WO2014143061A1 - Ballonnet électrophorétique et revêtement de ballonnet conducteur - Google Patents

Ballonnet électrophorétique et revêtement de ballonnet conducteur Download PDF

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Publication number
WO2014143061A1
WO2014143061A1 PCT/US2013/032654 US2013032654W WO2014143061A1 WO 2014143061 A1 WO2014143061 A1 WO 2014143061A1 US 2013032654 W US2013032654 W US 2013032654W WO 2014143061 A1 WO2014143061 A1 WO 2014143061A1
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WO
WIPO (PCT)
Prior art keywords
therapeutic agent
balloon
optionally
coating
catheter
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.)
Ceased
Application number
PCT/US2013/032654
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English (en)
Inventor
Stephen D. Pacetti
Dariush Davalian
John Stankus
Mikael Trollsas
Syed Hossainy
Michael Ngo
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Abbott Cardiovascular Systems Inc
Original Assignee
Abbott Cardiovascular Systems Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Abbott Cardiovascular Systems Inc filed Critical Abbott Cardiovascular Systems Inc
Priority to PCT/US2013/032654 priority Critical patent/WO2014143061A1/fr
Priority to EP13716899.3A priority patent/EP2968685A1/fr
Priority to CN201380074673.5A priority patent/CN105228663A/zh
Publication of WO2014143061A1 publication Critical patent/WO2014143061A1/fr
Anticipated expiration legal-status Critical
Priority to CR20150562A priority patent/CR20150562A/es
Ceased legal-status Critical Current

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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
    • 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
    • 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
    • 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
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/056—Transvascular endocardial electrode systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/325—Applying electric currents by contact electrodes alternating or intermittent currents for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force 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
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
    • 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
    • A61L2420/04—Coatings containing a composite material such as inorganic/organic, i.e. material comprising different phases
    • 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

Definitions

  • the disclosed subject matter is related to the delivery of drugs from an insertable medical device. More particularly, the disclosed subject matter relates to a medical device including a balloon for delivery of a therapeutic agent, the balloon configured to release the therapeutic agent upon application of electric current.
  • Atherosclerosis is a syndrome affecting arterial blood vessels. It leads to a chronic inflammatory response in the walls of arteries, which is in large part due to the accumulation of lipid, macrophages, foam cells and the formation of plaque in the arterial wall. Atherosclerosis is commonly referred to as hardening of the arteries although the pathophysiology of the disease manifests itself with several different types of lesions ranging from fibrotic to lipid laden to calcific.
  • Angioplasty is a vascular interventional technique involving mechanically widening an obstructed blood vessel, typically caused by atherosclerosis.
  • angioplasty a catheter having a tightly folded balloon is inserted into the vasculature of the patient and is passed to the narrowed location of the blood vessel at which point the balloon is inflated to a fixed size using an inflation fluid, typically a solution of angiographic contrast media.
  • PCI Percutaneous coronary intervention
  • coronary angioplasty is a therapeutic procedure to treat the stenotic coronary arteries of the heart, often found in coronary heart disease.
  • peripheral angioplasty commonly known as percutaneous transluminal angioplasty (PTA) refers to the use of mechanical widening of blood vessels other than the coronary arteries.
  • PTA is most commonly used to treat narrowing of the arteries of the leg, especially, the iliac, external iliac, superficial femoral and popliteal arteries. PTA can also treat narrowing of veins and other blood vessels.
  • a stent is a device, typically a metal tube or scaffold, which was inserted into the blood vessel following angioplasty, in order to hold the blood vessel open.
  • stents While the advent of stents eliminated many of the complications of abrupt vessel closure after angioplasty procedures, within about six months of stenting, a re-narrowing of the blood vessel can form, which is a condition known as restenosis. Restenosis was discovered to be a response to the injury of the angioplasty procedure and is characterized by a growth of smooth muscle cells— analogous to a scar forming over an injury.
  • drug eluting stents were developed to address the reoccurrence of the narrowing of blood vessels.
  • a drug eluting stent is a metal stent that has been coated with a drug that is known to interfere with the process of restenosis.
  • a potential drawback of certain drug eluting stents is known as late stent thrombosis, which is an event in which blood clots form inside the stent.
  • Drug coated balloons are believed to be a viable alternative to drug eluting stents in the treatment of atherosclerosis.
  • restenosis and the rate of major adverse cardiac events such as heart attack, bypass, repeat stenosis, or death in patients treated with drug coated balloons and drug eluting stents
  • the patients treated with drug coated balloons experienced only 3.7 percent restenosis and 4.8% MACE as compared to patients treated with drug eluting stents, in which restenosis was 20.8 percent and 22.0 percent MACE rate.
  • drug coated balloons are a viable alternative and in some cases may have greater efficacy than drug eluting stents as suggested by the PEPCAD II study, drug coated balloons present challenges due to the very short period of contact between the drug coated balloon surface and the blood vessel wall.
  • the drug delivery time period for a drug coated balloon differs from that of a controlled release drug eluting stent, which is typically weeks to months.
  • the balloon may only be inflated for less than one minute, and is often inflated for only thirty seconds. Therefore, an efficacious, therapeutic amount of drug must be transferred to the vessel wall within a thirty-second to one-minute time period.
  • the allowable inflation times can be greater than one minute, but are still measured in minutes.
  • there are challenges specific to drug delivery via a drug coated balloon because of the necessity of a short inflation time, and therefore time for drug or coating transfer— a challenge not presented by a drug eluting stent, which remains in the patient's vasculature once implanted.
  • a catheter for intraluminal delivery of a therapeutic agent to a subject includes an elongate shaft having a proximal end portion, a distal end portion, and an inflation lumen defined therebetween.
  • the catheter further includes an expandable member coupled at the distal end portion of the elongate shaft, the expandable member having a proximal end, a distal end, an interior chamber defined therein, and an outer surface.
  • the expandable member further includes an electrode disposed proximate the outer surface of the expandable member and a coating disposed on at least a portion of the outer surface, the coating including a therapeutic agent.
  • the catheter additionally includes a power source in electrical communication with the electrode.
  • the electrode is a film of conductive material.
  • the conductive material is a metal material.
  • the metal material is selected from the group consisting of gold, platinum, platinum iridium, silver, palladium, tantalum and niobium.
