[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

WO2001047451A1 - Apparatus and method for delivering compounds to a living organism - Google Patents

Apparatus and method for delivering compounds to a living organism Download PDF

Info

Publication number
WO2001047451A1
WO2001047451A1 PCT/US2000/035641 US0035641W WO0147451A1 WO 2001047451 A1 WO2001047451 A1 WO 2001047451A1 US 0035641 W US0035641 W US 0035641W WO 0147451 A1 WO0147451 A1 WO 0147451A1
Authority
WO
WIPO (PCT)
Prior art keywords
hormone
sex
local
combination
delivery device
Prior art date
Application number
PCT/US2000/035641
Other languages
French (fr)
Inventor
Gishel New
Jeffrey W. Moses
Nicholas Kipshidze
Gary S. Roubin
Martin B. Leon
Original Assignee
Gishel New
Moses Jeffrey W
Nicholas Kipshidze
Roubin Gary S
Leon Martin B
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Gishel New, Moses Jeffrey W, Nicholas Kipshidze, Roubin Gary S, Leon Martin B filed Critical Gishel New
Priority to EP00989608A priority Critical patent/EP1278493A4/en
Priority to AU26094/01A priority patent/AU2609401A/en
Publication of WO2001047451A1 publication Critical patent/WO2001047451A1/en
Priority to US09/943,648 priority patent/US6471979B2/en
Priority to US10/260,954 priority patent/US20030039677A1/en
Priority to US10/661,820 priority patent/US20040127475A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A61F2/915—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4196—1,2,4-Triazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/451—Non condensed piperidines, e.g. piperocaine having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4535—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A61K31/566—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol having an oxo group in position 17, e.g. estrone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A61K31/567—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in position 17 alpha, e.g. mestranol, norethandrolone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
    • A61K31/5685—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone having an oxo group in position 17, e.g. androsterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A61L29/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—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
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A61F2/915—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
    • A61F2002/91533—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other characterised by the phase between adjacent bands
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A61F2/915—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
    • A61F2002/9155—Adjacent bands being connected to each other
    • A61F2002/91575—Adjacent bands being connected to each other connected peak to trough
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2230/00—Geometry of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2230/0002—Two-dimensional shapes, e.g. cross-sections
    • A61F2230/0028—Shapes in the form of latin or greek characters
    • A61F2230/0054—V-shaped
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
    • A61F2250/0067—Means for introducing or releasing pharmaceutical products into the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/43—Hormones, e.g. dexamethasone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602—Type of release, e.g. controlled, sustained, slow
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606—Coatings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/0043—Catheters; Hollow probes characterised by structural features
    • A61M2025/0057—Catheters delivering medicament other than through a conventional lumen, e.g. porous walls or hydrogel coatings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M2025/1043—Balloon catheters with special features or adapted for special applications
    • A61M2025/105—Balloon catheters with special features or adapted for special applications having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters
    • A61M2025/1043—Balloon catheters with special features or adapted for special applications
    • A61M2025/1072—Balloon catheters with special features or adapted for special applications having balloons with two or more compartments
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/10—Balloon catheters

