Potential therapy device

Abstract

To provide an electric potential treatment device that can stimulate cells in a living body by negatively charging the living body and then removing the charge from the living body, thereby activating the cells. [Solution] The electric potential therapy device 1 comprises a negative voltage application means 2, an electrostatic charge removal means 3, and a controller 4 for controlling the negative voltage application means 2 and the electrostatic charge removal means 3 during a predetermined treatment time in which a treatment cycle consisting of a first period and a second period is repeated multiple times. The negative voltage application means 2 comprises a negative voltage generator 21 and an application electrode 22, and the negative voltage generated by the negative voltage generator 21 is applied to the living body P via the application electrode 22. The controller 4 causes the negative voltage application means 2 to apply a negative voltage to the living body P, thereby negatively charging the living body P during the first period, and causes the electrostatic charge removal means 3 to remove the electrostatic charge from within the living body P during the second period, leaving the living body P in an uncharged state.

Description

[Technical Field]

[0001] The present invention relates to an electric potential therapeutic device. [Background technology]

[0002] Electric potential therapy devices have been proposed that apply a high electric potential to the human body to improve symptoms such as stiff shoulders, headaches, insomnia, and chronic constipation. These electric potential therapy devices include those that apply a positive high electric potential and a negative high electric potential alternately to the human body, those that apply only a positive high electric potential, and those that apply only a negative high electric potential (see, for example, Patent Documents 1 and 2). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. 10-272191 [Patent Document 2] Registered Utility Model No. 3212573 Summary of the Invention [Problem to be solved by the invention]

[0004] The present invention aims to provide an electric potential therapy device that can negatively charge a living body and then remove the charge from the living body, thereby providing an electrostatic stimulus to the cells of the living body and activating them.

[0005] An electric potential therapy device according to one aspect of the present invention comprises a negative voltage application means for applying a negative voltage to a living body, an electrostatic charge removal means for removing electrostatic charge from within the living body, and a controller for controlling the negative voltage application means and the electrostatic charge removal means during a predetermined treatment time in which a treatment cycle consisting of a first period and a second period is repeated multiple times, the negative voltage application means comprising a negative voltage generator for generating a negative voltage and a first electrode connected to the negative voltage generator, the negative voltage generated by the negative voltage generator being applied to the living body via the first electrode, and the controller causing the negative voltage application means to apply a negative voltage to the living body, thereby negatively charging the living body during the first period, and causing the electrostatic charge removal means to remove electrostatic charge from within the living body during the second period, leaving the living body in an uncharged state. [Effects of the Invention]

[0006] According to one aspect of the electric potential therapy device of the present invention, the controller controls the negative voltage application means and the charge removal means so that in each treatment cycle, the living body is negatively charged in the first period and is left uncharged in the second period, and this treatment cycle is repeated multiple times, thereby providing an electrical charging stimulus to the cells of the living body and activating them. [Brief explanation of the drawings]

[0007] [Figure 1] 1 is a functional block diagram of an electric potential therapeutic device according to a first embodiment of the present invention. [Figure 2] 2 is a plan view showing an example of a conductive member on which electrodes provided in the electric potential treatment device shown in FIG. 1 are formed. FIG. [Figure 3] 3 is a graph showing the timing at which application signals and removal signals are output in the electric potential treatment device shown in FIG. [Figure 4] 3 is a graph illustrating the timing at which the electric charge is removed from the living body by the electric potential treatment device shown in FIG. 1. [Figure 5] 2 is a graph showing the charged state of a living body when potential treatment is performed on the living body using the potential treatment device shown in FIG. 1. [Figure 6]FIG. 5 is a functional block diagram of an electric potential therapeutic device according to a second embodiment of the present invention. [Figure 7] 7 is a diagram for explaining how the value of the potential applied to a living body by the electric potential therapy device shown in FIG. 6 fluctuates. [Figure 8] 6 is a graph showing the timing at which application signals and removal signals are output in an electric potential treatment device according to a first modified embodiment of the present invention. [Figure 9] FIG. 10 is a functional block diagram showing the electrostatic charge removing means provided in an electric potential therapy device according to a second modified embodiment of the present invention. [Figure 10] FIG. 2 is a diagram illustrating the electric potential treatment method for mice in Example 1. [Figure 11] Graph showing the amount of albumin in urine in Example 1. [Figure 12] Graph showing dROMs (U.CARR) values ​​in Example 1. [Figure 13] 1 is a micrograph showing the results of acrolein red staining in Example 1. [Figure 14] 14 is a graph showing numerical values ​​of the acrolein red-positive area in FIG. 13. [Figure 15] 1 is a micrograph showing the results of desmin staining in Example 1. [Figure 16] Graph showing the quantification of the positive areas in FIG. 15. [Figure 17] (a) is a scanning electron micrograph of the ultrastructure of podocyte foot processes in the glomerulus in Example 1, and (b) is a transmission electron micrograph thereof. [Figure 18] Graph showing the analysis results of body weight and plasma samples in Example 1. [Figure 19] FIG. 2 is an explanatory diagram showing an example of attachment of an application electrode and a removal electrode to a living body. [Figure 20] 1(a) is a phase-contrast micrograph of blood before use of the electric potential treatment device in Example 2, and FIG. 1(b) is a phase-contrast micrograph of blood after use of the electric potential treatment device in Example 2. FIG. [Figure 21]1(a) is a phase-contrast micrograph of blood before use of the electric potential treatment device in Example 3, and FIG. 1(b) is a phase-contrast micrograph of blood after use of the electric potential treatment device in Example 3. FIG. BEST MODE FOR CARRYING OUT THE INVENTION

