KR20220086431A - Device of nerve signal recording and stimulating for disagnosis and treatment of chronic pain or alzheimer's disease - Google Patents

Abstract

The present invention relates to a stimulation device equipped with an electrode element for measurement and stimulation of a nerve signal for diagnosis and treatment of chronic pain or Alzheimer's disease, and more particularly, electrical stimulation of an Alzheimer's-inducing protein that induces chronic pain or Alzheimer's disease. A stimulation apparatus for providing or measuring a biosignal, comprising: a controller; a substrate coupled to the lower portion of the control unit, capable of receiving power wirelessly, and on which power receiving and signal transmitting electrodes for wirelessly transmitting biosignals are mounted integrally or separately; and an electrode element coupled to a lower portion of the substrate and capable of delivering electrical stimulation to a tissue in the body; a stimulation device equipped with an electrode element for measuring and stimulating nerve signals for diagnosis and treatment of chronic pain or Alzheimer's disease, comprising: provides

Description

Stimulator equipped with electrode elements for measuring and stimulating nerve signals for diagnosis and treatment of chronic pain or Alzheimer's disease

The present invention relates to a device for measuring and stimulating a neural signal equipped with an electrode element, and more particularly, an electrode with improved energy transfer efficiency to generate and deliver sufficient energy despite a small amount of energy applied by improving the structure of the electrode element. It is to use the device, thereby accurately diagnosing and effectively treating chronic pain or Alzheimer's disease from the above device.

If continuous stimulation occurs during the pain transmission process, it can develop into chronic pain. Chronic pain has the characteristic that various pains appear even with stimuli below the threshold, and patients with chronic pain have a loss of pain suppression function and show a lack of pain control response compared to normal people. Diseases that cause chronic pain include musculoskeletal disorders, tension headaches, chronic neck pain, back pain, conversion disorders, and somatization disorders.

In particular, in the case of spinal cord injury, it is caused by various causes, and since these causes are closely related to daily life, many patients occur worldwide every year. In addition, according to the Korea Spinal Cord Disorders Association, the number of domestic patients is estimated to increase every year. More than 75% of spinal cord injury patients experience chronic pain, and most patients live with pain every day and throughout the day. The worst pain is high enough to have an average intensity of 8.6 based on the maximum value of 10.

Among the various treatment methods for spinal cord injury, in the case of spinal cord stimulation (SCS), an electric pulse is delivered directly to the nerve. It follows the principle of buffering and transmitting other signals to the brain. The spinal cord stimulation device is in the form of a pulse generator implantable in the spine, and delivers electrical stimulation to the spinal cord through a wire implanted together. By delivering electrical stimulation through a wire called a lead from the electrode, which is a major component of the spinal cord stimulation device, to a specific location where pain occurs, it gives a dampening action to the pain signal and allows the buffered signal to be transmitted to the cerebrum, The pain is relieved or the pain is not felt.

On the other hand, the existing spinal cord stimulation apparatus has the following disadvantages. First, the spinal cord stimulation device is installed in the pelvis, and the wires and leads are extended along the spinal cord to the affected area. In some cases, since the connection state is poor and the signal cannot be transmitted properly, it may need to be corrected through surgery, and there is also a risk of disconnection. Next, in the case of the electrode, a scar may be created around the installation location. Next, a battery for driving the pulse generator may be damaged, and there is also a problem in that energy efficiency is lowered over time.

In addition, when an electrode having a conventional shape is used, it is necessary to buffer the pain accompanying high intensity pain with a more amplified electrical signal. At this time, high electrical energy must be transmitted. However, in this case, since the amplified power may give a shock to the body in the process of being applied, there is a great risk in use, so the applied power is inevitably limited. Therefore, as a result of the transmission of the weakened electrical signal, there is a problem in that the effect of pain relief is reduced because the degree of buffering against pain is inevitably lowered.

Therefore, improvement of these shortcomings should be sought, and through this, it is desired to develop a spinal cord stimulation device that is more convenient to use and has a reinforced function and other pain relief devices for chronic pain.

