Medical magnetic generator

Abstract

To provide a medical magnetic generator which is non-invasive, can easily act on a brain without directly applying a stimulation to the head of a human body, and can treat or prevent nervous and mental diseases such as depression and dementia.SOLUTION: There is provided a medical magnetic generator which radiates an alternating magnetic field to a part other than the head of a human body for generating an eddy current, for treating or preventing, mental and nervous diseases.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a medical magnetic field generating device that acts on the brain non-invasively and simply by irradiating a magnetic field to parts of the human body other than the head, thereby treating or preventing mental and neurological disorders such as dementia and depression. [Background technology]

[0002] Psychiatric and neurological disorders are a general term for diseases that cause functional disorders of the brain, spinal cord, peripheral nerves, etc., and include a wide range of conditions, such as cerebrovascular disorders, cognitive disorders, psychiatric disorders, degenerative diseases, demyelinating diseases, neuroimmune diseases, central nervous system diseases, peripheral nervous system diseases, and muscle diseases, and include stroke, dementia, depression, schizophrenia, Parkinson's disease, epilepsy, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Guillain-Barre syndrome, myasthenia gravis, etc. For example, there is a repetitive transcranial magnetic stimulation (rTMS) device as a method for treating depression. According to Anke Post et al., "Transcranial magnetic stimulation as a therapeutic tool in psychiatry: what do we know about the neurobiological mechanisms?", (2001), Journal of Psychiatric Research, 35(4):193-215 (Non-Patent Document 1), and Shinsuke Kito et al., "Regional cerebral blood flow changes after low-frequency transcranial magnetic stimulation of the right dorsolateral prefrontal cortex in treatment-resistant depression", (2008), Neuropsychobiology, 58(1):29-36 (Non-Patent Document 2), the rTMS device non-invasively applies magnetic stimulation to the "left dorsolateral prefrontal cortex" from a magnetic coil placed on the head, activating the brain by promoting the release of neurotransmitters, and it is expected that treatment of about 40 minutes, five times a week, for a total of 20 to 30 times, will reduce or eliminate depressive symptoms.

[0003] Figure 15 is a schematic diagram of magnetic stimulation by an rTMS device. In an rTMS device, an electric field is induced in the cortex in the area directly under the treatment coil by a pulsed magnetic field, which induces local eddy currents, which accumulate electric charges in the neuronal membrane. When the charge density becomes high enough to activate the neuronal potential, neurotransmitters are released. Regular, repeated stimulation can bring about physiological changes and improve depression symptoms.

[0004] However, in treatment using an rTMS device, high-output magnetic fields (0.5T (tesla) or 1.2-2.4T depending on the device) are directly irradiated to the head, so headaches, tinnitus, dizziness, and discomfort are relatively frequent, and fainting and convulsions have also been reported as serious side effects, making it highly invasive. In addition, there are problems such as the need to fix the head during treatment in order to irradiate local areas of the brain, and the long restraint time, making it inconvenient. A large-scale device and coil are required to generate high-output magnetic fields, and the treatment location is limited to hospitals from the perspective of electromagnetic protection, which places a heavy burden on patients and practitioners. Systems and methods using transcranial magnetic stimulation have been proposed in, for example, JP 2020-36704 A (Patent Document 1), but they are thought to have similar problems.

[0005] In addition, as a method of stimulating parts of the human body other than the head (these parts are collectively referred to as "periphery"), for example, JP 2021-166665 A (Patent Document 2) proposes transcutaneous electrical nerve stimulation (TENS), and for example, JP 2022-134700 A (Patent Document 3) proposes a magnetic stimulation device, and JP 2013-103121 A (Patent Document 4) proposes a magnetic stimulation device for rehabilitation treatment. However, all of these are rehabilitation treatment devices aimed at controlling the periphery by inducing muscle contraction.

[0006] Japanese Patent Publication No. 2022-168040 (Patent Document 5) proposes a system for treating tremors by electrically stimulating the periphery to affect the brain. It has also been known for some time that electrical stimulation of the periphery at around 2 kHz (low frequency) is conducted from the posterior horn of the spinal cord to the medulla oblongata and midbrain in synchronization with Aβ fibers, which are tactile nerves. Neurometer, a neurological function diagnostic device (商標) In a current perception threshold test using a Neurotron 2000 (manufactured by Neurotron), Aβ fibers can be selectively excited by 2kHz current stimulation. Aβ fibers transmit the sense of touch (sensory nerves) to the III layer of the gray matter of the dorsal horn of the spinal cord. However, low-frequency therapeutic devices using this principle have the problem that, because they apply electrical stimulation to the muscles from the skin, electrical resistance in the skin causes discomfort and pain. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] JP 2020-36704 A [Patent Document 2] Patent Publication No. 2021-166665 [Patent Document 3] Patent Publication No. 2022-134700 [Patent Document 4] JP 2013-103121 A [Patent Document 5] Patent Publication No. 2022-168040 [Non-patent literature]