Definitions

  • the invention relates to local-delivery devices and methods for treating and preventing vascular diseases in a living organism. More particularly, the invention relates to local-delivery devices coated with a composition comprising a sex hormone, anti- hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or a combination thereof.
  • the local- delivery device e.g. a stent, catheter or balloon-injection catheter, is inserted into an affected area of a living organism to treat or prevent the vascular disease.
  • Vascular diseases include diseases that affect areas of a living organism relating to or containing blood vessels.
  • stenosis is a narrowing or constricting of arterial lumen in a living organism (e.g., a human) usually due to atherosclerosis/coronary heart disease (CHD).
  • Restenosis is a recurrence of stenosis after a percuteneous intervention such as angioplasty and stenting.
  • the underlying mechanisms of restenosis comprise a combination of effects from vessel recoil, negative vascular remodeling, thrombus formation and neointimal hyperplasia. It has been shown that restenosis after balloon angioplasty is mainly due to vessel remodeling and neointimal hyperplasia.
  • Treatment for stenosis and restenosis varies. Stenosis caused by CHD often forces individuals to restrict and limit their activity levels in order to avoid complications, stroke, heart attack, sudden death and loss of limb or function of a limb stemming from the stenosis.
  • the reconstruction of blood vessels, arteries and veins may also be needed to treat individuals suffering from stenosis and restenosis.
  • Coronary bypass can also be utilized to revascularize the heart and restore normal blood flow.
  • balloon angioplasty may be conducted to increase the orifice size of affected areas. Overall, these treatments address the problems associated with stenosis, but they also create a high rate of restenosis that can result in recurrence of cardiac symptoms and mortality.
  • Atherosclerosis affects medium and large arteries and is characterized by a patchy, intramural thickening that encroaches on the arterial lumen and, in most severe form, causes obstruction.
  • the atherosclerotic plaque consists of an accumulation of intracellular and extracellular lipids, smooth muscle cells and connective tissue.
  • the earliest lesion of atherosclerosis is the fatty streak that evolves into a fibrous plaque coating the artery.
  • Atherosclerotic vessels have reduced systolic expansion and abnormal wave propagation.
  • Atherosclerosis Treatment of atherosclerosis is usually directed at its complications, for example, arrhythmia, heart failure, kidney failure, stroke, and peripheral arterial occlusion.
  • New and improved methods and devices are being sought for treatment and prevention of vascular diseases such as stenosis, restenosis and atherosclerosis.
  • the present invention provides a method of treating or preventing vascular disease in a living organism.
  • the method includes applying an effective amount of a composition comprising a sex hormone, anti-hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or a combination thereof, to a local-delivery device.
  • a composition comprising a sex hormone, anti-hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or a combination thereof.
  • SERM selective estrogen receptor modulator
  • the method also includes inserting the local-delivery device into an affected area of a living organism and allowing at least a portion of the sex hormone, anti-hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or combination thereof, to gradually release or inject into the affected area of the living organism.
  • SERM selective estrogen receptor modulator
  • the invention also provides a local-delivery system effective for treating and preventing vascular disease in a living organism.
  • the system includes a local-delivery device and a composition at least partially applied thereto.
  • the composition comprises a sex hormone, anti-hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or a combination thereof.
  • SERM selective estrogen receptor modulator
  • Figure 1 is a perspective view of a stent embodying the invention.
  • Figure 2 is a cross-sectional view taken along line 2—2 in Figure 1.
  • Figure 3 is a perspective view of a balloon-injection catheter embodying the invention.
  • Figure 4 is cross-sectional view taken along line 4—4 of Figure 3.
  • Figure 5 is a cross-sectional view taken along line 5—5 in Figure 5, wherein the catheter is inserted into an affected area of a living organism.
  • Figure 6 is a cross-sectional view taken along line 6—6 of Figure 1.
  • the present invention provides apparatuses and methods for delivering a composition to a localized area of a living organism. More particularly, the invention provides apparatuses and methods for locally delivering a sex hormone (e.g. estrogen), an anti-hormone, a sex-hormone agonist, a steroid-hormone inhibitor/antagonist (partial or full) or a selective estrogen receptor modulator (SERM), or a combination thereof, to a portion of a living organism inflicted by or susceptible to a vascular disease such as stenosis or restenosis.
  • a sex hormone e.g. estrogen
  • an anti-hormone e.g. estrogen
  • a sex-hormone agonist e.g. sex-hormone agonist
  • a steroid-hormone inhibitor/antagonist e.g., partial or full
  • SERM selective estrogen receptor modulator
  • Estrogen is known to favorably alter the atherogenic lipid profile and may also have a direct action on blood vessel walls. Estrogen can have both rapid and long-term effects on the vasculature including the local production of coagulation and fibrinolytic factors, antioxidants and the production of other vasoactive molecules, such as nitric oxide and prostaglandins, all of which are known to influence the development of vascular disease. Experimental work suggests that estrogen can also act on the endothelium and smooth muscle cells either directly or via estrogen receptors in both men and women. This appears to have an inhibitory effect on many steps in the atherosclerotic process.
  • Estrogen appears to inhibit the response to balloon injury to the vascular wall.
  • Estrogen can repair and accelerate endothehal cell growth in- vitro and in-vivo. Early restoration of endothehal cell integrity may contribute to the attenuation of the response to injury by increasing the availability of nitric oxide. This in turn can directly inhibit the proliferation of smooth muscle cells.
  • estrogen has been shown to inhibit the proliferation and migration of smooth muscle cells in response to balloon injury. Estrogen has also proved to inhibit adventitial fibroblast migration which may in turn have an effect on negative remodeling.
  • Sex hormones and sex-hormone agonists may be helpful in preventing and treating certain vascular diseases.
  • suitable sex hormones include, but are in no way limited to, estrogens, progesterones, testosterones, dehydroepiandrostrones (DHEAs) and dehydroepiandrosteronesulfates (DHEAs).
  • DHEAs dehydroepiandrostrones
  • DHEAs dehydroepiandrosteronesulfates
  • estrogen has proven to be the most effective in preventing and treating vascular diseases.
  • Naturally occurring/plant estrogens or phytoestrogens including isoflavones such as genistein, daidzein and resveratrol are also useful in the treatment of vascular disease.
  • Suitable sex- hormone agonists include, but are in no way limited to, estradiol, estrone, ethinyl estradiol and conjugated equine estrogens.
  • anti-hormones and steroid-hormone inhibitors/antagonist may be effective in preventing vascular diseases.
  • Anti-hormones inhibit or prevent the usual effects of certain other hormones, thereby increasing the relative effectiveness of hormones that are not being inhibited or prevented by these anti-hormones.
  • Anti- hormones effective in preventing vascular diseases include, but are not limited to, anti- estrogens (e.g. Faslodex), anti-androgens (e.g. cyproterone acetate) and anti-testosterone (e.g. anti-testosterone wild-type Fab fragment and mutant Fab fragments).
  • Examples of steroid-hormone inhibitors/antagonist include, but are not limited to, aminogluthemide, anastrazole and letrozole.
