectional (BIDI) text
US20130109721A1 (en) 2009-12-08 2013-05-02 Ironwood Pharmaceuticals, Inc. FAAH Inhibitors
US8951595B2 (en) * 2009-12-11 2015-02-10 Abbott Cardiovascular Systems Inc. Coatings with tunable molecular architecture for drug-coated balloon
US20110144577A1 (en) * 2009-12-11 2011-06-16 John Stankus Hydrophilic coatings with tunable composition for drug coated balloon
US8480620B2 (en) * 2009-12-11 2013-07-09 Abbott Cardiovascular Systems Inc. Coatings with tunable solubility profile for drug-coated balloon
NZ600421A (en) 2009-12-15 2014-06-27 Metabolic Solutions Dev Co Llc Ppar-sparing thiazolidinediones and combinations for the treatment of neurodegenerative diseases
EP2512471A1 (en) 2009-12-15 2012-10-24 Metabolic Solutions Development Company LLC Ppar-sparing thiazolidinediones and combinations for the treatment of diabetes mellitus and other metabolic diseases
ES2658168T3 (en) 2009-12-15 2018-03-08 Cirius Therapeutics, Inc. PPAR-sparing thiazolidinedione salts for the treatment of metabolic diseases
AU2010340061A1 (en) 2009-12-15 2012-06-21 Metabolic Solutions Development Company, Llc PPAR-sparing thiazolidinediones and combinations for the treatment of obesity and other metabolic diseases
EP2338534A2 (en) * 2009-12-21 2011-06-29 Biotronik VI Patent AG Medical implant, coating method and implantation method
JP5731538B2 (en) 2009-12-23 2015-06-10 アイアンウッド ファーマシューティカルズ インコーポレイテッド CRTH2 modulator
WO2011085216A2 (en) 2010-01-08 2011-07-14 Ironwood Pharmaceuticals, Inc. Use of faah inhibitors for treating parkinson's disease and restless legs syndrome
KR101808874B1 (en) 2010-01-22 2018-01-18 에이스틸론 파마수티컬스 인코포레이티드 Reverse amide compounds as protein deacetylase inhibitors and methods of use thereof
US8808353B2 (en) 2010-01-30 2014-08-19 Abbott Cardiovascular Systems Inc. Crush recoverable polymer scaffolds having a low crossing profile
US8568471B2 (en) 2010-01-30 2013-10-29 Abbott Cardiovascular Systems Inc. Crush recoverable polymer scaffolds
WO2011100359A1 (en) 2010-02-09 2011-08-18 Ironwood Pharmaceuticals, Inc. Cannabinoid agonists
US20130196960A1 (en) 2010-02-09 2013-08-01 Ironwood Pharmaceuticals, Inc. Cannabinoid Receptor Agonists
US20140018379A1 (en) 2010-02-18 2014-01-16 Concert Pharmaceuticals Inc. Pyrimidine derivatives
WO2011106703A2 (en) 2010-02-26 2011-09-01 Anchor Therapeutics, Inc. Cxcr4 receptor compounds
CN102946859B (en) 2010-02-26 2016-03-02 泽农医药公司 For the pharmaceutical composition of the spiral shell-oxindole compounds of topical and the purposes as therapeutic agent thereof
EP3144296A1 (en) 2010-03-02 2017-03-22 Concert Pharmaceuticals, Inc. Deuterated tetrahydronaphthalene derivatives
US8575361B2 (en) 2010-03-02 2013-11-05 Concert Pharmaceuticals Inc. Tetrahydronaphthalene derivatives
US8398916B2 (en) 2010-03-04 2013-03-19 Icon Medical Corp. Method for forming a tubular medical device
US20110230946A1 (en) * 2010-03-16 2011-09-22 Abbott Laboratories Easy marker placement balloon mold
WO2011115804A1 (en) 2010-03-17 2011-09-22 Ironwood Pharmaceuticals, Inc. Sgc stimulators
US8471029B2 (en) 2010-03-19 2013-06-25 Vertex Pharmaceutical Incorporated Solid forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
WO2011119536A1 (en) 2010-03-22 2011-09-29 Abbott Cardiovascular Systems Inc. Stent delivery system having a fibrous matrix covering with improved stent retention
US8802868B2 (en) 2010-03-25 2014-08-12 Vertex Pharmaceuticals Incorporated Solid forms of (R)-1(2,2-difluorobenzo[D][1,3]dioxo1-5-yl)-N-(1-(2,3-dihydroxypropyl-6-fluoro-2-(1-hydroxy-2-methylpropan2-yl)-1H-Indol-5-yl)-Cyclopropanecarboxamide
RU2573830C2 (en) 2010-03-25 2016-01-27 Вертекс Фармасьютикалз Инкорпорейтед SOLID FORMS OF (R)-1-(2,2-DIFLUOROBENZO[d][1,3]DIOXOL-5-YL)-N-(2,3-DIHYDROXYPROPYL)-6-FLUORO-2-(1-HYDROXY-2-METHYLPROPAN-2-YL)-1H-INDOL-5-YL)CYCLOPROPANE CARBOXAMIDE
WO2011123719A2 (en) 2010-03-31 2011-10-06 Ironwood Pharmaceuticals, Inc. Use of faah inhibitors for treating abdominal, visceral and pelvic pain
US8685433B2 (en) 2010-03-31 2014-04-01 Abbott Cardiovascular Systems Inc. Absorbable coating for implantable device
CA2795748C (en) 2010-04-07 2020-12-08 Vertex Pharmaceuticals Incorporated Solid forms of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid
AU2011242844A1 (en) 2010-04-21 2012-11-01 Metabolic Solutions Development Company, Llc Thiazolidinedione analogues
EP2560649A1 (en) 2010-04-22 2013-02-27 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
KR20190061096A (en) 2010-04-22 2019-06-04 버텍스 파마슈티칼스 인코포레이티드 Process of producing cycloalkylcarboxamido-indole compounds
WO2011133953A1 (en) 2010-04-22 2011-10-27 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions and administrations thereof
NZ603044A (en) 2010-04-22 2015-08-28 Vertex Pharma Pharmaceutical compositions comprising cftr modulators and administrations thereof
WO2011140425A1 (en) 2010-05-06 2011-11-10 Vertex Pharmaceuticals Incorporated Heterocyclic chromene-spirocyclic piperidine amides as modulators of ion channels
US8404849B2 (en) 2010-05-20 2013-03-26 Vertex Pharmaceuticals Processes for producing modulators of cystic fibrosis transmembrane conductance regulator
JP2013527195A (en) 2010-05-27 2013-06-27 バーテックス ファーマシューティカルズ インコーポレイテッド Aminopyrazole triazolothiadiazole inhibitors of c-Met protein kinase
US8389041B2 (en) 2010-06-17 2013-03-05 Abbott Cardiovascular Systems, Inc. Systems and methods for rotating and coating an implantable device
US8748442B2 (en) 2010-06-30 2014-06-10 Ironwood Pharmaceuticals, Inc. sGC stimulators
US20120010691A1 (en) * 2010-07-06 2012-01-12 Medtronic Vascular, Inc. Particle Embedded Polymer Stent and Method of Manufacture
WO2012009137A1 (en) 2010-07-12 2012-01-19 Ironwood Pharmaceuticals, Inc. Crth2 modulators
WO2012009134A1 (en) 2010-07-12 2012-01-19 Ironwood Pharmaceuticals, Inc. Crth2 modulators
US9107922B2 (en) 2010-07-16 2015-08-18 Concert Pharmaceuticals, Inc. Pyrimidinecarboxamide derivatives
EP2637659B1 (en) 2010-11-09 2016-05-18 Ironwood Pharmaceuticals, Inc. Sgc stimulators
JP6041808B2 (en) 2010-11-16 2016-12-14 アセチロン ファーマシューティカルズ インコーポレイテッドAcetylon Pharmaceuticals,Inc. Pyrimidine hydroxyl amide compounds as protein deacetylase inhibitors and methods of use thereof
WO2012079075A1 (en) 2010-12-10 2012-06-14 Concert Pharmaceuticals, Inc. Deuterated phthalimide derivatives
CA2822057A1 (en) 2010-12-16 2012-06-21 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
AR084433A1 (en) 2010-12-22 2013-05-15 Ironwood Pharmaceuticals Inc FAAH INHIBITORS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
WO2012088431A1 (en) 2010-12-23 2012-06-28 Ironwood Pharmaceuticals, Inc. Faah inhibitors
US8911427B2 (en) 2010-12-28 2014-12-16 Medtronic, Inc. Therapeutic agent reservoir delivery system
SG192248A1 (en) 2011-02-02 2013-09-30 Vertex Pharma Pyrrolopyrazine-spirocyclic piperidine amides as modulators of ion channels
US8447329B2 (en) 2011-02-08 2013-05-21 Longsand Limited Method for spatially-accurate location of a device using audio-visual information
CN103443105A (en) 2011-02-18 2013-12-11 沃泰克斯药物股份有限公司 Chroman-spirocyclic piperidine amides as modulators of ion channels
JP5707518B2 (en) 2011-02-28 2015-04-30 カリトル サイエンシズ, エルエルシー Substituted quinoline compounds and methods of use
BR112013023241B1 (en) 2011-03-11 2019-07-02 W. L. Gore & Associates, Inc. Hyper-branched cationic polymer molecule and device
CN103517910B (en) 2011-03-14 2016-12-14 沃泰克斯药物股份有限公司 Morpholine-spirocyclic piperidine amide as ion channel modulators
WO2012129381A1 (en) 2011-03-22 2012-09-27 Concert Pharmaceuticals Inc. Deuterated preladenant
ES2866698T3 (en) 2011-04-01 2021-10-19 Aureogen Biosciences Inc Aureobasidine derivatives and synthesis methods
WO2012149083A1 (en) 2011-04-28 2012-11-01 Metabolic Solutions Development Company, Llc Ppar-sparing thiazolidinediones for the treatment of kidney related diseases
WO2012151361A1 (en) 2011-05-03 2012-11-08 Concert Pharmaceuticals Inc. Carbamoylpyridone derivatives
US20140128469A1 (en) 2011-05-10 2014-05-08 Concert Pharmaceuticals Inc. Deuterated n-butyl bumetanide
FR2975911A1 (en) 2011-06-06 2012-12-07 Univ Strasbourg BISACODYL AND THE LIKE AS MEDICAMENTS FOR THE TREATMENT OF CANCER
WO2012177956A1 (en) 2011-06-23 2012-12-27 Metabolic Solutions Development Comapny, Llc Ppar-sparing compounds for use in the treatment of diabetes and other metabolic diseases