[0008] [Non-Patent Document 1] Anke Post et al., "Transcranial magnetic stimulation as a therapeutic tool in psychiatry: what do we know about the neurobiological mechanisms?", (2001), Journal of Psychiatric Research, 35(4):193-215 [Non-Patent Document 2] Shinsuke Kito et al., "Regional cerebral blood flow changes after low-frequency transcranial magnetic stimulation of the right dorsolateral prefrontal cortex in treatment-resistant depression", (2008), Neuropsychobiology, 58(1): 29-36 Summary of the Invention [Problem to be solved by the invention]

[0009] The present invention has been made to solve the above-mentioned problems, and its purpose is to provide a medical magnetic generating device that is non-invasive, acts easily on the brain without directly stimulating the human head, and can treat or prevent mental and neurological disorders including dementia and depression. [Means for solving the problem]

[0010] The medical magnetic field generator of the present invention is characterized by irradiating an alternating magnetic field to a part of the human body other than the head to generate eddy currents, thereby treating or preventing mental and neurological disorders.

[0011] In the medical magnetic field generator of the present invention, it is preferable to generate eddy currents by irradiating an alternating magnetic field controlled to a frequency within the range of 1 to 3 kHz.

[0012] In the medical magnetic field generator of the present invention, the output magnetic flux density of the alternating magnetic field controlled to a frequency within the range of 1 to 3 kHz is preferably 10 mT or less.

[0013] In the medical magnetic field generator of the present invention, it is preferable to generate eddy currents by further irradiating an alternating magnetic field controlled to a frequency within a range of 225 to 275 MHz in synchronization with the alternating magnetic field controlled to a frequency within a range of 1 to 3 kHz.

[0014] In the medical magnetic field generating device of the present invention, it is preferable that the psychiatric / neurological disease is at least one selected from the group consisting of stroke, dementia, depression, schizophrenia, Parkinson's disease, epilepsy, multiple sclerosis, amyotrophic lateral sclerosis, Guillain-Barré syndrome, myasthenia gravis, fibromyalgia, adjustment disorder, and sleep disorder. Effect of the Invention

[0015] According to the present invention, it is possible to provide a medical magnetic generating device that is non-invasive, acts easily on the brain without directly stimulating the human head, and can treat or prevent mental and neurological disorders including dementia and depression. [Brief description of the drawings]

[0016] [Figure 1] 1 is a schematic diagram showing a specific example of a medical magnetic field generating device of the present invention. [Diagram 2] 1A is a schematic diagram showing an irradiation unit in a medical magnetic field generating device according to one embodiment, in which (a) is a top view, (b) is a rear view, and (c) is an AA cross-sectional view. [Diagram 3] 1A and 1B are printed wiring diagrams showing the coil arrangement of a medical magnetic field generating device according to one embodiment, in which FIG. [Figure 4] FIG. 1 shows a numerical human body model and a coil placed on the surface of the lower back used in calculations for an experiment to examine the penetration of a magnetic field into the body in Experimental Example 1. [Diagram 5] 1 shows the results of an experiment to investigate the penetration of a magnetic field into the body in Experimental Example 1, in which (a) is the magnetic field distribution in the XY plane and XZ plane of the maximum coordinates of the high frequency wave, the straight lines in the figure are X-ray straight lines passing through the maximum coordinates, and (b) is a graph showing the magnetic field strength (enlarged maximum point) on the straight line (X-axis) passing through the maximum coordinate of the high frequency wave. [Figure 6] 1 shows the results of an experiment to investigate the penetration of a magnetic field into the body in Experimental Example 1, in which (a) is the magnetic field distribution in the XY plane and XZ plane of the maximum coordinates of the low frequency, the straight lines in the figure are X-ray straight lines passing through the maximum coordinates, and (b) is a graph showing the magnetic field strength (enlarged maximum point) on the straight line (X-axis) passing through the maximum coordinates of the low frequency. [Figure 7] FIG. 1 is a diagram for explaining the behavioral pharmacological test in Experimental Example 2 (Morris water maze test using a rat model with spatial cognition disorder). [Figure 8] 13 is a graph showing the results of the platform arrival time in a transient spatial cognitive impairment model in Experimental Example 2. [Figure 9] 13 is a graph showing the results of the proportion of stays in a section in a model of transient spatial cognitive impairment in Experimental Example 2. [Figure 10] 13 is a graph showing the results of the platform arrival time according to the persistent spatial dementia model in Experimental Example 2. [Figure 11] 13 is a graph showing the results of the proportion of stays in a section by the persistent spatial dementia model in Experimental Example 2. [Figure 12] 13 is a photograph showing the texture evaluation in Experimental Example 2. [Figure 13] FIG. 13 is a diagram for explaining a forced swimming test in Experimental Example 3. [Figure 14] 13 is a graph showing the results of Experimental Example 3. [Figure 15] FIG. 1 is a schematic diagram illustrating magnetic stimulation by a prior art rTMS device. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] According to the medical magnetic generator of the present invention, an alternating magnetic field is applied to a portion (periphery) of the human body other than the head to generate an eddy current. Here, the peripheral portion to which the alternating magnetic field is applied is not particularly limited, and may be any portion other than the head, such as the neck, shoulders, chest, abdomen, back, waist, arms, buttocks, thighs, hands, or feet. The irradiated portion may be the head. According to the medical magnetic generator of the present invention, the peripheral nerves are stimulated with an alternating magnetic field of lower output than that of a conventional rTMS device, which acts on the brain non-invasively and simply, and it is possible to treat or prevent mental and neurological disorders such as dementia and depression. In addition, since the magnetic field is not directly applied to the head, the invasiveness is low, and headaches, tinnitus, dizziness, discomfort, fainting, and convulsions are unlikely to occur, there is no restraint during the treatment, and no large-scale device or coil is required. In addition, since no electrical stimulation is used, discomfort or stimulation pain due to electrical resistance in the skin does not occur.