[0008] [First embodiment] An electric potential therapy device according to a first embodiment of the present invention will now be described with reference to the accompanying drawings. Referring to Fig. 1, an electric potential therapy device 1 according to this embodiment comprises negative voltage application means (negative voltage application unit) 2 for applying a negative voltage to a living body P, electrostatic charge removal means (electrostatic charge removal unit) 3 for removing electrostatic charge from within the living body P, a processor 4 for controlling the negative voltage application means 2 and the electrostatic charge removal means 3, a memory 5, an operation interface 6, and an AC adapter 7. The living body P is a human or animal body.

[0009] The negative voltage application means 2 includes a negative voltage generator 21 that generates a negative voltage, an application electrode 22 (first electrode) connected to the negative voltage generator 21, and an output resistor 23 provided between the negative voltage generator 21 and the application electrode 22, and the negative voltage generated by the negative voltage generator 21 is applied to the living body P via the application electrode 22. The output resistor 23 prevents current from flowing from the negative voltage generator 21 to the application electrode 22. As a result, the negative voltage generated by the negative voltage generator 21 is applied to the living body P, but no current flows into the living body P.

[0010] The charged charge removal means 3 includes a charge consumption means (charge consumption unit) 31, a switch 32 connected to the charge consumption means 31, a removal electrode 33 (second electrode) connected to the switch 32, and a limiting resistor 34 interposed between the switch 32 and the removal electrode 33.

[0011] The charge consuming means 31 is, for example, a power consuming resistor. When the switch 32 is turned on, the charge consuming means 31 and the removal electrode 33 are electrically connected, and the charged charge is removed from the living body P and flows to the charge consuming means 31, where it is consumed by the charge consuming means 31. On the other hand, when the switch 32 is turned off, the charge consuming means 31 and the removal electrode 33 are electrically cut off, and the charged charge is not removed from the living body P via the removal electrode 33. It is preferable to use a relay switch as the switch 32.

[0012] The processor 4 is an arithmetic processing unit such as a CPU (Central Processing Unit) or an MPU (Multi Processing Unit), and functions as a control unit (controller) that controls each part of the electric potential therapy device 1 by reading and executing programs stored in the memory 5.

[0013] The memory 5 stores programs executed by the processor 4, data used by the processor 4, and the like.

[0014] The operation interface 6 receives operation inputs for the electric potential therapy device 1 and includes various dials and buttons, and when the user operates these dials or buttons, a signal resulting from the operation is input to the processor 4. In this embodiment, the dials included in the operation interface 6 include a voltage setting dial 61 and a timer setting dial 62, and the buttons included in the operation interface 6 include a start button 63.

[0015] The AC adapter 7 is electrically connected to the negative voltage application means 2 and the processor 4. When the AC adapter 7 is connected to the commercial power source S, the AC adapter 7 converts commercial power (for example, commercial power of 100 V, 60 Hz) supplied from the commercial power source S into a predetermined DC power and supplies it to the negative voltage application means 2 and the processor 4.

