WO2001041865A1 - Electrochemical treatment of malignant tumors - Google Patents
Electrochemical treatment of malignant tumors Download PDFInfo
- Publication number
- WO2001041865A1 WO2001041865A1 PCT/US1999/029564 US9929564W WO0141865A1 WO 2001041865 A1 WO2001041865 A1 WO 2001041865A1 US 9929564 W US9929564 W US 9929564W WO 0141865 A1 WO0141865 A1 WO 0141865A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- tumor
- electrodes
- set forth
- voltage
- cytotoxic agent
- Prior art date
Links
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
- A61N1/205—Applying electric currents by contact electrodes continuous direct currents for promoting a biological process
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0601—Apparatus for use inside the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0613—Apparatus adapted for a specific treatment
- A61N5/062—Photodynamic therapy, i.e. excitation of an agent
Definitions
- This invention relates generally to the electrochemical treatment of malignant tumors and neoplasms by applying a voltage across working and counterelectrodes implanted m the tumor to cause a direct current to flow through the tumor producing an electrochemical reaction yielding multiple reaction products some of which act as cytotoxic agents to destroy cancer cells, and more particularly to a treatment of this type in which the voltage applied to the electrodes is regulated to maintain it at a value which optimizes the yield of those cytotoxic agents having the greatest efficacy.
- Oncology is the branch of medical science dealing with tumors.
- the concern of the present invention is with tumors and other forms of neoplasm which are malignant and therefore cancerous.
- the distinction between a benign and a malignant tumor is that the latter will invade surrounding tissues and spread or metastasize to other sites, whereas a benign tumor will not spread.
- the common practice m the field of oncology to cure or ameliorate a cancerous condition is by appropriate surgery, radiotherapy or chemotherapy, sometimes used singly, but more often in combination.
- Radiotherapy which produces its biologic effect on cancerous tissue by ionization is carried out by megavolt energy radiation in the form of X-rays from a linear accelerator or gamma rays from a cobalt 60 source. Radiation is highly penetrating, but in order to reach the region of the tumor being treated, the radiation beam must pass through regions containing healthy tissue and may therefore destroy these as well as the malignant tumor.
- Chemotherapy dictates the utmost care in monitoring and controlling the administration of cytotoxic drugs, for the biochemistries of malignant and non-malignant cells are so similar that it is difficult to destroy cancerous cells without concurrently destroying healthy cells.
- the adverse effects of chemotherapy are notorious.
- the problem with surgery to excise a malignant tumor is that the location of the tumor, as in the case of a tumor in the brain, may be such as to render the tumor inoperable. But even where the tumor is accessible to the surgeon's scalpel, then in order to reach this tumor, one must cut through and damage healty tissue. Moreover with surgery, one cannot be sure that all malignant cells have been removed, and the residual cells may metastasize.
- ETC electrochemical treatment
- Electrodes are implanted at spaced positions in or around the malignant tumor to be treated. Applied across these electrodes is a low d-c voltage usually having a magnitude of less than 10 volts, causing a current to flow between the electrodes through the tumor. Due to an electrochemical reaction, reaction products are yielded which include cytotoxic agents that act to destroy the tumor.
- a d-c voltage usually having a magnitude of less than 10 volts, causing a current to flow between the electrodes through the tumor. Due to an electrochemical reaction, reaction products are yielded which include cytotoxic agents that act to destroy the tumor.
- ECT technique disclosed by Li et al . , in Bioelectromagnetic 18:2-7 (1997), in the article 'Effects of Direct Current on Dog Liver: Possible Mechanisms For Tumor Electrochemical Treatment" two platinum anode and cathode electrodes were inserted in a dog's liver with a 3cm separation therebetween. Applied across these electrodes was a d-
- the concentration of selected ions near the anode and cathode were measured.
- the concentration of Na + and K + ions were found to be higher around the cathode, whereas the concentration of Cl " ions was higher around the anode.
- Water content and pH were determined near the anode and cathode, the pH values being 2.1 near the anode and 12.9 near the cathode.
- the released gases were identified as chlorine at the anode and hydrogen at the cathode.
- the series of electrochemical reactions which took place during ECT resulted in the rapid and complete destruction of both normal and tumor cells in the liver.
- Electrochemical reactions as a function of pH and electrode potential can be predicted by means of a Pourbaix diagram, as disclosed in the Atlas of
- H s Hi ⁇ rr 3 H- O tr TJ Hi ⁇ C ⁇ H rt a 3 " o £ o O 3 (D SD 0 TJ ⁇ - ⁇ C ⁇ rt o O o r ⁇ CD H H- o ⁇ * ⁇ H- rt H o C ⁇ ⁇ - Hi O Hi Hi ⁇ O CD a H rt i J. rr N ⁇ - CD rt rt o Hi rt
- Yet another object of this invention is to provide an apparatus for carrying out an ECT procedure in conjunction with photochemically-activated drugs delivered to the malignant tumor whereby as current passes through the tumor to produce an electrochemical reaction, the tumor is at the same time exposed to light rays to activate the drugs.