[0018] In the medical magnetic generator of the present invention, an eddy current is generated by utilizing an alternating magnetic field. As described later in the device configuration, the generation of eddy currents by utilizing an alternating magnetic field can be achieved by setting an irradiation unit (probe) containing coils arranged in a concentric circle on the surface of the peripheral living body to which the alternating magnetic field is to be irradiated, and passing electricity through the coils. The principle is the same as that shown in FIG. 15 and explained above, and the action of the alternating magnetic field causes an induced current (eddy current) to flow in the peripheral living body, and this eddy current acts on the brain. In this way, in the present invention, by generating eddy currents in the living body, it is possible to stimulate nerves in the same way as electrical stimulation, without causing pain.

[0019] The medical magnetic field generator of the present invention can treat or prevent mental and neurological disorders such as dementia and depression by irradiating an alternating magnetic field to a part of the human body other than the head to generate an eddy current as described above. Here, the mental and neurological disorders are at least one selected from the group consisting of stroke, dementia (Alzheimer's dementia, vascular dementia, and dementia with Lewy bodies), depression, schizophrenia, Parkinson's disease, epilepsy, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Guillain-Barré syndrome, myasthenia gravis, fibromyalgia, adjustment disorder, and sleep disorder. Drug therapy is the first choice for these diseases, but since taking the medication affects the entire body, it comes with significant side effects such as gastrointestinal disorders, headaches, nausea, dizziness, drowsiness, and fatigue. However, the magnetic field output by the medical magnetic generator of the present invention meets the reference levels of the 2010 General Public Guidelines of ICNIRP (International Commission on Non-Ionizing Radiation Protection) for low frequencies, and meets the basic restrictions on local SAR (Specific Energy Absorption Rate) of the 2010 General Public Guidelines of ICNIRP for high frequencies, allowing for safe treatment with few side effects.

[0020] As demonstrated in Experimental Example 2 described later, in an evaluation of spatial cognitive impairment by a Morris water maze test using a rat spatial cognitive impairment model, the medical magnetic generator of the present invention improved spatial cognitive impairment in both the transient spatial dementia model and the persistent spatial dementia model (FIGS. 8 to 12). In addition, as demonstrated in Experimental Example 3 described later, in an evaluation of depressive behavior by a forced swimming test using a rat chronic pain / depression (CCI: chronic constriction injury / chronic sciatic nerve constriction injury) model, the medical magnetic generator of the present invention improved depressive symptoms (FIG. 14). From these experimental results, the medical magnetic generator of the present invention is particularly useful in the treatment or prevention of vascular dementia and the treatment of depression.

[0021] Furthermore, since the medical magnetic generating device of the present invention treats ischemic vascular disorders, it is preferable that it be used to treat or prevent cerebral strokes, including cerebral infarction, cerebral hemorrhage, and subarachnoid hemorrhage, and ischemic heart diseases, including angina pectoris and myocardial infarction, which are caused by arteriosclerosis due to high blood pressure, diabetes, obesity, etc.

[0022] The medical magnetic generator of the present invention preferably generates eddy currents by irradiating an alternating magnetic field controlled to a frequency (low frequency) in the range of 1 to 3 kHz. The alternating magnetic field may be controlled to a harmonic or subharmonic of a frequency in the range of 1 to 3 kHz, and a harmonic of 1 to 3 kHz may be generated when generating an alternating magnetic field of less than 1 kHz. By using an alternating magnetic field controlled to such a frequency, the induced eddy current stimulates the living body and acts on the brain. Specifically, 1 to 3 kHz is extracted from an external signal by a bandpass filter, the signal is processed to convert it into data, and the data is output randomly according to the data. The alternating magnetic field may be a hybrid wave, a low frequency alone, or a high frequency alone.

