KR102529408B1 - 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 stimulator equipped with an electrode element for measuring and stimulating nerve signals for the diagnosis and treatment of chronic pain or Alzheimer's disease, and more particularly, electrical stimulation of Alzheimer's-inducing protein that causes chronic pain or Alzheimer's disease. In the stimulation device for providing or measuring bio-signals, a control unit; a substrate coupled to the lower portion of the control unit, capable of receiving power wirelessly, and having power receiving and signal transmitting electrodes integrally mounted or separately mounted for transmitting biosignals wirelessly; and an electrode element coupled to a lower portion of the substrate and capable of transmitting electrical stimulation to body tissues; a stimulator 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

Device of nerve signal recording and stimulating for disagnosis and treatment of chronic pain or alzheimer's disease}

The present invention relates to a nerve signal measurement and stimulator equipped with an electrode element, and more particularly, an electrode with improved energy transfer efficiency so that sufficient energy can be generated and delivered 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 is characterized by the appearance of various pains even with stimuli below the threshold, and patients with chronic pain suffer from loss of pain suppression function, resulting in 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 are generated every year around the world. In addition, according to the Korea Spinal Cord Disability Association, it is estimated that the number of domestic patients is increasing every year. More than 75% of spinal cord injury patients experience chronic pain, and most patients live with pain every day and all day. The worst pain shows a level so high that it has an average intensity of 8.6 based on the maximum value of 10.

Among the various treatment methods for spinal cord injury, spinal cord stimulation (SCS) is a method of directly transmitting electric pulses to nerves. 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 electrical stimulation is transmitted to the spinal cord through a wire implanted therewith. By transmitting electrical stimulation through a wire called a lead from the electrode, which is the main component of the spinal cord stimulation device, to a specific location where pain occurs, giving a buffering effect to the pain signal, and allowing the buffered signal to be transmitted to the cerebrum, Pain is relieved or no pain is felt.

On the other hand, existing spinal cord stimulation devices have the following disadvantages. First, a spinal cord stimulation device is installed in the pelvis, and wires and leads are extended along the spinal cord to the affected area. Sometimes, the signal is not transmitted properly due to poor connection, so there is a case that needs to be corrected through a procedure, and there is also a risk of disconnection. Next, in the case of electrodes, scars may be created around the installation location. Next, a battery for driving the pulse generator may be damaged, and energy efficiency may deteriorate over time.

In addition, in the case of using an electrode having a conventional shape, it is necessary to buffer pain accompanying high intensity pain with a more amplified electrical signal, and 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 danger in use, so the applied power is inevitably limited. Therefore, as a result of the transmission of the weakened electrical signal, the buffer against pain is inevitably lowered, resulting in a decrease in the effect of relieving pain.

Therefore, it is necessary to seek improvement for these disadvantages, and through this, it is desired to develop a spinal cord stimulation device and other pain relief devices for chronic pain that are more convenient to use and have enhanced functions.

On the other hand, in the case of Alzheimer's disease, neurofibrillary tangles (plaques, Alzheimer's-induced protein plaques) are aggregated and accumulated in the brain, thereby causing the disease. Various approaches are currently being tried for the management of Alzheimer's disease. Representatively, invasive and non-invasive methods are included, and 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 proteins, Alzheimer's-induced protein fibers, aggregates For example, how to remove the back. In particular, in the case of 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, ultimately treating Alzheimer's disease. 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 physical methods has recently been attempted to change the state of Alzheimer's-induced protein aggregation. Ultrasound, light, laser, magnetic field, direct current, alternating current, etc. are being applied, and it has been reported that they show the effect of reducing Alzheimer's-induced protein plaques.

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

The present invention has been made to solve the above-mentioned problems of the prior art, and the present invention improves the shape of the electrode to achieve high energy efficiency despite applying less electrical energy to play a sufficient role in relieving pain. It aims to enable

That is, since the conventional electrode is a method of stimulating the outside of the tissue, a higher amount of power must be applied for the desired electrical stimulation, whereas the present invention is implanted into the tissue, so a relatively low amount of power is equivalent or less. More electrical stimulation is possible.

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

In addition, 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 of the present invention, a more subdivided specific signal is detected as it is, thereby preventing diseases or Another object is to enable precise control of signals according to pain or to more accurately determine the degree of disease or pain.

