AN ELECTRIC FIELD OR ELECTRIC VOLTAGE DELIVERING ELECTRODE SYSTEM FOR THE TREATMENT OF INTERNAL ORGAN OEDEMA

Abstract

The present invention relates to an electrode assembly system for treatment of internal organ oedema by electro-osmosis and/or electrophoresis by delivering an electric field, the system comprising a first electrode, a second electrode, and a control unit, wherein the first electrode and second electrode are electrically connected to the control unit, the control unit being adapted to charge the first electrode negatively and the second electrode positively, and to directly control a strength of an electric field induced by the first electrode and the second electrode to a preset value for generating a treatment-specific electric flux. The present invention also relates to the use of such system, as well as a process of treatment of internal organ oedema using such system.

Claims

1. An electrode assembly system for treatment of internal organ oedema by electro-osmosis and/or electrophoresis by delivering an electric field, the system comprising a first electrode, a second electrode, and a control unit, wherein the first electrode and second electrode are electrically connected to the control unit, characterized in that the control unit is adapted to charge the first electrode negatively and the second electrode positively, and the control unit is adapted to directly control a strength of an electric field induced by the first electrode and the second electrode to a preset value for generating a treatment-specific electric flux.

2. The electrode assembly system according to claim 1, wherein the control unit is adapted to switch the polarity of the charged first and second electrodes.

3. The electrode assembly system according to claim 1, wherein the first electrode is a patch electrode and the second electrode is a patch electrode to be positioned opposite one the other of the internal organ so that the electric field generated by the negatively and positively charged first and second electrodes is spanned through the internal organ.

4. The electrode assembly system according to claim 1, wherein the first electrode is a coil electrode, and the second electrode is a patch electrode, wherein the first electrode is to be positioned inside a liquid vessel of the internal organ and the second electrode is to be positioned outside of the internal organ so that the electric field generated by the negatively and positively charged first and second electrodes is spanned through the internal organ oedema part.

5. The electrode assembly system according to claim 1, wherein the first electrode is a coil electrode and the second electrode is a coil electrode, wherein the first electrode is to be positioned inside a liquid vessel of the internal organ and the second electrode is to be positioned inside a liquid vessel of the internal organ so that the electric field generated by the negatively and positively charged first and second electrodes is spanned through the internal organ oedema part.

6. The electrode assembly system according to claim 1, wherein the control unit is adapted to control the charge of the negatively and positively charged first and second electrodes to control the strength of the electric field at the place of the internal organ oedema.

7. The electrode assembly system according to claim 1, wherein the control unit is configured to allow the preset value of the strength of the electric field to be set and/or entered into the control unit by a user, the control unit is configured to automatically control the strength of the electric field to the preset value for the strength of the electric field, and/or the control unit is configured to cause and maintain the strength of the electric field at the preset value for the strength of the electric field independently of external influences.

8. The electrode assembly system according to claim 1, wherein the first electrode and the second electrode have each an electrically isolating sheath, preferably wherein the electrically isolating sheath comprises a material taken from the group encompassing silicone, thermoplast, PEEK, PHA and PHB.

9. The electrode assembly system according to claim 1, wherein the electrodes are positioned extracorporally, preferably wherein the electrodes are positioned in physical contact with the external skin surface, more preferably wherein the electrodes can be attached or adhered to the skin surface.

10. Use of an electrode assembly system according to claim 1, for inducing an osmotic-like and/or electrophoretic-like effect for treatment of internal organ oedema by means of inducing an electric field, wherein the control unit of the electrode assembly is set to a value for the strength of the electric field by a user to directly control an electric field induced by the first electrode and the second electrode to the preset value for generating a treatment-specific electric flux, wherein the preset value of strength of the electric field is preferably caused and maintained by the control unit independent of external influences.

11. A process of treatment of internal organ oedema using an electrical field delivering electrode system comprising two patch electrodes and a control unit, wherein the two patch electrodes are to be positioned at two places on the outer surface of the internal organ, wherein the two patch electrodes are connected to the control unit and wherein the control unit is adapted to provide an electric field between the electrodes to induce electro-osmosis and/or electrophoresis.