[0023] The medical magnetic field generator of the present invention preferably has an output magnetic flux density of 10 mT or less, more preferably 1 mT or less, of an alternating magnetic field controlled to a frequency within a range of 1 to 3 kHz. Thus, unlike conventional rTMS devices, which had high outputs of 0.5 T or 1.2 to 2.4 T depending on the device, the medical magnetic field generator of the present invention can achieve sufficient therapeutic / preventive effects with a significantly lower output.

[0024] The medical magnetic field generator of the present invention preferably further irradiates an alternating magnetic field controlled to a frequency (high frequency) in the range of 225 to 275 MHz in synchronization with an alternating magnetic field controlled to a frequency in the range of 1 to 3 kHz to generate an eddy current. The alternating magnetic field may be controlled to a harmonic or subharmonic of a frequency in the range of 225 to 275 MHz, and a harmonic of 225 to 275 MHz may be generated when generating an alternating magnetic field of less than 225 MHz. By irradiating a high-frequency alternating magnetic field in synchronization with such a low-frequency alternating magnetic field to generate an eddy current, the therapeutic / preventive effect of the medical magnetic field generator of the present invention can be further improved. Specifically, the output is synchronized with the low frequency and AM (Amplitude Modulation) modulation is performed.

[0025] The medical magnetic field generator of the present invention preferably has an output magnetic flux density of 10 mT or less, more preferably 1 μT or less, of an alternating magnetic field controlled to a frequency within the range of 225 to 275 MHz. Thus, unlike conventional rTMS devices, which had high outputs of 0.5 T or 1.2 to 2.4 T depending on the device, the medical magnetic field generator of the present invention can achieve sufficient therapeutic / preventive effects with a significantly lower output.

[0026] Hereinafter, specific examples of the medical magnetic generator of the present invention will be described with reference to the drawings. Note that the drawings are schematic and may differ from the actual ones. The following description is an example of a method for embodying the technical idea of ​​the present invention, and the configuration is not limited to the one described below. The technical idea of ​​the present invention can be modified in various ways within the technical scope described in the claims.

[0027] Here, Fig. 1 is a schematic diagram showing a specific example of a medical magnetic field generator of the present invention. The medical magnetic field generator shown in Fig. 1 includes a device main body 1 and a probe 11 connected to the device main body 1 via a signal cable 21, and the device main body 1 also includes a power cable (not shown) that is detachably inserted and attached.

[0028] The device body 1 of the medical magnetic generator shown in Fig. 1 has a resin casing 2, a touch panel display 3 housed diagonally upward in the front part of the casing 2 and exposed from the front opening of the casing 2, a signal wave output unit housed in the upper part of the rear part of the casing 2, and a power supply unit housed in the lower part of the rear part of the casing 2. An alarm stop button and a power switch button are provided on the left and right sides of the lower part of the front opening of the casing 2 of the device body 1. Further below these buttons, multiple sockets for plugging in signal cables 21 are provided side by side to enable connection of multiple probes 11 to the device body 1.

[0029] 2A is a top view, B is a rear view, and C is an AA cross-sectional view of the probe 11 of the medical magnetic field generator of this embodiment. In this embodiment, the probe 11 has a roughly quadrilateral exterior 12 made of a flexible material, and a circuit section 13 that is piled up in a truncated pyramid shape for the purpose of protecting the electric circuit, etc. A signal cable 21 is drawn out from the back of the circuit section.

[0030] As shown in Fig. 2(c), the probe 11 contains a flexible thin plate 14, which is a printed circuit board on which a coil and an electric circuit are arranged, in an exterior 12 made of soft resin such as an elastomer or rubber material. The probe 11 can be manufactured by resin molding such as injection molding or RIM molding. Since resin molding involves self-heating, it is preferable to apply a resin mold to the circuit part 13 in advance in order to protect the electric circuit, etc.

[0031] FIG. 3 is a printed wiring diagram showing the coil arrangement of the medical magnetic generator of this embodiment, showing a top view (a) and a bottom view (b). A circuit section, a high-frequency output coil, a high-frequency detection coil, a low-frequency output coil, etc. are arranged on a printed circuit board. In this embodiment, the high-frequency output coil is arranged as an annular disk on the upper surface of the printed circuit board, and the high-frequency detection coil is arranged as an annular ring on the outside. In addition, a spiral-shaped low-frequency output coil is arranged inside the high-frequency output coil. The high-frequency output coil and the low-frequency output coil are also arranged on the lower surface of the printed circuit board, and are configured to be plane symmetrical, so that the high-frequency current and the low-frequency current flow in the same direction on both the upper and lower surfaces. By doing so, the centers of the magnetic fields generated by the coils on both the upper and lower surfaces can be aligned. The high-frequency output coil, the high-frequency detection coil, and the low-frequency output coil may be changed from an annular shape to a square shape.

