US20120046640A1 - Coating Comprising An Elastin-Based Copolymer - Google Patents
Coating Comprising An Elastin-Based Copolymer Download PDFInfo
- Publication number
- US20120046640A1 US20120046640A1 US13/225,165 US201113225165A US2012046640A1 US 20120046640 A1 US20120046640 A1 US 20120046640A1 US 201113225165 A US201113225165 A US 201113225165A US 2012046640 A1 US2012046640 A1 US 2012046640A1
- Authority
- US
- United States
- Prior art keywords
- medical device
- poly
- rapamycin
- peptide
- polymer
- 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
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/28—Materials for coating prostheses
- A61L27/34—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/08—Materials for coatings
- A61L29/085—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/043—Proteins; Polypeptides; Degradation products thereof
- A61L31/047—Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05D3/00—Pretreatment of surfaces to which liquids or other fluent materials are to be applied; After-treatment of applied coatings, e.g. intermediate treating of an applied coating preparatory to subsequent applications of liquids or other fluent materials
- B05D3/007—After-treatment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08H—DERIVATIVES OF NATURAL MACROMOLECULAR COMPOUNDS
- C08H1/00—Macromolecular products derived from proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/25—Peptides having up to 20 amino acids in a defined sequence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/02—Methods for coating medical devices
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/31504—Composite [nonstructural laminate]
- Y10T428/3154—Of fluorinated addition polymer from unsaturated monomers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/31504—Composite [nonstructural laminate]
- Y10T428/31855—Of addition polymer from unsaturated monomers
- Y10T428/31909—Next to second addition polymer from unsaturated monomers
Definitions
- This invention generally relates to elastin-based copolymers for coating an implantable device such as a drug delivery stent or for forming a composition as cell therapy carrier.
- Blood vessel occlusions are commonly treated by mechanically enhancing blood flow in the affected vessels, such as by employing a stent.
- Stents are used not only for mechanical intervention but also as vehicles for providing biological therapy.
- the stent can be coated with a biocompatible polymeric coating.
- the biocompatible polymeric coating can function either as a permeable layer or a carrier to allow a controlled delivery of the agent.
- the existing polymeric coating on a stent can have different types of limitations.
- some poly(ester amide) based coatings can have poor mechanical properties so as to compromise coating integrity
- coating based on hydrophobic polymers can have problems in controlling release of a hydrophilic drug.
- the copolymer can be used to form a coating on a medical device.
- the coating can further include a polymer, a biobeneficial material, a bioactive agent, or combinations of these.
- bioactive agent examples include, but are not limited to, paclitaxel, docetaxel, estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O—[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), pimecrolimus, imatinib mesylate, midostaurin, clobetasol, mometasone, bioactive RGD, CD-34
- the elastin-based copolymer can be used as hydrogel-like scaffold.
- one can use it as cell delivery using a depot platform.
- a matrix including the polymer described herein can be injected into depots that sit on a carrier platform such as depot stents.
- a medical device having a coating or depot platform described herein can be used to treat, prevent, or ameliorate a vascular medical condition.
- vascular medical conditions include atherosclerosis, thrombosis, restenosis, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, urethra obstruction, tumor obstruction, and combinations thereof.
- FIG. 1 shows that B-9 coating is crimping/icy hot onto catheters, followed after E-beam.
- FIG. 2 shows the OD of B9 coated stent after simulated use test.
- FIG. 3 shows a B-9 coated stent after chandler loop test.
- FIG. 4 shows a typical OD surface of B-9 coated stent after chandler loop test.
- FIG. 5 shows a typical ID surface of B-9 coated stent after chandler loop study.
- FIG. 6 shows thrombi weight of different type of coatings.
- the copolymer can be used to form a coating on a medical device.
- the coating can further include a polymer, a biobeneficial material, a bioactive agent, or combinations of these.
- bioactive agent examples include, but are not limited to, paclitaxel, docetaxel, estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O—[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), pimecrolimus, imatinib mesylate, midostaurin, clobetasol, mometasone, bioactive RGD, CD-34
- the elastin-based copolymer can be used as hydrogel-like scaffold.
- one can use it as cell delivery using a depot platform.
- a matrix including the polymer described herein can be injected into depots that sit on a carrier platform such as depot stents.
- elastin-based copolymer is sometimes referred to as the “elastin-based polymer”. These two terms can be used interchangeably.
- Other names include protein elastomer, protein polymer, protein tri-block copolymer, and elastin mimetic.
- a medical device having a coating or depot platform described herein can be used to treat, prevent, or ameliorate a vascular medical condition.
- vascular medical conditions include atherosclerosis, thrombosis, restenosis, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, urethra obstruction, tumor obstruction, and combinations thereof.
- Elastin is a protein that is found in the walls of arteries, in lungs, intestines and skin in the body of an animal. Elastin imparts elasticity to the body. Working in partnership with collagen, elastin allows the body organs to stretch and relax. Thus, while collagen provides rigidity, elastin allows the blood vessels and heart tissues, for example, to stretch and then revert to their original positions, i.e. to recoil. Therefore, elastin provides for structural integrity and for the compliance of the vessel at low pressure whereas collagen gives the tensile resistance required at high pressures.
- VGVPG valyl-glycyl-valyl-prolyl-glycine
- the elastin-based polymer described herein can be an ABA or BAB type polymer, where A represents a unit that includes the pentapeptide sequence VGVPG (SEQ ID NO: 1) and B represents a unit which can be a peptide sequence or a unit derived from a monomer.
- the copolymer can be a block or random copolymer.
- the BAB block copolymers are comprised such that the B-block is hydrophobic while the A-block is more hydrophilic.
- the elastin-based copolymer is an ABA triblock copolymer, where A is a block comprising the VGVPG (SEQ ID NO: 1) sequence and B is a block derived from a peptide or monomer(s).
- B can be a hydrophilic variant of the VGVPG (SEQ ID NO: 1) peptide.
- variant refers to any form of VGVPG (SEQ ID NO: 1) modification.
- an amino acid in the peptide can be replaced with another amino acid.
- the sequence of VGVPG (SEQ ID NO: 1) can be varied so as to form a variant of the VGVPG (SEQ ID NO: 1) peptide.
- the VGVPG (SEQ ID NO: 1) peptide can be modified to include lysine (lysine block).
- This lysine block can be used as the middle block to form the ABA triblock copolymer with the VGVPG (SEQ ID NO: 1) pentapeptide.
- the lysine block can be modified to conjugate a molecule or polymer such as phosphoryl choline (PC), poly(ethylene glycol) (PEG), or a bioactive moiety such as nitric oxide generating catalyst or TEMPO as pendant groups. These pendant groups can impart different physical, chemical, or biological properties to the elastin-based polymer.
- degradable linkages can be formed between the peptide blocks so that the newly formed elastin-based materials could be degradable.
- Any biodegradable polymers described below can be used as the linkage.
- Some examples of these degradable linkages are poly(lactic acid) (PLA), poly(glycolic acid) (PLGA), polycaprolactone (PCL), poly(3-hydroxybutyric acid (PHB), poly(4-hydroxybutyrate (P4HB), or combinations of these.
- Some other clearance mechanisms can be enzymatically degradable (via elastase) or biosoluble when the polymer is sufficiently hydrophilic.
- the elastin-based copolymer is an ABA triblock copolymer where A is a block comprising the VGVPG (SEQ ID NO: 1) peptide and B is a hydrophilic synthetic polymer.
- a synthetic polymer can be, for example, a hydrophilic polymer such as PEG, PVP (poly vinylpyrrolidinone), polyacrylamide, poly(PEG acrylate), poly (HEMA), poly(acrylic acid) or combinations of these polymers.
- the elastin-based copolymer is an ABA triblock copolymer where A is a block comprising the VGVPG (SEQ ID NO: 1) peptide and B is a hydrophilic natural polymer such as protein or peptide.
- a hydrophilic natural polymer can be, for example, collagen or collagen derivative, hyaluronic acid, alginate or combinations of these.
- the elastin-based polymer can include a peptide sequence that promotes proliferation and/or migration of endothelial cells (ECs).
- ECs endothelial cells
- Such peptide sequence can be, for example, RGD, cRGD, or EC specific sequences such as SIKVAV (SEQ ID NO: 2), CNP, YIGSRG (SEQ ID NO: 3), mimetics of these sequences, or combinations of these.
- the elastin-based copolymer can include an enzyme susceptible segment(s) or hydrolytically susceptible segment(s). These segment(s) can modify the absorption rate of the polymer so as to allow fine tuning of the absorption rate of the polymer. For example, the absorption rate of the elastin-based polymer can be increased or decreased by the content of these enzyme susceptible segment(s) or hydrolytically susceptible segment(s).
- the term “content” refers to molar ratio of the total units in the enzyme susceptible segment(s) and/or hydrolytically susceptible segment(s) to the total units in the polymer and can range from e.g., above 0 to about 0.5, for example.
- enzyme susceptible segment(s) or hydrolytically susceptible segment(s) include, but are not limited to, poly-lactic acid, poly(glycolic) acid, polycaprolactone, poly(alkene succinate), aliphatic-aromatic copolyesters, poly(orthoesters), polyanhydrides, polycarbonates/polyiminocarbonates, or natural degradable polymers including starch, fibre, fibre-starch composites, cellulose, etc.
- enzyme susceptible segment(s) refers to a segment(s) that comprises a bonding that can be cleaved by enzyme(s).
- hydrolytically susceptible segment(s) refers to a segment(s) that comprises a bonding that can be cleaved by hydrolysis.
- the elastin-based polymer can be used in a composition for cell therapy carrier.
- the composition can include the elastin-based polymer, cells such as stem cells and optionally other materials and agents.
- the composition can be delivered to a dysfunctional part of the body (e.g., an organ such as heart or blood vessel) while the cells are still viable.
- the composition can include a pharmaceutically acceptable carrier.
- Delivery of the composition can be achieved by any established modes of delivery.
- the delivery can be achieved via delivery from a coating on a medical device (e.g., a stent).
- the delivery can be injection or delivery through catheter.
- the composition can also be delivered using surgical method such as creating a depot within the muscle and releasing the pharmaceutical agent(s) out of the depot.
- the elastin-based copolymer can be used as hydrogel-like scaffold.
- one can use it as cell delivery using a depot platform.
- a matrix including the polymer described herein can be injected into depots that sit on a carrier platform such as depot stents.
- the elastin-based polymer can form a layer of coating as a topcoat, a matrix layer or a primer layer.
- the coating can be formed by dipping in an aqueous solution of the elastin-based polymer.
- a solution of an elastin-based polymer described here can be provided.
- a medical device such as a stent can be dipped in (rinsed) the solution at a temperature below ambient temperature (e.g., 4° C.).
- the rinsed medical device can be subject to heat treatment at a temperature in the range of about 15° C.-30° C. higher than the lower critical solution temperature (LCST) of the elastin-based polymer to generate a coating with biomimcry effect.
- FIG. 1 shows stent coated with an elastin-based polymer of the present invention after wet expansion.
- a solution of the elastin-based polymer can have a concentration of the polymer ranging from about 1 wt % to about 50 wt %.
- the solution has a concentration of the elastin-based polymer in the range between about 5 wt % and about 30%, for example, about 10 wt %, about 15 wt %, about 20 wt % or about 25 wt %.
- the solution can include a solvent such as water or a biocompatible organic solvent such as dimethylformamide (DMF), dimethyl sulfoxide (DMSO), dimethyl acetamide (DMAC), methyl ethyl ketone (MEK), ethylene glycol or combinations of these.
- the solvent can be trifluoroethanol (TFE).
- TFE has a boiling temperature of about 80° C., making the solvent a good solvent for use in coating a medical device.
- the concentration can be varied and determined according to the molecular weight of the elastin-based polymer for forming the coating. For example, with a elastin-based polymer with a weight average molecular weight about 160K Daltons, a solution of the polymer of about 2 wt % in TFE can be used to form a coating on a medical device using spray coating method at room temperature.
- the solution can be an acidic solution having a pH lower than 7.
- an acidic solution of the elastin-based polymer is used to form the coating on a medical device
- medical device rinsed or sprayed with the acidic solution shall be rinsed (or sprayed) with a solution of basic pH (>7) buffered solution.
- the basic buffered solution can be any basic buffer solution in the art.
- the mechanical property of the film cast from elastin-based polymer depends on the solution used in the cast. For example, for elongation of the film, generally a pH>7 coating system will lead to a higher elongation than a neutral or acidic water coating system, and a neutral or acidic water coating system will lead to a higher elongation than a TFE coating system.
- the elastin-based polymer can be coated on a nano- or micro-porous device (e.g., a stent from Blue-Membranes, GmbH, Germany) for controlled release of an agent (e.g., a drug) by modulating the porosity and porous coating thickness.
- a nano- or micro-porous device e.g., a stent from Blue-Membranes, GmbH, Germany
- an agent e.g., a drug
- the elastin-based polymer can be coated on the abluminal side of an implantable device as a thin or very thin topcoat.
- the term “thin” or “very thin” refers to a thickness of less than about 1 ⁇ m, less than about 500 nm, less than about 100 nm, less than about 50 nm, or less than about 10 nm.
- the elastin-based polymer can be coated on a hydrophobic surface of an implantable device (e.g., a stent).
- the hydrophobic surface of the implantable device can be modified to include a thin layer of a hydrophilic polymer such as a polymer comprising poly(vinyl alcohol) (PVOH).
- a hydrophilic polymer such as a polymer comprising poly(vinyl alcohol) (PVOH).
- PVOH poly(vinyl alcohol)
- the surface comprising a fluoropolymer such as a poly(vinylidene fluoride) (SOLEFTM) polymer can be modified by forming a thin layer of PVOH thereon and then forming a thin layer of the elastin-based polymer on top of the PVOH layer.
- the layer of PVOH can be formed by exposing a hydrophobic surface to a dilute PVOH solution (e.g., a concentration of less than about 5 mass %, less than about 1 mass %, less than about 0.5 mass %, less than about 0.1 mass %, less than about 0.05 or mass % less than about 0.01 mass %) and allowing the PVOH molecule to adsorb onto the hydrophobic surface.
- a dilute PVOH solution e.g., a concentration of less than about 5 mass %, less than about 1 mass %, less than about 0.5 mass %, less than about 0.1 mass %, less than about 0.05 or mass % less than about 0.01 mass %.
- the term “thin” or “very thin” refers to a thickness of less than about 1 ⁇ m, less than about 500 nm, less than about 100 nm, less than about 50 nm, or less than about 10 nm.
- the elastin-based copolymers described herein can be used with other biocompatible polymers.
- One of the exemplary constructs with other polymers is that the elastin-based copolymer form a topcoat, where the other polymer serves as the controlled release coating and the elastin-based polymer is a topcoat.
- the biocompatible polymer can be biodegradable (either bioerodible or bioabsorbable or both) or nondegradable and can be hydrophilic or hydrophobic.
- biocompatible polymers include, but are not limited to, poly(ester amide), polyhydroxyalkanoates (PHA), poly(3-hydroxyalkanoates) such as poly(3-hydroxypropanoate), poly(3-hydroxybutyrate), poly(3-hydroxyvalerate), poly(3-hydroxyhexanoate), poly(3-hydroxyheptanoate) and poly(3-hydroxyoctanoate), poly(4-hydroxyalkanaote) such as poly(4-hydroxybutyrate), poly(4-hydroxyvalerate), poly(4-hydroxyhexanote), poly(4-hydroxyheptanoate), poly(4-hydroxyoctanoate) and copolymers including any of the 3-hydroxyalkanoate or 4-hydroxyalkanoate monomers described herein or blends thereof, poly(D,L-lactide), poly(L-lactide), polyglycolide, poly(D,L-lactide-co-glycolide), poly(L-lactide-co-gly
- poly(ethylene oxide-co-lactic acid) PEO/PLA
- polyalkylene oxides such as poly(ethylene oxide), poly(propylene oxide), poly(ether ester), polyalkylene oxalates, phosphoryl choline containing polymer, choline, poly(aspirin), polymers and co-polymers of hydroxyl bearing monomers such as 2-hydroxyethyl methacrylate (HEMA), hydroxypropyl methacrylate (HPMA), hydroxypropylmethacrylamide, PEG acrylate (PEGA), PEG methacrylate, methacrylate polymers containing 2-methacryloyloxyethylphosphorylcholine (MPC) and n-vinyl pyrrolidone (VP), carboxylic acid bearing monomers such as methacrylic acid (MA), acrylic acid (AA), alkoxymethacrylate, alkoxyacrylate, and 3-trimethylsilylpropyl methacrylate (TMSPMA), poly(styrene-iso
- elastin protein mimetics include (LGGVG) n (SEQ ID NO: 4), (VPGVG) n (SEQ ID NO: 5), Val-Pro-Gly-Val-Gly (SEQ ID NO: 6), or synthetic biomimetic poly(L-glytanmate)-b-poly(2-acryloyloxyethyllactoside)-b-poly(1-glutamate) triblock copolymer.