[0016] 2, the application electrode 22 and the removal electrode 33 are preferably formed on conductive members 8 and 9, respectively. In this case, by attaching these conductive members 8 and 9 to the living organism P, the application electrode 22 and the removal electrode 33 come into electrical contact with the living organism P via the conductive members 8 and 9. There are no limitations on the shape of the conductive members 8 and 9, and they can be, for example, sheet-like, clip-like, belt-like, etc. In another embodiment, the application electrode 22 and the removal electrode 33 are formed on a single conductive sheet and come into electrical contact with the living organism P via the conductive sheet.

[0017] 3, during treatment time T0 when treatment is administered to living body P by electric potential treatment device 1, treatment cycles Ts are repeated multiple times in succession, and each treatment cycle Ts consists of a first period t1 and a second period t2 following the first period t1. In other words, during treatment time T0, the first period t1 and the second period t2 are repeated in succession, and the first period t1 and the second period t2 constitute a treatment cycle Ts.

[0018] The processor 4 then controls the negative voltage application means 2 and the charge removal means 3 so as to negatively charge the living body P during each first period t1 and to remove the charge from the living body P during each second period t2.

[0019] More specifically, as shown in Fig. 3, the processor 4 outputs an application signal to the negative voltage application means 2 (negative voltage generator 21) over the entire treatment time T0, and outputs a removal signal to the electrostatic charge removal means 3 (switch 32) during the second period t2. That is, the processor 4 generates and outputs the application signal but does not generate a removal signal during the first period t1, and generates and outputs the application signal and the removal signal during the second period t2.

[0020] When the negative voltage application means 2 receives an application signal from the processor 4, it generates a negative voltage and applies it to the living body P. That is, the negative voltage application means 2 continuously applies a constant negative voltage to the living body P over the entire treatment time T0.

[0021] When the electrostatic charge removal means 3 receives the removal signal from the processor 4, it removes the electrostatic charge from the living body P. That is, the electrostatic charge removal means 3 removes the electrostatic charge from the living body P during the second period t2 of each treatment cycle Ts during the treatment time T0.

[0022] In this embodiment, the switch 32 is composed of a relay switch, and when a removal signal from the processor 4 is input to the switch 32, the switch 32 (relay switch) is turned on, the removal electrode 33 and the charge consuming means 31 are electrically connected, and the charged charge in the living body P is removed to the charge consuming means 31 through the switch 32 and consumed.

[0023] On the other hand, if there is no removal signal from the processor 4 to the charge removal means 3, the switch 32 (relay switch) is turned off, the electrical connection between the removal electrode 33 and the charge consumption means 31 is cut off, and the charge in the living body P is not removed through the switch 32.

[0024] As a result, the timing at which the electric charge is removed from the living body P by the electric potential treatment device 1 is as shown in FIG. 4, and the charged state in the living body P is as shown in FIG.

[0025] In this way, during the first period t1 of each treatment cycle Ts, the inside of the living body P is negatively charged by the negative voltage applied by the negative voltage application means 2, and during the second period t2, the charged charge is removed from the inside of the living body P by the charged charge removal means 3, and the living body P becomes uncharged.

[0026] Here, the charged charges removed from the living body P by the charged charge removal means 3 include positive (+) charged charges and negative (-) charged charges present in the living body P, as well as negative (-) charged charges accumulated by the application of a negative voltage by the negative voltage application means 2.

[0027] The limiting resistor 34 prevents the charge removed from the living body P by the charge removal means 3 from flowing back into the living body P, and also suppresses the bioelectric current flowing through the epidermis of the living body P when the charge is removed, thereby preventing overstimulation of the nerves.

[0028] The voltage setting dial 61 is configured by, for example, a rotary encoder, and the user can set the value of the voltage to be applied to the living body P by the negative voltage application means 2 by rotating the voltage setting dial 61.

[0029] The timer setting dial 62 is configured by, for example, a rotary encoder, and the user can set the length of the treatment time T0 (hereinafter referred to as "treatment time length") by rotating the timer setting dial 62.

[0030] In this embodiment, the voltage applied to the living body P by the negative voltage application means 2 is a high voltage, and the value of this high voltage is preferably −600 V to −3600 V. If the voltage value is less than −600 V, the voltage difference (potential difference) between the uncharged and charged states becomes small, and there is a risk that a sufficient activating stimulus will not be given to the living body P, and if the voltage value is greater than −3600 V, there is a risk that the reflexes (autonomic reflexes, etc.) of the living body P will become strong, which is undesirable.

