WO1994005369A1 - Circuit et formes d'ondes electriques pour ionophorese interne - Google Patents

Circuit et formes d'ondes electriques pour ionophorese interne Download PDF

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Publication number
WO1994005369A1
WO1994005369A1 PCT/US1992/010850 US9210850W WO9405369A1 WO 1994005369 A1 WO1994005369 A1 WO 1994005369A1 US 9210850 W US9210850 W US 9210850W WO 9405369 A1 WO9405369 A1 WO 9405369A1
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WO
WIPO (PCT)
Prior art keywords
drug
drug delivery
electric current
catheter
wave
Prior art date
Application number
PCT/US1992/010850
Other languages
English (en)
Inventor
James E. Shapland
Keith R. Hildebrandt
Mark B. Knudson
Original Assignee
Cortrak Medical, 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
Priority claimed from US07/937,464 external-priority patent/US5286254A/en
Application filed by Cortrak Medical, Inc. filed Critical Cortrak Medical, Inc.
Priority to AU33217/93A priority Critical patent/AU3321793A/en
Publication of WO1994005369A1 publication Critical patent/WO1994005369A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/20—Applying electric currents by contact electrodes continuous direct currents
    • A61N1/30—Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
    • A61N1/303—Constructional details
    • A61N1/306—Arrangements where at least part of the apparatus is introduced into the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/325—Applying electric currents by contact electrodes alternating or intermittent currents for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/056—Transvascular endocardial electrode systems
    • A61N2001/0585—Coronary sinus electrodes

Definitions

  • the present invention relates generally to a drug delivery apparatus and method for selectively and locally delivering a drug to internal body tissue. More specifically, the present invention relates to an apparatus and method for providing a net flow of electrical current in a desired direction for iontophoresis in conjunction with a catheter to selectively and locally deliver a drug to internal body tissue.
  • PTCA percutaneous transluminal coronary angioplasty
  • catheters are inserted into the cardiovascular system under local anesthesia and an expandable balloon portion is then inflated to compress the atherosclerosis and dilate the lumen of the artery.
  • high restenosis rates (reported to be as high as 47%) continue to be a major problem.
  • Various techniques have been tried to treat stenosed vessels including the use of lasers, application of heat and the use of intravascular stents. However, many of these are still under investigation with mixed results, while others have generally not been successful.
  • the ability to administer a drug locally to the dilated portion of the artery in PTCA procedures, without significantly affecting other tissues, would greatly enhance the ability to address the restenosis proble .
  • a second example of specific application for a local drug delivery system for delivering a drug to an internal body tissue is in the treatment of cancerous tumors or the like.
  • an objective is to administer the drug so that it localizes, as much as possible, in the tumor itself.
  • Such drugs are commonly administered systemically through the blood stream.
  • Various means are then utilized for causing the drug to localize in the cancer tumor. Nevertheless, significant portions of the drug still circulate through the blood stream, thereby affecting noncancerous tissue, producing undesirable side effects, and limiting the dosages of the drug which can be safely administered.
  • electrophoresis iontophoresis
  • alternating current to accomplish drug delivery through iontophoresis is, however, not very effective.
  • a sinusoidal alternating current has increasing and decreasing current, to the point where flow can stop or actually reverse direction, thereby hampering the drug delivery effect.
  • the disclosed preferred 80-100 msec pulses will not prevent vascular muscle stimulation resulting in vaso- constriction and may cause other unwanted stimulation or sensations. Accordingly, there is a need in the art for a method and apparatus for delivering a drug selectively and locally to internal body tissue using iontophoresis in conjunction with a catheter, without significantly affecting other tissue or inducing cardiac arrhythmias or other unwanted effects.
  • an apparatus and method for delivering a drug or combination of drugs selectively and locally to internal body tissue using iontophoresis in conjunction with a catheter, without inducing cardiac arrhythmias or other unwanted effects. More specifically, the invention involves an apparatus and method for iontophoretically delivering a drug or combination of drugs substantially transversely to a body passageway such as blood vessel, urinary tract, intestinal tract, kidney ducts, etc., to treat a localized region of the passageway itself and/or tissue located adjacent to the passageway. Also contemplated is delivery of a drug or combination of drugs directly to internal body tissue using the apparatus of the present invention.
  • the apparatus includes a flexible member adapted for insertion into the body passageway or tissue and a drug delivery means connected with the flexible member for delivering the drug to or through a local area of the passageway wall or tissue.
