WO2002076547A1 - Ultrasonic catheter drug delivery method and device - Google Patents

Ultrasonic catheter drug delivery method and device Download PDF

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Publication number
WO2002076547A1
WO2002076547A1 PCT/US2002/008503 US0208503W WO02076547A1 WO 2002076547 A1 WO2002076547 A1 WO 2002076547A1 US 0208503 W US0208503 W US 0208503W WO 02076547 A1 WO02076547 A1 WO 02076547A1
Authority
WO
WIPO (PCT)
Prior art keywords
catheter
transducer
catheter system
distal
ultrasound
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/US2002/008503
Other languages
English (en)
French (fr)
Inventor
Eilaz Babaev
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.)
Celleration Inc
Original Assignee
Celleration 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 Celleration Inc filed Critical Celleration Inc
Priority to DE60228058T priority Critical patent/DE60228058D1/de
Priority to JP2002575056A priority patent/JP2004528889A/ja
Priority to EP02717674A priority patent/EP1370321B1/en
Priority to CA002448808A priority patent/CA2448808C/en
Publication of WO2002076547A1 publication Critical patent/WO2002076547A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • 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
    • A61B17/00—Surgical instruments, devices or methods
    • A61B17/32—Surgical cutting instruments
    • A61B17/3203—Fluid jet cutting instruments
    • A61B17/32037—Fluid jet cutting instruments for removing obstructions from inner organs or blood vessels, e.g. for atherectomy
    • 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
    • A61B2017/22014—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 the ultrasound transducer being outside patient's body; with an ultrasound transmission member; with a wave guide; with a vibrated guide wire
    • 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
    • A61B2017/22014—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 the ultrasound transducer being outside patient's body; with an ultrasound transmission member; with a wave guide; with a vibrated guide wire
    • A61B2017/22015—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 the ultrasound transducer being outside patient's body; with an ultrasound transmission member; with a wave guide; with a vibrated guide wire with details of the transmission member
    • 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
    • A61B2017/22082—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 after introduction of a substance
    • A61B2017/22084—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 after introduction of a substance stone- or thrombus-dissolving
    • 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
    • A61B17/225—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 for extracorporeal shock wave lithotripsy [ESWL], e.g. by using ultrasonic waves
    • A61B17/2251—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 for extracorporeal shock wave lithotripsy [ESWL], e.g. by using ultrasonic waves characterised by coupling elements between the apparatus, e.g. shock wave apparatus or locating means, and the patient, e.g. details of bags, pressure control of bag on patient
    • A61B2017/2253—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 for extracorporeal shock wave lithotripsy [ESWL], e.g. by using ultrasonic waves characterised by coupling elements between the apparatus, e.g. shock wave apparatus or locating means, and the patient, e.g. details of bags, pressure control of bag on patient using a coupling gel or liquid