On the other hand, in the case of Alzheimer's disease, nerve fiber plaques (plaques, Alzheimer's-induced protein plaque) aggregate and accumulate in the brain, thereby causing the disease. Currently, various approaches for the management of Alzheimer's disease are being tried. Representatively, invasive methods and non-invasive methods are included. As a method for inhibiting the production of Alzheimer's-induced protein plaques, for example, beta-amyloid plaques, a method for inhibiting the production of Alzheimer's-induced protein, Alzheimer's-induced protein fibers, aggregates A typical example is how to remove the back. In particular, in the latter method, Alzheimer's-induced protein immunotherapy is expected to be the most promising, but like other protein drugs, this therapy has poor metabolic instability and permeability through the blood-brain barrier, and ultimately treats Alzheimer's disease. It has not been evaluated as a successful drug for

On the other hand, in order to overcome the limitations of such chemotherapy, the use of a physical method has recently been attempted to change the state of Alzheimer's-induced protein aggregation. Ultrasound, light, laser, magnetic field, direct current, alternating current, etc. have been applied, and it has been reported that it has the effect of reducing Alzheimer's-induced protein plaque.

However, in this case, although directionality is desirable, there are cases in which high input energy, for example, high power, voltage, etc. must be applied for effective stimulation. In this case, high applied energy separately from stimulation may be harmful to the human body Also, there is a problem in that it is difficult to monitor the acclimatization change of the Alzheimer's-inducing protein under an electric field acting in real time due to the strong cohesive force and tendency of the Alzheimer's-induced protein and the non-uniformity of the aggregation state.

The present invention has been devised to solve the problems of the prior art, and the present invention improves the shape of an electrode to achieve high energy efficiency in spite of applying less electrical energy to perform a sufficient role in pain relief. It is intended to enable

That is, since the conventional electrode is a method of stimulating from the outside of the tissue, a higher amount of power needs to be applied for a desired electrical stimulation, whereas the present invention is implanted in the tissue, so it is the same or the same even with a relatively low amount of power. More electrical stimulation is possible.

In addition, since the present invention requires a low amount of power, a wireless power technology can be introduced. Since the operation of the battery is not required, problems such as leakage or damage to the battery do not occur, and the stable operation of the device is not required. To make it possible is another purpose.

In addition, in the present invention, while the conventional planar electrode is sensed in the form of an ensemble signal despite the occurrence of a specific signal, in the case of the electrode of the present invention, a more subdivided specific signal is detected as it is, so that disease or Another purpose is to enable detailed control of signals according to pain or to more accurately grasp the degree of disease or pain.

In addition, according to the present invention, stimulation and recording are performed simultaneously, and when an abnormal signal is detected while continuously sensing a nerve signal, chronic pain can be treated early by providing electrical stimulation. Another purpose is to enable observation of the prognosis after treatment.

In addition, the present invention is combined with a storage device, so that the collection and storage of biosignal big data accumulated during the operation of the device is possible, and from this, it is possible to optimize a stimulation protocol through a deep learning process. The purpose.

In addition, another object of the present invention is to minimize tissue damage and reduce the burden on the patient when implanted into the patient's body, since the device can be miniaturized.

Another object of the present invention is to locally select and focus energy required for electrical or magnetic stimulation through structural adjustment of electrodes or coils required for electrical or magnetic stimulation.

In addition, another object of the present invention is to be able to adjust the size and region of energy required for electrical or magnetic stimulation through structural adjustment of electrodes or coils required for electrical or magnetic stimulation.

In addition, the present invention provides a sufficient barrier-overcoming free energy necessary for dismantling the aggregation structure of Alzheimer's-inducing protein under low-voltage conditions by being directly mounted in the cell, while observing changes in adaptation of Alzheimer's-inducing protein molecules in real time. serve another purpose.

In order to achieve the above object, the present invention provides an electrical stimulation for an Alzheimer's-inducing protein that induces chronic pain or Alzheimer's, or a stimulation apparatus for measuring a biological signal, comprising: a control unit; a substrate coupled to the lower portion of the control unit, capable of receiving power wirelessly, and on which power receiving and signal transmitting electrodes for wirelessly transmitting biosignals are mounted integrally or separately; and an electrode element coupled to a lower portion of the substrate and capable of delivering electrical stimulation to a tissue in the body; a stimulation device equipped with an electrode element for measuring and stimulating nerve signals for diagnosis and treatment of chronic pain or Alzheimer's disease, comprising: provides

The electrode element may include a base substrate; At least one column protruding from the base substrate, or a planar shape in which an insulating coating layer with a plurality of holes is processed thereon, or an electrode part in a coil shape; and, when the electrode part is in a pillar shape, a tip A non-conductive coating layer is included in at least a portion of the electrode part excluding the portion or at least one region of the upper portion of the base substrate, and when the electrode part is in the form of a coil, a hole is formed in the central portion, and at least one slit extending outward from the hole is provided. It is preferable that at least one conductive plate to be formed is stacked at a distance from the electrode part.

