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WO1992000113A1 - Procede et catheter pour administration intravasculaire de medicaments - Google Patents

Procede et catheter pour administration intravasculaire de medicaments Download PDF

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Publication number
WO1992000113A1
WO1992000113A1 PCT/US1991/004336 US9104336W WO9200113A1 WO 1992000113 A1 WO1992000113 A1 WO 1992000113A1 US 9104336 W US9104336 W US 9104336W WO 9200113 A1 WO9200113 A1 WO 9200113A1
Authority
WO
WIPO (PCT)
Prior art keywords
catheter
macroporous matrix
macroporous
distal end
tubular member
Prior art date
Application number
PCT/US1991/004336
Other languages
English (en)
Inventor
Robert A. Graor
Original Assignee
Cardiovascular Therapeutic Technologies, 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 Cardiovascular Therapeutic Technologies, Inc. filed Critical Cardiovascular Therapeutic Technologies, Inc.
Priority to JP3512898A priority Critical patent/JPH06503972A/ja
Priority to CA002085470A priority patent/CA2085470A1/fr
Publication of WO1992000113A1 publication Critical patent/WO1992000113A1/fr

Links

Classifications

    • 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
    • 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

Definitions

  • the present invention relates generally to apparatus and methods for intravascular drug delivery and more particularly to a catheter and method for the controlled infusion of therapeutic agents into an extended region within a blood vessel over a prolonged time period.
  • catheters may be used for the localized administration of thrombolytic agents to dissolve clots within the vascular system.
  • the catheter is percutaneously introduced to the vascular system at the distal end located adjacent to or within the region of clot or thrombus.
  • the thrombolytic agent is then delivered through the catheter and released through one or more discrete perfusion ports formed near the distal end of the catheter.
  • two or more catheters may be utilized simultaneously in an attempt to release the thrombolytic agent throughout the entire clotted region.
  • the need to increase the delivery rate is wasteful and results in an increased release of the thrombolytic agent throughout the remainder of the vascular system which can have undesirable side effects.
  • the uneven release of the thrombolytic agent further slows the overall dissolution rate of the thrombus which results in a lengthening of the total time required for each treatment. As the treatment time can frequently be many hours, any increase is highly undesirable.
  • the use of discrete perfusion ports makes it more difficult to control the release rate which may be as low as several ml/min. Any deviation from the desired release rate can in turn cause the release of excess thrombolytic agent which is wasteful or the release of less than the desired thrombolytic agent which increases the necessary treatment time.
  • the catheters should be suitable for percutaneous introduction to a desired location within the vascular system, preferably utilizing conventional guide wire introduction techniques.
  • the catheter should further be able to provide highly uniform and controllable delivery rates over an extended axial length thereof so that the therapeutic agent may be released within the vascular system under optimum conditions. It would be further desirable if the catheters were suitable for vascular placement over extended periods of hours.
  • the catheter is intended primarily for blood analysis, but it is suggested that it would also be useful for introducing medicaments. It would not, however, be useful for introducing macromolecules as the membrane is macroporous and selected to block proteins and other larger molecules.
  • U.S. Patent No. 4,671,287 describes a catheter having an oxygen permeable bag intended for gastrointestinal oxygenation.
  • U.S. Patent No. 4,274,417 describes a blood gas analysis probe having a permeable tip.
  • U.S. Patent No. 4,318,402 describes a liquid infusion catheter having a perforated outer tube and an unperforated inner tube.
  • the present invention comprises an invention and method for the intravascular introduction of therapeutic agents, particularly high molecular weight macromolecular therapeutic agents such as thrombolytic proteins and other polypeptides.
  • the apparatus comprises a catheter having an elongate catheter body with proximal and distal ends. At least one lumen extends axially from the proximal end of the catheter body to a macroporous matrix which is located on the catheter body, typically being at or near the distal end of the catheter body.
  • the macroporous matrix has permeability characteristics which permit the controlled infusion (under a pressure gradient) of macromolecules from the lumen to a region