Definitions

  • the present invention generally relates to medical devices and methods. More particularly, the present invention relates to apparatus and methods for the ultrasonically enhanced delivery of therapeutic or contrast agents within the vascular and lung areas or other corporeal lumens.
  • vascular and lung diseases as well as arterial thrombosis (blood clots in arteries), remain frequent, costly and serious problems in health care.
  • Current methods of treatment such as drugs, interventional devices, and/or bypass surgery are usually expensive and not always effective, even sometimes causing additional problems.
  • drugs can also dissolve beneficial clots or interventional devices can injure healthy tissue to cause potentially fatal bleeding complications or to form scarring or cellular growth which may itself eventually become a serious obstruction in, for example, a blood vessel (a process known as restenosis).
  • Ultrasonic energy has been used for enhancing the intra vascular delivery of drug, to dissolve clot acoustically, disrupt mechanically and inhibit restenosis.
  • Such energy can be delivered intravascularly using specialized catheters having ultrasonically vibrating surface at or near their distal ends.
  • One type of ultrasonic catheter delivery system uses a wire or other axial transmission element to deliver energy from an ultrasonic energy source, located outside the patient to the internal organs, to desired corporeal lumens. (See, for example, U.S. Patents Nos. 5,002,059, 5,324,255, 5,345,940, and 5,699,805, each of which is incorporated herein by reference.)
  • Such catheters are rigid and cannot be easily inserted through narrow and tortuous vessels and may cause serious damage to vascular walls.
  • a second type of catheter has ultrasonic transducers mounted directly on their distal ends. See, for example; U.S. Patents Nos. 5,362,309, 5,318,014, 5,315,998, 5,269,291, 5, 197,946, 6,001069, and 6,024,718, each of which is incorporated herein by reference.
  • these catheters suffer from limited ultrasound energy, and the transducer-catheter design is still problematic.
  • Another type of catheter has an ultrasonic transducer or ultrasound transmission element with a central orifice in the distal end to impart ultrasonic energy into liquid and simultaneously deliver it to a corporeal lumen. See, for example, U.S. Patents Nos. 5,735,811 and 5,197,946, each of which is incorporated herein by reference. Although these catheters are more effective and liquid delivery is more convenient, there are design difficulties and limitation of ultrasound energy from longitudinal waves.
  • a gas for example, saline with oxygen
  • the present invention relates to apparatus and method for the ultrasonically enhanced delivery of therapeutic or contrast agents within the vascular and lung area or other desired corporeal lumens.
  • Ultrasonic waves are applied to a vascular area, lung or any corporeal lumen without requiring direct contact between ultrasound transducer tip and the patient's body, particularly to dissolve blood clots.
  • a catheter system comprises an ultrasound transducer having a distal tip with a radial surface and a distal end surface.
  • the ultrasound transducer is disposed in a chamber at the proximal end of the catheter, and the transducer radiation surface or tip directs ultrasound waves or energy forward into the catheter coaxially via liquid; Longitudinal ultrasound waves induce wave motion in fluid adjacent to the transducer distal end.
  • the catheter system of the present invention is also useful for the delivery of ultrasonic energy to a desired location.
  • the transducer radiation surface or transducer tip may be cylindrical, flat, concave, convex, irregular or have a different shape-geometry to radiate ultrasound energy into catheter.
  • the catheter of the present invention may comprise a proximal tubing for delivering therapeutic agent from a reservoir by pump or syringe.
  • the tubing may be located in front of or behind the radiation surface.
  • an ultrasound transducer and tip are mounted in a proximal portion of a catheter body, located outside of the body of a patient.
  • the remainder of the catheter distal to the proximal portion may be inserted into a blood vessel or attached to a body lumen, to drive a therapeutic agent ultrasonically and/or deliver ultrasonic energy.
  • the catheter system comprises a catheter body, mechanically coupled with an ultrasound transducer through a housing or tip node, which is where the transducer body is outside the catheter.
  • the catheter body can be provided with two or more tubing inlets (sleeves) for different therapeutic agents, even one or more different gases such as oxygen, and agents to be mixed and delivered ultrasonically.
  • the catheter system of the invention is particularly advantageous on tissues for which local topical application of a therapeutic agent is desirable but contact with the tissue is to be avoided. Furthermore, ultrasound waves used in the method energize the drug, dissolve the clots and cause the penetration of the drug within the narrow and blocked vessels.
  • FIG. 1 is a perspective, partly cross-sectional view of an ultrasonic catheter drug delivery system for use according to the present invention
  • FIG. 2 is a lateral view of an ultrasonic catheter system chamber of the invention with two horizontally located sleeves;
  • FIG. 3 is a frontal view of an ultrasonic catheter system chamber of the invention with three peripherally located sleeves;
  • FIG. 4 is a lateral, cross-sectional view of a catheter system chamber, mechanically coupled with an ultrasound transducer through the tip;
  • FIG. 5 is a lateral, cross-sectional view of an ultrasonic catheter drug delivery system for delivering therapeutic agent to the catheter body or chamber through a central orifice of the ultrasonic tip.
  • the present invention is a method and device, which provides treatment of luminal conditions, particularly for the treatment of coronary and peripheral arterial disease and thrombosis, where the purpose is to dissolve or disrupt the clot, plague or other stenotic lesions which cause the disease, and for dilation of narrowed vessels.
  • the method and device of the present invention also useful to enhance the administration of therapeutic agents primarily responsible for the disruption of the clots or other stenotic material.
  • the ultrasonic energy agitates and promotes the penetration of the drug into the stenotic material.
  • this method and device of the present invention are further useful for treatment of other body lumens, such as the urethra, ureter, fallopian tubes, or urological disorders related with prostate gland (BPH - Benigh Proctatic Hyperplasia), and can be used for impotency (erectile dysfunction) treatment by ultrasonically stimulating sexual organs, urinary tract, and the like.
  • other body lumens such as the urethra, ureter, fallopian tubes, or urological disorders related with prostate gland (BPH - Benigh Proctatic Hyperplasia)
  • impotency erectile dysfunction
  • the present invention can be used for targeted and localized drug delivery for treatment of lung, vasculature, vasopasm and tumor treatment.
  • this invention is very useful for the treatment of closed wounds as a fistulas, canals, etc., by destroying bacteria cells and stimulating healthy tissue cells.
  • FIG. 1 is a perspective view of ultrasound catheter drug delivery system 2, comprising an ultrasound generator 4, a connector 6 operatively connecting ultrasound generator 4 with a transducer 8, a housing 10 surrounding transducer 8, and a catheter 12 having a proximal portion 14 with a chamber 16 containing a therapeutic agent 18.
  • Transducer 8 has a tip 20 with a radial surface 22 and a distal radiation surface 24.
  • Chamber 16 is in fluid communication through tubing 26 with a fluid source 28, and directly with at least one lumen 30 of the distal portion 32 of catheter 12 that extends to catheter distal end 34.
  • Fluid source 28 can be, for example, a reservoir with a pressure pump or syringe.
  • proximal section 36 of catheter proximal portion 14 sealingly engages housing 10.
  • inner surface 38 of proximal section 3 has threads 40 that engage reciprocal threads 42 on the outer surface 44 of housing 10. This arrangement will allow the operator to vary the distance between distal radiation surface 24 and the distal end 46 of chamber 16 to regulate ultrasonic pressure and energy level.
  • radial surface 22 can be smooth or substantially smooth, it is preferred that this surface is not smooth, for example, with rings, threads, barbs, or the like, which will create more ultrasonic pressure in catheter 12.
  • ultrasonic energy at a preselected frequency is sent through the catheter 10 with fluid such as a therapeutic agent as a transmission member.
  • Ultrasound energy will pass through therapeutic agent 18 to catheter distal end 34.
  • Catheter 12 may be formed from a conventional rigid or flexible material, dependent upon the application. It would be appropriate for catheter 12 to be flexible if the catheter is to be inserted into tortuous vascularity or if catheter distal end 34 is to be attached to a vessel, fistula, or the like.
  • transducer 50 is fixedly, optionally removably, attached to the proximal section 52 of the proximal portion 54 of a catheter 56.
  • Transducer 50 has a tip 58 with a radial surface 60 and a distal radiation surface 62.
  • Catheter proximal portion 54 has a chamber 64 with a therapeutic agent 66 that is in fluid communication with each of two fluid sources 68,70 through lumens 72,74, respectively.
  • Fluid sources 68,70 may provide two or more fluids, e.g., liquid or gas, such as saline or oxygen, to be ultrasonically mixed and delivered through lumen 76 to catheter distal end 78.
  • Fig. 3 is a semi-cross-sectional view of the proximal end of a catheter according to the invention wherein three fluid sources 80 are each in fluid communication through a lumen 82 with chamber 84 of catheter proximal section 86.
  • the distal radiation surface 88 of a transducer (not shown) is positioned within chamber 84.
  • a connector 110 operatively connects an ultrasound generator (not shown) with a transducer 112, which has a tip 114 with a radial surface 116 and a distal end surface 118.
  • a catheter 120 has a proximal portion 122 with a chamber 124 containing a therapeutic agent 126. Chamber 124 is in fluid communication through tubing 130 with a fluid source 132, and directly with at least one lumen 134 of the distal portion 136 of catheter 120 that extends to catheter distal end 140.
  • Fluid source 132 can be, for example, a reservoir with a pressure pump or syringe.
  • the proximal section 142 of catheter proximal portion 122 sealingly engages radial surface 116.
  • Chamber 124 must be attached to ultrasonic transducer distal tip 114 at the mechanical resonant node, such as node 144. If chamber 124 is not connected to the resonant node (either a little before or a little after the mechanical node), the intensity of the ultrasound energy at distal end 140 will be attenuated, i.e., damped, and ultrasound waves and/or energy will be transferred to the walls of chamber 126, possibly damaging the chamber 126 structure assembly, which may cause leakage.
  • a connector 150 operatively connects an ultrasound generator (not shown) with a transducer 152, which has a distal tip 154 with a radial surface 156 and a distal end surface 158.
  • a catheter 160 has a proximal portion 162 with a chamber 164 containing a therapeutic agent 166.
  • Transducer distal tip 154 has a central orifice 170.
  • Chamber 164 is in fluid communication with at least one fluid source 172 through central orifice 170, which can be smooth, waved, ringed, slotted, grooved, or threaded, and infusion lumen 174 within tubing 176. Two or more fluid sources 172 and infusion lumens 174 can mix and deliver different therapeutic agents.
  • Chamber 164 is also in fluid communication with lumen 180 in the distal portion 182 of catheter 160 that extends to distal end 184.
  • the non-smooth surface of orifice 170 such as rings or threads, increases the pressure of liquid in chamber 164.
  • Chamber 164 should be attached to ultrasonic transducer distal tip 158 at a mechanical resonant node, such as node 190. Similarly, each lumen 174 should intersect central orifice 170 at a resonant node, such as node 192.
  • the catheter systems herein are comprised of conventional materials.
  • the transducer and catheter chamber are preferably comprised of suitable metallic or even polymeric substances.
  • Most preferably the transducer distal tip is comprised of a metal such as titanium or nitinol.
  • the invention here can deliver one or more liquid or gaseous substances to a catheter distal end.
  • Such substances include, but are not limited to, therapeutic agents such as antibiotics or antiseptics, saline, oil, water, oxygen, anticoagulants such as heparin or cumadine, or even liquid medical polymers, or mixtures of two or more thereof.
  • the distal radiation surface is driven with a constant, modulated or pulsed frequency. It is also provided that the distal radiation surface is driven with a sinusoidal, rectangular, trapezoidal or triangular wave form. It is further provided that the transducer is capable of being operated at a frequency from 10 kHz to 10,000 MHz.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Surgery (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Vascular Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Dermatology (AREA)
  • Anesthesiology (AREA)
  • Hematology (AREA)
  • Media Introduction/Drainage Providing Device (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Ultra Sonic Daignosis Equipment (AREA)
PCT/US2002/008503 2001-03-21 2002-03-21 Ultrasonic catheter drug delivery method and device Ceased WO2002076547A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
DE60228058T DE60228058D1 (de) 2001-03-21 2002-03-21 Vorrichtung zur arzneistoffabgabe mit einem ultraschallkatheter
JP2002575056A JP2004528889A (ja) 2001-03-21 2002-03-21 超音波カテーテル薬剤移送方法及び装置
EP02717674A EP1370321B1 (en) 2001-03-21 2002-03-21 Ultrasonic catheter drug delivery device
CA002448808A CA2448808C (en) 2001-03-21 2002-03-21 Ultrasonic catheter drug delivery method and device

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US09/813,577 2001-03-21
US09/813,577 US6623444B2 (en) 2001-03-21 2001-03-21 Ultrasonic catheter drug delivery method and device

Publications (1)

Publication Number Publication Date
WO2002076547A1 true WO2002076547A1 (en) 2002-10-03

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PCT/US2002/008503 Ceased WO2002076547A1 (en) 2001-03-21 2002-03-21 Ultrasonic catheter drug delivery method and device

Country Status (8)

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US (2) US6623444B2 (cg-RX-API-DMAC10.html)
EP (1) EP1370321B1 (cg-RX-API-DMAC10.html)
JP (1) JP2004528889A (cg-RX-API-DMAC10.html)
AT (1) ATE403464T1 (cg-RX-API-DMAC10.html)
CA (1) CA2448808C (cg-RX-API-DMAC10.html)
DE (1) DE60228058D1 (cg-RX-API-DMAC10.html)
ES (1) ES2307740T3 (cg-RX-API-DMAC10.html)
WO (1) WO2002076547A1 (cg-RX-API-DMAC10.html)

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US7846341B2 (en) 2006-12-04 2010-12-07 Bacoustics, Llc Method of ultrasonically treating a continuous flow of fluid
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US8016208B2 (en) 2008-02-08 2011-09-13 Bacoustics, Llc Echoing ultrasound atomization and mixing system
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US9067015B2 (en) 2007-12-21 2015-06-30 Carticept Medical, Inc. System for injecting fluids in a subject
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DE60228058D1 (de) 2008-09-18
US20020138036A1 (en) 2002-09-26
EP1370321B1 (en) 2008-08-06
EP1370321A1 (en) 2003-12-17
US20030229304A1 (en) 2003-12-11
CA2448808A1 (en) 2002-10-03
US6623444B2 (en) 2003-09-23
ES2307740T3 (es) 2008-12-01
ATE403464T1 (de) 2008-08-15
US6723064B2 (en) 2004-04-20
CA2448808C (en) 2008-12-09
JP2004528889A (ja) 2004-09-24

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