  • Selective estrogen receptor modulators including but not limited to raloxifene, tamoxifen and idoxifene, may also be effective in treating or preventing vascular diseases such as stenosis and restenosis.
  • these compounds are generally found in a powdered form.
  • the powder In order to apply the compound to a local-delivery device or to locally inject the compound into an affected area, the powder is generally mixed with a solution of saline or ethanol. This facilitates coating the local-delivery devices or injecting the composition as described below.
  • the composition can also be mixed into another solution, gel or substance to control the rate of release from the stent and into the tissue.
  • compositions in the exact area of disease or potential disease avoids the negative systemic effects these compounds can produce when administered generally.
  • oral use of conjugated equine estrogen in combination with a progestin may have effects on the coagulation pathways that attenuate the benefits that may potentially occur to a vascular wall.
  • hyperplastic effects of estrogen on the uterus and breast tissue may exist when estrogen is administered systemically.
  • general administration may result in potential feminizing effects in males.
  • the local delivery of estrogen and the other compositions described above to atherosclerotic plaque is a promising alternative to the systemic use of this hormone.
  • the basic anti-atherogenic properties of these compositions and their potential to inhibit neointimal proliferation while simultaneously attenuating endothehal repair make them ideal for local administration in the coronary artery to inhibit restenosis.
  • Localized delivery of other compositions comprising sex hormones, anti-hormones, sex-hormone agonists, steroid-hormone inhibitors/antagonist (partial or full) or selective estrogen receptor modulators (SERMS), or combinations thereof, to the vasculature may prevent and treat vascular diseases such as stenosis, restenosis and atherosclerosis.
  • SERMS selective estrogen receptor modulators
  • the local-delivery systems generally comprise a local-delivery device and at least one of the effective compositions described above.
  • the compositions can be delivered locally to tissue, tubular organs, blood vessels, the coronary or peripheral of organs as well as to muscles (myocardium, skeletal or smooth muscles).
  • the compositions can also be injected directly into the vessel, vessel wall or muscle.
  • the local-delivery system is a stent that delivers the above-described compositions to the localized portion of the body of a living organism.
  • Figure 1 illustrates a stent 10, which is a hollow member that lies within the lumen of a tubular structure and provides support and assures patency of an intact but contracted lumen. Stents may be made from stainless steel or any other suitable material. Effective compositions as described above coat or are applied to the stent.
  • Figure 2 shows a portion of the stent 10 coated with a composition 12 in cross-section.
  • the stent Because the stent remains in the artery after the angioplasty procedure is performed, it enables the composition 12 to slowly diffuse from the outside of its surface 10 into the adjacent atherosclerotic plaque to which it can affect. The rate of this diffusion varies according to the molecular weight of the compound being administered. Also, the structure of the stent and the type of coating applied thereto also affect the rate of diffusion.
  • an effective composition is applied to an injection catheter, and more particularly to a balloon-injection catheter 14.
  • a balloon-injection catheter 14 is similar to a balloon angioplasty, except for the added feature of a chamber 16 including injection ports 18 for injecting the compositions described above.
  • Figure 5 illustrates a balloon-injection catheter 14 in cross-section after being injected into an affected area 20 of a living organism.
  • the hormone can be injected directly into the plaque, vessel wall or tissue 22 via these injection ports 18. If an injection catheter injects the compound into the plaque 22, the composition releases immediately after injection. Accordingly, there is no residual release of the composition once the injection catheter is removed.
  • Angiographic, angioplasty, delivery and infusion catheters may also be used to deliver these compounds to affected areas.
  • the above-described compositions can be locally delivered to a variety of body structures including grafts, saphenos vein grafts, arterial grafts, synthetic grafts, implants, prostheses or endoprostheses, homo or zeno grafts, cardiac muscle, skeletal or smooth muscle body structure. Applving the Effective Compositions to the Local-Delivery Devices
  • compositions to a stent or other local-delivery device can be achieved in a number of different ways.
  • the compound can be mechanically or electromechanically bonded to the delivery device, e.g. by a covalent bonding process.
  • the compounds are directly embedded into a metal or other suitable substance from which the local-delivery system is comprised.
  • the effective composition can also be applied using a chemical coating/bonding process, whereby layers of a suitable pharmaceutical agent, vehicle, or carrier entrap the compound.
  • a biological or pharmacological coating already present on the local-delivery device acts as a platform for coating the compounds described above.
  • platforms include, but are not limited to, silicon carbide, carbon, diamond or diamond-like coating, e.g. polytetrafluoroethylene, hylauronic acid or polyactone.
  • suitable synthetic pharmaceutical agents include, but are not limited to, polyurethane, segmented polyurethane, poly-L-lactic acid, cellulose ester, polyethylene glycol as well as polyphosphate esters.
  • Naturally occurring vehicles or carriers include collagens, laminens, heparins, fibrins, and other naturally occurring substances that absorb to cellulose.
  • Using a chemical coating of the stent or other device is particularly advantageous in that it allows the compound or sex hormone to slowly release from the carrier, vehicle, or agent. This extends the time that the affected portion of the body sustains the efficacious effects of the compounds.
  • the manner in which these carriers or vehicles interact with the device material as well as the inherent structure of these carriers and vehicles provide a diffusion barrier, thereby controlling the release of the entrapped compounds or sex hormones.
  • Estrogen and the other effective compositions described above can also be coated onto or delivered with other drugs or compounds in order to administer synergistic treatment.
  • Suitable drugs and compounds include antibodies, oligonucleotides (e.g. antisense oligonucleotides), antiproliferatives, anticancer or antimicrotubular agents (e.g. rapamycin, paclitaxel), antiproliferative agents, growth factors, genes, antisense or antithrombotic agents or any other chemical or biological compound that will act synergistically to increase the effectiveness of the primary hormone or compound.
  • stent coatings can absorb and release these materials, thus providing an inert depot for controlled drug administration. Loading of the drug can occur for example via diffusion of the drug solution into the coating by hydration/swelling of the polymer matrix.
  • Example 1 powdered estrogen is mixed with a carrier such as ethanol to form a solution or gel.
  • the estrogen gel is then applied to a stainless steel stent using chemical coating methods that are well-known in the art.
  • the coated stent is inserted into an arterial lumen of a human being suffering from atherosclerosis.
  • the coated stent is inserted into an artery plagued by patchy, intramural plaque.
  • the estrogen in the coating slowly diffuses into and penetrates the plaque, thereby providing treatment for this vascular disease.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Molecular Biology (AREA)
  • Transplantation (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Hematology (AREA)
  • Anesthesiology (AREA)
  • Pulmonology (AREA)
  • Surgery (AREA)
  • Biophysics (AREA)
  • Urology & Nephrology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Materials For Medical Uses (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