[0032] There is no particular limitation on the shape of the probe 11, but by making it a roughly quadrilateral, particularly a roughly rectangular flat plate as in the example shown in FIG. 2, it has the advantage that it can be easily attached to an application object and fixed with tape.

[0033] The flexible thin plate 14 is a film-like printed circuit board, and preferably has a base layer made of a flexible insulating material film, and an adhesive layer as necessary. The base layer can be made of polyimide resin, polyester resin, polyamide paper-based epoxy resin, glass cloth-based epoxy resin, glass-based BT resin, or the like. Each coil may be a conductor printed or etched on the printed circuit board 14, such as metal foil.

[0034] In the medical magnetic generator of the present invention, the power supply unit is, for example, a circuit configured with a CPU and two AC-DC converters (not shown), and a predetermined DC power supply is obtained from a commercial AC power supply of 100V supplied via a power cable (not shown) by the two AC-DC converters, and the DC power supplies are connected in series to obtain a charging voltage for the battery to charge the battery, and the predetermined DC power supply is stepped down from the DC power supplies by a switching power supply and a linear regulator to supply the signal wave output unit and screen control unit of the device main body 1 and the operation state detection unit of the probe 11 as DC power supplies of the required voltages, respectively. During normal use of the medical magnetic generator without a power cable attached, the power supply unit steps down the DC power supply from the battery to the signal wave output unit and screen control unit of the device main body 1 and the operation state detection unit of the probe 11 by the switching power supply and linear regulator to DC of the required voltages, respectively, thereby making the medical magnetic generator portable and usable.

[0035] The present invention will be described in more detail below with reference to experimental examples, but the present invention is not limited to these.

[0036] <Experimental Example 1> Numerical study of magnetic field penetration into the body Numerical calculations were performed using the FDTD method and the finite element method using a numerical human body model Duke with anatomical structures, numerical calculation software Sim4life (manufactured by ZMS Zurich MedTech AG), and the low-frequency analysis option "QS-SOLVER". Simulations were performed under the condition that the coil serving as the wave source was placed on the surface of the human lower back (nearest value: 2 mm from the surface of the human body). Here, FIG. 4 is a diagram showing the numerical human body model and the coil placed on the lower back surface used in the calculation of the experiment on the penetration of the magnetic field into the body in Experimental Example 1. FIG. 4 shows, from the left side of the page, the XY plane (top), YZ plane (back), XZ plane (side), and YZ plane (front), and the YZ plane (back) and XZ plane (side) are schematic diagrams showing the coil placed on the lower back.

[0037] For the high-frequency magnetic field distribution, a sine wave with a frequency of 250 MHz was input to a 1-turn coil, and for the low-frequency magnetic field distribution, a sine wave with a frequency of 2 kHz was input to a 7-turn coil, and the three-dimensional magnetic field distribution in the body was calculated. Figures 5 and 6 are graphs showing the results, where Figure 5(a) shows the magnetic field distribution in the XY plane and the XZ plane of the maximum coordinates of the high frequency, the straight line in the figure is an X-ray straight line passing through the maximum coordinates, and Figure 5(b) is a graph showing the magnetic field strength (maximum point enlargement) on the straight line (X axis) passing through the maximum coordinates of the high frequency. Figure 6(a) shows the magnetic field distribution in the XY plane and the XZ plane of the maximum coordinates of the low frequency, the straight line in the figure is an X-ray straight line passing through the maximum coordinates, and Figure 6(b) is a graph showing the magnetic field strength (maximum point enlargement) on the straight line (X axis) passing through the maximum coordinates of the low frequency. It was revealed that the stimulation of the very weak alternating magnetic field output irradiated from the medical magnetic generator of the present invention reaches the inside of the living body.

[0038] <Experimental Example 2> [1] Behavioral pharmacology test - Morris water maze test using rat models of spatial cognitive impairment (evaluation of spatial cognitive impairment) FIG. 7 is a diagram for explaining the behavioral pharmacology test in Experimental Example 2. FIG. 7(a) is a schematic diagram showing the state in which the test is being performed, and FIG. 7(b) is a schematic diagram showing an example of the platform. The Morris water maze is used to test the spatial memory of rats or mice in behavioral experiments. It usually consists of a pool of water with a diameter of 1.5 to 2 m and a depth of 0.5 m, and an escape platform hidden a few mm below the water surface. When a rat is released into this pool, it swims around looking for an exit and finds the escape platform. After training for four consecutive days, the rat becomes able to reach the platform position more quickly. The escape latency, that is, the time it takes to find the platform under the water surface, is measured (spatial learning). On the sixth day, the animal is released into the pool from which the platform has been removed, and the time it spends in the position where the platform was located is measured (durability and accuracy of spatial memory).