In the case of the pillar-shaped electrode, it is preferable that a feeding is configured in a region buried in the base substrate among the lower portions of at least one of the electrode parts.

In the case of the pillar-shaped electrode, it is preferable that a tip portion of the electrode portion and a portion of a side portion extending from the tip portion are exposed.

When there are two or more conductive plates, it is preferable that the positions of the slits of the conductive plates are different from each other and stacked.

The substrate is preferably divided into a substrate including a power receiving electrode capable of wirelessly receiving power and a substrate including a signal transmitting electrode capable of wirelessly transmitting a biosignal.

According to the present invention as described above, the effect of improving the shape of the electrode to achieve high energy efficiency despite the application of less electrical energy to perform a sufficient role in alleviating pain is expected.

In addition, since the present invention requires a low amount of power, a wireless power technology can be introduced. Since the operation of the battery is not required, problems such as leakage or damage to the battery do not occur, and the stable operation of the device is not required. The effect of making it possible is expected.

In addition, in the present invention, while the conventional planar electrode is detected in the form of an ensemble signal despite the occurrence of a specific signal, in the case of the electrode presented in the present invention, a more subdivided specific signal is detected as it is, so that the disease However, it is expected that the signal can be controlled closely depending on the pain or the effect of more accurately grasping the degree of disease or pain.

In addition, according to the present invention, stimulation and recording are performed simultaneously, and when an abnormal signal is detected while continuously sensing a nerve signal, chronic pain can be treated early by providing electrical stimulation. It is expected to have an effect that allows the prognosis to be observed after treatment.

In addition, since the present invention is combined with a storage device, it is possible to collect and store biosignal big data accumulated during the operation of the device, and from this, the effect of optimizing the stimulation protocol through the deep learning process is expected do.

In addition, since the present invention can miniaturize the device, the effect of minimizing tissue damage and reducing the burden on the patient when transplanted into the patient's body is expected.

In addition, the present invention is expected to have an effect of locally selecting and concentrating energy required for electrical or magnetic stimulation through structural adjustment of electrodes or coils required for electrical or magnetic stimulation.

In addition, the present invention is expected to have an effect of allowing the size and region of energy required for electrical or magnetic stimulation to be adjusted through structural adjustment of electrodes or coils required for electrical or magnetic stimulation.

In addition, the present invention provides a sufficient barrier-overcoming free energy necessary for dismantling the aggregation structure of Alzheimer's-inducing protein under low-voltage conditions by being directly mounted in the cell, while observing changes in adaptation of Alzheimer's-inducing protein molecules in real time. The effect is expected.

1 is a schematic diagram showing an installation state of a conventional spinal cord stimulation device.
2 is a schematic diagram showing various forms of a conventional spinal cord stimulation device.
3 is a diagram showing waveforms generated from a conventional spinal cord stimulation apparatus.
4 is a schematic diagram showing the installation state of the conventional spinal cord stimulation apparatus and the spinal cord stimulation apparatus of the present invention.
5 is an exploded perspective view showing the spinal cord stimulation apparatus according to an embodiment of the present invention.
6 is an operation diagram of the spinal cord stimulation device of FIG.
7 is an electric field distribution diagram when the conventional spinal cord stimulation apparatus and the spinal cord stimulation apparatus according to an embodiment of the present invention are respectively applied.
8 is a schematic diagram showing the installation of the spinal cord stimulation apparatus according to the present invention and the conventional installation state of the spinal cord stimulation apparatus using a human body as an example.
9 is a view showing the distribution and direction of an electric field generated in an electrode having a conventional shape.
10 is a diagram illustrating an electric field field distribution appearing in a columnar electrode according to an embodiment of the present invention.
11 is a view showing the formation of a non-conductive coating layer on the base substrate including the lower portion of the columnar electrode in the columnar electrode according to an embodiment of the present invention and the electric field field distribution according thereto.
12 is a view showing the formation of a non-conductive coating layer on the side except for the upper end of the columnar electrode in the columnar electrode according to an embodiment of the present invention and the electric field field distribution accordingly.
Fig. 13 is a view showing Figs. 11 and 12 in combination.
14 is a view showing the formation of a non-conductive coating layer on the columnar electrode of the present invention according to various embodiments and an electric field field distribution according thereto.
15 is a view showing the formation of a non-conductive coating layer on the columnar electrode of the present invention according to various embodiments and the electric field field distribution according thereto, in which a feeding is formed under the columnar electrode.
16 is a view showing that a non-conductive coating is performed on an electrode having a conventional planar shape according to embodiments of the present invention, and a hole is made on the non-conductive coating to expose the electrode.
17 is a view illustrating various embodiments in which metal plates are stacked at intervals on the coil-type electrode of the present invention or slits are formed in the metal plate.
18 is a graph comparing the magnitude of electric field energy according to an interval between a coil-type electrode and a laminated metal plate according to an embodiment of the present invention.
19 is a graph comparing the magnitude of the electric field energy according to the hole size of the metal plate laminated on the coil-type electrode according to an embodiment of the present invention.
20 is a view showing a plurality of metal plates stacked on a coil-type electrode according to an embodiment of the present invention, with different directions of slits formed on each metal plate.
21 is a graph comparing the magnitude of electric field energy according to the number of electrode turns of the coil-type electrode according to an embodiment of the present invention.
22 shows electrical stimulation by using the stimulation apparatus according to an embodiment of the present invention by varying the voltage values to 50mV, 1V, and 10V in order to derive the most ideal power parameters required to disassemble Alzheimer's-induced protein aggregates therefrom. These are the CD spectral results compared after performing electrical stimulation with a flat stimulator under the same conditions.
23 is a real-time monitoring of the conformation change of the Alzheimer's-inducing protein 42 protein structure by the CD spectrum in order to investigate the effect of the stimulation apparatus on the conformation of the Alzheimer-inducing protein according to an embodiment of the present invention, but using a conventional flat film This is the CD spectrum result compared with the manufactured electrical stimulation system.