- a technique and apparatus therefor adapted to treat in situ a malignant tumor use being made of a working electrode and a counterelectrode implanted in the tumor at spaced positions.
- a d-c voltage Applied across the electrodes is a d-c voltage causing a direct current to flow through the tumor producing an electrochemical reaction yielding multiple reaction products, some of which are cytotoxic agents destructive of cancer cells.
- Coupled to the electrodes is a control unit which acts to regulate the voltage applied thereto so as to optimize the yield of those cytotoxic agents having the greatest efficacy.
- Fig. 1 is a schematic diagram of an electrochemical treatment system (ECT) in accordance with the invention for destroying a malignant tumor or other form of neoplasm
- Fig. 2 illustrates an electrode included in an ECT system adapted to deliver a chemotherapy drug to the tumor being treated;
- Fig. 3 illustrates an electrode to be included in an ECT system adapted to apply light energy to a tumor being treated.
- Fig. 1 Shown in Fig. 1 is an ECT system in accordance with the invention for treating a malignant tumor 10.
- the treatment is carried out in situ by passing a direct electrical current through the tumor to produce an electrochemical reaction therein yielding multiple reaction products some of which have cytotoxic properties.
- the electrochemistry of the tumor depends on its organic nature. Thus the organic solutions permeating a cancerous liver are somewhat different from those found in a cancerous pancreas.
- Typical reaction products resulting from passing direct current through tissues are hydrogen and oxygen, as well as chlorine and hydrogen peroxide.
- Hydrogen peroxide which is a highly probable intermediate is known to have strong cytotoxic properties, whereas other reaction products yielded in an ECT procedure vary in their effectiveness in destroying cancer cells.
- the system operates to optimize the yield of those reaction products that have the greatest ability to destroy cancer cells.
- a working electrode 11 In the system shown in Fig. 1 there are implanted in tumor 10 a working electrode 11 and space therefrom, a counterelectrode 12. These electrodes may be formed of platinum or other noble metals or alloys thereof.
- the electrodes may be formed of high-strength, non- reactive metals, such as titanium and stainless steel. Electrodes made of conductive oxides and semiconductors can also be used.
- the electrodes, especially the counterelectrodes are preferably fabricated of porous material to enlarge their effective surface area and thereby reduce the current density per unit crossectional area of the electrode. Also more than one counterelectrode can be used in conjunction with one working electrode in order to distribute current flow throughout the tumor.
- Applied across electrode 11 and 12 to cause a current to flow through the regions of the tumor bridging these electrodes is a voltage derived from a battery or other d-c voltage source 13 under the control of a potentiostat 14.
- a potentiostat is an instrument used in an electrochemical process which is adapted to automatically control the potential of a test or working electrode to within certain limits during an electrochemical reaction.
- Potentiostat 14 in the system disclosed in Fig. 1 acts to govern the d-c voltage derived from battery 13 which is applied to working electrode 11 so that the multiple reaction products yielded by the electrochemical reaction when current passes through tumor 10, includes products which have the cytotoxic properties most effective in destroying cancer cells.
- Potentiostat 14 maintains at a substantially constant level the potential difference between working electrode 11 and the electrochemical solution in tumor 10 (the working electrode potential) , measured with respect to a reference electrode 15.
- Reference electrode 15 is implanted in the tumor as close as possible to the working electrode 11.
- the working electrode 11 and reference electrode 15 implanted in the tissue of the tumor are connected in series with a potentiometer 16.
- a voltmeter 17 is connected between the variable tap on potentiometer 16 and one end of battery 13 whose other end is connected through the resistance of potentiometer 16 to reference electrode 15.
- the circuit is completed through input 18 of potentiostat 14.
- Potentiometer 16 is monitored by means of voltmeter 17 to obtain the required electromotive force (EMF) which is equal and opposite to the desired working electrode-reference electrode EMF.
- EMF electromotive force
- the voltage developed at the input 18 of this potentiostat is not zero, but constitutes an error signal. This signal operates the electronic feedback to give an output that restores the desired electrode potential .
- the potential to be maintained on working electrode 11 by potentiostat 14 is that potential which, for the tumor being treated, gives rise to a current flow through the tumor that produces an electrochemical reaction therein yielding those reaction products which includes cytotoxic agents having the greatest ability to destroy cancer cells.
- a highly effective cytotoxic agent included in the multiple reaction products yielded by the electrochemical reaction reaches its higher level when the potential on the working electrode is in aa 1.00 to 1.25 volt range, then the potentiostat system is adjusted to maintain the potential in this range. Or the potentiostatic system operates in whatever other range yields reaction products having optimal cytotoxic characteristics.
- the adjustable potentiometer 16 makes it possible to operate the system manually. In order to operate the system so that it automatically maintains the voltage in the desired range with respect to a selected variable in the electrochemical process indicative of the desired cytotoxic reaction products being generated, this variable is sensed by a sensor 21.