A method of treating or preventing vascular disease in a living organism. The method includes delivering an effective amount of a composition including a sex hormone, anti-hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or a combination thereof, to an affected area of a living organism.

Description

APPARATUS AND METHOD FOR DELIVERING COMPOUNDS TO A LIVING ORGANISM
FIELD OF THE INVENTION The invention relates to local-delivery devices and methods for treating and preventing vascular diseases in a living organism. More particularly, the invention relates to local-delivery devices coated with a composition comprising a sex hormone, anti- hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or a combination thereof. The local- delivery device, e.g. a stent, catheter or balloon-injection catheter, is inserted into an affected area of a living organism to treat or prevent the vascular disease.
BACKGROUND OF THE INVENTION Vascular diseases include diseases that affect areas of a living organism relating to or containing blood vessels.
For example, stenosis is a narrowing or constricting of arterial lumen in a living organism (e.g., a human) usually due to atherosclerosis/coronary heart disease (CHD). Restenosis is a recurrence of stenosis after a percuteneous intervention such as angioplasty and stenting. The underlying mechanisms of restenosis comprise a combination of effects from vessel recoil, negative vascular remodeling, thrombus formation and neointimal hyperplasia. It has been shown that restenosis after balloon angioplasty is mainly due to vessel remodeling and neointimal hyperplasia.
Treatment for stenosis and restenosis varies. Stenosis caused by CHD often forces individuals to restrict and limit their activity levels in order to avoid complications, stroke, heart attack, sudden death and loss of limb or function of a limb stemming from the stenosis. The reconstruction of blood vessels, arteries and veins may also be needed to treat individuals suffering from stenosis and restenosis. Coronary bypass can also be utilized to revascularize the heart and restore normal blood flow. In other cases, balloon angioplasty may be conducted to increase the orifice size of affected areas. Overall, these treatments address the problems associated with stenosis, but they also create a high rate of restenosis that can result in recurrence of cardiac symptoms and mortality. Moreover, these treatments are not preventative in nature, and therefore generally are not utilized until the patient or individual has already developed stenosis. One type of stenosis and restenosis is atherosclerosis. Atherosclerosis affects medium and large arteries and is characterized by a patchy, intramural thickening that encroaches on the arterial lumen and, in most severe form, causes obstruction. The atherosclerotic plaque consists of an accumulation of intracellular and extracellular lipids, smooth muscle cells and connective tissue. The earliest lesion of atherosclerosis is the fatty streak that evolves into a fibrous plaque coating the artery. Atherosclerotic vessels have reduced systolic expansion and abnormal wave propagation. Treatment of atherosclerosis is usually directed at its complications, for example, arrhythmia, heart failure, kidney failure, stroke, and peripheral arterial occlusion. New and improved methods and devices are being sought for treatment and prevention of vascular diseases such as stenosis, restenosis and atherosclerosis.
SUMMARY OF THE INVENTION The present invention provides a method of treating or preventing vascular disease in a living organism. The method includes applying an effective amount of a composition comprising a sex hormone, anti-hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or a combination thereof, to a local-delivery device. The method also includes inserting the local-delivery device into an affected area of a living organism and allowing at least a portion of the sex hormone, anti-hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or combination thereof, to gradually release or inject into the affected area of the living organism.
The invention also provides a local-delivery system effective for treating and preventing vascular disease in a living organism. The system includes a local-delivery device and a composition at least partially applied thereto. The composition comprises a sex hormone, anti-hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or a combination thereof. Other features and advantages of the invention will become apparent to those skilled in the art upon review of the following detailed description and claims. Before embodiments of the invention are explained in detail, it is to be understood that the invention is not limited in its application to the details of the composition and concentration of components set forth in the following description. The invention is capable of other embodiments and of being practiced or being carried out in various ways. Also, it is understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting.
BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a perspective view of a stent embodying the invention.
Figure 2 is a cross-sectional view taken along line 2—2 in Figure 1. Figure 3 is a perspective view of a balloon-injection catheter embodying the invention.
Figure 4 is cross-sectional view taken along line 4—4 of Figure 3. Figure 5 is a cross-sectional view taken along line 5—5 in Figure 5, wherein the catheter is inserted into an affected area of a living organism.
Figure 6 is a cross-sectional view taken along line 6—6 of Figure 1.
DESCRIPTION OF THE INVENTION The present invention provides apparatuses and methods for delivering a composition to a localized area of a living organism. More particularly, the invention provides apparatuses and methods for locally delivering a sex hormone (e.g. estrogen), an anti-hormone, a sex-hormone agonist, a steroid-hormone inhibitor/antagonist (partial or full) or a selective estrogen receptor modulator (SERM), or a combination thereof, to a portion of a living organism inflicted by or susceptible to a vascular disease such as stenosis or restenosis.
