Transdermal energy patch

Abstract

To provide a transdermal energy patch capable of enhancing an improvement action in the object part of the subject's body.SOLUTION: A transdermal energy patch 1 includes an anode electrode 11, a cathode electrode 12, and conductive parts 20A, 20B that correspond to and contact each of the anode electrode 11 and the cathode electrode 12. The transdermal energy patch 1 is configured to apply a direct electric current to an organism by making the anode electrode 11 and the cathode electrode 12 contact the organism via the conductive parts 20A, 20B. The transdermal energy patch 1 is so configured that the current density of a direct current flowing after the lapse of ten minutes after an electric circuit formed to include the anode electrode 11, the cathode electrode 12 and the conductive parts 20A, 20B is connected to a resistor of 5 kΩ is 10 μA / cm2 or more and less than 500 μA / cm2, and this current density is the current density at the conductive parts 20A, 20B.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a transdermal electrical patch. [Background technology]

[0002] Patent Documents 1 to 3 disclose various examples of electro-patch capable of providing electro-stimulation. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] JP 2016-144634 A [Patent Document 2] JP 2016-067401 A [Patent Document 3] JP 2021-115330 A Summary of the Invention [Problem to be solved by the invention]

[0004] Patent Document 1 discloses an electric patch that can pass a very small amount of current through a living body. It has been confirmed by experiments that this electric patch can pass a very small amount of current, for example, 0.1 μA to 2 μA or 4 μA to 5 μA (see paragraphs 0029 and 0030 of Patent Document 1), and the current density of the current passing through this electric patch is, for example, 0.5 μA / cm according to a simulation test described later. 2 It is smaller than the size of the patch. Although Patent Document 1 proposes using such an electric current patch for treatment, the improvement effect when the electric current patch is used for treatment has not been verified, and the improvement effect is unknown. However, there is a demand for using a small treatment tool such as an electric current patch to improve a target site in a living body (for example, to relieve pain), and it is desired that such an electric current patch be provided.

[0005] An object of the present invention is to provide a transdermal electropigment patch that can improve the improving effect on the target area. [Means for solving the problem]

[0006] (1) One aspect of the present invention relates to a transdermal electropatch. The transdermal electropatch includes a positive electrode, a negative electrode, and conductive parts that are arranged to correspond to and contact the positive electrode and the negative electrode. The transdermal electropatch is configured to pass a direct current through a living body by bringing the positive electrode and the negative electrode into contact with the living body via the conductive parts. The transdermal electropatch is configured such that the current density of the direct current flowing 10 minutes after an electric circuit formed by the positive electrode, the negative electrode, and the conductive parts is connected to a resistance of 5 kΩ is 10 μA / cm. 2 More than 500μA / cm 2 less than the current density in the conductive portion.

[0007] This transdermal electropatch is configured to pass a direct current through a living body by contacting the positive and negative electrodes with the living body via the conductive parts. This transdermal electropatch is configured such that the current density of the direct current passing through the patch is 10 μA / cm 10 minutes after the electric circuit formed by the positive and negative electrodes and the conductive parts is connected to a resistance of 5 kΩ. 2 More than 500μA / cm 2 According to the findings of the present inventors, the weak current flowing through the living body is set to an extremely small current (for example, 0.2 μA / cm 2 ) which is higher than 10μA / cm 2 It has been found that by using a direct current of 500μA / cm or more (when connected to a 5kΩ resistor), the improving effect on the target area can be significantly improved. Therefore, this transdermal electropatch can improve the improving effect on the target area. In addition, when the current density of the current applied to the body is 500μA / cm 2 If the current density exceeds this level, the user may feel irritation. For this reason, the current density of this transdermal electropatch is set to 500 μA / cm 2The electrical circuit is formed so that the resistance is less than 5 kΩ (when connected to a resistor). This makes it possible to use the transdermal electropatch for a long period of time (for example, by attaching it to a specific part of the user's body), further improving the improvement effect on the target part.

[0008] (2) The transdermal electropatch described in (1) above has a direct current density of 10 μA / cm 5 hours after the electrical circuit is connected to a resistance of 5 kΩ. 2 More than 500μA / cm 2 In this case, by attaching the transdermal electrolyzing patch to the target area for a long period of time, it is possible to continuously improve the improving effect on the target area.

[0009] (3) The transdermal electropatch described in (1) or (2) above has a direct current density of 5 μA / cm 10 minutes after the electrical circuit is connected to a resistance of 10 kΩ. 2 More than 30μA / cm 2 The present invention may be configured as follows. In this case, the improving effect on the target site can be improved more reliably.

[0010] (4) The transdermal electropatch described in (1) or (2) above has a direct current density of 10 μA / cm 10 minutes after the electrical circuit is connected to a resistance of 10 kΩ. 2 More than 45μA / cm 2 The present invention may be configured as follows. In this case, the improving effect on the target site can be improved more reliably.

[0011] (5) The transdermal electropatch described in (1) or (2) above has a direct current density of 175 μA / cm 10 minutes after the electrical circuit is connected to a resistance of 5 kΩ. 2 The present invention may be configured as follows: Even in this case, the improving effect on the target site can be further improved.

[0012] (6) The transdermal electropatch described in (1) or (2) above has a direct current density of 10 μA / cm 10 minutes after the electrical circuit is connected to a resistance of 5 kΩ. 2 More than 30μA / cm 2 The current density of the direct current flowing one hour after connecting to a 5 kΩ resistor is 10 μA / cm 2 More than 30μA / cm 2 The present invention may be configured as follows: Even in this case, the improving effect on the target site can be further improved.

[0013] (7) Any of the above (1) to (6) transdermal electropatch may further include a connection part that electrically connects the positive electrode and the negative electrode, and each of the conductive parts may have a sponge and a buffer agent made of an electrolyte, or the buffer agent may be contained in the sponge. In this case, the configuration of the conductive part for forming an electric circuit can be specifically realized.

[0014] (8) In any of the above (1) to (7) transdermal electropatch, at least one of the positive and negative electrodes may carry an enzyme that catalyzes an oxidation-reduction reaction. In this case, it is preferable that an electron transfer mediator is fixed to the electrode carrying the enzyme, and it is more preferable that the electron transfer mediator is a quinone compound or a phenylenediamine compound. With this configuration, it is possible to more reliably achieve the DC current flowing through the living body within any of the above ranges, and more reliably improve the improving effect on the target site.

[0015] (9) In another aspect, the present invention relates to a method for operating a transdermal electrophoretic patch, the method comprising the step of passing a direct current through an electric circuit of the transdermal electrophoretic patch of any one of (1) to (8) above. The method comprises the step of supplying water to the sponge of the transdermal electrophoretic patch of (7) above. Such a method can improve the improving effect on the target area. Effect of the Invention

[0016] According to the present invention, the improving effect on the target site can be improved. [Brief description of the drawings]

[0017] [Figure 1] FIG. 1 is an exploded perspective view of a transdermal energizing patch according to one embodiment of the present invention. [Diagram 2] FIG. 2 is a schematic diagram showing the relationship between a catalyst and an electron transfer mediator in the anode electrode of the transdermal current patch shown in FIG. [Diagram 3] FIG. 3 is a graph showing the current density flowing through a living body via the transdermal current-carrying patch shown in FIG. [Figure 4] FIG. 4 is a graph showing an example of the current density of the transdermal energizing patch shown in FIG. [Diagram 5] FIG. 5 is a diagram showing a schematic diagram of a method for measuring the current density. [Figure 6] FIG. 6 is a graph showing the results of evaluating delayed onset muscle pain using a transdermal electroconductive patch. [Figure 7] FIG. 7 is a graph showing the results of evaluating exercise performance using a transdermal electroconductive patch. [Figure 8] FIG. 8 is a graph showing the results of an evaluation of the relief of stiff shoulders using a transdermal electroconductive patch. [Figure 9] FIG. 9 is a graph showing an example of the results of evaluating the relief of temporomandibular joint disorders using a transdermal electroconductive patch. [Figure 10] FIG. 10 is a graph showing another example of the results of evaluating the relief of temporomandibular joint disorders using a transdermal electroconductive patch. [Figure 11] FIG. 11 is a schematic diagram showing a test method for a patch of a comparative example. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] Hereinafter, a transdermal electroconductive patch according to an embodiment of the present invention will be described in detail with reference to the drawings. In the description, the same elements or elements having the same functions may be designated by the same reference numerals, and duplicated descriptions will be omitted.