[0039] Specifically, using a water maze pool (Labotech) and the "EthoVision XT" (Noldus) video tracking system for automatic behavior tracking and analysis, rats are placed in a pool with the water temperature adjusted to 25±1°C, and the time it takes to reach the platform below the water surface before and after magnetic stimulation (platform arrival time) and the percentage of time spent in the area with the platform (platform area stay percentage) are measured once a day for 5 minutes for 14 days. The video behavior tracking system is used to analyze the rats' behavior in the pool. It is confirmed whether magnetic stimulation shortens the time to reach the platform and extends the percentage of time spent in the platform area. (Improvement of memory and learning disorders) [1-1] Effect on transient spatial cognitive impairment As a model of transient spatial dementia (molecular mechanism disorder), rats administered with MK801 (MK801-administered rats) were used to confirm the effect on transient spatial cognitive impairment by the Morris water maze test. Specifically, after obtaining rats (Crl:CD (SD), male) (obtained from Charles River Co., Ltd.), they were allowed to acclimate to the environment for about one week, and then MK801, a non-competitive antagonist of NMDA receptors (glutamate receptor N-methyl D aspartate), was administered intraperitoneally 30 minutes before the Morris water maze test, and the test was performed 30 minutes after administration. In normal rats, the position of the platform was recognized and the time to reach it was shortened with each repeated trial (learning acquisition). In addition, the proportion of time spent in the platform section also increased, making learning acquisition clear and the method was established. On the other hand, in the MK801-administered rats, the trial was repeated in the same way, but no shortening of the time to reach the platform or an increase in the proportion of reaching the section was observed, and it was determined that it is useful as a dementia model (spatial cognitive impairment).

[0040] On the 8th to 12th days, the probe of the prototype magnetic generator was attached to the area of ​​the lumbar dorsal side of the MK801-administered rats where the skin was relatively thin, and magnetic stimulation (hybrid wave -1 to 3 kHz + 250 MHz) was performed for 10 minutes under inhalation anesthesia by irradiating an alternating magnetic field. A similar test was performed, and the results for the platform arrival time are shown in Figure 8, and the results for the proportion of stay in the compartment are shown in Figure 9. In Figures 8 and 9, the horizontal axis is the number of days, the vertical axis of Figure 8 is the platform arrival time (seconds), and the vertical axis of Figure 9 is the proportion of stay in the platform compartment (%). As can be seen from Figures 8 and 9, the platform arrival time and the proportion of stay in the compartment were improved to the same level as normal rats, and an improvement in spatial cognition impairment was obtained.

[0041] [1-2] Effects on persistent spatial cognitive impairment As a model of persistent spatial dementia, rats with bilateral common carotid artery ligation were used to confirm the effect on persistent spatial cognitive impairment. Bilateral common carotid artery ligation was performed by incising the skin along the midline of the rat's neck under inhalation anesthesia, carefully exposing the common carotid artery with a cotton swab, and then detaching the common carotid artery from the surrounding tissue, ligating it in two places on one side, both the left and right sides, and suturing the skin. The following groups were used: Sham-operated group: A group in which the bilateral common carotid arteries were not ligated, and the rats were anesthetized and underwent incision surgery only. -Non-treatment group: After bilateral common carotid artery ligation, magnetic stimulation was not performed. Treatment group: A group that underwent magnetic stimulation for one week (total of seven times) three weeks after bilateral common carotid artery ligation. Pre-treatment group: The group that received magnetic stimulation for one week (total of seven times) before bilateral common carotid artery ligation. The Morris water maze test was performed on the rats 4 weeks after bilateral common carotid artery ligation. The probe of the prototype magnetic generator was attached to the relatively thin skin on the back of the lumbar region of the rat, and magnetic stimulation (hybrid wave -1 to 3 kHz + 250 MHz) was performed for 10 minutes under inhalation anesthesia by irradiating an alternating magnetic field.

[0042] Figure 10 is a graph showing the results for the time to reach the platform, and Figure 11 is a graph showing the results for the proportion of time spent in the compartment. In Figures 10 and 11, the horizontal axis is the number of days, the vertical axis in Figure 10 is the time to reach the platform (seconds), and the vertical axis in Figure 11 is the proportion of time spent in the platform compartment (%). In the non-treatment group, arrival at the platform was slower than in the sham-operated group, confirming that the surgery caused spatial cognitive impairment. On the other hand, in the treatment group, the arrival time was shorter than in the non-treatment group, and the proportion of time spent in the compartment also increased. In the pre-treatment group, the arrival time and proportion of time spent in the compartment were similar to those in the sham-operated group, and spatial cognitive impairment was alleviated despite cellular damage in local brain areas caused by ischemia.

[0043] [2] Organizational evaluation Damage to hippocampal CA1 pyramidal cells in an ischemic state caused by bilateral common carotid artery ligation was examined, and the therapeutic effect on intracerebral changes at the cellular level was confirmed. After behavioral pharmacological testing, brain tissue was extracted by rapid cooling from each of the non-treated, treated, pre-treated, and sham-operated groups. After fractionating the hippocampal region, the tissue was thinly sliced ​​using a freezing microtome to prepare sections. The slides on which the specimens were placed were dried at room temperature for approximately 1 hour, and then stained with HE, TUNEL, and LFB (Luxol Fast Blue).