[0031] The length of the first period t1 is preferably 5 to 30 seconds. If the length of the first period t1 is shorter than 5 seconds, the frequency of bioelectric currents flowing through the epidermis of the living organism P when removing the charged charge increases, which may damage the epidermis of the living organism P. On the other hand, if the length of the first period t1 is longer than 30 seconds, the intervals between occurrences of the second period t2 during which the living organism P is in an uncharged state become too long, which may result in insufficient activation stimulation being applied to the living organism P.

[0032] The length of the second period t2 is preferably 1 / 1000 second (1 ms) to 1 / 200 second (5 ms). If the length of the second period t2 exceeds 1 / 200 second (5 ms), the bioelectric current generated when removing the charged charge may chemically react with sodium in the epidermis of the living body P, potentially damaging the epidermis.

[0033] The treatment time length is preferably 1 to 60 minutes. The treatment time length is appropriately selected depending on the symptoms of the living body P, the frequency of use of the electric potential treatment device 1, the physique of the living body P, etc., but if it exceeds 60 minutes, the living body P may develop a resistance to the electric charge stimulation, which may impair the therapeutic effect.

[0034] Next, we will explain the electric potential treatment method using the electric potential treatment device 1. The user first operates the voltage setting dial 61 to set the value of the voltage to be applied to the living body P (for example, -800 V), and then operates the timer setting dial 62 to set the length of treatment time (for example, 20 minutes).

[0035] Next, the application electrode 22 and the removal electrode 33 are brought into electrical contact with the living body P, for example, by attaching the conductive members 8 and 9 to the living body P.

[0036] Next, when the user operates the start button 63, the processor 4 continuously outputs an application signal to the negative voltage application means 2 for the set treatment time T0 (e.g., 20 minutes), and outputs a removal signal to the charge removal means 3 during the second period t2 of each treatment cycle Ts.

[0037] As a result, during the first period t1, a negative charge is stored in the living body P due to the negative voltage (negative high voltage) applied to the living body P, and the living body P becomes negatively charged. As a result, the oxidized substances (positively charged) and oxidized internal organ tissues (positively charged) that have accumulated in the living body P due to external and internal factors become negatively charged (-).

[0038] In addition, in the second period t2 following the first period t1, the switch 32 is turned on, thereby removing the charged charge from within the living body P to the charge consumption means 31, and the living body P is forced into an uncharged state (±0 charge).

[0039] By repeating the first period t1 and the second period t2, the living body P is not placed in a positively charged state, but alternates between a negatively charged state and an uncharged state. As a result, the oxidized blood, body fluids, and internal organs of the living body P are induced from a positive charge (+) to a negative charge (-), gradually restoring the charge balance of the living body P and reducing oxidative stress.

[0040] In other words, reactive oxygen species (ROS) are generated during the metabolic process in biological P, which uses oxygen to generate energy. While ROS are necessary for life, they are known to oxidize and damage the cells that make up biological P. Biological P possesses antioxidant functions to prevent the adverse effects of oxidation caused by ROS, and this homeostasis maintains the health of the organism. A state in which the balance between oxidation and antioxidant activity is disrupted and oxidation becomes excessive is called oxidative stress.

[0041] In addition, positive and negative charges always exist within biological P, and as cellular oxidation progresses, the biological P becomes more positively charged, causing an imbalance in the charge balance. However, conversely, when the charge balance in biological P is restored, oxidative stress and, ultimately, various oxidative stress diseases are alleviated.

[0042] The electric potential therapy device 1 according to this embodiment adjusts the charge balance of the living body P by repeatedly putting the living body P in a negatively charged state and an uncharged state, without putting the living body P in a positively charged state as described above.

[0043] [Second embodiment] Next, an electric potential therapy device according to a second embodiment of the present invention will be described. Referring to Figure 6, an electric potential therapy device 101 according to this embodiment is substantially the same as the above-described electric potential therapy device 1, except that the electric potential therapy device 101 includes negative voltage application means (negative voltage application unit) 102 instead of the negative voltage application means 2, and the negative voltage application means 102 includes an input voltage variable device 120 in addition to the above-described negative voltage generator 21, application electrode 22, and output resistor 23. The voltage setting dial (61) is also omitted.

[0044] The input voltage variable device 120 is electrically connected to the AC adapter 7 and changes the voltage of the DC power supplied from the AC adapter 7. Negative voltage generator 21 In addition to outputting the above-mentioned application signal and removal signal to negative voltage generator 21 and switch 32, processor 4 also outputs a voltage control signal to input voltage variable device 120. Input voltage variable device 120 changes the value of the voltage to be output to negative voltage generator 21 in response to the voltage control signal from processor 4.