  • the conductive material of the electrode is a conductive polymeric material.
  • the conductive polymeric material is disposed on the balloon surface as a coating.
  • the polymer coating includes carbon particles and/or metallic particles to improve conductivity of the coating.
  • the therapeutic agent has no net electrical charge.
  • the therapeutic agent is a cytostatic drug.
  • the cytostatic drug is selected from the group consisting of rapamycin, sirolimus, zotarolimus, everolimus, tacrolimus, and biolimus.
  • the therapeutic agent is zotarolimus.
  • a charged moiety such as a micelle, nanoparticle or liposome is employed to encapsulate the therapeutic agent.
  • the therapeutic agent is neutral (i.e. possesses no net electrical charge)
  • the unencapsulated therapeutic agent would otherwise not be subject to a net electromotive force in the presence of an electric field.
  • the therapeutic agent is disposed in an emulsifier.
  • the emulsifier is a surfactant.
  • the surfactant is anionic.
  • Suitable anionic surfactants for use with certain embodiments of the disclosed subject matter include phosphatidylglycerols, phosphatic acids, lysophospholipids, and saturated and unsaturated fatty acids.
  • the surfactant is a phosphatidylglycerol selected from the group consisting of egg phosphatidylglycerol (EPG), dimyristoyl-phosphatidylglycerol (DMPG), palmitoly-oleoyl phosphatidylglycerol (POPG), and l,2-distearoyl-sn-glycerol-3- phosphoglycerol sodium salt (DSPG).
  • EPG egg phosphatidylglycerol
  • DMPG dimyristoyl-phosphatidylglycerol
  • POPG palmitoly-oleoyl phosphatidylglycerol
  • DSPG l,2-distearoyl-sn-glycerol-3
  • phosphatidic acid selected from the group consisting of dimyristoyl-phosphatidic acid (DMPA), dipalmitoyl-phosphatidic acid (DPPA), and l,2-distearoyl-sn-glycero-3-phosphatidic acid (DSPA).
  • the surfactant is a lysophospolipid selected from the group consisting of lysophosphatidic acid (LPA), lyso-phosphatidylcholine (LPC), and sphingosine-1 -phosphate (S IP).
  • the therapeutic agent is encapsulated with a liposome comprising an anionic fatty acid.
  • the neutral therapeutic agent is encapsulated in a nanosphere comprising an anionic fatty acid.
  • the neutral therapeutic agent is encapsulated in a microsphere comprising an anionic fatty acid.
  • Suitable anionic fatty acids include phospholipids selected from the group consisting of phosphatidylethanolamine, purified 90% soya phosphatidylcholine (trade name LECIVA-S90), and purified egg lecithin (trade name LIPOVA-E120).
  • the balloon electrode is a conductive polymer coating.
  • Suitable conductive polymers include polypyrrole, polyacetylene derivatives, poly(phenyl sulfide), polythiopene, and poly (3,4-ethylenedioxythiopene).
  • the conductive polymer is disposed as nanoparticles in the coating. In further embodiments, the conductive polymer is combined as a composite with an additional conductive polymer. In some embodiments, the conductive polymer is disposed as nanoparticles and combined as a composite with an additional conductive polymer. Suitable conductive polymers for combination as a composite include poly(vinylidene fluoride), poly(vinylidene fluoride-co- hexafluoropropylene), poly(ester-amide), and polyesters. [0020] In some embodiments, the conductive polymer coating comprises a conductive polymer and a therapeutic agent disposed in a matrix configuration.
  • the coating is configured to absorb ions and water upon balloon inflation and temporary application of an electric field from the external power source, leading to swelling of the coating.
  • the therapeutic agent elutes from the coating to the vessel lumen.
  • the coating releases the fluids and verses its initial configuration.
  • the catheter balloon includes a surface coating comprising a conductive polymer that is piezoelectric.
  • the catheter does not necessarily comprise an external power source and an electrode in electric communication with the power source.
  • Suitable piezoelectric conductive polymers include poled poly(vinylidene fluoride) and poled poly(vinylidene-triflouroethylene).
  • the piezoelectric coating further comprises graphitic carbon.
  • the therapeutic agent is encapsulated in a complex that dissolves in electric current.
  • Suitable complexes that dissolve in response to electric current include of gold, silver, porous gold nanoparticles, porous silver nanoparticles, gold-coated poly(vinylidene fluoride) nanoparticles, and silver-coated poly(vinylidene fluoride)
  • the therapeutic agent is selected from the class of antithrombotics, anticoagulants, antiplatelet agents, anti-lipid agents, thrombolytics, antiproliferatives, anti-inflammatories, agents that inhibit hyperplasia, smooth muscle cell inhibitors, antibiotics, growth factor inhibitors, cell adhesion inhibitors, cytostatic agents, cell adhesion promoters, antimitotics, antifibrins, antioxidants, antineoplastics, agents that promote endothelial cell recovery, antiallergic substances, viral vectors, nucleic acids, monoclonal antibodies, antisense compounds, oligonucleotides, cell permeation enhancers, radiopaque agent markers, HMG CoA reductase inhibitors, pro-drugs and combinations thereof.
  • the balloon coating further comprises a plasticizer.
  • plasticizers include, without limitation, glycerin, polyethylene glycol, and polypropylene glycol propylene glycol, polysorbates, N-methyl pyrrolidone, dimethyl sulfoxide, benzyl benzoate, ethyl benzoate, benzyl alcohol, and phenoxyethanol.
  • the plasticizer increases the elongation capacity of the coating to maintain coating integrity during balloon inflation and deflation.
  • the power source is a direct current power source external to the body of the subject.
  • the power source includes a timer.
  • the power source includes a fast acting fuse.
  • the power source is connected to the electrode by an insulated electrical lead.
  • the electrical lead engages the electrode at the proximal end of the expandable member.
  • FIGURE 1A is a schematic view of one representative balloon catheter in accordance with the disclosed subject matter.
  • FIGURE IB is a schematic cross-sectional end view taken along lines A-A in FIGURE 1A.
  • FIGURE 1C is a schematic cross-sectional end view taken along lines B-B in FIGURE 1A..
  • FIGURE 2 is a schematic view of a system in accordance with the disclosed subject matter, including a representative balloon catheter and an electrode in electrical communication with an external power source.