Hereinafter, with reference to the accompanying drawings, the embodiments of the present invention will be described in detail so that those of ordinary skill in the art to which the present invention pertains can easily implement them. However, the present invention may be embodied in several different forms and is not limited to the embodiments described herein. And in order to clearly explain the present invention in the drawings, parts irrelevant to the description are omitted, and similar reference numerals are attached to similar parts throughout the specification.

Throughout the specification, when a part "includes" a certain element, it means that other elements may be further included, rather than excluding other elements, unless otherwise stated.

In addition, terms such as "... unit" and "... group" described in the specification mean a unit that processes at least one function or operation.

<Chronic pain>

Here, the spinal cord stimulation apparatus 100 for diagnosing and treating pain occurring in the spine has been described as an example, but the stimulation apparatus 100 of the present invention can be used for the purpose of diagnosis and treatment of various pains as well as stimulation of the spinal cord. There is no limit to the area of application as long as it can be transplanted.

1 is a schematic diagram showing an installation state of a conventional spinal cord stimulation apparatus 100. As shown in FIG. As shown, the conventional spinal cord stimulation apparatus 100 usually has a planar shape, an electric stimulator with a built-in battery is implanted in the body, for example, the buttocks, and an electrode connected to the electric stimulator is applied to the spine. Install so that it is located near the affected part of

That is, the conventional spinal cord stimulation apparatus 100 is different from the present invention in that it is not inserted into the spinal cord and is located outside the spine. Therefore, for effective stimulation, input power as high as possible is required. However, as the input power value is higher, it acts as a burden on the human body and may sometimes cause tissue damage. Therefore, there is a need for an alternative to this.

The conventional spinal cord stimulation apparatus 100 has been developed in various forms as shown in FIG. 2 . In addition, FIG. 3 is a diagram showing a waveform of an electrical signal generated from the conventional spinal cord stimulation apparatus 100, and is characterized in that it is generally a periodic wave.

4 is a schematic diagram showing the installation state of the conventional spinal cord stimulation apparatus 100 and the spinal cord stimulation apparatus 100 of the present invention. As shown, in the case of the conventional spinal cord stimulation apparatus 100, periodic waves are transmitted as an ensemble signal, whereas the spinal cord stimulation apparatus 100 of the present invention transmits a specific signal by the shape or spacing of the electrodes. In this respect, there is an advantage that it is possible to closely control a signal according to a disease or pain, or to more accurately grasp the degree of a disease or pain.

Here, if pain occurs, electrical stimulation is performed through an electrode so that stimulation is applied to the corresponding area, and the amount of electricity applied is monitored and data is generated. If the pain is not completely relieved, the amount of applied electricity can be adjusted. Matching data can be obtained by matching the adjusted applied electric quantity with the biosignal of the nerve site, which can be generated as a platform necessary for operating a stimulation device to improve chronic pain in the future.

