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WO1998018391A1 - Dispositif d'administration de medicament par les parois intraluminales - Google Patents

Dispositif d'administration de medicament par les parois intraluminales Download PDF

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Publication number
WO1998018391A1
WO1998018391A1 PCT/US1997/019993 US9719993W WO9818391A1 WO 1998018391 A1 WO1998018391 A1 WO 1998018391A1 US 9719993 W US9719993 W US 9719993W WO 9818391 A1 WO9818391 A1 WO 9818391A1
Authority
WO
WIPO (PCT)
Prior art keywords
emitter
catheter
vessel
injection site
puncturing
Prior art date
Application number
PCT/US1997/019993
Other languages
English (en)
Inventor
Katsuro Tachibana
Douglas R. Hansmann
Original Assignee
Ekos Corporation
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 Ekos Corporation filed Critical Ekos Corporation
Publication of WO1998018391A1 publication Critical patent/WO1998018391A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods
    • A61B17/22—Implements for squeezing-off ulcers or the like on inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; for invasive removal or destruction of calculus using mechanical vibrations; for removing obstructions in blood vessels, not otherwise provided for
    • A61B17/22004—Implements for squeezing-off ulcers or the like on inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; for invasive removal or destruction of calculus using mechanical vibrations; for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves
    • A61B17/22012—Implements for squeezing-off ulcers or the like on inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; for invasive removal or destruction of calculus using mechanical vibrations; for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves in direct contact with, or very close to, the obstruction or concrement
    • 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
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0092—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/14—Probes or electrodes therefor
    • A61B18/1477—Needle-like probes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods
    • A61B17/22—Implements for squeezing-off ulcers or the like on inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; for invasive removal or destruction of calculus using mechanical vibrations; for removing obstructions in blood vessels, not otherwise provided for
    • A61B2017/22072—Implements for squeezing-off ulcers or the like on inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; for invasive removal or destruction of calculus using mechanical vibrations; for removing obstructions in blood vessels, not otherwise provided for with an instrument channel, e.g. for replacing one instrument by the other
    • A61B2017/22074—Implements for squeezing-off ulcers or the like on inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; for invasive removal or destruction of calculus using mechanical vibrations; for removing obstructions in blood vessels, not otherwise provided for with an instrument channel, e.g. for replacing one instrument by the other the instrument being only slidable in a channel, e.g. advancing optical fibre through a channel
    • A61B2017/22077—Implements for squeezing-off ulcers or the like on inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; for invasive removal or destruction of calculus using mechanical vibrations; for removing obstructions in blood vessels, not otherwise provided for with an instrument channel, e.g. for replacing one instrument by the other the instrument being only slidable in a channel, e.g. advancing optical fibre through a channel with a part piercing the tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/14—Probes or electrodes therefor
    • A61B2018/1405—Electrodes having a specific shape
    • A61B2018/1425—Needle
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/36—Image-producing devices or illumination devices not otherwise provided for
    • A61B90/37—Surgical systems with images on a monitor during operation
    • A61B2090/378—Surgical systems with images on a monitor during operation using ultrasound
    • 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
    • A61M25/0067—Catheters; Hollow probes characterised by the distal end, e.g. tips
    • A61M25/0082—Catheter tip comprising a tool
    • A61M25/0084—Catheter tip comprising a tool being one or more injection needles
    • A61M2025/0085—Multiple injection needles protruding axially, i.e. along the longitudinal axis of the catheter, from the distal tip
    • A61M2025/0086—Multiple injection needles protruding axially, i.e. along the longitudinal axis of the catheter, from the distal tip the needles having bent tips, i.e. the needle distal tips are angled in relation to the longitudinal axis of the catheter
    • 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
    • A61M2205/00—General characteristics of the apparatus
    • A61M2205/33—Controlling, regulating or measuring
    • A61M2205/3368—Temperature

Definitions

  • This invention relates to improved catheters for introduction of medication into a body vessel.
  • vascular diseases of the vascular system are localized to short lengths of arterial tissue in the wall of body vessels.
  • the etiology of the diseases may be due to an underlying disease process such as atherosclerosis, or may be a reaction due to injury associated with balloon angioplasty or rotational atherectomy, for example.
  • various responses including hyperplasia and vessel remodeling can cause vessel narrowing (e.g., restenosis) with subsequent risk of total occlusion and hypoxia of distal tissue.
  • Another treatment used balloons either distal or proximal to the lesion to temporarily stop vessel flow during the treatment period.
  • Appropriate drugs were then introduced into the vessel in the area of the lesion.
  • the resulting longer residence time of the drug in the vessel was intended to increase efficacy of the treatment.
  • the disadvantage of this approach is that many patients are not able to tolerate such stoppage of blood flow for more than a few minutes.
  • side branches to the artery may still rapidly dissipate the drug.
  • U.S. Patent No. 5,197,946 to Tachibana provides for injection instruments with an ultrasonic oscillating element having a proximal tubular part characterized by means for introducing medicinal fluid or the like and an ultrasonic oscillator or connector which is electrically connected to an ultrasonic oscillating element located at the distal tubular part of the injection instrument.
  • Use of such an apparatus demonstrated remarkable improvements in the diffusion and penetration in the area of injection compared with previous methods.
  • this method of Tachibana suffers from the disadvantage, as noted above, that drugs will only be momentarily available at the lesion site because blood flow will rapidly sweep the drugs downstream.
  • Shapland discloses a drug delivery apparatus and method for iontophoretically delivering a drug locally to an internal body tissue.