  • the drug delivery means includes a drug transport wall for engagement with a local area of the passageway wall or tissue and a drug chamber for receiving a selected drug.
  • the chamber is defined in part by the drug transport wall which is constructed of a material that permits selective transport of a drug therethrough, i.e. constructed of at least perforated, permeable, microporous or semipermeable material through which the drug is intended to selectively pass, that is, selectively permeable.
  • the apparatus and method of the present invention includes iontophoresis means connected to the drug delivery means to provide waveforms which iontophoretically transport drugs or other medicaments across the selectively permeable membrane.
  • the preferred waveforms can include, among others, square waves, rectangular waves, saw-toothed waves, sinusoidal waves which do not reverse polarity, and rectified sinusoidal waves. Also contemplated are modified rectangular waveforms which reverse polarity, but offer a net current flow in a desired direction. Regardless of the specific waveform chosen, the preferred frequency of the waves is 200 Hz-100 kHz, most preferably 5-15 kHz.
  • the iontophoresis means of the present invention overcomes the disadvantages associated with known internal iontophoretic delivery methods and apparatus.
  • the high frequency waveforms of the present invention maximize iontophoretic delivery in conjunction with a catheter while minimizing the negative side effects associated with iontophoresis.
  • Those side effects include cardiac arrhythmias, muscle stimulation or other unwanted side effects.
  • FIG. 1 is a fragmentary view, partially in section, of a first embodiment of the drug delivery apparatus of the type employing the present invention in the form of a catheter with a modified dilatation balloon in its deflated state.
  • Figure 2 is a fragmentary view, partially in section, of the drug delivery apparatus of the present invention positioned in a blood vessel depicting iontophoresis means to transport the drug across the balloon surface.
  • Figure 3 is a fragmentary view, partially in section, of a further embodiment of the drug delivery apparatus of the present invention positioned in a blood vessel.
  • Figure 4 is a fragmentary view, partially in section, of the drug delivery apparatus of the present invention positioned in a blood vessel, embodying iontophoresis to transport a drug across the balloon surface where the solution containing the drug is circulated through the balloon.
  • Figure 5 is a fragmentary view, partially in section, of a still further alternate design of a drug delivery apparatus in accordance with the present invention in the form of a catheter with a drug delivery component to transport a drug to an internal body tissue.
  • Figure 6 is a fragmentary view, partially in section, of a still further alternate design of the drug delivery apparatus for drug transport to an internal body tissue in which a selectively permeable membrane forms a portion of the outer wall of the drug delivery component.
  • Figures 7A-7F depict a variety electric waveforms for use in iontophoresis with the catheters of the present invention.
  • Figures 8A & 8B depict two rectangular electric waveforms for use in iontophoresis with the catheters of the present invention.
  • Figure 9 depicts a block diagram of the preferred circuit used to supply the electric waveforms for use in iontophoresis with the catheters of the present invention.
  • Figures 1-6 illustrate the preferred and various alternate designs of the drug delivery apparatus in accordance with the present invention.
  • this apparatus provides a means and a system for delivering a drug or combination of drugs to, or through, a localized area of a passageway in order to treat the localized area of the passageway or to treat a localized area of tissue located adjacent to the passageway, with minimal, if any, undesirable effect on other body tissue.
  • the drug delivery apparatus includes a modified catheter balloon design which can be used in conjunction with existing catheters.
  • catheter as used in the present application is intended to broadly include any medical device designed for insertion into a body passageway to permit injection or withdrawal of fluids, to keep a passage open or for any other purpose. It is contemplated that the drug delivery apparatus of the present invention has applicability for use with any body passageways including, among others, blood vessels, urinary tract, intestinal tract, kidney ducts, wind pipe and the like.
  • FIGS. 5 and 6 illustrate further alternate designs of the drug delivery apparatus in accordance with the present invention.
  • the embodiments shown in these figures are specifically designed to provide means and a system for delivering a drug or combination of drugs to a localized area of an internal body tissue.
  • the apparatus includes a flexible catheter connected to a drug delivery component having a fluid delivery passageway with an outer wall and selectively permeable outer membrane portion through which a drug passes to an internal body tissue target area.
  • catheters are commonly used in percutaneous transluminal coronary angioplasty (PTCA) procedures to dilate stenosed blood vessels or arteries. These include so-called over the wire catheters of the type illustrated generally in U.S. Patent No.