Here, the specific signal is a signal sent from the affected part for diagnosis as a biological signal, and is called an action potential. It is defined as an analog-type bio-signal that comes out while transmitting nerve impulses from nerve cells called neurons.

5 is an exploded perspective view showing the spinal cord stimulation apparatus 100 according to an embodiment of the present invention. As shown, the spinal cord stimulation apparatus 100 of the present invention comprises: a control unit 101; a board 103 coupled to the lower portion of the control unit 101, capable of receiving power wirelessly, and on which power receiving and signal transmitting electrodes for wirelessly transmitting biosignals are mounted integrally or separately; and an electrode element coupled to a lower portion of the substrate 103 and capable of delivering an electrical stimulus to a tissue in the body.

On the other hand, the substrate 103 may operate as a functionally integrated unit as described above, but as another type, a substrate 103 including a power receiving electrode capable of wirelessly receiving power and a wirelessly transmitting biosignal are provided. It may be divided into a substrate 103 including a signal transfer electrode. That is, the substrate 103 for power reception and signal transmission, respectively, is mounted so that it can be operated individually as a separate module.

Here, the electrode element is in the form of a base substrate 105, at least one column protruding on the base substrate 105, or a planar form in which an insulating coating layer having a plurality of holes 115 formed thereon is implemented, It includes a coil-shaped electrode part 107, a junction part for receiving a signal or power or transmitting a signal, which is formed in a region where the electrode part 107 and the base substrate 105 are combined.

In the present invention, the main feature of the electrode unit 107 is that the electrode unit 107 serves to efficiently perform electrical stimulation with respect to a low or adequate input power that the body can accept. To this end, variously shaped electrode parts 107 were derived as follows.

First, by forming the non-conductive coating layer 109 on at least the electrode part 107 or the base substrate 105 except for the upper end of the column-shaped electrode, the non-conductive coating layer 109 is not formed on the exposed electrode. The electric field is selectively and strongly generated in the region, so that the electrical stimulation is precisely performed according to the law of selection and concentration.

Second, a non-conductive coating layer 109 is formed on a conventional planar electrode, and an electric field is formed in the hole 115 by locally processing the hole 115 to the extent that the surface of the electrode is exposed. It was designed to perform a function similar to the shape of the electrode.

Third, in the case of a coil-shaped electrode, the electrode part 107 was formed by stacking conductive plates 119 at a distance from the electrode. At this time, a hole 115 was formed in the center of the electrode plate, and the upper hole 115 was formed. ), a slit 123 extending along a specific direction of the conductive plate 119 was machined. Accordingly, a magnetic field was formed through the hole 115 and the slit 123 by the electric power supplied from the coil-shaped electrode.

These electric and magnetic fields become energy for electrical and magnetic stimulation, which is the purpose of the stimulation apparatus 100 of the present invention, and can perform such stimulation more precisely and precisely, and more precisely grasp the degree of pain and the location of the affected area. be able to

6 is an operation diagram of the spinal cord stimulation apparatus 100 of FIG. 5 . As shown, the stimulation apparatus 100 of the present invention can be controlled to generate a stimulus, receive a result from the stimulus, record it, and generate a new stimulus suitable for the stimulus from the result. When these results are accumulated, they are used as big data, and can be helped to improve the device and its operation method to derive a more improved treatment effect.

7 is an electric field distribution diagram when the conventional spinal cord stimulation apparatus 100 and the spinal cord stimulation apparatus 100 according to an embodiment of the present invention are respectively applied. As shown, the conventional spinal cord stimulation device 100 has a characteristic that the strength of the electric field is small, wide, and distributed without any characteristics. It can be confirmed that

8 is a schematic diagram illustrating the installation of the spinal cord stimulation apparatus 100 according to the present invention and the conventional installation state of the spinal cord stimulation apparatus 100 using a human body as an example. As shown, the present invention can deliver stimulation more precisely into the spinal cord by being directly implanted into the spine, and the stimulation device 100 can be operated more accurately and effectively from feedback provided through acquisition of big data and deep learning. have. This can be said to be different from the conventional spinal cord stimulation apparatus 100 that merely provides stimulation.

Hereinafter, it will be described that the concentration effect of an electric field or a magnetic field can be derived by adjusting various shapes of the electrode part 107 in the electrode element of the present invention. As described above, it is possible to manufacture the stimulation apparatus 100 effectively applied to various types of chronic pain from various shape adjustments of the whole country.