[0019] FIG. 1 is an exploded perspective view of a transdermal electropatch according to one embodiment of the present invention. The transdermal electropatch 1 is a current patch that utilizes a biobattery using an enzyme, and as shown in FIG. 1, is configured to include an electrode body 10 (multiple electrodes), two conductive parts 20 (conductive layer, multiple conductive parts), an adhesive layer 30, a separator 40, and a surface film 50. When using the transdermal electropatch 1, the separator 40 is removed, and the patch is attached to the skin (living body) of a part of the body of a subject (user) (e.g., shoulder, arm, chin) by the adhesive layer 30. As will be described in detail later, by attaching the patch in this manner, in the transdermal electropatch 1, each electrode of the electrode body 10 contacts a part of the subject via the conductive part 20, forming an electric circuit that passes a weak current. In this embodiment, the weak current that this electric circuit passes to the part of the subject and its adjacent area is, for example, 0.5 μA / cm 2 More than 500μA / cm 2 The current density of the transdermal current is less than 500 μA / cm, which is slightly stronger than an extremely weak current. However, the transdermal current patch 1 has a current density of 500 μA / cm, which is the standard at which subjects feel stimulation. 2 The current density of the transdermal current-carrying patch 1 is set to generate a current with a weaker current density than that of the subject's body. 2 It may be more than that.

[0020] The electrode body 10 has an anode electrode 11 (negative electrode), a cathode electrode 12 (positive electrode), and a lead 13 (connection part). The lead 13 connects the anode electrode 11 and the cathode electrode 12. The anode electrode 11, the lead 13, and the cathode electrode 12 may be arranged in this order and formed as an integrated member. The electrode body 10 has a thickness of, for example, about 0.1 mm to 2.0 mm. The size of the transdermal electro-conductive patch 1 is preferably, for example, 1 cm to 10 cm in width and 1 cm to 10 cm in length. The size (area) of the electrode body 10 in the transdermal electro-conductive patch 1 is smaller than the overall size of the transdermal electro-conductive patch 1, and the size of the anode electrode 11 and the cathode electrode 12 (the area of ​​each electrode when viewed from the thickness direction of each electrode (the vertical direction perpendicular to each electrode)) may be appropriately changed depending on the site to which the electrodes are attached and the range through which a weak current is desired to flow, and may be, for example, 80 cm. 2 Less than or equal to 50cm 2 Less than or equal to 40cm 2 Less than or equal to 30cm 2 Less than or equal to 20cm 2 Less than or equal to 10cm 2 Less than or equal to 1 cm 2 Less than 0.5cm 2 Less than 0.1cm 2 The following can be used. One such small transdermal electropatch 1 may be applied to the painful area, or multiple transdermal electropatch 1 may be applied to the painful area. The transdermal electropatch 1 may be configured to have one electrode body 10 arranged therein, or to have two or more electrode bodies 10 arranged therein. The shape of the transdermal electropatch 1 may be any shape, such as a polygon, pentagon, square, triangle, or circle.

[0021] Examples of materials for the anode electrode 11, the cathode electrode 12, and the lead 13 include carbon materials such as carbon nanotubes, Ketjen Black (registered trademark), glassy carbon (registered trademark), graphene, fullerene, carbon fiber, carbon fabric, and carbon aerogel; conductive polymers such as polyaniline, polyacetylene, polypyrrole, poly(p-phenylene vinylene), polythiophene, and poly(p-phenylene sulfide); semiconductors such as silicone, germanium, indium tin oxide (ITO), titanium oxide, copper oxide, and silver oxide; and metals such as gold, platinum, titanium, aluminum, tungsten, copper, silver, zinc, magnesium, iron, and palladium. In particular, from the viewpoint of flexibility and electrochemical stability, carbon materials such as carbon fabric and carbon nanotubes are preferred as the material for the electrode body 10. In particular, when an enzyme is immobilized on the electrode at a high density, the material for the electrode body 10 is preferably carbon fabric modified with carbon nanotubes.

[0022] A catalyst that catalyzes an oxidation reaction may be supported on the anode electrode 11. Examples of such catalysts include oxidoreductases such as glucose oxidase, glucose dehydrogenase (GDH), fructose dehydrogenase (D-fructose dehydrogenase (FDH), alcohol oxidase, alcohol dehydrogenase, lactate oxidase, and lactate dehydrogenase. In addition to the enzymes, an electrode made of one or more of magnesium and an alloy containing magnesium, aluminum and an alloy containing aluminum, calcium, iron, zinc, and the like may be used.

[0023] 2, an electron transfer mediator 15 is fixed to the anode electrode 11, which promotes electron transfer between an electrode (anode electrode 11) in the biobattery and an enzyme 14 that functions as a catalyst. In the anode electrode 11, the enzyme 14 and the electron transfer mediator 15 fixed to the electrode allow for efficient extraction of electrons from, for example, glucose, which is a fuel. As the electron transfer mediator 15 used here, various types can be used, and examples thereof include phenazines, viologens, cytochromes (e.g., cytochrome b, cytochrome c), phenoxazines, phenothiazines, ferricyanides, such as potassium ferricyanide, ferredoxins, ferrocenes, osmium complexes, and derivatives thereof, and examples of phenazine compounds include, but are not limited to, mediators such as phenazine methosulfate (PMS), methoxy PMS, quinone compounds, and phenylenediamine compounds. As the quinone compound used as the mediator, preferably, 1,4-naphthoquinone, 1,2-naphthoquinone, and 2-methyl-1,4-naphthoquinone are listed. As the phenylenediamine compound, N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD), N,N'-diphenyl-p-phenylenediamine (DPPD), and N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) are listed. By using such an electron transfer mediator, it is possible to increase the current of the electric circuit to the above-mentioned range when the transdermal electrochemical patch 1 is attached to a predetermined part of the subject.

[0024] A catalyst that catalyzes the reduction reaction is supported on the cathode electrode 12. Examples of such catalysts include enzymes such as bilirubin oxidase (BOD), laccase, Cu efflux oxidase (Cueo), and ascorbic acid oxidase; transition metal complexes such as iron (II) phthalocyanine; and metal oxides made of at least one metal selected from platinum, titanium, nickel, stainless steel, iron, manganese, zinc, copper, and molybdenum, or at least one metal selected from calcium, iron, manganese, zinc, copper, and molybdenum.

[0025] The conductive part 20 is a water absorbent disposed so as to be in surface contact with the anode electrode 11 and the cathode electrode 12. The conductive part 20 has a structure in which a dried fuel or electrolyte is contained inside a sponge. The conductive part 20A in contact with the anode electrode 11 contains a fuel such as an organic substance that causes an oxidation reaction at the anode electrode 11. Examples of the fuel include glucose, fructose, ascorbic acid (vitamin C), alcohol, and lactic acid (see also FIG. 2).

[0026] The water absorbent constituting the conductive part 20 contains a buffer as an electrolyte. The buffer is an electrolyte that becomes a buffer solution when it is made into an aqueous solution. Examples of the buffer include salts of weak acids and weak bases. The water absorbent may contain electrolytes other than the buffer, such as salts of strong acids and strong bases, or may not contain them. Examples of electrolytes constituting the buffer include weak acids such as phosphoric acid, acetic acid, citric acid, and tartaric acid; sodium salts and potassium salts of these weak acids; weak bases such as organic amines, and salts thereof. The buffer may be composed of two or more electrolytes. When the buffer is not contained in the water absorbent, the buffer may be contained in the water to be absorbed, or the buffer may be contained in both the water absorbent and the water to be absorbed.