12. A process of treatment of internal organ oedema using an electrical field delivering electrode system comprising a patch electrode, a coil electrode and a control unit, wherein the patch electrode is positioned on the outer surface of the internal organ, wherein the coil electrode is positioned in a liquid carrying vessel of the internal organ, the patch electrode and the coil electrode are connected to the control unit and the control unit is adapted to provide an electric field between the two electrodes to induce electro-osmosis and/or electrophoresis, wherein optionally the patch electrode is positioned for the heart on the epicardial side of the heart and wherein the coil electrode is positioned for the heart inside the ventricular cavity.

13. A process of treatment of internal organ oedema using an electric field delivering electrode system comprising two coil electrodes, wherein the two coil electrodes are positioned in different liquid carrying vessels within the internal organ, the two coil electrodes are connected each to the control unit and the control unit is adapted to deliver an electric field between the two electrodes to induce electro osmosis and/or electrophoresis, wherein optionally one of the two coil electrodes is placed in the coronary sinus and the other of the two electrodes is positioned in the right or left ventricular cavity.

14. The process of treatment of internal organ oedema according to claim 11, wherein the internal organ oedema is a myocardial oedema or an oedema of the kidney or an oedema of the liver, and wherein the electro-osmosis and/or electrophoresis is generated for a reduction up to a removal of the internal organ oedema and wherein the electroosmotic and/or electrophoretic effect comprises an accumulation of oedema fluid at the electrodes to be carried away from the electrodes and/or an increased lymphatic flow in the lymphatic vessels induced by the electric field.

15. The process of treatment of internal organ oedema according to claim 11, wherein the control unit is configured to switch the polarity of the electrodes in predetermined time intervals, preferably wherein the predetermined time intervals comprise intervals between ten minutes and three months, especially between 12 hours and 7 days.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0072] Preferred embodiments of the invention are described in the following with reference to the drawings, which are for the purpose of illustrating the present preferred embodiments of a device to execute the process according to the invention and not for the purpose of limiting the same. In the drawings,

[0073] FIG. 1 shows a two internal electrode disposition (two internal coil electrodes) of electrodes in the heart as internal organ;

[0074] FIG. 2 shows a mixed (one internal coil electrode, one external patch electrode) disposition of electrodes in and outside the heart;

[0075] FIG. 3 shows a two external electrodes (external patches with segmented electrodes) disposition of electrodes on external heart surfaces according to the invention during use;

[0076] FIG. 4 shows an electrode according to the invention comprising a one-way valve;

[0077] FIG. 5 shows a two external electrodes (external patches with single electrodes) disposition of electrodes on external kidney surfaces according to the invention during use; and

[0078] FIG. 6 shows a mixed (one internal coil electrode, one external patch electrode) disposition of electrodes in and outside the kidney.

DESCRIPTION OF PREFERRED EMBODIMENTS

[0079] FIG. 1 shows a schematic representation of a heart 10 with an electrode assembly 20 according to a first illustrative embodiment of the invention. The implantable electrode assembly 20 comprises two implantable electrodes 30 and 40 and a control circuit 50, usually arranged in a separate housing in which the battery for the power supply is likewise provided.

[0080] The two electrodes 30 and 40 are connected to the control circuit 50 via two single-conductor cables 51 and 52.

[0081] The control circuit 50 is designed to establish a potential difference between the two electrodes 30 and 40, such that an electric field is generated between these electrodes 30 and 40.

[0082] One electrode 30 is a ventricular electrode, provided for positioning in the right ventricle, and is designed as a coil electrode. It is therefore designated below as a ventricular coil electrode 30. The length of the ventricular coil electrode 30, defined by the one conductive metallic sheath surface or coil surface defining a sheath, is ca. 4 to 10 centimeters and is designed to fill as far as possible the entire length of the right ventricle after passage through the right cardiac tricuspid valve. Here, the ventricular coil electrode 30 is placed loosely into the right ventricle, but it can touch the wall of the right ventricle. To prevent the electrode from falling into the outflow tract of the right ventricle (pulmonary valve), it is anchored actively (by screw) with its tip or passively with barbs in the tip of the right ventricle which hook into the trabecular meshwork of the right ventricle and thus fix the electrode tip.