  • PTCA percutaneous transluminal coronary angioplasty
  • Figure 1 illustrates the distal end of a catheter with the modified catheter balloon in its deflated state.
  • the catheter includes a guide wire 10, an elongated, flexible catheter body 11, a drug delivery means in the form of a balloon 12 positioned on the catheter body 11 near its distal end and a balloon lumen or passageway 14 extending along the catheter body 11 to the proximal end of the body 11 for inflation and deflation of the balloon 12.
  • the material from which the balloon 12 is constructed is a permeable or semipermeable material which is effective to permit transport or passage of the fixative or other drug across the balloon surface as a result of iontophoresis according to the present invention.
  • the structure of the guide wire 10, the catheter body 11 and the balloon lumen 14 is similar to conventional catheter design which is known in the art and an example of which is shown in U.S. Patent No. 4,323,071.
  • the balloon 12 of Figure 1 is distinguishable from conventional catheter balloons in that the balloon 12 is constructed from a material which selectively permits the transport or passage of a drug or fixative across the balloon surface.
  • the balloon 12 is inflated by introducing a fixation or other drug solution through the balloon lumen 14 and into the interior of the balloon portion 12.
  • Iontophoresis technology is known in the art and is commonly used in transdermal drug delivery. In general, iontophoresis technology uses an electrical potential or current across a semipermeable barrier to drive ionic fixatives or drugs or drag nonionic fixatives or drugs in an ionic solution. Iontophoresis can be useful in certain applications of the present invention because it facilitates both transport of the fixative or drug across the selectively permeable membrane and enhances tissue penetration. In the application of iontophoresis, two electrodes, one on each side of the barrier, are utilized to develop the required potential or current flow. In particular, one electrode may be located inside of the catheter in opposed relation to the drug delivery wall of the catheter while the other electrode may be located at a remote site on a patient's skin.
  • the embodiment of Figure 2 illustrates a structure utilizing iontophoresis to assist in driving the fixative or other drug across the balloon wall 12 and into contact with the vessel walls 15.
  • one electrode 20, the catheter electrode is located on or within the catheter body 11 while the other electrode 22, the body surface electrode, is located on the body surface or within the body of the patient.
  • the fixative or other drug within the balloon chamber 13 requires specific characteristics. Ideally, such fixative or other drug should have an ionic nature or have other ionic molecules bound to the fixative or the active components of the drug to promote the iontophoretic movement or transport across the balloon wall 12.
  • An electrical current for the iontophoretic process of Figure 2 is produced between the electrodes 20 and 22 by an external power source 30 through the electrical leads 24 and 26, respectively.
  • iontophoresis by itself, or in combination with a solvent like DMSO as a carrier, could yield fixative or drug transport into or through a vessel wall at pressures less than about 20 mm Hg above normal ambient vessel wall pressure and preferably at less than about 5 mm Hg, thereby avoiding substantial damage to the vessel wall known to occur at higher pressures.
  • the polarity of the iontophoretic electrodes may be reversed to create a net flow of current in the opposite direction to recapture excess fixative or drug delivered to or through the vessel wall.
  • the particular material from which the balloon 12 is constructed will depend to some extent on the specific composition of the fixative or other drug to be delivered as well as the driving pressures which may be developed within the balloon chamber 13.
  • the preferred material from which the balloon 12 is constructed is an elastomer and the pressure generated within the balloon chamber 13 to aid in transport of the drug or fixation solution across the balloon walls is between about 1 and about 90 psi.
  • FIG. 3 A further modified balloon structure is illustrated in Figure 3.
  • the embodiment of Figure 3 is similar to the embodiment of Figures 1 and 2 except that the balloon structure in Figure 3 is constructed of two different materials.
  • the balloon structure in Figure 3 can be constructed of a permeable material that is modified to have one or more impermeable portions (i.e., increased thickness).
  • the balloon end portions 34 are a totally impermeable material, while an intermediate portion 32 of the balloon positioned between the end portions 34 is a permeable or semipermeable material.
  • the purpose of this structure is to enable more specific and precise delivery of the fixation solution or other drug desired to be administered. For example, with the end portions 34 constructed of an impermeable material, inadvertent passage of the fixation solution or other drug through such end portions is prevented.