[0027] After the transdermal electrostatic patch 1 is manufactured, the water absorbent of the conductive part 20 is in a dry state before it is used. When the transdermal electrostatic patch 1 is used, water is supplied to the transdermal electrostatic patch 1, so that the water absorbent absorbs water and an electrolyte solution containing electrolytes is contained inside the water absorbent. This electrically connects the anode electrode 11 and the cathode electrode 12 to the skin through the electrolyte solution, and an ion migration path is formed that includes the anode electrode 11, the conductive part 20A, the skin, the conductive part 20B, and the cathode electrode 12. For example, cations such as hydrogen ions and sodium ions are transported from the anode electrode 11 to the cathode electrode 12.

[0028] In the water absorbent of the conductive part 20, the buffer is contained in a porous sponge. Examples of the material of the sponge include synthetic resins such as polyurethane and polyvinyl alcohol; natural polymers such as cellulose, and derivatives thereof. Fine continuous pores are formed inside the sponge. Therefore, by absorbing an electrolyte solution consisting of an aqueous solution of the electrolyte into the sponge and then drying it, the solute electrolyte becomes dry in the sponge. It is considered that at least a part of the electrolyte is exposed in a solid state on the inner wall surface of the pores without being taken into the material of the sponge. In addition to the electrolyte, the sponge can contain fuel for a biobattery, a drug that can act on a living body, other additives, etc.

[0029] The sponge of the conductive part 20 has excellent water absorption properties due to capillary action, surface tension, hydrophilicity, etc., so it quickly absorbs water by simply immersing a part of its underside in water. Furthermore, solutes such as electrolytes dissolve in water in the internal space of the sponge's pores to prepare an electrolyte solution. Due to the water absorption power of the sponge, the electrolyte solution is mixed uniformly and spreads throughout the entire absorbent body, making it possible to connect the anode electrode 11 and the cathode electrode 12 with the skin through the electrolyte solution. The absorbent body made of a sponge is capable of moving water in a direction against gravity, even if it has a complex shape such as a three-dimensional shape.

[0030] The sponge constituting the conductive part 20 has a pore size of, for example, 10 to 500 μm. Specific examples of the pore size include 10 μm, 20 μm, 25 μm, 30 μm, 50 μm, 80 μm, 100 μm, 150 μm, 200 μm, 300 μm, 500 μm, and the like, or intermediate values ​​or values ​​close to these, but are not limited thereto. The porosity of the sponge is, for example, 60 to 95%. As the sponge, polyurethane sponge is preferable, but sponges with similarly excellent performance such as water absorption can also be suitably used. As the sponge constituting the conductive part 20, for example, Sofras (trade name, manufactured by AION Co., Ltd.) can be used. The thickness of the sponge constituting the conductive part 20 is about 0.5 mm to 2 mm, but since it has a large number of pores, it is possible to adjust the thickness when it is incorporated into the transdermal electric patch 1.

[0031] The transdermal electrostatic patch 1 using a biobattery can use one or more types of enzyme electrodes for the anode electrode 11 or the cathode electrode 12. When the water absorbing body of the conductive part 20 absorbs water, electricity is started to flow through the biobattery, and the transdermal electrostatic patch 1 is driven by the biobattery. The water absorbing body of the conductive part 20 retains the electrolyte like a tank, and enables the transfer of substances such as ions and fuel between the anode electrode 11 and the cathode electrode 12 and the skin.

[0032] The adhesive layer 30 is a member for attaching the transdermal electroconductive patch 1 to the skin of a certain part of the subject. The adhesive layer 30 can be composed of, for example, an insulating double-sided adhesive tape. For example, an acrylic adhesive or a silicone adhesive can be used as the adhesive layer 30. The adhesive strength of the adhesive layer 30 is preferably 1 N / cm or more, 2 N / cm or more, and preferably 20 N / cm or less, 12 N / cm or less, 6 N / cm or less, or 3 N / cm or less. If the adhesive strength is too weak, the patch may peel off unintentionally while it is attached. On the other hand, if the adhesive strength is too strong, the patch may be attached for a long period of time and may cause strong irritation to the skin when peeled off from the skin. The adhesive layer 30 has two openings 31 and 32, and the anode electrode 11 is housed in one opening 31, and the cathode electrode 12 is housed in the other opening 32. The lead 13 between the anode electrode 11 and the cathode electrode 12 is attached on the part 33 between the openings 31 and 32. This fixes the position of the electrode body 10 relative to the adhesive layer 30. In addition, in the adhesive layer 30, the anode electrode 11 housed in the opening 31 comes into contact with the conductive portion 20A, and the cathode electrode 12 housed in the opening 32 comes into contact with the conductive portion 20B. At this time, the outer frame portions of the conductive portions 20A and 20B are also fixed to the adhesive layer 30. With this configuration, ionic insulation is achieved between the conductive portion 20A and the conductive portion 20B. The adhesive layer 30 has a thickness of, for example, about 0.1 mm to 0.5 mm. By using a double-sided adhesive tape preferably having insulating properties as the adhesive layer 30, it is possible to achieve both the fixing of the positions of the electrode body 10 and the conductive portions 20A and 20B relative to the adhesive layer 30 and the ionic insulation between the conductive portion 20A and the conductive portion 20B, while miniaturizing the transdermal electropatch 1. In particular, the thinner thickness makes it easier to attach the patch to joints and cutaneous areas.

[0033] The separator 40, together with the adhesive layer 30, is a member for achieving ionic insulation between the conductive portion 20A and the conductive portion 20B, and can be formed, for example, from a release paper whose surface is coated with silicone or the like on a film or paper made of polyester, polyethylene terephthalate, or the like. The separator 40 has two openings 41, 42, and the conductive portion 20A is housed in one opening 41, and the conductive portion 20B is housed in the other opening 42. The separator 40 has a thickness of, for example, about 0.05 mm to 0.1 mm.

[0034] The surface film 50 is a member that covers and protects the electrode body 10 and the conductive part 20, and can be formed, for example, from a polyvinyl chloride film. When oxygen is used as a catalyst, a window part 51 is formed in the surface film 50 at a position corresponding to the cathode electrode 12 in order to supply an enzyme to the cathode electrode 12. To prevent the cathode electrode 12 from being exposed, the window part 51 may be made of an oxygen-permeable material such as cotton to protect the cathode electrode 12.

[0035] The transdermal electropatch 1 having such a configuration can be configured as a small, thin electropatch, and can be easily attached to a predetermined part of a subject for a long period of time. When the transdermal electropatch 1 is attached to a predetermined part of a subject after it has absorbed water, the anode electrode 11 and the cathode electrode 12 come into contact with the living body via the conductive parts 20A, 20B, and an electrical circuit can be formed that passes a weak current to the predetermined part (including adjacent areas). In the transdermal electropatch 1, the weak current that this electrical circuit passes to the living body is a current density of 10 μA / cm when the resistance is 5 kΩ. 2 The DC current is configured to be equal to or greater than this.

[0036] Here, the electrical resistance of a living body to which the transdermal electric patch 1 is applied will be described. The electrical resistance of a living body can be divided into the resistance of the skin and the resistance inside the human body. The resistance of the skin changes depending on the wetness of the contact surface, etc. (see Chapter 4 of the Electrical Equipment Work Safety and Health Handbook, Japan Marine Electrical Equipment Association). When the skin is dry and hardened, the skin resistance is about 10 kΩ, but when the skin is sweating, this drops to one-twelfth of that. Furthermore, since the skin resistance when sweating is about 1 kΩ, the transdermal electric patch 1 according to this embodiment has a current of 500 μA / cm when connected to a resistance of 1 kΩ. 2 It is desirable to have a configuration in which a direct current of less than 1000 mA flows, thereby reducing the sensation of stimulation felt by the subject.