  • the macroporous matrix has a tubular geometry and forms a portion of the exterior of the catheter body, extending over a desired axial length. In this way, highly uniform and controlled flow of the therapeutic agent can be achieved over extended lengths of the catheter body in a manner which is unattainable with the perforate structures heretofore employed.
  • the catheter is percutaneously introduced and transluminally positioned so that the macroporous matrix is located within or adjacent to a region within a blood vessel which requires therapy, usually a region of thrombus.
  • a desired therapeutic agent may then be introduced through the lumen, such as a solution containing a thrombolytic polypeptide.
  • Therapeutic agents can be introduced at a concentration and for a time sufficient to achieve the desired therapeutic effect. The controlled and uniform delivery rate of the therapeutic agent can be carefully selected to optimize the treatment conditions.
  • FIG. 1 is a perspective view of a controlled perfusion catheter constructed in accordance with the principles of the present invention.
  • Fig. 2 is a detailed elevational view of the distal end of the catheter of Fig. 1 shown in cross- section.
  • Fig. 3 is a cross-sectional view taken along line 3-3 of Fig. 2.
  • Fig. 4 is a cross-sectional view taken along
  • Fig. 5 is a cross-sectional view taken along line 5-5 of Fig. 2.
  • Fig. 6 illustrates a first alternate embodiment of the catheter of the present invention.
  • Fig. 7 illustrates a second alternate embodiment of the catheter of the present invention.
  • Fig. 8 illustrates the method of the present invention using the catheter of Fig. 1 to introduce a thrombolytic polypeptide to a region of thrombus within a patient's vascular system. DESCRIPTION OF THE PREFERRED EMBODIMENTS
  • the present invention is useful for intravascular delivery of a wide variety of therapeutic agents including both low molecular weight drugs, such as antiproliferative drugs, e.g., methotrexate and high molecular weight macromolecules.
  • the invention is particularly useful for the delivery of high molecular weight macromolecular therapeutic agents such as proteins, polypeptides, polysaccharides, mucopolysaccharides, and other biomolecules having a desired therapeutic activity.
  • therapeutic biomolecules include thrombolytic polypeptides, blood thinning agents such as heparin (a mucopolysaccharide) , vasodialators, antibodies, immunotoxins, and the like.
  • the present invention is particularly useful when site-specific delivery of a therapeutic agent is required, such as treatment of a solid tumor with an immunotoxin or antiproliferative drug proximate the tumor site, treatment of a stenotic region within the vascular system with a thrombolytic polypeptide, and the like.
  • a therapeutic agent such as treatment of a solid tumor with an immunotoxin or antiproliferative drug proximate the tumor site, treatment of a stenotic region within the vascular system with a thrombolytic polypeptide, and the like.
  • TPA tissue plasminogen activator
  • streptokinase streptokinase
  • urokinase urokinase
  • the catheter of the present invention comprises an elongate, flexible catheter body having proximal and distal ends.
  • the length and diameter of the catheter body will vary depending on the intended application, typically having a length in the range from about 60 to 150 cm and a diameter in the range from about 3 to 11 F (one French (F) is equal to 0.33 mm).
  • the catheter body When the catheter is intended to reach the coronary blood vessels, the catheter body will typically have a length in the range from about 120 to 150 cm and a diameter in the range from about 3 to 8 F.
  • the catheter body When intended to reach the peripheral blood vessels, the catheter body will usually have a length from about 60 to 150 cm and a diameter from about 3 to 11 F.
  • the catheter body may include one or more tubular elements with multiple tubes usually being arranged coaxially.
  • the tube(s) will typically be formed by extrusion of an organic polymer, typically a thermoplastic such as nylon, polyurethane, polyethyleneterephthalate (PET) , polyvinylchloride (PVC) , polyethylene, or the like.
  • the tubes so formed may be reinforced or unreinforced, with reinforcement being optionally provided by metal wires, metal braided cables, or the like. Processes and techniques for forming intravascular catheter bodies are well known in the art and well described in the patent, scientific, and medical literature.
  • the tube(s) will define one or more lumens extending axially within the catheter body from the proximal end.
  • At least one lumen will be provided for delivering the therapeutic agent from the proximal end of the catheter to near the distal end, as described in more detail hereinafter. Additional lumens may be provided for a variety of purposes, such as to allow introduction and placement of the catheter over a guide wire, and the like. Alternatively, the catheter may employ a fixed guide wire at its distal end to allow for positioning of the catheter within the vascular system.