- the variable being sensed may simply be the pH in the vicinity of the counterelectrode or at the working electrode.
- Sensor 21 produces an electrical signal that depends on the variable being sensed, this signal being applied to an electronic controller 22 which compares the signal with a set point signal to produce an error signal that depends on the deviation of the sensor signal from the set point; that is the extent to which the sensed pH deviates from the pH value that reflects an optimum condition.
- Controller 22 is couplet to potentiometer 16 in the potentiostat system, acting to adjust the voltage to maintain the desired voltage at which the ECT system is most effective in destroying cancer cells. In practice, one may dispense with the potentiostat, and use the electronic controller to regulate the voltage applied to the electrodes.
- Electrodes To minimize polarization at the electrodes of the electrochemical system, the polarity of the voltage applied to the electrodes may on occasion be reversed, in which case the counterelectrode becomes the working electrode. And the direct voltage applied to the electrodes need not be continuous, but may be pulsed or undulatory. Electrodes :
- the electrodes must be appropriate to the tumor or other form of neoplasm being treated.
- the electrodes must then be applied to the skin surface, and for this purpose flexible patch electrodes are suitable.
- the appropriate electrodes depend on the character of the tumor.
- the electrode may take the form of a flexible pin capable of penetrating the tumor, whereas for relatively hard tumors, a screw-type electrode may be preferable.
- either the working electrode or the counterelectrode may take the form of a hollow tubular metal electrode 23 having a cutting tip 24 to facilitate its insertion in a tumor .
- Electrode 23 is provided with a series of apertures 25 along its length. Delivered through a suitable line 26 feeding electrode 23 is a flowable drug from a chemotherapy source 27. Hence in this arrangement, the tumor is subjected to a cytotoxic agent derived from a chemotherapy source as well as cytotoxic agents yielded by the electrochemical ECT process.
- a photochemically activated drug which is absorbed by the tumor, or delivered thereto through the electrodes, but until such time as it is activated by light energy, remains inactive and innocuous .
- the metal electrode 27, as shown in Fig. 3 is hollow and has myriad apertures 29 which are circumferentially distributed.
- Received within the hollow electrode is a flexible fiber optics light pipe 30 which is coupled to an external high-intensity light source 31.
- the tumor impregnated with the light- activatable drug undergoes an ECT procedure
- the tumor is at the same time (or in alternate sessions) subjected to light energy to activate the drug, thereby releasing cytotoxic agents whose activity is combined with the agents released as reaction products.
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/985,287 US6021347A (en) | 1996-12-05 | 1997-12-04 | Electrochemical treatment of malignant tumors |
PCT/US1999/029564 WO2001041865A1 (en) | 1996-12-05 | 1999-12-10 | Electrochemical treatment of malignant tumors |
AU19392/00A AU1939200A (en) | 1996-12-05 | 1999-12-10 | Electrochemical treatment of malignant tumors |
US09/733,023 US6708066B2 (en) | 1999-12-10 | 2000-12-08 | Electrochemical treatment of tissues, especially tumors |
US10/608,829 US7526334B2 (en) | 1999-12-10 | 2003-06-26 | Electrochemical treatment of tissues, especially tumors |
US11/151,967 US20060089751A1 (en) | 1997-01-27 | 2005-06-14 | Electronic delivery systems and methods with feedback |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US3322396P | 1996-12-05 | 1996-12-05 | |
US08/985,287 US6021347A (en) | 1996-12-05 | 1997-12-04 | Electrochemical treatment of malignant tumors |
PCT/US1999/029564 WO2001041865A1 (en) | 1996-12-05 | 1999-12-10 | Electrochemical treatment of malignant tumors |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2001041865A1 true WO2001041865A1 (en) | 2001-06-14 |
Family
ID=27364347
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1999/029564 WO2001041865A1 (en) | 1996-12-05 | 1999-12-10 | Electrochemical treatment of malignant tumors |
Country Status (3)
Country | Link |
---|---|
US (1) | US6021347A (en) |
AU (1) | AU1939200A (en) |
WO (1) | WO2001041865A1 (en) |
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- 1997-12-04 US US08/985,287 patent/US6021347A/en not_active Expired - Lifetime
-
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- 1999-12-10 AU AU19392/00A patent/AU1939200A/en not_active Abandoned
- 1999-12-10 WO PCT/US1999/029564 patent/WO2001041865A1/en active Application Filing
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US4289135A (en) * | 1978-11-23 | 1981-09-15 | Tekniska Rontgencentralen Ab | Apparatus for destroying a selected part of biological tissue |
US4846950A (en) * | 1983-09-08 | 1989-07-11 | Montefiore Hospital Assn Of Western Pa | Cyclic controlled electrolysis apparatus |
US5468223A (en) * | 1992-11-30 | 1995-11-21 | C.N.R.S. Paris | Electrochemotherapy |
Also Published As
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AU1939200A (en) | 2001-06-18 |
US6021347A (en) | 2000-02-01 |
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