[0083] From FIGS. 1 and 2, the electrode 30 seems to float freely in the right ventricle. However, this is only apparently the case, because the figures are schematic two-dimensional depictions. Generally, the electrode 30 will nestle on the wall of the ventricle; in the depiction in FIG. 2, this could be the posterior wall, which is not visible there. The electrode 30 is flexible in order to adopt these gentle curvatures, which amount to less than 30 degrees with respect to the longitudinal axis.

[0084] The other electrode 40 of FIG. 1 is a coronary sinus electrode, provided for positioning in the coronary sinus, and is likewise designed as a coil electrode. This coronary sinus coil electrode 40 has a smaller diameter than the ventricular coil electrode 30 since it is intended to be advanced far into the coronary sinus in order then to come to lie in the narrowing end region there. This electrode thus lies at a position substantially predefined by the vessel walls, which position the operating surgeon otherwise establishes by advancing it in the longitudinal direction.

[0085] When the two electrodes 30 and 40 are connected to a predetermined voltage by the control circuit 50 via the attachment wires or cables 51, 52 insulated from the environment, an electric field is generated with electric field lines shown very schematically according to the arrow 55 through the myocardium. Of course, the electric field lines are directly running from one electrode to the other. In a manner predetermined by the control circuit, the electrode 30 can be the cathode for a predetermined time of between a few minutes and up to chronically, whereby the direction of the electric field is predefined. The control circuit can then switch the polarity of the voltage and change the direction of the electric field after a correspondingly predetermined time, whereby the electrode 40 becomes the cathode. The strength of the electric flux can also change, since the dielectric property of the volume between the two electrodes 30 and 40 can be dependent on the direction of the electric field. In a further illustrative embodiment, the control device controls the electric flux at a uniform predetermined value.

[0086] FIG. 2 shows a schematic representation of a heart 10 with an electrode assembly 120 according to a second illustrative embodiment of the invention. The implantable electrode assembly 120 comprises two implantable electrodes 30 and 140 and also a control circuit 50.

[0087] Identical features are provided with identical reference signs, similar features with correspondingly similar reference signs.

[0088] The control circuit 50 can be designed in the same way as described in FIG. 1. The two electrodes 30 and 140 are also connected to the control circuit 50 via two single-conductor cables 51 and 52.

[0089] The control circuit 50 is also designed here to establish an electric field between the two electrodes 30 and 140, such that an electro-osmotic and/or electrophoretic effect can exist between these electrodes 30 and 140 for a predetermined time of several minutes, e.g. 5 minutes, to several days, e.g. 3 days or even chronically.

[0090] One electrode 30 is once again a ventricular electrode, provided for positioning in the right ventricle, and is designed as a coil electrode. It is therefore also designated here as a ventricular coil electrode 30. The length of the ventricular coil electrode 30, defined by the one conductive metallic sheath surface or coil surface defining a sheath, is ca. 4 to 10 centimeters and is designed to fill as far as possible the entire length of the right ventricle in the longitudinal axis after passage through the right cardiac valve (tricuspid valve). Here, the ventricular coil electrode 30 is placed loosely into the right ventricle, is passively anchored at the distal end and can bear on the wall of the ventricle or on the septum. To prevent the electrode from falling into the outflow tract of the right ventricle (pulmonary valve), it is anchored actively (by screw) with its tip or passively with barbs in the tip of the right ventricle.

[0091] The other electrode 140 is a surface electrode (patch electrode), provided for positioning on the epicardium, the pericardium or close to the epicardium (e. g. even subcutaneously). It can be designed, for example, according to the teaching of US 2008/0195163 A1. This surface electrode 140 is applied to the left side of the myocardium, epicardially opposite the right ventricle.