9 is a diagram illustrating the distribution and direction of an electric field generated in an electrode having a conventional shape, and FIG. 10 is a diagram illustrating an electric field field distribution in a columnar electrode according to an embodiment of the present invention.

As shown in FIG. 9 , the electrode having a conventional shape is a flat electrode or a simple coil shape. In the former case, it can be seen that the electric field is strongly generated in the corner portion, not the flat portion. This is because the electric field gathers where the curvature of the metal surface is small, and it is a general phenomenon that appears in all electrodes. Therefore, in order to apply a large electric field to the flat portion occupying most of the electrode area, a very large voltage must be applied. In this case, damage to the tissue may occur due to a large electric field, and there may be a great risk in use.

In the latter case, as an embodiment, it is possible to check the loop antenna coil-shaped electrode for forming the magnetic field and the magnetic field field formed therefrom. At this time, the maximum magnetic field appears at the center of the coil, and it is a general phenomenon that the field distribution decreases toward the end. The reason that the magnetic field is not generated on the bottom surface but only on the top surface is because a magnetic material for shielding the magnetic field is disposed on the bottom surface when the coil electrode is formed.

On the other hand, as shown in FIG. 10 , when the columnar structure is introduced into the electrode, some fields are formed in the inner part of the electrode as compared to the planar structure electrode, and it can be seen that a more uniform field distribution is formed. However, it is still showing the result that the field is not well formed in the central part of the electrode.

11 illustrates a case in which the electrode part 107 according to an embodiment of the present invention is a columnar electrode part 107 , and a non-conductive coating layer 109 is formed on the base substrate 105 including the lower part of the columnar electrode part 107 . ) is a diagram showing the formation and the electric field field distribution accordingly.

As shown, it can be seen that the electric field is partially formed more clearly than in FIG. 10 . Through this, a higher electric field energy may be transmitted in each columnar electrode part 107 as compared to the conventional columnar electrode part 107 . This is also the same in the case of FIG. 12 , and it can be seen that an electric field is formed in each of the columnar electrode parts 107 similar to the result of FIG. 11 .

13 is a combination of FIGS. 11 and 12 , wherein the non-conductive coating layer 109 is formed on both the side surface of the columnar electrode and the upper surface of the base substrate 105 . It seems that a stronger electric field is formed compared to FIGS. 11 and 12 , and it is reasonable to introduce the non-conductive coating layer 109 to the columnar electrode part 107 in FIG. 13 as in FIGS. 11 and 12 . it will show

11 to 13 , the introduction of the non-conductive coating layer 109 to the remaining regions including the base substrate 105 except for a part of the columnar electrode part 107, preferably the upper part, is the formation of an electric field. By controlling the position, the direction of the electric field formation, and the electric field distribution, it has the potential to be applied in various ways.

In particular, according to the present invention, by adjusting the formation position of the non-conductive coating layer 109 on the columnar electrode part 107 and the density of the columnar electrode per unit area according to the range and intensity of chronic pain, the same input power value is obtained. Since various output values (electrical stimulation) can be derived, it can be said that pain can be controlled without increasing the input power value to a level dangerous to the human body for high pain intensity, which is very desirable.

14 is a view showing the formation of the non-conductive coating layer 109 on the columnar electrode part 107 of the present invention according to various embodiments and the electric field field distribution according thereto. That is, the non-conductive coating layer 109 can be variously implemented as shown in FIG. 14 , and from this, the electric field

15 is an electric field distribution according to the formation of a non-conductive coating layer 109 on the columnar electrode of the present invention according to various embodiments, and a feeding 111 to the lower portion of the columnar electrode part 107 is shown. It is a diagram showing the formation of The feeding 111 may be partially formed on one or more electrodes, or may be formed on all electrodes. When only one feeding 111 is provided, a phenomenon in which an electric field is mainly concentrated on one column-shaped electrode fed 111 appears. Therefore, it is possible to effectively control the distribution of the electric field depending on where the feeding 111 is formed.

Looking at the strength of the electric field, the strength of the electric field formed around each of the pillar-shaped electrode units 107 is about 4,000 V/m. It was experimentally confirmed that the electric field strength increased by about 10 times to about 40,000 V/m. Therefore, it is possible to concentrate energy by variously adjusting the method of feeding 111 to the columnar electrode part 107 .