[0037] FIG. 3 shows the current density (μA / cm ) of the electric current flowing through the electric circuit formed by the transdermal electropatch 1. 2 ) versus elapsed time (min). This current density is the current density when the electric circuit of the transdermal electrophoretic patch 1 is connected to a resistance of 10 kΩ. Here, the electric circuit of the transdermal electrophoretic patch 1 is formed including the anode electrode 11, the cathode electrode 12, and the conductive parts 20A and 20B. The electric circuit of the transdermal electrophoretic patch 1 of this embodiment is formed including the lead 13. In this specification, "current density" means the current density in the conductive part 20. Specifically, the current density means the value obtained by dividing the current flowing in the electric circuit formed by the transdermal electrophoretic patch 1 by the area of ​​the conductive part 20. Here, the area of ​​the conductive part 20 is the area of ​​the surface of the conductive part 20 located on the living body side. The current flowing in the electric circuit passes through the surface of the conductive part 20 in the direction intersecting the surface of the conductive part 20. In the transdermal electrophoretic patch 1, the current density is slightly high immediately after the start, but it settles down to the above-mentioned weak current range over time. More specifically, the transdermal electropatch 1 has a current density of 5 μA / cm when an electric circuit is connected to a resistance of 10 kΩ. 2 More than 100μA / cm 2 Preferably, the transdermal electropatch 1 is configured so that a weak current flowing through a predetermined site of a subject is 10 μA / cm2 or less after a predetermined time (for example, at least 10 minutes) has elapsed since the electric circuit was brought into contact with the predetermined site of the subject. 2More than 175μA / cm 2 More specifically, the transdermal electropatch 1 is configured so that the current density of the weak current flowing at the time when the electric circuit is connected to a resistance of 5 kΩ at the latest 10 minutes is 10 μA / cm 2 More than 500μA / cm 2 It is preferable that the transdermal electro-patch 1 is configured so that the current density of the weak current flowing at the time when the electric circuit is connected to a resistance of 5 kΩ at the latest is less than 10 μA / cm. 2 More than 175μA / cm 2 More preferably, the transdermal electropatch 1 is configured so that the current density of the weak current flowing 5 hours or more after the electric circuit is connected to a resistance of 5 kΩ is 10 μA / cm 2 More than 175μA / cm 2 It is preferable that the patch is configured to maintain the following: That is, the transdermal electroconductive patch 1 of the present embodiment can be attached to a predetermined part of a subject for a long period of time, and a weak current within a predetermined range can be continuously provided.

[0038] FIG. 4 shows an example of the current density of the transdermal electrophoretic patch 1. This is a graph of the current density of one sample of the transdermal electrophoretic patch 1 that was actually fabricated. When this transdermal electrophoretic patch was connected to a resistance of 5 kΩ, the current density of the weak current was 10 μA / cm after 10 minutes (600 seconds) had elapsed. 2 ~30μA / cm 2 Even after more than an hour had passed, the weak current density was within 10 μA / cm 2 ~30μA / cm 2 The DC current flowing through the electric circuit of the transdermal electrophoretic patch 1 can be controlled to the above-mentioned range by changing and adjusting the type and amount of the catalyst and electron transfer mediator used in the transdermal electrophoretic patch 1. However, the transdermal electrophoretic patch 1 is configured so that the current density when this electric circuit is connected to a resistance of 5 kΩ is 35 μA / cm. 2 or more, and when connected to a resistance of 5 kΩ, the current density is 60 μA / cm 2The current density may be measured by the method described in Example 1 below.

[0039] The amount of energy generated in the transdermal electrostatic patch 1 is, for example, 5 mJ or more when the transdermal electrostatic patch 1 is connected to a resistance of 10 kΩ for 1 hour. The amount of energy generated in the transdermal electrostatic patch 1 is, for example, 50 mJ or more when the transdermal electrostatic patch 1 is connected to a resistance of 10 kΩ for 10 hours. The amount of energy generated in the transdermal electrostatic patch 1 when connected to a resistance of 10 kΩ may be 3600 mJ or less, or may be 5000 mJ or less.

[0040] The time for which a direct current is passed through the electric circuit of the transdermal electrostatic patch 1, i.e., the electrostatic time, when electrostatic application is continuous, is, for example, 72 hours or less, 60 hours or less, 48 ​​hours or less, 36 hours or less, 24 hours or less, 1 hour or more, 2 hours or more, 3 hours or more, 4 hours or more, 6 hours or more, 8 hours or more, or 12 hours or more. The electrostatic time is, for example, 1 to 72 hours, 2 to 48 hours, or 3 to 24 hours. EXAMPLES

[0041] Here, the effects of using the transdermal electropatch 1, which can supply the DC current in the above-mentioned range to a specific part of the subject, on a subject will be described using several experimental examples with reference to Figures 6 to 10. Experimental examples 1 to 4 were the following (1) to (4). (1) Evaluate delayed onset muscle pain using transdermal electrochemical patch 1 (see Figure 6). (2) Results of evaluation of exercise performance using transdermal electrochemical patch 1 (see Figure 7). (3) Results of evaluation of the relief of stiff shoulders using transdermal electrochemical patch 1 (see Figure 8). (4) Results of evaluation of the relief of temporomandibular joint disorders using the transdermal electroconductive patch 1 (see Figures 9 and 10).

[0042] First, a large number of transdermal energizing patches 1 (first example) were produced for use in Experimental Examples (1) to (4). In producing the first example of the transdermal energizing patch 1, the following materials were prepared.

[0043] Electrode body 10: An electrode body 10 having the configuration shown in FIG. 1 was fabricated (prepared) using carbon fiber (manufactured by Toho Tenax) carrying multi-walled carbon nanotubes (manufactured by Baytube) as a material. The carbon nanotubes may be manufactured by Meijo Nano Carbon, and are not particularly limited. The carbon fiber may be manufactured by Toray, and are not particularly limited. The thickness of the electrode body 10 was 0.3 mm. The areas of the anode electrode 11 and the cathode electrode 12 were each 0.8 cm2. 2 The anode electrode 11 was supported with 4-isopropylaminodiphenylamine and glucose dehydrogenase as catalysts. The cathode electrode 12 was made of carbon fiber supporting multi-walled carbon nanotubes and polytetrafluoroethylene. Iron phthalocyanine (manufactured by Tokyo Chemical Industry Co., Ltd.) was supported as a catalyst. The lead 13 was made of carbon fiber. The anode electrode 11 and the cathode electrode 12 were joined to this lead 13 by thermal adhesion.

[0044] Conductive part 20: 300 μL of 50 mM McIlvaine buffer solution (pH 5) and 200 mM glucose solution were added to a polyurethane sponge (Sofras (product name), manufactured by AION Co., Ltd.), and the sponge was dried to produce (prepare) the conductive part 20. The thickness of the conductive part 20 was 1 mm, and conductive parts 20A and 20B were arranged so as to correspond to and contact the anode electrode 11 and the cathode electrode 12, respectively. The area of ​​each of the conductive parts 20A and 20B was approximately 1.7 cm2. 2 It was.

[0045] Adhesive layer 30: A medical double-sided adhesive tape (manufactured by 3M Japan) was used as the double-sided tape for skin to prepare the adhesive layer 30. The thickness of the adhesive layer 30 was 0.16 mm.

[0046] Separator 40: The separator 40 was made of polyester and had the structure shown in Fig. 1. However, the separator 40 may also be made of one-sided polyethylene-coated paper, polypropylene, or the like.

[0047] Surface film 50: A polyvinyl chloride film was used as the material to produce the separator 40 having the structure shown in FIG.

[0048] After preparing the above-mentioned materials, the electrode body 10, the conductive parts 20 (20A, 20B), the adhesive layer 30, the separator 40 and the surface film 50 were assembled in the order and arrangement shown in FIG. 1 to produce a large number of first examples of the transdermal electroconductive patch 1. The current density of the electric circuit of the patch according to the first example was measured using an ALS electrochemical analyzer 814D (manufactured by BAS), and the results were as shown in Table 1 below. A specific method for measuring the current density will be described with reference to FIG. 5. FIG. 5 is a diagram that illustrates a method for measuring the current density. As shown in FIG. 5, the electric circuit formed by the anode electrode 11, the cathode electrode 12, the conductive parts 20A, 20B, and the lead 13 was connected to the resistors shown in Table 1, and the voltage value of the electric circuit was measured using the above analyzer (voltmeter). Then, the current value obtained from the voltage value and resistance value obtained by the measurement was calculated based on the area (approximately 1.7 cm2) of the conductive parts 20 (20A, 20B, respectively). 2 ) to measure the current density. In Examples 2 and 3 described below, the current density was measured in a similar manner. The "current density" in Table 1 is the value approximately 10 minutes after the addition of the solution containing the substrate, and the value slightly decreased after 60 minutes had passed. The current density 10 hours after the addition of the solution containing the substrate was approximately 7 μA / cm when the resistance was 10 kΩ. 2 As shown in Fig. 4, in the case of the transdermal current-carrying patch 1, the current density gradually decreases after a certain amount of time has passed. Therefore, even after 15 hours or 20 hours, the current density was about 7 µA / cm2, which was the current density after 10 hours. 2 It is believed to be a value slightly smaller than that.