In addition, the present invention enables stimulation and recording to be performed at the same time, and continuously detects nerve signals, and when an abnormal signal is detected, chronic pain can be treated early by providing electrical stimulation. Another purpose is to be able to observe the prognosis after treatment.

In addition, the present invention is coupled with a storage device, enabling the collection and storage of bio-signal big data accumulated during the operation of the device, and from this, it is possible to optimize the stimulation protocol through a deep learning process. The purpose.

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

Another object of the present invention is to enable local selection and concentration of energy required for electrical or magnetic stimulation through structural adjustment of electrodes or coils required for electrical or magnetic stimulation.

Another object of the present invention is to adjust the size and region of energy required for electrical or magnetic stimulation by adjusting the structure of electrodes or coils required for electrical or magnetic stimulation.

In addition, the present invention is directly mounted in cells to provide sufficient barrier-overcoming folding free energy necessary for disassembling the aggregation structure of Alzheimer's-inducing proteins under low voltage conditions, enabling real-time observation of changes in adaptation of Alzheimer's-inducing protein molecules. that serves another purpose.

In order to achieve the above object, the present invention provides electrical stimulation for an Alzheimer's-inducing protein that causes chronic pain or Alzheimer's or provides a stimulation device for measuring a biosignal, comprising: a control unit; a substrate coupled to the lower portion of the control unit, capable of receiving power wirelessly, and having power receiving and signal transmitting electrodes integrally mounted or separately mounted for transmitting biosignals wirelessly; and an electrode element coupled to a lower portion of the substrate and capable of transmitting electrical stimulation to body tissues; a stimulator 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 pillar shape protruding on the base substrate, a planar shape in which an insulating coating layer having a plurality of holes is implemented, or a coil shape electrode part; includes, when the electrode part has a pillar shape, A non-conductive coating layer is included in at least one region of at least a portion of the electrode unit except for the portion or an upper portion of the base substrate, and when the electrode unit is in the form of a coil, a through hole is formed in the central portion, and at least one slit extending outward from the through hole is provided. It is preferable that at least one conductive plate is laminated at a distance from the electrode part.

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

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

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

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

According to the present invention as described above, despite the application of less electric energy by improving the shape of the electrode, high energy efficiency is achieved, so that it can play a sufficient role in relieving pain.

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

In addition, 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, thereby preventing disease Depending on the condition or pain, it is expected that the signal can be closely controlled or the effect of more accurately grasping the degree of disease or pain is expected.

In addition, the present invention enables stimulation and recording to be performed at the same time, and continuously detects nerve signals, and when an abnormal signal is detected, chronic pain can be treated early by providing electrical stimulation. The effect of allowing the prognosis to be observed after treatment is expected.

In addition, since the present invention is coupled with a storage device, it is possible to collect and store bio-signal big data accumulated during the operation of the device, and from this, it is expected that the stimulation protocol can be optimized through a deep learning process. do.

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

In addition, the present invention is expected to have an effect of enabling local selection and concentration 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 is expected to have the effect of adjusting the size and region of energy required for electrical or magnetic stimulation by adjusting the structure of electrodes or coils required for electrical or magnetic stimulation.