Recent research has uncovered that different sex hormones may have different effects on vascular functions. For example, gender differences in cardiovascular disease have largely been attributed to the protective effects of estrogen in women; premenopausal women have a lower incidence of Coronary Heart Disease. In particular, estrogen has well-known beneficial effects on lipid profile. More importantly, estrogen may directly affect vascular reactivity, which is an important component of atherosclerosis. Recent epidemiological studies suggest that hormone replacement therapy (HRT) may reduce the risk of coronary-artery disease in post-menopausal women. More particularly, many epidemiological studies suggest that estrogen replacement therapy (ERT) may be cardioprotective in postmenopausal women. The beneficial effects of these hormone therapies may also be applicable to males.
The mechanisms for these beneficial effects are probably multifactorial. Estrogen is known to favorably alter the atherogenic lipid profile and may also have a direct action on blood vessel walls. Estrogen can have both rapid and long-term effects on the vasculature including the local production of coagulation and fibrinolytic factors, antioxidants and the production of other vasoactive molecules, such as nitric oxide and prostaglandins, all of which are known to influence the development of vascular disease. Experimental work suggests that estrogen can also act on the endothelium and smooth muscle cells either directly or via estrogen receptors in both men and women. This appears to have an inhibitory effect on many steps in the atherosclerotic process. With respect to the interventional cardiology, estrogen appears to inhibit the response to balloon injury to the vascular wall. Estrogen can repair and accelerate endothehal cell growth in- vitro and in-vivo. Early restoration of endothehal cell integrity may contribute to the attenuation of the response to injury by increasing the availability of nitric oxide. This in turn can directly inhibit the proliferation of smooth muscle cells. In experimental studies, estrogen has been shown to inhibit the proliferation and migration of smooth muscle cells in response to balloon injury. Estrogen has also proved to inhibit adventitial fibroblast migration which may in turn have an effect on negative remodeling.
Effective Compositions
Sex hormones and sex-hormone agonists may be helpful in preventing and treating certain vascular diseases. Examples of suitable sex hormones include, but are in no way limited to, estrogens, progesterones, testosterones, dehydroepiandrostrones (DHEAs) and dehydroepiandrosteronesulfates (DHEAs). Of these compounds, estrogen has proven to be the most effective in preventing and treating vascular diseases. Naturally occurring/plant estrogens or phytoestrogens including isoflavones such as genistein, daidzein and resveratrol are also useful in the treatment of vascular disease. Suitable sex- hormone agonists include, but are in no way limited to, estradiol, estrone, ethinyl estradiol and conjugated equine estrogens.
In addition, anti-hormones and steroid-hormone inhibitors/antagonist (partial or full) may be effective in preventing vascular diseases. Anti-hormones inhibit or prevent the usual effects of certain other hormones, thereby increasing the relative effectiveness of hormones that are not being inhibited or prevented by these anti-hormones. Anti- hormones effective in preventing vascular diseases include, but are not limited to, anti- estrogens (e.g. Faslodex), anti-androgens (e.g. cyproterone acetate) and anti-testosterone (e.g. anti-testosterone wild-type Fab fragment and mutant Fab fragments). Examples of steroid-hormone inhibitors/antagonist (partial or full) include, but are not limited to, aminogluthemide, anastrazole and letrozole.
Selective estrogen receptor modulators (SERMS), including but not limited to raloxifene, tamoxifen and idoxifene, may also be effective in treating or preventing vascular diseases such as stenosis and restenosis.
These compounds are generally found in a powdered form. In order to apply the compound to a local-delivery device or to locally inject the compound into an affected area, the powder is generally mixed with a solution of saline or ethanol. This facilitates coating the local-delivery devices or injecting the composition as described below. The composition can also be mixed into another solution, gel or substance to control the rate of release from the stent and into the tissue.
Local-Delivery Systems
Local delivery of the above-listed compositions in the exact area of disease or potential disease avoids the negative systemic effects these compounds can produce when administered generally. For example, oral use of conjugated equine estrogen in combination with a progestin may have effects on the coagulation pathways that attenuate the benefits that may potentially occur to a vascular wall. In addition, hyperplastic effects of estrogen on the uterus and breast tissue may exist when estrogen is administered systemically. Moreover, general administration may result in potential feminizing effects in males.
The local delivery of estrogen and the other compositions described above to atherosclerotic plaque is a promising alternative to the systemic use of this hormone. The basic anti-atherogenic properties of these compositions and their potential to inhibit neointimal proliferation while simultaneously attenuating endothehal repair make them ideal for local administration in the coronary artery to inhibit restenosis. Localized delivery of other compositions comprising sex hormones, anti-hormones, sex-hormone agonists, steroid-hormone inhibitors/antagonist (partial or full) or selective estrogen receptor modulators (SERMS), or combinations thereof, to the vasculature may prevent and treat vascular diseases such as stenosis, restenosis and atherosclerosis.