[0049] [Table 1]

[0050] In the first embodiment of the transdermal electrophoretic patch 1, the current density of the weak current that flows when the electrical circuit of the patch is connected to a resistance of 10 kΩ is 5 μA / cm at the latest 10 minutes after water is added to the transdermal electrophoretic patch. 2 ~30μA / cm 2 More specifically, in the first embodiment of the transdermal electrophoretic patch 1, the current density of the weak current flowing when the electrical circuit of the patch is connected to a resistance of 10 kΩ is within the range of 5 μA / cm at the latest 10 minutes after water is added to the transdermal electrophoretic patch. 2 ~25μA / cm 2 In other words, even after more than an hour had passed, the weak current flowing through the subject's designated area was within 5 μA / cm 2 The patch was constructed to maintain the above value. The open circuit voltage of the transdermal current patch was about 300 mV. As shown in Table 1, the patch of the first embodiment had a current density of 23 μA / cm when connected to 5 kΩ. 2 , current density at 1kΩ connection is 63μA / cm 2 That is, the current density of the first embodiment of the transdermal current-carrying patch 1 used in the test was 500 μA / cm 2 It was confirmed that the level was below this level and there was no risk of skin irritation.

[0051] In addition, a second embodiment of the transdermal electroconductive patch 1 was produced. To produce the patch according to the second embodiment, the following materials were first prepared. For the anode electrode 11, 1,4-naphthoquinone (manufactured by Tokyo Chemical Industry Co., Ltd.) was used instead of 4-isopropylaminodiphenylamine used in the first embodiment. For the cathode electrode 12, a platinum mesh (manufactured by BAS) was used, and for the lead 13, a stainless steel wire was used. The anode electrode 11 and the cathode electrode 12 were fixed to this lead 13 with instant adhesive. The rest of the assembly was performed in the same manner as in the first embodiment. Power generation was started by adding 100 mM potassium phosphate buffer (pH 7) containing 200 mM glucose to the sponge of the conductive part 20. The current density by the electric circuit of the patch according to the second embodiment was as shown in Table 2 below. The "current density" in Table 2 is the value about 10 minutes after the solution containing the substrate was added, and the value slightly decreased after 60 minutes.

[0052] [Table 2]

[0053] In the second embodiment of the transdermal electroconductive patch 1, similarly to the first embodiment, the current density of the weak current flowing when the electrical circuit of the patch is connected to a resistance of 10 kΩ is 10 μA / cm at the latest 10 minutes after the substrate is added. 2 ~45μA / cm 2 More specifically, in the second embodiment of the transdermal electroconductive patch 1, similarly to the first embodiment, the current density of the weak current flowing when the electrical circuit of the patch is connected to a resistance of 10 kΩ is within the range of 10 μA / cm at the latest 10 minutes after the addition of the substrate. 2 ~30μA / cm 2 In other words, even after more than an hour had passed, the weak current flowing through the subject's designated area was within 10 μA / cm 2 The patch in the second embodiment was designed to maintain a current density of 34 μA / cm when connected to 5 kΩ. 2 , current density at 1kΩ connection is 91μA / cm 2That is, the current density of the second embodiment of the transdermal current-carrying patch 1 used in the test was 500 μA / cm 2 It was confirmed that the level was below this level and there was no risk of skin irritation.

[0054] In addition, a third embodiment of the transdermal current patch 1 was produced. To produce the patch according to the third embodiment, the following materials were first prepared. Both the anode electrode 11 and the cathode electrode 12 were made of carbon fiber carrying multi-walled carbon nanotubes. This carbon fiber was electrically connected to an alkaline button battery (1.5V, LR44, manufactured by Panasonic). The anode electrode 11 and the cathode electrode 12 were connected with a stainless steel wire (corresponding to the lead 13). The rest of the assembly was performed in the same manner as in the first embodiment of the transdermal current patch 1. Electricity generation was started by adding 100 mM potassium phosphate buffer (pH 7) to the sponge of the conductive part 20. The current density by the electric circuit of the patch according to the third embodiment was as shown in Table 3 below. The "current density" in Table 3 is the value about 10 minutes after the electric circuit was connected, and the value slightly decreased after 60 minutes.

[0055] [Table 3]

[0056] In the third embodiment of the transdermal electroconductive patch 1, similarly to the first embodiment, the current density of the weak current flowing when the electrical circuit of the patch is connected to a resistance of 10 kΩ is 50 μA / cm at the latest 10 minutes after the addition of the substrate. 2 ~100μA / cm 2 More specifically, in the third embodiment of the transdermal electroconductive patch 1, similarly to the first embodiment, the current density of the weak current flowing when the electrical circuit of the patch is connected to a resistance of 10 kΩ is within the range of 50 μA / cm at the latest 10 minutes after the addition of the substrate. 2 ~70μA / cm 2 In other words, even after more than an hour had passed, the weak current flowing through the subject's designated area was within the range of 50 μA / cm 2The patch in the third embodiment was designed to maintain a current density of 87 μA / cm when connected to 5 kΩ. 2 , current density at 1kΩ connection is 242μA / cm 2 That is, the current density of the third embodiment of the transdermal electro-patch 1 used in the test was 500 μA / cm 2 It was confirmed that the level was below this level and there was no risk of skin irritation.

[0057] The amount of energy generated in the transdermal current-carrying patch according to the first to third examples will be described. The amount of energy generated in the transdermal current-carrying patch according to the first example was calculated when the transdermal current-carrying patch was connected to a resistance of 10 kΩ, and the amount of energy was 8 mJ when connected for 1 hour, and 60 mJ when connected for 10 hours. The amount of energy generated in the transdermal current-carrying patch according to the second example was calculated when the transdermal current-carrying patch was connected to a resistance of 10 kΩ, and the amount of energy was 30 mJ when connected for 1 hour. The amount of energy generated in the transdermal current-carrying patch according to the second example when connected for 10 hours is estimated to be 225 mJ from the calculation result of the transdermal current-carrying patch according to the first example. The amount of energy generated in the transdermal current-carrying patch according to the third example when connected to a resistance of 10 kΩ was calculated, and the amount of energy was 480 mJ when connected for 1 hour. The amount of energy when the transdermal electrostatic patch of the third embodiment is connected for 10 hours is estimated to be 3600 mJ based on the calculation results for the transdermal electrostatic patch of the first embodiment.

[0058] [Experimental Example 1] In Experimental Example 1, the delayed muscle pain was evaluated using the transdermal electroconductive patch 1 (first embodiment). In addition, a negative control product that does not conduct electricity and does not contain glucose dehydrogenase or iron phthalocyanine, which are involved in the transfer of electrons, was also used in the test. In this test, the subjects held a dumbbell (male: 7.5 kg, female: 5 kg) with their elbows on a pedestal, and repeated the exercise of lifting the dumbbell and returning it to the initial position in one round trip of 4 seconds twice in a row until they could no longer maintain the pace. There were 13 subjects (6 males and 7 females). After the dumbbell exercise was completed, the transdermal electroconductive patch 1 or the negative control product prepared above was attached to the long muscle of the biceps brachii of the subjects so that a current would flow along the muscle fibers, and the current density was 5 μA / cm 2 ~30μA / cm 2 A weak current in the range of was continuously applied to a predetermined part of the subject. This test was conducted without the subject knowing whether the transdermal electroconductive patch 1 or the negative control product was applied. This weak current was applied for 12 hours between the end of the exercise and one day, and for another 12 hours between the end of the one day and the end of the two days. Each of the 12 hours included the time spent sleeping. After the above-mentioned dumbbell exercise was completed, the subject again performed a similar dumbbell test after an interval of at least two weeks. The subject who applied the transdermal electroconductive patch 1 in the first dumbbell test applied the negative control product and performed the test in the same way. On the other hand, the subject who applied the negative control product in the first dumbbell test applied the transdermal electroconductive patch 1 and performed the test in the same way.