[0045] Here, the processor 4 controls the input voltage variable device 120 via a voltage control signal so that the value of the negative voltage output from the input voltage variable device 120 to the negative voltage generator 21 varies randomly or according to a predetermined pattern.

[0046] As a result, the value of the negative voltage generated by the negative voltage generator 21 and applied to the living body P varies within a predetermined range. Note that this range can be selected arbitrarily, but is preferably set to, for example, -600V to -3600V.

[0047] As a result, as shown in FIG. 7, the value of the potential applied to the living body P during the first period t1 of each treatment cycle Ts varies within a predetermined range.

[0048] In this way, by varying the value of the voltage applied to the living body P randomly or in a predetermined pattern, it is possible to prevent the tissues of the living body P from becoming resistant to the activation stimulus, compared to when a constant voltage is applied to the living body P as in the first embodiment, thereby increasing the effect of the activation stimulus on the living body P and further shortening the treatment time.

[0049] Such a voltage control signal is generated by, for example, the processor 4 executing a predetermined control program stored in the memory 5.

[0050] [First transformation form] Next, an electric potential therapy device according to a first modification of the first and second embodiments will be described. In the above embodiments, the processor 4 outputs an application signal throughout the entire treatment time T0. However, in this modification, as shown in Fig. 8, the processor 4 outputs an application signal during the first period t1 of each treatment cycle Ts, but does not output an application signal during the second period t2. With this configuration, the living body P is negatively charged during the first period t1, and the charge is removed from the living body P during the second period t2, leaving the living body P in an uncharged state, just as described above.

[0051] [Second transformation form] Next, an electric potential therapy device according to a second modified embodiment of the first and second embodiments will be described. In the above embodiments, the electrostatic charge removing means 3 consumes the electrostatic charge removed from the living body P using the electric charge consuming means 31. However, in this modified embodiment, as shown in Fig. 9, the electrostatic charge removing means 3 does not include the electric charge consuming means 31, and the switch 32 is connected to the ground. As a result, when the switch 32 is turned on, the removal electrode 33 is electrically connected to the ground, and the electrostatic charge removed from the living body P is released to the ground via the switch 32.

[0052] [Third transformation form] Next, a third modified embodiment of the first and second embodiments will be described. In the above embodiments, the electric potential treatment device 1 includes a single application electrode 22 and a single elimination electrode 33, but in this modified embodiment, the electric potential treatment device includes two or more (for example, four) application electrodes 22. In this case, for example, two application electrodes 22 are attached so as to be in electrical contact with both arms of the living body P, and the remaining two application electrodes 22 are attached so as to be in electrical contact with both ankles of the living body P. Note that in other modified embodiments, the electric potential treatment device includes two or more elimination electrodes 33.

[0053] [Example 1] An experiment was conducted to verify the effect of the above-described electric potential therapeutic device 1. The experiment was carried out using db / db mice, which are type 2 diabetes model mice.

[0054] (1) Experiment Overview For the experiment, 10 7-week-old male mice (db / db mice) were purchased and used for the test after three days of preliminary breeding. These db / db mice were randomly divided into treatment and non-treatment groups, with five mice each. Only the treatment group received potential treatment using the potential treatment device 1.

[0055] The treatment period was 28 days (4 weeks), and the db / db mice in the treatment group were treated twice a day, in the morning and afternoon, with an 8-hour interval between treatments. The applied voltage was -1000V, and the treatment duration was 30 minutes.

[0056] 10, the electric potential treatment was performed by placing mouse M in the treatment group on a conductive metal plate PL and connecting the application electrode 22 and the removal electrode 33 to the metal plate PL. That is, mouse M's hairless paw Ma came into contact with the metal plate PL, thereby electrically contacting the application electrode 22 and the removal electrode 33 via the metal plate PL, and the electric potential treatment was performed on mouse M by alternately repeating a "negatively charged (-)" and "uncharged (±0 charge)" state with respect to the metal plate PL.

[0057] (2) Collection of urine samples Before the start of treatment (hereinafter referred to as "week 0") and at week 4, 24-hour urine collection was performed, and urine samples were collected.

[0058] (3) Weight measurement Body weight was measured after the 0th week and the final day of treatment.