  • FIGURE 3 is a schematic representation of a system in accordance with the disclosed subject matter, with the balloon catheter positioned in a lumen of a blood vessel and an external electrode applied to the skin of the patient to complete an electric circuit to permit temporary application of a current to the balloon.
  • FIGURE 4 is an illustration of electropolymerization of pyrrole into polypyrrole to form a conductive polymer.
  • a catheter for intraluminal delivery of a therapeutic agent to a subject includes an elongate shaft having a proximal end portion, a distal end portion, and an inflation lumen defined therebetween.
  • the catheter further includes an expandable member coupled at the distal end portion of the elongate shaft, the expandable member having a proximal end, a distal end, an outer surface, and an interior chamber defined therein.
  • the expandable member further includes an electrode disposed proximate the outer surface of the expandable member and a coating disposed on at least a portion of the outer surface, the coating including a therapeutic agent.
  • the catheter additionally includes a power source in electrical communication with the electrode.
  • the electrode can be a conductive polymer which reversibly attracts water in response to voltage supplied from the power source.
  • the expandable member is coated with a piezoelectric coating and the therapeutic agent is encapsulated in particles which dissolve upon application of electric current.
  • the terms “comprising,” “including,” and “having” can also be used interchangeably.
  • the terms “amount” and “level” are also interchangeable and can be used to describe a concentration or a specific quantity.
  • the term “selected from the group consisting of refers to one or more members of the group in the list that follows, including mixtures (i.e. combinations) of two or more members.
  • the term “about” or “approximately” means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, “about” can mean within 3 or more than 3 standard deviations, per the practice in the art. Alternatively, “about” can mean a range of up to +/-20%, or up to +/- 10%, or up to +1-5%, or up to +/-1% of a given value. Alternatively, particularly with respect to biological systems or processes, the term can mean within an order of magnitude, or within 5-fold, or within 2-fold, of a value. With reference to pharmaceutical compositions, the term “about” refers to a range that is acceptable for quality control standards of a product approved by regulatory authorities.
  • the systems and methods presented can be used for delivery of a therapeutic agent to a vessel wall of a subject.
  • the methods and systems presented herein can also be used for manufacture and assembly of medical devices such as a drug coated balloon catheter. While the disclosed subject matter references application of a therapeutic agent, it is to be understood that a variety of coatings including polymeric, therapeutic, or matrix coatings, can be applied to various surfaces of medical devices, as so desired.
  • the balloon catheter device 10 generally includes an elongated catheter shaft 12 having a proximal end and having a distal end and an expandable member or balloon 30 located proximate to the distal end of the catheter shaft.
  • an electrode 50 is applied to at least a portion of the working length of the balloon catheter.
  • the expandable balloon has an outer surface and an inner surface disposed at the distal end portion of the catheter shaft.
  • an elongated catheter shaft 12 having a coaxial arrangement comprising an outer tubular member 14 and an inner tubular member 16.
  • the outer tubular member 14 defines an inflation lumen 20 disposed between the proximal end portion and the distal end portion of the catheter shaft 12.
  • the coaxial relationship between the inner tubular member 16 and the outer tubular member 14 defines an annular inflation lumen 20.
  • the expandable member 30 is in fluid communication with the inflation lumen 20. The inflation lumen therebetween can supply fluid under pressure to the expandable member 30, and establish negative pressure to draw fluid from the expandable member 30. The expandable member 30 can thus be inflated and deflated.
  • the elongated catheter is sized and configured for delivery through a tortuous anatomy, and can further include a guidewire lumen 22 that permits it to be delivered over a guidewire 18.
  • the inner tubular member 16 defines the guidewire lumen 22 for the guidewire 18.
  • FIGURES 1A and IB illustrate the guidewire lumen as having an over- the-wire (OTW) construction
  • the guidewire lumen can be configured as a rapid-exchange (RX) construction, as is well known in the art.
  • the shaft can be provided as a multilumen member, or composition of two or more tubular members, as is known in the art.
  • the expandable member or balloon 30 has a distal end 32, a proximal end 34 and a working length "L" therebetween.
  • the expandable member embodied herein has a an interior chamber 36 in fluid communication with the inflatable lumen 20 of the elongated shaft 12. Any of a number of suitable expandable member constructions and shapes can be used, as described further below.
  • At least one therapeutic agent 40 is disposed along at least a portion of the working length "L" of the expandable member 30.
  • the at least a portion of the working length can be a selected length of the working length or the working length in its entirety. Furthermore, the at least a portion can reference a pattern on the surface of the working length, such as rings, dots, linear or curvilinear segments, or another design.
  • the at least one therapeutic agent can be disposed along the portion of the working length of the expandable member in any suitable manner that will allow for release from the expandable member to the vessel wall. For example, the at least one therapeutic agent can be applied as a coating to the outer surface of the expandable member. Additionally or
  • the expandable member can be provided with reservoirs or similar surface features to contain therapeutic agent for release therefrom. Furthermore, pores or channels can be defined along a portion of the working length for infusion-type release of the therapeutic agent therefrom.
  • the at least one therapeutic agent can be disposed alone, e.g., neat, or in combination with a suitable additive, such as a surfactant, plasticizer or the like. Additionally, and as described further below, the at least one therapeutic agent can be disposed for delivery over an electrode 50.
  • the therapeutic agent 40 can be applied as a layer over the electrode, and/or the therapeutic agent can be mixed with or encapsulated in further coating components as appropriate.
  • an electrode 50 can be provided to provide an electromotive force to the coating and/or therapeutic agent upon application of current or voltage from a power source.
  • the electrode 50 can be an anode or a cathode, as described further below.
  • Suitable electrodes include without limitation metallic or conductive polymer films, as described further below.
  • the catheter balloon includes an electrode disposed proximate to the surface of the balloon.
  • the electrode is in electric communication with a power supply.
  • the coating comprising the therapeutic agent of the system disclosed herein can be disposed over the surface of the electrode or can form the electrode itself.
  • electrical communication between the balloon electrode 50 and the power supply 60 is established by an insulated electrical lead 70 provided inside the catheter.
  • the lead 70 extends along the catheter to a point proximate to the proximal end of the balloon.
  • the lead 70 is attached to the external surface of the balloon taper in contact with the balloon electrode 50.