[0059] Two days after completing the dumbbell exercise, each subject was asked to evaluate their state of delayed onset muscle soreness (a type of muscle pain). The evaluation criteria were the Japanese version of the Talag scale, as follows (24 levels in 0.25 increments between 0 and 6). (See Physical Therapy Science, 22(1), 125-131(2007)) 0: No pain. 1: Discomfort 2: Slightly obvious pain 3: A more pronounced pain 4: Definite pain 5: Severe pain 6: Unbearable pain.

[0060] Figure 6 shows the results of the pain intensity after two days. As shown in Figure 6, it was confirmed that the pain intensity when the transdermal electro-patch 1 (first embodiment, with current) was used and an electro-patch treatment was performed twice for 12 hours after dumbbell exercise was lower than the pain intensity when the negative control product (without current) was applied and no electro-patch treatment was performed. The p-value was calculated using the Wilcoxon signed rank test, and it was confirmed that p<0.05. Thus, according to Experimental Example 1, which used the patch of the first embodiment, the pain intensity was lower when the current density was 5 μA / cm 2 ~30μA / cm 2 It was confirmed that pain in a specific area can be alleviated by passing a weak current in the range of 1000 to the specific area. Muscle pain is not considered to be a superficial pain, which is pain on the surface of the skin, but a deep pain originating from the muscle, which is an internal tissue. For this reason, it cannot be assumed that muscle pain can be alleviated by passing a small current on the surface of the skin for a short period of time. It is believed that the pain of muscle pain, which is a deep pain, can be alleviated by continuously passing a weak current using the transdermal electropatch 1.

[0061] [Experimental Example 2] In Experimental Example 2, exercise performance using the transdermal electroconductive patch 1 (first embodiment) was evaluated. In this test, dumbbell exercise similar to that in Experimental Example 1 was performed, and the number of times the dumbbell was pressed for the first time was counted. The number of subjects was 13, the same as in Experimental Example 1. After completing this dumbbell exercise, the above-mentioned transdermal electroconductive patch 1 (first embodiment) or negative control product was attached to the biceps for 12 hours (12 hours x 2 times) on the first and second days, as in Experimental Example 1. Experimental Example 2 was performed without the subjects knowing whether they had been applied with the transdermal electroconductive patch 1 or the negative control product. When the transdermal electroconductive patch 1 was applied, the current density was 5 μA / cm 2 ~30μA / cm 2 A weak electric current in the range of 5μA / cm was continuously applied to the subjects' designated areas. On the other hand, when the negative control product was applied, the current density was 5μA / cm 2 ~30μA / cm 2This means that the process of passing a weak current in this range was not performed.

[0062] Three days after the first dumbbell exercise, each subject was asked to perform the same dumbbell exercise as the first one, and continued until they could no longer raise their arms, and the number of times the dumbbell was used for the second time was counted. After that, the ratio of "number of times the dumbbell was used for the second time / number of times the dumbbell was used for the first time" was calculated as the exercise number ratio (%) for each subject. As in Example 1, after a gap of more than two weeks without applying load to the biceps, the same test was performed again. At this time, the negative control product was applied to the subjects who had applied the transdermal electric patch 1 in the previous dumbbell test, and the test was performed in the same manner. On the other hand, the transdermal electric patch 1 (first embodiment) was applied to the subjects who had applied the negative control product in the previous dumbbell test, and the test was performed in the same manner. FIG. 7 shows the exercise number ratio calculated in this way, divided into the first group (with electric current treatment) and the second group (without electric current treatment). As shown in Figure 7, it was confirmed that the first group, which used the transdermal electroconductive patch 1 (first embodiment) and received electroconductive treatment twice for 12 hours after dumbbell exercise, improved the number of times they could lift the dumbbell. The p-value was calculated using the Wilcoxon signed rank test, and it was confirmed that p<0.01. Thus, according to Experimental Example 2, which used the patch of the first embodiment, 2 ~30μA / cm 2 It was confirmed that the continuous application of a weak current in the range of 1000 to 10 ...

[0063] Next, a test similar to that of Experimental Example 2 was carried out using the patch of the second embodiment instead of the patch of the first embodiment. However, the application time was 1 hour on the first day and 4 hours on the second day. The subject was a man in his 40s (1 person). As a result, the percentage of number of movements (%) when the negative control product was applied was 46%. On the other hand, the percentage of number of movements (%) when the patch of the second embodiment was applied was 152%. Therefore, when the current density was 10 μA / cm 2~45μA / cm 2 It was confirmed that athletic ability can be improved by continuously applying a weak electric current in the range of

[0064] Next, a test similar to that of Experimental Example 2 was conducted using the patch of the third embodiment instead of the patch of the first embodiment. However, the application time was 4 hours on the first day and 4 hours on the second day. The subject was a man in his 30s (1 person). As a result, the percentage of number of movements when the negative control product was applied was 88%. On the other hand, the percentage of number of movements when the patch of the third embodiment was applied was 108%. Therefore, when the current density was 50 μA / cm 2 ~100μA / cm 2 It was confirmed that the exercise ability was improved by continuously applying a weak current in the range of 100%. In addition, when the pain was evaluated after two days, the pain when the negative control product was applied was rated as "3", while the pain when the patch of the third embodiment was applied was rated as "0". In other words, it was confirmed that the above-mentioned current has a pain-reducing effect.

[0065] [Experimental Example 3] In Experimental Example 3, the relief of stiff shoulders was evaluated using the transdermal electroconductive patch 1. In this test, the above-mentioned transdermal electroconductive patch 1 (first embodiment) was applied to the painful area of ​​the shoulder of a first group of subjects (15 subjects) for 12 hours, and the current density was 5 μA / cm 2 ~30μA / cm 2A weak electric current in the range of 100 to 200 mm was continuously applied to a predetermined part of the subject. Then, the pain relief after a certain period of time (12 hours, 24 hours, 36 hours, and 60 hours) was investigated. On the other hand, a negative control product was applied to the painful part of the shoulder of the second group of subjects (15 subjects), and the pain relief due to natural healing over time was investigated. The subjects were not aware of which patch was applied. The evaluation criteria were the same as in Experimental Example 1, and the extent to which the pain changed from the pain before application was recorded. Figure 8 shows the test results. As shown in Figure 8, it was confirmed that the pain was improved more in the first group, which had undergone 12 hours of electric current treatment on the painful part of the shoulder using the transdermal electric patch 1 (first embodiment), than in the second group, which had not undergone electric current treatment.

[0066] As a comparative example, a general magnetic therapy device was used and the change in pain was recorded in the same manner. 12 subjects were included in the study. The general magnetic therapy device was attached for three consecutive days. As a result, the change in pain was -1 24 hours after the start of attachment of the magnetic therapy device, -0.9 36 hours after, and -0.79 60 hours after, showing a tendency for improvement. However, the results showed that the transdermal electric patch (first embodiment) had a higher pain reduction effect. The results showed that the transdermal electric patch (first embodiment) had a shorter attachment time and a higher pain reduction effect than the comparative example.

[0067] [Experimental Example 4] In Experimental Example 4, the degree of relief from pain caused by temporomandibular joint disorder was evaluated using the transdermal electropatch 1 (first embodiment). In this test, one subject (woman in her 30s) who had been diagnosed with temporomandibular joint disorder was asked to apply the above-mentioned transdermal electropatch 1 to the painful area of ​​the temporomandibular joint while sleeping for four days so that a current would flow along the muscle fibers of the masseter muscle. 2 ~30μA / cm 2A weak electric current in the range of 0 to 100 was continuously applied to the subjects' designated areas. Then, every morning, the subjects were asked to evaluate the degree of improvement in pain using a visual analogue scale (VAS) with a range of intensity 0 (no pain) to 100 (most severe pain). The degree of improvement in pain was evaluated by tenderness, pain when opening the mouth, pain when chewing, and the degree of interference with daily life. Tenderness indicates muscle pain when 1 kg pressure is applied to the jaw, pain when opening the mouth indicates pain in the jaw when opening the mouth, and pain when chewing indicates pain in the jaw when chewing food. The degree of interference with daily life is a standard of the degree to which jaw pain interferes with daily life, and was evaluated with a range of 0 (no interference) to 100 (extreme interference).