  • the catheters of Figures 1-3 may be coated on their outer surfaces, or at least that portion of the outer surface which is to contact the vessel wall, with hydrogel to improve contact with the vessel wall.
  • the hydrogel so described may also contain the fixative or drug to be delivered where solution passing from the catheter through the hydrogel will dissolve the fixative or drug and transport the fixative or drug to the vessel wall.
  • drug impregnated hydrogel may be coated on the inside wall of a catheter for similar drug delivery as solution passes through the hydrogel and catheter wall.
  • iontophoresis and pressure are the force which can be utilized to transport the fixative or other drug from the interior balloon chamber across the balloon wall to the vessel wall.
  • DMSO dimethyl methacrylate
  • Other fluid diffusion enhancement compositions include propylene glycol, azone and ionic or non-ionic surfactants.
  • FIG. 4 A still further embodiment of_a drug delivery apparatus in accordance with the present invention is illustrated in Figure 4. This embodiment would be useful for delivery of a fixative, but would be particularly useful for delivery of antitumor drugs.
  • Figure 4 illustrates a modified catheter balloon design having a balloon 44 positioned on catheter body 11 near its distal end.
  • One delivery lumen or passageway 45 extends along the catheter body 11 to the proximal end of the body 11 and a recovery lumen or passageway 46 also extends along the catheter body 11 to the proximal end, said delivery lumen 45 and recovery lumen 46 useful for circulating solution containing a fixative or drug to and from the catheter balloon.
  • the outlets 47 and 48 may be positioned in the balloon to achieve optimal circulation within the balloon.
  • This embodiment may be most useful in delivering antitumor drugs which are difficult to dissolve where the delivery solution accordingly is very low in concentration of the antitumor drug and easily depleted of such drug. Circulation in this case would be important for continuous delivery over long time periods.
  • This embodiment may be combined with reversing the polarity of the electrodes of iontophoresis in order to remove excess drug after treatment.
  • each of the above embodiments of Figures 1-4 may be used for such drug delivery and each embodiment would be useful for delivering an antitumor, antihyperplastic or other agent through a vessel wall to a nearby or adjacent tumor or other internal body tissue.
  • a drug may be delivered substantially transversely to the longitudinal axis of a body passageway in order to treat a localized region of tissue located adjacent to the passageway.
  • tumors may be treated by delivering certain drugs through blood vessels or the intestinal tract or whatever to adjacent tumor sites.
  • the present invention is well suited to delivery of sensitizer and immunomodulator drugs.
  • sensitizer and immunomodulator drugs for the purposes of primary or adjuvant treatment or other circumstances where drug delivery to a specific local or regional internal body tissue site such as a solid tumor, abscess, regional lymph nodes or the like is desired, further embodiments of the present invention as shown in Figures 5 and 6 are preferred.
  • the tissue delivery system shown in Figures 5 and 6 includes a drug delivery apparatus 60 that is positioned into a specific tissue, such as a tumor.
  • a preferred drug delivery apparatus 60 for treating an internal body tissue includes a flexible catheter body 11' and drug delivery component 69 having a drug delivery passageway 64 including an outer wall 66, and an outer selectively permeable membrane portion 67 proximate the distal end 61.
  • the outer selectively permeable membrane 67 prevents escape of the drug from passageway 64 and drug delivery component 69 until the desired time of delivery. It is to be understood that the selectively permeable membrane 67 also controls the rate of release of the drug.
  • the drug is then driven across membrane 67 by a voltage gradient (iontophoresis) or other force.
  • selectively permeable membrane 67 material is a dialysis membrane, nylon, or polysulfone.
  • Drug delivery passageway 64 of drug delivery component 69 extends from proximal end 63 to distal end 61 of apparatus 60. As seen in Figures 5 and 6, drug delivery component 69 is preferably coaxially aligned about catheter body 11'. It is to be appreciated that drug delivery component 69 can be connected with catheter body 11' by a variety of adjacent configurations by one of skill in the art.
  • the embodiments of apparatus 60 in Figures 5 and 6 utilize iontophoresis to assist in driving the drug across selectively permeable membrane 67.
  • iontophoresis is preferred because it facilitates both transport of a fixative or drug across the selectively permeable membrane and enhances tissue penetration.
  • one electrode 28', the catheter electrode is located on or within catheter body 11', while the other electrode (31) is located on the body surface of the patient.