[0092] When the two electrodes 30 and 140 are subjected to a potential difference by the control circuit 50 via the attachment wires or cables 51, 52 insulated from the environment, an electric field is generated with field lines very schematically in the direction according to the arrows 155 through the myocardium. These electric field lines are symbolized here by two arrows which essentially show the approximate direction of the field lines, since the field lines emerge and fan out from a substantially longitudinally dimensional face of the substantially longitudinally oriented surface of the coil electrode 30 toward the surface electrode 140 and thus sweeps across a fan. Seen physically, the main portion of the electric field lines are inside a prism; that is to say proceeding from an edge (of the prism) to its base on the patch electrode.

[0093] A prism is by definition a geometric body whose side edges are parallel and of equal length and which has a polygon as base. It arises from parallel displacement of a plane polygon along a straight line not lying in this plane and is therefore a special polyhedron. Here, the straight line is predefined by the longitudinal axis of the coil electrode 30, and the polygon is a triangle with the apex at the coil electrode 30 and with a base that corresponds to the width of the surface electrode (patch electrode) 140. If these side edges 141 of the surface electrode 140 do not come to lie parallel to the orientation of the coil electrode, it is a rotated prism. In all cases, the two electrodes 30 and 140 define a not inconsiderable spatial body, which guarantees that the electric field spans through a likewise not inconsiderable sub region of the left cardiac muscle and to a slightly lesser extent also of the right cardiac muscle. Describing the geometry of the body through which the electric field has a substantive strength as a prism is an approximation, since it can be assumed from this that the electrode does not float freely but is instead passively fixed at its distal tip and then bears on the wall of the ventricle. The boundary lines of the body are then certainly not straight but curved, and the defined body is then obtained only approximately as a prism. Of importance, however, is the narrow “edge” on the one side formed by the coil electrode, and the “broad bottom face” on the other side, which is formed by the patch electrode.

[0094] FIG. 3 shows two patch electrodes 240 and 340, which are connected with lines 51 and 52 to a control and power supply unit 50. Here, each patch electrode 240 and 340 as such is a segmented electrode 240 or 340. This means, each electrode 240 or 340 is or comprises a plurality of electrode segments 241 or 341, which are shown as smaller rectangles in FIG. 3.

[0095] Although the organ 10 can be a heart, it is also possible that the organ 10 is a kidney with applied electrodes 240 and 340. In other embodiments, it could be a liver.

[0096] The electrode 240 or 340 optionally comprises at least one one-way valve 70, which essentially comprises an opening 72 and a diaphragm 73 covering the opening 72 on the far side of the internal organ. A schematic sectional view of the one-way valve 70 is depicted in FIG. 4. The diaphragm is made from silicone, for example. The one-way valve 70 is situated within the electrode surface 75.

[0097] The apparatus as described in connection with FIG. 1, 2 or 3 provides a constant electric field with defined polarity for a given time as hours or days applied to the tissue of an internal organ, here the heart. This electric field acts immediately or at least extremely fast on the internal organ, here the heart.

[0098] Extremely fast means that the first signs of improvement starts to appear within minutes after the electric field is applied. Irrespective of the fact that the patient describes a better feeling of well-being, echocardiography can be used to objectify a reduction in the size of the ventricle very quickly as the first positive sign. In this short period of time, this immediate improvement cannot be explained by molecular biological processes in the heart musculature; the improvement is due to electro-osmosis, a process by which an aqueous solution, such as water for example, is transported osmotically (used, for example, to dry damp walls or in cosmetics), and/or electrophoresis, a process by which charged components, such as proteins, electrolytes, or molecules, are transported.

[0099] It can be assumed that diseased organs are always also inflamed organs and inflammation is always associated with oedema. In relation to the heart, this means that there is an intra- and/or extracellular excess of fluid (oedema), which causes the heart muscles to swell and limits their pumping function. By applying an electric field or voltage, an electrokinetic-like effect, i.e. an osmotic-like and/or electrophoretic-like effect is induced, by which aqueous solution is extracted from the heart muscles, which was before enlarged and bloated by oedema and flow in the lymphatic system is increased and the cardiac interstitium is drained.