- the polymer can be poly(ethylene-co-vinyl alcohol), poly(methoxyethyl methacrylate), poly(dihydroxylpropyl methacrylate), polymethacrylamide, aliphatic polyurethane, aromatic polyurethane, nitrocellulose, poly(ester amide benzyl), co-poly- ⁇ [N,N′-sebacoyl-bis-(L-leucine)-1,6-hexylene diester] 0.75 -[N,N′-sebacoyl-L-lysine benzyl ester] 0.25 ⁇ (PEA-Bz), co-poly- ⁇ [N,N′-sebacoyl-bis-(L-leucine)-1,6-hexylene diester] 0.75 -[N,N′-sebacoyl-L-lysine-4-amino-TEMPO amide] 0.25 ⁇ (PEA-TEMPO), aliphatic polyester, aromatic polyester
- the polymer when it is a copolymer, it can be a block copolymer that can be, e.g., di-, tri-, tetra-, or oligo-block copolymers or a random copolymer. In some embodiments, the polymer can also be branched polymers such as star polymers.
- a coating having the features described herein can exclude any one of the aforementioned polymers.
- poly(D,L-lactide), poly(L-lactide), poly(D,L-lactide-co-glycolide), and poly(L-lactide-co-glycolide) can be used interchangeably with the terms poly(D,L-lactic acid), poly(L-lactic acid), poly(D,L-lactic acid-co-glycolic acid), or poly(L-lactic acid-co-glycolic acid), respectively.
- the elastin-based copolymer can optionally used with a biobeneficial material.
- the biobeneficial material can be a polymeric material or non-polymeric material.
- the biobeneficial material is preferably non-toxic, non-antigenic and non-immunogenic.
- a biobeneficial material is one which enhances the biocompatibility of the particles or device by being non-fouling, hemocompatible, actively non-thrombogenic, or antiinflammatory, all without depending on the release of a pharmaceutically active agent.
- biobeneficial materials include, but are not limited to, polyethers such as poly(ethylene glycol), copoly(ether-esters) (e.g. PEO/PLA), polyalkylene oxides such as poly(ethylene oxide), polypropylene oxide), poly(ether ester), polyalkylene oxalates, polyphosphazenes, phosphoryl choline, choline, poly(aspirin), polymers and co-polymers of hydroxyl bearing monomers such as hydroxyethyl methacrylate (HEMA), hydroxypropyl methacrylate (HPMA), hydroxypropylmethacrylamide, poly(ethylene glycol)acrylate (PEGA), PEG methacrylate, 2-methacryloyloxyethylphosphorylcholine (MPC) and n-vinyl pyrrolidone (VP), carboxylic acid bearing monomers such as methacrylic acid (MA), acrylic acid (AA), alkoxymethacrylate, alkoxyacrylate, and 3-trimethyls
- a coating described herein can exclude any one of the aforementioned polymers.
- POLYACTIVETM refers to a block copolymer having flexible poly(ethylene glycol) and poly(butylene terephthalate) blocks (PEGT/PBT). POLYACTIVETM is intended to include AB, ABA, BAB copolymers having such segments of PEG and PBT (e.g., poly(ethylene glycol)-block-poly(butyleneterephthalate)-block poly(ethylene glycol) (PEG-PBT-PEG).
- the biobeneficial material can be a polyether such as poly(ethylene glycol) (PEG) or polyalkylene oxide.
- the elastin-based copolymer can form a coating on a medical device.
- the coating can include one or more bioactive agent(s), which can be therapeutic, prophylactic, or diagnostic agent(s). These agents can have anti-proliferative or anti-inflammatory properties or can have other properties such as antineoplastic, antiplatelet, anti-coagulant, anti-fibrin, antithrombogenic, antimitotic, antibiotic, antiallergic, antifibrotic, and antioxidant.
- the agents can be cystostatic agents, agents that promote the healing of the endothelium such as NO releasing or generating agents, agents that attract endothelial progenitor cells, agents that promote the attachment, migration or proliferation of endothelial cells (e.g., natriuretic peptides such as CNP, ANP or BNP peptide or an RGD or cRGD peptide), while impeding smooth muscle cell proliferation.
- suitable therapeutic and prophylactic agents include synthetic inorganic and organic compounds, proteins and peptides, polysaccharides and other sugars, lipids, and DNA and RNA nucleic acid sequences having therapeutic, prophylactic or diagnostic activities.
- bioactive agent examples include antibodies, receptor ligands, enzymes, adhesion peptides, blood clotting factors, inhibitors or clot dissolving agents such as streptokinase and tissue plasminogen activator, antigens for immunization, hormones and growth factors, oligonucleotides such as antisense oligonucleotides, small interfering RNA (siRNA), small hairpin RNA (shRNA), aptamers, ribozymes and retroviral vectors for use in gene therapy.
- oligonucleotides such as antisense oligonucleotides, small interfering RNA (siRNA), small hairpin RNA (shRNA), aptamers, ribozymes and retroviral vectors for use in gene therapy.
- anti-proliferative agents examples include rapamycin and its functional or structural derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), and its functional or structural derivatives, paclitaxel and its functional and structural derivatives.
- rapamycin derivatives include 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin.
- paclitaxel derivatives examples include docetaxel.
- antineoplastics and/or antimitotics examples include methotrexate, azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride (e.g. ADRIAMYCIN® from Pharmacia & Upjohn, Peapack N.J.), and mitomycin (e.g. MUTAMYCIN® from Bristol-Myers Squibb Co., Stamford, Conn.).
- antiplatelets examples include sodium heparin, low molecular weight heparins, heparinoids, hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor antagonist antibody, recombinant hirudin, thrombin inhibitors such as ANGIOMAXTM (bivalirudin, Biogen, Inc., Cambridge, Mass.), calcium channel blockers (such as nifedipine), colchicine, fibroblast growth factor (FGF) antagonists, fish oil (omega 3-fatty acid), histamine antagonists, lovastatin (an inhibitor of HMG-CoA reductase, a cholesterol lowering drug, brand name MEVACOR
- anti-inflammatory agents including steroidal and non-steroidal anti-inflammatory agents include tacrolimus, dexamethasone, clobetasol, mometasone, or combinations thereof.
- cytostatic substances include angiopeptin, angiotensin converting enzyme inhibitors such as captopril (e.g. CAPOTEN® and CAPOZIDE® from Bristol-Myers Squibb Co., Stamford, Conn.), cilazapril or lisinopril (e.g. PRINIVIL® and PRINZIDE® from Merck & Co., Inc., Whitehouse Station, N.J.).
- An example of an antiallergic agent is permirolast potassium.
- therapeutic substances or agents which can be appropriate include alpha-interferon, pimecrolimus, imatinib mesylate, midostaurin, bioactive RGD, SIKVAV (SEQ ID NO: 2) peptides, growth factor vascular endothelial growth factor (VEGF), elevating agents such as cANP or cGMP peptides, and genetically engineered endothelial cells.
- VEGF growth factor vascular endothelial growth factor
- elevating agents such as cANP or cGMP peptides
- genetically engineered endothelial cells vascular endothelial cells.
- the foregoing substances can also be used in the form of prodrugs or co-drugs thereof.
- the foregoing substances also include metabolites thereof and/or prodrugs of the metabolites.
- the foregoing substances are listed by way of example and are not meant to be limiting. Other active agents which are currently available or that may be developed in the future are equally applicable.
- the dosage or concentration of the bioactive agent required to produce a favorable therapeutic effect should be less than the level at which the bioactive agent produces toxic effects and greater than non-therapeutic levels.
- the dosage or concentration of the bioactive agent can depend upon factors such as the particular circumstances of the patient, the nature of the trauma, the nature of the therapy desired, the time over which the administered ingredient resides at the vascular site, and if other active agents are employed, the nature and type of the substance or combination of substances.
- Therapeutically effective dosages can be determined empirically, for example by infusing vessels from suitable animal model systems and using immunohistochemical, fluorescent or electron microscopy methods to detect the agent and its effects, or by conducting suitable in vitro studies. Standard pharmacological test procedures to determine dosages are understood by one of ordinary skill in the art.
- a medical device can be any suitable medical substrate that can be implanted in a human or veterinary patient.
- medical devices include self-expandable stents, balloon-expandable stents, stent-grafts, grafts (e.g., aortic grafts), heart valve prostheses, cerebrospinal fluid shunts, electrodes, pacemaker electrodes, catheters, sensors, endocardial leads (e.g., FINELINE® and ENDOTAK®, available from Abbott Vascular, Santa Clara, Calif.), anastomotic devices and connectors, orthopedic implants such as screws, spinal implants, and electro-stimulatory devices.
- the underlying structure of the device can be of virtually any design.
- the device can be made of a metallic material or an alloy such as, but not limited to, cobalt chromium alloy (ELGILOY), stainless steel (316L), high nitrogen stainless steel, e.g., BIODUR 108, cobalt chrome alloy L-605, “MP35N,” “MP20N,” ELASTINITE® (Nitinol), tantalum, nickel-titanium alloy, platinum-iridium alloy, gold, magnesium, or combinations thereof “MP35N” and “MP20N” are trade names for alloys of cobalt, nickel, chromium and molybdenum available from Standard Press Steel Co., Jenkintown, Pa.
- cobalt chromium alloy ELGILOY
- stainless steel 316L
- high nitrogen stainless steel e.g., BIODUR 108, cobalt chrome alloy L-605, “MP35N,” “MP20N,” ELASTINITE® (Nitinol), tantalum, nickel-titanium alloy, platinum-iridium alloy, gold, magnesium
- “MP35N” consists of 35% cobalt, 35% nickel, 20% chromium, and 10% molybdenum. “MP20N” consists of 50% cobalt, 20% nickel, 20% chromium, and 10% molybdenum.
- Devices made from bioabsorbable or biostable polymers or bioabsorbable metals such as magnesium could also be used with the embodiments of the present invention.
- the device is a bioabsorbable stent.
- a medical device having a coating that includes the elastin-based polymer described herein can be used for treating, preventing or ameliorating a medical condition.
- the medical device is a stent.
- the stent described herein is useful for a variety of medical procedures, including, by way of example, treatment of obstructions caused by tumors in bile ducts, esophagus, trachea/bronchi and other biological passageways.
- a stent having the above-described coating is particularly useful for treating diseased regions of blood vessels caused by lipid deposition, monocyte or macrophage infiltration, or dysfunctional endothelium or a combination thereof, or occluded regions of blood vessels caused by abnormal or inappropriate migration and proliferation of smooth muscle cells, thrombosis, and restenosis.
- Stents can be placed in a wide array of blood vessels, both arteries and veins.
- the device described herein can be in dialysis, as grafts, or fistulae.
- sites include the iliac, renal, carotid and coronary arteries.
- an angiogram is first performed to determine the appropriate positioning for stent therapy.
- An angiogram is typically accomplished by injecting a radiopaque contrasting agent through a catheter inserted into an artery or vein as an x-ray is taken.
- a guidewire is then advanced through the lesion or proposed site of treatment.
- Over the guidewire is passed a delivery catheter which allows a stent in its collapsed configuration to be inserted into the passageway.
- the delivery catheter is inserted either percutaneously or by surgery into the femoral artery, radial artery, brachial artery, femoral vein, or brachial vein, and advanced into the appropriate blood vessel by steering the catheter through the vascular system under fluoroscopic guidance.
- a stent having the above-described features can then be expanded at the desired area of treatment.
- a post-insertion angiogram can also be utilized to confirm appropriate positioning.
- 1% of an elastin-based copolymer (B-9 polymer) in TFE was coated onto VISIONTM 18 mm small stents, available from Abbott Vascular, Santa Clara, Calif., with a thickness of about 4 ⁇ m. Coated stents were then sent out for E-beam at 25 kGy.
- Particulate counting The particulate counting test was done in the similar format as that for simulated use test.
- the stent was expanded in a Tygon vessel. Distilled water was continuously flowing through the stent for 1 hour. The water flow rate is 100 ml/min. Any particulate generated was counted by a detector at each minute interval.
- the particulate size set was 10-25 ⁇ m, 25-165 ⁇ m, and >165 ⁇ m (these are based on USP and also set for XIENCETM V product). In this experiment, XIENCETM V was used as the control group.
- ID means lumen surface, which is exposed to water during simulated use test; OD is the abluminal surface, which was against the PVA tubing during the test.
- XIENCETM V is a coating formed of PVDF-HFP polymer (fluorinated polymer) with everolimus. BMS stands for “bare metal stent.”
- the chandler loop study showed B-9 coated stents had less thrombosis than bare metal Vision stent. B-9 coated stents also had more thrombosis than XIENCETM stents. But they are all very clean.
- the SEM image for the stent after chandler loop study showed no polymer dissolving or peeling on ID.
- the coatings formed in this Example were subjected to scanning electron micrograph (SEM) studies ( FIGS. 1-2 ).
- FIG. 1 shows that B-9 coating is crimping/icy hot onto catheters, followed after E-beam. It is noted that the surface is rough due to the choice of solvent.
- FIG. 2 shows the OD of B9 coated stent after simulated use test. The coating is still holding on the stent. It is also noted that the surface is smoother than that on the control sample in FIG. 1 .
- FIG. 3 shows a B-9 coated stent after chandler loop test. The coating is not impacted by 2-hour blood flow.
- FIG. 4 shows a typical OD surface of B-9 coated stent after chandler loop test. There is no peeling or cracking at the high strain area. The debris left on the surface are from the blood. But it is also seen that the surface has been smoothen as comparing to the control in FIG. 1 .
- FIG. 5 shows a typical ID surface of B-9 coated stent after chandler loop study. The stent was still covered by polymer and there was so sign of polymer peeling and dissolving.
- FIG. 6 shows thrombi weight of different type of coatings.
- the statistics parameters are shown below:
- B-9 polymer was able to be coated onto Vision stents with good coating integrity after expansion.
- the particulate count results showed comparable results as comparing to the XIENCETM V control and all passed the XIENCETM V particulate count specification.
- the chandler loop results did not show any adverse effect on thrombosis on this coating.
- a higher thrombosis than XIENCETM control probably is due to the fact that XIENCETM coat had very low surface energy that, by nature, does not adhere proteins. The less thrombosis of B-9 coating than bare metal VISION stents is positive.
Abstract
The present invention is directed to medical devices including coatings. The coatings include a topcoat which includes a copolymer comprising a block of an elastin pentapeptide. The topcoat is over a layer of poly(vinyl alcohol) on a hydrophobic coating or over a porous coating comprising pores or depots that include a bioactive agent.
Description
- This application is a continuation of U.S. application Ser. No. 11/803,031, filed on May 10, 2007 and published as U.S. Patent Application Publication No. 20080038310 A1 on Feb. 14, 2008, which is a continuation-in-part application of U.S. application Ser. No. 11/449,896, filed on Jun. 9, 2006 and published as U.S. Patent Application Publication No. 20070286885 A1 on Dec. 13, 2007, and both of application Ser. Nos. 11/803,031 and 11/449,896 are incorporated by reference herein in their entirety, including any drawings.
- This application incorporates by reference the material in the ASCII text file “SEQ.txt” of 1437 bytes created on Oct. 27, 2010 and filed in the parent application, application Ser. No. 11/803,031, on Nov. 3, 2010.
- 1. Field of the Invention
- This invention generally relates to elastin-based copolymers for coating an implantable device such as a drug delivery stent or for forming a composition as cell therapy carrier.
- 2. Description of the Background
- Blood vessel occlusions are commonly treated by mechanically enhancing blood flow in the affected vessels, such as by employing a stent. Stents are used not only for mechanical intervention but also as vehicles for providing biological therapy. To effect a controlled delivery of an active agent in stent medication, the stent can be coated with a biocompatible polymeric coating. The biocompatible polymeric coating can function either as a permeable layer or a carrier to allow a controlled delivery of the agent.
- The existing polymeric coating on a stent can have different types of limitations. For example, some poly(ester amide) based coatings can have poor mechanical properties so as to compromise coating integrity, and coating based on hydrophobic polymers can have problems in controlling release of a hydrophilic drug.
- Therefore, there is a need for new carrier materials for controlled delivery of an agent. There is a further need for coating materials for coating a medical device. There is also a need for polymers such as protein polymers that bioabsorb through a dissolution mechanism which are more vascularly biocompatible than synthetic polymers
- The polymer and methods of making the polymer disclosed herein address the above described problems.