  • the other electrode may in certain applications be positioned at other regions of the patient including appropriate internal areas.
  • the tissue delivery system of the present invention can use pressure as an additional force to transport a drug to a target area of internal body tissue.
  • regulation means known to those skilled in the art (e.g., compressor, regulator or syringe pump) can be used to apply sufficient pressure to deliver the drug to the target area.
  • iontophoresis will be adequate to drive the drug across selectively permeable membrane 67 to the target area without further traumatization of the internal body tissue to be treated.
  • iontophoresis can be used with iontophoresis to enhance or otherwise control the speed of drug transport to an internal body tissue according to the present invention.
  • one of skill in the art could utilize pressure, DMSO, propylene glycol, azone, or various surfactants as a carrier to transport the drug through selectively permeable membrane portion 67 to the target area of internal body tissue.
  • the introducer (not shown) is placed into the target area, which may be a tumor or the like, after identification of the position of the lesion mechanically, radiographically, thermally, ultrasonically, or through some other like methodology.
  • the trocar/probe can be designed for steerability to facilitate positioning into the tumor. This can be accomplished by simply placing a bend in the trocar or by other mechanical design techniques known to those skilled in the art.
  • the active apparatus 60 is then passed through or over the introducing element directly over the inducer or through the void left in the intervening tissue by the withdrawal of the introducer. After apparatus 60 is in place, as confirmed by one of the foregoing methods, the active compound is delivered through passageway 64 into drug compartment 69 and across membrane 67 into the local or regional tissue. Using an embodiment of apparatus 60 of the type seen in df Figures 5 or 6, the delivery is accomplished iontophoretically.
  • the active compounds delivered to an internal body tissue using apparatus 60 include, but are not limited to, antitumor agents such as the vinca alkaloids, anthracycline antibiotics, platinum analogs, antimetabolites (e.g., methotrexate) ; antibiotics; sensitizers or other compounds.
  • the advantage of this method is that it allows delivery of the drug into the interstitial fluid and into the cells of the target area themselves even if the vasculature of the area is severely compromised and the cells do not preferentially take up the drug.
  • microporous membrane in conjunction with the active delivery mechanisms, aids in controlling drug transfer from the catheter by minimizing passive diffusion or flow under the slight pressure involved in filling the drug chamber or inflating the balloon to make contact with a vessel wall.
  • drug delivery into the tissue under active iontophoretic delivery will not be inhibited by the membrane.
  • micropores also reduce the likelihood that a significant portion of the membrane could become blocked with blood components, secretions, lubricants, or other material.
  • blood or other secretions will not cross the microporous membrane and enter the drug chamber during deflation of the balloon.
  • the microporous material will also allow rapid balloon deflation without blood reflux into the catheter, which is an important feature in coronary arterial applications.
  • the microporous material will allow the use of a neutral or charged membrane surface to promote or control drug transfer and delivery.
  • the microporous membrane can have either an isotropic (asymmetric) or symmetric structure.
  • the pore size of the membrane can vary from about 10 A to 10,000 A (i.e., 1 micron).
  • Microporous membranes that satisfy the requirements of the invention can be manufactured in any of several ways, most of which are readily understood by those skilled in the art of manufacturing microfiltration and ultrafiltration membranes.
  • iontophoresis as a driving force to transport a drug and/or fixative across a membrane.
  • Direct current is theorized to be most effective for iontophoresis, although, as discussed above, direct current may cause cardiac arrhythmias, vascular spasms, muscle stimulation and other undesirable side effects.
  • the present invention involves the use of electrical waveforms which provide a net flow of current to or from the catheter electrodes.
  • Possible waveforms contemplated for use in the invention are depicted in Figures 7A-7F and include square waves 100, rectangular waves 102, saw-toothed waves 104, sinusoidal waves that do not reverse polarity 106, rectified sinusoidal waves 108, and modified rectangular waves 110 (or other waveform shapes as desired) which do reverse polarity but provide a net flow of current in a desired direction.
  • the primary characteristic of the preferred waveforms used in the present invention is that they all provide net flow of current from the catheter electrode.
  • the majority of the preferred waveforms never reverse polarity, while others can reverse polarity briefly to provide better control over the inducement of cardiac arrhythmias. Even in those waveforms which do reverse polarity, however, there is a net flow of current in one direction as depicted by waveform 110 in Figure 7F.