  • the therapeutic agent 40 shown mixed into or encapsulated in a coating, is disposed over the balloon electrode 50.
  • an electrical circuit is formed, such as by providing an opposite electrode placed on the body of the subject.
  • electrodes are common in medical practice, such as EKG electrodes, which can be affixed to the patient with a conductive gel layer.
  • power is provided from the power source 60 for about 30 seconds to about 60 seconds.
  • the power source 60 can include a timer and/or a fast-acting fuse to prevent undesired electrical circuits within the body of the subject.
  • the power source can be an external power source.
  • the power source can be integrated as a component of the catheter system.
  • the integrated power source can be battery powered.
  • the battery of the integrated power source can be replaceable or can be disposable.
  • the balloon electrode can be provided in a variety of forms.
  • the balloon electrode can be a film disposed on all or a part of the working surface of the balloon.
  • the electrode can be formed within the balloon wall or within the interior of the balloon.
  • the electrode can be provided in any desired shape or pattern on the balloon surface.
  • the electrode can comprise a conductive metal, including, for example and not limitation, platinum, platinum iridium, silver, tantalum, niobium, palladium, or gold.
  • the conductive film or layer of the electrode is disposed on the balloon surface by, for example, sputtering, metal evaporation, electroless plating, or mechanical adherence of the electrode material.
  • a metallic electrode layer is provided on a low compliance balloon to preserve mechanical integrity of the metallic electrode layer upon balloon inflation.
  • the electrode can comprise a conductive polymeric coating, such as a polymer capable of expanding when inflated. The conductivity of the polymer coating can be increased by the inclusion of suitable carbon or metallic particles. Suitable conductive polymeric coatings are provided below.
  • Electric potential is provided from the power source to the electrode to impart an electric field to the balloon. This electric field will exert an electrostatic force on charged molecules in the vicinity of the field.
  • the therapeutic agent itself can be provided as a charged molecule.
  • the therapeutic agent can be encapsulated in a charged moiety, such as a micelle.
  • the balloon electrode can be configured as an anode to provide the desired electromotive force.
  • the balloon electrode can be configured as a cathode to provide the desired effect.
  • the electric field can be generated by delivery of voltage to the balloon electrode.
  • the voltage can be between about 10 millivolts and about 5 volts; or the voltage can be between about 100 millivolts and about 2 volts; or the voltage can be between about 1 volt and about 2 volts.
  • the therapeutic agent is a cytostatic drug, including, for example, zotarolimus, sirolimus, rapamycin, everolimus, biolimus, umirolimus, myolimus, novolimus, temsirolimus, deforolimus, ridaforolimus, tacrolimus, pimecrolimus, and combinations thereof.
  • the therapeutic agent can be an anti-proliferative drug, including for example, paclitaxel, protaxel, docetaxel and combinations thereof.
  • Such cytostatic and anti-proliferative drugs can have a net neutral charge, and can be encapsulated in a charged moiety to permit electrophoretic delivery.
  • Suitable negatively-charged surfactants for micellar encapsulation include, for example, phospholipids, such as phosphatidylglycerols, phosphatidic acids, lysophospholipids, and fatty acids.
  • Suitable positively charged surfactant encapsulants include positively charged sorbitan esters, polysorbates, and poloxamers.
  • low critical micelle concentration (CMC) surfactants can be selected to produce stable micelles, or high CMC surfactants can be selected to produce relatively less stable micelles.
  • Suitable phosphatidylglycerols include, without limitation, egg phosphatidylglycerol (EPG), dimyristoyl-phosphatidylglycerol (DMPG), palmitoly-oleoyl phosphatidylglycerol (POPG), and l,2-distearoyl-sn-glycerol-3-phosphoglycerol sodium salt (DSPG).
  • EPG egg phosphatidylglycerol
  • DMPG dimyristoyl-phosphatidylglycerol
  • POPG palmitoly-oleoyl phosphatidylglycerol
  • DSPG l,2-distearoyl-sn-glycerol-3-phosphoglycerol sodium salt
  • Smaller phosphatidylglycerols, including DMPA are particularly suitable for the formation of micelles encapsulating hydrophobic drugs.
  • Suitable phosphatidic acids include, for example, dimyristoyl- phosphatidic acid (DMPA), dipalmitoyl-phosphatidic acid (DPPA), and 1,2-distearoyl-sn- glycero-3-phosphatidic acid (DSPA).
  • Suitable lysophospholipids include, for example, sphingosine-1 -phosphate and lysophosphatidic acid. Lysophospholipids contain a single fatty acid chain, which have relatively large polar head groups in comparison to single acyl side chains, and therefore are especially suited to micelle formation. With respect to fatty acids, both saturated and unsaturated fatty acids are suitable for micellar encapsulation of hydrophobic agents.
  • Suitable anionic fatty acids include, without limitation, phosphatidylserine, phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-triphosphate.
  • a hydrophobic therapeutic agent such as a cytostatic or cytotoxic drug
  • a hydrophobic therapeutic agent can be solubilized in a positively or negatively charged polymer.
  • Suitable positively charged polymers include, without limitation, poly(vinylbenzyl trialkyl ammonium), poly (4-vinyl-N-alkyl-pyridiumiun), and poly(acryloyl-trialkyl ammonium), as well as positively charged polysaccharides, such as cellulose, dextran and starch.
  • Suitable negatively charged polymers include, without limitation, carboxymethyl cellulose, sodium carboxymethyl cellulose, carboxymethyl celluiose-cysteine, poly(acrylic acid), poly(methacrylic acid), poly(L-aspartic acid), poly(D-aspartic acid), poly(L-aspartic acid) sodium salt, poly(L-glutamic acid), poly(D- glutamic acid), and poly(L-glutamic acid) sodium salt.
  • Polyionic polymers exhibit significant tissue adhesion, and can in some embodiments promote adhesion and retention of the coating and therapeutic agent after delivery from the balloon.
  • Electrophoresis generally will occur more rapidly with smaller moieties having greater diffusivity. Accordingly, micelles, liposomes and nanoparticles generally will electrophorese more rapidly than microspheres.
  • Therapeutic agent-encapsulating moieties can be formed by dispersing or sonicating an organic solution of the therapeutic agent and the selected encapsulant. The therapeutic agent-encapsulating moieties can then applied over the balloon electrode by dipping, spraying, or by other techniques known in the art.