The local-delivery systems generally comprise a local-delivery device and at least one of the effective compositions described above. The compositions can be delivered locally to tissue, tubular organs, blood vessels, the coronary or peripheral of organs as well as to muscles (myocardium, skeletal or smooth muscles). The compositions can also be injected directly into the vessel, vessel wall or muscle.
Examples of local-delivery devices include, but are not limited to, stents and catheters. In one embodiment of the invention, the local-delivery system is a stent that delivers the above-described compositions to the localized portion of the body of a living organism. Figure 1 illustrates a stent 10, which is a hollow member that lies within the lumen of a tubular structure and provides support and assures patency of an intact but contracted lumen. Stents may be made from stainless steel or any other suitable material. Effective compositions as described above coat or are applied to the stent. Figure 2 shows a portion of the stent 10 coated with a composition 12 in cross-section. Because the stent remains in the artery after the angioplasty procedure is performed, it enables the composition 12 to slowly diffuse from the outside of its surface 10 into the adjacent atherosclerotic plaque to which it can affect. The rate of this diffusion varies according to the molecular weight of the compound being administered. Also, the structure of the stent and the type of coating applied thereto also affect the rate of diffusion.
In another embodiment, an effective composition is applied to an injection catheter, and more particularly to a balloon-injection catheter 14. As shown in Figs. 3 and 4, a balloon-injection catheter 14 is similar to a balloon angioplasty, except for the added feature of a chamber 16 including injection ports 18 for injecting the compositions described above. Figure 5 illustrates a balloon-injection catheter 14 in cross-section after being injected into an affected area 20 of a living organism. The hormone can be injected directly into the plaque, vessel wall or tissue 22 via these injection ports 18. If an injection catheter injects the compound into the plaque 22, the composition releases immediately after injection. Accordingly, there is no residual release of the composition once the injection catheter is removed.
Angiographic, angioplasty, delivery and infusion catheters may also be used to deliver these compounds to affected areas. Using these devices, the above-described compositions can be locally delivered to a variety of body structures including grafts, saphenos vein grafts, arterial grafts, synthetic grafts, implants, prostheses or endoprostheses, homo or zeno grafts, cardiac muscle, skeletal or smooth muscle body structure. Applving the Effective Compositions to the Local-Delivery Devices
Application of these effective compositions to a stent or other local-delivery device can be achieved in a number of different ways.
First, the compound can be mechanically or electromechanically bonded to the delivery device, e.g. by a covalent bonding process. When using such a physical application the compounds are directly embedded into a metal or other suitable substance from which the local-delivery system is comprised.
Second, the effective composition can also be applied using a chemical coating/bonding process, whereby layers of a suitable pharmaceutical agent, vehicle, or carrier entrap the compound. In this manner, a biological or pharmacological coating already present on the local-delivery device acts as a platform for coating the compounds described above. Examples of platforms include, but are not limited to, silicon carbide, carbon, diamond or diamond-like coating, e.g. polytetrafluoroethylene, hylauronic acid or polyactone. Other suitable synthetic pharmaceutical agents include, but are not limited to, polyurethane, segmented polyurethane, poly-L-lactic acid, cellulose ester, polyethylene glycol as well as polyphosphate esters. Naturally occurring vehicles or carriers include collagens, laminens, heparins, fibrins, and other naturally occurring substances that absorb to cellulose. Using a chemical coating of the stent or other device is particularly advantageous in that it allows the compound or sex hormone to slowly release from the carrier, vehicle, or agent. This extends the time that the affected portion of the body sustains the efficacious effects of the compounds. The manner in which these carriers or vehicles interact with the device material as well as the inherent structure of these carriers and vehicles provide a diffusion barrier, thereby controlling the release of the entrapped compounds or sex hormones. Estrogen and the other effective compositions described above can also be coated onto or delivered with other drugs or compounds in order to administer synergistic treatment. Examples of other suitable drugs and compounds include antibodies, oligonucleotides (e.g. antisense oligonucleotides), antiproliferatives, anticancer or antimicrotubular agents (e.g. rapamycin, paclitaxel), antiproliferative agents, growth factors, genes, antisense or antithrombotic agents or any other chemical or biological compound that will act synergistically to increase the effectiveness of the primary hormone or compound. For example, stent coatings can absorb and release these materials, thus providing an inert depot for controlled drug administration. Loading of the drug can occur for example via diffusion of the drug solution into the coating by hydration/swelling of the polymer matrix.
Example In one preferred example, powdered estrogen is mixed with a carrier such as ethanol to form a solution or gel. The estrogen gel is then applied to a stainless steel stent using chemical coating methods that are well-known in the art. Subsequently, the coated stent is inserted into an arterial lumen of a human being suffering from atherosclerosis. In other words, the coated stent is inserted into an artery plagued by patchy, intramural plaque. The estrogen in the coating slowly diffuses into and penetrates the plaque, thereby providing treatment for this vascular disease.