In addition, the present invention is directly mounted in cells to provide sufficient barrier-overcoming folding free energy necessary for disassembling the aggregation structure of Alzheimer's-inducing proteins under low voltage conditions, enabling real-time observation of changes in adaptation of Alzheimer's-inducing protein molecules. 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 types of conventional spinal cord stimulation devices.
3 is a diagram showing waveforms generated from a conventional spinal cord stimulation device.
4 is a schematic diagram showing installation states of the conventional spinal cord stimulation device and the spinal cord stimulation device of the present invention.
5 is an exploded perspective view showing a spinal cord stimulation device according to an embodiment of the present invention.
6 is an operation diagram of the spinal cord stimulation device of FIG. 5;
7 is an electric field distribution diagram appearing when a conventional spinal cord stimulation device and a spinal cord stimulation device according to an embodiment of the present invention are respectively applied.
8 is a schematic diagram showing the installation of the spinal cord stimulation device of the present invention and the installation state of the conventional spinal cord stimulation device by taking the human body as an example, respectively.
9 is a diagram showing the distribution and direction of an electric field generated from an electrode having a conventional shape.
10 is a diagram showing electric field distribution appearing in a columnar electrode according to an embodiment of the present invention.
FIG. 11 is a diagram illustrating a formation of a non-conductive coating layer on a base substrate including a lower portion of a columnar electrode in a columnar electrode according to an embodiment of the present invention and a corresponding electric field distribution.
12 is a view showing a non-conductive coating layer formed on the side surface of the pillar-shaped electrode except for the upper end of the pillar-shaped electrode according to an embodiment of the present invention and the resulting electric field distribution.
Fig. 13 is a view showing a combination of Figs. 11 and 12;
FIG. 14 is a view showing the formation of a non-conductive coating layer on a pillar-shaped electrode according to various embodiments of the present invention and the resulting electric field distribution.
FIG. 15 is a view showing the formation of a non-conductive coating layer on a columnar electrode according to various embodiments of the present invention and the resultant electric field distribution, showing the formation of a feeding 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 drilled on the non-conductive coating to expose the electrode.
17 is a view showing various embodiments in which metal plates are laminated at intervals on the coil-type electrode or slits are formed in the metal plate according to the present invention.
18 is a graph comparing the magnitude of electric field energy according to the distance between the coiled electrode and the stacked metal plates according to an embodiment of the present invention.
19 is a graph comparing the magnitude of electric field energy according to the size of through holes of metal plates stacked on coil-type electrodes 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, but with different directions of slits formed in each metal plate.
21 is a graph comparing electric field energy according to the number of electrode turns of a coiled electrode according to an embodiment of the present invention.
22 shows electrical stimulation using a stimulator according to an embodiment of the present invention and varying voltage values at 50 mV, 1 V, and 10 V in order to derive the most ideal power parameters required to dismantle Alzheimer's-induced protein aggregates therefrom. This is a CD spectrum result shown by comparison after performing electrical stimulation with a planar stimulator under the same conditions.
Figure 23 monitors the adaptation change of the Alzheimer's induction protein 42 protein structure in real time by the CD spectrum in order to investigate the effect of the stimulator on the adaptation of the Alzheimer's induction protein according to an embodiment of the present invention, but with a conventional flat film. This is the CD spectrum result shown in comparison with the fabricated electrical stimulation system.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings so that those skilled in the art can easily carry out the present invention. However, the present invention may be embodied in many 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 certain component is said to "include", it means that it may further include other components without excluding other components 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 device 100 for diagnosing and treating pain occurring in the spine has been described as an example, but the stimulation device 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. As long as it can be transplanted, there is no limit to the application area.

1 is a schematic diagram showing an installation state of a conventional spinal cord stimulation device 100. As shown, the conventional spinal cord stimulation device 100 usually has a planar shape, implants an implanted stimulator with a built-in battery into the body, for example, the hip, and connects electrodes connected to the electrical stimulator to the spine. It is installed so that it is located near the affected part of

That is, the conventional spinal cord stimulation device 100 is different from the present invention in that it is not inserted into the spinal cord but located outside the spinal cord. Therefore, an input power as high as possible is required for effective stimulation. However, as the input power value increases, it acts as a burden on the human body and sometimes causes tissue damage. Therefore, an alternative to this is needed.

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

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

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

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

5 is an exploded perspective view showing the spinal cord stimulation device 100 according to an embodiment of the present invention. As shown, the spinal cord stimulation device 100 of the present invention provides electrical stimulation for chronic pain or the stimulation device 100 for measuring bio-signals, including a control unit 101; A substrate 103 coupled to the lower part of the controller 101, capable of receiving power wirelessly, and having power receiving and signal transmitting electrodes integrally mounted or separately mounted for transmitting biosignals wirelessly; and an electrode element coupled to a lower portion of the substrate 103 and capable of transmitting electrical stimulation to body tissues.

On the other hand, the substrate 103 may be functionally operated as an integral type as described above, but as a different type, the substrate 103 including a power receiving electrode capable of receiving power wirelessly, and a biosignal capable of transmitting a biosignal wirelessly It may be divided into a substrate 103 including a signal transfer electrode. That is, the board 103 with separate power reception and signal transmission may be mounted so that it may operate individually as a separate module.