[0059] (4) Collection of plasma samples Approximately 150 μL of blood was collected from the tail vein as a blood sample at week 0. After the final day of treatment, whole blood was collected under anesthesia as a blood sample at week 4. To prevent potential adverse effects on the analytical kit, only sodium heparin was used as an anticoagulant. The collected blood samples were centrifuged at a centrifugal acceleration of 1000 × g for 15 minutes, and the supernatant (plasma sample) was collected.

[0060] (5) Kidney sample collection After the collection of whole blood as described in (4) above, the animals were perfused with phosphate-buffered saline (PBS) to completely remove blood, and then the left kidney was removed (first kidney sample).

[0061] The right kidney was then removed after perfusion with fixative and fixation. Some of the right kidneys were immersed in 10% formalin, embedded in paraffin, and sliced ​​into 4 μm thin sections using a microtome to prepare kidney paraffin sections.

[0062] The other right zona was immersed in 10% formalin for 16 hours and then ultrathinly sliced ​​(100 nm) to prepare a second kidney sample.

[0063] (6) Analysis results of urine samples Albumin was detected in urine samples collected as described above. Specifically, albumin in the urine samples was separated by electrophoresis (SDS-PAGE) using 10% acrylamide gel, followed by Coomassie Brilliant Blue (CBB) staining. After staining, the gel was scanned, the scanned data was imported into a computer, and the albumin amount was quantified by comparing it with an albumin standard using the image analysis software ImageJ. The results are shown in Figure 11.

[0064] As shown in Figure 11, in both groups, a significant increase in urinary albumin levels was observed at week 4 compared to week 0, due to the progression of diabetes, but the increase in urinary albumin levels was significantly suppressed in the treatment group compared to the untreated group.

[0065] (7) Whole-body oxidative stress measurement results To measure whole-body oxidative stress, dROMs (one of the indicators of oxidative stress) in plasma samples was measured using the redox analyzer "REDOKLIBRA2" (manufactured by WISMERLL). The operation of the device was carried out according to the manual. The results are shown in Figure 12.

[0066] As can be seen from Figure 12, the dROMs value was significantly reduced in the treatment group after treatment compared with the untreated group, suggesting that oxidative stress in the blood, which is increased by diabetes, may have been reduced in the treatment group.

[0067] (8) Detection of oxidative stress in the kidney To detect oxidative stress in the kidney, acrolein was examined in the tissue of the first kidney sample described above. Specifically, the left kidney was divided in half in the sagittal plane and then further divided into one-third in the transverse plane. The kidney pieces were stained by immersion in 20 μmol / L Acrolein-RED (Funakoshi Co., Ltd.) (1:100) for 30 minutes. The kidney pieces were then washed four times with PBS and frozen into blocks. The frozen blocks were sliced ​​at 8 μm, fixed, stained with DAPI, mounted with cover slips, and observed under a confocal microscope.

[0068] Figure 13 shows a micrograph of the results of acrolein red staining, and Figure 14 shows a graph quantifying the acrolein red-positive area. The amount of acrolein in the kidneys of the untreated group was increased, but the amount of acrolein in the kidneys of the treated group was significantly reduced compared to the untreated group.

[0069] (9) Desmin staining The kidney paraffin sections were then boiled in citrate buffer for 15 minutes for antigen retrieval, permeabilized with 0.1% Triton X-100 (Union Carbide Corporation) as a permeabilization reagent, and blocked with 3% skim milk. Primary antibodies were diluted in blocking solution and incubated at 4°C. One After overnight incubation, the sections were incubated with a fluorescent dye-labeled secondary antibody for 1 hour at room temperature.

[0070] The antibodies used were as follows: ·Anti-nephrin guinea pig polyclonal (Cat. No. GP-N2) - 1:300 (Progen) ·Anti-desmin rabbit monoclonal (Clone D93F5, Cat. No. 5332) - 1:300 (Cell Signaling Technology) ·Alexa Fluor 488 or 555 goat anti-rabbit - 1:1000 (Thermo Fisher Scientific) ·Alexa Fluor 488 or 555 goat anti-mouse - 1:1000 (Thermo Fisher Scientific)

[0071] Figure 15 is a micrograph showing the results of desmin staining. Figure 16 is a graph showing the quantification of the positive areas by desmin staining. thread Although the amount of desmin deposition in the glomeruli was high, desmin deposition in the renal glomeruli was significantly suppressed in the treatment group compared to the untreated group.