[0100] Such drainage of the heart muscle, i.e. the reduction of myocardial oedema, might be difficult to monitor in living organisms, but the inventors of the present invention have found that the subsequent improvement of the heart function is substantially based on the effect known as electroosmosis and/or electrophoresis.

[0101] This effect is transferable to other internal organs in which the intra- and/or extracellular excess of fluid (oedema) leads to restricted cell function and thus reduces organ function as a whole. In general, it is pointed out that the described liquid drainage of oedema-afflicted organs or vessels can also be referred to as lymphatic drainage since the lymphatic vessels are one of the transport routes, or the most important transport route, that remove the oedema and are stimulated by electroosmosis.

[0102] This presently described function is based on the insight, that the human body is a so-called ion conductor. The electric field mainly causes ion movement (electrokinesis), i.e. the migration of negatively charged anions (e.g. Cl−, CO.sub.2− etc) to the anode and of positively charged cations (e.g. Na+. Mg++. etc) to the cathode. Electro-chemical reactions occur on metals (electrodes, but also metallic foreign bodies). A migration of protein fractions, i.e. electrophoresis, and a shift of aqueous solution in the direction of the cathode, i.e. electro-osmosis, takes place in the applied electric field, i.e. transudation is caused.

[0103] Also, as is known, the smallest vessels that regulate liquid content in myocardial tissue are the capillaries. In this regard, it is pointed out that the capillaries and other vessels as well are lined with a layer called glycocalyx, which controls the permeability of the vessel walls to fluid and other substances and exhibits a strong negative charge when in a healthy state.

[0104] However, in case this negative charge is disturbed, for example by disease or the like, the permeability of the vessels can increase and more fluid and other substances can leak out of the vessel, which then results in the occurrence of oedema of the myocardium. In addition to the above described effect, the charge of the glycocalyx can be restored by the applied electric field, thereby supporting the reduction of the oedema and consequently the improvement of cardiac function.

[0105] The above described effect is as such independent from the application with two internal coil electrodes, one coil electrode and one patch electrode or two patch electrodes applied on opposite parts of the internal organ like the on the left and the right ventricle.

[0106] This can be achieved with electrodes in the blood vessel system of the organ in question or in the lymphatic system.

[0107] This can further be achieved by exposing the affected organ or parts of the organ and the blood vessel system, in particular the capillaries of the blood vessel system, to a suitable electric field or current with an inherent electric field generated by any electrode configuration as described herein. The lymphatic system, as part of the affected organ, is thus simultaneously exposed to the field or current and responds by an increased and accelerated lymphatic flow.

[0108] Although the drawings FIGS. 1 to 4 only show the heart in the application, similar coil electrodes can be used for the treatment of a liver and/or a kidney. They can be used in blood vessels or the lymphatic system. Flat electrodes can be positioned on or near the liver or kidney with the flat electrodes on mainly opposite sides of the organ, so that the electric field and its field lines passes through the organ. This can also be done subcutaneously or from the exterior of the human body.

[0109] As an example of the clinical success of the above described osmotic-like and/or electrophoretic effect achieved by directly controlling an electric field applied onto the oedema-afflicted organs or vessels, the following results have been reported (Kosevic, D et al. (2021). Cardio-microcurrent device for chronic heart failure: first-in-human clinical study. ESC heart failure. 10.1002/ehf2.13242).

[0110] The average of patients included in the study reported therein is a New York Heart Association (NYHA) Class III non-ischemic patient in the age group of 29 to 67 years, with a body mass index of 22.5 to 35.9 and a history of heart failure, and in particular with a significantly reduced left ventricular ejection fraction (LVEF) and a 6 minute walk under about 250 m. The “6 min walk test” or “6MWT” has been developed by the American Thoracic Society as a reliable indicator in the form of a sub-maximal exercise test for assessing aerobic capacity and endurance, wherein the walking distance covered over a time of 6 minutes by the patient is used as the outcome by which to compare changes in performance capacity. Here, the average patient (as described before) achieved between ˜170 and ˜250 m at hospitalization, between ˜350 and ˜450 m after 14 days, and between ˜370 and ˜470 m after 6 months of device use, and, furthermore, the average patient's classification according to the NYHA improved to a significantly less critical class after this time period.