Here, the electrode element is a base substrate 105, at least one pillar shape protruding on the base substrate 105, or a flat shape in which an insulating coating layer having a plurality of holes 115 processed thereon is implemented, An electrode unit 107 in the form of a coil, and a bonding portion formed in a region where the electrode unit 107 and the base substrate 105 are combined to receive or transmit signals or power are included.

The main feature of the present invention is the electrode unit 107, and the role of the electrode unit 107 is to enable electrical stimulation efficiently with low or adequate input power that the body can accept. To this end, variously shaped electrode units 107 were derived as follows.

First, the exposed electrode on which the non-conductive coating layer 109 is not formed 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 pillar-shaped electrode. The electric field is generated selectively and strongly in the area, and therefore, the electric stimulation is made precisely according to the law of selection and concentration.

Second, a non-conductive coating layer 109 is formed on the conventional flat electrode, but the hole 115 is locally processed to the extent that the surface of the electrode is exposed, so that an electric field is formed in the hole 115, thereby forming a pillar. It was designed to perform a function similar to the shape of the electrode.

Third, in the case of a coil-type electrode, the electrode part 107 was formed by stacking the conductive plates 119 at intervals from the electrodes, and at this time, a hole 115 was formed in the center of the electrode plate, and the upper hole 115 From ), a slit 123 extending along a specific direction of the conductive plate 119 was processed. Thus, 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 stimulator 100 of the present invention, and these stimulations can be performed more precisely and accurately, and the degree of pain and the location of the affected area can be more accurately grasped. be able to

FIG. 6 is an operation view of the spinal cord stimulation device 100 of FIG. 5 . As shown, the stimulator 100 of the present invention generates a stimulus, receives a result from it, records it, and can be controlled to generate a new stimulus suitable for this from the result. When these results are accumulated, they are used as big data, and help can be provided to improve the device and its operation method so that more improved treatment effects can be derived.

7 is an electric field distribution diagram appearing when a conventional spinal cord stimulation device 100 and a spinal cord stimulation device 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 feature, but in the case of the stimulation device 100 of the present invention, a high density electric field can be formed around the electrode can confirm that it can.

8 is a schematic diagram showing the installation of the spinal cord stimulation device 100 of the present invention and the installation state of the conventional spinal cord stimulation device 100 by taking the human body as an example, respectively. As shown, the present invention can deliver stimulation more precisely into the spinal cord by directly implanting it in the spine, and more accurately and effectively operate the stimulation device 100 from feedback provided through acquisition of big data and deep learning. there is. This can be said to be a point of distinction from the conventional spinal cord stimulation device 100 that simply stops at providing stimulation.

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

9 is a view showing the distribution and direction of an electric field generated in an electrode having a conventional shape, and FIG. 10 is a view showing the distribution of an electric field appearing 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 planar electrode or a simple coil shape. In the case of the former, it can be confirmed that the electric field is strongly generated at the corner rather than the flat plate. 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 part that occupies most of the electrode area, a very large voltage must be applied. In the case of doing so, damage to tissues may occur due to a large electric field, and thus, there may be a great risk in use.

In the latter case, as an example, a loop antenna coil-shaped electrode for forming a magnetic field and a magnetic field formed therefrom can be confirmed. At this time, it is a general phenomenon that the maximum magnetic field appears at the center of the coil and shows a field distribution that decreases toward the end. The reason why the magnetic field is not generated on the lower surface but only on the upper surface is that a magnetic material for shielding the magnetic field is disposed on the lower surface when the coil electrode is formed.

On the other hand, as shown in FIG. 10, in the case of introducing a columnar structure to the electrode, it can be seen that a more uniform field distribution is formed because some fields are formed even in the inner part of the electrode compared to the planar structure electrode. However, the field is still not well formed in the center of the electrode.

11 shows a base substrate 105 including a lower portion of the columnar electrode unit 107 with a non-conductive coating layer 109 when the electrode unit 107 according to an embodiment of the present invention is a columnar electrode unit 107. ) is a diagram showing the electric field field distribution formed on it.