  • One technique particularly suited to the application of positively-charged moieties is disclosed in U.S. Patent No. 8,298,607, incorporated herein by reference in its entirety.
  • the balloon electrode comprises a conductive polymer disposed on the surface of the catheter balloon.
  • the conductive polymer can further be doped with suitable dopants as desired to permit oxidation or reduction of the conductive polymer.
  • the conductive polymer becomes oxidized and temporarily attracts ions and aqueous fluid.
  • a polypyrrole conductive polymer doped with an anion can be reversibly oxidized upon provision of voltage from the power source to the conductive polymer. In its oxidized state, the conductive polymer will attract ions and acqueous fluid.
  • the conductive polymer In its reduced state, the conductive polymer will expel ions and water from the bloodstream and/or tissue into the coating. Where the conductive polymer is disposed as a coating or a coating comprising the therapeutic agent is disposed over the conductive polymer, hydration of the coating promotes swelling and release of the coating comprising the therapeutic agent. By subsequently ceasing provision of voltage or reversing the voltage in the circuit, the conductive polymer returns to its reduced state and/or is oxidized to release the water and ions to the surrounding tissue by diffusion. This cycle of oxidation and reduction to attract and release solvent can be repeated several times during balloon deployment as desired.
  • drug delivery can be achieved by both the electromotive force that results from application of voltage to the conductive polymer and the reversible reduction (i.e. hydration) of the coating polymer.
  • the coating can include charged surfactant particles encapsulating a hydrophobic drug as set forth above.
  • the resulting electromotive force will repel the charged encapsulants from the surface of the balloon into the tissue.
  • the oxidation of the conductive polymer will promote the flow of ions and water into the balloon coating, resulting in hydration and swelling of the coating. Coating swelling will permit more rapid diffusion of the charged surfactant encapsulants to the vessel wall.
  • the conductive polymer itself can be loaded with drug in a matrix format at up to 50 percent therapeutic agent by weight.
  • the polymer Upon application of voltage to the conductive polymer, the polymer will hydrate and swell, permitting elution of the drug. Additionally, by reversing the direction of voltage from the power supply, the flow of water and ions into the coating is reversed, permitting diffusion of the drug from the polymer coating to the vessel wall.
  • Conductive polymers suitable for the disclosed subject matter generally can be characterized by alternating single and double bonds along the polymer chain.
  • Such conductive polymers for use as the balloon electrode include, without limitation, polypyrrole, polyacetylene derivatives, poly(phenylene sulfide), polythiopene, and poly(3,4-ethylenedioxythiopene).
  • the conductive polymers listed above can be provided as nanoparticles and composited with an additional conductive polymer such as poly(vinylidene fluoride), poly(ester-amide) or a polyester to augment coating conductivity. Additionally or alternatively, the therapeutic agent itself can be disposed as nanoparticles in the conductive polymer.
  • the conductive coating is loaded with the therapeutic agent in a matrix format, as known to those in the art.
  • the therapeutic agent can be disposed without an encapsulant.
  • the therapeutic agent can be encapsulated, such as within microspheres, or by encapsulating nanoparticles or surfactant liposomes, microspheres as disclosed above.
  • the conductive polymer is polypyrrole.
  • the coating of conductive polymer can be formed by electrochemical oxidation of pyrrole on an anode surface, such as the surface of the balloon itself or a separate surface. If a separate surface is employed, the polypyrrole coating is subsequently applied to the balloon surface using suitable techniques known in the art.
  • the conductive coating can include a piezoelectric property.
  • cyclical inflation and deflation of the balloon itself can be configured to generate a local electrical current.
  • This intrinsically supplied current can, in certain embodiments, dissolve susceptible coatings to release a therapeutic agent.
  • the piezoelectric coating includes a therapeutic agent encapsulated in porous nanoparticles of a colloidable metal, such as gold or silver. Additionally or alternatively, the therapeutic agent-encapsulating nanoparticles can be included with the piezoelectric polymer. Upon generation of voltage by the piezoelectric effect, the nanoparticles encapsulating the therapeutic agent can dissolve for release of the therapeutic agent. Repeated cycles of balloon inflation and contraction thus can mechanically force the released therapeutic agent against and into the vessel wall.
  • Suitable piezoelectric coatings include without limitation poled poly(vinylidene fluoride). Piezoelectric coatings can additionally include graphitic carbon to improve coating conductivity. [0066] In accordance with the subject matter disclosed above, encapsulation of the therapeutic agent can mitigate undesired effects associated with systemic release of the therapeutic agent during catheter delivery, and drug uptake into the vessel wall can be increased by the application of low voltage or current, e.g. via electroporation of the endothelium.
  • the encapsulant can be modified to provide moieties for ligand targeting to further improve drug delivery and retention.
  • the balloon can include microcapsules on its outer surface.
  • the microcapsules are configured to encompass the therapeutic agent.
  • the microcapsules located on the surface of the balloon contact the tissue of the arterial wall.
  • the microcapsules can be formed in the wall of the balloon surface.
  • the therapeutic agent can be released from the microcapsules by fracturing of the microcapsules and/or diffusion from the microcapsule into the arterial wall.
  • the microcapsules can be fabricated in accordance with the methods disclosed in U.S. Patent No. 5,1023,402 to Dror or U.S. Patent No.
  • the microcapsules can be configured to dissolve or fracture upon exposure to electric current or voltage. Additionally or alternatively, the microcapsules can be configured to fracture upon swelling of the coating and/or conductive polymer upon reduction/oxidation of the conductive polymer and concomitant solvent absorption and swelling.
  • an outer fibrous coating can be electrospun or stretched onto the medical device or balloon catheter.
  • the therapeutic formulation or coating is stretched and allows for coating solubilization and release.
  • the fiber diameters and material properties can be fine tuned for optimal pore size and to release the particles containing the therapeutic agent. Fibrous coatings on expandable members are described in U.S. Patent Application Serial No. 12/237,998 to R. von Oepen and U.S. Patent Application Serial No. 12/238,026 to K. Ehrenreich, the disclosures of which are incorporated by reference in their entirety.
  • the fiber coating can be composed of a conductive polymer, such as polyaniline.
  • the fiber coating can be loaded with drug and configured to electophoretically repel drug and/or to reversibly oxidize and hydrate to permit elution of the therapeutic agent by diffusion.