Claims

CLAIMSI claim:
1. A method of treating or preventing vascular disease in a living organism, the method comprising: applying an effective amount of a composition comprising a sex hormone, anti-hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or a combination thereof, to a local- delivery device; inserting the local-delivery device into an affected area of a living organism; and allowing at least a portion of the sex hormone, anti-hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or combination thereof, to gradually release or be injected into the affected area of the living organism.
2. The method of claim 1, wherein the local-delivery device is a stent.
3. The method of claim 1 , wherein the local-delivery device is a balloon- injection catheter.
4. The method of claim 1, wherein the composition comprises a sex hormone and the sex hormone is estrogen, progesterone, testosterone, dehydroepiandrostrone (DHEA), dehydroepiandrosteronesulfate (DHEA) or a combination thereof.
5. The method of claim 4, wherein the composition comprises a sex hormone and the sex hormone is estrogen.
6. The method of claim 1, wherein the composition comprises a sex-hormone agonist and the sex-hormone agonist is estradiol, estrone, ethinyl estradiol, conjugated equine estrogen, or a combination thereof.
7. The method of claim 1, wherein the composition comprises an anti- hormone and the anti-hormone is an anti-estrogen, Faslodex, an anti-androgen, cyproterone acetate, an anti-testosterone, or a combination thereof.
8. The method of claim 1, wherein the composition comprises a steroid- hormone inhibitor/antagonist (partial or full) and the steroid-hormone inhibitor/antagonist (partial or full) is aminogluthemide, anastrazole, letrozole, or a combination thereof.
9. The method of claim 1, wherein the composition comprises a SERM and the SERM is a raloxifene, tamoxifen, idoxifene, or a combination thereof.
10. The method of claim 1, wherein the affected area of the living organism is tissue, tubular organ, blood vessels, coronary or peripheral of organs, myocardium, skeletal, smooth muscles or a combination thereof.
11. The method of claim 1 , wherein the composition is applied to the local- delivery device using a chemical coating comprising a suitable pharmaceutical agent, vehicle or carrier.
12. The method of claim 1, wherein the composition is applied to the local- delivery device using a mechanical or electromechanical bond.
13. A local-delivery system effective for treating and preventing vascular disease in a living organism comprising: a local-delivery device; and a composition comprising a sex hormone, anti-hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or a combination thereof, the composition being applied to the local- delivery device.
14. The system of claim 13, wherein the local-delivery device is a stent.
15. The system of claim 13, wherein the catheter is a balloon-injection catheter.
16. The system of claim 13, wherein the composition comprises a sex hormone and the sex hormone is estrogen, progesterone, testosterone, dehydroepiandrostrone (DHEA), dehydroepiandrosteronesulfate (DHEA), or a combination thereof.
17. The system of claim 16, wherein the sex hormone is estrogen.
18. The system of claim 13, wherein the composition comprises a sex-hormone agonist and the sex-hormone agonist is estradiol, estrone, ethinyl estradiol, conjugated equine estrogen, or a combination thereof.
19. The system of claim 13, wherein the composition comprises an anti- hormone and the anti-hormone is an anti-estrogen, Faslodex, an anti-androgen, cyproterone acetate, an anti-testosterone, or a combination thereof.
20. The system of claim 13, wherein the composition comprises a steroid- hormone inhibitor/antagonist (partial or full) and the steroid-hormone inhibitor/antagonist (partial or full) is aminogluthemide, anastrazole, letrozole, or a combination thereof.
21. The system of claim 13, wherein the composition comprises a SERM and the SERM is raloxifene, tamoxifen, idoxifene, or a combination thereof.
22. The system of claim 13, wherein the affected area of the living organism is tissue, tubular organ, blood vessels, coronary or peripheral of organs, myocardium, skeletal, smooth muscles or combinations thereof.
23. The system of claim 13 further comprising a compound synergistically increasing the effectiveness of the composition, the compound being applied to the local- delivery device.
24. The system of claim 13, wherein the composition is applied to the local- delivery device using a chemical coating.
25. The system of claim 13, wherein the composition is applied to the local- delivery device using a mechanical or electromechanical bond.
PCT/US2000/035641 1999-12-29 2000-12-29 Apparatus and method for delivering compounds to a living organism WO2001047451A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP00989608A EP1278493A4 (en) 1999-12-29 2000-12-29 Apparatus and method for delivering compounds to a living organism
AU26094/01A AU2609401A (en) 1999-12-29 2000-12-29 Apparatus and method for delivering compounds to a living organism
US09/943,648 US6471979B2 (en) 1999-12-29 2001-08-30 Apparatus and method for delivering compounds to a living organism
US10/260,954 US20030039677A1 (en) 1999-12-29 2002-09-30 Apparatus and method for delivering compounds to a living organism
US10/661,820 US20040127475A1 (en) 1999-12-29 2003-09-12 Apparatus and method for delivering compounds to a living organism

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US17345199P 1999-12-29 1999-12-29
US60/173,451 1999-12-29

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US09/943,648 Continuation-In-Part US6471979B2 (en) 1999-12-29 2001-08-30 Apparatus and method for delivering compounds to a living organism

Publications (1)

Publication Number Publication Date
WO2001047451A1 true WO2001047451A1 (en) 2001-07-05

Family

ID=22632100

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/035641 WO2001047451A1 (en) 1999-12-29 2000-12-29 Apparatus and method for delivering compounds to a living organism

Country Status (3)

Country Link
EP (1) EP1278493A4 (en)
AU (1) AU2609401A (en)
WO (1) WO2001047451A1 (en)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003020329A1 (en) * 2001-08-30 2003-03-13 Estrogen Vascular Technology, Lcc Hormone-coated stent for preventing stenosis or atherosclerosis
WO2004024206A1 (en) * 2002-09-12 2004-03-25 Estrogen Vascular Technology, Llc Apparatus and method for delivering compounds to a living organism
DE10311729A1 (en) * 2003-03-18 2004-09-30 Schultheiss, Heinz-Peter, Prof. Dr. Endovascular implant with an at least sectionally active coating of ratjadon and / or a ratjadon derivative
EP1594510A2 (en) * 2003-01-21 2005-11-16 Dimera Inc. Method and kit for reducing the symptoms of peripheral vascular disease
FR2880796A1 (en) * 2005-01-18 2006-07-21 Novatech Sa Sa ENDOPROTHESIS FOR ANOTOMIC CHANNEL
US7273655B2 (en) 1999-04-09 2007-09-25 Shojiro Miyake Slidably movable member and method of producing same
US7771821B2 (en) 2003-08-21 2010-08-10 Nissan Motor Co., Ltd. Low-friction sliding member and low-friction sliding mechanism using same
US8096205B2 (en) 2003-07-31 2012-01-17 Nissan Motor Co., Ltd. Gear
US8152377B2 (en) 2002-11-06 2012-04-10 Nissan Motor Co., Ltd. Low-friction sliding mechanism
DE10107795B4 (en) * 2001-02-13 2014-05-15 Berlex Ag Vascular support with a basic body, method for producing the vascular support, apparatus for coating the vascular support

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5242397A (en) * 1989-06-20 1993-09-07 Cedars-Sinai Medical Center Catheter device and method of use for intramural delivery of protein kinase C and tyrosine protein kinase inhibitors to prevent restenosis after balloon angioplasty
US5866561A (en) * 1997-08-21 1999-02-02 Scimed Life Systems, Inc. Local delivery of estrogen for angiogenesis
US5962475A (en) * 1996-10-25 1999-10-05 Eli Lilly And Company Substituted benzo(B)thiophene compounds having activity as selective estrogen receptor modulators

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100389223B1 (en) * 1993-07-19 2003-10-08 안지오제네시스 테크놀로지스, 인코포레이티드 Stent for maintaining open passageway in vivo and its manufacturing method
CA2178541C (en) * 1995-06-07 2009-11-24 Neal E. Fearnot Implantable medical device
ATE358456T1 (en) * 1998-05-05 2007-04-15 Boston Scient Ltd STENT WITH SMOOTH ENDS