[0072] (10) Ultrastructural analysis of renal glomeruli using electron microscopy The ultrastructure of podocyte foot processes in the glomeruli of the second kidney samples described above was observed by scanning electron microscopy and transmission electron microscopy.

[0073] Figure 17(a) shows a scanning electron microscope image. In the untreated group, podocytes had thickening of the primary processes and shortening of the foot processes. As the foot processes shortened, they lost their regular interlocking and gaps formed. When this type of foot process shortening (or disappearance) occurs, protein leaks from the gaps between the foot processes, resulting in proteinuria. In the treated group, these findings were alleviated.

[0074] Figure 17(b) shows a transmission electron micrograph. Here, the observation focuses on the foot processes branching from the primary processes. In the untreated group, the foot processes were shortened, indicating damage to the podocytes. In the treated group, the foot process length was preserved and longer than in the untreated group.

[0075] (11) Analysis of body weight and plasma samples Blood glucose, triglyceride, and total cholesterol concentrations were measured. As can be seen from Figure 18, body weight and all blood concentration measurements showed an increasing trend over time, but no significant difference was observed between the two groups.

[0076] From the above, it was confirmed that potential therapy using potential therapy device 1 is effective in suppressing urinary albumin excretion, improving blood oxidative stress indicated by dROMs and renal oxidative stress indicated by acrolein levels, and improving the amount of desmin deposition, which is an indicator of renal glomerular damage.

[0077] Furthermore, since there was no effect on blood glucose, triglyceride, or total cholesterol concentrations, it is suggested that the effect of reducing kidney damage caused by the progression of diabetes is due to a reduction in oxidative stress (dROMs, acrolein, etc.). It is believed that the electric potential treatment using the electric potential treatment device 1 of this embodiment exerts an inhibitory effect on oxidative stress in the blood and kidneys, and that this effect also significantly reduced the amount of albumin in the urine (i.e., kidney damage was suppressed).

[0078] Traditionally, among ROS, hydroxyl radicals in particular have been thought to be the main cause of oxidative stress, but in recent years, it has been discovered that acrolein contributes to oxidative stress diseases. Acrolein is a strong oxidizing substance that is several dozen times more toxic than hydroxyl radicals, and since reducing acrolein leads to improvement of oxidative stress diseases, it is believed that the effect of reducing acrolein through electric potential therapy using the electric potential therapy device 1 of this embodiment is significant.

[0079] For these reasons, the electric potential therapy devices 1, 101 according to the above-described embodiments and modifications can be used as kidney disease treatment devices, oxidative stress reduction devices, acrolein reduction devices, and the like.

[0080] Here, when the electric potential therapy device 1 (101) is used as a kidney disease treatment device, it is preferable to attach the application electrode 22 to the back side of the living body P and the removal electrode 33 to the ventral side so that the kidney Pa is located between the application electrode 22 and the removal electrode 33, as shown in Figures 1 and 19.

[0081] [Example 2] Blood was collected from a man in his 50s and observed under a phase-contrast microscope. Figure 20(a) shows the state of the man's blood before the electric potential therapy device 1 was used, and "aggregated red blood cells" were observed, in which red blood cells clumped together and were completely immobile. Figure 20(b) shows the state of the man's blood after the electric potential therapy device 1 was used (the electric potential therapy device 1 was used once, the applied voltage was -1000V, and the duration of use (T0) was 15 minutes). Compared to the blood before the use of the electric potential therapy device 1, it was confirmed that the "aggregated red blood cells" had changed into "aggregated red blood cells," which were mobile.

[0082] Red blood cell clumps (chain red blood cells, aggregated red blood cells) occur when the charge on the surface of the red blood cells weakens and the repulsive force between them decreases, but it was confirmed that by using the electric potential therapy device 1, polar repulsion occurs in the red blood cells, and clumps of red blood cells (chain red blood cells, aggregated red blood cells) are reduced.

[0083] [Example 3] Blood was collected from a man in his 40s and observed under a phase-contrast microscope. Figure 21(a) shows the condition of the man's blood before the electric potential therapy device 1 was used, and many "chain-like red blood cells" and "irregularly shaped red blood cells" that were not spherical were confirmed. Figure 21(b) shows the condition of the man's blood after the electric potential therapy device 1 was used (the electric potential therapy device 1 was used once, the applied voltage was -1000V, and the usage time (T0) was 15 minutes). Compared to the blood before the electric potential therapy device 1 was used, there was a clear decrease in clumps of red blood cells (chain-like red blood cells), and although there were still "fragmented red blood cells," the irregularly shaped red blood cells had changed to a normal, nearly round shape.