- Described in this invention is an elastin-based copolymer. The copolymer can be used to form a coating on a medical device. In some embodiments, the coating can further include a polymer, a biobeneficial material, a bioactive agent, or combinations of these. Some examples of the bioactive agent include, but are not limited to, paclitaxel, docetaxel, estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O—[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), pimecrolimus, imatinib mesylate, midostaurin, clobetasol, mometasone, bioactive RGD, CD-34 antibody, abciximab (REOPRO), progenitor cell capturing antibody, prohealing drugs, growth factor vascular endothelial growth factor (VEGF), prodrugs thereof, co-drugs thereof, or a combination thereof. In some embodiments, the coating can include a combination of two drugs, such as both an anti-proliferative and an anti-inflammatory.
- In some embodiments, the elastin-based copolymer can be used as hydrogel-like scaffold. For example, one can use it as cell delivery using a depot platform. In some embodiments, a matrix including the polymer described herein can be injected into depots that sit on a carrier platform such as depot stents.
- A medical device having a coating or depot platform described herein can be used to treat, prevent, or ameliorate a vascular medical condition. Some exemplary vascular medical conditions include atherosclerosis, thrombosis, restenosis, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, urethra obstruction, tumor obstruction, and combinations thereof.
-
FIG. 1 shows that B-9 coating is crimping/icy hot onto catheters, followed after E-beam. -
FIG. 2 shows the OD of B9 coated stent after simulated use test. -
FIG. 3 shows a B-9 coated stent after chandler loop test. -
FIG. 4 shows a typical OD surface of B-9 coated stent after chandler loop test. -
FIG. 5 shows a typical ID surface of B-9 coated stent after chandler loop study. -
FIG. 6 shows thrombi weight of different type of coatings. - Described in this invention is an elastin-based copolymer. The copolymer can be used to form a coating on a medical device. In some embodiments, the coating can further include a polymer, a biobeneficial material, a bioactive agent, or combinations of these. Some examples of the bioactive agent include, but are not limited to, paclitaxel, docetaxel, estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O—[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), pimecrolimus, imatinib mesylate, midostaurin, clobetasol, mometasone, bioactive RGD, CD-34 antibody, abciximab (REOPRO), progenitor cell capturing antibody, prohealing drugs, growth factors such as vascular endothelial growth factor (VEGF), prodrugs thereof, co-drugs thereof, or a combination thereof. In some embodiments, the coating can include a combination of two drugs, such as both an anti-proliferative and an anti-inflammatory.
- In some embodiments, the elastin-based copolymer can be used as hydrogel-like scaffold. For example, one can use it as cell delivery using a depot platform. In some embodiments, a matrix including the polymer described herein can be injected into depots that sit on a carrier platform such as depot stents.
- As used herein, the term “elastin-based copolymer” is sometimes referred to as the “elastin-based polymer”. These two terms can be used interchangeably. Other names include protein elastomer, protein polymer, protein tri-block copolymer, and elastin mimetic.
- A medical device having a coating or depot platform described herein can be used to treat, prevent, or ameliorate a vascular medical condition. Some exemplary vascular medical conditions include atherosclerosis, thrombosis, restenosis, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, urethra obstruction, tumor obstruction, and combinations thereof.
- Elastin is a protein that is found in the walls of arteries, in lungs, intestines and skin in the body of an animal. Elastin imparts elasticity to the body. Working in partnership with collagen, elastin allows the body organs to stretch and relax. Thus, while collagen provides rigidity, elastin allows the blood vessels and heart tissues, for example, to stretch and then revert to their original positions, i.e. to recoil. Therefore, elastin provides for structural integrity and for the compliance of the vessel at low pressure whereas collagen gives the tensile resistance required at high pressures.
- Elastin is found to contain short peptides. The most frequent pentapeptide sequence is valyl-glycyl-valyl-prolyl-glycine (VGVPG) (SEQ ID NO: 1). VGVPG (SEQ ID NO: 1) is found to exhibit elastin-like properties (see, e.g., Reiersen, H., et al., J. Mol. Biol. 283:255-264 (1998)). See also: Biomaterials 26 (2005) 4695-4706.
- In some embodiments, the elastin-based polymer described herein can be an ABA or BAB type polymer, where A represents a unit that includes the pentapeptide sequence VGVPG (SEQ ID NO: 1) and B represents a unit which can be a peptide sequence or a unit derived from a monomer. The copolymer can be a block or random copolymer. Commonly the BAB block copolymers are comprised such that the B-block is hydrophobic while the A-block is more hydrophilic.
- In some embodiments, the elastin-based copolymer is an ABA triblock copolymer, where A is a block comprising the VGVPG (SEQ ID NO: 1) sequence and B is a block derived from a peptide or monomer(s). In some embodiments, B can be a hydrophilic variant of the VGVPG (SEQ ID NO: 1) peptide. The term “variant” refers to any form of VGVPG (SEQ ID NO: 1) modification. For example, an amino acid in the peptide can be replaced with another amino acid. In some embodiments, the sequence of VGVPG (SEQ ID NO: 1) can be varied so as to form a variant of the VGVPG (SEQ ID NO: 1) peptide. In some embodiments, the VGVPG (SEQ ID NO: 1) peptide can be modified to include lysine (lysine block). This lysine block can be used as the middle block to form the ABA triblock copolymer with the VGVPG (SEQ ID NO: 1) pentapeptide. In these embodiments, the lysine block can be modified to conjugate a molecule or polymer such as phosphoryl choline (PC), poly(ethylene glycol) (PEG), or a bioactive moiety such as nitric oxide generating catalyst or TEMPO as pendant groups. These pendant groups can impart different physical, chemical, or biological properties to the elastin-based polymer.
- As one of the properties for the natural elastin materials are usually non-degradable or very slow degradation, degradable linkages can be formed between the peptide blocks so that the newly formed elastin-based materials could be degradable. Any biodegradable polymers described below can be used as the linkage. Some examples of these degradable linkages are poly(lactic acid) (PLA), poly(glycolic acid) (PLGA), polycaprolactone (PCL), poly(3-hydroxybutyric acid (PHB), poly(4-hydroxybutyrate (P4HB), or combinations of these. Some other clearance mechanisms can be enzymatically degradable (via elastase) or biosoluble when the polymer is sufficiently hydrophilic.
- In some embodiments, the elastin-based copolymer is an ABA triblock copolymer where A is a block comprising the VGVPG (SEQ ID NO: 1) peptide and B is a hydrophilic synthetic polymer. Such a synthetic polymer can be, for example, a hydrophilic polymer such as PEG, PVP (poly vinylpyrrolidinone), polyacrylamide, poly(PEG acrylate), poly (HEMA), poly(acrylic acid) or combinations of these polymers.
- In some embodiments, the elastin-based copolymer is an ABA triblock copolymer where A is a block comprising the VGVPG (SEQ ID NO: 1) peptide and B is a hydrophilic natural polymer such as protein or peptide. In some embodiments, such a hydrophilic natural polymer can be, for example, collagen or collagen derivative, hyaluronic acid, alginate or combinations of these.
- In some embodiments, the elastin-based polymer can include a peptide sequence that promotes proliferation and/or migration of endothelial cells (ECs). Such peptide sequence can be, for example, RGD, cRGD, or EC specific sequences such as SIKVAV (SEQ ID NO: 2), CNP, YIGSRG (SEQ ID NO: 3), mimetics of these sequences, or combinations of these.
- In some embodiments, the elastin-based copolymer can include an enzyme susceptible segment(s) or hydrolytically susceptible segment(s). These segment(s) can modify the absorption rate of the polymer so as to allow fine tuning of the absorption rate of the polymer. For example, the absorption rate of the elastin-based polymer can be increased or decreased by the content of these enzyme susceptible segment(s) or hydrolytically susceptible segment(s). As used herein, the term “content” refers to molar ratio of the total units in the enzyme susceptible segment(s) and/or hydrolytically susceptible segment(s) to the total units in the polymer and can range from e.g., above 0 to about 0.5, for example. Examples of enzyme susceptible segment(s) or hydrolytically susceptible segment(s) include, but are not limited to, poly-lactic acid, poly(glycolic) acid, polycaprolactone, poly(alkene succinate), aliphatic-aromatic copolyesters, poly(orthoesters), polyanhydrides, polycarbonates/polyiminocarbonates, or natural degradable polymers including starch, fibre, fibre-starch composites, cellulose, etc.
- As used herein, the term “enzyme susceptible segment(s)” refers to a segment(s) that comprises a bonding that can be cleaved by enzyme(s). The term “hydrolytically susceptible segment(s)” refers to a segment(s) that comprises a bonding that can be cleaved by hydrolysis.
- In some embodiments, the elastin-based polymer can be used in a composition for cell therapy carrier. For example, the composition can include the elastin-based polymer, cells such as stem cells and optionally other materials and agents. The composition can be delivered to a dysfunctional part of the body (e.g., an organ such as heart or blood vessel) while the cells are still viable. In some embodiments, the composition can include a pharmaceutically acceptable carrier.
- Delivery of the composition can be achieved by any established modes of delivery. Preferably, the delivery can be achieved via delivery from a coating on a medical device (e.g., a stent). In some embodiments, the delivery can be injection or delivery through catheter. In some embodiments, the composition can also be delivered using surgical method such as creating a depot within the muscle and releasing the pharmaceutical agent(s) out of the depot.
- In some embodiments, the elastin-based copolymer can be used as hydrogel-like scaffold. For example, one can use it as cell delivery using a depot platform. In some embodiments, a matrix including the polymer described herein can be injected into depots that sit on a carrier platform such as depot stents.
- The elastin-based polymer can form a layer of coating as a topcoat, a matrix layer or a primer layer. The elastin-based polymer coated on a medical device such as a stent according to an established coating process such as dipping, spray or other processes.
- In some embodiments, the coating can be formed by dipping in an aqueous solution of the elastin-based polymer. For example, in some embodiments, a solution of an elastin-based polymer described here can be provided. A medical device such as a stent can be dipped in (rinsed) the solution at a temperature below ambient temperature (e.g., 4° C.). The rinsed medical device can be subject to heat treatment at a temperature in the range of about 15° C.-30° C. higher than the lower critical solution temperature (LCST) of the elastin-based polymer to generate a coating with biomimcry effect.
FIG. 1 shows stent coated with an elastin-based polymer of the present invention after wet expansion. - A solution of the elastin-based polymer can have a concentration of the polymer ranging from about 1 wt % to about 50 wt %. Preferably, the solution has a concentration of the elastin-based polymer in the range between about 5 wt % and about 30%, for example, about 10 wt %, about 15 wt %, about 20 wt % or about 25 wt %. The solution can include a solvent such as water or a biocompatible organic solvent such as dimethylformamide (DMF), dimethyl sulfoxide (DMSO), dimethyl acetamide (DMAC), methyl ethyl ketone (MEK), ethylene glycol or combinations of these.
- In some embodiments, the solvent can be trifluoroethanol (TFE). TFE has a boiling temperature of about 80° C., making the solvent a good solvent for use in coating a medical device. The concentration can be varied and determined according to the molecular weight of the elastin-based polymer for forming the coating. For example, with a elastin-based polymer with a weight average molecular weight about 160K Daltons, a solution of the polymer of about 2 wt % in TFE can be used to form a coating on a medical device using spray coating method at room temperature.
- In some embodiments, the solution can be an acidic solution having a pH lower than 7. Where an acidic solution of the elastin-based polymer is used to form the coating on a medical device, medical device rinsed or sprayed with the acidic solution shall be rinsed (or sprayed) with a solution of basic pH (>7) buffered solution. Upon pH increase, the elastin-based polymer will come out of the solution and result in a coating on the medical device. The basic buffered solution can be any basic buffer solution in the art.
- The mechanical property of the film cast from elastin-based polymer depends on the solution used in the cast. For example, for elongation of the film, generally a pH>7 coating system will lead to a higher elongation than a neutral or acidic water coating system, and a neutral or acidic water coating system will lead to a higher elongation than a TFE coating system.
- In some embodiments, the elastin-based polymer can be coated on a nano- or micro-porous device (e.g., a stent from Blue-Membranes, GmbH, Germany) for controlled release of an agent (e.g., a drug) by modulating the porosity and porous coating thickness. For example, the elastin-based polymer can be coated on the abluminal side of an implantable device as a thin or very thin topcoat. As used herein, the term “thin” or “very thin” refers to a thickness of less than about 1 μm, less than about 500 nm, less than about 100 nm, less than about 50 nm, or less than about 10 nm.
- In some embodiments, the elastin-based polymer can be coated on a hydrophobic surface of an implantable device (e.g., a stent). To form this coating, the hydrophobic surface of the implantable device can be modified to include a thin layer of a hydrophilic polymer such as a polymer comprising poly(vinyl alcohol) (PVOH). For example, the surface comprising a fluoropolymer such as a poly(vinylidene fluoride) (SOLEF™) polymer can be modified by forming a thin layer of PVOH thereon and then forming a thin layer of the elastin-based polymer on top of the PVOH layer. The layer of PVOH can be formed by exposing a hydrophobic surface to a dilute PVOH solution (e.g., a concentration of less than about 5 mass %, less than about 1 mass %, less than about 0.5 mass %, less than about 0.1 mass %, less than about 0.05 or mass % less than about 0.01 mass %) and allowing the PVOH molecule to adsorb onto the hydrophobic surface. Methods of forming a thin PVOH layer on a hydrophobic surface have been described by U.S. application Ser. No. 11/365,392, the teaching of which is incorporated herein by reference in its entirety. As used herein, the term “thin” or “very thin” refers to a thickness of less than about 1 μm, less than about 500 nm, less than about 100 nm, less than about 50 nm, or less than about 10 nm.
- The elastin-based copolymers described herein can be used with other biocompatible polymers. One of the exemplary constructs with other polymers is that the elastin-based copolymer form a topcoat, where the other polymer serves as the controlled release coating and the elastin-based polymer is a topcoat. The biocompatible polymer can be biodegradable (either bioerodible or bioabsorbable or both) or nondegradable and can be hydrophilic or hydrophobic. Representative biocompatible polymers include, but are not limited to, poly(ester amide), polyhydroxyalkanoates (PHA), poly(3-hydroxyalkanoates) such as poly(3-hydroxypropanoate), poly(3-hydroxybutyrate), poly(3-hydroxyvalerate), poly(3-hydroxyhexanoate), poly(3-hydroxyheptanoate) and poly(3-hydroxyoctanoate), poly(4-hydroxyalkanaote) such as poly(4-hydroxybutyrate), poly(4-hydroxyvalerate), poly(4-hydroxyhexanote), poly(4-hydroxyheptanoate), poly(4-hydroxyoctanoate) and copolymers including any of the 3-hydroxyalkanoate or 4-hydroxyalkanoate monomers described herein or blends thereof, poly(D,L-lactide), poly(L-lactide), polyglycolide, poly(D,L-lactide-co-glycolide), poly(L-lactide-co-glycolide), polycaprolactone, poly(lactide-co-caprolactone), poly(glycolide-co-caprolactone), poly(dioxanone), poly(ortho esters), poly(anhydrides), poly(tyrosine carbonates) and derivatives thereof, poly(tyrosine ester) and derivatives thereof, poly(imino carbonates), poly(glycolic acid-co-trimethylene carbonate), polyphosphoester, polyphosphoester urethane, poly(amino acids), polycyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), polyphosphazenes, silicones, polyesters, polyolefins, polyisobutylene and ethylene-alphaolefin copolymers, acrylic polymers and copolymers, vinyl halide polymers and copolymers, such as polyvinyl chloride, polyvinyl ethers, such as polyvinyl methyl ether, polyvinylidene halides, such as polyvinylidene chloride, polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics, such as polystyrene, polyvinyl esters, such as polyvinyl acetate, copolymers of vinyl monomers with each other and olefins, such as ethylene-methyl methacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins, and ethylene-vinyl acetate copolymers, polyamides, such as Nylon 66 and polycaprolactam, alkyd resins, polycarbonates, polyoxymethylenes, polyimides, polyethers, poly(glyceryl sebacate), poly(propylene fumarate), poly(n-butyl methacrylate), poly(sec-butyl methacrylate), poly(isobutyl methacrylate), poly(tert-butyl methacrylate), poly(n-propyl methacrylate), poly(isopropyl methacrylate), poly(ethyl methacrylate), poly(methyl methacrylate), epoxy resins, polyurethanes, rayon, rayon-triacetate, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ethers, carboxymethyl cellulose, polyethers such as poly(ethylene glycol) (PEG), copoly(ether-esters) (e.g. poly(ethylene oxide-co-lactic acid) (PEO/PLA)), polyalkylene oxides such as poly(ethylene oxide), poly(propylene oxide), poly(ether ester), polyalkylene oxalates, phosphoryl choline containing polymer, choline, poly(aspirin), polymers and co-polymers of hydroxyl bearing monomers such as 2-hydroxyethyl methacrylate (HEMA), hydroxypropyl methacrylate (HPMA), hydroxypropylmethacrylamide, PEG acrylate (PEGA), PEG methacrylate, methacrylate polymers containing 2-methacryloyloxyethylphosphorylcholine (MPC) and n-vinyl pyrrolidone (VP), carboxylic acid bearing monomers such as methacrylic acid (MA), acrylic acid (AA), alkoxymethacrylate, alkoxyacrylate, and 3-trimethylsilylpropyl methacrylate (TMSPMA), poly(styrene-isoprene-styrene)-PEG (SIS-PEG), polystyrene-PEG, polyisobutylene-PEG, polycaprolactone-PEG (PCL-PEG), PLA-PEG, poly(methyl methacrylate)-PEG (PMMA-PEG), polydimethylsiloxane-co-PEG (PDMS-PEG), poly(vinylidene fluoride)-PEG (PVDF-PEG), PLURONIC™ surfactants (polypropylene oxide-co-polyethylene glycol), poly(tetramethylene glycol), hydroxy functional poly(vinyl pyrrolidone), molecules such as collagen, chitosan, alginate, fibrin, fibrinogen, cellulose, starch, dextran, dextrin, hyaluronic acid, fragments and derivatives of hyaluronic acid, heparin, fragments and derivatives of heparin, glycosamino glycan (GAG), GAG derivatives, polysaccharide, elastin, elastin protein mimetics, or combinations thereof. Some examples of elastin protein mimetics include (LGGVG)n (SEQ ID NO: 4), (VPGVG)n (SEQ ID NO: 5), Val-Pro-Gly-Val-Gly (SEQ ID NO: 6), or synthetic biomimetic poly(L-glytanmate)-b-poly(2-acryloyloxyethyllactoside)-b-poly(1-glutamate) triblock copolymer.