WO2012178142A1 (en) 2011-06-23 2012-12-27 Metabolic Solutions Development Company, Llc Ppar-sparing compounds and combinations fort the treatment of diabetes and other metabolic diseases
US8726483B2 (en) 2011-07-29 2014-05-20 Abbott Cardiovascular Systems Inc. Methods for uniform crimping and deployment of a polymer scaffold
UA118010C2 (en) 2011-08-01 2018-11-12 Вертекс Фармасьютікалз Інкорпорейтед INFLUENCES OF INFLUENZA VIRUS REPLICATION
WO2013067248A1 (en) 2011-11-04 2013-05-10 Vertex Pharmaceuticals Incorporated Benzoxazines as modulators of ion channels
WO2013070961A1 (en) 2011-11-08 2013-05-16 Vertex Pharmaceuticals Incorporated Modulators of atp-binding cassette transporters
AU2012335009B2 (en) 2011-11-10 2017-08-31 Kai Pharmaceuticals, Inc. Calcimimetics and methods for their use
US9139564B2 (en) 2011-12-27 2015-09-22 Ironwood Pharmaceuticals, Inc. 2-benzyl, 3-(pyrimidin-2-yl) substituted pyrazoles useful as sGC stimulators
WO2013106437A1 (en) 2012-01-09 2013-07-18 Anchor Therapeutics, Inc. Apj receptor compounds
MX2014008591A (en) 2012-01-16 2014-08-22 Vertex Pharma Pyran-spirocyclic piperidine amides as modulators of ion channels.
US10328458B2 (en) 2012-02-28 2019-06-25 Microvention, Inc. Coating methods
WO2013130849A1 (en) 2012-02-29 2013-09-06 Concert Pharmaceuticals, Inc. Substituted dioxopiperidinyl phthalimide derivatives
WO2013155422A1 (en) 2012-04-12 2013-10-17 Ironwood Pharmaceuticals, Inc. Methods of treating alopecia and acne
AU2013245662A1 (en) 2012-04-13 2014-10-30 Concert Pharmaceuticals, Inc. Substituted xanthine derivatives
CA2869847A1 (en) 2012-04-20 2013-10-24 Vertex Pharmaceuticals Incorporated Solid forms of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
US9249093B2 (en) 2012-04-20 2016-02-02 Concert Pharmaceuticals, Inc. Deuterated rigosertib
JP6549482B2 (en) 2012-06-01 2019-07-24 サーモディクス,インコーポレイテッド Device and method for coating a balloon catheter
US9827401B2 (en) 2012-06-01 2017-11-28 Surmodics, Inc. Apparatus and methods for coating medical devices
WO2013188783A1 (en) 2012-06-15 2013-12-19 Concert Pharmaceuticals, Inc. Deuterated derivatives of ruxolitinib
WO2014004676A1 (en) 2012-06-26 2014-01-03 Ironwood Pharmaceuticals, Inc. Use of faah inhibitors as neuroprotective agents in the cns
EP2885267B1 (en) 2012-07-12 2018-09-05 Concert Pharmaceuticals, Inc. Deuterated idebenone
WO2014014841A1 (en) 2012-07-16 2014-01-23 Vertex Pharmaceuticals Incorporated Pharmaceutical compositions of (r)-1-(2,2-diflurorbenzo[d][1,3]dioxol-5-yl)-n-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1h-indol-5-yl) cyclopropanecarboxamide and administration thereof
US8969388B1 (en) 2012-07-28 2015-03-03 Sunshine Lake Pharma Co., Ltd. Substituted pyrazolone compounds and methods of use
WO2014022639A1 (en) 2012-08-01 2014-02-06 Vertex Pharmaceuticals Incorporated Solid forms of (4-isopropoxy-3-methoxyphenyl)(2'-methyl-6'-(trifluoromethyl)-3',4'-dihydro-2'h-spiro[piperidine-4,1'-pyrrolo[1,2-a]pyrazine]-1-yl)methanone
ES2717279T3 (en) 2012-08-17 2019-06-20 Concert Pharmaceuticals Inc Deuterated baricitinib
US9309235B2 (en) 2012-09-18 2016-04-12 Ironwood Pharmaceuticals, Inc. SGC stimulators
US9487508B2 (en) 2012-09-19 2016-11-08 Ironwood Pharmaceuticals, Inc. SGC stimulators
EP3345597A3 (en) 2012-09-19 2018-08-22 Faller & Williams Technology, LLC Pkc delta inhibitors for use as therapeutics
TWI574962B (en) 2012-11-14 2017-03-21 加拓科學公司 Heteroaromatic compounds as pi3 kinase modulators and methods of use
EP2931274A1 (en) 2012-12-11 2015-10-21 Metabolic Solutions Development Company LLC Ppar-sparing thiazolidinediones and combinations for the treatment of neurodegenerative diseases
AU2013361320A1 (en) 2012-12-20 2015-07-02 Concert Pharmaceuticals, Inc. Deuterated ALK inhibitors
WO2014110322A2 (en) 2013-01-11 2014-07-17 Concert Pharmaceuticals, Inc. Substituted dioxopiperidinyl phthalimide derivatives
WO2014120808A1 (en) 2013-01-31 2014-08-07 Vertex Parmaceuticals Incorporated Pyridone amides as modulators of sodium channels
KR102226587B1 (en) 2013-01-31 2021-03-11 버텍스 파마슈티칼스 인코포레이티드 Quinoline and quinazoline amides as modulators of sodium channels
BR112015018318A2 (en) 2013-02-21 2017-08-22 Sunshine Lake Pharma Co Ltd COMPOUND, PHARMACEUTICAL COMPOSITION, USE OF A COMPOUND OR PHARMACEUTICAL COMPOSITION, AND, METHODS TO PREVENT, MANAGE, TREAT, OR DECREASE THE SEVERITY OF A PROLIFERATIVE DISORDER IN A PATIENT AND TO INHIBIT OR MODULATE THE ACTIVITY OF A PROTEIN KINASE IN A BIOLOGICAL SAMPLE
CA2905419C (en) 2013-03-12 2020-04-28 Micell Technologies, Inc. Bioabsorbable biomedical implants
WO2014150043A1 (en) 2013-03-15 2014-09-25 Concert Pharmaceuticals Inc. Inhibitors of the enzyme udp-glucose: n-acyl-sphingosine glucosyltransferase
EP3492470A1 (en) 2013-03-15 2019-06-05 Concert Pharmaceuticals, Inc. Deuterated palbociclib with improved metabolic stability
EA033168B1 (en) 2013-03-15 2019-09-30 Сайклерион Терапьютикс, Инк. STIMULATORS OF sGC
HU231191B1 (en) 2013-04-15 2021-08-30 Szegedi Tudományegyetem Isotope containing morphine molecules
AU2014256955B2 (en) 2013-04-25 2018-02-22 Innovative Surface Technologies, Inc. Coatings for controlled release of highly water soluble drugs
EP2815749A1 (en) 2013-06-20 2014-12-24 IP Gesellschaft für Management mbH Solid form of 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione having specified X-ray diffraction pattern
EP3021861A1 (en) 2013-07-18 2016-05-25 Anchor Therapeutics, Inc. Apj receptor compounds
WO2015009889A1 (en) 2013-07-18 2015-01-22 Concert Pharmaceuticals, Inc. Deuterated intedanib derivatives and their use for the treatment of proliferative disorders
RU2680401C2 (en) 2013-07-19 2019-02-21 Вертекс Фармасьютикалз Инкорпорейтед Sulfonamides as modulators of sodium channels
HUE050549T2 (en) 2013-07-22 2020-12-28 Metabolic Solutions Dev Co Llc Ppar-sparing compounds for the treatment of metabolic diseases
US9676790B2 (en) 2013-08-30 2017-06-13 Concert Pharmaceuticals, Inc. Substituted thienotriazolodiazapines
LT3068782T (en) 2013-11-13 2018-09-10 Vertex Pharmaceuticals Incorporated Methods of preparing inhibitors of influenza viruses replication
SG10201804026WA (en) 2013-11-13 2018-06-28 Vertex Pharma Inhibitors of influenza viruses replication
EP3092231B1 (en) 2013-12-11 2018-06-27 Ironwood Pharmaceuticals, Inc. Sgc stimulators
TWI703154B (en) 2013-12-13 2020-09-01 美商維泰克斯製藥公司 Prodrugs of pyridone amides useful as modulators of sodium channels
US20160324856A1 (en) 2014-01-13 2016-11-10 Ironwood Pharmaceuticals, Inc. Use of sgc stimulators for the treatment of neuromuscular disorders
JP6577479B2 (en) 2014-02-27 2019-09-18 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングMerck Patent Gesellschaft mit beschraenkter Haftung Heterocyclic compounds and their use as NAV channel inhibitors
SG10201913575VA (en) 2014-04-15 2020-02-27 Vertex Pharma Pharmaceutical compositions for the treatment of cystic fibrosis transmembrane conductance regulator mediated diseases
WO2015179772A1 (en) 2014-05-23 2015-11-26 Concert Pharmaceuticals, Inc. Deuterated phenylquinazolinone and phenylisoquinolinone compounds
CN106459004B (en) 2014-06-06 2020-09-15 研究三角协会 Apelin receptor (APJ) agonists and uses thereof
CN106535826A (en) 2014-06-24 2017-03-22 怡康医疗股份有限公司 Improved metal alloys for medical devices
MX2017003518A (en) 2014-09-17 2017-07-28 Ironwood Pharmaceuticals Inc Sgc stimulators.
US20170298055A1 (en) 2014-09-17 2017-10-19 Ironwood Pharmaceuticals, Inc. sGC STIMULATORS
WO2016044447A1 (en) 2014-09-17 2016-03-24 Ironwood Pharmaceuticals, Inc. Pyrazole derivatives as sgc stimulators
WO2016061488A1 (en) 2014-10-17 2016-04-21 Concert Pharmaceuticals, Inc. Amine reuptake inhibitors
WO2016073545A1 (en) 2014-11-06 2016-05-12 Concert Pharmaceuticals, Inc. Phenyloxadiazole benzoic acids
WO2016089814A1 (en) 2014-12-02 2016-06-09 Concert Pharmaceuticals, Inc. Deuterated analogues of daclatasvir
JP6815318B2 (en) 2014-12-23 2021-01-20 ダナ−ファーバー キャンサー インスティテュート,インコーポレイテッド How to Induce Targeted Proteolysis by Bifunctional Molecules
AR103636A1 (en) 2015-02-05 2017-05-24 Teva Pharmaceuticals Int Gmbh METHODS OF TREATMENT OF POSTERPEPTIC NEURALGY WITH A TOPICAL FORMULATION OF AN ESPIRO-OXINDOL COMPOUND
US9999527B2 (en) 2015-02-11 2018-06-19 Abbott Cardiovascular Systems Inc. Scaffolds having radiopaque markers
US20180044375A1 (en) 2015-03-06 2018-02-15 Concert Pharmaceuticals, Inc. Deuterated emricasan
WO2016144860A1 (en) 2015-03-06 2016-09-15 Ironwood Pharmaceuticals, Inc. Faah inhibitors for the treatment or prevention of nausea
WO2016160945A1 (en) 2015-03-31 2016-10-06 Concert Pharmaceuticals, Inc. Deuterated vx-661
WO2016176335A1 (en) 2015-04-27 2016-11-03 Concert Pharmaceuticals, Inc. Deuterated otx-015
WO2016183120A1 (en) 2015-05-13 2016-11-17 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
JP6704416B2 (en) 2015-05-13 2020-06-03 バーテックス ファーマシューティカルズ インコーポレイテッドVertex Pharmaceuticals Incorporated Methods for preparing inhibitors of influenza virus replication
US9700443B2 (en) 2015-06-12 2017-07-11 Abbott Cardiovascular Systems Inc. Methods for attaching a radiopaque marker to a scaffold
WO2017020005A1 (en) 2015-07-30 2017-02-02 Concert Pharmaceuticals, Inc. Morphinan compounds for use in treating agitation
US20180243289A1 (en) 2015-07-30 2018-08-30 Concert Pharmaceuticals, Inc. Deuterated morphinan compounds for treating agitation
WO2017024317A2 (en) 2015-08-06 2017-02-09 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
WO2017067447A1 (en) 2015-10-19 2017-04-27 Sunshine Lake Pharma Co., Ltd. A salt of egfr inhibitor, crystalline form and uses thereof
EP3377179B1 (en) 2015-11-19 2021-04-07 Concert Pharmaceuticals Inc. Deuterated epi-743
MX2018006979A (en) 2015-12-09 2019-05-16 Res Triangle Inst Improved apelin receptor (apj) agonists and uses thereof.
EA201891416A1 (en) 2015-12-14 2018-12-28 Айронвуд Фармасьютикалз, Инк. APPLICATION of sGC STIMULATORS FOR THE TREATMENT OF GASTRIC AND INTESTINAL SPINKLIN TREATMENT
EP3419682A4 (en) 2016-02-24 2019-11-13 Innovative Surface Technologies, Inc. Crystallization inhibitor compositions for implantable urological devices
WO2017147003A1 (en) 2016-02-26 2017-08-31 Novobiotic Pharmaceuticals, Llc Novel macrocyclic antibiotics and uses thereof
EP3423429B1 (en) 2016-03-03 2023-07-12 Universite De Moncton Modulators of lipoxygenase and cyclooxygenase enzyme activity
WO2017151548A1 (en) 2016-03-04 2017-09-08 Mirus Llc Stent device for spinal fusion
EP4122919A1 (en) 2016-07-04 2023-01-25 Avanir Pharmaceuticals, Inc. Methods for the synthesis of deuterated dextromethorphan
US11066447B2 (en) 2016-08-08 2021-07-20 AueroGen Biosciences, Inc. Aureobasidium derivatives and methods of synthesis
RS63872B1 (en) 2016-08-19 2023-02-28 Univ Bristol Cytisine derivatives for the treatment of addiction
PT3507291T (en) 2016-09-02 2021-08-30 Cyclerion Therapeutics Inc Fused bicyclic sgc stimulators
SG11201900602XA (en) 2016-09-19 2019-02-27 Biotronik Ag Polymer-free drug eluting vascular stents
US10543299B2 (en) 2016-10-03 2020-01-28 Microvention, Inc. Surface coatings
EA201991147A1 (en) 2016-11-08 2019-11-29 TREATMENT OF DISEASES OF THE CENTRAL NERVOUS SYSTEM USING sGC STIMULANTS
MA46755A (en) 2016-11-08 2021-06-02 Cyclerion Therapeutics Inc CMS STIMULATORS
WO2018111795A2 (en) 2016-12-13 2018-06-21 Ironwood Pharmaceuticals, Inc. Use of sgc stimulators for the treatment of esophageal motility disorders
US10772996B2 (en) 2017-02-09 2020-09-15 Med-El Elektromedizinische Geraete Gmbh Dexamethasone coating for use with electrode carrier
DK3592393T3 (en) 2017-03-10 2022-03-07 Quiapeg Pharmaceuticals Ab RELEASABLE CONJUGATES
US11439494B2 (en) * 2017-05-12 2022-09-13 Microvention, Inc. Medical devices
UA124857C2 (en) 2017-05-16 2021-12-01 Вертекс Фармасьютикалз Інкорпорейтед Deuterated pyridone amides and prodrugs thereof as modulators of sodium channels
US11278025B2 (en) 2017-05-17 2022-03-22 The General Hospital Corporation Antibiotic compounds
US20210137898A1 (en) 2017-06-15 2021-05-13 Mayo Foundation For Medical Education And Research Methods to treat gliomas using a stat3 inhibitor
US11396516B2 (en) 2017-06-16 2022-07-26 The General Hospital Corporation Tricyclic compounds as Cyp1 inhibitors
AU2018290246A1 (en) 2017-06-21 2020-01-30 Access Vascular, Inc High strength porous materials incorporating water soluble polymers
EP3651752A1 (en) 2017-07-11 2020-05-20 Vertex Pharmaceuticals Incorporated Carboxamides as modulators of sodium channels
WO2019079297A1 (en) 2017-10-16 2019-04-25 Dana-Farber Cancer Institute, Inc. Compounds and methods for treating cancer
CN107998458B (en) * 2017-12-22 2021-02-19 鼎科医疗技术(苏州)有限公司 Balloon drug coating and drug balloon
WO2019152733A1 (en) 2018-01-31 2019-08-08 Mayo Foundation For Medical Education And Research Methods of treating fibrotic pathologies
US11529337B2 (en) 2018-02-12 2022-12-20 Vertex Pharmaceuticals Incorporated Method of treating pain
US10874775B2 (en) 2018-04-05 2020-12-29 Stephen Kuperberg Method and apparatus for a stent with a capped-release mechanism (CRM)
CA3104521A1 (en) 2018-07-05 2020-01-09 Mayo Foundation For Medical Education And Research Pikfyve inhibitors
US11666681B2 (en) 2018-08-13 2023-06-06 Ethicon, Inc. Abradable therapeutic coatings and devices including such coatings
JP2021535920A (en) 2018-09-12 2021-12-23 キアペグ ファーマシューティカルズ アクチエボラグ Emissible GLP-1 conjugate
US11628466B2 (en) 2018-11-29 2023-04-18 Surmodics, Inc. Apparatus and methods for coating medical devices
US20200230295A1 (en) * 2018-12-19 2020-07-23 Access Vascular, Inc. High strength porous materials for controlled release
US20220112218A1 (en) 2019-01-03 2022-04-14 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Methods and materials for increasing transcription factor eb polypeptide levels
US20230062053A1 (en) 2019-01-10 2023-03-02 Vertex Pharmaceuticals Incorporated Carboxamides as modulators of sodium channels
US20220110923A1 (en) 2019-01-10 2022-04-14 Vertex Pharmaceuticals Incorporated Esters and carbamates as modulators of sodium channels
DE102019108190A1 (en) 2019-03-29 2020-10-01 Karl Leibinger Medizintechnik Gmbh & Co. Kg Implant made from carrier material interspersed with biologically active donor material and process for its production
US11819590B2 (en) 2019-05-13 2023-11-21 Surmodics, Inc. Apparatus and methods for coating medical devices
KR20220041847A (en) 2019-07-30 2022-04-01 메이오 파운데이션 포 메디칼 에쥬케이션 앤드 리써치 Compounds and methods for treating fibrotic pathology
IL293592A (en) 2019-12-06 2022-08-01 Vertex Pharma Substituted tetrahydrofurans as modulators of sodium channels
CA3221788A1 (en) 2021-06-04 2022-12-08 Vertex Pharmaceuticals Incorporated Substituted tetrahydrofuran-2-carboxamides as modulators of sodium channels
CA3221960A1 (en) 2021-06-04 2022-12-08 Vertex Pharmaceuticals Incorporated Hydroxy and (halo)alkoxy substituted tetrahydrofurans as modulators of sodium channels
AU2022286438A1 (en) 2021-06-04 2023-11-30 Vertex Pharmaceuticals Incorporated N-(hydroxyalkyl (hetero)aryl) tetrahydrofuran carboxamide analogs as modulators of sodium channels
AU2022284886A1 (en) 2021-06-04 2023-11-30 Vertex Pharmaceuticals Incorporated N-(hydroxyalkyl (hetero)aryl) tetrahydrofuran carboxamides as modulators of sodium channels
WO2022256708A1 (en) 2021-06-04 2022-12-08 Vertex Pharmaceuticals Incorporated Solid dosage forms and dosing regimens comprising (2r,3s,4s,5r)-4-[[3-(3,4-difluoro-2-methoxy-phenyl)-4,5-dimethyl-5-(trifluoromethyl) tetrahydrofuran-2-carbonyl]amino]pyridine-2-carboxamide
WO2022256676A1 (en) 2021-06-04 2022-12-08 Vertex Pharmaceuticals Incorporated Substituted tetrahydrofuran analogs as modulators of sodium channels
WO2022265984A1 (en) 2021-06-14 2022-12-22 Curtails Llc Use of nep inhibitors for the treatment of gastrointestinal sphincter disorders
WO2023018795A1 (en) 2021-08-11 2023-02-16 Curtails Llc Nep inhibitors for the treatment of laminitis
WO2023039276A1 (en) 2021-09-13 2023-03-16 Curtails Llc Use of ibat inhibitors and antimicrobials for the treatment of diseases
WO2023205465A1 (en) 2022-04-22 2023-10-26 Vertex Pharmaceuticals Incorporated Heteroaryl compounds for the treatment of pain
US20230382910A1 (en) 2022-04-22 2023-11-30 Vertex Pharmaceuticals Incorporated Heteroaryl compounds for the treatment of pain
WO2023205468A1 (en) 2022-04-22 2023-10-26 Vertex Pharmaceuticals Incorporated Heteroaryl compounds for the treatment of pain
WO2023205463A1 (en) 2022-04-22 2023-10-26 Vertex Pharmaceuticals Incorporated Heteroaryl compounds for the treatment of pain

Citations (92)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US478500A (en) * 1892-07-05 clark
US3279996A (en) * 1962-08-28 1966-10-18 Jr David M Long Polysiloxane carrier for controlled release of drugs and other agents
US3526005A (en) * 1967-06-29 1970-09-01 Gulf General Atomic Inc Method of preparing an intravascular defect by implanting a pyrolytic carbon coated prosthesis
US3738365A (en) * 1969-07-22 1973-06-12 R Schulte Spring reinforced extensible catheter
US3879516A (en) * 1972-12-07 1975-04-22 Technibiotics Method of constructing a catheter
US3932627A (en) * 1974-02-04 1976-01-13 Rescue Products, Inc. Siver-heparin-allantoin complex
US3952334A (en) * 1974-11-29 1976-04-27 General Atomic Company Biocompatible carbon prosthetic devices
US4219520A (en) * 1978-08-30 1980-08-26 Medical Evaluation Devices And Instruments Corp. Method of making thrombo-resistant non-thrombogenic objects formed from a uniform mixture of a particulate resin and colloidal graphite
US4292965A (en) * 1978-12-29 1981-10-06 The Population Council, Inc. Intravaginal ring
US4613665A (en) * 1982-02-09 1986-09-23 Olle Larm Process for covalent coupling for the production of conjugates, and polysaccharide containing products thereby obtained
US4655771A (en) * 1982-04-30 1987-04-07 Shepherd Patents S.A. Prosthesis comprising an expansible or contractile tubular body
US4656083A (en) * 1983-08-01 1987-04-07 Washington Research Foundation Plasma gas discharge treatment for improving the biocompatibility of biomaterials
US4678466A (en) * 1981-06-25 1987-07-07 Rosenwald Peter L Internal medication delivery method and vehicle
US4687482A (en) * 1984-04-27 1987-08-18 Scripps Clinic And Research Foundation Vascular prosthesis
US4689046A (en) * 1985-03-11 1987-08-25 Carbomedics, Inc. Heart valve prosthesis
US4739762A (en) * 1985-11-07 1988-04-26 Expandable Grafts Partnership Expandable intraluminal graft, and method and apparatus for implanting an expandable intraluminal graft
US4753652A (en) * 1984-05-04 1988-06-28 Children's Medical Center Corporation Biomaterial implants which resist calcification
US4768507A (en) * 1986-02-24 1988-09-06 Medinnovations, Inc. Intravascular stent and percutaneous insertion catheter system for the dilation of an arterial stenosis and the prevention of arterial restenosis
US4872867A (en) * 1985-06-19 1989-10-10 Ube Industries, Ltd. Compositions having antithrombogenic properties and blood contact medical devices using the same
US4894231A (en) * 1987-07-28 1990-01-16 Biomeasure, Inc. Therapeutic agent delivery system
US4916193A (en) * 1987-12-17 1990-04-10 Allied-Signal Inc. Medical devices fabricated totally or in part from copolymers of recurring units derived from cyclic carbonates and lactides
US4922905A (en) * 1985-11-30 1990-05-08 Strecker Ernst P Dilatation catheter
US4990158A (en) * 1989-05-10 1991-02-05 United States Surgical Corporation Synthetic semiabsorbable tubular prosthesis
US4994071A (en) * 1989-05-22 1991-02-19 Cordis Corporation Bifurcating stent apparatus and method
US5019096A (en) * 1988-02-11 1991-05-28 Trustees Of Columbia University In The City Of New York Infection-resistant compositions, medical devices and surfaces and methods for preparing and using same
US5034265A (en) * 1983-08-01 1991-07-23 Washington Research Foundation Plasma gas discharge treatment for improving the compatibility of biomaterials
US5053048A (en) * 1988-09-22 1991-10-01 Cordis Corporation Thromboresistant coating
US5059166A (en) * 1989-12-11 1991-10-22 Medical Innovative Technologies R & D Limited Partnership Intra-arterial stent with the capability to inhibit intimal hyperplasia
US5061275A (en) * 1986-04-21 1991-10-29 Medinvent S.A. Self-expanding prosthesis
US5092877A (en) * 1988-09-01 1992-03-03 Corvita Corporation Radially expandable endoprosthesis
US5102417A (en) * 1985-11-07 1992-04-07 Expandable Grafts Partnership Expandable intraluminal graft, and method and apparatus for implanting an expandable intraluminal graft
US5180376A (en) * 1990-05-01 1993-01-19 Cathco, Inc. Non-buckling thin-walled sheath for the percutaneous insertion of intraluminal catheters
US5180366A (en) * 1990-10-10 1993-01-19 Woods W T Apparatus and method for angioplasty and for preventing re-stenosis
US5182317A (en) * 1988-06-08 1993-01-26 Cardiopulmonics, Inc. Multifunctional thrombo-resistant coatings and methods of manufacture
US5185408A (en) * 1987-12-17 1993-02-09 Allied-Signal Inc. Medical devices fabricated totally or in part from copolymers of recurring units derived from cyclic carbonates and lactides
US5192308A (en) * 1991-04-19 1993-03-09 E. I. Du Pont De Nemours And Company Vascular prosthesis with an elastomer coating
US5199951A (en) * 1990-05-17 1993-04-06 Wayne State University Method of drug application in a transporting medium to an arterial wall injured during angioplasty
US5222971A (en) * 1990-10-09 1993-06-29 Scimed Life Systems, Inc. Temporary stent and methods for use and manufacture
US5226913A (en) * 1988-09-01 1993-07-13 Corvita Corporation Method of making a radially expandable prosthesis
US5282823A (en) * 1992-03-19 1994-02-01 Medtronic, Inc. Intravascular radially expandable stent
US5288711A (en) * 1992-04-28 1994-02-22 American Home Products Corporation Method of treating hyperproliferative vascular disease
US5292802A (en) * 1988-11-21 1994-03-08 Collagen Corporation Collagen-polymer tubes for use in vascular surgery
US5304121A (en) * 1990-12-28 1994-04-19 Boston Scientific Corporation Drug delivery system making use of a hydrogel polymer coating
US5318779A (en) * 1988-01-30 1994-06-07 Olympus Optical Co., Ltd. Drug-impregnated ceramic
US5338770A (en) * 1988-06-08 1994-08-16 Cardiopulmonics, Inc. Gas permeable thrombo-resistant coatings and methods of manufacture
US5342348A (en) * 1992-12-04 1994-08-30 Kaplan Aaron V Method and device for treating and enlarging body lumens
US5344411A (en) * 1991-02-27 1994-09-06 Leonard Bloom Method and device for inhibiting HIV, hepatitis B and other viruses and germs when using a catheter in a medical environment
US5356433A (en) * 1991-08-13 1994-10-18 Cordis Corporation Biocompatible metal surfaces
US5378475A (en) * 1991-02-21 1995-01-03 University Of Kentucky Research Foundation Sustained release drug delivery devices
US5380299A (en) * 1993-08-30 1995-01-10 Med Institute, Inc. Thrombolytic treated intravascular medical device
US5383928A (en) * 1992-06-10 1995-01-24 Emory University Stent sheath for local drug delivery
US5391378A (en) * 1993-02-22 1995-02-21 Elizabeth-Hata International, Inc. Two-part medicinal tablet and method of manufacture
US5399352A (en) * 1993-04-14 1995-03-21 Emory University Device for local drug delivery and methods for using the same
US5415619A (en) * 1989-12-13 1995-05-16 Korea Research Institute Of Chemical Tech. Method of manufacturing a vascular graft impregnated with polysaccharide derivatives
US5419760A (en) * 1993-01-08 1995-05-30 Pdt Systems, Inc. Medicament dispensing stent for prevention of restenosis of a blood vessel
US5429618A (en) * 1992-10-30 1995-07-04 Medtronic, Inc. Thromboresistant articles
US5443500A (en) * 1989-01-26 1995-08-22 Advanced Cardiovascular Systems, Inc. Intravascular stent
US5447724A (en) * 1990-05-17 1995-09-05 Harbor Medical Devices, Inc. Medical device polymer
US5449382A (en) * 1992-11-04 1995-09-12 Dayton; Michael P. Minimally invasive bioactivated endoprosthesis for vessel repair
US5486357A (en) * 1990-11-08 1996-01-23 Cordis Corporation Radiofrequency plasma biocompatibility treatment of inside surfaces
US5492895A (en) * 1992-02-14 1996-02-20 Corvas International, Inc. Inhibitors of thrombosis
US5496557A (en) * 1990-01-30 1996-03-05 Akzo N.V. Article for the controlled delivery of an active substance, comprising a hollow space fully enclosed by a wall and filled in full or in part with one or more active substances
US5500013A (en) * 1991-10-04 1996-03-19 Scimed Life Systems, Inc. Biodegradable drug delivery vascular stent
US5510077A (en) * 1992-03-19 1996-04-23 Dinh; Thomas Q. Method of making an intraluminal stent
US5512055A (en) * 1991-02-27 1996-04-30 Leonard Bloom Anti-infective and anti-inflammatory releasing systems for medical devices
US5523092A (en) * 1993-04-14 1996-06-04 Emory University Device for local drug delivery and methods for using the same
US5545208A (en) * 1990-02-28 1996-08-13 Medtronic, Inc. Intralumenal drug eluting prosthesis
US5551954A (en) * 1991-10-04 1996-09-03 Scimed Life Systems, Inc. Biodegradable drug delivery vascular stent
US5591227A (en) * 1992-03-19 1997-01-07 Medtronic, Inc. Drug eluting stent
US5591224A (en) * 1992-03-19 1997-01-07 Medtronic, Inc. Bioelastomeric stent
US5605696A (en) * 1995-03-30 1997-02-25 Advanced Cardiovascular Systems, Inc. Drug loaded polymeric material and method of manufacture
US5607463A (en) * 1993-03-30 1997-03-04 Medtronic, Inc. Intravascular medical device
US5609629A (en) * 1995-06-07 1997-03-11 Med Institute, Inc. Coated implantable medical device
US5624411A (en) * 1993-04-26 1997-04-29 Medtronic, Inc. Intravascular stent and method
US5629077A (en) * 1994-06-27 1997-05-13 Advanced Cardiovascular Systems, Inc. Biodegradable mesh and film stent
US5632840A (en) * 1994-09-22 1997-05-27 Advanced Cardiovascular System, Inc. Method of making metal reinforced polymer stent
US5637113A (en) * 1994-12-13 1997-06-10 Advanced Cardiovascular Systems, Inc. Polymer film for wrapping a stent structure
US5643580A (en) * 1994-10-17 1997-07-01 Surface Genesis, Inc. Biocompatible coating, medical device using the same and methods
US5662712A (en) * 1993-04-28 1997-09-02 Focal, Inc. Apparatus for intraluminal photothermoforming
US5716981A (en) * 1993-07-19 1998-02-10 Angiogenesis Technologies, Inc. Anti-angiogenic compositions and methods of use
US5722984A (en) * 1996-01-16 1998-03-03 Iso Stent, Inc. Antithrombogenic radioactive coating for an intravascular stent
US5735897A (en) * 1993-10-19 1998-04-07 Scimed Life Systems, Inc. Intravascular stent pump
US5749915A (en) * 1988-08-24 1998-05-12 Focal, Inc. Polymeric endoluminal paving process
US5779732A (en) * 1997-03-31 1998-07-14 Medtronic, Inc. Method and apparatus for implanting a film with an exandable stent
US5877224A (en) * 1995-07-28 1999-03-02 Rutgers, The State University Of New Jersey Polymeric drug formulations
US5879034A (en) * 1997-10-17 1999-03-09 Johns; Ernest W. Automatic locking device
US5900246A (en) * 1993-03-18 1999-05-04 Cedars-Sinai Medical Center Drug incorporating and releasing polymeric coating for bioprosthesis
US6042875A (en) * 1997-04-30 2000-03-28 Schneider (Usa) Inc. Drug-releasing coatings for medical devices
US6099562A (en) * 1996-06-13 2000-08-08 Schneider (Usa) Inc. Drug coating with topcoat
US6110483A (en) * 1997-06-23 2000-08-29 Sts Biopolymers, Inc. Adherent, flexible hydrogel and medicated coatings
US6120536A (en) * 1995-04-19 2000-09-19 Schneider (Usa) Inc. Medical devices with long term non-thrombogenic coatings
US6198016B1 (en) * 1998-12-01 2001-03-06 3M Innovative Properties Company Wet skin adhesive article

Family Cites Families (87)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3168565A (en) * 1959-11-20 1965-02-02 Richardson Merrell Inc Trifluoromethyl derivatives of amino triarylethanols, -ethanes, and -ethylenes
US3634517A (en) * 1968-08-19 1972-01-11 Richardson Merrell Inc Triarylalkenones
US5082834A (en) * 1978-05-30 1992-01-21 Sorensen John R J Anti-inflammatory and anti-ulcer compounds and process
JPS5640710B2 (en) * 1973-01-18 1981-09-22
US4070484A (en) * 1973-01-18 1978-01-24 Kissei Pharmaceutical Co., Ltd. Antiallergic composition containing aromatic carboxylic amide derivatives and method of using the same
US4133814A (en) * 1975-10-28 1979-01-09 Eli Lilly And Company 2-Phenyl-3-aroylbenzothiophenes useful as antifertility agents
US4317915A (en) * 1976-08-23 1982-03-02 Hoffmann-La Roche Inc. Novel thiophene derivatives
US4428963A (en) * 1976-08-23 1984-01-31 Hoffmann-La Roche Inc. Novel thiophene derivatives
DE2817157A1 (en) * 1978-04-17 1979-10-25 Schering Ag USE OF ANTIOESTROGEN AND ANTIGONADOTROP ACTING ANTIANDROGEN FOR PROPHYLAXIS AND THERAPY OF PROSTATE HYPERPLASIA
US4732763A (en) * 1978-10-17 1988-03-22 Stolle Research And Development Corporation Active/passive immunization of the internal female reproductive organs
US4315028A (en) * 1978-12-22 1982-02-09 Scheinberg Israel H Method of treatment of rheumatoid arthritis
GB2126576B (en) * 1982-06-25 1985-06-19 Farmos Group Limited Alkane and alkene derivatives
US5491173A (en) * 1982-06-25 1996-02-13 Orion-Yhtyma Oy Tri-phenyl alkene derivatives and their preparation and use
US5705477A (en) * 1982-09-24 1998-01-06 The United States Of America As Represented By The Department Of Health And Human Services Compositions of transforming growth factor β(TGF-β) which promotes wound healing and methods for their use
US4577636A (en) * 1982-11-23 1986-03-25 The Beth Israel Hospital Association Method for diagnosis of atherosclerosis
US4491574A (en) * 1983-03-02 1985-01-01 Albert Einstein College Of Medicine Of Yeshiva University, A Division Of Yeshiva University Reduction of high dose aspirin toxicity by dietary vitamin A
US4897255A (en) * 1985-01-14 1990-01-30 Neorx Corporation Metal radionuclide labeled proteins for diagnosis and therapy
US5284763A (en) * 1985-03-22 1994-02-08 Genentech, Inc. Nucleic acid encoding TGF-β and its uses
US4744981A (en) * 1985-10-17 1988-05-17 Neorx Corporation Trichothecene antibody conjugates
US4999347A (en) * 1986-08-28 1991-03-12 Sorenson John R J Analgesic method
US4994384A (en) * 1986-12-31 1991-02-19 W. R. Grace & Co.-Conn. Multiplying bovine embryos
US4886062A (en) * 1987-10-19 1989-12-12 Medtronic, Inc. Intravascular radially expandable stent and method of implant
US4997652A (en) * 1987-12-22 1991-03-05 Visionex Biodegradable ocular implants
US5262451A (en) * 1988-06-08 1993-11-16 Cardiopulmonics, Inc. Multifunctional thrombo-resistant coatings and methods of manufacture
US5705609A (en) * 1988-06-28 1998-01-06 La Jolla Cancer Research Foundation Decorin fragments inhibiting cell regulatory factors
US5393785A (en) * 1988-10-31 1995-02-28 Endorecherche, Inc. Therapeutic antiestrogens
US5380716A (en) * 1988-12-15 1995-01-10 Glycomed, Inc. Sulfated polysaccharides as inhibitors of smooth muscle cell proliferation
US4900561A (en) * 1989-01-03 1990-02-13 Zinpro Corporation Copper complexes of alpha-amino acids that contain terminal amino groups, and their use as nutritional supplements
US5284869A (en) * 1991-12-17 1994-02-08 Emil Bisaccia Photophoresis methods for treating atherosclerosis and for preventing restenosis following angioplasty
US5288735A (en) * 1989-05-02 1994-02-22 Trager Seymour F Treatment of glaucoma
US4994033A (en) * 1989-05-25 1991-02-19 Schneider (Usa) Inc. Intravascular drug delivery dilatation catheter
US4990538A (en) * 1989-08-23 1991-02-05 Harris Adrian L Use of toremifene and its metabolites for the reversal of multidrug resistance of cancer cells against cytotoxic drugs
IL95500A (en) * 1989-09-11 1997-03-18 Matrix Pharma ANTI-PROLIFERATIVE COMPOSITIONS CONTAINING TGF-b PROTEIN IN A VISCOUS MATRIX AND THEIR USE
US4984594A (en) * 1989-10-27 1991-01-15 Shell Oil Company Vacuum method for removing soil contamination utilizing surface electrical heating
US5176617A (en) * 1989-12-11 1993-01-05 Medical Innovative Technologies R & D Limited Partnership Use of a stent with the capability to inhibit malignant growth in a vessel such as a biliary duct
JPH05502179A (en) * 1990-02-28 1993-04-22 メドトロニック インコーポレーテッド Tubular organ drug elution device
US5123917A (en) * 1990-04-27 1992-06-23 Lee Peter Y Expandable intraluminal vascular graft
WO1991019529A1 (en) * 1990-06-15 1991-12-26 Cortrak Medical, Inc. Drug delivery apparatus and method
US5189046A (en) * 1990-08-14 1993-02-23 Nova Pharmaceutical Corporation Protein kinase C modulators
US5189212A (en) * 1990-09-07 1993-02-23 University Of Georgia Research Foundation, Inc. Triarylethylene carboxylic acids with estrogenic activity
US5258020A (en) * 1990-09-14 1993-11-02 Michael Froix Method of using expandable polymeric stent with memory
US5163952A (en) * 1990-09-14 1992-11-17 Michael Froix Expandable polymeric stent with memory and delivery apparatus and method
US5280016A (en) * 1991-03-29 1994-01-18 Glycomed Incorporated Non-anticoagulant heparin derivatives
DE4115819A1 (en) * 1991-05-15 1992-11-19 Schloemann Siemag Ag METHOD FOR TREATMENT OF COOLING AND / OR LUBRICANTS USED IN ROLLING MILLS, AND A TREATMENT SYSTEM FOR THIS
US5185260A (en) * 1991-08-29 1993-02-09 The United States Of America As Represented By The United States Department Of Energy Method for distinguishing normal and transformed cells using G1 kinase inhibitors
US5811447A (en) * 1993-01-28 1998-09-22 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US6515009B1 (en) * 1991-09-27 2003-02-04 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
CA2079417C (en) * 1991-10-28 2003-01-07 Lilip Lau Expandable stents and method of making same
CA2126465C (en) * 1992-01-17 2002-03-05 Kazuhisa Kodama Inhibitor for restenosis after percutaneous coronary arterioplasty
US5280109A (en) * 1992-01-27 1994-01-18 Ludwig Institute For Cancer Research Isolated, large latent complexes of TGF-β2 and TGF-β3, and new binding protein for latent form TGF-β1, TGF-β2 and TGF-β3 LTBP-2
DE69326631T2 (en) * 1992-03-19 2000-06-08 Medtronic Inc Intraluminal expansion device
GB9207437D0 (en) * 1992-04-03 1992-05-20 Orion Yhtymae Oy Topical administration of toremifene and its metabolites
US5283257A (en) * 1992-07-10 1994-02-01 The Board Of Trustees Of The Leland Stanford Junior University Method of treating hyperproliferative vascular disease
TW366342B (en) * 1992-07-28 1999-08-11 Lilly Co Eli The use of 2-phenyl-3-aroylbenzothiophenes in inhibiting bone loss
JP2617407B2 (en) * 1992-09-14 1997-06-04 キッセイ薬品工業株式会社 Preventive and therapeutic agent for intimal cell hyperproliferative disease
US6491938B2 (en) * 1993-05-13 2002-12-10 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US5595722A (en) * 1993-01-28 1997-01-21 Neorx Corporation Method for identifying an agent which increases TGF-beta levels
US5451603A (en) * 1993-03-11 1995-09-19 Zymogenetics, Inc. 3,4-diarylchromans for treatment of dermatitis
US5280040A (en) * 1993-03-11 1994-01-18 Zymogenetics, Inc. Methods for reducing bone loss using centchroman derivatives
US5482949A (en) * 1993-03-19 1996-01-09 Eli Lilly And Company Sulfonate derivatives of 3-aroylbenzo[b]thiophenes
BE1006819A7 (en) * 1993-03-24 1994-12-13 Dsb Nv Polyurethane coated prostheses (stents) FOR THE TREATMENT OF VESSEL CHOKES.
WO1994026303A1 (en) * 1993-05-13 1994-11-24 Neorx Corporation Prevention and treatment of pathologies associated with abnormally proliferative smooth muscle cells
US5387680A (en) * 1993-08-10 1995-02-07 American Home Products Corporation C-22 ring stabilized rapamycin derivatives
US5457113A (en) * 1993-10-15 1995-10-10 Eli Lilly And Company Methods for inhibiting vascular smooth muscle cell proliferation and restinosis
US5391557A (en) * 1993-10-15 1995-02-21 Eli Lilly And Company Methods for the treatment of peri-menopausal syndrome
US5482950A (en) * 1993-10-15 1996-01-09 Eli Lilly And Company Methods for lowering serum cholesterol
US5480904A (en) * 1993-10-28 1996-01-02 Eli Lilly And Company Methods for inhibiting uterine fibrosis
US5393772A (en) * 1993-11-24 1995-02-28 Boehringer Mannheim Pharmaceuticals Corporation Use of, and method of treatment using, hydroxycarbazole compounds for inhibition of smooth muscle migration and proliferation
HU213407B (en) * 1993-12-09 1997-06-30 Egyt Gyogyszervegyeszeti Gyar Process for producing tablet with diffusive-osmotic release
US5389670A (en) * 1993-12-21 1995-02-14 Eli Lilly Company Methods of inhibiting the symptoms of premenstrual syndrome/late luteal phase dysphoric disorder
US5492927A (en) * 1993-12-21 1996-02-20 Eli Lilly And Company Non-peptide tachykinin receptor antagonists to treat allergy
US5384332A (en) * 1994-05-11 1995-01-24 Eli Lilly And Company Methods for inhibiting aortal smooth muscle cell proliferation and restenosis with 1,1,2-triphenylbut-1-ene derivatives
DE4422336A1 (en) * 1994-06-27 1996-01-04 Basf Ag Use of leukotriarylmethanes for marking hydrocarbons
US5491159A (en) * 1994-08-30 1996-02-13 American Home Products Corporation 2-(3,5-di-tert-butyl-4-hydroxy-phenyl)-oxazoles as anti-atherosclerotic agents
US7501441B1 (en) * 1994-09-20 2009-03-10 Eli Lilly And Company Naphthyl compounds, intermediates, processes, compositions, and methods
US5484798A (en) * 1994-09-20 1996-01-16 Eli Lilly And Company Benzothiopene compounds, compositions, and method of inhibiting restenosis
US5489587A (en) * 1995-01-20 1996-02-06 Eli Lilly And Company Benzofurans used to inhibit bone loss
US5484808A (en) * 1995-02-09 1996-01-16 Eli Lilly And Company Methods of inhibiting cell-cell adhesion
US5510357A (en) * 1995-02-28 1996-04-23 Eli Lilly And Company Benzothiophene compounds as anti-estrogenic agents
CA2216943C (en) 1995-04-19 2003-06-17 Schneider (Usa) Inc. Drug release coated stent
US5837313A (en) * 1995-04-19 1998-11-17 Schneider (Usa) Inc Drug release stent coating process
US5820917A (en) * 1995-06-07 1998-10-13 Medtronic, Inc. Blood-contacting medical device and method
AU716005B2 (en) * 1995-06-07 2000-02-17 Cook Medical Technologies Llc Implantable medical device
US5980972A (en) * 1996-12-20 1999-11-09 Schneider (Usa) Inc Method of applying drug-release coatings
US5824054A (en) * 1997-03-18 1998-10-20 Endotex Interventional Systems, Inc. Coiled sheet graft stent and methods of making and use
US6013099A (en) * 1998-04-29 2000-01-11 Medtronic, Inc. Medical device for delivering a water-insoluble therapeutic salt or substance
US6168619B1 (en) * 1998-10-16 2001-01-02 Quanam Medical Corporation Intravascular stent having a coaxial polymer member and end sleeves

Patent Citations (103)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US478500A (en) * 1892-07-05 clark
US3279996A (en) * 1962-08-28 1966-10-18 Jr David M Long Polysiloxane carrier for controlled release of drugs and other agents
US3526005A (en) * 1967-06-29 1970-09-01 Gulf General Atomic Inc Method of preparing an intravascular defect by implanting a pyrolytic carbon coated prosthesis
US3738365A (en) * 1969-07-22 1973-06-12 R Schulte Spring reinforced extensible catheter
US3879516A (en) * 1972-12-07 1975-04-22 Technibiotics Method of constructing a catheter
US3932627A (en) * 1974-02-04 1976-01-13 Rescue Products, Inc. Siver-heparin-allantoin complex
US3952334A (en) * 1974-11-29 1976-04-27 General Atomic Company Biocompatible carbon prosthetic devices
US4219520A (en) * 1978-08-30 1980-08-26 Medical Evaluation Devices And Instruments Corp. Method of making thrombo-resistant non-thrombogenic objects formed from a uniform mixture of a particulate resin and colloidal graphite
US4292965A (en) * 1978-12-29 1981-10-06 The Population Council, Inc. Intravaginal ring
US4678466A (en) * 1981-06-25 1987-07-07 Rosenwald Peter L Internal medication delivery method and vehicle
US4613665A (en) * 1982-02-09 1986-09-23 Olle Larm Process for covalent coupling for the production of conjugates, and polysaccharide containing products thereby obtained
US4655771A (en) * 1982-04-30 1987-04-07 Shepherd Patents S.A. Prosthesis comprising an expansible or contractile tubular body
US4954126A (en) * 1982-04-30 1990-09-04 Shepherd Patents S.A. Prosthesis comprising an expansible or contractile tubular body
US4655771B1 (en) * 1982-04-30 1996-09-10 Medinvent Ams Sa Prosthesis comprising an expansible or contractile tubular body
US4954126B1 (en) * 1982-04-30 1996-05-28 Ams Med Invent S A Prosthesis comprising an expansible or contractile tubular body
US5034265A (en) * 1983-08-01 1991-07-23 Washington Research Foundation Plasma gas discharge treatment for improving the compatibility of biomaterials
US4656083A (en) * 1983-08-01 1987-04-07 Washington Research Foundation Plasma gas discharge treatment for improving the biocompatibility of biomaterials
US4687482A (en) * 1984-04-27 1987-08-18 Scripps Clinic And Research Foundation Vascular prosthesis
US4753652A (en) * 1984-05-04 1988-06-28 Children's Medical Center Corporation Biomaterial implants which resist calcification
US4689046A (en) * 1985-03-11 1987-08-25 Carbomedics, Inc. Heart valve prosthesis
US4872867A (en) * 1985-06-19 1989-10-10 Ube Industries, Ltd. Compositions having antithrombogenic properties and blood contact medical devices using the same
US4739762A (en) * 1985-11-07 1988-04-26 Expandable Grafts Partnership Expandable intraluminal graft, and method and apparatus for implanting an expandable intraluminal graft
US5102417A (en) * 1985-11-07 1992-04-07 Expandable Grafts Partnership Expandable intraluminal graft, and method and apparatus for implanting an expandable intraluminal graft
US4776337B1 (en) * 1985-11-07 2000-12-05 Cordis Corp Expandable intraluminal graft and method and apparatus for implanting an expandable intraluminal graft
US4776337A (en) * 1985-11-07 1988-10-11 Expandable Grafts Partnership Expandable intraluminal graft, and method and apparatus for implanting an expandable intraluminal graft
US4739762B1 (en) * 1985-11-07 1998-10-27 Expandable Grafts Partnership Expandable intraluminal graft and method and apparatus for implanting an expandable intraluminal graft
US4922905A (en) * 1985-11-30 1990-05-08 Strecker Ernst P Dilatation catheter
US4768507A (en) * 1986-02-24 1988-09-06 Medinnovations, Inc. Intravascular stent and percutaneous insertion catheter system for the dilation of an arterial stenosis and the prevention of arterial restenosis
US5061275A (en) * 1986-04-21 1991-10-29 Medinvent S.A. Self-expanding prosthesis
US4894231A (en) * 1987-07-28 1990-01-16 Biomeasure, Inc. Therapeutic agent delivery system
US4916193A (en) * 1987-12-17 1990-04-10 Allied-Signal Inc. Medical devices fabricated totally or in part from copolymers of recurring units derived from cyclic carbonates and lactides
US5185408A (en) * 1987-12-17 1993-02-09 Allied-Signal Inc. Medical devices fabricated totally or in part from copolymers of recurring units derived from cyclic carbonates and lactides
US5318779A (en) * 1988-01-30 1994-06-07 Olympus Optical Co., Ltd. Drug-impregnated ceramic
US5019096A (en) * 1988-02-11 1991-05-28 Trustees Of Columbia University In The City Of New York Infection-resistant compositions, medical devices and surfaces and methods for preparing and using same
US5338770A (en) * 1988-06-08 1994-08-16 Cardiopulmonics, Inc. Gas permeable thrombo-resistant coatings and methods of manufacture
US5182317A (en) * 1988-06-08 1993-01-26 Cardiopulmonics, Inc. Multifunctional thrombo-resistant coatings and methods of manufacture
US5749915A (en) * 1988-08-24 1998-05-12 Focal, Inc. Polymeric endoluminal paving process
US5226913A (en) * 1988-09-01 1993-07-13 Corvita Corporation Method of making a radially expandable prosthesis
US5092877A (en) * 1988-09-01 1992-03-03 Corvita Corporation Radially expandable endoprosthesis
US5053048A (en) * 1988-09-22 1991-10-01 Cordis Corporation Thromboresistant coating
US5308889A (en) * 1988-11-21 1994-05-03 Collagen Corporation Dehydrated collagen-polymer strings
US5292802A (en) * 1988-11-21 1994-03-08 Collagen Corporation Collagen-polymer tubes for use in vascular surgery
US5443500A (en) * 1989-01-26 1995-08-22 Advanced Cardiovascular Systems, Inc. Intravascular stent
US4990158A (en) * 1989-05-10 1991-02-05 United States Surgical Corporation Synthetic semiabsorbable tubular prosthesis
US4994071A (en) * 1989-05-22 1991-02-19 Cordis Corporation Bifurcating stent apparatus and method
US5059166A (en) * 1989-12-11 1991-10-22 Medical Innovative Technologies R & D Limited Partnership Intra-arterial stent with the capability to inhibit intimal hyperplasia
US5415619A (en) * 1989-12-13 1995-05-16 Korea Research Institute Of Chemical Tech. Method of manufacturing a vascular graft impregnated with polysaccharide derivatives
US5496557A (en) * 1990-01-30 1996-03-05 Akzo N.V. Article for the controlled delivery of an active substance, comprising a hollow space fully enclosed by a wall and filled in full or in part with one or more active substances
US5545208A (en) * 1990-02-28 1996-08-13 Medtronic, Inc. Intralumenal drug eluting prosthesis
US5180376A (en) * 1990-05-01 1993-01-19 Cathco, Inc. Non-buckling thin-walled sheath for the percutaneous insertion of intraluminal catheters
US5569463A (en) * 1990-05-17 1996-10-29 Harbor Medical Devices, Inc. Medical device polymer
US5199951A (en) * 1990-05-17 1993-04-06 Wayne State University Method of drug application in a transporting medium to an arterial wall injured during angioplasty
US5447724A (en) * 1990-05-17 1995-09-05 Harbor Medical Devices, Inc. Medical device polymer
US5222971A (en) * 1990-10-09 1993-06-29 Scimed Life Systems, Inc. Temporary stent and methods for use and manufacture
US5180366A (en) * 1990-10-10 1993-01-19 Woods W T Apparatus and method for angioplasty and for preventing re-stenosis
US5486357A (en) * 1990-11-08 1996-01-23 Cordis Corporation Radiofrequency plasma biocompatibility treatment of inside surfaces
US5304121A (en) * 1990-12-28 1994-04-19 Boston Scientific Corporation Drug delivery system making use of a hydrogel polymer coating
US5378475A (en) * 1991-02-21 1995-01-03 University Of Kentucky Research Foundation Sustained release drug delivery devices
US5344411A (en) * 1991-02-27 1994-09-06 Leonard Bloom Method and device for inhibiting HIV, hepatitis B and other viruses and germs when using a catheter in a medical environment
US5512055A (en) * 1991-02-27 1996-04-30 Leonard Bloom Anti-infective and anti-inflammatory releasing systems for medical devices
US5192308A (en) * 1991-04-19 1993-03-09 E. I. Du Pont De Nemours And Company Vascular prosthesis with an elastomer coating
US5356433A (en) * 1991-08-13 1994-10-18 Cordis Corporation Biocompatible metal surfaces
US5500013A (en) * 1991-10-04 1996-03-19 Scimed Life Systems, Inc. Biodegradable drug delivery vascular stent
US5551954A (en) * 1991-10-04 1996-09-03 Scimed Life Systems, Inc. Biodegradable drug delivery vascular stent
US5492895A (en) * 1992-02-14 1996-02-20 Corvas International, Inc. Inhibitors of thrombosis
US5591227A (en) * 1992-03-19 1997-01-07 Medtronic, Inc. Drug eluting stent
US5282823A (en) * 1992-03-19 1994-02-01 Medtronic, Inc. Intravascular radially expandable stent
US5510077A (en) * 1992-03-19 1996-04-23 Dinh; Thomas Q. Method of making an intraluminal stent
US5599352A (en) * 1992-03-19 1997-02-04 Medtronic, Inc. Method of making a drug eluting stent
US5591224A (en) * 1992-03-19 1997-01-07 Medtronic, Inc. Bioelastomeric stent
US5288711A (en) * 1992-04-28 1994-02-22 American Home Products Corporation Method of treating hyperproliferative vascular disease
US5383928A (en) * 1992-06-10 1995-01-24 Emory University Stent sheath for local drug delivery
US5429618A (en) * 1992-10-30 1995-07-04 Medtronic, Inc. Thromboresistant articles
US5449382A (en) * 1992-11-04 1995-09-12 Dayton; Michael P. Minimally invasive bioactivated endoprosthesis for vessel repair
US5342348A (en) * 1992-12-04 1994-08-30 Kaplan Aaron V Method and device for treating and enlarging body lumens
US5419760A (en) * 1993-01-08 1995-05-30 Pdt Systems, Inc. Medicament dispensing stent for prevention of restenosis of a blood vessel
US5391378A (en) * 1993-02-22 1995-02-21 Elizabeth-Hata International, Inc. Two-part medicinal tablet and method of manufacture
US5900246A (en) * 1993-03-18 1999-05-04 Cedars-Sinai Medical Center Drug incorporating and releasing polymeric coating for bioprosthesis
US5607463A (en) * 1993-03-30 1997-03-04 Medtronic, Inc. Intravascular medical device
US5523092A (en) * 1993-04-14 1996-06-04 Emory University Device for local drug delivery and methods for using the same
US5399352A (en) * 1993-04-14 1995-03-21 Emory University Device for local drug delivery and methods for using the same
US5624411A (en) * 1993-04-26 1997-04-29 Medtronic, Inc. Intravascular stent and method
US5776184A (en) * 1993-04-26 1998-07-07 Medtronic, Inc. Intravasoular stent and method
US5662712A (en) * 1993-04-28 1997-09-02 Focal, Inc. Apparatus for intraluminal photothermoforming
US5716981A (en) * 1993-07-19 1998-02-10 Angiogenesis Technologies, Inc. Anti-angiogenic compositions and methods of use
US5380299A (en) * 1993-08-30 1995-01-10 Med Institute, Inc. Thrombolytic treated intravascular medical device
US5735897A (en) * 1993-10-19 1998-04-07 Scimed Life Systems, Inc. Intravascular stent pump
US5629077A (en) * 1994-06-27 1997-05-13 Advanced Cardiovascular Systems, Inc. Biodegradable mesh and film stent
US5632840A (en) * 1994-09-22 1997-05-27 Advanced Cardiovascular System, Inc. Method of making metal reinforced polymer stent
US5643580A (en) * 1994-10-17 1997-07-01 Surface Genesis, Inc. Biocompatible coating, medical device using the same and methods
US5637113A (en) * 1994-12-13 1997-06-10 Advanced Cardiovascular Systems, Inc. Polymer film for wrapping a stent structure
US5605696A (en) * 1995-03-30 1997-02-25 Advanced Cardiovascular Systems, Inc. Drug loaded polymeric material and method of manufacture
US6120536A (en) * 1995-04-19 2000-09-19 Schneider (Usa) Inc. Medical devices with long term non-thrombogenic coatings
US6096070A (en) * 1995-06-07 2000-08-01 Med Institute Inc. Coated implantable medical device
US5609629A (en) * 1995-06-07 1997-03-11 Med Institute, Inc. Coated implantable medical device
US5877224A (en) * 1995-07-28 1999-03-02 Rutgers, The State University Of New Jersey Polymeric drug formulations
US5722984A (en) * 1996-01-16 1998-03-03 Iso Stent, Inc. Antithrombogenic radioactive coating for an intravascular stent
US6099562A (en) * 1996-06-13 2000-08-08 Schneider (Usa) Inc. Drug coating with topcoat
US5779732A (en) * 1997-03-31 1998-07-14 Medtronic, Inc. Method and apparatus for implanting a film with an exandable stent
US6042875A (en) * 1997-04-30 2000-03-28 Schneider (Usa) Inc. Drug-releasing coatings for medical devices
US6110483A (en) * 1997-06-23 2000-08-29 Sts Biopolymers, Inc. Adherent, flexible hydrogel and medicated coatings
US5879034A (en) * 1997-10-17 1999-03-09 Johns; Ernest W. Automatic locking device
US6198016B1 (en) * 1998-12-01 2001-03-06 3M Innovative Properties Company Wet skin adhesive article

Cited By (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7815675B2 (en) 1996-11-04 2010-10-19 Boston Scientific Scimed, Inc. Stent with protruding branch portion for bifurcated vessels
US20030099682A1 (en) * 1998-11-20 2003-05-29 Francis Moussy Apparatus and method for control of tissue/implant interactions
US8236048B2 (en) 2000-05-12 2012-08-07 Cordis Corporation Drug/drug delivery systems for the prevention and treatment of vascular disease
US8303609B2 (en) 2000-09-29 2012-11-06 Cordis Corporation Coated medical devices
US20050131532A1 (en) * 2000-12-22 2005-06-16 Avantec Vascular Corporation Apparatus and methods for controlled substance delivery from implanted prostheses
US8303643B2 (en) 2001-06-27 2012-11-06 Remon Medical Technologies Ltd. Method and device for electrochemical formation of therapeutic species in vivo
US8425590B2 (en) 2001-09-24 2013-04-23 Boston Scientific Scimed, Inc. Stent with protruding branch portion for bifurcated vessels
US7951192B2 (en) 2001-09-24 2011-05-31 Boston Scientific Scimed, Inc. Stent with protruding branch portion for bifurcated vessels
US8449901B2 (en) 2003-03-28 2013-05-28 Innovational Holdings, Llc Implantable medical device with beneficial agent concentration gradient
US8016878B2 (en) 2005-12-22 2011-09-13 Boston Scientific Scimed, Inc. Bifurcation stent pattern
US8840660B2 (en) 2006-01-05 2014-09-23 Boston Scientific Scimed, Inc. Bioerodible endoprostheses and methods of making the same
US8089029B2 (en) 2006-02-01 2012-01-03 Boston Scientific Scimed, Inc. Bioabsorbable metal medical device and method of manufacture
US8048150B2 (en) 2006-04-12 2011-11-01 Boston Scientific Scimed, Inc. Endoprosthesis having a fiber meshwork disposed thereon
US8052743B2 (en) 2006-08-02 2011-11-08 Boston Scientific Scimed, Inc. Endoprosthesis with three-dimensional disintegration control
WO2008017814A1 (en) 2006-08-09 2008-02-14 Sinclair Pharmaceuticals Limited Prevention and treatment of microbial infection
US20080057053A1 (en) * 2006-08-31 2008-03-06 Cardiac Pacemakers, Inc Bispecific antibodies and agents to enhance stem cell homing
US8372399B2 (en) 2006-08-31 2013-02-12 Cardiac Pacemakers, Inc. Bispecific antibodies and agents to enhance stem cell homing
US20080057027A1 (en) * 2006-08-31 2008-03-06 Cardiac Pacemakers, Inc Methods and devices to regulate stem cell homing
US20080058922A1 (en) * 2006-08-31 2008-03-06 Cardiac Pacemakers, Inc. Methods and devices employing vap-1 inhibitors
US8636995B2 (en) 2006-08-31 2014-01-28 Cardiac Pacemakers, Inc. Methods and devices to regulate stem cell homing
US8057534B2 (en) 2006-09-15 2011-11-15 Boston Scientific Scimed, Inc. Bioerodible endoprostheses and methods of making the same
US7955382B2 (en) 2006-09-15 2011-06-07 Boston Scientific Scimed, Inc. Endoprosthesis with adjustable surface features
US8808726B2 (en) 2006-09-15 2014-08-19 Boston Scientific Scimed. Inc. Bioerodible endoprostheses and methods of making the same
US8052744B2 (en) 2006-09-15 2011-11-08 Boston Scientific Scimed, Inc. Medical devices and methods of making the same
US8128689B2 (en) 2006-09-15 2012-03-06 Boston Scientific Scimed, Inc. Bioerodible endoprosthesis with biostable inorganic layers
US8002821B2 (en) 2006-09-18 2011-08-23 Boston Scientific Scimed, Inc. Bioerodible metallic ENDOPROSTHESES
US7951191B2 (en) 2006-10-10 2011-05-31 Boston Scientific Scimed, Inc. Bifurcated stent with entire circumferential petal
US7842082B2 (en) 2006-11-16 2010-11-30 Boston Scientific Scimed, Inc. Bifurcated stent
US8147539B2 (en) 2006-12-20 2012-04-03 Boston Scientific Scimed, Inc. Stent with a coating for delivering a therapeutic agent
US8715339B2 (en) 2006-12-28 2014-05-06 Boston Scientific Scimed, Inc. Bioerodible endoprostheses and methods of making the same
US8080055B2 (en) 2006-12-28 2011-12-20 Boston Scientific Scimed, Inc. Bioerodible endoprostheses and methods of making the same
US8133553B2 (en) 2007-06-18 2012-03-13 Zimmer, Inc. Process for forming a ceramic layer
US8663337B2 (en) 2007-06-18 2014-03-04 Zimmer, Inc. Process for forming a ceramic layer
US8309521B2 (en) 2007-06-19 2012-11-13 Zimmer, Inc. Spacer with a coating thereon for use with an implant device
US7959669B2 (en) 2007-09-12 2011-06-14 Boston Scientific Scimed, Inc. Bifurcated stent with open ended side branch support
US8052745B2 (en) 2007-09-13 2011-11-08 Boston Scientific Scimed, Inc. Endoprosthesis
US8602290B2 (en) 2007-10-10 2013-12-10 Zimmer, Inc. Method for bonding a tantalum structure to a cobalt-alloy substrate
US8608049B2 (en) 2007-10-10 2013-12-17 Zimmer, Inc. Method for bonding a tantalum structure to a cobalt-alloy substrate
US7833266B2 (en) 2007-11-28 2010-11-16 Boston Scientific Scimed, Inc. Bifurcated stent with drug wells for specific ostial, carina, and side branch treatment
US8277501B2 (en) 2007-12-21 2012-10-02 Boston Scientific Scimed, Inc. Bi-stable bifurcated stent petal geometry
US7998192B2 (en) 2008-05-09 2011-08-16 Boston Scientific Scimed, Inc. Endoprostheses
US8932340B2 (en) 2008-05-29 2015-01-13 Boston Scientific Scimed, Inc. Bifurcated stent and delivery system
US8236046B2 (en) 2008-06-10 2012-08-07 Boston Scientific Scimed, Inc. Bioerodible endoprosthesis
US7985252B2 (en) 2008-07-30 2011-07-26 Boston Scientific Scimed, Inc. Bioerodible endoprosthesis
WO2010014690A3 (en) * 2008-07-31 2010-09-30 Boston Scientific Scimed, Inc. Medical devices for therapeutic agent delivery
WO2010014690A2 (en) 2008-07-31 2010-02-04 Boston Scientific Scimed, Inc. Medical devices for therapeutic agent delivery
US20100028403A1 (en) * 2008-07-31 2010-02-04 Boston Scientific Scimed, Inc. Medical devices for therapeutic agent delivery
US8382824B2 (en) 2008-10-03 2013-02-26 Boston Scientific Scimed, Inc. Medical implant having NANO-crystal grains with barrier layers of metal nitrides or fluorides
US8267992B2 (en) 2009-03-02 2012-09-18 Boston Scientific Scimed, Inc. Self-buffering medical implants
US8668732B2 (en) 2010-03-23 2014-03-11 Boston Scientific Scimed, Inc. Surface treated bioerodible metal endoprostheses

Also Published As

Publication number Publication date
EP1980278A3 (en) 2009-08-26
JPH11199471A (en) 1999-07-27
US6284305B1 (en) 2001-09-04
US20040049265A1 (en) 2004-03-11
EP1980278A2 (en) 2008-10-15
US6099562A (en) 2000-08-08
EP0923953B1 (en) 2008-08-13
DE69839869D1 (en) 2008-09-25
EP0923953A3 (en) 2000-11-29
US20020004101A1 (en) 2002-01-10
US20050208200A1 (en) 2005-09-22
EP0923953A2 (en) 1999-06-23
US6620194B2 (en) 2003-09-16
JP3556837B2 (en) 2004-08-25

Similar Documents

Publication Publication Date Title
US6620194B2 (en) Drug coating with topcoat
US6120536A (en) Medical devices with long term non-thrombogenic coatings
US6358556B1 (en) Drug release stent coating
US20060088654A1 (en) Drug release coated stent
CA2470709C (en) Stent with drug release coating
CA2598946A1 (en) Drug release stent coating process
MXPA97004436A (en) Coating and procedure to cover a farm release fixer

Legal Events

Date Code Title Description
AS Assignment

Owner name: SCHNEIDER (USA) INC.,MINNESOTA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:DING, NI;HELMUS, MICHAEL N.;SIGNING DATES FROM 19971209 TO 19971210;REEL/FRAME:024552/0893

AS Assignment

Owner name: BOSTON SCIENTIFIC SCIMED, INC.,MINNESOTA

Free format text: CHANGE OF NAME;ASSIGNOR:SCHNEIDER (USA) INC.;REEL/FRAME:024564/0518

Effective date: 19990427

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION