EP1054633A1 - Vorrichtung und verfahren zur vorbeugung von restenose durch behandlung mittels ultraschallenergie in kombination mit medikamenten - Google Patents

Vorrichtung und verfahren zur vorbeugung von restenose durch behandlung mittels ultraschallenergie in kombination mit medikamenten

Info

Publication number
EP1054633A1
EP1054633A1 EP99904565A EP99904565A EP1054633A1 EP 1054633 A1 EP1054633 A1 EP 1054633A1 EP 99904565 A EP99904565 A EP 99904565A EP 99904565 A EP99904565 A EP 99904565A EP 1054633 A1 EP1054633 A1 EP 1054633A1
Authority
EP
European Patent Office
Prior art keywords
smc
ultrasound
cells
blood vessel
energy
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.)
Withdrawn
Application number
EP99904565A
Other languages
English (en)
French (fr)
Inventor
Uri Rosenschein
Arie Rozeszjan
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.)
Angiosonics Inc
Original Assignee
Angiosonics 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 Angiosonics Inc filed Critical Angiosonics Inc
Publication of EP1054633A1 publication Critical patent/EP1054633A1/de
Withdrawn legal-status Critical Current

Links

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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • 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
    • A61B2017/22005—Effects, e.g. on tissue
    • A61B2017/22007—Cavitation or pseudocavitation, i.e. creation of gas bubbles generating a secondary shock wave when collapsing
    • A61B2017/22008—Cavitation or pseudocavitation, i.e. creation of gas bubbles generating a secondary shock wave when collapsing used or promoted
    • 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
    • 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
    • A61B2017/22088—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 ultrasound absorbing, drug activated by ultrasound

Definitions

  • SMC obtained from confluent cultures were well suspended (2.5x1 O ⁇ mL), sonicated and seeded in flat-bottomed, 96 microwell plate (0.2 ml/well) in DMEM- 10% CS and cultured at 37 °C in a humidified atmosphere of 10% CS in air for 48 hours.
  • the culture medium was replaced by DMEM-0.5% CS for 48 hours and the SMC synchronized to the quiescent state.
  • ⁇ H-thymidine Nuclear Research Center, Negev, Israel
  • the 3H-thymidine was not significantly different whether the SMC were sonicated before initiation of culture with 10% CS or before the starvation step with 0.5% CS.
  • the data regarding DNA biosynthesis of SMC, as reflected by radioactive thymidine inco ⁇ oration, indicate that the proliferative capacity of these cells was not significantly affected by sonication, whether the cells were stimulated or not.
  • Radiolabeled IP samples after fractionation were analyzed (10 ml scintillation liquid/vial: Quicksafe A, Zinsser, Germany) in a liquid scintillation analyzer (1600 TR, Packard, CT), and the separation of inositol mono (IP j ), di (IP 2 ) and tri (IP 3 ) phosphates verified using standards of tritiated inositol phosphates.
  • IP j inositol mono
  • IP 2 di
  • IP 3 tri phosphates
  • Bradykinin-stimulated and non-stimulated SMC were studied. Bradykinin-stimulation was expressed as fold stimulation: the ratio of the mean CPM of stimulated SMC to the mean of non-stimulated cells. Non-sonicated SMC served as controls.
  • SMC were cultured in 24-well culture dishes and sonication performed before full confluence of the cultures. Ten minutes after sonication, the cultures were washed gently with PBS, fixed in situ with 2.5% glutaraldehyde and 2% paraformaldehyde in PBS for 2 hours at 4°C. The fixed cells were washed in PBS, post-fixed with 1% osmium tetroxide in 0.1 mole/L cacodylate buffer (pH 7.3) and dehydrated through a graded ethanol series. Cells were dried with liquid CO 2 at the critical point, coated with gold by sputtering in a vacuum evaporator. The mo ⁇ hology of two hundred cells was studied by scanning electron microscope (Jeol SEM 840, Tokyo, Japan).
  • the frequency level of ultrasound energy used is typically 20 kHz in vitro, in vivo and in human peripheral arterial studies, and 20-45 kHz in coronary artery studies.
  • the device can be made compatible with ultrasound imaging systems by the addition of a dedicated therapeutic ultrasound probe.
  • the combined system can serve as both an imaging probe and a treatment probe, thereby transmitting the required treatment energy to the selected target under ultrasound imaging.
  • a software package can add the capability to support the visualization of the target, and the activation of the therapeutic energy transmission at the target.
  • a system for the prevention of restenosis in a blood vessel of a mammal following angioplasty in accordance with the present invention may typically include a therapeutic ultrasound probe, preferably containing therapeutic and imaging capabilities.
  • the therapeutic ultrasound element can be based on any method for focusing ultrasound (e.g., geometric, annular array, phase array).
  • the system will typically also include a control unit for controlling the ultrasonic energy output, which may preferably include a monitor, similar to regular imaging monitors, and more preferably, along with the software and hardware, suitable for operating the combined imaging and therapeutic transducer.
  • An ultrasound thrombolysis device used was a 140 cm long solid aluminum alloy probe, ensheathed in a plastic catheter and connected at its proximal end to a piezoelectric transducer available from Angiosonics Inc., Morrisville, North Carolina. Ultrasonic energy is transmitted from the transducer as longitudinal vibrations of the probe which directs the energy into the arterial system.
  • the last 18 cm of the device is a three-wire flexible segment with a 1.6 mm tip designed to optimize the thrombolytic effect of the ultrasound energy by promoting cavitation.
  • the three wire flexible segment permits the use of a solid metal transmitter for optimal ultrasound transmission, while remaining flexible.
  • Power output at the handpiece was controlled by an integrated computer designed to ensure constant output at the distal tip under variable loading conditions encountered during the procedure, and was set at about 18 watts.
  • IVUS intravascular ultrasound
  • SMC Smooth muscle cells
  • the sonicator consists of a resonant 90 mm long, 2 mm diameter, vertically suspended, thin titanium probe, which resonated at a frequency of 20 kHz and variable power levels. To prevent aerosol formation during sonication, the depth of immersion of the probe was adjusted so that the meniscus of the liquid came in contact with the ultrasonic wire at a displacement node.
  • the cells were washed three times with DMEM. Sonication on cytochalasin B treated cells or non-treated was followed as described in the above sonication protocol. The sonicated SMC number was adjusted to 10 6 viable cells/ml in DMEM-0.5%CS. In the migration assay, the bottom wells contained DMEM supplemented with 10% CS, which acted as chemoattractant. The SMC samples, treated or non-treated, 50 ⁇ L, were placed in the upper wells of the chamber. A 5 ⁇ m pore size polyvinyl pyrrolidone-free polycarbonate filter membrane (Neuro Probe, Inc.) was placed above the lower wells.
  • the chamber was assembled and incubated at 37°C in a humidified atmosphere of 10% CO 2 in air for 90 min.
  • the filter was then removed and the SMC that had migrated through the filter membrane were stained with MayGmnwald Giemsa (Sigma, St. Louis, MO).
  • the filter was then mounted on a glass slide. Cells that had migrated across the filter were counted using a light microscope with a micrometered eye piece (Carl Zeiss, Oberkochen, Germany) and a magnification of 320X.
  • the migration capacity was expressed as the average number of migrating SMC/field, counted in 9 fields, in triplicate wells. Nonsonicated SMC served as controls. As shown in Fig. 10, the combination of sonication and cytochalasin B leads to a very significant reduction in cell migration capability in comparison to those obtained by ultrasound or cytochalasin B alone.

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • Surgery (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Hematology (AREA)
  • Cardiology (AREA)
  • Anesthesiology (AREA)
  • Mechanical Engineering (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Vascular Medicine (AREA)
  • Dermatology (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Media Introduction/Drainage Providing Device (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
EP99904565A 1998-02-10 1999-02-03 Vorrichtung und verfahren zur vorbeugung von restenose durch behandlung mittels ultraschallenergie in kombination mit medikamenten Withdrawn EP1054633A1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US21162 1987-03-03
US2116298A 1998-02-10 1998-02-10
PCT/US1999/002332 WO1999039647A1 (en) 1998-02-10 1999-02-03 Apparatus and method for inhibiting restenosis by applying ultrasound energy together with drugs

Publications (1)