As shown, it can be seen that some electric fields are more clearly formed than in FIG. 10 . Through this, a higher electric field energy can be transmitted in each columnar electrode unit 107 than in the conventional columnar electrode unit 107 . This is the same in the case of FIG. 12, and similar to the result of FIG. 11, it can be confirmed that an electric field is formed in each columnar electrode part 107.

FIG. 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 . Compared to FIGS. 11 and 12, it seems that a stronger electric field is formed, and FIG. 13 also shows that it is feasible to introduce a non-conductive coating layer 109 to the columnar electrode part 107 as in FIGS. 11 and 12. it will show

11 to 13, introducing the non-conductive coating layer 109 to the remaining area, including the base substrate 105, except for a part of the columnar electrode unit 107, preferably the upper end, forms an electric field. It contains the possibility of various applications by controlling the location, direction of electric field formation, and electric field distribution.

In particular, according to the present invention, the formation position of the non-conductive coating layer 109 relative to the columnar electrode unit 107 and the density of the columnar electrode per unit area are adjusted according to the range and intensity of chronic pain, thereby providing the same input power value. 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.

FIG. 14 is a diagram illustrating the formation of a non-conductive coating layer 109 on a columnar electrode unit 107 according to various embodiments of the present invention and the resultant electric field distribution. That is, the non-conductive coating layer 109 can be implemented in various ways as shown in FIG.

15 shows the formation of the non-conductive coating layer 109 on the pillar-shaped electrode of the present invention according to various embodiments and the electric field distribution accordingly, the feeding 111 (feeding) at the bottom of the pillar-shaped electrode part 107 It is a drawing 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 performed, a phenomenon in which an electric field is mainly concentrated on one feeding 111 columnar electrode appears. Accordingly, the distribution of the electric field can be effectively controlled 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 parts 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, energy can be concentrated by variously adjusting the method of feeding 111 to the columnar electrode unit 107 .

16 shows that a non-conductive coating is performed on an 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 that represents

As shown, a strong electric field is observed at the part where the hole 115 is machined, and the strength or formation position of the electric field can be adjusted while changing the size, position, number, etc. of the hole 115, Effects similar to those of the aforementioned columnar electrode unit 107 can be achieved. Therefore, the diversity of applications is recognized in that it is possible to select between forming the pillar-shaped electrode part 107 and the non-conductive coating layer 109 on the electrode part 113 and then processing the hole 115 as needed. do.

FIG. 17 is a view showing 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 according to the present invention. As shown, when the conductive plate 119 without the slit 123 is stacked at intervals on the coil-type electrode part 117, it can be seen that no magnetic field is radiated to the outside. However, when the slit 123 is created, it can be confirmed that the magnetic field is radiated through the slit 123 and the through hole 121, and the radiation effect of the magnetic field through the through hole 121 is particularly noticeable. Here, the intensity 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 the magnetic field was measured to be greater as the distance between the conductive plate 119 and the coil-type electrode part 117 was narrowed. As shown in FIG. 19, the strength of the magnetic field was measured as The smaller the size of (115), the larger it was measured.

Meanwhile, as shown in FIG. 20, a plurality of conductive plates 119 may be stacked on the coil-type electrode part 117 at intervals from each other. At this time, the direction of the slits 123 may be different. In this case, The magnetic field at the point where the through hole 121 is located is particularly strongly observed. That is, as a method for suppressing the passage of a magnetic field through the through hole 121 region but passing through the slit 123, the slit 123 is formed while stacking two conductive plates 119 in this way. direction can be different. Looking at the formation of the magnetic field, it can be seen that the magnetic field passes through only the through hole 121 area, and the magnetic field does not pass through other parts. As a result, only the magnetic field passes through the desired area to concentrate energy, and the area where the magnetic field energy is irradiated can be precisely controlled.

21 is a graph comparing electric field energy according to the number of coil turns of the coiled electrode unit 117 according to an embodiment of the present invention. If the number of turns is greater, it can be confirmed that the magnitude of the magnetic field increases because the energy of the magnetic field is concentrated. Thus, 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's>

By using the stimulator of the present invention, the state in which the aggregation state of Alzheimer's inducing proteins is disintegrated and the state in which Alzheimer's inducing protein oligomers are adaptively changed were evaluated, respectively. The stimulator 100 of the present invention used for chronic pain and Alzheimer's disease is the same in terms of structure and method of use. However, the operating method (treatment method) of the device for the disease is specific to the disease, and may be different from each other.