  • a lumen will be provided in the distal tip of the catheter to allow a bypass blood flow through the catheter.
  • a bypass blood flow is particularly useful when the catheter is inserted into relatively tight regions of stenosis where blood flow would be otherwise blocked and when the catheter is to be left for extended periods of time.
  • one or more additional lumens are provided to deliver different therapeutic or other agents to different locations on the catheter. For example, while a thrombolytic agent is being delivered to the distal end of the catheter, a separate lumen might simultaneously deliver an anti-clotting agent along the remaining length of the catheter to inhibit clotting which might otherwise be induced by the catheter.
  • the catheter of the present invention will include or be attachable to a proximal housing which provides for access to the internal lumen(s) within the catheter body.
  • the proximal housing will include one or more conventional fittings, e.g., luer connectors, which provide for attachment of tubes and introduction of guide wires, as described in more detail hereinafter.
  • the therapeutic agent delivered by the catheter will be released under a preselected pressure gradient through a macroporous matrix disposed along an axial length of the catheter body, usually although not necessarily disposed near the distal end of the catheter.
  • the macroporous matrix will be in fluid connection with the lumen which carries the therapeutic agent so that the matrix provides a rate-controlling barrier for releasing the therapeutic agent from the catheter.
  • the macroporous matrix will form a portion of the outer surface of the catheter body with the lumen disposed along the entire interior length of the matrix.
  • the therapeutic agent can perfuse outward through the macroporous matrix to the exterior environment surrounding the catheter in a highly uniform and controlled manner, where the rate of perfusion is controlled both by the characteristics of the matrix and 8 by the level of internal pressurization as described in more detail hereinafter. It would be possible, of course, to provide additional structure on the catheter to control or direct the flow of therapeutic agent in some manner. In all cases, however, the macroporous matrix will act as a rate controlling element in the delivery system.
  • the macroporous matrix is formed as a close-ended tube or cylinder where the lumen opens into an interior volume within the tube.
  • a close-ended tube or cylinder where the lumen opens into an interior volume within the tube.
  • the length of the macroporous membrane may vary widely, usually being at least 1 cm in length and extending up to the entire catheter length, e.g., 160 cm.
  • the length of the macroporous matrix will be in the range from about 2 to 50 cm, more usually being in the range from about 2 to 20 cm, and frequently being in the range from 5 to 15 cm.
  • the macroporous matrix may be formed as a sheath over an internal tubular structure which defines one or more therapeutic agent delivery lumens.
  • a structure allows the sheath to be divided into two or more delivery zones where different agents may be simultaneously released from different locations on the catheter.
  • the delivery zones may be axially spaced-apart, radially spaced-apart, or spaced-apart both axially and radially.
  • a first lumen can deliver a therapeutic agent to a macroporous matrix located near the catheter tip while a second lumen delivers an anti-clotting agent, such as heparin, to a macroporous matrix which extends over a portion of or the entire length of the catheter shaft.
  • an anti-clotting agent such as heparin
  • the macroporous matrix will be formed from a material which is sufficiently porous to allow passage or diffusion of the active molecular species of the therapeutic agent while providing sufficient flow resistance so that the solution containing the therapeutic agent can be released at a desired rate uniformly across the length of the matrix.
  • the material will usually be selected to pass molecules having a molecular weight of at least ten kilodaltons (kD) , more usually of at least about 25 kD, preferably of at least about 50 kD, and more preferably of at least about 100 kD.
  • the release rate of the solution which carries the therapeutic agent will depend on a number of factors in addition to the nature of the matrix material, including the delivery pressure, matrix area, matrix thickness, functionalization of the matrix material, and the like.
  • the macroporous matrix will be composed of a biocompatible material, typically being formed from an organic polymer, although in certain cases it may be possible to form the matrix from metals, e.g., stainless steel, or ceramics, e.g., alumina.