[0068] Here, we will explain temporomandibular joint disorder. Temporomandibular joint disorder is said to be the third dental disease after tooth decay and periodontal disease. The number of patients with some kind of symptoms in the temporomandibular joint is estimated to be about 19 million in Japan. It is recommended that the first choice of treatment for temporomandibular joint disorder be a conservative, reversible, and evidence-based treatment (see Guidelines for the Treatment of Temporomandibular Joint Disorders 2020, Japan Temporomandibular Joint Society). The basic treatment for masticatory muscle pain disorder (type I), which is the most common type of temporomandibular joint disorder, is based on physical therapy. This includes not only patients who only have type I, but also those who also have temporomandibular joint pain disorder (type II), temporomandibular joint disc disorder (type III), and osteoarthritis of the temporomandibular joint (type IV). Specifically, there are self-massage of the affected area, hot compresses to warm the affected area, and pain relief therapy using electrical stimulation (transcutaneous electrical stimulation therapy). Transcutaneous electrical stimulation therapy is said to cause muscle contraction and relaxation by electrical stimulation, relieving hypertonia. However, there are cases where these physical therapies cannot adequately treat the condition. A systematic review has also shown that transcutaneous electrical stimulation therapy has not been shown to be sufficiently effective (T. List, S. Axelsson, Journal of Oral Rehabilitation (2010)). Therefore, there is a need for more effective treatment and physical therapy that can relieve pain.

[0069] Electrical therapy devices other than transcutaneous electrical stimulation therapy have only been applied to the lower part of the body below the neck, and their effectiveness in treating temporomandibular joint disorders was unclear. In particular, there have been no reported cases of weak direct current being applied to temporomandibular joint disorders, and it was unclear how much current was needed to treat them.

[0070] Figure 9 is a table showing the degree of improvement of the temporomandibular joint syndrome in Experimental Example 4. As shown in Figure 9, it was confirmed that the pain of the temporomandibular joint syndrome, which is difficult to cure, can be significantly improved by attaching the transdermal electroconductive patch 1 to the painful part of the jaw while sleeping for four consecutive days and continuously passing a weak current in the above-mentioned range. It was confirmed that the pain improved dramatically especially on the fifth day.

[0071] Another test was conducted on one subject (female, in her 60s) who was diagnosed with temporomandibular joint disorder in the same manner as above. This subject also had temporomandibular joint disorder of types I, II, III, and IV, and underwent self-massage and transcutaneous electrical stimulation therapy, which are normal physical therapy, but the pain could not be relieved. As in the above, the transdermal electric patch 1 (Example 1) was applied while sleeping. However, it was applied once a day for two weeks. As a result, as shown in FIG. 10, the pain relief was observed from the fifth day of use for tenderness and from the first day of use for pain when opening the mouth. The pain relief continued even after two weeks of use, and a higher effect than existing treatment methods was observed. In addition, the transdermal electric patch 1 used in this test was 2 cm wide and 5 cm long. Depending on the subject, pain may occur over a wider area, and the size of the patch is 1 cm wide or more, preferably 3 cm wide or more, and more preferably 4 cm or more. The length of the patch is 1 cm or more, preferably 3 cm or more, and more preferably 4 cm or more, 5 cm or more, or 6 cm or more. When the area of ​​the electric current patch was considered, it was found that it would take 50cm to apply to the painful area. 2 Less than 40cm, preferably 40cm 2 Less than 30cm, more preferably 2 It was found that it is desirable to have a distance of 1 cm or less. 2 More than 5cm, preferably 5cm 2The above patches are preferable, and multiple small patches can be applied to adjust the area to an appropriate level.

[0072] Types I, II, III, and IV of temporomandibular joint disorders are not considered to be superficial pain, but rather deep pain originating from internal tissues such as muscles and bones. For this reason, it is not expected that the pain of temporomandibular joint disorders will be alleviated by simply passing a small current through the skin surface for a short period of time. In Experimental Example 4, it is considered that the deep pain of temporomandibular joint disorders was alleviated by continuously passing a weak current through the transdermal electropatch 1.

[0073] In the above-mentioned Experimental Examples 1 to 4 (first embodiment), the weak current (current density) supplied to the subject was 5 μA / cm 2 ~30μA / cm 2 On the other hand, the slightly higher weak current (10-45μA / cm 2 ) (Example 2) was used, the effect of recovering damaged cells was considered to be higher. Therefore, in the treatment of temporomandibular joint disorders, the patch of Example 2 was used with a current of 10 to 45 A / cm 2 By passing a current with a current density of 10 kΩ (when a 10 kΩ resistor is connected), it is expected that the same or even better improvement effects will be obtained.

[0074] Since the weak current passed through the living body using the transdermal electrostatic patch 1 is a direct current, it is expected that the cell migration speed will be faster than when an alternating current is used, and as a result, the cell repair speed will be faster.

[0075] In addition, the current density of the patch in the example of JP 2016-144634 A was verified. Figure 11 shows the test method used for the verification. The verification results were as follows. The metal batteries in the prior art were of the following three types. 1) Titanium and silver 2) Titanium and copper 3) Titanium and zinc In this verification method, 10 mL of physiological saline (PBS) was soaked into the nonwoven fabric, and as shown in Figure 11, two metal electrodes were placed on the nonwoven fabric and electrically connected to form an electrical circuit. This simulated an actual application (attachment to a living body). The current value of each of these electrical circuits was measured. The measurement results are shown in Table 4 below. That is, the current density of the current flowing through the electric patch of the prior art was 0.5 μA / cm 2 It was smaller than that.

[0076] [Table 4]

[0077] In a verification method in which titanium and zinc electrodes were immersed in physiological saline and electrically connected while stirring, when connected to a resistance of 1000 kΩ, the current was 700 mV and 0.7 μA / cm 2 Therefore, when a current of 650 μA is applied as described in the example of JP 2016-144634 A, the cross-sectional area through which the current passes is 100 cm. 2 It was confirmed that an electrode area of ​​more than 100 mm was required, resulting in a very large structure.

[0078] As described above, the transdermal electropatch 1 according to this embodiment is configured to pass a direct current to a part of a subject by contacting the anode electrode 11 and the cathode electrode 12 with the part via the conductive parts 20A and 20B. The transdermal electropatch 1 is configured such that the current density of the direct current flowing 10 minutes after the electric circuit formed by the anode electrode 11, the cathode electrode 12, and the conductive parts 20A and 20B is connected to a resistance of 5 kΩ is 10 μA / cm 2 More than 500μA / cm 2 According to the findings of the present inventors, as described above, the weak current flowing through the living body is set to an extremely small current (0.2 μmA / cm 2 (below) is slightly higher than 10 μA / cm 2It was found that by using a direct current having a current density of 500 μA / cm or more (when connected to a 5 kΩ resistor), the improving effect on the target area can be significantly improved. Therefore, this transdermal electropatch 1 can improve the improving effect on the target area. In addition, when the current density of the current passed through the living body is 500 μA / cm 2 If the current density exceeds this level, the user may feel irritation. For this reason, the current density of the transdermal electropatch 1 is set to 500 μA / cm 2 The electrical circuit is formed so that the current density is less than 175 μA / cm (when a 5 kΩ resistor is connected). This allows the transdermal electropatch 1 to be used for a long period of time (by attaching it to a specific part of the user's body), and the improvement effect on the target part can be further improved. Note that when the electrical circuit is connected to a 5 kΩ resistor and 10 minutes have passed, the current density of the direct current flowing through the patch is 175 μA / cm 2 The electric circuit may be configured so that the current density of the direct current flowing 10 minutes after the electric circuit is connected to a resistance of 5 kΩ is 10 μA / cm or less. 2 More than 30μA / cm 2 The current density of the direct current flowing one hour after connecting to a 5 kΩ resistor is 10 μA / cm 2 More than 30μA / cm 2 It may be configured as follows:

[0079] In addition, in the transdermal electropatch 1 according to this embodiment, the current density of the direct current flowing 5 hours after the electric circuit is connected to a resistance of 5 kΩ is 10 μA / cm 2 More than 500μA / cm 2 This makes it possible to continuously improve the improving effect on the target area by attaching the transdermal electrolyzing patch 1 to the target area for a long period of time.