  • the iontophoretic delivery apparatus and method include a current source producing a net flow of current in a desired direction with high frequency wave forms that enhance delivery and minimize side effects typically associated with iontophoresis.
  • the Shapland patent contemplates positioning a drug delivery device in a body passageway or within body tissue and then selectively introducing a selected drug so that it is iontophoretically transported across a drug transport wall of the device for direct contact with the passageway wall or body tissue.
  • the method of Shapland suffers from the defects mentioned above, namely that blood flow will sweep any injected drugs rapidly downstream.
  • This document discussed a local delivery device with a polyethylene catheter possessing a central lumen for a guide wire and six needles positioned symmetrically. With the catheter placed in the vessel lumen, the needles were designed to be advanced by a mechanism at the distal end thus extending the needles laterally at the proximal tip. The needles were preshaped so that they could penetrate the vascular wall, and drugs could be injected in the perivascular tissue.
  • U.S. Patent No. 5,538,504 to Linden et al. shows another type of needle injection catheter having a puncturing element for puncturing the inner wall of a vessel and then injecting a selected drug.
  • needle injection catheters suffer from some difficulties with diffusing and penetrating of the injected medications into the body tissues.
  • current treatments for cancer tumors or other undesirable growths often focus on systemic administration of various medications, as opposed to a local treatment.
  • administering levels of those medications high enough to achieve effective bioavailability at the tumor location can often lead to undesirable side effects for a patient.
  • the invention relates to an apparatus for delivering a medicament into an injection site in or beyond a vessel wall or vessel obstruction
  • an intraluminal catheter containing, internal to the catheter: at least one puncturing element that is laterally extendable to the catheter longitudinal axis at the distal end of the catheter; an ultrasound emitter located in the proximity of the extendable puncturing element(s); and an introducer element that introduces the medicament into an injection site that is in or beyond the vessel wall, but within a portion of the vessel wall that has been penetrated by the puncturing element.
  • the invention also relate to methods for treating a stenosis or obstruction in a vessel comprising introducing an intraluminal catheter into the vessel, wherein the catheter contains, internal to the catheter, at least one puncturing element, an ultrasound emitter located in the proximity of the puncturing element(s), and an introducer element that introduces the medicament into an injection site in or beyond the vessel wall, but within a portion of the vessel wall that has been penetrated by the puncturing element; introducing a drug using the introducer element into the injection site; and irradiating the injection site with ultrasound using the emitter.
  • the invention additionally relates to methods for creating a stenosis or obstruction in a vessel comprising introducing an intraluminal catheter into the vessel, wherein the catheter contains, internal to the catheter, at least one puncturing element, an ultrasound emitter located in the proximity of the puncturing element(s), and an introducer element that introduces the medicament into an injection site in or beyond the vessel wall, but within a portion of the vessel wall that has been penetrated by the puncturing element; introducing a drug using the introducer element into the injection site; and irradiating the injection site with ultrasound using the emitter.
  • Figure 1 shows a catheter structure according to the invention.
  • Figure 2 shows a catheter structure according to the invention.
  • Figure 3 shows a catheter structure according to the invention.
  • Figure 4 shows a catheter system layout according to the invention.
  • Figure 5 shows an cross section of a catheter structure according to the invention.
  • Figure 6 shows a catheter structure according to the invention.
  • Figure 7 shows an cross section of a catheter structure according to the invention.
  • Figure 8 shows a catheter structure according to the invention.
  • Figure 9 shows a catheter structure according to the invention.
  • Figure 10 shows an cross section of a catheter structure according to the invention.
  • FIG. 11 shows operation of an embodiment of the invention.
  • Figure 12 shows operation of an embodiment of the invention.
  • Figure 13 shows operation of an embodiment of the invention.
  • Figure 14 shows ultrasound emitters according to the invention.
  • FIG. 15 shows operation of an embodiment of the invention.
  • Figure 16 shows operation of an embodiment of the invention.
  • Figure 17 shows operation of an embodiment of the invention.
  • Figure 18 shows operation of an embodiment of the invention.
  • Figure 19 shows operation of an embodiment of the invention.
  • Figure 20 shows operation of an embodiment of the invention.
  • Figure 21 shows an embodiment of the invention for treating a tumor.
  • Figure 22 shows an embodiment of the invention for treating a tumor.
  • Figure 23 shows an embodiment of the invention for treating a tumor.
  • Figure 24 shows a structure of esophageal varices.
  • Figure 25 shows an embodiment of the invention for treating esophageal varices.
  • Figure 26 shows an embodiment of the invention for treating a tumor.
  • Figure 27 shows an embodiment of the invention for treating a tumor.
  • Figure 28 shows an embodiment of the invention for treating a tumor.
  • Figure 29 shows an embodiment of the invention for treating a tumor.
  • Figure 30 shows an embodiment of the invention for treating a tumor.
  • Figure 31 shows an embodiment of the invention showing application of ultrasound external to a body part.
  • an apparatus for delivering a medicament into an injection site in or beyond a vessel wall or vessel obstruction comprising: an intraluminal catheter containing, internal to the catheter: at least one puncturing element that is laterally extendable to the catheter longitudinal axis at the distal end of the catheter; an ultrasound emitter located in the proximity of the extendable puncturing element(s); and an introducer element that introduces the medicament into an injection site that is in or beyond the vessel wall, but within a portion of the vessel wall that has been penetrated by the puncturing element.