  • the macroporous matrix will usually be a single layer of material, although in certain cases it may be desirable to form the matrix as a composite of two or more layers where one layer provides the necessary mechanical strength and another layer provides for the desired molecular weight cutoff and flow resistance.
  • the macroporous matrix may be flexible or rigid, usually being flexible to facilitate manipulation through the vascular system.
  • the matrix material will usually not be substantially expandable, i.e., it will not dilate substantially in response to internal pressurization, but in some cases may be expandable.
  • the macroporous matrix may be formed as a woven fabric, non-woven fabric, polymeric film or membrane, or the like.
  • Woven fabrics will typically be formed from organic polymer fibers, such as polyethylene, polypropylene, polyester, nylon, polytetrafluoroethylene (PTFE) , polycarbonate, polystyrene, cellulose, polyacetonitrile, and the like.
  • Individual fibers or bundles of fibers (yarns) may be woven into the fabric by conventional techniques, including weaving, braiding, knitting, and the like.
  • the porosity of woven fabrics will be determined primarily by the interstitial spaces between the woven fibers or yarns, with tighter weaves providing a greater flow resistance.
  • woven fabrics will have a very high molecular weight cutoff since the interstices in the weave pattern will be large relative to molecular dimensions.
  • the flow resistance will depend primarily on the thickness of the fabric and can be controlled accordingly.
  • the use of woven fabrics as the macroporous matrix material will be preferred.
  • Particularly preferred will be the use of woven polyethyleneterephthalate (PET) fabrics, available under the tradename Dacron®.
  • Non-woven fabrics typically spunbonded fabrics, may also find use as the macroporous matrix material.
  • Non-woven fabrics can be prepared from most of the fiber materials listed above with a wide range of porosity and resistance to flow.
  • the macroporous matrix layers may also be formed from macroporous membranes produced from a wide variety of organic polymers.
  • the preparation of porous membranes having desired characteristics is well described in the technical and patent literature. See, for example, Kirk-Othmer, Encyclopedia of Chemical Technology, 3rd ed. , Vol. 15, John Wiley & Sons, New York (1979) , pp. 93-131, the disclosure of which is incorporated herein by reference.
  • Exemplary organic membrane materials include polyethylene, polypropylene, polystyrene, nylon, poly(methacrylates) , polyvinyl chlorides, and the like.
  • any of the organic polymers described above it may be desirable to provide functional groups on the polymeric backbone in order to achieve a desired effect, typically governing the controlled release of the therapeutic agent.
  • functional groups on the polymeric backbone typically governing the controlled release of the therapeutic agent.
  • hydrophilic or hydrophobic groups might be introduced in order to affect the release rate of therapeutic agents having either hydrophobic or hydrophilic characteristics.
  • cationic and/or anionic functionalities may be introduced in order to affect the release of charged therapeutic agents.
  • the macroporous matrix be "wettable" and capable of retaining a residual volume of therapeutic agent with its structure, such as woven and non-woven fabrics composed of hydrophilic materials, such as polyethyleneterephthalate, and the like.
  • a residual volume of therapeutic agent with its structure, such as woven and non-woven fabrics composed of hydrophilic materials, such as polyethyleneterephthalate, and the like.
  • the catheter 10 comprises a catheter body 12 having a proximal end 14 and a distal end 16.
  • the catheter body 12 includes an inner flexible tubular member 18 and an outer flexible tubular member 20.
  • the inner flexible tube 18 has a central lumen 22 extending from proximal end 14 to distal end 16, while the inner tube 18 and outer tube 20 together define an annular lumen 24 which also extends from the proximal end to the distal end of the catheter.
  • a proximal housing 30 is secured to the proximal end 14 of catheter body 12.
  • the housing 30 includes a central port 32 which communicates with the central lumen 22 of the inner flexible tube 18.
  • the housing further includes a side port 34 which communicates with the annular lumen 24.
  • the central lumen 22 and port 32 will be used to introduce the catheter 10 over a movable guide wire 36 (shown in broken line) in a conventional manner.
  • the side port 34 will be used to introduce a solution carrying the therapeutic agent of interest.
  • Catheter 10 includes a tubular macroporous matrix 40 formed near the distal end 16.
  • the distal end of tubular macroporous matrix 40 is attached to the outer surface of tubular member 18 in order to close the end of the annular lumen 24.
  • the tubular macroporous matrix forms a continuous surface with the outer flexible tubular member 20 so that, in effect, the catheter body includes a single continuous outer tubular member having a non-porous or impermeable portion and a second porous portion defined by the tubular matrix 40.