  • Current flow in a first direction is indicated by area 111 above line 112 and current flow in a second
  • any waveforms used in the present invention can be varied to provide the maximum iontophoretic transfer rate while avoiding potential problems caused by the electrical current.
  • the preferred frequency range begins at about 200 Hz and increases to a maximum of about 100 kHz, with the most preferred range lying between 5-15kHz. It will be understood that the frequency can be varied within these ranges to maximize the rate of iontophoretic transfer for a given drug or fixative used in the catheters of the present invention.
  • One preferred embodiment waveform is a rectangular waveform.
  • Such a waveform has a duty cycle that is determined by the ratio of the time that the current is flowing to the time that no current is flowing.
  • the duty cycle of the rectangular waveform 114 is b/a while the duty cycle of waveform 116 is d/c.
  • the preferred range for the duty cycle is broad, i.e., between 5-95%, with a nominal value of 50%.
  • Figure 9 depicts a block diagram of the preferred electrical circuit 120 used to provide the waveforms described above.
  • the circuit 120 must provide waveforms with the required frequency and duty cycle and must also deliver the desired current under varying impedances encountered by the catheter in surrounding tissues and fluids.
  • the preferred circuit 120 incorporates a current sensor 122 and a current controller 124 used to monitor the actual current levels delivered at the catheter and adjust the voltage to maintain a desired current level.
  • the current sensor 122 is preferably connected to an isolated ground 123 to ensure the accuracy of the current sensor readings.
  • the reaction time of this portion of the circuit 120 is preferably about 100 microseconds to prevent unwanted changes in the current due to sudden changes in the impedance of the catheter system (including surrounding body tissues) .
  • the preferred circuit also includes adjustments for setting a desired current level 126, waveform frequency 128 and duty cycle 130. Because the preferred waveform is rectangular, the frequency and duty cycle are both preferably controlled by adjusting a chopper to provide the desired values.
  • the preferred circuit also includes a test duration adjustment 132. Each of the above adjustments are optional and, in their place, a set configuration can be designed in the circuit 120.
  • Voltage across the circuit is supplied by a DC voltage supply 134 and a pulse width modulator 136 and control voltage chopper 138 are used to produce the actual desired waveform.
  • the voltage sensor 140 depicted in Figure 9 is optional, but does supply a means to measure and display the voltage used to produce the desired current.
  • Figure 9 also depicts the catheter electrode 142 and return electrode 144.
  • the catheter electrode is incorporated into the drug delivery chambers of the preferred catheters. Examples include electrode 20 in Figures 2 & 3 and 28' in Figure 6.
  • the surface area of the electrodes used in the present invention should be as large as possible to allow desired current levels to be maintained while preventing undesired oxidative/reductive reactions from occurring at the electrode.
  • the surface area can be increased by using coils, as depicted in Figure 5, or other geometric shapes which increase the surface area of the electrode.
  • the surface of the electrode can be roughened to increase the exposed surface area.
  • the preferred electrode materials should minimize undesired oxidative/reductive reactions or production of competitive ions during the iontophoresis.
  • the preferred electrode materials are silver for anodal electrodes and silver/silver chloride for cathodal electrodes.
  • a drug can be delivered to an internal body tissue through a selectively permeable membrane portion of a drug delivery component connected to a catheter.
  • a drug delivery component connected to a catheter.
  • the catheter and connected drug delivery component are directed to a body tissue target area over a rigid probe or trocar the amount of drug delivered to the tissue to be treated is maximized and the leakage of drug back along the catheter and away from the target area is minimized.
  • many different waveforms other than those specifically mentioned could be used. Accordingly, it is intended that the scope of the present invention be dictated by the appended claims, rather than by the description of the preferred embodiment and method.

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Abstract

L'invention concerne un appareil d'administration locale d'un médicament dans un tissu du corps par ionophorèse. L'appareil d'administration par ionophorèse comprend une source de courant (30) produisant un flux net de courant dans une direction souhaitée avec des formes d'onde à haute fréquence qui augmentent l'apport du médicament et réduisent au minimum les effets secondaires associés normalement à l'ionophorèse. Selon un aspect de l'invention, on positionne un dispositif d'administration d'un médicament dans un passage du corps ou dans des tissus du corps et ensuite on introduit sélectivement un médicament choisi (13) pour qu'il soit transporté par ionophorèse à travers une paroi de transport de médicament du dispositif, pour assurer un contact direct avec la paroi du passage ou les tissus du corps. Dans un autre aspect de la présente invention, on traite un vaisseau dilaté dans la zone d'une lésion sténosée avec un médicament (13) pour rendre le vaisseau (15) inerte biologiquement et pour empêcher une resténose. Dans un autre aspect encore de la présente invention, on traite localement une tumeur ou une masse de tissus avec des agents sensibilisants antitumeur, des agents modificateurs biologiques ou des antibiotiques.