  • the apparatus further comprises an element to extend and retract the puncturing element such that when the puncturing element is retracted, the catheter outside surface is relatively smooth and can be moved within a vessel lumen, and such that, when the puncturing element is extended, it extends sufficiently laterally to the catheter surface to penetrate into or beyond the vessel wall.
  • the apparatus further comprises an electrical connector element to provide power to the ultrasound emitter.
  • the apparatus further comprises at least one element to generate an ultrasonic signal external to the body and connected to the emitter by a connection mechanism.
  • the apparatus further comprises an element to connect a container of medicament to the introducer element such that the medicament can be injected through the introducer element into the injection site.
  • the invention in another embodiment, relates to an apparatus wherein the catheter outside diameter is between 1.0 mm and 3.0 mm. Another aspect of the invention relates to the apparatus wherein the catheter size is between 3.5 french and 6.0 french.
  • Yet another aspect of the invention relates to the apparatus wherein the puncturing element and the introducer element are the same.
  • the invention relates to the apparatus wherein the puncturing element and the introducer element are a hollow needle.
  • the needle outside diameter is approximately 0.250 mm.
  • the needle is stainless steel.
  • Another aspect of the invention relates to the apparatus wherein the needle is NiTi.
  • the invention relates to the apparatus wherein the needle is pre-shaped to extend in an angular manner.
  • Another aspect of the invention relates to the apparatus wherein the extension angle is approximately 15-20°.
  • Yet another aspect of the invention relates to the apparatus wherein the number of puncturing elements is between 1 and approximately 10,000. Another aspect of the invention relates to the apparatus wherein the number of puncturing elements is between 2 to 30. Still another aspect of the invention relates to the apparatus wherein the number of puncturing elements is between 3 and 6.
  • Still another aspect of the invention relates to the apparatus wherein the obstruction is a thrombus.
  • Another aspect of the invention relates to the apparatus wherein the obstruction is an atherosclerotic plaque.
  • the invention relates to the apparatus wherein the emitter is equipositional with respect to the injection site. Another aspect of the invention relates to the apparatus wherein the emitter is distal with respect to the injection site. Yet another aspect of the invention relates to the apparatus wherein the emitter is proximal with respect to the injection site.
  • Still another aspect of the invention relates to the apparatus wherein the ultrasound frequency is between 200KHz and 1.3MHz. Yet another aspect of the invention relates to the apparatus further comprising a guidewire. Another aspect of the invention relates to the apparatus wherein the ultrasound emitter is located within the catheter. Yet another aspect of the invention relates to the apparatus wherein the ultrasound emitter is located external to the catheter.
  • the invention in another embodiment, relates to a method for treating a stenosis or obstruction in a vessel comprising introducing an intraluminal catheter into the vessel, wherein the catheter contains, internal to the catheter, at least one puncturing element, an ultrasound emitter located in the proximity of the puncturing element(s), and an introducer element that introduces the medicament into an injection site that is in or beyond the vessel wall, but within a portion of the vessel wall that has been penetrated by the puncturing element; introducing a drug using the introducer element into the injection site; and irradiating the injection site with ultrasound using the emitter.
  • Another aspect of the invention relates to the method wherein the puncturing element and the introducer element are the same.
  • Still another aspect of the invention relates to the method wherein the puncturing element and the introducer element are a hollow needle. Yet another aspect of the invention relates to the method wherein the vessel wall is an artery, a urethra, an esophagus, a colon, a rectum, a bronchus, a trachea, or a bile duct.
  • Another aspect of the invention relates to the method wherein the vessel is a human vessel. Another aspect of the invention relates to the method wherein the obstruction is a thrombus. Another aspect of the invention relates to the method wherein the obstruction is an atherosclerotic plaque.
  • Still another aspect of the invention relates to the method wherein the emitter is equipositional with respect to the injection site. Another aspect of the invention relates to the method wherein the emitter is distal with respect to the injection site. Yet another aspect of the invention relates to the method wherein the emitter is proximal with respect to the injection site. Another aspect of the invention relates to the method wherein the ultrasound emitter is located external to the catheter.
  • the invention in another embodiment, relates to a method for creating a stenosis or obstruction in a vessel comprising introducing an intraluminal catheter into the vessel, wherein the catheter contains, internal to the catheter, at least one puncturing element, an ultrasound emitter located in the proximity of the puncturing element(s), and an introducer element that introduces the medicament into an injection site in or beyond the vessel wall, but within a portion of the vessel wall that has been penetrated by the puncturing element; introducing a drug using the introducer element into the injection site; and irradiating the injection site with ultrasound using the emitter.
  • Another aspect of the invention relates to the method wherein the puncturing element and the introducer element are the same. Still another aspect of the invention relates to the method wherein the puncturing element and the introducer element are a hollow needle. Yet another aspect of the invention relates to the method wherein the vessel wall is an artery, a urethra, an esophogus, a colon, a rectum, a bronchus, a trachea, or a bile duct. Another aspect of the invention relates to the method wherein the vessel is a human vessel. Another aspect of the invention relates to the method wherein the obstruction is a thrombus. Another aspect of the invention relates to the method wherein the obstruction is an atherosclerotic plaque.
  • the inventors have discovered that drug diffusion and distribution may be markedly and unexpectedly improved by introducing treatment drugs into an area near or in a vessel wall through a puncturing element or elements located at the distal end of a catheter and then irradiating that area with ultrasound.
  • Figure 1 shows a portion of a catheter according to the invention.
  • Distal end of catheter 104 is located at the distal end of catheter body 103.