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5242397A (en) * 1989-06-20 1993-09-07 Cedars-Sinai Medical Center Catheter device and method of use for intramural delivery of protein kinase C and tyrosine protein kinase inhibitors to prevent restenosis after balloon angioplasty
US5962475A (en) * 1996-10-25 1999-10-05 Eli Lilly And Company Substituted benzo(B)thiophene compounds having activity as selective estrogen receptor modulators
US5866561A (en) * 1997-08-21 1999-02-02 Scimed Life Systems, Inc. Local delivery of estrogen for angiogenesis

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP1278493A4 *

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7273655B2 (en) 1999-04-09 2007-09-25 Shojiro Miyake Slidably movable member and method of producing same
DE10107795B4 (en) * 2001-02-13 2014-05-15 Berlex Ag Vascular support with a basic body, method for producing the vascular support, apparatus for coating the vascular support
WO2003020329A1 (en) * 2001-08-30 2003-03-13 Estrogen Vascular Technology, Lcc Hormone-coated stent for preventing stenosis or atherosclerosis
WO2004024206A1 (en) * 2002-09-12 2004-03-25 Estrogen Vascular Technology, Llc Apparatus and method for delivering compounds to a living organism
US8152377B2 (en) 2002-11-06 2012-04-10 Nissan Motor Co., Ltd. Low-friction sliding mechanism
EP1594510A4 (en) * 2003-01-21 2008-07-23 Dimera Inc Method and kit for reducing the symptoms of peripheral vascular disease
US7572780B2 (en) 2003-01-21 2009-08-11 Dimera, Incorporated Method and kit for reducing the symptoms of peripheral vascular disease
EP1594510A2 (en) * 2003-01-21 2005-11-16 Dimera Inc. Method and kit for reducing the symptoms of peripheral vascular disease
US8182833B2 (en) 2003-01-21 2012-05-22 Dimera Incorporated Method and kit for reducing the symptoms of peripheral vascular disease with topical progesterone
US8420111B2 (en) 2003-01-21 2013-04-16 Dimera Incorporated Method and kit for reducing the symptoms of peripheral vascular disease
DE10311729A1 (en) * 2003-03-18 2004-09-30 Schultheiss, Heinz-Peter, Prof. Dr. Endovascular implant with an at least sectionally active coating of ratjadon and / or a ratjadon derivative
US8096205B2 (en) 2003-07-31 2012-01-17 Nissan Motor Co., Ltd. Gear
US7771821B2 (en) 2003-08-21 2010-08-10 Nissan Motor Co., Ltd. Low-friction sliding member and low-friction sliding mechanism using same
FR2880796A1 (en) * 2005-01-18 2006-07-21 Novatech Sa Sa ENDOPROTHESIS FOR ANOTOMIC CHANNEL
US7520903B2 (en) 2005-01-18 2009-04-21 Novatech Sa Endoprosthesis with projections for delivering active agents

Also Published As

Publication number Publication date
EP1278493A1 (en) 2003-01-29
AU2609401A (en) 2001-07-09
EP1278493A4 (en) 2006-09-27

Similar Documents

Publication Publication Date Title
US6471979B2 (en) Apparatus and method for delivering compounds to a living organism
US7396538B2 (en) Apparatus and method for delivery of mitomycin through an eluting biocompatible implantable medical device
US20040127475A1 (en) Apparatus and method for delivering compounds to a living organism
Abizaid et al. First human experience with the 17-beta-estradiol–eluting stent: The estrogen and stents to eliminate restenosis (EASTER) trial
Lambert et al. Localized arterial wall drug delivery from a polymer-coated removable metallic stent. Kinetics, distribution, and bioactivity of forskolin.
US20050180919A1 (en) Stent with radiopaque and encapsulant coatings
US20050159809A1 (en) Implantable medical devices for treating or preventing restenosis
EP1802361B1 (en) Angiotensin-(1-7) eluting polymer-coated medical device to reduce restenosis and improve endothelial cell function
EP1362603A2 (en) Coated stent for release of active agents
CN102151185A (en) Biodegradable stent with laminated coatings
Bottner et al. High‐speed rotational ablation for in‐stent restenosis
WO2001047451A1 (en) Apparatus and method for delivering compounds to a living organism
Grube et al. Drug eluting stents: initial experiences
EP1539268A1 (en) Apparatus and method for delivering compounds to a living organism
Kyriakides et al. Estrogen decreases neointimal hyperplasia and improves re-endothelialization in pigs
Ponde et al. Multiple stent implantation in single coronary arteries: Acute results and six‐month angiographic follow‐up
WO2024222834A1 (en) Drug coating and medical device comprising same, system, and preparation method
Baumbach et al. Local delivery of a low molecular weight heparin following stent implantation in the pig coronary artery
WO2006115279A1 (en) Composition for preservation of vascular endothelium
Bauters et al. Prevention of restenosis: Future directions
Pohl et al. Angiographic and clinical outcome for the treatment of in-stent restenosis with sirolimus-eluting stent compared to vascular brachytherapy
Schuler Polymer-sirolimus-eluting stents in de novo lesions
Curcio et al. Coated stents: a novel approach to prevent in-stent restenosis
Franck et al. Local heparin delivery for prevention of second in-stent restenosis. Acute and long-term results in 47 consecutive cases
WO2009089632A1 (en) Implantable devices for promoting reendothelialization and methods of use thereof

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 09943648

Country of ref document: US

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2000989608

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWP Wipo information: published in national office

Ref document number: 2000989608

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Ref document number: 2000989608

Country of ref document: EP