PCT/US1992/010850 1992-08-28 1992-12-15 Circuit et formes d'ondes electriques pour ionophorese interne WO1994005369A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU33217/93A AU3321793A (en) 1992-08-28 1992-12-15 Internal iontophoresis electrical circuit and waveforms

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US937,464 1986-12-02
US07/937,464 US5286254A (en) 1990-06-15 1992-08-28 Drug delivery apparatus and method
US95720992A 1992-10-06 1992-10-06
US957,209 1992-10-06

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Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996016693A1 (fr) * 1994-12-02 1996-06-06 The University Of Queensland Procede et appareil d'iontophorese
WO1996022805A1 (fr) * 1995-01-23 1996-08-01 Cortrak Medical, Inc. Catheter microporeux
US6587718B2 (en) 1999-10-08 2003-07-01 Scimed Life Systems, Inc. Iontophoretic delivery to heart tissue
WO2005093064A1 (fr) 2004-03-29 2005-10-06 Galpharma Co., Ltd. Protéine de modification de galectine-9 novatrice et utilisation de celle-ci
WO2006102724A1 (fr) * 2005-03-30 2006-10-05 Universite Libre De Bruxelles Dispositif de mesure de la valeur d'un tremblement musculaire d'un sujet
EP2039768A1 (fr) 1996-11-13 2009-03-25 Novartis Vaccines and Diagnostics, Inc. Formules mutantes de ligand FAS et utilisations associées
US9050442B2 (en) 1999-01-25 2015-06-09 Atrium Medical Corporation Expandable fluoropolymer device for delivery of therapeutic agents and method of making
US9731122B2 (en) 2013-04-29 2017-08-15 Rainbow Medical Ltd. Electroosmotic tissue treatment
US9770591B2 (en) 2015-12-29 2017-09-26 Rainbow Medical Ltd. Disc therapy
US9950156B2 (en) 2016-09-13 2018-04-24 Rainbow Medical Ltd. Disc therapy
US10173063B2 (en) 2015-10-29 2019-01-08 Rainbow Medical Ltd. Electrical substance clearance from the brain for treatment of alzheimer's disease
US10518085B2 (en) 2015-12-29 2019-12-31 Rainbow Medical Ltd. Disc therapy
US10532204B2 (en) 2015-07-08 2020-01-14 Rainbow Medical Ltd. Electrical treatment of hydrocephalus
US10569086B2 (en) 2017-01-11 2020-02-25 Rainbow Medical Ltd. Electrical microglial cell activation
US10758722B2 (en) 2017-05-03 2020-09-01 Rainbow Medical Ltd. Electrical treatment of Parkinson's disease
US10881858B1 (en) 2019-09-18 2021-01-05 Rainbow Medical Ltd. Electrical substance clearance from the brain
US10898716B2 (en) 2015-10-29 2021-01-26 Rainbow Medical Ltd. Electrical substance clearance from the brain
US11123197B2 (en) 2019-09-03 2021-09-21 Rainbow Medical Ltd. Hydropneumatic artificial intervertebral disc
US11202905B2 (en) 2018-03-14 2021-12-21 Rainbow Medical Ltd. Electrical substance clearance from the brain
US11298530B1 (en) 2021-05-03 2022-04-12 Discure Technologies Ltd. Synergistic therapies for intervertebral disc degeneration
US11344721B1 (en) 2021-08-16 2022-05-31 Rainbow Medical Ltd. Cartilage treatment
US11413455B1 (en) 2022-02-08 2022-08-16 Rainbow Medical Ltd. Electrical treatment of Alzheimer's disease
US11484706B2 (en) 2015-12-29 2022-11-01 Discure Technologies Ltd Disc therapy

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WO1996016693A1 (fr) * 1994-12-02 1996-06-06 The University Of Queensland Procede et appareil d'iontophorese
WO1996022805A1 (fr) * 1995-01-23 1996-08-01 Cortrak Medical, Inc. Catheter microporeux