  • the distal end of catheter 104 includes puncturing element port 101 , ultrasound emitter 102, and guidewire 105.
  • Guidewire 105 passes through catheter body 103 and serves to guide the catheter during insertion.
  • FIG. 2 shows another embodiment of the invention.
  • Catheter body 203 possesses a distal end and shows another view of puncturing element 201 , ultrasound emitter 202, and protruding through the end of catheter body 203 is guidewire 205.
  • FIG 3 shows another view of the catheter according to the invention.
  • Catheter body 303 possesses a distal portion.
  • the distal portion has puncturing element 301 , ultrasound emitter 302 and puncturing elements 306 that comprise drug needles.
  • the drug needles in Figure 3 are shown in the extended position.
  • FIG. 4 shows the catheter system layout according to an embodiment of the invention.
  • Catheter body 403 possesses a distal portion 404 and a proximal portion possessing a junction block 410. Protruding from the junction block are drug lumen 415 possessing a drug delivery container 414. Also extending from junction block 410 is a guidewire port 416 possessing guidewire 405 running through the guidewire port. Additionally, needle extender/retractor device 413 passes through junction block 410. Ultrasound generator 411 is connected to electrical power connector 412 then to the catheter itself through junction block 410. While Figure 4 shows one embodiment of a catheter system according to the invention, other arrangements of the various system components will occur to one of skill in the art. For example, instead of a guidewire based system, the present invention can be practiced in a monorail configuration as well.
  • Figure 5 shows a cross-section of an embodiment of the invention. Shown is catheter outside body 503 containing within puncturing elements 506, wherein the puncturing elements are needles possessing needle drug lumen 518. Within the catheter outside body 503 is electronics lumen 524. Contained within electronics lumen 524 are ultrasound power wires 520 and thermocouple wires 522. Contained within electronics lumen 524 is catheter inner guidewire sleeve 519.
  • Figure 6 shows the distal tip 603 of a catheter according to the invention.
  • the distal tip of the catheter 603 possesses puncturing elements 604 that are vibrating needles that can be extended and retracted 605.
  • Distal tip 603 possesses vibrating element 606 located in distal tip 603 that induces puncturing element 604 to vibrate.
  • Drug 607 can be infused through puncturing element 604 and introduced into a into or around vessel wall or a lumen area. Puncturing element(s) 604 may be connected to the proximal end of the catheter directly or via a manifold.
  • Figure 7 shows another embodiment of the invention having distal end of a catheter 701 containing within lumen space 702 a puncturing element of a hollow vibrating needle 703 for use in introducing medication or other substances.
  • Figure 8 shows yet another embodiment of the invention.
  • Distal tip of catheter 803 possesses puncturing element 802 and a diagnostic ultrasound array 805. Also included in the distal portion of catheter 803 is therapeutic ultrasound emitter 806.
  • Figure 9 shows yet another embodiment of the invention. Shown is proximal end of catheter 903.
  • the proximal end of catheter 903 possesses puncturing element 904 that are drug delivery needles, ultrasound emitter 905, and element for diagnostic echo imaging 906.
  • Figure 10 shows a cross-section of an embodiment of the invention possessing distal end of catheter 1003, passages for puncturing element 1007 and ultrasound emitter 1005.
  • Figure 11 shows another embodiment of the invention.
  • Puncturing element 1102 is contained within distal end of catheter 1103, and is extended into vessel wall 1104 puncturing the wall at 1105.
  • Drug 1106 is injected into the vessel wall area 1104.
  • Ultrasound emitter 1107 is positioned such that it irradiates injected drug 1106 as shown by element 1108. This addition of ultrasound energy 1108 delivered proximal to the needle injection site 1106 further mixes, delivers and/or can activate the drug.
  • Figure 12 shows another embodiment of the invention.
  • Distal end of catheter 1201 contains puncturing element 1203 used to deliver drug 1204 into vessel wall 1202.
  • Ultrasound emitter 1205 is positioned such that it irradiates in area of drug injection 1204.
  • the angle of the emitter 1205 as described by angle 1208 is measured based on the distance 1207 between the center of the transmitter 1205 and the injection site 1204, and by the distance between the center of the emitter 1205 and the puncturing element 1203.
  • Distance 1206 represents the lateral distance from the ultrasound element to the delivery site.
  • Element 1207 represents the actual distance from the puncturing element tip to the center of the ultrasound element.
  • Figure 13 shows an embodiment of the invention, designed to illustrate positioning of the ultrasonic emitter proximally and within the treatment catheter, as opposed to Figure 12 where the emitter is located distally and within the catheter.
  • Distal end of catheter 1301 is inserted such that puncturing element 1303 penetrates vessel wall 1302, whereupon drug 1304 is injected into the vessel wall area.
  • Angle 1308 describes the angle from perpendicular formed by emitter 1305. This angle 1308 is the angle between center axis of the ultrasound element in this embodiment and aligned perpendicular to the catheter axis contained in the plane defined by the puncture element and the drug delivery area.
  • Element 1306 describes the lateral distance from the ultrasound element to the drug delivery site.
  • Element 1307 describes the axial distance from the puncture element tip to the center of the ultrasound emitter 1305.
  • Figure 14 shows embodiments of ultrasonic emitters according to the invention.
  • Element 1401 is a circular emitter
  • element 1402 is a square emitter
  • element 1403 is an octagonal emitter.
  • Figure 15 shows an embodiment of the invention.
  • Distal end of catheter 1501 contains puncturing element 1503 which is puncturing vessel wall 1502.
  • Drug 1504 has been injected into vessel wall 1502.
  • the emitter 1505 is located equipositionally within the catheter 1501 with respect to drug injection site 1504.
  • Figure 16 shows an embodiment of the invention having multiple puncturing elements.
  • Distal end of catheter 1601 contains puncturing elements 1604 used to puncture vessel walls 1602.
  • Drug injection sites 1606 are then irradiated by equipositionally located emitter 1605.
  • Emitter 1605 is an example of a hollow cylinder emitter geometry.
  • Figure 17 shows an embodiment of the invention.
  • Distal end of catheter 1701 contains puncturing element 1702 which is used to introduce drug injection site 1703.
  • Catheter 1702 is passed within hollow cylinder emitter 1704.
  • Emitter 1704 is excited such that the primary vibration mode directs the ultrasound forward along the axis of the catheter 1701 and puncturing element 1702.
  • Figure 18 shows another embodiment to the claimed invention.
  • Catheter 1801 contains puncturing element 1802 used to introduce drug injection site 1803.
  • Emitter 1804 is located such that puncturing element 1802 can pass through the distal portion of catheter 1801 , and can also irradiate along the axis of the catheter 1801 and puncturing element 1802. This embodiment shows that puncturing element 1802 need not be moved along a particular central axis.
  • Ultrasound emitters according to the invention can be of any conventional configuration designed to be used in intravascular application.
  • Acceptable emitter geometries include, but are not limited to hollow cylinder, hemispherical, flat plate, round, and polygon geometries. Suitable emitter geometries are discussed, for example, in U.S. Patent No. 5,362,309 and in U.S. Patent No. 5,197,946, both of which are incorporated by reference.
  • Multiple emitters may be included in the catheter system.
  • the emitter may be located within the catheter, or it may be located externally to the catheter.
  • the emitter may be externally located in another catheter or the emitter may be located externally to a patient being treated.
  • Typical ultrasound operating frequencies for emitters according to the invention are from 200 kilohertz to 1.3 megahertz.
  • the puncturing element(s) according to the invention can be laid out according to the Figures discussed above and/or according to the teachings in Gonschior P, Goetz A, Huehns T.
  • Alternate puncturing element arrangements such as the needle arrangements disclosed in U.S. Patent No. 5,538,504, are also useful within the scope of this invention so long as they provide a puncturing mechanism for penetrating into the vessel wall.
  • Alternate puncture element structures might also include pointed or sharp puncturing elements used to score a vessel wall and permit increased uptake of medication into the vessel wall. For example, balloons studded with sharp points may be used to incise a vessel wall, followed by introduction of a drug into the area near or in the incision and subsequent or contemporaneous application of ultrasound.
  • the needles are made stiff enough to efficiently transmit externally generated ultrasound, they will generally be too large in diameter to serve as flexible and retractable puncturing mechanisms.
  • the vibrating wire is disclosed as being 1.6 mm in diameter at the distal end. Therefore, after much research, the present inventors have concluded that vibrating wires with external emitters are significantly less useful than ultrasonic emitters located at the distal end of the catheter, or application of an externally applied ultrasound beam. Distally located emitters offer relatively high intensities of ultrasound emission at or near the treatment site, without the difficulties presented by ultrasonic or vibrating wires. Additionally, such a catheter architecture would be flexible enough to use in typical applications, such as coronary applications. Application of an externally applied ultrasound beam offers the possibility of using catheters with puncturing mechanisms that may be optimized for drug delivery together with easily adaptable external therapeutic ultrasound beam emitters.
  • the needles When using needles as the puncturing elements, the needles should have a diameter suitable for drug delivery into the vessel walls or tissue surrounding the distal end of the catheter system when in use.
  • the needle diameters should be approximately 0.25 millimeters.
  • the needles may be made of materials known to be suitable by one of skill.
  • the needles are made of stainless steel or NiTi. Needles may be designed to be flexible to facilitate their being extended and retracted through ports present in the distal end of the catheter. Typically, the needles will be preshaped and will have an extension angle of between 15 to 20 degrees.
  • the number of puncturing elements used in practicing the invention will vary according to the indication for treatment. For example, if the treating physician decides that more medication must be delivered to a treatment site, the physician may select a treatment catheter with additional puncturing elements. Conversely if less medication is needed, fewer puncturing elements may be included in the treatment catheter. Preferably the number of puncturing element ranges from 1 to approximately 10,000, more preferably from 2 to 30, and most preferably from 3 to 6. Often more puncturing elements will be needed when the vessel in which the treatment catheter is being deployed is larger. For example, fewer puncturing elements may be needed in a arterial application than would be needed for an esophageal or a colon application. Catheters according to the invention can be used to deliver a variety of drugs useful in treatment or therapy.
  • a representative list of drugs useful in the practice of this invention is given in, but not limited to, the disclosure of U.S. Patent No. 5,538,504, especially in Table I.
  • Drugs that create or cause or induce stenosis, stenotic lesions, thrombosis, etc. are also examples of drugs useful according to the invention.
  • Catheters according to the invention can be used to deliver drugs between the inner and outer surfaces of a vessel wall, to the adventitial side or outer surface of a vessel wall, between the tissue surrounding a vessel wall and the outer surface of the vessel wall, or in other locations that one of ordinary skill might determine to be appropriate delivery sites.
  • One advantage of the catheter according to the invention is that the invention allows one who practices the invention more latitude in how drug is provided to a particular site. For example, drugs provided using a catheter according to the Gonschior techniques or the '504 patent require that a puncturing element actually penetrate to the site of desired drug delivery.
  • the catheter according to the present invention need not penetrate completely to the site. Rather, ultrasound can be used to distribute the drug to the desired site after or in the course of its initial introduction.
  • ultrasound can be used to distribute the drug to the desired site after or in the course of its initial introduction.
  • Such a technique substantially reduces the possibility of undesirable internal bleeding caused by the puncturing of a vessel wall.
  • Catheters according to the invention can be deployed in a variety of vessels in a body. Suitable vessels include, but are not limited to, the artery, the urethra, the esophagus, the colon, the rectum, the bronchial passages, the trachea, the bile duct, and other luminal spaces within the body.
  • catheters according to the invention can be expected to provide unexpectedly superior results as compared to prior art approaches.
  • the catheters according to the invention may, for example, be used to clear obstructions within the vessels. This is generally accomplished by administering medication through the catheter and into the punctures created by the puncturing element.
  • Ultrasound, emitted from the therapeutic ultrasound array or arrays, can then be used to increase uptake through diffusion, distribution, etc., of the medication introduced through the needles into the vessel wall.
  • Figure 19 illustrates the operation of an embodiment of the invention. Shown is distal end of catheter 1903 with puncturing element
  • Puncturing elements 506 are used to inject drug 1907 into vessel wall 1908. Also shown is thermocouple sensor 1921.
  • Figure 20 shows an embodiment of the invention. Shown is distal end of catheter 2003 with puncturing elements 2006. As Figure 20 suggests the puncturing elements 2006 may be withdrawn when activating or incorporating injected drug 2007B into the vessel walls 2008.
  • Ultrasound emitter 2002 is used to radiate ultrasound energy
  • Catheters according to the invention can also be used to create stenosis or thrombi. Such stenoses or thrombi can be valuable in treatment of various diseases, such as cancers, that are characterized by undesirable tissue growth.
  • the catheter according to the invention could be used to deliver thrombin into the arterial wall of a vessel which is feeding into a tumor, thus cutting off blood supply to the tumor and causing tumor necrosis.
  • the catheter according to the invention can be used to create chemical and/or physical damage to a vessel wall. Such damage may block flow through the vessel by creating or initiating a stenosis or a thrombus, depending on the methods used and the nature of the vessel.
  • These techniques can be used, for example, to deliver drug into the hepatic artery wall for treatment of liver cancer, or could be used to deliver drug into a brain artery wall for treatment of a brain tumor.
  • Catheters according to the invention can additionally be used with or introduced using endoscopes, such as the endoscope used in urology or bronchus endoscopy, for example.
  • Figure 21 shows another embodiment of a catheter according to the invention possessing catheter body 2101 , ultrasound horn emitter 2102 and drug introducing lumen 2103.
  • Catheter 2101 can be introduced into tumor 2104.
  • Figure 22 shows one embodiment of the invention as applied to treatment of liver tumors.
  • Catheter 2201 is inserted through the abdominal aorta 2202 and the hepatic artery 2203 to come to rest in or near hyper vascular hematoma 2206 in position 2204. Hematoma 2206 is present inside liver 2205.
  • Figure 23 shows another view of treatment of tumors showing distal catheter tip 2301 having emitter 2303 and puncturing elements
  • Puncturing elements 2302 inject drug 2304 into a vessel wall creating the stenosis 2305 proximal of tumor 2306.
  • Figure 24 shows an embodiment of the invention for treatment of esophageal varices can be used when varices 2402 are near the surface of esophagus 2401 near stomach 2404. In such situations, it is possible for varices 2402 to begin bleeding significantly, as shown by element 2403, into esophagus 2401 and stomach 2404.
  • Figure 25 shows treatment of such conditions using a catheter according to the invention may be performed by introducing endoscope 2505 into esophagus 2501 and then introducing drug delivery and ultrasound, as shown by element 2506, according to the invention into the area of varices 2502. This prevents rupture 2507 of varices 2502 into esophagus 2501 or stomach 2504.
  • Figure 26 shows treatment of a colon cancer tumor (i.e., a tumor stenosis of the colon) 2602.
  • Endoscope 2603 is inserted through rectum 2606 to come to rest near stenosis 2602.
  • Catheter 2604 is extended through endoscope 2603 to come to rest inside of lumen 2601 and inside stenosis 2602.
  • Puncturing elements 2605 are extended from catheter 2604 and can be used to introduce medication that is then subject to ultrasound emission from an emitter or emitters in catheter
  • Figure 23 shows another embodiment of the invention, for use in treatment of prostate cancer.
  • Catheter 2304 is inserted proximal to prostate cancer tumor 2302 which is located proximal to bladder 2301. Needles 2303 are then extended from catheter 2304, drug is injected through puncturing elements 2303, and then ultrasound is emitted from the therapeutic emitter in catheter 2304.
  • Figure 28 shows yet another embodiment of the invention used in treatment of prostate cancer.
  • Bladder 2801 is proximal to prostate tumor 2802, therapy catheter 2805 is introduced into the area in or near tumor 2802 whereupon puncturing elements 2806 are extended, drug is injected through puncturing elements 2806, and ultrasound is applied to further the therapy.
  • Echo imaging device 2804 is inserted through rectum 2803 to image the procedure.
  • Figure 29 shows treatment of a liver tumor using a percutaneous method.
  • Therapy catheter 2904 is inserted through surface of skin 2903 to come to rest in or near tumor 2901 inside of liver 2905.
  • Echo imaging element 2902 is placed externally on skin 2903 to image the procedure.
  • Figure 30 shows another embodiment of the invention used for treating a tumor wherein distal tip of catheter 3003 is placed in or near tumor 3001 , therapy ultrasound emitter 3004 is passed within catheter
  • 3003 and puncturing elements 3005 are extended for introducing treatment medication, followed by ultrasound emission from emitter 3004.
  • Figure 31 shows another embodiment of the invention.
  • Distal end of catheter 3101 contains puncturing element 3102 which is penetrating vessel wall 3103 and is used to introduce drug into drug injection site 3104.
  • Externally applied ultrasound emitter 3106 is placed on surface of epidermis 3105 and ultrasound energy 3107 is applied externally to the body and then passing through to drug injection site 3104. This is an example of ultrasound energy being applied externally to a body.

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Abstract

L'invention concerne un appareil servant à administrer un médicament dans un site d'injection à l'intérieur ou au-delà d'une paroi d'un vaisseau ou d'une obstruction d'un vaisseau, ledit appareil comprenant un cathéter intraluminal comportant au moins un élément de perforation; un émetteur à ultrasons situé à proximité de l'élément de perforation extensible; et un élément d'introduction permettant d'introduire le médicament dans un site d'injection à l'intérieur ou au-delà de la paroi de vaisseau, mais à l'intérieur d'une partie du vaisseau où l'élément de perforation a pénétré. L'invention concerne également des méthodes de traitement d'une sténose ou d'une obstruction dans un vaisseau, ainsi que des méthodes pour créer une sténose ou une obstruction dans un vaisseau.
PCT/US1997/019993 1996-10-30 1997-10-29 Dispositif d'administration de medicament par les parois intraluminales WO1998018391A1 (fr)

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US2940196P 1996-10-30 1996-10-30
US60/029,401 1996-10-30

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WO2000000095A1 (fr) * 1998-06-29 2000-01-06 Ekos Corporation Manchon destine a etre utilise avec un element ultrasonore
EP0970717A1 (fr) * 1998-07-10 2000-01-12 Boehm, Hans-Georg, Dr. rer. nat. Appareil à main, ultrason et pulvérisateur pour les cartouches pharmaceutiques
WO2000018468A1 (fr) * 1998-09-25 2000-04-06 Ekos Corporation Procede, dispositif et necessaire pour la mise en oeuvre d'une therapie genique
WO2000038580A1 (fr) 1998-12-30 2000-07-06 Pharmasonics, Inc. Catheter ultrasonore therapeutique permettant l'administration d'une dose d'energie uniforme
EP1066070A1 (fr) * 1998-03-25 2001-01-10 Transvascular, Inc. Systemes et procedes pour la liberation de medicaments dans des endroits du corps selectionnes
EP1107702A1 (fr) * 1998-07-29 2001-06-20 Pharmasonics, Inc. Ameliorations par ultra-sons de l'injection de medicaments
US6372498B2 (en) 1997-12-31 2002-04-16 Pharmasonics, Inc. Methods, systems, and kits for intravascular nucleic acid delivery
US6428491B1 (en) 1999-08-27 2002-08-06 Dan Weiss Delivery of ultrasound to percutaneous and intrabody devices
US6575956B1 (en) 1997-12-31 2003-06-10 Pharmasonics, Inc. Methods and apparatus for uniform transcutaneous therapeutic ultrasound
US6595958B1 (en) 2000-08-08 2003-07-22 Scimed Life Systems, Inc. Tortuous path injection device and method
US6613017B1 (en) 2000-08-08 2003-09-02 Scimed Life Systems, Inc. Controlled depth injection device and method
EP1389064A2 (fr) * 2001-01-26 2004-02-18 Yoni Iger Procede et appareil permettant la delivrance de substances a des composants biologiques
US6794369B2 (en) 1997-12-31 2004-09-21 Pharmasonics Methods, systems, and kits for intravascular nucleic acid delivery
WO2004101028A2 (fr) 2003-05-13 2004-11-25 The Foundry, Inc. Procede et dispositif pour traiter l'asthme au moyen de neurotoxine
US6893421B1 (en) 2000-08-08 2005-05-17 Scimed Life Systems, Inc. Catheter shaft assembly
US7186246B2 (en) 1997-05-01 2007-03-06 Ekos Corporation Ultrasound catheter with utility lumen
US7384407B2 (en) 2001-12-03 2008-06-10 Ekos Corporation Small vessel ultrasound catheter
US8852166B1 (en) 2002-04-01 2014-10-07 Ekos Corporation Ultrasonic catheter power control
US8911439B2 (en) 2009-11-11 2014-12-16 Holaira, Inc. Non-invasive and minimally invasive denervation methods and systems for performing the same
US8932289B2 (en) 2009-10-27 2015-01-13 Holaira, Inc. Delivery devices with coolable energy emitting assemblies
US8961508B2 (en) 2008-05-09 2015-02-24 Holaira, Inc. Systems, assemblies, and methods for treating a bronchial tree
US9107590B2 (en) 2004-01-29 2015-08-18 Ekos Corporation Method and apparatus for detecting vascular conditions with a catheter
US9125643B2 (en) 2008-02-15 2015-09-08 Holaira, Inc. System and method for bronchial dilation
US9149328B2 (en) 2009-11-11 2015-10-06 Holaira, Inc. Systems, apparatuses, and methods for treating tissue and controlling stenosis
US9192566B2 (en) 2010-02-17 2015-11-24 Ekos Corporation Treatment of vascular occlusions using ultrasonic energy and microbubbles
US9398933B2 (en) 2012-12-27 2016-07-26 Holaira, Inc. Methods for improving drug efficacy including a combination of drug administration and nerve modulation
US9415242B2 (en) 2001-12-03 2016-08-16 Ekos Corporation Catheter with multiple ultrasound radiating members
US9849273B2 (en) 2009-07-03 2017-12-26 Ekos Corporation Power parameters for ultrasonic catheter
US10092742B2 (en) 2014-09-22 2018-10-09 Ekos Corporation Catheter system
US10182833B2 (en) 2007-01-08 2019-01-22 Ekos Corporation Power parameters for ultrasonic catheter
US10188410B2 (en) 2007-01-08 2019-01-29 Ekos Corporation Power parameters for ultrasonic catheter
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
US12290309B2 (en) 2022-07-18 2025-05-06 Nuvaira, Inc. Systems, apparatuses, and methods for treating tissue and controlling stenosis

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US7186246B2 (en) 1997-05-01 2007-03-06 Ekos Corporation Ultrasound catheter with utility lumen
US8690818B2 (en) 1997-05-01 2014-04-08 Ekos Corporation Ultrasound catheter for providing a therapeutic effect to a vessel of a body
US6372498B2 (en) 1997-12-31 2002-04-16 Pharmasonics, Inc. Methods, systems, and kits for intravascular nucleic acid delivery
US6575956B1 (en) 1997-12-31 2003-06-10 Pharmasonics, Inc. Methods and apparatus for uniform transcutaneous therapeutic ultrasound
US6794369B2 (en) 1997-12-31 2004-09-21 Pharmasonics Methods, systems, and kits for intravascular nucleic acid delivery
EP1066070A1 (fr) * 1998-03-25 2001-01-10 Transvascular, Inc. Systemes et procedes pour la liberation de medicaments dans des endroits du corps selectionnes
EP1066070A4 (fr) * 1998-03-25 2009-08-05 Transvascular Inc Systemes et procedes pour la liberation de medicaments dans des endroits du corps selectionnes
WO2000000095A1 (fr) * 1998-06-29 2000-01-06 Ekos Corporation Manchon destine a etre utilise avec un element ultrasonore
US7413556B2 (en) 1998-06-29 2008-08-19 Ekos Corporation Sheath for use with an ultrasound element
US6723063B1 (en) 1998-06-29 2004-04-20 Ekos Corporation Sheath for use with an ultrasound element
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EP1107702A4 (fr) * 1998-07-29 2002-10-09 Pharmasonics Inc Ameliorations par ultra-sons de l'injection de medicaments
AU754022B2 (en) * 1998-07-29 2002-10-31 Pharmasonics, Inc. Ultrasonic enhancement of drug injection
EP1107702A1 (fr) * 1998-07-29 2001-06-20 Pharmasonics, Inc. Ameliorations par ultra-sons de l'injection de medicaments
US6135976A (en) * 1998-09-25 2000-10-24 Ekos Corporation Method, device and kit for performing gene therapy
WO2000018468A1 (fr) * 1998-09-25 2000-04-06 Ekos Corporation Procede, dispositif et necessaire pour la mise en oeuvre d'une therapie genique
US6296619B1 (en) 1998-12-30 2001-10-02 Pharmasonics, Inc. Therapeutic ultrasonic catheter for delivering a uniform energy dose
WO2000038580A1 (fr) 1998-12-30 2000-07-06 Pharmasonics, Inc. Catheter ultrasonore therapeutique permettant l'administration d'une dose d'energie uniforme
US6524271B2 (en) 1998-12-30 2003-02-25 Pharmasonics, Inc. Therapeutic ultrasound catheter for delivering a uniform energy dose
US6428491B1 (en) 1999-08-27 2002-08-06 Dan Weiss Delivery of ultrasound to percutaneous and intrabody devices
US6893421B1 (en) 2000-08-08 2005-05-17 Scimed Life Systems, Inc. Catheter shaft assembly
US7044934B2 (en) 2000-08-08 2006-05-16 Boston Scientific Scimed, Inc. Tortuous path injection device
US6613017B1 (en) 2000-08-08 2003-09-02 Scimed Life Systems, Inc. Controlled depth injection device and method
US6595958B1 (en) 2000-08-08 2003-07-22 Scimed Life Systems, Inc. Tortuous path injection device and method
US7399294B2 (en) 2000-08-08 2008-07-15 Boston Scientific Scimed, Inc. Controlled depth injection device
US7625356B2 (en) 2000-08-08 2009-12-01 Boston Scientific Scimed, Inc. Tortuous path injection device
EP1389064A4 (fr) * 2001-01-26 2005-12-28 Yoni Iger Procede et appareil permettant la delivrance de substances a des composants biologiques
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US9415242B2 (en) 2001-12-03 2016-08-16 Ekos Corporation Catheter with multiple ultrasound radiating members
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US9339618B2 (en) 2003-05-13 2016-05-17 Holaira, Inc. Method and apparatus for controlling narrowing of at least one airway
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US10149714B2 (en) 2008-05-09 2018-12-11 Nuvaira, Inc. Systems, assemblies, and methods for treating a bronchial tree
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US9668809B2 (en) 2008-05-09 2017-06-06 Holaira, Inc. Systems, assemblies, and methods for treating a bronchial tree
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