[0044] Specifically, HE staining is (1) Immerse in hematoxylin solution for 5 minutes. (2) Rinse with running water for 5 minutes and then replace with pure water. (3) Immerse in eosin solution for 5 minutes. (4) Immerse in 95% ethanol (5 times x 2), (5) Immerse in 100% ethanol (5 times x 3), (6) Perform clearing with Lemosol (5 minutes x 3), (7) Encapsulate, The procedure was as follows.

[0045] Specifically, TUNEL staining was performed using the TACS2 TdT-DAB In situ apoptosis detection kit (Trevigen Instructions, Cat Sharp 4810-30-K) according to the product protocol. (1) Immerse in 1x PBS and leave at room temperature for 10 minutes. (2) Cover with 50 μl of proteinase K solution and leave at 37° C. for 15 minutes. (3) Immerse in distilled water and wash at room temperature for 2 minutes (x2), (4) Cover with 100 μl of quenching solution and leave at room temperature for 5 minutes. (5) Immerse in 1x PBS and wash at room temperature for 1 minute. (6) Cover with 100 μl of 1× TdT labeling buffer and leave at room temperature for 5 minutes. (7) Cover with 50 μl of labeling reaction mix and leave at 37° C. for 1 hour. (8) Cover with 100 μl of 1× TdT Stop buffer and leave at room temperature for 5 minutes. (9) Immerse in distilled water and wash at room temperature for 5 minutes (x2), (10) Cover with 50 μl of Strep-HRP solution and leave at 37° C. for 10 minutes. (11) Immerse in 1x PBS and wash at room temperature for 2 minutes (x2), (12) Cover with 100 μl of DAB solution and leave at room temperature for 5 minutes. (13) Immerse in 1x PBS and wash at room temperature for 2 minutes (x2), (14) Wash with distilled water for 2 minutes at room temperature (x2), (15) Immerse in methyl green and leave at room temperature for 5 minutes. (16) Immerse in each of the following solutions 10 times and wash in sequence: Distilled water → 70% ethanol → 70% ethanol → 95% ethanol → 95% ethanol (17) Immerse in 99% ethanol (5 times x 3), (18) Perform clearing with Lemosol (5 minutes x 3), (19) Enclose, The procedure was as follows.

[0046] LFB staining was performed using the Luxol Fast Blue Stain Kit (ScyTek Laboratories, Inc., Cat Sharp LBC-2) according to the manufacturer's protocol. (1) Surround with liquid blocker and place in a humid box. (2) Apply 8 to 10 drops of Luxol Fast Blue Solution to the tissue piece. (3) Place the humidified box in a thermostatic chamber and leave it at 60°C for 10 to 12 hours (overnight). (4) Remove the wet box and wash it with 95% ethanol to remove the crystals. (5) Wash with distilled water to remove Luxol Fast Blue Solution and ethanol. (6) Continue dripping lithium carbonate solution (0.05%) and perform fractionation (up to 20 seconds). (7) Continue dripping alcohol and reagent (70%) and perform moderate separation so that the gray matter becomes colorless and the white matter remains bluish. (8) Wash with distilled water. (9) Add 4 to 5 drops of Cresyl Etcht Violet (0.1%) to the slide and leave it at 37°C for 2 to 5 minutes. (10) Quickly wash with distilled water (x2), (11) Dehydrate with absolute ethanol (10 times x 4), (12) Perform clearing with Lemosol (5 minutes x 3), (13) Encapsulate, The procedure was as follows.

[0047] Figure 12 shows photographs (10x) of hippocampal CA1 pyramidal cells observed with BZ-X710. The left column of Figure 12 shows the results of HE staining, the center column shows the results of TUNEL staining, and the right column shows the results of LFB staining. The bottom photograph of Figure 12 shows the results of TUNEL staining for a normal rat (positive control). In the non-treated group, hippocampal CA1 pyramidal cells were lost and cell arrangement was disrupted. However, in the pre-treated group, cell loss was minor and cell arrangement was maintained, suggesting the possibility that it may exert a protective effect against cell death induced by ischemia. In the pre-treated group, cell loss was minor on the tissue, revealing a neuroprotective effect.

[0048] [3] Consideration The above-mentioned experiment confirmed that the medical magnetic generator of the present invention has an effect of improving spatial cognitive impairment, and is considered to be useful in treating vascular dementia, which accounts for approximately 20% of dementia patients. In addition, in the behavioral test of the pre-treatment group, the platform arrival time was equivalent to that of the sham operation group, spatial cognitive impairment was suppressed, and a neuroprotective effect was revealed in which cell loss was minor in the tissue. This result suggests the possibility of a preventive effect of the medical magnetic generator of the present invention, and the medical magnetic generator of the present invention may be useful in treating pre-dementia patients (prevention of dementia).