- In some embodiments, the polymer can be poly(ethylene-co-vinyl alcohol), poly(methoxyethyl methacrylate), poly(dihydroxylpropyl methacrylate), polymethacrylamide, aliphatic polyurethane, aromatic polyurethane, nitrocellulose, poly(ester amide benzyl), co-poly-{[N,N′-sebacoyl-bis-(L-leucine)-1,6-hexylene diester]0.75-[N,N′-sebacoyl-L-lysine benzyl ester]0.25} (PEA-Bz), co-poly-{[N,N′-sebacoyl-bis-(L-leucine)-1,6-hexylene diester]0.75-[N,N′-sebacoyl-L-lysine-4-amino-TEMPO amide]0.25} (PEA-TEMPO), aliphatic polyester, aromatic polyester, fluorinated polymers such as poly(vinylidene fluoride-co-hexafluoropropylene), poly(vinylidene fluoride) (PVDF), and TEFLON™ (polytetrafluoroethylene), a biopolymer such as elastin mimetic protein polymer, star or hyper-branched SIBS (styrene-block-isobutylene-block-styrene), or combinations thereof. In some embodiments, where the polymer is a copolymer, it can be a block copolymer that can be, e.g., di-, tri-, tetra-, or oligo-block copolymers or a random copolymer. In some embodiments, the polymer can also be branched polymers such as star polymers.
- In some embodiments, a coating having the features described herein can exclude any one of the aforementioned polymers.
- As used herein, the terms poly(D,L-lactide), poly(L-lactide), poly(D,L-lactide-co-glycolide), and poly(L-lactide-co-glycolide) can be used interchangeably with the terms poly(D,L-lactic acid), poly(L-lactic acid), poly(D,L-lactic acid-co-glycolic acid), or poly(L-lactic acid-co-glycolic acid), respectively.
- The elastin-based copolymer can optionally used with a biobeneficial material. The biobeneficial material can be a polymeric material or non-polymeric material. The biobeneficial material is preferably non-toxic, non-antigenic and non-immunogenic. A biobeneficial material is one which enhances the biocompatibility of the particles or device by being non-fouling, hemocompatible, actively non-thrombogenic, or antiinflammatory, all without depending on the release of a pharmaceutically active agent.
- Representative biobeneficial materials include, but are not limited to, polyethers such as poly(ethylene glycol), copoly(ether-esters) (e.g. PEO/PLA), polyalkylene oxides such as poly(ethylene oxide), polypropylene oxide), poly(ether ester), polyalkylene oxalates, polyphosphazenes, phosphoryl choline, choline, poly(aspirin), polymers and co-polymers of hydroxyl bearing monomers such as hydroxyethyl methacrylate (HEMA), hydroxypropyl methacrylate (HPMA), hydroxypropylmethacrylamide, poly(ethylene glycol)acrylate (PEGA), PEG methacrylate, 2-methacryloyloxyethylphosphorylcholine (MPC) and n-vinyl pyrrolidone (VP), carboxylic acid bearing monomers such as methacrylic acid (MA), acrylic acid (AA), alkoxymethacrylate, alkoxyacrylate, and 3-trimethylsilylpropyl methacrylate (TMSPMA), poly(styrene-isoprene-styrene)-PEG (SIS-PEG), polystyrene-PEG, polyisobutylene-PEG, polycaprolactone-PEG (PCL-PEG), PLA-PEG, poly(methyl methacrylate)-PEG (PMMA-PEG), polydimethylsiloxane-co-PEG (PDMS-PEG), poly(vinylidene fluoride)-PEG (PVDF-PEG), PLURONIC™ surfactants (polypropylene oxide-co-polyethylene glycol), poly(tetramethylene glycol), hydroxy functional poly(vinyl pyrrolidone), molecules such as fibrin, fibrinogen, cellulose, starch, collagen, dextran, dextrin, hyaluronic acid, fragments and derivatives of hyaluronic acid, heparin, fragments and derivatives of heparin, glycosamino glycan (GAG), GAG derivatives, polysaccharide, elastin, chitosan, alginate, silicones, POLYACTIVE™, and combinations thereof. In some embodiments, a coating described herein can exclude any one of the aforementioned polymers. The term POLYACTIVE™ refers to a block copolymer having flexible poly(ethylene glycol) and poly(butylene terephthalate) blocks (PEGT/PBT). POLYACTIVE™ is intended to include AB, ABA, BAB copolymers having such segments of PEG and PBT (e.g., poly(ethylene glycol)-block-poly(butyleneterephthalate)-block poly(ethylene glycol) (PEG-PBT-PEG).
- In a preferred embodiment, the biobeneficial material can be a polyether such as poly(ethylene glycol) (PEG) or polyalkylene oxide.
- The elastin-based copolymer can form a coating on a medical device. The coating can include one or more bioactive agent(s), which can be therapeutic, prophylactic, or diagnostic agent(s). These agents can have anti-proliferative or anti-inflammatory properties or can have other properties such as antineoplastic, antiplatelet, anti-coagulant, anti-fibrin, antithrombogenic, antimitotic, antibiotic, antiallergic, antifibrotic, and antioxidant. The agents can be cystostatic agents, agents that promote the healing of the endothelium such as NO releasing or generating agents, agents that attract endothelial progenitor cells, agents that promote the attachment, migration or proliferation of endothelial cells (e.g., natriuretic peptides such as CNP, ANP or BNP peptide or an RGD or cRGD peptide), while impeding smooth muscle cell proliferation. Examples of suitable therapeutic and prophylactic agents include synthetic inorganic and organic compounds, proteins and peptides, polysaccharides and other sugars, lipids, and DNA and RNA nucleic acid sequences having therapeutic, prophylactic or diagnostic activities. Some other examples of the bioactive agent include antibodies, receptor ligands, enzymes, adhesion peptides, blood clotting factors, inhibitors or clot dissolving agents such as streptokinase and tissue plasminogen activator, antigens for immunization, hormones and growth factors, oligonucleotides such as antisense oligonucleotides, small interfering RNA (siRNA), small hairpin RNA (shRNA), aptamers, ribozymes and retroviral vectors for use in gene therapy. Examples of anti-proliferative agents include rapamycin and its functional or structural derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), and its functional or structural derivatives, paclitaxel and its functional and structural derivatives. Examples of rapamycin derivatives include 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, and 40-O-tetrazole-rapamycin. Examples of paclitaxel derivatives include docetaxel. Examples of antineoplastics and/or antimitotics include methotrexate, azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride (e.g. ADRIAMYCIN® from Pharmacia & Upjohn, Peapack N.J.), and mitomycin (e.g. MUTAMYCIN® from Bristol-Myers Squibb Co., Stamford, Conn.). Examples of such antiplatelets, anticoagulants, antifibrin, and antithrombins include sodium heparin, low molecular weight heparins, heparinoids, hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor antagonist antibody, recombinant hirudin, thrombin inhibitors such as ANGIOMAX™ (bivalirudin, Biogen, Inc., Cambridge, Mass.), calcium channel blockers (such as nifedipine), colchicine, fibroblast growth factor (FGF) antagonists, fish oil (omega 3-fatty acid), histamine antagonists, lovastatin (an inhibitor of HMG-CoA reductase, a cholesterol lowering drug, brand name MEVACOR® from Merck & Co., Inc., Whitehouse Station, N.J.), monoclonal antibodies (such as those specific for Platelet-Derived Growth Factor (PDGF) receptors), nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitors, suramin, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist), nitric oxide or nitric oxide donors, super oxide dismutases, super oxide dismutase mimetic, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), estradiol, anticancer agents, dietary supplements such as various vitamins, and a combination thereof. Examples of anti-inflammatory agents including steroidal and non-steroidal anti-inflammatory agents include tacrolimus, dexamethasone, clobetasol, mometasone, or combinations thereof. Examples of cytostatic substances include angiopeptin, angiotensin converting enzyme inhibitors such as captopril (e.g. CAPOTEN® and CAPOZIDE® from Bristol-Myers Squibb Co., Stamford, Conn.), cilazapril or lisinopril (e.g. PRINIVIL® and PRINZIDE® from Merck & Co., Inc., Whitehouse Station, N.J.). An example of an antiallergic agent is permirolast potassium. Other therapeutic substances or agents which can be appropriate include alpha-interferon, pimecrolimus, imatinib mesylate, midostaurin, bioactive RGD, SIKVAV (SEQ ID NO: 2) peptides, growth factor vascular endothelial growth factor (VEGF), elevating agents such as cANP or cGMP peptides, and genetically engineered endothelial cells. The foregoing substances can also be used in the form of prodrugs or co-drugs thereof. The foregoing substances also include metabolites thereof and/or prodrugs of the metabolites. The foregoing substances are listed by way of example and are not meant to be limiting. Other active agents which are currently available or that may be developed in the future are equally applicable.
- The dosage or concentration of the bioactive agent required to produce a favorable therapeutic effect should be less than the level at which the bioactive agent produces toxic effects and greater than non-therapeutic levels. The dosage or concentration of the bioactive agent can depend upon factors such as the particular circumstances of the patient, the nature of the trauma, the nature of the therapy desired, the time over which the administered ingredient resides at the vascular site, and if other active agents are employed, the nature and type of the substance or combination of substances. Therapeutically effective dosages can be determined empirically, for example by infusing vessels from suitable animal model systems and using immunohistochemical, fluorescent or electron microscopy methods to detect the agent and its effects, or by conducting suitable in vitro studies. Standard pharmacological test procedures to determine dosages are understood by one of ordinary skill in the art.
- As used herein, a medical device can be any suitable medical substrate that can be implanted in a human or veterinary patient. Examples of such medical devices include self-expandable stents, balloon-expandable stents, stent-grafts, grafts (e.g., aortic grafts), heart valve prostheses, cerebrospinal fluid shunts, electrodes, pacemaker electrodes, catheters, sensors, endocardial leads (e.g., FINELINE® and ENDOTAK®, available from Abbott Vascular, Santa Clara, Calif.), anastomotic devices and connectors, orthopedic implants such as screws, spinal implants, and electro-stimulatory devices. The underlying structure of the device can be of virtually any design. The device can be made of a metallic material or an alloy such as, but not limited to, cobalt chromium alloy (ELGILOY), stainless steel (316L), high nitrogen stainless steel, e.g., BIODUR 108, cobalt chrome alloy L-605, “MP35N,” “MP20N,” ELASTINITE® (Nitinol), tantalum, nickel-titanium alloy, platinum-iridium alloy, gold, magnesium, or combinations thereof “MP35N” and “MP20N” are trade names for alloys of cobalt, nickel, chromium and molybdenum available from Standard Press Steel Co., Jenkintown, Pa. “MP35N” consists of 35% cobalt, 35% nickel, 20% chromium, and 10% molybdenum. “MP20N” consists of 50% cobalt, 20% nickel, 20% chromium, and 10% molybdenum. Devices made from bioabsorbable or biostable polymers or bioabsorbable metals such as magnesium could also be used with the embodiments of the present invention. In some embodiments, the device is a bioabsorbable stent.
- In accordance with embodiments of the invention, a medical device having a coating that includes the elastin-based polymer described herein can be used for treating, preventing or ameliorating a medical condition. Preferably, the medical device is a stent. The stent described herein is useful for a variety of medical procedures, including, by way of example, treatment of obstructions caused by tumors in bile ducts, esophagus, trachea/bronchi and other biological passageways. A stent having the above-described coating is particularly useful for treating diseased regions of blood vessels caused by lipid deposition, monocyte or macrophage infiltration, or dysfunctional endothelium or a combination thereof, or occluded regions of blood vessels caused by abnormal or inappropriate migration and proliferation of smooth muscle cells, thrombosis, and restenosis. Stents can be placed in a wide array of blood vessels, both arteries and veins. In some embodiments, the device described herein can be in dialysis, as grafts, or fistulae.
- Representative examples of sites include the iliac, renal, carotid and coronary arteries.
- For implantation of a stent, an angiogram is first performed to determine the appropriate positioning for stent therapy. An angiogram is typically accomplished by injecting a radiopaque contrasting agent through a catheter inserted into an artery or vein as an x-ray is taken. A guidewire is then advanced through the lesion or proposed site of treatment. Over the guidewire is passed a delivery catheter which allows a stent in its collapsed configuration to be inserted into the passageway. The delivery catheter is inserted either percutaneously or by surgery into the femoral artery, radial artery, brachial artery, femoral vein, or brachial vein, and advanced into the appropriate blood vessel by steering the catheter through the vascular system under fluoroscopic guidance. A stent having the above-described features can then be expanded at the desired area of treatment. A post-insertion angiogram can also be utilized to confirm appropriate positioning.
- 1% of an elastin-based copolymer (B-9 polymer) in TFE was coated onto VISION™ 18 mm small stents, available from Abbott Vascular, Santa Clara, Calif., with a thickness of about 4 μm. Coated stents were then sent out for E-beam at 25 kGy.
- The following tests were then conducted on these stents:
- 1) Simulated use test—stent was expanded in PVA vessel following by 37 C distilled water flowing through the stent for 1 hour. The water flow rate is 50 ml/min.
- 2) Particulate counting—The particulate counting test was done in the similar format as that for simulated use test. The stent was expanded in a Tygon vessel. Distilled water was continuously flowing through the stent for 1 hour. The water flow rate is 100 ml/min. Any particulate generated was counted by a detector at each minute interval. The particulate size set was 10-25 μm, 25-165 μm, and >165 μm (these are based on USP and also set for XIENCE™ V product). In this experiment, XIENCE™ V was used as the control group.
- 3) Chandler loop study, bare metal vision stent and XIENCE™ V stent were used as control. The whole porcine blood was flowing through the stent (relative movement) for 2 hours. The theoretical flow rate is about 75 ml/min.
- As used herein, ID means lumen surface, which is exposed to water during simulated use test; OD is the abluminal surface, which was against the PVA tubing during the test. XIENCE™ V is a coating formed of PVDF-HFP polymer (fluorinated polymer) with everolimus. BMS stands for “bare metal stent.”
- After simulated use test, the most of OD surface was not affected by the simulated use. The particulate count data showed similar results as compared to the control group (XIENCE™ V) and they all passed the XIENCE™ V specification (Table 1). The stents were also examined using SEM after the particulate count test.
-
TABLE 1 Particulate Count Result 5 min 10 min 20 min 40 min 60 min 10-25 um Blank Ave 34 55 73 108 115 SD 30 60 85 87 94 Control Ave 99 100 101 103 105 SD 146 146 146 145 148 B-9 Ave 107 108 113 138 153 SD 118 121 120 121 127 25-165 um Blank Ave 35 91 101 172 274 SD 34 80 92 147 247 Control Ave 20 20 20 20 20 SD 33 33 33 33 33 B-9 Ave 20 21 23 24 26 SD 28 30 33 32 32 >165 um Blank Ave 3 8 8 17 17 SD 6 13 14 14 14 Control Ave 5 5 5 5 5 SD 8 8 8 8 8 B-9 Ave 7 7 7 7 7 SD 12 12 12 12 12 n = 3 for blank, n = 6 for XIENCE ™ control, n = 6 for B-9 coating Criteria for XIENCE ™ V Bin 10 <= 2100/per sample Bin 25 <= 200/per sample Ben 165 <= 200/per sample - The chandler loop study showed B-9 coated stents had less thrombosis than bare metal Vision stent. B-9 coated stents also had more thrombosis than XIENCE™ stents. But they are all very clean. The SEM image for the stent after chandler loop study showed no polymer dissolving or peeling on ID.