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

Circular dichroism (CD) spectra of Alzheimer's-inducing protein 42 before and after application of the electric field were compared, and no particular change was observed except for an increase in intensity at approximately 195 nm. Although the intensity of the electric field does not significantly affect the CD spectrum, the possibility that the stimulator 100 of the present invention affects the structure of the Alzheimer's-induced protein 42 protein was confirmed.

And, as shown in FIG. 22B, an electric field was applied to the Alzheimer's-inducing protein 42 protein solution cultured for 16 days under four conditions, and the behavior of the protein solution was examined.

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

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

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

On the other hand, as shown in FIG. 23b, when the same electric field as in FIG. 23a is applied to the Alzheimer's-inducing protein 42 cultured for 30 days, the Au film-based stimulator 100 converts the Alzheimer's-inducing protein 42 protein in an atypical form to β. -On the other hand, the stimulator 100 of the present invention shows a distinct negative band at about 222 nm, showing an aspect of converting to an α-helix commonly seen in TFE (Tetrafluoroeethylene) conditions, and the positive stimulator (100 ) results were clearly distinguished.

Here, it can be interpreted that an insoluble plaque-like structure is intensively subjected to a high-intensity multidirectional local electric field when precipitated, whereas a dispersed water-soluble oligomer is less affected by an electric field. Furthermore, it is possible to realize conversion to an α-helical structure by the stimulator 100 of the present invention. Since the disaggregated Alzheimer's-induced protein 42 protein strongly aggregated again in a short time, this result was observed only in an electric field system (electric stimulation device) applied to a living body. This result is consistent with previous theoretical demonstrations of a close correlation between adaptation of Alzheimer's-inducing proteins and electric fields.

It should be noted that the foregoing embodiments are illustrative and not limiting. In addition, those skilled in the art will understand that various embodiments are possible within the scope of the technical spirit 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 115: hole
119: conductive plate 121: through hole
123: slit

Claims (6)

In a stimulator for providing electrical stimulation for Alzheimer's-inducing protein that causes 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 having power receiving and signal transmitting electrodes integrally mounted or separately mounted for transmitting biosignals wirelessly; and an electrode element coupled to a lower portion of the substrate and capable of transmitting electrical stimulation to body tissues,
The electrode element may include a base substrate; At least one pillar shape protruding on the base substrate, a planar shape with an insulating coating layer having a plurality of holes processed thereon, or a coil shape electrode part; includes,
When the electrode unit has a pillar shape, a non-conductive coating layer is included in at least one region of at least a portion of the electrode unit excluding the tip portion or an upper portion of the base substrate, and a feeding area is included in the lower portion of at least one of the electrode units buried in the base substrate. ) A stimulator equipped with an electrode element for measuring and stimulating nerve signals for the diagnosis and treatment of chronic pain or Alzheimer's disease, characterized in that the configuration. In a stimulator for providing electrical stimulation for Alzheimer's-inducing protein that causes 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 having power receiving and signal transmitting electrodes integrally mounted or separately mounted for transmitting biosignals wirelessly; and an electrode element coupled to a lower portion of the substrate and capable of transmitting electrical stimulation to body tissues,
The electrode element may include a base substrate; At least one pillar shape protruding on the base substrate, a planar shape with an insulating coating layer having a plurality of holes processed thereon, or a coil shape electrode part; includes,
When the electrode part is in the form of a coil, at least one conductive plate having a through hole formed in the central portion and provided with at least one slit extending outward from the through hole is stacked at a distance from the electrode part. A stimulator equipped with an electrode element for measuring and stimulating nerve signals for diagnosis and treatment of chronic pain or Alzheimer's disease, characterized in that the positions of the slits of the conductive plate are stacked differently. delete According to claim 1 or 2,
When the electrode is in the form of a pillar, an electrode element for measuring and stimulating a nerve signal for diagnosis and treatment of chronic pain or Alzheimer's disease is mounted, characterized in that the tip of the electrode part and a part of the side part extending from the tip are exposed. stimulator. delete According to claim 1 or 2,
Diagnosis and Stimulator equipped with electrode elements for nerve signal measurement and stimulation for treatment.

Images