[0080] In addition, in the transdermal electropatch 1 according to this embodiment, the current density of the direct current flowing 10 minutes after the electric circuit is connected to a resistance of 10 kΩ is 5 μA / cm 2 More than 30μA / cm 2The present invention is configured as follows. This makes it possible to more reliably improve the improving effect on the target area.

[0081] In addition, in the transdermal electropatch 1 according to this embodiment, the current density of the direct current flowing 10 minutes after the electric circuit is connected to a resistance of 10 kΩ is 10 μA / cm 2 More than 45μA / cm 2 The present invention is configured as follows. This makes it possible to more reliably improve the improving effect on the target area.

[0082] Moreover, in the percutaneous electroconductive patch 1 according to this embodiment, the conductive part 20 is composed of conductive parts 20A, 20B corresponding to the anode electrode 11 and the cathode electrode 12, respectively, and each of the conductive parts 20A, 20B has a sponge and a buffering agent made of an electrolyte, and the buffering agent is contained in the sponge. This makes it possible to specifically realize the configuration of the conductive parts 20A, 20B for forming an electric circuit.

[0083] Moreover, in the transdermal electropatch 1 according to this embodiment, at least one of the anode electrode 11 and the cathode electrode 12 carries an enzyme that catalyzes an oxidation-reduction reaction. Furthermore, the electrode carrying the enzyme (for example, the anode electrode 11) has an electron transfer mediator 15 fixed thereto, the electron transfer mediator 15 being a mediator of a quinone compound or a phenylenediamine compound. With this configuration, it is possible to more reliably achieve the direct current applied to the living body being within any of the above-mentioned ranges, and more reliably improve the improving effect on the target site.

[0084] The method for operating the transdermal electrophoretic patch 1 according to this embodiment includes a step of passing a direct current through an electric circuit of the transdermal electrophoretic patch 1. The method for operating the transdermal electrophoretic patch 1 includes a step of supplying water to the sponge of the transdermal electrophoretic patch 1. This method for operating the transdermal electrophoretic patch 1 can improve the improving effect on the target area.

[0085] The transdermal electrostatic patch 1 according to the present embodiment has been described above, but the present invention is not limited to the above embodiment and various modifications can be applied. For example, the above embodiment illustrates the use of a biobattery, but the transdermal electrostatic patch may be a patch of other configurations. For example, the electrostatic patch may be configured to use a button battery as shown in the third embodiment described above, or a thin-film battery may be used instead of the button battery. However, in order to attach the transdermal electrostatic patch to a part of the subject for a long period of time, a small, thin transdermal electrostatic patch is preferable.

[0086] The transdermal current patch may include a diode and a means for supplying power by wireless communication. Examples of such means include those described in the following references. In such a transdermal current patch, the potential difference between the anode electrode and the cathode electrode, i.e., the voltage, can be a sine wave that fluctuates only in the voltage range of 0V or more, or a sine wave that fluctuates only in the voltage range of 0V or less, by combining the diode and the means. It should be noted that the voltage does not fluctuate across the positive voltage range and the negative voltage range. The current application time in such a transdermal current patch is, for example, the same as the current application time when a direct current is applied to the transdermal current patch. The frequency is, for example, 0.1 to 200 kHz, 1 to 100 kHz, or 5 to 80 kHz. Reference: Jiang, Y., Trotsyuk, AA, Niu, S. et al. Wireless, closed-loop,smart bandage with integrated sensors and stimulators for advanced wound careand accelerated healing. Nat Biotechnol 41, 652-662 (2023).https: / / doi.org / 10.1038 / s41587-022-01528-3

[0087] The transdermal electric patch may include a DC / pulse converter. In such a transdermal electric patch, a pulsed DC voltage is applied to cause a pulsed current (intermittent DC current) to flow. The pulsed current may be an intermittent pulse that does not flow when the voltage is 0V and flows when the voltage is a positive value. The pulsed current may be an intermittent pulse that does not flow when the voltage is 0V and flows when the voltage is a negative value. The pulsed DC voltage is a voltage that fluctuates only in a voltage range of 0V or more, or a voltage that fluctuates only in a voltage range of 0V or less. It should be noted that the pulsed DC voltage does not fluctuate across a positive voltage range and a negative voltage range. The frequency of the pulsed current is, for example, 0.1 to 200kHz, 1 to 100kHz, or 5 to 80kHz. The on / off ratio of the pulsed DC voltage is, for example, 1 / 10 to 20, 1 / 50 to 15, or 1 / 30 to 10. The energizing time for such a transdermal energizing patch is the same as the energizing time for when a direct current is passed through the transdermal energizing patch, for example.

[0088] The transdermal electrical patch may be used to relieve eye fatigue, alleviate trigeminal neuralgia, or improve the symptoms of sinusitis. [Explanation of symbols]

[0089] 1...transdermal electroconductive patch, 10...electrode body (multiple electrodes), 11...anode electrode (negative electrode), 12...cathode electrode (positive electrode), 13...lead (connection part), 14...enzyme, 15...electron transfer mediator, 20, 20A, 20B...conductive part (conductive layer, multiple conductive parts).

Claims

1. A positive electrode and a negative electrode, Conductive portions arranged to correspond to and be in contact with the positive electrode and the negative electrode, A transdermal electrical patch comprising: The transdermal electropatch is configured to pass a direct current through a living body by contacting the positive electrode and the negative electrode with the living body via the conductive portion, The transdermal electroconductive patch has a current density of 10 μA / cm when 10 minutes have elapsed since the electric circuit formed by the positive electrode, the negative electrode, and the conductive portion was connected to a resistance of 5 kΩ. ２ More than 500μA / cm ２ The transdermal current patch is configured so that the current density is less than the current density in the conductive portion.

2. The transdermal electroconductive patch has a direct current density of 10 μA / cm 5 hours after the electrical circuit is connected to a resistance of 5 kΩ. ２ More than 500μA / cm ２ is configured to be less than The transdermal electrical patch according to claim 1.

3. The transdermal electroconductive patch has a direct current density of 5 μA / cm 10 minutes after the electrical circuit is connected to a resistance of 10 kΩ. ２ 30 μA / cm or more ２ It is configured to: The transdermal electrical patch according to claim 1.

4. The transdermal electropatch has a current density of 10 μA / cm 10 minutes after the electrical circuit is connected to a resistance of 10 kΩ. ２ 45 μA / cm or more ２ It is configured to: The transdermal electrical patch according to claim 1.

5. The transdermal current patch had a current density of 175 μA / cm 10 minutes after the electrical circuit was connected to a resistance of 5 kΩ. ２ It is configured to: The transdermal electrical patch according to claim 1.

6. The transdermal electroconductive patch has a direct current density of 10 μA / cm 10 minutes after the electrical circuit is connected to a resistance of 5 kΩ. ２ 30 μA / cm or more ２ or less, and the current density of the direct current flowing one hour after connection to a 5 kΩ resistor is 10 μA / cm ２ 30 μA / cm or more ２ It is configured to: The transdermal electrical patch according to claim 1.

7. A connection part electrically connecting the positive electrode and the negative electrode is further provided, Each of the conductive parts has a sponge and a buffer agent made of an electrolyte, and the buffer agent is contained in the sponge. The transdermal electropatch according to any one of claims 1 to 6.

8. At least one of the positive electrode and the negative electrode supports an enzyme that catalyzes an oxidation-reduction reaction. The transdermal electropatch according to any one of claims 1 to 6.

9. An electron transfer mediator is immobilized on the electrode carrying the enzyme. The transdermal electrical patch according to claim 8.

10. The electron transfer mediator is a quinone compound or a phenylenediamine compound. The transdermal electrical patch according to claim 9.

11. A method for operating a transdermal current patch, comprising the step of passing the direct current through the electrical circuit of the transdermal current patch according to claim 1.

12. A method for operating a transdermal electrical current patch, comprising the step of supplying water to the sponge of the transdermal electrical current patch according to claim 7.

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