[0049] <Experimental Example 3> [1] Behavioral pharmacology test - Forced swimming test using rat chronic pain and depression (CCI (chronic constriction injury)) model (evaluation of depressive-like behavior) FIG. 13 is a diagram for explaining the behavioral pharmacology test in Experimental Example 3. FIG. 13(a) and (b) are schematic diagrams of the forced swimming test, and FIG. 13(c) is a schematic diagram showing the procedure of the forced swimming test. In Experimental Example 4, the forced swimming test was used to evaluate depressive-like behavior. The forced swimming test is a test method for measuring depressive-like behavior using an animal model, and is widely used as a screening method for antidepressants. When a rat is placed in a cylindrical tank filled with water and cannot escape, it shows escape behavior such as swimming and climbing, but then becomes immobile (with only its head above the water surface and floating without moving its limbs). When the rat is placed in the tank again the next day, the immobility state appears early, so this immobility time is evaluated as depressive-like behavior. FIG. 13(a) shows a rat with hope struggling to escape from the tank, and FIG. 13(b) shows a rat that has lost all hope floating vaguely in the tank.

[0050] FIG. 13(c) shows the procedure when magnetic stimulation was applied. Sham-operated group: No CCI surgery was performed, and the rats were anesthetized and only underwent incision surgery. Non-treatment group: CCI surgery was performed but magnetic stimulation was not performed. Hybrid wave -1~3kHz+250MHz group: A group that received magnetic stimulation (low frequency: 1~3kHz, high frequency: 250MHz) using a prototype magnetic generator 7~14 days after CCI surgery. Single-wave 2kHz group: A group that received magnetic stimulation (low frequency: 2kHz) using a prototype magnetic generator 7 to 14 days after CCI surgery. Single-wave 250MHz group: A group that received magnetic stimulation (high frequency: 250MHz) using a prototype magnetic generator 7 to 14 days after CCI surgery. The rats were subjected to a forced swimming test.

[0051] More specifically, the CCI surgery was performed by incising the skin of the left hind leg of the rat under inhalation anesthesia, exposing the sciatic nerve, and ligating it incompletely at 4 locations with 1 mm intervals using 4-0 silk thread, and then suturing the skin. When administering magnetic stimulation, the rat was sedated with inhalation anesthesia from 7 days after surgery, and a prototype magnetic generator was applied to the ligated site of the left hind leg, irradiating it for 10 minutes once a day for one week.

[0052] In the forced swimming test, the subjects were forced to swim for 5 minutes in a cylindrical tank with the water temperature adjusted to 25±1℃ before and after magnetic stimulation, and the immobility time (seconds) during that time was measured. It was confirmed whether the immobility time was shortened by magnetic stimulation (improvement of the depressed state).

[0053] 14 is a graph showing the results of Experimental Example 3, with the vertical axis representing immobility time (seconds). In the non-treatment group, the immobility time was extended (depression-like symptoms) compared to the sham operation group, while the increase in immobility time was suppressed in the -1 to 3 kHz + 250 MHz hybrid group.

[0054] The embodiments disclosed herein should be considered to be illustrative and not restrictive in all respects. The scope of the present invention is defined by the claims, not the above description, and is intended to include all modifications within the meaning and scope of the claims. [Explanation of symbols]

[0055] 1 Main body of medical magnetic generator, 2 Casing, 3 Display (touch panel display), 11 Probe, 12 Exterior, 13 Circuit section, 14 Flexible thin plate (printed circuit board), 21 Signal cable.

Claims

1. A medical magnetic generator that irradiates an alternating magnetic field onto parts of the human body other than the head to generate eddy currents and treat or prevent mental and neurological disorders.

2. 2. The medical magnetic field generator according to claim 1, which generates eddy currents by irradiating an alternating magnetic field controlled to a frequency within a range of 1 to 3 kHz.

3. 3. The medical magnetic field generator according to claim 2, wherein the output magnetic flux density of the alternating magnetic field controlled to a frequency within a range of 1 to 3 kHz is 10 mT or less.

4. 3. The medical magnetic field generating device according to claim 2, further irradiating an alternating magnetic field controlled to a frequency within a range of 225 to 275 MHz in synchronization with the alternating magnetic field controlled to a frequency within a range of 1 to 3 kHz to generate an eddy current.

5. 2. The medical magnetic field generating device according to claim 1, wherein the psychiatric / neurological disease is at least one selected from the group consisting of stroke, dementia, depression, schizophrenia, Parkinson's disease, epilepsy, multiple sclerosis, amyotrophic lateral sclerosis, Guillain-Barré syndrome, myasthenia gravis, fibromyalgia, adjustment disorder, and sleep disorder.

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