- The coatings formed in this Example were subjected to scanning electron micrograph (SEM) studies (
FIGS. 1-2 ). -
FIG. 1 shows that B-9 coating is crimping/icy hot onto catheters, followed after E-beam. It is noted that the surface is rough due to the choice of solvent. -
FIG. 2 shows the OD of B9 coated stent after simulated use test. The coating is still holding on the stent. It is also noted that the surface is smoother than that on the control sample inFIG. 1 . - The coatings formed above were subjected to Chandler loop study. Some representative results are shown in
FIGS. 3-6 . -
FIG. 3 shows a B-9 coated stent after chandler loop test. The coating is not impacted by 2-hour blood flow. -
FIG. 4 shows a typical OD surface of B-9 coated stent after chandler loop test. There is no peeling or cracking at the high strain area. The debris left on the surface are from the blood. But it is also seen that the surface has been smoothen as comparing to the control inFIG. 1 . -
FIG. 5 shows a typical ID surface of B-9 coated stent after chandler loop study. The stent was still covered by polymer and there was so sign of polymer peeling and dissolving. -
FIG. 6 shows thrombi weight of different type of coatings. InFIG. 6 , the statistics parameters are shown below: - XIENCE™ vs BMS: p value=0.0025
- B9 vs BMS: p value=0.0678
- B9 vs XIENCE™: p value=0.0584
- B-9 polymer was able to be coated onto Vision stents with good coating integrity after expansion. The particulate count results showed comparable results as comparing to the XIENCE™ V control and all passed the XIENCE™ V particulate count specification. The chandler loop results did not show any adverse effect on thrombosis on this coating. A higher thrombosis than XIENCE™ control probably is due to the fact that XIENCE™ coat had very low surface energy that, by nature, does not adhere proteins. The less thrombosis of B-9 coating than bare metal VISION stents is positive.
- The coating after 2 hours in chandler loop (flow rate as 75 ml/min) showed that the coating was not impacted at all, without any cracking at high strain area. This result indicates that the B-9 coating behave differently in blood as comparing in water.
- While particular embodiments of the present invention have been shown and described, it will be obvious to those skilled in the art that changes and modifications can be made without departing from this invention in its broader aspects. Therefore, the appended claims are to encompass within their scope all such changes and modifications as fall within the true spirit and scope of this invention.
Claims (25)
1. A medical device comprising a topcoat of a copolymer on top of a coating, wherein the copolymer comprises a block comprising an elastin pentapeptide VGVPG (SEQ ID NO:1) (A) and a hydrophilic block (B),
wherein the coating comprises a layer of a hydrophobic polymer underneath a thin layer of a polymer comprising poly(vinyl alcohol) (PVOH), and the topcoat on top of the thin layer of polymer comprising PVOH.
2. The medical device of claim 1 , wherein the copolymer is an ABA triblock copolymer.
3. The medical device of claim 1 , wherein the hydrophilic block comprises lysine.
4. The medical device of claim 2 , wherein the hydrophilic block comprises lysine.
5. The medical device of claim 2 , wherein the hydrophilic block comprises a synthetic polymer.
6. The medical device of claim 2 , wherein the hydrophilic block comprises a natural polymer.
7. The medical device of claim 2 , wherein the hydrophilic block is a variant of the VGVPG obtained by replacing one amino acid in VGVPG (SEQ ID NO:1) with another amino acid.
8. The medical device of claim 4 , wherein the copolymer further comprises a phosphoryl choline (PC) or poly(ethylene glycol) (PEG) pendant group,
wherein the PC or PEG is conjugated to the block copolymer via lysine in the hydrophilic block.
9. The medical device of claim 5 , wherein the synthetic polymer is selected from PEG, PVP (poly vinylpyrrolidinone), polyacrylamide, poly(PEG acrylate), poly (HEMA), poly(acrylic acid), and combinations of these.
10. The medical device of claim 6 , wherein the natural polymer is selected from collagen, collagen derivative, hyaluronic acid, alginate, and combinations of these.
11. The medical device of claim 1 , wherein the copolymer further comprises, an ANP peptide, a BNP peptide, an RGD peptide, a cRGD peptide, a SIKVAV peptide (SEQ ID NO: 2), a CNP peptide, a YIGSRG peptide (SEQ ID NO: 3), a hydrolytic segment, or a combination thereof.
12. The medical device of claim 2 , wherein the copolymer further comprises an ANP peptide, a BNP peptide, an RGD peptide, a cRGD peptide, a SIKVAV peptide (SEQ ID NO: 2), a CNP peptide, a YIGSRG peptide (SEQ ID NO: 3), a hydrolytic segment, or a combination thereof.
13. The medical device of claim 1 , wherein the copolymer further comprises a biodegradable linkage between the A block and the B block.
14. The medical device of claim 1 , wherein the copolymer further comprises a biodegradable linkage selected from poly(lactic acid) (PLA), poly(glycolic acid) (PLGA), polycaprolactone (PCL), poly(3-hydroxybutyric acid (PHB), poly(4-hydroxybutyrate (P4HB), and combinations of these.
15. The medical device of claim 1 , wherein the hydrophobic polymer comprises a polymer of a fluoroolefin.
16. The medical device of claim 16 , wherein the hydrophobic polymer is poly(vinylidene fluoride) (PVDF).
17. The medical device of claim 1 , wherein the layer of the hydrophobic polymer further comprises a bioactive agent.
18. The medical device of claim 1 , wherein the coating comprises a bioactive agent selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutase mimetics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, midostaurin, vascular endothelial growth factor (VEGF), and prodrugs, co-drugs, and combinations of these.
19. The medical device of claim 18 , wherein the bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutase mimetics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, rapamycin derivatives, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, midostaurin, vascular endothelial growth factor (VEGF), and prodrugs, co-drugs, and combinations of these.
20. The medical device of claim 1 , wherein the coating comprises a bioactive agent comprising a combination of an anti-proliferative and an anti-inflammatory.
21. The medical device of claim 18 , wherein the bioactive agent comprises a combination of an anti-proliferative and an anti-inflammatory.
22. The medical device of claim 19 , which is a stent.
23. The medical device of claim 20 , which is a stent.
24. A method of treating, preventing or ameliorating a disorder in a patient comprising implanting in the patient the medical device of claim 19 , wherein the disorder is selected from the group consisting of atherosclerosis, thrombosis, restenosis, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, urethra obstruction, tumor obstruction, diabetic vascular disease, and combinations thereof.
25. A method of treating, preventing or ameliorating a disorder in a patient comprising implanting in the patient the medical device of claim 20 , wherein the disorder is selected from the group consisting of atherosclerosis, thrombosis, restenosis, hemorrhage, vascular dissection or perforation, vascular aneurysm, vulnerable plaque, chronic total occlusion, claudication, anastomotic proliferation for vein and artificial grafts, bile duct obstruction, urethra obstruction, tumor obstruction, diabetic vascular disease, and combinations thereof.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US13/225,165 US20120046640A1 (en) | 2006-06-09 | 2011-09-02 | Coating Comprising An Elastin-Based Copolymer |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/449,896 US8778376B2 (en) | 2006-06-09 | 2006-06-09 | Copolymer comprising elastin pentapeptide block and hydrophilic block, and medical device and method of treating |
US11/803,031 US8029816B2 (en) | 2006-06-09 | 2007-05-10 | Medical device coated with a coating containing elastin pentapeptide VGVPG |
US13/225,165 US20120046640A1 (en) | 2006-06-09 | 2011-09-02 | Coating Comprising An Elastin-Based Copolymer |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/803,031 Continuation US8029816B2 (en) | 2006-06-09 | 2007-05-10 | Medical device coated with a coating containing elastin pentapeptide VGVPG |
Publications (1)
Publication Number | Publication Date |
---|---|
US20120046640A1 true US20120046640A1 (en) | 2012-02-23 |
Family
ID=38722714
Family Applications (6)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/449,896 Expired - Fee Related US8778376B2 (en) | 2006-06-09 | 2006-06-09 | Copolymer comprising elastin pentapeptide block and hydrophilic block, and medical device and method of treating |
US11/803,031 Expired - Fee Related US8029816B2 (en) | 2006-06-09 | 2007-05-10 | Medical device coated with a coating containing elastin pentapeptide VGVPG |
US13/225,165 Abandoned US20120046640A1 (en) | 2006-06-09 | 2011-09-02 | Coating Comprising An Elastin-Based Copolymer |
US13/224,515 Expired - Fee Related US9078958B2 (en) | 2006-06-09 | 2011-09-02 | Depot stent comprising an elastin-based copolymer |
US14/308,444 Abandoned US20140356519A1 (en) | 2006-06-09 | 2014-06-18 | Elastin-based copolymers and method of using |
US14/308,412 Abandoned US20140363563A1 (en) | 2006-06-09 | 2014-06-18 | Elastin-based copolymers |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/449,896 Expired - Fee Related US8778376B2 (en) | 2006-06-09 | 2006-06-09 | Copolymer comprising elastin pentapeptide block and hydrophilic block, and medical device and method of treating |
US11/803,031 Expired - Fee Related US8029816B2 (en) | 2006-06-09 | 2007-05-10 | Medical device coated with a coating containing elastin pentapeptide VGVPG |
Family Applications After (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US13/224,515 Expired - Fee Related US9078958B2 (en) | 2006-06-09 | 2011-09-02 | Depot stent comprising an elastin-based copolymer |
US14/308,444 Abandoned US20140356519A1 (en) | 2006-06-09 | 2014-06-18 | Elastin-based copolymers and method of using |
US14/308,412 Abandoned US20140363563A1 (en) | 2006-06-09 | 2014-06-18 | Elastin-based copolymers |
Country Status (2)
Country | Link |
---|---|
US (6) | US8778376B2 (en) |
WO (1) | WO2007146228A2 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109381750A (en) * | 2018-05-09 | 2019-02-26 | 张锋 | Anticoagulation facilitates the cardiac stent of taking-up |
Families Citing this family (49)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007517550A (en) | 2004-01-02 | 2007-07-05 | アドヴァンスド カーディオヴァスキュラー システムズ, インコーポレイテッド | Medical device coated with high density lipoprotein |
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 |
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 |
US8815275B2 (en) | 2006-06-28 | 2014-08-26 | Boston Scientific Scimed, Inc. | Coatings for medical devices comprising a therapeutic agent and a metallic material |
CA2655793A1 (en) | 2006-06-29 | 2008-01-03 | Boston Scientific Limited | Medical devices with selective coating |
US8293318B1 (en) | 2006-08-29 | 2012-10-23 | Abbott Cardiovascular Systems Inc. | Methods for modulating the release rate of a drug-coated stent |
CA2662808A1 (en) | 2006-09-14 | 2008-03-20 | Boston Scientific Limited | Medical devices with drug-eluting coating |
US8070797B2 (en) * | 2007-03-01 | 2011-12-06 | Boston Scientific Scimed, Inc. | Medical device with a porous surface for delivery of a therapeutic agent |
US8431149B2 (en) | 2007-03-01 | 2013-04-30 | Boston Scientific Scimed, Inc. | Coated medical devices for abluminal drug delivery |
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 |
US8815273B2 (en) | 2007-07-27 | 2014-08-26 | Boston Scientific Scimed, Inc. | Drug eluting medical devices having porous layers |
WO2009018340A2 (en) | 2007-07-31 | 2009-02-05 | Boston Scientific Scimed, Inc. | Medical device coating by laser cladding |
EP2185103B1 (en) | 2007-08-03 | 2014-02-12 | Boston Scientific Scimed, Inc. | Coating for medical device having increased surface area |
US8216632B2 (en) | 2007-11-02 | 2012-07-10 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US20090118812A1 (en) * | 2007-11-02 | 2009-05-07 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
WO2009131911A2 (en) | 2008-04-22 | 2009-10-29 | Boston Scientific Scimed, Inc. | Medical devices having a coating of inorganic material |
WO2009132176A2 (en) | 2008-04-24 | 2009-10-29 | Boston Scientific Scimed, Inc. | Medical devices having inorganic particle layers |
EP2296629B1 (en) * | 2008-05-09 | 2014-07-02 | Evonik Corporation | Biocompatible and biodegradable elastomeric polymers |
EP2303350A2 (en) | 2008-06-18 | 2011-04-06 | Boston Scientific Scimed, Inc. | Endoprosthesis coating |
US8562669B2 (en) * | 2008-06-26 | 2013-10-22 | Abbott Cardiovascular Systems Inc. | Methods of application of coatings composed of hydrophobic, high glass transition polymers with tunable drug release rates |
US20100057188A1 (en) * | 2008-08-28 | 2010-03-04 | Boston Scientific Scimed, Inc. | Endoprostheses with porous regions and non-polymeric coating |
AU2009295960A1 (en) | 2008-09-29 | 2010-04-01 | Cardiaq Valve Technologies, Inc. | Heart valve |
EP2341871B1 (en) | 2008-10-01 | 2017-03-22 | Edwards Lifesciences CardiAQ LLC | Delivery system for vascular implant |
WO2010053918A1 (en) * | 2008-11-05 | 2010-05-14 | Hancock Jaffe Laboratories, Inc. | Composite containing collagen and elastin as a dermal expander and tissue filler |
US8231980B2 (en) | 2008-12-03 | 2012-07-31 | Boston Scientific Scimed, Inc. | Medical implants including iridium oxide |
AU2010236288A1 (en) | 2009-04-15 | 2011-10-20 | Cardiaq Valve Technologies, Inc. | Vascular implant and delivery system |
US8287937B2 (en) | 2009-04-24 | 2012-10-16 | Boston Scientific Scimed, Inc. | Endoprosthese |
US8579964B2 (en) | 2010-05-05 | 2013-11-12 | Neovasc Inc. | Transcatheter mitral valve prosthesis |
KR101245253B1 (en) | 2010-10-18 | 2013-03-25 | 재단법인대구경북과학기술원 | Multi-block Biopolymer, Gene thereof and Expression Vector thereof |
US8981025B2 (en) | 2011-02-10 | 2015-03-17 | Corning Incorporated | Polymerizable catonic peptide monomers and polymers |
US9554897B2 (en) | 2011-04-28 | 2017-01-31 | Neovasc Tiara Inc. | Methods and apparatus for engaging a valve prosthesis with tissue |
US9308087B2 (en) | 2011-04-28 | 2016-04-12 | Neovasc Tiara Inc. | Sequentially deployed transcatheter mitral valve prosthesis |
WO2013090924A1 (en) * | 2011-12-16 | 2013-06-20 | William Marsh Rice University | Implantable modular hydrogel for salivary gland restoration |
US9220759B2 (en) | 2012-02-23 | 2015-12-29 | Abbott Cardiovascular Systems Inc. | Treatment of diabetic patients with a drug eluting stent and adjunctive therapy |
US20130261723A1 (en) * | 2012-03-30 | 2013-10-03 | Abbott Cardiovascular Systems Inc. | Treatment Of Diabetic Patients With A Drug Eluting Stent And A Drug Coated Balloon |