16 is a view showing that a non-conductive coating is performed on the electrode part 113 having a conventional shape according to an embodiment of the present invention, and a hole 115 is processed on the non-conductive coating layer 109 to expose the electrode. It is a drawing showing

As shown, a strong electric field is observed in the part where the hole 115 is processed, and the strength or formation position of the electric field can be adjusted while changing the size, position, number, etc. of the hole 115 in this way, An effect similar to that of the above-described columnar electrode part 107 can be achieved. Therefore, the versatility of application is recognized in that it can be selected from processing the hole 115 after forming the non-conductive coating layer 109 on the columnar electrode part 107 and the electrode part 113 as needed. do.

17 is a view illustrating various embodiments in which conductive plates 119 are stacked on the coil-type electrode part 117 at intervals or slits 123 are formed in the conductive plate 119 of the present invention. As shown, when the conductive plates 119 without the slits 123 are stacked on the coil-type electrode part 117 at intervals, it can be seen that no magnetic field is radiated to the outside. However, when the slit 123 is generated, it can be confirmed that the magnetic field is radiated through the slit 123 and the through hole 121 , and in particular, it was found that the radiation effect of the magnetic field through the through hole 121 is remarkable. Here, the strength of the magnetic field can be controlled by adjusting the size of the through hole 121 and the distance between the conductive plate 119 and the coil-type electrode part 117 .

In this regard, as shown in FIG. 18, the strength of this magnetic field was measured to be larger as the distance between the conductive plate 119 and the coil-type electrode part 117 was narrower, and as shown in FIG. 19, the strength of the magnetic field was the Hall The smaller the size of (115), the larger it was measured.

On the other hand, as shown in FIG. 20 , a plurality of conductive plates 119 may be stacked on the coil-type electrode part 117 at a distance from each other, and at this time, the direction of the slit 123 may be changed. The magnetic field at the point where the through hole 121 is located is observed particularly strongly. That is, in the through hole 121 region, the magnetic field passes, but the slit 123 is formed while stacking the two conductive plates 119 as a method for suppressing the passage of the magnetic field to the portion where the slit 123 is located. direction can be different. Looking at the formation aspect of the magnetic field, it can be seen that only the through hole 121 region passes the magnetic field, and the magnetic field does not pass through the other parts. can be precisely adjusted.

21 is a graph comparing the magnitude of electric field energy according to the number of coil turns of the coil-type electrode part 117 according to an embodiment of the present invention. If the number of turns is larger, it can be seen that the magnetic field energy is concentrated, so that the size of the magnetic field becomes larger. Accordingly, by adjusting the number of turns of the coil, it is possible to adjust the size and area of the concentrated magnetic field energy.

<Alzheimer>

By using the stimulation device of the present invention, the mode in which the aggregation state of the Alzheimer's-induced protein is dismantled and the mode in which the Alzheimer's-induced protein oligomer changes adaptively were evaluated, respectively. The stimulation apparatus 100 of the present invention used for chronic pain and Alzheimer's disease is the same in structure and usage method. However, the operating method (treatment method) of the device for a disease may be different from each other as it is specialized for the disease.

In order to derive the most ideal power parameters required to dismantle Alzheimer's-induced protein aggregates, the experiment was conducted with different voltage values of 50mV, 1V, and 10V, and the voltage application time was 1 second, and the target protein was cultured in distilled water for 8 days. Alzheimer's-inducing protein 42 was used as a protein solution (see Fig. 22A).

Circular dichroism (CD) spectra of Alzheimer's-inducing protein 42 protein before and after application of an electric field are compared, and no particular change is observed except for an increase in intensity at approximately 195 nm. Although the strength of the electric field has no significant effect on the CD spectrum, the possibility that the stimulation apparatus 100 of the present invention affects the structure of the Alzheimer's-inducing protein 42 protein was confirmed.

Then, as shown in FIG. 22B, an electric field was applied to the Alzheimer's-induced protein 42 protein solution cultured for 16 days under four conditions to examine the aspect of the protein solution.