  • the solution carrying the therapeutic agent may be introduced through port 34, travel through the annular lumen 24, and be released under controlled conditions through the macroporous matrix 40.
  • the length of the tubular macroporous matrix 40 can vary widely within the limits set forth above.
  • the porosity characteristics of the matrix 40 will generally be uniform over the entire surface area so that the release rate of the therapeutic solution will be the same at all locations. It would, of course, be possible to modify the porosity and other characteristics of the matrix 40 in cases where it is desired to provide a non- uniform release rate of the therapeutic solution.
  • a second exemplary catheter 50 is illustrated in Fig. 6 and includes an inner flexible tubular member 52 having four isolated axial lumens 54a, b, c, and d extending therethrough.
  • a fifth central lumen 56 is also provided for introducing the catheter 50 over a guide wire (not illustrated) in a conventional manner.
  • the catheter 50 further includes a tubular macroporous matrix 58 disposed coaxially about the inner flexible tubular member 52 so that an annular lumen 60 remains therebetween.
  • the annular lumen 60 is divided into a proximal region 62 and a distal region 64 by a partition 66 so that the different lumens 54a, b, c, and d may be used to deliver different therapeutic agents to each region.
  • ports 64 are provided in lumen 54d and lumen 54b (the latter are not visible in Fig. 6) in order to deliver a therapeutic agent to the distal region 64 of the annular lumen 60. From this region, the therapeutic agent is able to infuse in a uniform, controlled manner into the surrounding blood vessel.
  • a second set of ports 70 are provided in lumen 54a and lumen 54c (the latter ports are not visible in Fig. 6) in order to deliver a second therapeutic or other agent to the proximal region 62 of the annular lumen 60.
  • the second agent can be administered to a different region of the blood vessel simultaneously with the first agent.
  • the use of multiple delivery lumens and partitions can be extended to form any number of delivery regions along the length of the catheter.
  • the regions may be continuous or separated and may extend over the entire length or only a portion of the length of the catheter.
  • the embodiment illustrated in Fig. 6 will be particularly useful for delivering an anti-clotting agent, such as heparin, along the shaft of the catheter while the desired therapeutic agent is being delivered at the distal end.
  • the ability to delivery an anti-clotting agent at relatively low controlled rates for extended periods of time is advantageous since catheters can initiate clot formation when present in the vascular system.
  • a catheter 80 may be provided with a plurality of ports 82 which communicate with an internal lumen which allows blood to flow through the catheter.
  • the catheter 80 employs a central lumen 84 to provide the bypass flow path, where the central lumen is open at its distal end 86.
  • Other, separate lumens might also be provided.
  • the guide wire 36 is introduced through the left iliac artery I L into the right iliac artery I R and then into the superficial femoral artery SF using an introducer catheter 50 in a conventional manner.
  • the guide wire 36 is positioned so that its distal end passes into the deep femoral artery DF to reach the region of thrombus T. All such positioning steps can be performed under fluoroscopic guidance.
  • the catheter 10 may be introduced by passage over the guide wire until the macroporous membrane 40 lies within the region of thrombus T.
  • a perfusate solution containing the therapeutic agent of interest typically a thrombolytic polypeptide, is then introduced through port 34 at a rate and for a time sufficient to at least partly dissolve the thrombus T.
  • the perfusate is typically delivered from a reservoir 100 , such as a flexible pouch, through a pump 102 which is connected to inlet port 34 by tubing 104 .
  • the pump will typically be capable of delivering a preselected volumetric flow rate over a wide range of pressures .
  • Treatment conditions for two of the most commonly employed thrombolytic agents are as follows .
  • the pressure of the perfusate in the catheter will be determined primarily by the resistance to flow provided by the macroporous membrane 40, and may vary from about 0.1 psi to 500 psi, usually being in the range from about 25 psi to 100 psi.
  • the back pressure on the macroporous membrane 40 provides for highly uniform and controlled release of the thrombolytic agent throughout the region of thrombus T so that dissolution occurs at a constant rate, minimizing the total amount of agent required and reducing the chance that portions of the thrombus will be broken off and released as emboli.