[0111] FIG. 5 shows a two external electrodes (external patches with single electrodes) disposition of electrodes on external kidney surfaces according to the invention during use. There are two kidneys 11 with a symbolic central aorta or vena renalis 13. Ureters 12 connect the kidneys 11 with the bladder of the person. A patch electrode 440 is positioned on the outside of one kidney 11. A second patch electrode 440′ (with an identical outlay to the first patch electrode 440) is positioned on the opposite side of the kidney 11. Therefore, the core part of the kidney with its renal pyramids 17, renal calix 16 and the renal pelvis 18 is positioned between the two patches 440 and patches 440′.

[0112] The flat electrode patches 440 and 440′ are connected with a control unit 50, not shown in FIG. 5, via connection lines 51 and 52, respectively. The supply lines 51 and 52 provide an electric field between the flat electrode patches 440 and 440′ wherein the electric flux through the mentioned parts of the kidney then effectively reduces the oedema through electro-osmotic and/or electrophoretic effects. The electrode patches 440 and 440′ are shown as single electrodes but can also be segmented electrodes as shown in FIG. 3.

[0113] FIG. 6 shows a mixed (one internal coil electrode, one external patch electrode) disposition of electrodes in and outside the kidney. The kidney 11 is shown with its renal pyramids 17, renal calix 16 and the renal pelvis 18. The aorta renalis 14 and vena renalis 15 are shown as well. A first external electrode 440 is connected via line 51 to a control unit 50 (not shown). A renal coil electrode 540 is positioned in the vena renalis 15 to allow an electric field between this electrode 540 and said external patch electrode 440. The connection of the renal coil electrode 540 to the control unit 50 is effected via the catheter line 53 used to position the renal coil electrode 540. The coil electrode could in other embodiments also positioned in the renal lymphatic system.

[0114] Within the electrode assembly 20, 120, the lines 51, 52 and/or 53 are usually electrically isolated, e.g. in a catheter or in an isolating sheath. The two electrodes, independent from the fact if they are two patch electrodes 140, 240, 340, 440, 440′ especially non-segmented and having one single electrode surface each, two coil electrodes 30, 40 or one coil/one 5 patch electrode 30/140,440/540 can provide a first electrode and a second electrode which one or both can have electrically isolating sheaths. The electrically isolating sheaths are preferably completely encompassing the electrodes until the electric lines 51, 52 or 53 leading to the control unit 50 (and also encompassing these elements). Such electrically isolating sheath can comprise a material taken from the group encompassing silicone, thermoplast, PEEK, 10 PHA and PHB, i.e. use one or more of these and further material but it can also consist of one of these as e.g. silicone or PEEK alone. Then the effect of treatment of internal organ oedema is based on a voltage and a charge applied on the electrode and the dependency of the internal organ, and further body material between the electrodes as body liquids, vessels, organ tissue, and possibly skin), i.e. presetting and directly controlling the electric field between the isolated electrodes alone provides the desired electro-osmotic and/or electrophoretic effect which reduces the oedema of the internal organ, e.g. heart, liver or kidney.

TABLE-US-00001 LIST OF REFERENCE SIGNS 10 heart (internal organ)  60 person 11 kidney (internal organ)  70 patch electrode surface 12 ureter  72 opening 13 aorta or vena renalis  73 diaphragm valve 14 aorta renalis  75 electrode surface 15 vena renalis  77 flow of aqueous solution 16 renal calix 120 electrode assembly 17 renal pyramid 140 external patch electrode 18 renal pelvis 141 edge of the surface electrode 20 electrode assembly 152 single-conductor supply line 30 ventricular coil electrode 155 arrow indicating general direction of electric field lines 40 coil electrode for coronary sinus 240 first external patch electrode 50 control circuit 340 second external patch electrode 51 single-conductor supply line 440 first external patch electrode 52 single-conductor supply line 440′ second external patch electrode 53 renal catheter line 540 renal coil electrode 55 arrow indicating general direction of electric field lines