Although no significant voltage proportional change was observed, it was confirmed that red-shift occurred at 195 nm and 216 nm in addition to the increase in intensity at 197 nm. The result that the level of beta sheet conformation increases as the Alzheimer's-inducing protein 42 protein oligomer and amorphous aggregate, which are the steps before maturation into a plaque structure, are affected by the electric field applied by the stimulation device 100 of the present invention It could be confirmed that the

In order to further investigate the effect of the stimulation apparatus 100 of the present invention on the adaptation of the Alzheimer's-induced protein, the change in the adaptation of the Alzheimer's-induced protein 42 protein structure by the CD spectrum was monitored in real time, and the electrical stimulation system made of Au film compared with

As confirmed in FIG. 23a, when 50 mV was applied to the Alzheimer's-inducing protein 42 protein pre-cultured for 5 hours for 10 minutes, the stimulation device 100 of the present invention clearly showed the beta (β)-sheet characteristic. , the stimulation device 100 made of Au film showed slow conversion to beta (β)-sheet.

On the other hand, as confirmed in FIG. 23b, when the same electric field as in FIG. 23a was applied to the Alzheimer's-inducing protein 42 protein cultured for 30 days, the stimulation device 100 by the Au film reduced the Alzheimer's-inducing protein 42 protein in an atypical form to β - On the other hand, the stimulation device 100 of the present invention shows a clear negative band at about 222 nm, indicating a mode of conversion to α-helix, which is generally seen in TFE (Tetrafluoroeethylene) conditions, while the positive stimulation device 100 ) was clearly differentiated.

Here, it can be interpreted that the insoluble plaque-like structures are intensively subjected to a high-intensity multidirectional local electric field when settling, whereas the dispersed water-soluble oligomers are less affected by the electric field. Furthermore, conversion to the α-helical structure can be realized by the stimulation apparatus 100 of the present invention. This result was observed only in the electric field system (electric stimulation device) applied to the living body because the disaggregated Alzheimer's-inducing protein 42 protein strongly aggregated again in a short time. This result is consistent with the existing theoretical evidence for the close correlation between acclimatization and electric field of Alzheimer's-inducing proteins.

It should be noted that the above-described embodiment is for illustrative purposes only, and not for its limitation. In addition, those skilled in the art will understand that various embodiments are possible within the scope of the technical idea of the present invention.

100: stimulation device 101: control unit
103: substrate 105: base substrate
107, 113, 117: electrode part 109: non-conductive coating layer
111: feeding (feeding) 115: hole
119: conductive plate 121: through hole
123: slit

Claims (6)

In the stimulation apparatus for providing electrical stimulation to Alzheimer's-inducing protein that induces chronic pain or Alzheimer's, or for measuring bio-signals,
control unit;
a substrate coupled to the lower portion of the control unit, capable of receiving power wirelessly, and on which power receiving and signal transmitting electrodes for wirelessly transmitting biosignals are mounted integrally or separately; and
Electrode element coupled to the lower portion of the substrate and capable of delivering electrical stimulation to the body tissue; Stimulation equipped with an electrode element for measurement and stimulation of a nerve signal for diagnosis and treatment of chronic pain or Alzheimer's disease, characterized in that it comprises: Device. According to claim 1,
The electrode element is
base substrate;
At least one column protruding from the base substrate, a planar shape in which an insulating coating layer with a plurality of holes is processed thereon, or an electrode part in a coil shape;
When the electrode part has a columnar shape, a non-conductive coating layer is included in at least a portion of the electrode part except for the tip part or at least one area of the upper part of the base substrate,
Chronic pain or Alzheimer's disease, characterized in that when the electrode part is in the form of a coil, a through hole is formed in the central part, and at least one conductive plate provided with at least one slit extending outward from the through hole is stacked at a distance from the electrode part A stimulation device equipped with electrode elements for measurement and stimulation of nerve signals for diagnosis and treatment of 3. The method of claim 2,
When the electrode is in the form of a column, measuring and stimulating nerve signals for diagnosis and treatment of chronic pain or Alzheimer's disease, characterized in that a feeding is configured in a region buried in the base substrate among the lower portions of at least one of the electrode units Stimulation device equipped with electrode elements for use. 3. The method of claim 2,
When the electrode is in the form of a column, an electrode element for measuring and stimulating nerve signals for diagnosis and treatment of chronic pain or Alzheimer's disease, characterized in that the tip part of the electrode part and a part of the side part extending from the tip part are exposed stimulator. 3. The method of claim 2,
When there are two or more conductive plates, the slits of the conductive plates are stacked at different positions from each other. According to claim 1,
Diagnosis and treatment of chronic pain or Alzheimer's disease, characterized in that the substrate is divided into a substrate including a power receiving electrode capable of wirelessly transmitting power and a substrate including a signal transmitting electrode capable of wirelessly transmitting a biosignal A stimulation device equipped with electrode elements for measurement and stimulation of nerve signals for treatment.

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