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  • Life Sciences & Earth Sciences (AREA)
  • Biophysics (AREA)
  • Pulmonology (AREA)
  • Engineering & Computer Science (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Materials For Medical Uses (AREA)
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Abstract

Cathéter de perfusion vasculaire (10) comprenant un corps (12) doté d'une matrice macroporeuse (40) formant au moins une partie de son extrémité distale (16). Une solution contenant un agent thérapeutique désiré peut être introduite dans le cathéter (10) et libérée à travers la matrice macroporeuse (40) dans des conditions contrôlées. Grâce à la matrice en forme d'élément tubulaire (20), l'agent thérapeutique peut être libéré uniformément dans toutes les directions radiales sur une longueur présélectionnée au sein d'un vaisseau sanguin.
PCT/US1991/004336 1990-06-26 1991-06-18 Procede et catheter pour administration intravasculaire de medicaments WO1992000113A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP3512898A JPH06503972A (ja) 1990-06-26 1991-06-18 薬剤の血管内供給方法およびそのためのカテーテル
CA002085470A CA2085470A1 (fr) 1990-06-26 1991-06-18 Methode et catheter pour la delivrance intravasculaire de medicaments

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US54531190A 1990-06-26 1990-06-26
US545,311 1990-06-26

Publications (1)

Publication Number Publication Date
WO1992000113A1 true WO1992000113A1 (fr) 1992-01-09

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1991/004336 WO1992000113A1 (fr) 1990-06-26 1991-06-18 Procede et catheter pour administration intravasculaire de medicaments

Country Status (4)

Country Link
EP (1) EP0536296A4 (fr)
JP (1) JPH06503972A (fr)
CA (1) CA2085470A1 (fr)
WO (1) WO1992000113A1 (fr)

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EP0808190A4 (fr) * 1995-02-06 2001-08-16 Rtc Inc Sonde anti-infectieuse et ses procedes de fabrication et d'utilisation
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US7452353B2 (en) 1999-07-19 2008-11-18 I-Flow Corporation Catheter for uniform delivery of medication
US7510550B2 (en) 1999-07-19 2009-03-31 I-Flow Corporation Catheter for uniform delivery of medication
US7547302B2 (en) 1999-07-19 2009-06-16 I-Flow Corporation Anti-microbial catheter
US7569045B2 (en) 1999-07-19 2009-08-04 I-Flow Corporation Catheter for uniform delivery of medication
WO2010005714A1 (fr) * 2008-06-16 2010-01-14 Twin Star Medical, Inc. Cathéter souple
KR100946165B1 (ko) * 2006-10-02 2010-03-11 아이-플로우 코포레이션 치료제의 균일 운송을 위한 카테터
WO2010031515A1 (fr) * 2008-09-17 2010-03-25 Johanneum Research Forschungsgesellschaft Mbh Cathéter à base de filament
WO2014018595A1 (fr) * 2012-07-26 2014-01-30 Twin Star Medical, Inc. Cathéter macroporeux
US8852166B1 (en) 2002-04-01 2014-10-07 Ekos Corporation Ultrasonic catheter power control
US9415242B2 (en) 2001-12-03 2016-08-16 Ekos Corporation Catheter with multiple ultrasound radiating members
US10092742B2 (en) 2014-09-22 2018-10-09 Ekos Corporation Catheter system
US10656025B2 (en) 2015-06-10 2020-05-19 Ekos Corporation Ultrasound catheter
US11458290B2 (en) 2011-05-11 2022-10-04 Ekos Corporation Ultrasound system
US11672553B2 (en) 2007-06-22 2023-06-13 Ekos Corporation Method and apparatus for treatment of intracranial hemorrhages
US11925367B2 (en) 2007-01-08 2024-03-12 Ekos Corporation Power parameters for ultrasonic catheter

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Cited By (59)

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EP0536296A1 (fr) 1993-04-14
JPH06503972A (ja) 1994-05-12
EP0536296A4 (en) 1993-08-04
CA2085470A1 (fr) 1991-12-27

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