  • the coating exhibits sufficient flexibility and elasticity to retain its mechanical integrity upon balloon inflation and recover its initial configuration upon deflation of the balloon.
  • One or more plasticizers can be incorporated into the balloon coating and/or the conductive polymer coating to improve its mechanical integrity on inflation and deflation.
  • Plasticizers can improve the capacity for elongation of the conductive polymers disclosed herein, promoting mechanical integrity upon balloon inflation.
  • Suitable plasticizers are low molecular weight, and water soluble species that are essentially non- volatile.
  • the plasticizers include, for the purpose of illustration and without limitation, DMSO, polyethylene glycol (Molecular Weight ⁇ 40K), propylene glycol, polypropylene glycol, glycerol, N-methyl-2- pyrrolidone (NMP), DMAC, benzyl alcohol, and fatty alcohols.
  • Polyethylene glycol, polypropylene glycol, glycerin, and organic solvents are particularly suited to the applications disclosed herein.
  • the therapeutic agent or drug can antithrombotics, anticoagulants, antiplatelet agents, anti-lipid agents, thrombolytics, antiproliferatives, anti-inflammatories, agents that inhibit hyperplasia, smooth muscle cell inhibitors, antibiotics, growth factor inhibitors, cell adhesion inhibitors, cytostatic agents, cell adhesion promoters, antimitotics, antifibrins, antioxidants, antineoplastics, agents that promote endothelial cell recovery, antiallergic substances, viral vectors, nucleic acids, monoclonal antibodies, antisense compounds, oligonucleotides, cell permeation enhancers, radiopaque agent markers, HMG Co A reductase inhibitors, pro-drugs and combinations thereof.
  • anti-proliferative means an agent used to inhibit cell growth, such as chemotherapeutic drugs. Some non-limiting examples of anti-proliferative drugs include taxanes, paclitaxel, and protaxel. Anti-proliferative agents can be anti-mitotic.
  • anti-mitotic as used herein means an agent used to inhibit or affect cell division, whereby processes normally involved in cell division do not take place. One sub-class of anti-mitotic agents includes vinca alkaloids.
  • vinca alkaloids include, but are not limited to, vincristine, paclitaxel, etoposide, nocodazole, indirubin, and anthracycline derivatives, including, for example, daunorubicin, daunomycin, and plicamycin.
  • antimitotic agents include anti-mitotic alkylating agents, including, for example, tauromustine, bofumustine, and fotemustine, and anti-mitotic metabolites, including, for example,
  • Anti-mitotic alkylating agents affect cell division by covalently modifying DNA, RNA, or proteins, thereby inhibiting DNA replication, RNA transcription, RNA translation, protein synthesis, or combinations of the foregoing.
  • An example of an anti-mitotic agent includes, but is not limited to, paclitaxel.
  • paclitaxel includes the alkaloid itself and naturally occurring forms and derivatives thereof, as well as synthetic and semi- synthetic forms thereof.
  • Anti-platelet agents are therapeutic entities that act by (1) inhibiting adhesion of platelets to a surface, typically a thrombogenic surface, (2) inhibiting aggregation of platelets, (3) inhibiting activation of platelets, or (4) combinations of the foregoing.
  • Activation of platelets is a process whereby platelets are converted from a quiescent, resting state to one in which platelets undergo a number of morphologic changes induced by contact with a thrombogenic surface. These changes include changes in the shape of the platelets, accompanied by the formation of pseudopods, binding to membrane receptors, and secretion of small molecules and proteins, including, for example, ADP and platelet factor 4.
  • Anti-platelet agents that act as inhibitors of adhesion of platelets include, but are not limited to, eptifibatide, tirofiban, RGD (Arg-Gly-Asp)- based peptides that inhibit binding to gpllbllla or avb3, antibodies that block binding to gpllalllb or avb3, anti-P-selectin antibodies, anti-E-selectin antibodies, compounds that block P-selectin or E-selectin binding to their respective ligands, saratin, and anti-von Willebrand factor antibodies.
  • Agents that inhibit ADP-mediated platelet aggregation include, but are not limited to, disagregin and cilostazol.
  • At least one therapeutic agent can be an anti-inflammatory agent.
  • anti-inflammatory agents include prednisone, dexamethasone, hydrocortisone, estradiol, triamcinolone, mometasone, fluticasone, clobetasol, and non-steroidal anti-inflammatories, including, for example, acetaminophen, ibuprofen, naproxen, adalimumab and sulindac.
  • the arachidonate metabolite prostacyclin or prostacyclin analogs is an example of a vasoactive antiproliferative.
  • Anti-thrombotic agents include chemical and biological entities that can intervene at any stage in the coagulation pathway. Examples of specific entities include, but are not limited to, small molecules that inhibit the activity of factor Xa.
  • heparinoid-type agents that can inhibit both FXa and thrombin, either directly or indirectly, including, for example, heparin, heparin sulfate, low molecular weight heparins, including, for example, the compound having the trademark Clivarin®, and synthetic oligosaccharides, including, for example, the compound having the trademark Arixtra®.
  • direct thrombin inhibitors including, for example, melagatran, ximelagatran, argatroban, inogatran, and peptidomimetics of binding site of the Phe-Pro-Arg fibrinogen substrate for thrombin.
  • Another class of anti-thrombotic agents that can be delivered is factor Vll/VIIa inhibitors, including, for example, anti-factor Vll/VIIa antibodies, rNAPc2, and tissue factor pathway inhibitor (TFPI).
  • Thrombolytic agents which can be defined as agents that help degrade thrombi (clots), can also be used as adjunctive agents, because the action of lysing a clot helps to disperse platelets trapped within the fibrin matrix of a thrombus.
  • clots can also be used as adjunctive agents, because the action of lysing a clot helps to disperse platelets trapped within the fibrin matrix of a thrombus.
  • thrombolytic agents include, but are not limited to, urokinase or recombinant urokinase, pro- urokinase or recombinant pro-urokinase, tissue plasminogen activator or its recombinant form, and streptokinase.
  • the therapeutic agents include a cytostatic agent.
  • cytostatic as used herein means an agent that mitigates cell proliferation, allows cell migration, and does not induce cell toxicity.