US5800392A (en) * 1995-01-23 1998-09-01 Emed Corporation Microporous catheter
EP2039768A1 (fr) 1996-11-13 2009-03-25 Novartis Vaccines and Diagnostics, Inc. Formules mutantes de ligand FAS et utilisations associées
US9050442B2 (en) 1999-01-25 2015-06-09 Atrium Medical Corporation Expandable fluoropolymer device for delivery of therapeutic agents and method of making
US6587718B2 (en) 1999-10-08 2003-07-01 Scimed Life Systems, Inc. Iontophoretic delivery to heart tissue
WO2005093064A1 (fr) 2004-03-29 2005-10-06 Galpharma Co., Ltd. Protéine de modification de galectine-9 novatrice et utilisation de celle-ci
WO2006102724A1 (fr) * 2005-03-30 2006-10-05 Universite Libre De Bruxelles Dispositif de mesure de la valeur d'un tremblement musculaire d'un sujet
US9731122B2 (en) 2013-04-29 2017-08-15 Rainbow Medical Ltd. Electroosmotic tissue treatment
US10905875B2 (en) 2013-04-29 2021-02-02 Rainbow Medical Ltd. Electrical treatment of hydrocephalus
US11376422B2 (en) 2015-07-08 2022-07-05 Rainbow Medical Ltd. Electrical treatment of Alzheimer's disease
US10532204B2 (en) 2015-07-08 2020-01-14 Rainbow Medical Ltd. Electrical treatment of hydrocephalus
US11819685B2 (en) 2015-07-08 2023-11-21 Rainbow Medical Ltd. Electrical treatment of Alzheimer's disease
US11141588B2 (en) 2015-10-29 2021-10-12 Rainbow Medical Ltd. Electrical substance clearance from the brain
US10898716B2 (en) 2015-10-29 2021-01-26 Rainbow Medical Ltd. Electrical substance clearance from the brain
US10173063B2 (en) 2015-10-29 2019-01-08 Rainbow Medical Ltd. Electrical substance clearance from the brain for treatment of alzheimer's disease
US12005252B2 (en) 2015-12-29 2024-06-11 Discure Technologies Ltd Disc therapy
US11484706B2 (en) 2015-12-29 2022-11-01 Discure Technologies Ltd Disc therapy
US11612742B2 (en) 2015-12-29 2023-03-28 Discure Technologies Ltd. Disc therapy
US10518085B2 (en) 2015-12-29 2019-12-31 Rainbow Medical Ltd. Disc therapy
US11285317B2 (en) 2015-12-29 2022-03-29 Rainbow Medical Ltd. Disc therapy
US11129981B2 (en) 2015-12-29 2021-09-28 Rainbow Medical Ltd. Disc therapy
US9770591B2 (en) 2015-12-29 2017-09-26 Rainbow Medical Ltd. Disc therapy
US11253700B2 (en) 2016-09-13 2022-02-22 Rainbow Medical Ltd. Electrode for disc therapy
US11097098B2 (en) 2016-09-13 2021-08-24 Rainbow Medical Ltd. Disc therapy
US9950156B2 (en) 2016-09-13 2018-04-24 Rainbow Medical Ltd. Disc therapy
US10569086B2 (en) 2017-01-11 2020-02-25 Rainbow Medical Ltd. Electrical microglial cell activation
US10758722B2 (en) 2017-05-03 2020-09-01 Rainbow Medical Ltd. Electrical treatment of Parkinson's disease
US11202905B2 (en) 2018-03-14 2021-12-21 Rainbow Medical Ltd. Electrical substance clearance from the brain
US11123197B2 (en) 2019-09-03 2021-09-21 Rainbow Medical Ltd. Hydropneumatic artificial intervertebral disc
US10881858B1 (en) 2019-09-18 2021-01-05 Rainbow Medical Ltd. Electrical substance clearance from the brain
US11298530B1 (en) 2021-05-03 2022-04-12 Discure Technologies Ltd. Synergistic therapies for intervertebral disc degeneration
US11344721B1 (en) 2021-08-16 2022-05-31 Rainbow Medical Ltd. Cartilage treatment
US11413455B1 (en) 2022-02-08 2022-08-16 Rainbow Medical Ltd. Electrical treatment of Alzheimer's disease

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