US9220584B2 (en) | 2012-03-30 | 2015-12-29 | Abbott Cardiovascular Systems Inc. | Treatment of diabetic patients with a stent and locally administered adjunctive therapy |
US9345573B2 (en) | 2012-05-30 | 2016-05-24 | Neovasc Tiara Inc. | Methods and apparatus for loading a prosthesis onto a delivery system |
US9078740B2 (en) | 2013-01-21 | 2015-07-14 | Howmedica Osteonics Corp. | Instrumentation and method for positioning and securing a graft |
US10583002B2 (en) | 2013-03-11 | 2020-03-10 | Neovasc Tiara Inc. | Prosthetic valve with anti-pivoting mechanism |
US9681951B2 (en) | 2013-03-14 | 2017-06-20 | Edwards Lifesciences Cardiaq Llc | Prosthesis with outer skirt and anchors |
US9572665B2 (en) | 2013-04-04 | 2017-02-21 | Neovasc Tiara Inc. | Methods and apparatus for delivering a prosthetic valve to a beating heart |
CN103483591B (en) * | 2013-09-18 | 2015-10-28 | 天津大学 | Parents' comb shaped polymer containing antibody TRC105 and photographic developer and preparation |
KR101617673B1 (en) * | 2014-10-29 | 2016-05-03 | 재단법인대구경북과학기술원 | Pharmaceutical Composition for Promoting Wound-Healing Comprising Adult Stem Cell and Elastin Like Polypeptide |
CN106924812B (en) * | 2017-03-14 | 2019-11-22 | 浙江巴泰医疗科技有限公司 | A kind of medicine slow release stent and its preparation method and application |
EP3628333A1 (en) * | 2018-09-25 | 2020-04-01 | Institut Polytechnique De Bordeaux | Bionconjugates of polysaccharides and elastin-like polypeptides and uses thereof |
CN111378152B (en) * | 2020-04-27 | 2021-02-12 | 西北工业大学 | Method for catalytic oxidation and functional modification of hydrogel material |
CN111514373A (en) * | 2020-06-01 | 2020-08-11 | 关节动力安达(天津)生物科技有限公司 | I-type collagen gel matrix based on triblock polymerized choline phosphate surface directional assembly and preparation method thereof |
CN114601936B (en) * | 2022-03-28 | 2023-10-24 | 中国科学技术大学 | Tumor-targeted near infrared light response nitric oxide nano generator, preparation method and application thereof |
Family Cites Families (300)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR732895A (en) | 1932-10-18 | 1932-09-25 | Consortium Elektrochem Ind | Articles spun in polyvinyl alcohol |
US2386454A (en) | 1940-11-22 | 1945-10-09 | Bell Telephone Labor Inc | High molecular weight linear polyester-amides |
US3849514A (en) | 1967-11-17 | 1974-11-19 | Eastman Kodak Co | Block polyester-polyamide copolymers |
US3773737A (en) | 1971-06-09 | 1973-11-20 | Sutures Inc | Hydrolyzable polymers of amino acid and hydroxy acids |
US4329383A (en) | 1979-07-24 | 1982-05-11 | Nippon Zeon Co., Ltd. | Non-thrombogenic material comprising substrate which has been reacted with heparin |
US4226243A (en) | 1979-07-27 | 1980-10-07 | Ethicon, Inc. | Surgical devices of polyesteramides derived from bis-oxamidodiols and dicarboxylic acids |
SU790725A1 (en) | 1979-07-27 | 1983-01-23 | Ордена Ленина Институт Элементоорганических Соединений Ан Ссср | Process for preparing alkylaromatic polyimides |
SU811750A1 (en) | 1979-08-07 | 1983-09-23 | Институт Физиологии Им.С.И.Бериташвили | Bis-bicarbonates of aliphatic diols as monomers for preparing polyurethanes and process for producing the same |
SU872531A1 (en) | 1979-08-07 | 1981-10-15 | Институт Физиологии Им.И.С.Бериташвили Ан Гсср | Method of producing polyurethans |
SU876663A1 (en) | 1979-11-11 | 1981-10-30 | Институт Физиологии Им. Академика И.С.Бериташвили Ан Гсср | Method of producing polyarylates |
SU1016314A1 (en) | 1979-12-17 | 1983-05-07 | Институт Физиологии Им.И.С.Бериташвили | Process for producing polyester urethanes |
US4529792A (en) | 1979-12-17 | 1985-07-16 | Minnesota Mining And Manufacturing Company | Process for preparing synthetic absorbable poly(esteramides) |
US4343931A (en) | 1979-12-17 | 1982-08-10 | Minnesota Mining And Manufacturing Company | Synthetic absorbable surgical devices of poly(esteramides) |
SU905228A1 (en) | 1980-03-06 | 1982-02-15 | Институт Физиологии Им. Акад.И.С. Бериташвили Ан Гсср | Method for preparing thiourea |
SU1293518A1 (en) | 1985-04-11 | 1987-02-28 | Тбилисский зональный научно-исследовательский и проектный институт типового и экспериментального проектирования жилых и общественных зданий | Installation for testing specimen of cross-shaped structure |
US4656242A (en) | 1985-06-07 | 1987-04-07 | Henkel Corporation | Poly(ester-amide) compositions |
US4733665C2 (en) | 1985-11-07 | 2002-01-29 | Expandable Grafts Partnership | Expandable intraluminal graft and method and apparatus for implanting an expandable intraluminal graft |
US4611051A (en) | 1985-12-31 | 1986-09-09 | Union Camp Corporation | Novel poly(ester-amide) hot-melt adhesives |
US5250516A (en) * | 1986-04-17 | 1993-10-05 | Uab Research Foundation | Bioelastomeric materials suitable for the protection of burn areas or the protection of wound repair sites from the occurrence of adhesions |
US5336256A (en) * | 1986-04-17 | 1994-08-09 | Uab Research Foundation | Elastomeric polypeptides as vascular prosthetic materials |
US4882168A (en) | 1986-09-05 | 1989-11-21 | American Cyanamid Company | Polyesters containing alkylene oxide blocks as drug delivery systems |
JPH0696023B2 (en) | 1986-11-10 | 1994-11-30 | 宇部日東化成株式会社 | Artificial blood vessel and method for producing the same |
US5721131A (en) | 1987-03-06 | 1998-02-24 | United States Of America As Represented By The Secretary Of The Navy | Surface modification of polymers with self-assembled monolayers that promote adhesion, outgrowth and differentiation of biological cells |
US4800882A (en) | 1987-03-13 | 1989-01-31 | Cook Incorporated | Endovascular stent and delivery system |
US6387379B1 (en) | 1987-04-10 | 2002-05-14 | University Of Florida | Biofunctional surface modified ocular implants, surgical instruments, medical devices, prostheses, contact lenses and the like |
US4894231A (en) | 1987-07-28 | 1990-01-16 | Biomeasure, Inc. | Therapeutic agent delivery system |
US4886062A (en) | 1987-10-19 | 1989-12-12 | Medtronic, Inc. | Intravascular radially expandable stent and method of implant |
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 |
JP2561309B2 (en) | 1988-03-28 | 1996-12-04 | テルモ株式会社 | Medical material and manufacturing method thereof |
US4931287A (en) | 1988-06-14 | 1990-06-05 | University Of Utah | Heterogeneous interpenetrating polymer networks for the controlled release of drugs |
US5328471A (en) | 1990-02-26 | 1994-07-12 | Endoluminal Therapeutics, Inc. | Method and apparatus for treatment of focal disease in hollow tubular organs and other tissue lumens |
US4977901A (en) | 1988-11-23 | 1990-12-18 | Minnesota Mining And Manufacturing Company | Article having non-crosslinked crystallized polymer coatings |
IL90193A (en) | 1989-05-04 | 1993-02-21 | Biomedical Polymers Int | Polurethane-based polymeric materials and biomedical articles and pharmaceutical compositions utilizing the same |
US5272012A (en) | 1989-06-23 | 1993-12-21 | C. R. Bard, Inc. | Medical apparatus having protective, lubricious coating |
US5971954A (en) | 1990-01-10 | 1999-10-26 | Rochester Medical Corporation | Method of making catheter |
AU651084B2 (en) | 1990-01-30 | 1994-07-14 | 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 |
US5292516A (en) | 1990-05-01 | 1994-03-08 | Mediventures, Inc. | Body cavity drug delivery with thermoreversible gels containing polyoxyalkylene copolymers |
US5306501A (en) | 1990-05-01 | 1994-04-26 | Mediventures, Inc. | Drug delivery by injection with thermoreversible gels containing polyoxyalkylene copolymers |
US5300295A (en) | 1990-05-01 | 1994-04-05 | Mediventures, Inc. | Ophthalmic drug delivery with thermoreversible polyoxyalkylene gels adjustable for pH |
US5298260A (en) | 1990-05-01 | 1994-03-29 | Mediventures, Inc. | Topical drug delivery with polyoxyalkylene polymer thermoreversible gels adjustable for pH and osmolality |
AU7998091A (en) | 1990-05-17 | 1991-12-10 | Harbor Medical Devices, Inc. | Medical device polymer |
AU8074591A (en) | 1990-06-15 | 1992-01-07 | Cortrak Medical, Inc. | Drug delivery apparatus and method |
US6060451A (en) | 1990-06-15 | 2000-05-09 | The National Research Council Of Canada | Thrombin inhibitors based on the amino acid sequence of hirudin |
CA2038605C (en) | 1990-06-15 | 2000-06-27 | Leonard Pinchuk | Crack-resistant polycarbonate urethane polymer prostheses and the like |
US5112457A (en) | 1990-07-23 | 1992-05-12 | Case Western Reserve University | Process for producing hydroxylated plasma-polymerized films and the use of the films for enhancing the compatiblity of biomedical implants |
US5455040A (en) | 1990-07-26 | 1995-10-03 | Case Western Reserve University | Anticoagulant plasma polymer-modified substrate |
US5258020A (en) | 1990-09-14 | 1993-11-02 | Michael Froix | Method of using expandable polymeric stent with memory |
US6248129B1 (en) | 1990-09-14 | 2001-06-19 | Quanam Medical Corporation | Expandable polymeric stent with memory and delivery apparatus and method |
US5163952A (en) | 1990-09-14 | 1992-11-17 | Michael Froix | Expandable polymeric stent with memory and delivery apparatus and method |
US5462990A (en) | 1990-10-15 | 1995-10-31 | Board Of Regents, The University Of Texas System | Multifunctional organic polymers |
GB9027793D0 (en) | 1990-12-21 | 1991-02-13 | Ucb Sa | Polyester-amides containing terminal carboxyl groups |
US5330768A (en) | 1991-07-05 | 1994-07-19 | Massachusetts Institute Of Technology | Controlled drug delivery using polymer/pluronic blends |
US5500013A (en) | 1991-10-04 | 1996-03-19 | Scimed Life Systems, Inc. | Biodegradable drug delivery vascular stent |
US5573934A (en) | 1992-04-20 | 1996-11-12 | Board Of Regents, The University Of Texas System | Gels for encapsulation of biological materials |
US5599352A (en) | 1992-03-19 | 1997-02-04 | Medtronic, Inc. | Method of making a drug eluting stent |
GB9206736D0 (en) | 1992-03-27 | 1992-05-13 | Sandoz Ltd | Improvements of organic compounds and their use in pharmaceutical compositions |
US5219980A (en) | 1992-04-16 | 1993-06-15 | Sri International | Polymers biodegradable or bioerodiable into amino acids |
US5417981A (en) | 1992-04-28 | 1995-05-23 | Terumo Kabushiki Kaisha | Thermoplastic polymer composition and medical devices made of the same |
DE4224401A1 (en) | 1992-07-21 | 1994-01-27 | Pharmatech Gmbh | New biodegradable homo- and co-polymer(s) for pharmaceutical use - produced by polycondensation of prod. from heterolytic cleavage of aliphatic polyester with functionalised (cyclo)aliphatic cpd. |
FR2699168B1 (en) | 1992-12-11 | 1995-01-13 | Rhone Poulenc Chimie | Method of treating a material comprising a polymer by hydrolysis. |
EP0604022A1 (en) | 1992-12-22 | 1994-06-29 | Advanced Cardiovascular Systems, Inc. | Multilayered biodegradable stent and method for its manufacture |
US5824048A (en) | 1993-04-26 | 1998-10-20 | Medtronic, Inc. | Method for delivering a therapeutic substance to a body lumen |
US5464650A (en) | 1993-04-26 | 1995-11-07 | Medtronic, Inc. | Intravascular stent and method |
US20020055710A1 (en) | 1998-04-30 | 2002-05-09 | Ronald J. Tuch | Medical device for delivering a therapeutic agent and method of preparation |
JPH0767895A (en) | 1993-06-25 | 1995-03-14 | Sumitomo Electric Ind Ltd | Antimicrobial artificial blood vessel and suture yarn for antimicrobial operation |
US5716981A (en) | 1993-07-19 | 1998-02-10 | Angiogenesis Technologies, Inc. | Anti-angiogenic compositions and methods of use |
EG20321A (en) | 1993-07-21 | 1998-10-31 | Otsuka Pharma Co Ltd | Medical material and process for producing the same |
DE4327024A1 (en) | 1993-08-12 | 1995-02-16 | Bayer Ag | Thermoplastically processable and biodegradable aliphatic polyesteramides |
US5380299A (en) | 1993-08-30 | 1995-01-10 | Med Institute, Inc. | Thrombolytic treated intravascular medical device |
WO1995010989A1 (en) | 1993-10-19 | 1995-04-27 | Scimed Life Systems, Inc. | Intravascular stent pump |
US5723004A (en) | 1993-10-21 | 1998-03-03 | Corvita Corporation | Expandable supportive endoluminal grafts |
WO1995019796A1 (en) | 1994-01-21 | 1995-07-27 | Brown University Research Foundation | Biocompatible implants |
US6051576A (en) | 1994-01-28 | 2000-04-18 | University Of Kentucky Research Foundation | Means to achieve sustained release of synergistic drugs by conjugation |
AU710504B2 (en) | 1994-03-15 | 1999-09-23 | Brown University Research Foundation | Polymeric gene delivery system |
KR0141431B1 (en) * | 1994-05-17 | 1998-07-01 | 김상웅 | Biodegradable hydrogel copolymer |
US5567410A (en) | 1994-06-24 | 1996-10-22 | The General Hospital Corporation | Composotions and methods for radiographic imaging |
US5857998A (en) | 1994-06-30 | 1999-01-12 | Boston Scientific Corporation | Stent and therapeutic delivery system |
US5670558A (en) | 1994-07-07 | 1997-09-23 | Terumo Kabushiki Kaisha | Medical instruments that exhibit surface lubricity when wetted |
US5788979A (en) | 1994-07-22 | 1998-08-04 | Inflow Dynamics Inc. | Biodegradable coating with inhibitory properties for application to biocompatible materials |
US5516881A (en) | 1994-08-10 | 1996-05-14 | Cornell Research Foundation, Inc. | Aminoxyl-containing radical spin labeling in polymers and copolymers |
US5578073A (en) | 1994-09-16 | 1996-11-26 | Ramot Of Tel Aviv University | Thromboresistant surface treatment for biomaterials |
US5485496A (en) | 1994-09-22 | 1996-01-16 | Cornell Research Foundation, Inc. | Gamma irradiation sterilizing of biomaterial medical devices or products, with improved degradation and mechanical properties |
US5649977A (en) | 1994-09-22 | 1997-07-22 | Advanced Cardiovascular Systems, Inc. | Metal reinforced polymer stent |
FR2724938A1 (en) | 1994-09-28 | 1996-03-29 | Lvmh Rech | POLYMERS FUNCTIONALIZED BY AMINO ACIDS OR AMINO ACID DERIVATIVES, THEIR USE AS SURFACTANTS, IN PARTICULAR, IN COSMETIC COMPOSITIONS AND IN PARTICULAR NAIL POLISH. |
AU700903B2 (en) | 1994-10-12 | 1999-01-14 | Focal, Inc. | Targeted delivery via biodegradable polymers |
US5637113A (en) | 1994-12-13 | 1997-06-10 | Advanced Cardiovascular Systems, Inc. | Polymer film for wrapping a stent structure |
US5569198A (en) | 1995-01-23 | 1996-10-29 | Cortrak Medical Inc. | Microporous catheter |
US6017577A (en) | 1995-02-01 | 2000-01-25 | Schneider (Usa) Inc. | Slippery, tenaciously adhering hydrophilic polyurethane hydrogel coatings, coated polymer substrate materials, and coated medical devices |
US5919570A (en) | 1995-02-01 | 1999-07-06 | Schneider Inc. | Slippery, tenaciously adhering hydrogel coatings containing a polyurethane-urea polymer hydrogel commingled with a poly(N-vinylpyrrolidone) polymer hydrogel, coated polymer and metal substrate materials, and coated medical devices |
US5702754A (en) | 1995-02-22 | 1997-12-30 | Meadox Medicals, Inc. | Method of providing a substrate with a hydrophilic coating and substrates, particularly medical devices, provided with such coatings |
US5869127A (en) | 1995-02-22 | 1999-02-09 | Boston Scientific Corporation | Method of providing a substrate with a bio-active/biocompatible coating |