  • cytostatic agents include, for the purpose of illustration and without limitation, macrolide antibiotics, zotarolimus, sirolimus, rapamycin, everolimus, biolimus, umirolimus, myolimus, novolimus, temsirolimus, deforolimus, ridaforolimus, tacrolimus, pimecrolimus, derivatives and analogues thereof, any macrolide immunosuppressive drugs, and combinations thereof.
  • Other therapeutic agents include cytotoxic drugs, including, for example, apoptosis inducers, including TGF, and topoisomerase inhibitors, including, 10- hydroxycamptothecin, irinotecan, and doxorubicin.
  • the expandable member is fabricated from polymeric material such as compliant, non- compliant or semi-compliant polymeric material or polymeric blends (e.g., a mixture of polymers).
  • the polymeric material is compliant such as but not limited to a polyamide/polyether block copolymer (commonly referred to as PEBA or polyether-block- amide).
  • PEBA polyamide/polyether block copolymer
  • the polyamide and polyether segments of the block copolymers can be linked through amide or ester linkages.
  • the polyamide block can be selected from various aliphatic or aromatic polyamides known in the art.
  • the polyamide is aliphatic. Some non-limiting examples include nylon 12, nylon 11, nylon 9, nylon 6, nylon 6/12, nylon 6/11, nylon 6/9, and nylon 6/6. In some embodiments, the polyamide is nylon 12.
  • the polyether block can be selected from various polyethers known in the art. Some non- limiting examples of polyether segments include poly(tetramethylene ether), tetramethylene ether, polyethylene glycol, polypropylene glycol, poly(pentamethylene ether) and
  • PEBA material can also be utilized such as for example, PEBAX® materials supplied by Arkema (France).
  • Various techniques for forming a balloon from polyamide/polyether block copolymer is known in the art. One such example is disclosed in U.S. Patent No. 6,406,457 to Wang, the disclosure of which is incorporated by reference.
  • the balloon material is formed from polyamides.
  • the polyamide has substantial tensile strength, be resistant to pin-holing even after folding and unfolding, and be generally scratch resistant, such as those disclosed in U.S. Patent No. 6,500,148 to Pinchuk, the disclosure of which is incorporated herein by reference.
  • polyamide materials suitable for the balloon include nylon 12, nylon 11, nylon 9, nylon 69 and nylon 66. In some embodiments, the polyamide is nylon 12.
  • suitable materials for constructing non-compliant balloons are polyesters such as poly(ethylene terephthalate) (PET), Hytrel thermoplastic polyester, and polyethylene.
  • the balloon is formed of a polyurethane material, such as TECOTHANE® (Thermedics).
  • TECOTHANE® is a thermoplastic, aromatic, polyether polyurethane synthesized from methylene disocyanate (MDI), polytetramethylene ether glycol (PTMEG) and 1,4 butanediol chain extender.
  • MDI methylene disocyanate
  • PTMEG polytetramethylene ether glycol
  • 1,4 butanediol chain extender 1,4 butanediol chain extender.
  • TECOTHANE® grade 1065D is one suitable embodiment, and has a Shore durometer of 65D, an elongation at break of about 300%, and a high tensile strength at yield of about 10,000 psi.
  • other suitable grades can be used, including TECOTHANE® 1075D, having a Shore D hardness of 75.
  • Suitable compliant polymeric materials include ENGAGE® (DuPont Dow Elastomers (an ethylene alpha-olefin polymer) and EXACT® (Exxon Chemical), both of which are thermoplastic polymers.
  • Other suitable compliant materials include, but are not limited to, elastomeric silicones, latexes, and urethanes.
  • the compliant material can be cross linked or uncrosslinked, depending upon the balloon material and characteristics required for a particular application. Some suitable polyurethane balloon materials are not crosslinked. However, other suitable materials, such as the polyolefinic polymers ENGAGE® and EXACT®, can be crosslinked.
  • the final inflated balloon size can be controlled. Conventional crosslinking techniques can be used including thermal treatment and E-beam exposure. After crosslinking, initial pressurization, inflation, and preshrinking, the balloon will thereafter expand in a controlled manner to a reproducible diameter in response to a given inflation pressure, and thereby avoid overexpanding the stent (if used in a stent delivery system) to an undesirably large diameter.
  • the balloon is formed from a low tensile set polymer such as a silicone-polyurethane copolymer.
  • the silicone-polyurethane is an ether urethane and more specifically an aliphatic ether urethane such as PURSIL AL 575A and PURSIL ALIO, ( Polymer Technology Group), and ELAST-EON 3-70A, (Elastomedics), which are silicone polyether urethane copolymers, and more specifically, aliphatic ether urethane cosiloxanes.
  • the low tensile set polymer is a diene polymer.
  • diene polymers can be used such as but not limited to an isoprene such as an AB and ABA poly(styrene-block-isoprene), a neoprene, an AB and ABA poly(styrene-block- butadiene) such as styrene butadiene styrene (SBS) and styrene butadiene rubber (SBR), and 1,4- polybutadiene.
  • the diene polymer is an isoprene including isoprene copolymers and isoprene block copolymers such as poly(styrene-block-isoprene).
  • isoprene is a styrene-isoprene- styrene block copolymer, such as Kraton 1161K available from Kraton, Inc.
  • isoprenes can be used including HT 200 available from Apex Medical, Kraton R 310 available from Kraton, and isoprene (i.e., 2-methyl-l,3- butadiene) available from Dupont Elastomers.
  • Neoprene grades useful in the disclosed subject matter include HT 501 available from Apex Medical, and neoprene (i.e., polychloroprene) available from Dupont Elastomers, including Neoprene G, W, T and A types available from Dupont Elastomers.
  • HT 501 available from Apex Medical
  • neoprene i.e., polychloroprene
  • Dupont Elastomers including Neoprene G, W, T and A types available from Dupont Elastomers.
  • the outer surface of the balloon is modified.
  • the balloon surface can include a textured surface, roughened surface, voids, spines, channels, dimples, pores, or microcapsules or a combination thereof, as will be described below.
  • the balloon does not include a stent or is free of a stent.
  • a stent can be mounted onto the coated balloon.
  • the stent will not detrimentally affect coating integrity or drug delivery.
  • the type of stent that can be used includes, but is not limited to, bare metal stent, balloon expandable stent, self expanding stent, drug eluting stent, prohealing stent, and self-expanding vulnerable plaque implant.