[0084] Although the embodiments and modifications of the present invention have been described above, the present invention is not limited to these embodiments and modifications, and various modifications and alterations are possible without departing from the scope of the present invention.

[0085] For example, the value of the voltage applied to the living body P is constant in the first embodiment and varies randomly in the second embodiment, but in the electric potential therapy device of other embodiments, it is possible to select between a first mode and a second mode, and when the electric potential therapy device is set to the first mode, the value of the voltage applied to the living body P is constant, and when the electric potential therapy device is set to the second mode, the value of the voltage applied to the living body P varies randomly. [Explanation of symbols]

[0086] 1,101 Potential treatment device 2,102 Negative voltage application means (negative voltage application unit) 3. Electrostatic charge removal means (electrostatic charge removal unit) 4 processors (controllers) 22 Application electrode (first electrode) 33 Removal electrode (second electrode) P living organism

Claims

1. A negative voltage application means for applying a negative voltage to a living body; a charge removing means for removing charge from the living body; a controller for controlling the negative voltage application means and the static charge removal means during a predetermined treatment time in which a treatment cycle consisting of a first period and a second period is repeated a plurality of times; the negative voltage application means includes a negative voltage generator that generates a negative voltage, and a first electrode connected to the negative voltage generator; The negative voltage generated by the negative voltage generator is applied to the living body via the first electrode, The controller: by applying a negative voltage to the living body by the negative voltage application means, the living body is negatively charged in the first period; During the second period, the electrostatic charge removing means removes the electrostatic charge from within the living body, thereby making the living body in an uncharged state; The negative voltage application means continuously applies a negative voltage to the living body during the first period, and the value of the voltage applied to the living body during the first period increases or decreases randomly or in a predetermined pattern within the range of -600V to -3600V.

2. The negative voltage application means includes a negative voltage generator and an input voltage variable device that changes the voltage of DC power and outputs the changed voltage to the negative voltage generator; 2. The electric potential therapeutic device according to claim 1, wherein the processor controls the input voltage variable device so that the value of the voltage applied to the living body P increases or decreases randomly or in a predetermined pattern within a range of -600V to -3600V.

3. 2. The electric potential therapeutic device according to claim 1, wherein the time length of the first period is 5 seconds to 30 seconds, and the time length of the second period is 1 / 1000 seconds to 1 / 200 seconds.

4. The electric potential therapeutic device according to any one of claims 1 to 3, which is a renal disease therapeutic device.

5. The electric potential therapeutic device according to any one of claims 1 to 3, which is an oxidative stress reducing device.

6. The controller outputs an application signal and a removal signal; the negative voltage application means applies a negative voltage to the living body when the application signal is received from the controller; The charge removing means removes the charge from the living body when the charge removing signal is received from the controller, the controller outputs the application signal to the negative voltage application means during the entire treatment time, and outputs the removal signal to the charge removal means during the second period; 4. The electric potential therapeutic device according to claim 1, wherein said negative voltage application means applies a negative voltage to said living body for the entire treatment time by receiving said application signal.

7. The controller outputs an application signal and a removal signal; the negative voltage application means applies a negative voltage to the living body when the application signal is received from the controller; The charge removing means removes the charge from the living body when the charge removing signal is received from the controller, 4. The electric potential therapy device according to claim 1, wherein the controller outputs the application signal to the negative voltage application means during the first period, and outputs the removal signal to the charge removal means during the second period.

8. the charge removing means includes a charge consuming means, a switch, and a second electrode; The controller turns off the switch during the first period and turns on the switch during the second period; An electric potential therapeutic device as described in any one of claims 1 to 3, wherein when the switch is turned on, the second electrode is electrically connected to the charge consuming means via the switch, and the charged charge flows from the living body via the second electrode and the switch to the charge consuming means and is consumed by the charge consuming means.

9. The electrostatic charge removing means includes a switch and a second electrode. The controller turns off the switch during the first period and turns on the switch during the second period; An electric potential therapy device as described in any one of claims 1 to 3, wherein when the switch is turned on, the second electrode is electrically connected to earth via the switch, and the charged charge is removed from the living body and released to the earth via the second electrode and the switch.