US6231600B1 (en) | 1995-02-22 | 2001-05-15 | Scimed Life Systems, Inc. | Stents with hybrid coating for medical devices |
US5854376A (en) | 1995-03-09 | 1998-12-29 | Sekisui Kaseihin Kogyo Kabushiki Kaisha | Aliphatic ester-amide copolymer resins |
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 |
US20020091433A1 (en) | 1995-04-19 | 2002-07-11 | Ni Ding | Drug release coated stent |
AU5346896A (en) | 1995-04-19 | 1996-11-07 | Kazunori Kataoka | Heterotelechelic block copolymers and process for producing the same |
US6099562A (en) | 1996-06-13 | 2000-08-08 | Schneider (Usa) Inc. | Drug coating with topcoat |
US5837313A (en) | 1995-04-19 | 1998-11-17 | Schneider (Usa) Inc | Drug release stent coating process |
US5674242A (en) | 1995-06-06 | 1997-10-07 | Quanam Medical Corporation | Endoprosthetic device with therapeutic compound |
CA2178541C (en) | 1995-06-07 | 2009-11-24 | Neal E. Fearnot | Implantable medical device |
US7550005B2 (en) | 1995-06-07 | 2009-06-23 | Cook Incorporated | Coated implantable medical device |
US5820917A (en) | 1995-06-07 | 1998-10-13 | Medtronic, Inc. | Blood-contacting medical device and method |
US6010530A (en) | 1995-06-07 | 2000-01-04 | Boston Scientific Technology, Inc. | Self-expanding endoluminal prosthesis |
US7611533B2 (en) | 1995-06-07 | 2009-11-03 | Cook Incorporated | Coated implantable medical device |
US6129761A (en) | 1995-06-07 | 2000-10-10 | Reprogenesis, Inc. | Injectable hydrogel compositions |
US6774278B1 (en) | 1995-06-07 | 2004-08-10 | Cook Incorporated | Coated implantable medical device |
US5609629A (en) | 1995-06-07 | 1997-03-11 | Med Institute, Inc. | Coated implantable medical device |
US5667767A (en) | 1995-07-27 | 1997-09-16 | Micro Therapeutics, Inc. | Compositions for use in embolizing blood vessels |
US5877224A (en) | 1995-07-28 | 1999-03-02 | Rutgers, The State University Of New Jersey | Polymeric drug formulations |
US5723219A (en) | 1995-12-19 | 1998-03-03 | Talison Research | Plasma deposited film networks |
US5658995A (en) | 1995-11-27 | 1997-08-19 | Rutgers, The State University | Copolymers of tyrosine-based polycarbonate and poly(alkylene oxide) |
DE19545678A1 (en) | 1995-12-07 | 1997-06-12 | Goldschmidt Ag Th | Copolymers of polyamino acid esters |
ATE330644T1 (en) | 1995-12-18 | 2006-07-15 | Angiotech Biomaterials Corp | CROSS-LINKED POLYMER MATERIALS AND METHODS FOR USE THEREOF |
US6033582A (en) | 1996-01-22 | 2000-03-07 | Etex Corporation | Surface modification of medical implants |
US6054553A (en) | 1996-01-29 | 2000-04-25 | Bayer Ag | Process for the preparation of polymers having recurring agents |
SE509260C2 (en) * | 1996-04-03 | 1998-12-21 | Duni Ab | Slit material layer of tissue paper or polymer fibers and device for making the material layer |
US5932299A (en) | 1996-04-23 | 1999-08-03 | Katoot; Mohammad W. | Method for modifying the surface of an object |
US5955509A (en) | 1996-05-01 | 1999-09-21 | Board Of Regents, The University Of Texas System | pH dependent polymer micelles |
US5610241A (en) | 1996-05-07 | 1997-03-11 | Cornell Research Foundation, Inc. | Reactive graft polymer with biodegradable polymer backbone and method for preparing reactive biodegradable polymers |
US5876433A (en) | 1996-05-29 | 1999-03-02 | Ethicon, Inc. | Stent and method of varying amounts of heparin coated thereon to control treatment |
US5874165A (en) | 1996-06-03 | 1999-02-23 | Gore Enterprise Holdings, Inc. | Materials and method for the immobilization of bioactive species onto polymeric subtrates |
NL1003459C2 (en) | 1996-06-28 | 1998-01-07 | Univ Twente | Copoly (ester amides) and copoly (ester urethanes). |
US5711958A (en) | 1996-07-11 | 1998-01-27 | Life Medical Sciences, Inc. | Methods for reducing or eliminating post-surgical adhesion formation |
US5830178A (en) | 1996-10-11 | 1998-11-03 | Micro Therapeutics, Inc. | Methods for embolizing vascular sites with an emboilizing composition comprising dimethylsulfoxide |
US6060518A (en) | 1996-08-16 | 2000-05-09 | Supratek Pharma Inc. | Polymer compositions for chemotherapy and methods of treatment using the same |
US5783657A (en) | 1996-10-18 | 1998-07-21 | Union Camp Corporation | Ester-terminated polyamides of polymerized fatty acids useful in formulating transparent gels in low polarity liquids |
US6530951B1 (en) | 1996-10-24 | 2003-03-11 | Cook Incorporated | Silver implantable medical device |
US6120491A (en) | 1997-11-07 | 2000-09-19 | The State University Rutgers | Biodegradable, anionic polymers derived from the amino acid L-tyrosine |
US5980972A (en) | 1996-12-20 | 1999-11-09 | Schneider (Usa) Inc | Method of applying drug-release coatings |
US5997517A (en) | 1997-01-27 | 1999-12-07 | Sts Biopolymers, Inc. | Bonding layers for medical device surface coatings |
WO1998032779A1 (en) | 1997-01-28 | 1998-07-30 | United States Surgical Corporation | Polyesteramide, its preparation and surgical devices fabricated therefrom |
ES2235312T3 (en) | 1997-01-28 | 2005-07-01 | United States Surgical Corporation | POLYESTERAMIDE, ITS PREPARATION AND SURGICAL DEVICES MANUFACTURED FROM THE SAME. |
CA2279270C (en) | 1997-01-28 | 2007-05-15 | United States Surgical Corporation | Polyesteramides with amino acid-derived groups alternating with alpha-hydroxyacid-derived groups and surgical articles made therefrom |
US6240616B1 (en) | 1997-04-15 | 2001-06-05 | Advanced Cardiovascular Systems, Inc. | Method of manufacturing a medicated porous metal prosthesis |
US5879697A (en) | 1997-04-30 | 1999-03-09 | Schneider Usa Inc | Drug-releasing coatings for medical devices |
US6180632B1 (en) | 1997-05-28 | 2001-01-30 | Aventis Pharmaceuticals Products Inc. | Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases |
US6159978A (en) | 1997-05-28 | 2000-12-12 | Aventis Pharmaceuticals Product, Inc. | Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases |
US6245760B1 (en) | 1997-05-28 | 2001-06-12 | Aventis Pharmaceuticals Products, Inc | Quinoline and quinoxaline compounds which inhibit platelet-derived growth factor and/or p56lck tyrosine kinases |
US6056993A (en) | 1997-05-30 | 2000-05-02 | Schneider (Usa) Inc. | Porous protheses and methods for making the same wherein the protheses are formed by spraying water soluble and water insoluble fibers onto a rotating mandrel |
US6110483A (en) | 1997-06-23 | 2000-08-29 | Sts Biopolymers, Inc. | Adherent, flexible hydrogel and medicated coatings |
US6211249B1 (en) | 1997-07-11 | 2001-04-03 | Life Medical Sciences, Inc. | Polyester polyether block copolymers |
US5980928A (en) | 1997-07-29 | 1999-11-09 | Terry; Paul B. | Implant for preventing conjunctivitis in cattle |
US6034204A (en) | 1997-08-08 | 2000-03-07 | Basf Aktiengesellschaft | Condensation products of basic amino acids with copolymerizable compounds and a process for their production |
US6121027A (en) | 1997-08-15 | 2000-09-19 | Surmodics, Inc. | Polybifunctional reagent having a polymeric backbone and photoreactive moieties and bioactive groups |
US6316522B1 (en) | 1997-08-18 | 2001-11-13 | Scimed Life Systems, Inc. | Bioresorbable hydrogel compositions for implantable prostheses |
US6890546B2 (en) | 1998-09-24 | 2005-05-10 | Abbott Laboratories | Medical devices containing rapamycin analogs |
US6120788A (en) | 1997-10-16 | 2000-09-19 | Bioamide, Inc. | Bioabsorbable triglycolic acid poly(ester-amide)s |
US6015541A (en) | 1997-11-03 | 2000-01-18 | Micro Therapeutics, Inc. | Radioactive embolizing compositions |
US6110188A (en) | 1998-03-09 | 2000-08-29 | Corvascular, Inc. | Anastomosis method |
US6069129A (en) * | 1998-03-13 | 2000-05-30 | Mrs, Llc | Elastin derived composition and method of using same |
US6258371B1 (en) | 1998-04-03 | 2001-07-10 | Medtronic Inc | Method for making biocompatible medical article |
US20030040790A1 (en) | 1998-04-15 | 2003-02-27 | Furst Joseph G. | Stent coating |
US20010029351A1 (en) | 1998-04-16 | 2001-10-11 | Robert Falotico | Drug combinations and delivery devices for the prevention and treatment of vascular disease |
US7658727B1 (en) | 1998-04-20 | 2010-02-09 | Medtronic, Inc | Implantable medical device with enhanced biocompatibility and biostability |
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. |
US6113629A (en) | 1998-05-01 | 2000-09-05 | Micrus Corporation | Hydrogel for the therapeutic treatment of aneurysms |
KR100314496B1 (en) | 1998-05-28 | 2001-11-22 | 윤동진 | Non-thrombogenic heparin derivatives, process for preparation and use thereof |
US6153252A (en) | 1998-06-30 | 2000-11-28 | Ethicon, Inc. | Process for coating stents |
US6013122A (en) * | 1998-08-18 | 2000-01-11 | Option Technologies, Inc. | Tattoo inks |
AU771367B2 (en) | 1998-08-20 | 2004-03-18 | Cook Medical Technologies Llc | Coated implantable medical device |
US6248127B1 (en) | 1998-08-21 | 2001-06-19 | Medtronic Ave, Inc. | Thromboresistant coated medical device |
US6335029B1 (en) | 1998-08-28 | 2002-01-01 | Scimed Life Systems, Inc. | Polymeric coatings for controlled delivery of active agents |
US6011125A (en) | 1998-09-25 | 2000-01-04 | General Electric Company | Amide modified polyesters |
US6530950B1 (en) | 1999-01-12 | 2003-03-11 | Quanam Medical Corporation | Intraluminal stent having coaxial polymer member |
US6419692B1 (en) | 1999-02-03 | 2002-07-16 | Scimed Life Systems, Inc. | Surface protection method for stents and balloon catheters for drug delivery |
US6143354A (en) | 1999-02-08 | 2000-11-07 | Medtronic Inc. | One-step method for attachment of biomolecules to substrate surfaces |
US6258121B1 (en) | 1999-07-02 | 2001-07-10 | Scimed Life Systems, Inc. | Stent coating |
US6283947B1 (en) | 1999-07-13 | 2001-09-04 | Advanced Cardiovascular Systems, Inc. | Local drug delivery injection catheter |
US6494862B1 (en) | 1999-07-13 | 2002-12-17 | Advanced Cardiovascular Systems, Inc. | Substance delivery apparatus and a method of delivering a therapeutic substance to an anatomical passageway |
US6177523B1 (en) | 1999-07-14 | 2001-01-23 | Cardiotech International, Inc. | Functionalized polyurethanes |
US20040029952A1 (en) | 1999-09-03 | 2004-02-12 | Yung-Ming Chen | Ethylene vinyl alcohol composition and coating |
US6503556B2 (en) | 2000-12-28 | 2003-01-07 | Advanced Cardiovascular Systems, Inc. | Methods of forming a coating for a prosthesis |
US6287628B1 (en) | 1999-09-03 | 2001-09-11 | Advanced Cardiovascular Systems, Inc. | Porous prosthesis and a method of depositing substances into the pores |
US6759054B2 (en) | 1999-09-03 | 2004-07-06 | Advanced Cardiovascular Systems, Inc. | Ethylene vinyl alcohol composition and coating |
US6790228B2 (en) | 1999-12-23 | 2004-09-14 | Advanced Cardiovascular Systems, Inc. | Coating for implantable devices and a method of forming the same |
US6749626B1 (en) | 2000-03-31 | 2004-06-15 | Advanced Cardiovascular Systems, Inc. | Actinomycin D for the treatment of vascular disease |
US6379381B1 (en) | 1999-09-03 | 2002-04-30 | Advanced Cardiovascular Systems, Inc. | Porous prosthesis and a method of depositing substances into the pores |
US6713119B2 (en) | 1999-09-03 | 2004-03-30 | Advanced Cardiovascular Systems, Inc. | Biocompatible coating for a prosthesis and a method of forming the same |
US6503954B1 (en) | 2000-03-31 | 2003-01-07 | Advanced Cardiovascular Systems, Inc. | Biocompatible carrier containing actinomycin D and a method of forming the same |
US6203551B1 (en) | 1999-10-04 | 2001-03-20 | Advanced Cardiovascular Systems, Inc. | Chamber for applying therapeutic substances to an implant device |
US6331313B1 (en) | 1999-10-22 | 2001-12-18 | Oculex Pharmaceticals, Inc. | Controlled-release biocompatible ocular drug delivery implant devices and methods |
US6251136B1 (en) | 1999-12-08 | 2001-06-26 | Advanced Cardiovascular Systems, Inc. | Method of layering a three-coated stent using pharmacological and polymeric agents |
US6613432B2 (en) | 1999-12-22 | 2003-09-02 | Biosurface Engineering Technologies, Inc. | Plasma-deposited coatings, devices and methods |
US6908624B2 (en) | 1999-12-23 | 2005-06-21 | Advanced Cardiovascular Systems, Inc. | Coating for implantable devices and a method of forming the same |
US6283949B1 (en) | 1999-12-27 | 2001-09-04 | Advanced Cardiovascular Systems, Inc. | Refillable implantable drug delivery pump |
US20010007083A1 (en) | 1999-12-29 | 2001-07-05 | Roorda Wouter E. | Device and active component for inhibiting formation of thrombus-inflammatory cell matrix |
WO2001049338A1 (en) | 1999-12-30 | 2001-07-12 | Li Wei Pin | Controlled delivery of therapeutic agents by insertable medical devices |
JP4473390B2 (en) | 2000-01-07 | 2010-06-02 | 川澄化学工業株式会社 | Stent and stent graft |
US6527801B1 (en) | 2000-04-13 | 2003-03-04 | Advanced Cardiovascular Systems, Inc. | Biodegradable drug delivery material for stent |
US6270779B1 (en) | 2000-05-10 | 2001-08-07 | United States Of America | Nitric oxide-releasing metallic medical devices |
US20020007213A1 (en) | 2000-05-19 | 2002-01-17 | Robert Falotico | Drug/drug delivery systems for the prevention and treatment of vascular disease |
US6776796B2 (en) | 2000-05-12 | 2004-08-17 | Cordis Corportation | Antiinflammatory drug and delivery device |
US20020005206A1 (en) | 2000-05-19 | 2002-01-17 | Robert Falotico | Antiproliferative drug and delivery device |
US20020007214A1 (en) | 2000-05-19 | 2002-01-17 | Robert Falotico | Drug/drug delivery systems for the prevention and treatment of vascular disease |
US20020007215A1 (en) | 2000-05-19 | 2002-01-17 | Robert Falotico | Drug/drug delivery systems for the prevention and treatment of vascular disease |
US6395326B1 (en) | 2000-05-31 | 2002-05-28 | Advanced Cardiovascular Systems, Inc. | Apparatus and method for depositing a coating onto a surface of a prosthesis |
US6673385B1 (en) | 2000-05-31 | 2004-01-06 | Advanced Cardiovascular Systems, Inc. | Methods for polymeric coatings stents |
US6585765B1 (en) | 2000-06-29 | 2003-07-01 | Advanced Cardiovascular Systems, Inc. | Implantable device having substances impregnated therein and a method of impregnating the same |
US20020077693A1 (en) | 2000-12-19 | 2002-06-20 | Barclay Bruce J. | Covered, coiled drug delivery stent and method |
US6555157B1 (en) | 2000-07-25 | 2003-04-29 | Advanced Cardiovascular Systems, Inc. | Method for coating an implantable device and system for performing the method |
CA2771263A1 (en) | 2000-07-27 | 2002-02-07 | Rutgers, The State University | Therapeutic polyesters and polyamides |
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 |
US6503538B1 (en) | 2000-08-30 | 2003-01-07 | Cornell Research Foundation, Inc. | Elastomeric functional biodegradable copolyester amides and copolyester urethanes |
US6585926B1 (en) | 2000-08-31 | 2003-07-01 | Advanced Cardiovascular Systems, Inc. | Method of manufacturing a porous balloon |
US6805898B1 (en) | 2000-09-28 | 2004-10-19 | Advanced Cardiovascular Systems, Inc. | Surface features of an implantable medical device |