  • the balloon can be coated independently of the stent or in conjunction with the stent coating process.
  • the stent coating can contain the same or different therapeutic agents from the balloon catheter or expandable member. However, the particular coating on the balloon catheter or expandable member preferably has distinct release kinetics from the therapeutic coating on the stent.
  • the balloon is formed of a porous elastomeric material having at least one void formed in the wall of the balloon surface.
  • the entire cross section of the balloon can contain a plurality of voids.
  • the plurality of void can be distributed along select lengths of the balloon outer surface.
  • the plurality of voids can be distributed only along the working section of the balloon.
  • the voids define an open space within the outer surface of the balloon.
  • the therapeutic agent is dispersed within the space defined by the plurality of voids across the cross section of the balloon outer surface.
  • the therapeutic agent is released or is expelled from the pores upon inflation of the balloon.
  • the durometer of the polymeric material of the balloon surface and in particular the depression of the void is sufficiently flexible to allow for expulsion of the therapeutic agent and/or coating contained within the plurality of voids upon inflation of the balloon. The expelled coating with therapeutic agent is released into the vessel lumen or into the tissue surrounding and contacting the inflated balloon.
  • the balloon includes protrusions configured to contact or penetrate the arterial wall of a vessel upon inflation of the balloon.
  • a therapeutic formulation is disposed on the protrusions and when inflated the therapeutic formulation and/or therapeutic agent coats or adheres to the tissue of the arterial wall.
  • the balloon can include two concentric balloons in a nesting configuration. The therapeutic formulation is disposed between the two concentric balloons.
  • the space between the two concentric balloons; one being an interior balloon and the other being an exterior balloon acts as a reservoir.
  • the protrusions can include apertures for expulsion of the therapeutic formulation and/or therapeutic agent upon inflation of the interior and exterior concentric balloons.
  • the balloon can include longitudinal protrusions configured to form ridges on the balloon surface.
  • the ridges can be formed of filaments spaced equidistantly apart around the circumference of the balloon.
  • a protective sheath can be utilized to protect the therapeutic formulation from being rubbed off of the balloon during the movement of the coated balloon through the body lumen.
  • the sheath is made in certain embodiments from an elastic and resilient material which conforms to the shape of the balloon and in particular is capable of expanding upon inflation of the balloon.
  • the sheath can include apertures along a length thereof. In operation, the inflation of the balloon causes the apertures of the sheath to widen for release of the therapeutic formulation and/or therapeutic agent to the tissue of the arterial wall.
  • the sheath has a thickness less than 10 mils. However, other thicknesses are possible.
  • the sheath has at least one longitudinal line of weakness allowing the sheath to rupture upon inflation of the balloon and the release of the therapeutic formulation and/or therapeutic agent onto the tissue of the arterial wall of the vessel.
  • the sheath is formed from polymeric material known to be suitable for use in balloon catheters.
  • the sheath material is an elastomeric material which will also spring back when it splits to expose more of the body lumen to the coating.
  • the line of weakness could be provided by various techniques known in the art. However, one non- limiting examples include perforating the sheath material. In operation, the sheath is placed over the coated balloon while in the deflated state.

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Abstract

L'invention concerne un cathéter à ballonnet configuré pour administrer un agent thérapeutique lors de la fourniture d'un potentiel électrique au ballonnet, le cathéter comportant une électrode disposée près de la surface externe de l'élément extensible, un revêtement disposé sur au moins une partie de la surface externe, le revêtement comprenant un agent thérapeutique ; une source d'alimentation en communication électrique avec l'électrode.
PCT/US2013/032654 2013-03-15 2013-03-15 Ballonnet électrophorétique et revêtement de ballonnet conducteur Ceased WO2014143061A1 (fr)

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EP13716899.3A EP2968685A1 (fr) 2013-03-15 2013-03-15 Ballonnet électrophorétique et revêtement de ballonnet conducteur
CN201380074673.5A CN105228663A (zh) 2013-03-15 2013-03-15 电泳球囊和导电球囊涂层
CR20150562A CR20150562A (es) 2013-03-15 2015-10-15 Globo electroforético y revestimiento conductor para globos

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EP3200858A4 (fr) * 2014-09-30 2018-06-13 The Spectranetics Corporation Revêtement d'électrodéposition pour dispositifs médicaux
US20220016398A1 (en) * 2018-11-23 2022-01-20 Shanghai Microport Medical (Group) Co., Ltd. Drug eluting balloon and balloon catheter

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WO2019018255A1 (fr) * 2017-07-17 2019-01-24 Boston Scientific Scimed, Inc. Ballonnet poreux ayant un marqueur radio-opaque
RU2669052C1 (ru) * 2018-02-12 2018-10-05 Государственное Бюджетное Учреждение Здравоохранения Города Москвы "Научно-Исследовательский Клинический Институт Оториноларингологии Им. Л.И. Свержевского" Департамента Здравоохранения Города Москвы (Гбуз Никио Им. Л.И. Свержевского Дзм) Катетер для проведения электрофореза и введения лекарственных средств в барабанную полость
CN110292701B (zh) * 2019-06-27 2021-11-16 山东瑞安泰医疗技术有限公司 一种药物洗脱球囊导管及其制备方法
EP4114498A2 (fr) * 2020-03-02 2023-01-11 Advanced Nanotherapies, Inc. Systèmes de ballonnet ondulé et méthodes d'administration de médicament à base de nanoparticules
CN115887786B (zh) * 2022-11-16 2024-03-12 中国中医科学院望京医院(中国中医科学院骨伤科研究所) 一种聚偏氟乙烯涂覆的纳米复合管材及其制备方法

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US10973959B2 (en) 2014-09-30 2021-04-13 The Spectranetics Corporation Electrodeposition coating for medical devices
CN105833269A (zh) * 2015-01-13 2016-08-10 上海交通大学医学院附属第九人民医院 一种具有光热效应的聚吡咯纳米颗粒及其制备方法和应用
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US12151070B2 (en) * 2018-11-23 2024-11-26 Shanghai Microport Medical (Group) Co., Ltd Drug eluting balloon and balloon catheter

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EP2968685A1 (fr) 2016-01-20
CN105228663A (zh) 2016-01-06

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