Publication Number Publication Date
EP1054633A1 true EP1054633A1 (de) 2000-11-29

Family

ID=21802701

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99904565A Withdrawn EP1054633A1 (de) 1998-02-10 1999-02-03 Vorrichtung und verfahren zur vorbeugung von restenose durch behandlung mittels ultraschallenergie in kombination mit medikamenten

Country Status (7)

Country Link
EP (1) EP1054633A1 (de)
JP (1) JP2002502804A (de)
AR (1) AR014555A1 (de)
AU (1) AU2494199A (de)
CA (1) CA2320300A1 (de)
WO (1) WO1999039647A1 (de)
ZA (1) ZA991024B (de)

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US6582392B1 (en) 1998-05-01 2003-06-24 Ekos Corporation Ultrasound assembly for use with a catheter
US20040097996A1 (en) 1999-10-05 2004-05-20 Omnisonics Medical Technologies, Inc. Apparatus and method of removing occlusions using an ultrasonic medical device operating in a transverse mode
US6524251B2 (en) 1999-10-05 2003-02-25 Omnisonics Medical Technologies, Inc. Ultrasonic device for tissue ablation and sheath for use therewith
US6551337B1 (en) 1999-10-05 2003-04-22 Omnisonics Medical Technologies, Inc. Ultrasonic medical device operating in a transverse mode
AU2002359576A1 (en) 2001-12-03 2003-06-17 Ekos Corporation Catheter with multiple ultrasound radiating members
US8226629B1 (en) 2002-04-01 2012-07-24 Ekos Corporation Ultrasonic catheter power control
CA2535981C (en) * 2003-09-08 2014-10-28 Board Of Trustees Of The University Of Arkansas Ultrasound apparatus and method for augmented clot lysis
CA2553165A1 (en) 2004-01-29 2005-08-11 Ekos Corporation Method and apparatus for detecting vascular conditions with a catheter
US7794414B2 (en) 2004-02-09 2010-09-14 Emigrant Bank, N.A. Apparatus and method for an ultrasonic medical device operating in torsional and transverse modes
EP2015846A2 (de) 2006-04-24 2009-01-21 Ekos Corporation Ultraschalltherapiesystem
PL2111261T3 (pl) 2007-01-08 2015-08-31 Ekos Corp Parametry mocy cewnika ultradźwiękowego
US10182833B2 (en) 2007-01-08 2019-01-22 Ekos Corporation Power parameters for ultrasonic catheter
WO2009002881A1 (en) 2007-06-22 2008-12-31 Ekos Corporation Method and apparatus for treatment of intracranial hemorrhages
ES2503140T3 (es) 2009-07-03 2014-10-06 Ekos Corporation Parámetros de potencia para catéter ultrasónico
US8740835B2 (en) 2010-02-17 2014-06-03 Ekos Corporation Treatment of vascular occlusions using ultrasonic energy and microbubbles
EP2608730B1 (de) 2010-08-27 2019-07-24 Ekos Corporation Vorrichtung zur behandlung intrakranialer blutungen
US11458290B2 (en) 2011-05-11 2022-10-04 Ekos Corporation Ultrasound system
BR112015022067A2 (pt) 2013-03-14 2017-07-18 Ekos Corp método e aparato para a administração de droga a um sítio alvo
US10092742B2 (en) 2014-09-22 2018-10-09 Ekos Corporation Catheter system
EP3307388B1 (de) 2015-06-10 2022-06-22 Ekos Corporation Ultraschallkatheter
CN110214015A (zh) 2017-01-24 2019-09-06 Ekos公司 用于治疗血栓栓塞的方法

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US4474180A (en) 1982-05-13 1984-10-02 The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration Apparatus for disintegrating kidney stones
US4870953A (en) 1987-11-13 1989-10-03 Donmicheal T Anthony Intravascular ultrasonic catheter/probe and method for treating intravascular blockage
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Also Published As

Publication number Publication date
JP2002502804A (ja) 2002-01-29
AU2494199A (en) 1999-08-23
CA2320300A1 (en) 1999-08-12
WO1999039647A1 (en) 1999-08-12
ZA991024B (en) 2000-01-14
AR014555A1 (es) 2001-02-28

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