US6716444B1 (en) | 2000-09-28 | 2004-04-06 | Advanced Cardiovascular Systems, Inc. | Barriers for polymer-coated implantable medical devices and methods for making the same |
US6254632B1 (en) | 2000-09-28 | 2001-07-03 | Advanced Cardiovascular Systems, Inc. | Implantable medical device having protruding surface structures for drug delivery and cover attachment |
US20020111590A1 (en) | 2000-09-29 | 2002-08-15 | Davila Luis A. | Medical devices, drug coatings and methods for maintaining the drug coatings thereon |
US6746773B2 (en) | 2000-09-29 | 2004-06-08 | Ethicon, Inc. | Coatings for medical devices |
US20020051730A1 (en) | 2000-09-29 | 2002-05-02 | Stanko Bodnar | Coated medical devices and sterilization thereof |
US7261735B2 (en) | 2001-05-07 | 2007-08-28 | Cordis Corporation | Local drug delivery devices and methods for maintaining the drug coatings thereon |
US6506437B1 (en) | 2000-10-17 | 2003-01-14 | Advanced Cardiovascular Systems, Inc. | Methods of coating an implantable device having depots formed in a surface thereof |
US6558733B1 (en) | 2000-10-26 | 2003-05-06 | Advanced Cardiovascular Systems, Inc. | Method for etching a micropatterned microdepot prosthesis |
US6758859B1 (en) | 2000-10-30 | 2004-07-06 | Kenny L. Dang | Increased drug-loading and reduced stress drug delivery device |
US6770721B1 (en) * | 2000-11-02 | 2004-08-03 | Surface Logix, Inc. | Polymer gel contact masks and methods and molds for making same |
US20020082679A1 (en) | 2000-12-22 | 2002-06-27 | Avantec Vascular Corporation | Delivery or therapeutic capable agents |
US6824559B2 (en) | 2000-12-22 | 2004-11-30 | Advanced Cardiovascular Systems, Inc. | Ethylene-carboxyl copolymers as drug delivery matrices |
US7077859B2 (en) | 2000-12-22 | 2006-07-18 | Avantec Vascular Corporation | Apparatus and methods for variably controlled substance delivery from implanted prostheses |
US6544543B1 (en) | 2000-12-27 | 2003-04-08 | Advanced Cardiovascular Systems, Inc. | Periodic constriction of vessels to treat ischemic tissue |
US6663662B2 (en) | 2000-12-28 | 2003-12-16 | Advanced Cardiovascular Systems, Inc. | Diffusion barrier layer for implantable devices |
US6540776B2 (en) | 2000-12-28 | 2003-04-01 | Advanced Cardiovascular Systems, Inc. | Sheath for a prosthesis and methods of forming the same |
US20020087123A1 (en) | 2001-01-02 | 2002-07-04 | Hossainy Syed F.A. | Adhesion of heparin-containing coatings to blood-contacting surfaces of medical devices |
US6544223B1 (en) | 2001-01-05 | 2003-04-08 | Advanced Cardiovascular Systems, Inc. | Balloon catheter for delivering therapeutic agents |
US6645195B1 (en) | 2001-01-05 | 2003-11-11 | Advanced Cardiovascular Systems, Inc. | Intraventricularly guided agent delivery system and method of use |
US6544582B1 (en) | 2001-01-05 | 2003-04-08 | Advanced Cardiovascular Systems, Inc. | Method and apparatus for coating an implantable device |
US6740040B1 (en) | 2001-01-30 | 2004-05-25 | Advanced Cardiovascular Systems, Inc. | Ultrasound energy driven intraventricular catheter to treat ischemia |
US20030032767A1 (en) | 2001-02-05 | 2003-02-13 | Yasuhiro Tada | High-strength polyester-amide fiber and process for producing the same |
JP2004533277A (en) | 2001-02-09 | 2004-11-04 | エンドルミナル セラピューティクス, インコーポレイテッド | Intramural therapy |
CA2789997A1 (en) * | 2001-03-08 | 2002-12-19 | William F. Degrado | Facially amphiphilic polymers an anti-infective agents |
AU2002254158A1 (en) | 2001-03-08 | 2002-09-24 | Volcano Therapeutics, Inc. | Medical devices, compositions and methods for treating vulnerable plaque |
US6613077B2 (en) | 2001-03-27 | 2003-09-02 | Scimed Life Systems, Inc. | Stent with controlled expansion |
US6623448B2 (en) | 2001-03-30 | 2003-09-23 | Advanced Cardiovascular Systems, Inc. | Steerable drug delivery device |
US6645135B1 (en) | 2001-03-30 | 2003-11-11 | Advanced Cardiovascular Systems, Inc. | Intravascular catheter device and method for simultaneous local delivery of radiation and a therapeutic substance |
US6780424B2 (en) | 2001-03-30 | 2004-08-24 | Charles David Claude | Controlled morphologies in polymer drug for release of drugs from polymer films |
US6625486B2 (en) | 2001-04-11 | 2003-09-23 | Advanced Cardiovascular Systems, Inc. | Method and apparatus for intracellular delivery of an agent |
US6764505B1 (en) | 2001-04-12 | 2004-07-20 | Advanced Cardiovascular Systems, Inc. | Variable surface area stent |
US6712845B2 (en) | 2001-04-24 | 2004-03-30 | Advanced Cardiovascular Systems, Inc. | Coating for a stent and a method of forming the same |
EP1383504A1 (en) | 2001-04-26 | 2004-01-28 | Control Delivery Systems, Inc. | Sustained release drug delivery system containing codrugs |
US6660034B1 (en) | 2001-04-30 | 2003-12-09 | Advanced Cardiovascular Systems, Inc. | Stent for increasing blood flow to ischemic tissues and a method of using the same |
US6656506B1 (en) | 2001-05-09 | 2003-12-02 | Advanced Cardiovascular Systems, Inc. | Microparticle coated medical device |
US7651695B2 (en) | 2001-05-18 | 2010-01-26 | Advanced Cardiovascular Systems, Inc. | Medicated stents for the treatment of vascular disease |
US7862495B2 (en) | 2001-05-31 | 2011-01-04 | Advanced Cardiovascular Systems, Inc. | Radiation or drug delivery source with activity gradient to minimize edge effects |
US6605154B1 (en) | 2001-05-31 | 2003-08-12 | Advanced Cardiovascular Systems, Inc. | Stent mounting device |
US6743462B1 (en) | 2001-05-31 | 2004-06-01 | Advanced Cardiovascular Systems, Inc. | Apparatus and method for coating implantable devices |
US6666880B1 (en) | 2001-06-19 | 2003-12-23 | Advised Cardiovascular Systems, Inc. | Method and system for securing a coated stent to a balloon catheter |
US6572644B1 (en) | 2001-06-27 | 2003-06-03 | Advanced Cardiovascular Systems, Inc. | Stent mounting device and a method of using the same to coat a stent |
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 |
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 |
US6673154B1 (en) | 2001-06-28 | 2004-01-06 | Advanced Cardiovascular Systems, Inc. | Stent mounting device to coat a stent |
US6585755B2 (en) | 2001-06-29 | 2003-07-01 | Advanced Cardiovascular | Polymeric stent suitable for imaging by MRI and fluoroscopy |
US6527863B1 (en) | 2001-06-29 | 2003-03-04 | Advanced Cardiovascular Systems, Inc. | Support device for a stent and a method of using the same to coat a stent |
US6706013B1 (en) | 2001-06-29 | 2004-03-16 | Advanced Cardiovascular Systems, Inc. | Variable length drug delivery catheter |
US6656216B1 (en) | 2001-06-29 | 2003-12-02 | Advanced Cardiovascular Systems, Inc. | Composite stent with regioselective material |
EP1273314A1 (en) | 2001-07-06 | 2003-01-08 | Terumo Kabushiki Kaisha | Stent |
US6641611B2 (en) | 2001-11-26 | 2003-11-04 | Swaminathan Jayaraman | Therapeutic coating for an intravascular implant |
EP1429689A4 (en) | 2001-09-24 | 2006-03-08 | Medtronic Ave Inc | Rational drug therapy device and methods |
US7195640B2 (en) | 2001-09-25 | 2007-03-27 | Cordis Corporation | Coated medical devices for the treatment of vulnerable plaque |
US6753071B1 (en) | 2001-09-27 | 2004-06-22 | Advanced Cardiovascular Systems, Inc. | Rate-reducing membrane for release of an agent |
US20030059520A1 (en) | 2001-09-27 | 2003-03-27 | Yung-Ming Chen | Apparatus for regulating temperature of a composition and a method of coating implantable devices |
US20030073961A1 (en) | 2001-09-28 | 2003-04-17 | Happ Dorrie M. | Medical device containing light-protected therapeutic agent and a method for fabricating thereof |
US20030065377A1 (en) | 2001-09-28 | 2003-04-03 | Davila Luis A. | Coated medical devices |
US7585516B2 (en) | 2001-11-12 | 2009-09-08 | Advanced Cardiovascular Systems, Inc. | Coatings for drug delivery devices |
US6663880B1 (en) | 2001-11-30 | 2003-12-16 | Advanced Cardiovascular Systems, Inc. | Permeabilizing reagents to increase drug delivery and a method of local delivery |
US6709514B1 (en) | 2001-12-28 | 2004-03-23 | Advanced Cardiovascular Systems, Inc. | Rotary coating apparatus for coating implantable medical devices |
US7445629B2 (en) | 2002-01-31 | 2008-11-04 | Boston Scientific Scimed, Inc. | Medical device for delivering biologically active material |
US6887270B2 (en) | 2002-02-08 | 2005-05-03 | Boston Scientific Scimed, Inc. | Implantable or insertable medical device resistant to microbial growth and biofilm formation |
US6743463B2 (en) | 2002-03-28 | 2004-06-01 | Scimed Life Systems, Inc. | Method for spray-coating a medical device having a tubular wall such as a stent |
US6865810B2 (en) | 2002-06-27 | 2005-03-15 | Scimed Life Systems, Inc. | Methods of making medical devices |
US20040054104A1 (en) | 2002-09-05 | 2004-03-18 | Pacetti Stephen D. | Coatings for drug delivery devices comprising modified poly(ethylene-co-vinyl alcohol) |
US20040063805A1 (en) | 2002-09-19 | 2004-04-01 | Pacetti Stephen D. | Coatings for implantable medical devices and methods for fabrication thereof |
US7087263B2 (en) | 2002-10-09 | 2006-08-08 | Advanced Cardiovascular Systems, Inc. | Rare limiting barriers for implantable medical devices |
EP1560613A1 (en) | 2002-11-08 | 2005-08-10 | Conor Medsystems, Inc. | Method and apparatus for reducing tissue damage after ischemic injury |
CA2417634A1 (en) * | 2002-11-22 | 2004-05-22 | Emory University | Plastic and elastic protein copolymers |
EP1422242A1 (en) | 2002-11-22 | 2004-05-26 | Emory University | Plastic and elastic protein copolymers |
US6926919B1 (en) | 2003-02-26 | 2005-08-09 | Advanced Cardiovascular Systems, Inc. | Method for fabricating a coating for a medical device |
US8088404B2 (en) | 2003-03-20 | 2012-01-03 | Medtronic Vasular, Inc. | Biocompatible controlled release coatings for medical devices and related methods |
US7318944B2 (en) | 2003-08-07 | 2008-01-15 | Medtronic Vascular, Inc. | Extrusion process for coating stents |
US20050038497A1 (en) | 2003-08-11 | 2005-02-17 | Scimed Life Systems, Inc. | Deformation medical device without material deformation |
US20050037052A1 (en) | 2003-08-13 | 2005-02-17 | Medtronic Vascular, Inc. | Stent coating with gradient porosity |
US20050043786A1 (en) | 2003-08-18 | 2005-02-24 | Medtronic Ave, Inc. | Methods and apparatus for treatment of aneurysmal tissue |
US7344559B2 (en) * | 2003-08-25 | 2008-03-18 | Biophan Technologies, Inc. | Electromagnetic radiation transparent device and method of making thereof |
US20050049693A1 (en) | 2003-08-25 | 2005-03-03 | Medtronic Vascular Inc. | Medical devices and compositions for delivering biophosphonates to anatomical sites at risk for vascular disease |
US20050055078A1 (en) | 2003-09-04 | 2005-03-10 | Medtronic Vascular, Inc. | Stent with outer slough coating |
US7544381B2 (en) | 2003-09-09 | 2009-06-09 | Boston Scientific Scimed, Inc. | Lubricious coatings for medical device |
US20050054774A1 (en) | 2003-09-09 | 2005-03-10 | Scimed Life Systems, Inc. | Lubricious coating |
US20050060020A1 (en) | 2003-09-17 | 2005-03-17 | Scimed Life Systems, Inc. | Covered stent with biologically active material |
US7371228B2 (en) | 2003-09-19 | 2008-05-13 | Medtronic Vascular, Inc. | Delivery of therapeutics to treat aneurysms |
US20050065501A1 (en) | 2003-09-23 | 2005-03-24 | Scimed Life Systems, Inc. | Energy activated vaso-occlusive devices |
US7789891B2 (en) | 2003-09-23 | 2010-09-07 | Boston Scientific Scimed, Inc. | External activation of vaso-occlusive implants |
US7060319B2 (en) | 2003-09-24 | 2006-06-13 | Boston Scientific Scimed, Inc. | method for using an ultrasonic nozzle to coat a medical appliance |
US8801692B2 (en) | 2003-09-24 | 2014-08-12 | Medtronic Vascular, Inc. | Gradient coated stent and method of fabrication |
US7055237B2 (en) | 2003-09-29 | 2006-06-06 | Medtronic Vascular, Inc. | Method of forming a drug eluting stent |
US20050074406A1 (en) | 2003-10-03 | 2005-04-07 | Scimed Life Systems, Inc. | Ultrasound coating for enhancing visualization of medical device in ultrasound images |
US6984411B2 (en) | 2003-10-14 | 2006-01-10 | Boston Scientific Scimed, Inc. | Method for roll coating multiple stents |
US7795467B1 (en) * | 2005-04-26 | 2010-09-14 | Advanced Cardiovascular Systems, Inc. | Bioabsorbable, biobeneficial polyurethanes for use in medical devices |
US7601383B2 (en) | 2006-02-28 | 2009-10-13 | Advanced Cardiovascular Systems, Inc. | Coating construct containing poly (vinyl alcohol) |
US7713637B2 (en) * | 2006-03-03 | 2010-05-11 | Advanced Cardiovascular Systems, Inc. | Coating containing PEGylated hyaluronic acid and a PEGylated non-hyaluronic acid polymer |
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 |
-
2006
- 2006-06-09 US US11/449,896 patent/US8778376B2/en not_active Expired - Fee Related
-
2007
- 2007-05-10 US US11/803,031 patent/US8029816B2/en not_active Expired - Fee Related
- 2007-06-08 WO PCT/US2007/013687 patent/WO2007146228A2/en active Application Filing
-
2011
- 2011-09-02 US US13/225,165 patent/US20120046640A1/en not_active Abandoned
- 2011-09-02 US US13/224,515 patent/US9078958B2/en not_active Expired - Fee Related
-
2014
- 2014-06-18 US US14/308,444 patent/US20140356519A1/en not_active Abandoned
- 2014-06-18 US US14/308,412 patent/US20140363563A1/en not_active Abandoned
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109381750A (en) * | 2018-05-09 | 2019-02-26 | 张锋 | Anticoagulation facilitates the cardiac stent of taking-up |
Also Published As
Publication number | Publication date |
---|---|
US20140363563A1 (en) | 2014-12-11 |
US8029816B2 (en) | 2011-10-04 |
US8778376B2 (en) | 2014-07-15 |
US20080038310A1 (en) | 2008-02-14 |
WO2007146228A3 (en) | 2008-10-02 |
US20120263759A1 (en) | 2012-10-18 |
US20070286885A1 (en) | 2007-12-13 |
US20140356519A1 (en) | 2014-12-04 |
WO2007146228A2 (en) | 2007-12-21 |
US9078958B2 (en) | 2015-07-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US9078958B2 (en) | Depot stent comprising an elastin-based copolymer | |
US7601383B2 (en) | Coating construct containing poly (vinyl alcohol) | |
US7311980B1 (en) | Polyactive/polylactic acid coatings for an implantable device | |
US8703167B2 (en) | Coatings for implantable medical devices for controlled release of a hydrophilic drug and a hydrophobic drug | |
US7700659B2 (en) | Implantable devices formed of non-fouling methacrylate or acrylate polymers | |
US8048441B2 (en) | Nanobead releasing medical devices | |
US20070198080A1 (en) | Coatings including an antioxidant | |
US7591841B2 (en) | Implantable devices for accelerated healing | |
US20110144741A1 (en) | Coating Construct With Enhanced Interfacial Compatibility | |
US8333984B2 (en) | Coatings of acrylamide-based copolymers | |
US8105391B2 (en) | Merhods of treatment with devices having a coating containing pegylated hyaluronic acid and a pegylated non-hyaluronic acid polymer | |
US20160158420A1 (en) | Coatings formed from stimulus-sensitive material | |
US20080175882A1 (en) | Polymers of aliphatic thioester | |
US9381279B2 (en) | Implantable devices formed on non-fouling methacrylate or acrylate polymers |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |