JP6377385B2 - Biological tissue sticking kit and biological tissue sticking patch - Google Patents

Description

  The present invention relates to a biological tissue affixing kit and a biological tissue affixing patch, and in particular, a biological tissue affixing kit and a biological tissue affixing that can pass a current through a biological tissue while realizing high safety and a low environmental load. Related to patches.

  In recent years, as a technique for beauty and medical care, a technique for flowing electricity to a living tissue is attracting attention. As an apparatus for realizing the above technique, for example, a skin patch sheet provided with a general dry battery and an electrode is known (see Patent Document 1).

JP 2010-202577 A

  However, the existing patch for attaching a biological tissue using a general dry battery includes an existing battery containing an electrolytic solution containing a metal electrode or the like, so that there is room for reducing the influence on the human body and increasing safety, and There was room for simplifying disposal and reducing environmental impact.

  Then, an object of this invention is to provide the biological tissue sticking kit and the biological tissue sticking patch which can flow an electric current through a biological tissue, implement | achieving high safety | security and a low environmental load.

The gist of the present invention is as follows.
The biological tissue sticking kit of the present invention is a biological tissue sticking kit for producing a patch for sticking a biological tissue that is used by being attached to a biological tissue, and includes an electrode carrying an enzyme that catalyzes a redox reaction. It includes a plurality of electrodes, a conductive member for electrically connecting the plurality of electrodes, and a conductive layer substantially free of water .

In the biological tissue sticking kit of the present invention, the conductive layer preferably contains the enzyme substrate.

  Furthermore, in the biological tissue sticking kit of the present invention, the plurality of electrodes and the conductive layer are preferably in contact with each other when the kit is used.

  Furthermore, in the biological tissue sticking kit of the present invention, it is preferable that the conductive layer further includes at least one selected from the group consisting of drugs, cosmetics, and preparations.

  Furthermore, in the biological tissue sticking kit of the present invention, it is preferable that the plurality of electrodes do not substantially contain water.

  Furthermore, the biological tissue sticking kit of the present invention preferably further includes an outer surface cover for sealing the plurality of electrodes, the conductive member, and the conductive layer.

The patch for sticking a living tissue of the present invention is a patch for sticking a living tissue that is used by sticking to a living tissue, and includes a plurality of electrodes including an electrode carrying an enzyme that catalyzes a redox reaction, and the plurality of electrodes And a conductive layer that substantially does not contain water .

Moreover, it is preferable that the patch for biological tissue sticking of this invention is provided in the state in which the said conductive layer contains the substrate of the said enzyme, and the said conductive layer contacted with respect to these electrodes.

  Furthermore, in the patch for attaching a biological tissue of the present invention, it is preferable that the conductive layer further includes at least one selected from the group consisting of drugs, cosmetics, and preparations.

  Furthermore, in the patch for attaching a biological tissue of the present invention, it is preferable that the plurality of electrodes do not substantially contain water.

  Furthermore, it is preferable that the patch for attaching a biological tissue of the present invention further includes an outer surface cover that seals the plurality of electrodes, the conductive member, and the conductive layer.

  According to the biological tissue sticking kit of the present invention and the biological tissue sticking patch of the present invention, a current can be passed through the biological tissue while realizing high safety and low environmental load.

It is a figure which shows the kit for biological tissue sticking of 1st embodiment of this invention in the state before affixing on a biological tissue, (a) shows the kit before an assembly with a perspective view, (b) Shows a sectional view of the assembled kit. It is a figure which shows the kit for biological tissue sticking of 1st embodiment of this invention in the state currently affixed on a biological tissue, (a) shows a kit with an external view, (b) is a kit. Is shown in a cross-sectional view. It is a figure which shows the kit for biological tissue sticking of 2nd embodiment of this invention in the state before affixing on a biological tissue, (a) shows the kit before an assembly with a perspective view, (b) Shows a sectional view of the assembled kit. It is a figure which shows the kit for biological tissue sticking of 3rd embodiment of this invention in the state before affixing on a biological tissue, (a) shows the kit before an assembly with a perspective view, (b) Shows a sectional view of the assembled kit. It is a figure which shows the kit for biological tissue sticking of 4th embodiment of this invention in the state before affixing on a biological tissue, (a) shows the kit before an assembly with a perspective view, (b) Shows the assembled kit in a sectional view, and (c) shows the assembled kit in a state where water is added to the conductive layer in a sectional view. It is a figure which shows the patch for biological tissue sticking of 1st embodiment of this invention in the state before affixing on a biological tissue, (a) shows a patch with a perspective view, (b) is a patch. Is shown in a cross-sectional view. It is a figure which shows the patch for biological tissue sticking of 1st embodiment of this invention in the state currently affixed on a biological tissue, (a) shows the external view of a patch, (b) is a patch. Is shown in a cross-sectional view. It is a figure which shows the patch for biological tissue sticking of 2nd embodiment of this invention in the state before affixing on a biological tissue, (a) shows a patch with a perspective view, (b) is a patch. Is shown in a cross-sectional view. It is a figure which shows the patch for biological tissue sticking of 3rd embodiment of this invention in the state before affixing on a biological tissue, (a) shows a patch with a perspective view, (b) is a patch. Is shown in a cross-sectional view. It is a figure which shows the patch for biological tissue sticking of 4th embodiment of this invention in the state before affixing on a biological tissue, (a) shows a patch with a perspective view, (b) is a patch. (C) shows a patch in a state where water is added to the conductive layer. It is a figure which shows the patch for biological tissue sticking of the Example of this invention, (a) decomposes | disassembles a patch and shows it by a perspective view, (b) shows the assembled patch by sectional drawing. It is a figure which shows the relationship (result of output performance evaluation) with a cell voltage, the current density, and the output density in the patch for biological tissue sticking according to this invention which used fructose dehydrogenase (FDH) for the cathode. It is a figure which shows the relationship (result of durability performance evaluation) with the index | exponent of the time and the output of a patch in the patch for biological tissue sticking of an example of this invention. It is a figure which shows the relationship between the days after drying, and the ratio of the enzyme activity after drying with respect to the enzyme activity before drying in the fructose dehydrogenase (FDH) dried on various conditions. It is a figure which shows the relationship between the days after drying, and the ratio of the enzyme activity after drying with respect to the enzyme activity before drying in the bilirubin oxidase (BOD) dried on various conditions. It is a figure which shows the relationship (result of output performance evaluation) of an electric potential and current density in the patch for biological tissue sticking according to this invention which used glucose dehydrogenase (GDH) for the cathode.

(Biological tissue affixing kit)
Hereinafter, with reference to drawings, embodiment of the kit for biological tissue sticking of this invention is illustrated in detail.
The kit for attaching a biological tissue of the present invention is a kit for causing an electric current to flow inside the biological tissue through the surface of the living body by electricity generated by an enzyme reaction. This kit can be used for producing a patch for attaching a biological tissue (described later) to be used by being attached to a biological tissue.

1 (a) and 1 (b) show a biological tissue affixing kit according to the first embodiment of the present invention in a state before being attached to a biological tissue for use. FIG. 1A is a perspective view of the kit before assembly, and FIG. 1B is a cross-sectional view of the kit after assembly.
2 (a) and 2 (b) show the biological tissue affixing kit according to the first embodiment of the present invention in a state where it is attached to a biological tissue and used. FIG. 2A shows an external view of the kit, and FIG. 2B shows a cross-sectional view of the kit.

  A biological tissue affixing kit 10 (hereinafter also referred to as “kit 10”) according to a first embodiment of the present invention includes two electrodes 2 including an anode (cathode) 2a and a cathode (anode) 2b, and two electrodes. 2 (2a, 2b) and a conductive member 4 for electrical connection. Here, the anode 2a carries an enzyme 3a that catalyzes a reduction reaction, and the cathode 2b carries an enzyme 3b that catalyzes an oxidation reaction.

  As shown in FIG. 1A, the kit 10 is further used to fix the electrode 2 (2a, 2b) and the conductive member 4, and separates the two holes 6h from the holes 6h. A flat frame 6 having a bridge portion 6b and a communication portion 6t communicating between the holes, two electrodes 2 (2a, 2b), a conductive member 4, and an outer surface cover 7 for sealing the frame 6. Including. “Sealing” means sealing at least in a state where the assembly of the kit 10 is attached to the living tissue 1 for use.

  In this kit 10, the electrodes 2a and 2b carrying the enzyme 3 (3a and 3b) are dried by freeze drying or the like.

Here, an example of how to use the kit 10 will be described.
First, before using the kit 10, the user assembles the two electrodes 2 (2a, 2b), the conductive member 4, the frame 6, and the outer cover 7 as shown in FIG. Is made. In the assembly 10a, the two electrodes 2 (2a, 2b) and the conductive member 4 are in contact with each other. Then, as shown in FIGS. 2A and 2B, the user attaches the assembly 10 a so that the electrode 2 comes into contact with the living tissue 1.

Moreover, the effect at the time of use of the kit 10 is described.
There is a case where the biological drainage is attached to the biological tissue 1 (for example, when the skin is sweated). In this case, the substance contained in the biological drainage is the enzyme 3 (3a, 3b). May be a substrate. Electrons generated by the oxidation reaction by the enzyme 3b at the cathode 2b are delivered to the anode 2a through the conductive member 4, and are used for the reduction reaction by the enzyme 3a at the anode 2a. At this time, since the electrode 2 (2a, 2b) is in contact with the skin, electricity flows through the skin portion between the anode 2a and the cathode 2b.

  The biological tissue affixing kit 10 of the first embodiment of the present invention generates electricity using a substance harmless to the human body such as an enzyme or its substrate, while the existing biological tissue affixing kit uses a metallic electrode or the like. Use an existing battery with an electrolyte containing it. Therefore, according to the kit 10, the possibility of harming the human body can be reduced, safety can be improved, disposal processing can be facilitated, and the environmental load can be reduced.

Moreover, if the kit 10 is assembled and used for the living tissue 1, the kit can be placed under a temperature condition suitable for the enzyme reaction, so that the bio-power generation that generates electricity using the oxidation-reduction reaction of the enzyme is efficiently performed. It can be carried out.
Furthermore, if the kit 10 is assembled and used for the living tissue 1, the need for an expensive material such as metal can be reduced, so that a current can be passed through the living tissue 1 at a low cost.

In particular, according to the kit 10 using the substance contained in the biological effluent as a substrate of the enzyme 3 (3a, 3b), for example, a current having a magnitude depending on the concentration of a specific substance contained in the biological effluent is detected. And information about the living body can be obtained.
In addition, according to the kit 10, the living tissue 1 (for example, for example) in which at least one selected from the group consisting of drugs, cosmetics, and preparations (hereinafter also referred to as “drugs”, which will be described later) is applied in advance. By sticking on the skin), it is possible to efficiently administer (permeate / store) a medicine or the like to the living tissue 1.
Furthermore, according to the kit 10, it is possible to administer a drug or the like to the living tissue 1 based on this information while obtaining information on the living body.
In particular, according to the kit 10, the cells are activated by passing a weak current (microcurrent) through cells constituting the living tissue 1 (for example, stratum corneum cells constituting the stratum corneum located on the skin surface). It is also possible to do.

  In addition, in the kit 10, since the dried enzyme 3 and the electrode 2 are used, it can prevent that the enzyme 3 deactivates between the time of manufacture of a kit and use.

  The frame 6 included in the kit 10 makes it possible to dispose the conductive member 4 in the communication portion 6t, and to connect the two electrodes 2 including the anode 2a and the cathode 2b so as to be in contact with both ends of the conductive member 4. Allows to place.

  The outer surface cover 7 included in the kit 10 integrates the two electrodes 2 (2a, 2b), the conductive member 4, and the frame 6.

  In the kit 10 shown in FIG. 1 and FIG. 2, the assembly 10a is produced and this assembly 10a is affixed to the living tissue 1, but the method of using the living tissue affixing kit of the present invention is limited to this. Instead, the assembly 10a may be fabricated on the living tissue 1 by sequentially placing each member on the living tissue 1.

3 (a) and 3 (b) show a biological tissue affixing kit according to a second embodiment of the present invention in a state before being attached to a biological tissue for use. 3A is a perspective view of the kit before assembly, and FIG. 3B is a cross-sectional view of the kit after assembly.
The biological tissue sticking kit 20 (hereinafter also referred to as “kit 20”) of the second embodiment of the present invention is the same as the biological tissue sticking kit 10 of the first embodiment described above except that it further includes a conductive layer. It is the same.
Below, the same code | symbol is attached | subjected to the element similar to the biological tissue sticking kit 10 of 1st embodiment of this invention shown in FIG. 1, and the description is abbreviate | omitted.

  In addition to the electrode 2 (2a, 2b), the conductive member 4, the frame 6, and the outer surface cover 7, the biological tissue sticking kit 20 of the second embodiment of the present invention (hereinafter also referred to as “kit 20”) A conductive layer 5 containing a substrate of enzyme 3 (3a, 3b) is included.

  In the kit 20, the conductive layer 5 includes water, a drug, and an electrolyte in addition to the enzyme 3 substrate. In the kit 20, the electrodes 2a and 2b carrying the enzyme 3 (3a and 3b) are dried.

Here, an example of how to use the kit 20 will be described.
First, before using the kit 20, the user applies the conductive layer 5 to the living tissue 1 (in FIG. 3A, the surface of the cheek portion of the head) in advance, as shown in FIG. Then, the assembly 20a is produced by assembling the two electrodes 2 (2a, 2b), the conductive member 4, the frame 6, and the outer cover 7. In the assembly 20a, the two electrodes 2 (2a, 2b) and the conductive member 4 are in contact with each other. Then, the user attaches the assembly 20a to the region where the conductive layer 5 is formed so that the electrode 2 is in contact with the conductive layer 5 (not shown).

  As the operational effects when using the kit 20, the same operational effects as those obtained by the biological tissue sticking kit 10 of the first embodiment described above can be obtained.

In particular, since the kit 20 includes the conductive layer 5 including the substrate of the enzyme 3 (3a, 3b), the kit 20 can spontaneously generate an electric current by an enzyme reaction.
Moreover, in the kit 20, since the conductive layer 5 is not incorporated into the assembly 20a, the reaction can be started when the assembly 20a is attached.
Furthermore, according to the kit 20, the cells constituting the skin tissue can be stimulated to activate the cells, and the electroosmotic flow is generated in the water contained in the skin, for example, the effect of removing wrinkles on the skin. Can be obtained. Therefore, the kit 20 can be used, for example, as a cell stimulating device or a skin wrinkle mitigating device.
Furthermore, according to the kit 20, by measuring a parameter such as a skin resistance value, the electrical resistance of the skin tissue depending on the degree of mental sweating or rough skin of the subject can be measured to detect the biological state. it can. Therefore, the kit 20 can be used as, for example, a mental state measuring device or a rough skin measuring device.
Furthermore, according to this kit 20, after the kit 20 is affixed to the skin and, for example, the molecular structure of the stratum corneum of the skin is disturbed, the drug or the like is applied to the skin so that the drug or the like is efficiently It can also be administered. Therefore, the kit 20 can be used as, for example, a pretreatment device for medication.

  In addition, since the conductive layer 5 contains a drug and the like in addition to the enzyme 3 substrate, the kit 20 can introduce an ionic active ingredient into the current and introduce it into the living tissue 1 (for example, skin). It is possible (iontophoresis), the molecular structure of the surface of the living tissue 1 (for example, the stratum corneum of the skin) is disturbed (electroporation), and the active ingredient can be permeated and stored in the skin. Therefore, according to the kit 20, a drug or the like can be administered to the living tissue 1 through the surface of the living body (for example, transdermal administration), and the drug or the like can be efficiently administered.

  Furthermore, since the conductive layer 5 contains an electrolyte in addition to the enzyme 3 substrate, the kit 20 can reduce the resistance value of the conductive layer 5 and increase the conductivity.

  In FIG. 3, the user applies the conductive layer 5 to the biological tissue 1 in advance, but the method of using the kit of the present invention is not limited to this, and the user applies the conductive layer 5 to the biological tissue 1. It may be attached, deposited, laminated, etc.

  In the kit 20 shown in FIG. 3, the conductive layer 5 is applied to one continuous region on the biological tissue 1, but in the biological tissue sticking kit of the present invention, the conductive layer 5 is on the anode side. It is preferable that the conductive layer 5a (not shown) and the cathode side conductive layer 5b (not shown) are isolated. At this time, the assembly 2a is attached so that the anode 2a is in contact with the anode-side conductive layer 5a and the cathode 2b is in contact with the cathode-side conductive layer 5b, whereby the electrode 2 (2a, 2b) and the conductive member 4 are bonded. In addition to the current flow through the conductive layer 5, a current flow through the living tissue 1 can also be generated. Therefore, according to the above-described configuration in which the conductive layer 5 is separated from the anode side and the cathode side, it is possible to enhance the effect of flowing an electric current to the living tissue 1 by the living tissue sticking kit of the present invention.

  In the kit 20 shown in FIG. 3, the conductive layer 5 is applied in advance to the biological tissue 1, but in the biological tissue application kit of the present invention, the conductive layer 5 is applied in advance to the electrode 2 (2a, 2b). Then, the assembly 20a may be used after being attached to the living tissue 1 (not shown). Here, it is preferable that the anode side conductive layer 5a is applied in advance to the anode 2a, and the cathode side conductive layer 5b is applied in advance to the cathode 2b. According to this configuration, as described above, the effect of flowing an electric current to the living tissue 1 by the living tissue sticking kit of the present invention can be enhanced.

  4 (a) and 4 (b) show a biological tissue affixing kit according to a third embodiment of the present invention in a state before being attached to a biological tissue for use. FIG. 4A shows a kit before assembly in a perspective view, and FIG. 4B shows a kit after assembly in a cross-sectional view.

In the biological tissue sticking kit 30 (hereinafter also referred to as “kit 30”) of the third embodiment of the present invention, the conductive layer is not formed in the biological tissue separately from the assembly, but is incorporated in the assembly. Except for this, it is the same as the biological tissue sticking kit 20 of the second embodiment described above.
Below, the same code | symbol is attached | subjected to the element similar to the kit 20 for biological tissue sticking of 2nd embodiment of this invention shown in FIG. 3, and the description is abbreviate | omitted.

  In this kit 30, the conductive layer 5 contains water in addition to the enzyme 3 substrate, and optionally contains a drug or the like. In the kit 30, the electrodes 2a and 2b carrying the enzyme 3 (3a and 3b) are dried.

  In the kit 30, the conductive layer 5 containing the substrate of the enzyme 3 includes an anode side conductive layer 5a and a cathode side conductive layer 5b. In the kit 30, the conductive layer 5 (5a, 5b) is fixed to the conductive layer holder 5h including the conductive layer attachment portion 5ha and the frame attachment portion 5hf. Further, the bridge portion 6b of the frame 6 is provided with a groove 6d that fits the frame attachment portion 5hf of the conductive layer holder 5h.

  As the operational effects when the kit 30 is used, the same operational effects as those obtained by the biological tissue sticking kit 20 of the second embodiment described above can be obtained.

  In particular, in the kit 30, since the conductive layer 5 including the substrate of the enzyme 3 (3a, 3b) is incorporated in the assembly 30a, the assembly 30a can spontaneously generate an electric current by an enzyme reaction.

  In the kit 30 shown in FIG. 4, the conductive layer 5 is fixed to the conductive layer holder 5h. However, in the biological tissue sticking kit of the present invention, the conductive layer 5 is not fixed to the conductive layer holder 5h. May be.

5 (a) and 5 (b) show a biological tissue affixing kit according to a fourth embodiment of the present invention in a state before being attached to a biological tissue for use. FIG. 5 (a) shows the kit before assembly in a perspective view, FIG. 5 (b) shows the kit after assembly in a sectional view, and FIG. 5 (c) shows a state in which water is added to the conductive layer. The assembled kit is shown in cross section.
The biological tissue sticking kit 40 (hereinafter also referred to as “kit 40”) of the fourth embodiment of the present invention, except that the conductive layer 5 is substantially water-free from that containing water, This is the same as the biological tissue sticking kit 30 of the third embodiment described above.
Below, the same code | symbol is attached | subjected to the element similar to the biological tissue sticking kit 30 of 3rd embodiment of this invention shown in FIG. 3, and the description is abbreviate | omitted.

  In the kit 40, the conductive layer 5 optionally contains a drug or the like in addition to the enzyme 3 substrate. In the kit 40, the electrodes 2a and 2b carrying the enzyme 3 (3a and 3b) are dried.

  In the kit 40, the conductive layer 5 does not substantially contain water. “Substantially free of water” means that the weight ratio of water to the conductive layer is less than 10%. Incidentally, the ratio is preferably less than 5%, and more preferably less than 2%.

  In the kit 40, the enzyme 3 can be prevented from being exposed to the substrate of the enzyme 3 contained in the conductive layer 5 until water is added to the conductive layer 5 at the time of use. The reaction rate can be extremely reduced. On the other hand, as shown in FIG. 5C, when water is added to the conductive layer 5, the aqueous solution of the substrate mixes with the enzyme 3, so that a condition capable of an oxidation-reduction reaction by the enzyme 3 can be realized. As described above, in the kit 40, the redox reaction by the enzyme 3 can be started by adding water to the conductive layer 5 at the time of use. In other words, in the kit 40, the electrode 2 and the conductive layer 5 that do not substantially contain water serve as reaction starting means. This allows the time when the kit starts to generate current to be matched when the kit is used. Therefore, the usability of the kit can be improved.

(Patch for biological tissue application)
Hereinafter, with reference to drawings, embodiment of a patch for biological tissue sticking of the present invention is illustrated and explained in detail.
The patch for sticking a biological tissue of the present invention is a patch for causing an electric current to flow inside the biological tissue through the surface of the living body by electricity generated by an enzyme reaction. This patch is used by being affixed to a living tissue.
The biological tissue patch of the present invention may be produced using the biological tissue patch of the present invention.

6 (a) and 6 (b) show the biological tissue application patch of the first embodiment shown in FIG. 6 in a state before being applied to the biological tissue. FIG. 6A is a perspective view of the patch, and FIG. 6B is a cross-sectional view of the patch.
Moreover, the patch for biological tissue sticking of FIG. 6 1st embodiment in the state currently affixed and used for a biological tissue to FIG. 7 (a), (b) is shown. FIG. 7A shows an external view of the patch, and FIG. 7B shows a cross-sectional view of the patch.
Below, the same code | symbol is attached | subjected to the element similar to the kit for biological tissue sticking of 1st-4th embodiment of this invention shown in FIGS. 1-5, and the description is abbreviate | omitted.

  A patch 60 (hereinafter also referred to as “patch 60”) for attaching a biological tissue according to the first embodiment of the present invention includes two electrodes 2 each including an anode (cathode) 2a and a cathode 2b (anode), and two electrodes. 2 (2a, 2b) and a conductive member 4 for electrical connection. Here, the anode 2a carries an enzyme 3a that catalyzes a reduction reaction, and the cathode 2b carries an enzyme 3b that catalyzes an oxidation reaction.

  As shown in FIG. 1A, the patch 60 is further used to fix the electrode 2 (2a, 2b) and the conductive member 4, and separates the two holes 6h from the holes 6h. A flat frame 6 having a bridge portion 6b and a communication portion 6t communicating between the holes, two electrodes 2 (2a, 2b), a conductive member 4, and an outer surface cover 7 for sealing the frame 6, And an inner surface cover 9 attached to the surface of the frame 6 where the hole 6h is opened. “Sealing” means sealing at least in a state where the patch 60 is attached to the living tissue 1 and used.

  In this patch 60, the electrodes 2a and 2b carrying the enzyme 3 (3a and 3b) are dried by freeze drying or the like.

  As shown in FIGS. 7A and 7B, the user can use the patch 60 by applying the patch 60 so that the electrode 2 contacts the living tissue 1.

The effect of using the patch 60 will be described.
There is a case where the biological drainage is attached to the biological tissue 1 (for example, when the skin is sweated). In this case, the substance contained in the biological drainage is the enzyme 3 (3a, 3b). May be a substrate. Electrons generated by the oxidation reaction by the enzyme 3b at the cathode 2b are delivered to the anode 2a through the conductive member 4, and are used for the reduction reaction by the enzyme 3a at the anode 2a. At this time, since the electrode 2 (2a, 2b) can contact the skin, electricity flows through the skin portion between the anode 2a and the cathode 2b.

  The biological tissue patch 60 according to the first embodiment of the present invention generates electricity using a substance harmless to the human body such as an enzyme or its substrate, while the existing biological tissue patch includes metal electrodes or the like. Use an existing battery with an electrolyte containing it. Therefore, according to the kit for affixing a living tissue of the present invention, it is possible to reduce the risk of harming the human body, increase safety, facilitate disposal processing, and reduce environmental burden.

Moreover, if the patch 60 is used for the living tissue 1, the patch can be placed under a temperature condition suitable for the enzyme reaction, and therefore, bioelectric power generation that efficiently generates electricity using the oxidation-reduction reaction of the enzyme is performed. Can do.
Furthermore, if the patch 60 is used for the living tissue 1, the need for an expensive material such as a metal can be reduced, so that a current can be passed through the living tissue 1 at a low cost.

In particular, according to the patch 60 using the substance contained in the biological drainage as the substrate of the enzyme 3 (3a, 3b), for example, a current having a magnitude depending on the concentration of the specific substance contained in the biological drainage is detected. And information about the living body can be obtained.
In addition, according to the patch 60, the living tissue 1 (for example, for example) in which at least one selected from the group consisting of drugs, cosmetics, and preparations (hereinafter also referred to as “drugs”, which will be described later) is applied in advance. By sticking on the skin), it is possible to efficiently administer (permeate / store) a medicine or the like to the living tissue 1.
Furthermore, according to the patch 60, a drug or the like can be administered to the living tissue 1 based on this information while obtaining information on the living body.
In particular, according to the patch 60, a weak current (microcurrent) is applied to cells constituting the living tissue 1 (for example, stratum corneum cells constituting the stratum corneum located on the skin surface) to activate the cells. It is also possible to do.

  In addition, since the dried enzyme 3 and the electrode 2 are used in the patch 60, it is possible to prevent the enzyme 3 from being deactivated from the time of manufacture of the patch to the time of use.

  The frame 6 included in the patch 60 makes it possible to dispose the conductive member 4 in the communication portion 6t, and to connect the two electrodes 2 including the anode 2a and the cathode 2b so as to be in contact with both ends of the conductive member 4. Allows to place.

  The outer surface cover 7 included in the patch 60 integrates the two electrodes 2 (2a, 2b), the conductive member 4, the conductive layer 5, and the frame 6.

  The inner surface cover 9 included in the patch 60 protects the surface of the patch 60 that is attached to the living tissue 1.

FIGS. 8A and 8B show the biological tissue application patch according to the second embodiment of the present invention in a state before being applied to the biological tissue. FIG. 8A is a perspective view of the patch, and FIG. 8B is a cross-sectional view of the patch.
The biological tissue application patch 70 (hereinafter also referred to as “patch 70”) of the second embodiment of the present invention is the same as the biological tissue application patch 60 of the first embodiment except that it further includes a conductive layer. It is the same.
Below, the same code | symbol is attached | subjected to the element similar to the patch 60 for biological tissue sticking of 1st embodiment of this invention shown in FIG. 1, and the description is abbreviate | omitted.

  The patch 70 includes, in addition to the electrode 2 (2a, 2b), the conductive member 4, the frame 6, and the cover 7, a conductive layer 5 including a substrate for the enzyme 3 (3a, 3b), and the electrode 2 (2a, 2b). It further includes an isolation member 8 (sheet shape in FIG. 1) that isolates the conductive layer 5. This isolation member 8 is detachably provided.

  In this patch 70, the conductive layer 5 includes water, a drug, and an electrolyte in addition to the enzyme 3 substrate. In the patch 70, the conductive layer 5 includes an anode side conductive layer 5a and a cathode side conductive layer 5b. The anode side conductive layer 5 a and the cathode side conductive layer 5 b are attached to the conductive layer attachment portion 6 a connected to the bridge portion 6 b of the frame 6. Furthermore, in this patch 70, the electrodes 2a and 2b carrying the enzyme 3 (3a and 3b) are dried.

  As the operational effects when the patch 70 is used, the same operational effects as those of the biological tissue application patch 60 of the first embodiment described above can be obtained.

In particular, since the patch 70 includes the conductive layer 5 including the substrate of the enzyme 3 (3a, 3b), the patch 70 can spontaneously generate an electric current by an enzyme reaction.
Further, according to the patch 70, the cells constituting the skin tissue can be stimulated and activated, and an electroosmotic flow is generated in the water contained in the skin, for example, the effect of removing wrinkles on the skin. Can be obtained. Therefore, the patch 70 can be used as, for example, a cell stimulation device or a skin wrinkle alleviation device.
Furthermore, according to the patch 70, by measuring a parameter such as a skin resistance value, the electrical resistance of the skin tissue depending on the degree of mental sweating or rough skin of the subject can be measured to detect the biological state. it can. Therefore, the patch 70 can be used as, for example, a mental state measuring device or a rough skin measuring device.
Furthermore, according to the patch 70, the patch 70 is applied to the skin, for example, the molecular structure of the horny layer of the skin is disturbed, and then the drug or the like is applied to the skin so that the drug or the like can be efficiently applied. It can also be administered. Therefore, the patch 70 can be used as, for example, a pretreatment device for medication.

  In addition, since the conductive layer 5 contains a drug and the like in addition to the enzyme 3 substrate, the patch 70 can be introduced into the living tissue 1 (for example, the skin) with an ionic active ingredient on the current. It is possible (iontophoresis), the molecular structure of the surface of the living tissue 1 (for example, the stratum corneum of the skin) is disturbed (electroporation), and the active ingredient can be permeated and stored in the skin. Therefore, according to the patch 70, a medicine or the like can be administered to the living tissue 1 via the surface of the living body (for example, transdermal administration), and the medicine or the like can be efficiently administered.

  Furthermore, since the conductive layer 5 contains an electrolyte in addition to the enzyme 3 substrate, the patch 70 can reduce the resistance value of the conductive layer 5 and increase the conductivity.

  Furthermore, since the conductive layer 5 is isolated by the anode side conductive layer 5a and the cathode side conductive layer 5b, the patch 70 has the electrode 2 (2a, 2b), the conductive member 4, and the conductive layer 5 interposed therebetween. In addition to the current flow, a current flow through the living tissue 1 can also be generated. Therefore, according to the above-described configuration in which the conductive layer 5 is separated from the anode side and the cathode side, it is possible to enhance the effect of flowing an electric current to the living tissue 1 by the living tissue sticking patch.

Furthermore, since the patch 70 includes the detachable separating member 8, the following effects can be obtained. That is, as shown in FIGS. 8A and 8B, while the separating member 8 is attached between the electrode 2 and the conductive layer 5 and is not in contact with the electrode 2, it is carried by the anode 2a and the cathode 2b. Since the enzyme 3 (3a, 3b) does not come into contact with the conductive layer 5 containing the substrate and water, the enzyme 3 is left in a dry state (that is, an inactive state) while the reaction by the enzyme 3 is stopped. And inactivation of enzyme 3 can be prevented. Here, when the separating member 8 is removed from between the electrode 2 and the conductive layer 5 and both come into contact (not shown), the enzyme 3 is supplied with water and a substrate, and the redox reaction by the enzyme 3 is started. The For example, the user removes the sheet-shaped isolation member 8 from between the electrode 2 and the conductive layer 5 and attaches the electrode 2 and the conductive layer 5 to each other before applying the patch 70, thereby redoxing with an enzyme. The reaction can be started. In other words, in the patch 70, the isolation member 8 serves as a reaction start means.
Thereby, the time when the patch starts to generate current can be matched with the time when the patch is used. Therefore, the usability of the patch can be improved.

9 (a) and 9 (b) show a biological tissue application patch according to the third embodiment of the present invention in a state before being used by being applied to the biological tissue. FIG. 9A is a perspective view of the patch, and FIG. 9B is a cross-sectional view of the patch.
The biological tissue patch 80 (hereinafter also referred to as “patch 80”) according to the third embodiment of the present invention is the above-mentioned second except that the conductive layer is changed from a disposable type to a refillable type. This is the same as the biological tissue patch 70 of the embodiment.
Below, the same code | symbol is attached | subjected to the element similar to the patch 70 for biological tissue sticking of 2nd embodiment of this invention shown in FIG. 1, and the description is abbreviate | omitted.

  In the patch 80, the conductive layer 5 contains water in addition to the enzyme 3 substrate, and optionally contains a drug or the like. In the patch 80, the electrodes 2a and 2b carrying the enzyme 3 (3a and 3b) are dried.

  In the patch 80, the conductive layer 5 (5a, 5b) is fixed to a conductive layer holder 5h including a conductive layer attachment portion 5ha and a frame attachment portion 5hf. Further, the bridge portion 6b of the frame 6 is provided with a groove 6d that fits the frame attachment portion 5hf of the conductive layer holder 5h.

  As the operational effects when the patch 80 is used, the same operational effects as those obtained by the biological tissue application patch 70 of the second embodiment described above can be obtained.

  In particular, in the patch 80, since the conductive layer 5 is fixed to the conductive layer holder 5h, the conductive layer 5 can be removed from the patch 80 by removing the conductive layer holder 5h from the patch 80. By loading the holder 5h together, the conductive layer 5 can be loaded on the patch 80. Therefore, for example, when the substrate contained in the conductive layer 5 is lost due to consumption by the enzyme, or when the water contained in the conductive layer 5 is lost due to evaporation, the old conductive layer 5 is removed, and A new conductive layer 5 can be easily loaded without touching other parts of the patch 80.

10 (a) and 10 (b) show a biological tissue application patch according to a fourth embodiment of the present invention in a state before being applied to a biological tissue. FIG. 10A is a perspective view of the patch, FIG. 10B is a sectional view of the patch, and FIG. 10C is a sectional view of the patch with water added to the conductive layer. .
The biological tissue application patch 90 (hereinafter also referred to as “patch 90”) according to the fourth embodiment of the present invention is the same as that described above except that the conductive layer does not contain water from that containing water. This is the same as the biological tissue patch 70 of the second embodiment.
Below, the same code | symbol is attached | subjected to the element similar to the patch 70 for biological tissue sticking of 2nd embodiment of this invention shown in FIG. 8, and the description is abbreviate | omitted.

  In this patch 90, the conductive layer 5 optionally contains a drug or the like in addition to the enzyme 3 substrate. In the patch 90, the electrodes 2a and 2b carrying the enzyme 3 (3a and 3b) are dried.

  Furthermore, in this patch 90, the conductive layer 5 is substantially free of water. “Substantially free of water” means that the weight ratio of water to the conductive layer is less than 10%. Incidentally, the ratio is preferably less than 5%, and more preferably less than 2%.

  In the patch 90, since the enzyme 3 can be prevented from being exposed to the substrate of the enzyme 3 contained in the conductive layer 5 until water is added to the conductive layer 5, the reaction rate of the oxidation-reduction reaction by the enzyme 3 Can be made extremely small. On the other hand, when water is added to the conductive layer 5, the aqueous solution of the substrate mixes with the enzyme 3, so that a condition capable of an oxidation-reduction reaction by the enzyme 3 can be realized. As described above, the patch 90 can start an oxidation-reduction reaction by an enzyme by adding water to the conductive layer 5 at the time of use. In other words, in the patch 90, the electrode 2 and the conductive layer 5 that do not substantially contain water serve as reaction starting means. Thereby, the time when the patch starts to generate current can be matched with the time when the patch is used. Therefore, the usability of the patch can be improved.

  Hereinafter, each element included in the biological tissue sticking kit according to the embodiment of the present invention and the biological tissue sticking patch according to the embodiment of the present invention will be described in detail.

-Electrode-
Examples of the material of the electrode 2 (2a, 2b) include carbon materials such as carbon nanotube, ketjen black, glassy carbon, graphene, fullerene, carbon fiber, carbon fabric, and carbon airgel; polyaniline, polyacetylene, polypyrrole, poly (p-phenylene) Conductive polymers such as vinylene), polythiophene, poly (p-phenylene sulfide); semiconductors such as silicone, germanium, indium tin oxide (ITO), titanium oxide, copper oxide, silver oxide; gold, platinum, titanium, aluminum, tungsten In particular, carbon materials such as carbon fabric and carbon nanotubes are preferable from the viewpoints of flexibility and electrochemical stability, and more particularly, the enzyme is high in the electrode. Fixed by density From the viewpoint that, a modified version of the carbon nanotubes in the carbon fabric is preferred.

--Enzyme--
Examples of the enzyme 3a that catalyzes the reduction reaction supported on the anode (cathode) 2a include bilirubin oxidase (BOD), laccase, Cu efflux oxidase (Cueo), ascorbate oxidase, and the like. From the viewpoint of resistance to pH and chloride ions, bilirubin oxidase (BOD) is preferred.
Examples of the enzyme 3b that catalyzes the oxidation reaction supported on the cathode (anode) 2b include glucose oxidase, glucose dehydrogenase (Glucose Dehydrogenase, GDH), fructose dehydrogenase (D-Fructose Dehydrogenase, FDH), alcohol oxidase, alcohol dehydrogenase, Examples include oxidoreductases such as lactate oxidase and lactate dehydrogenase. Fructose dehydrogenase (FDH) is particularly preferred because it has resistance to pH and does not require a mediator.
In particular, the combination of BOD and FDH is preferable because it can exhibit high activity under the condition of pH 5 equivalent to the pH on the outer surface of the biological tissue 1.

  Note that the voltage stability is increased by serializing a plurality of electrodes 2 carrying the enzyme 3 or by paralleling a plurality of electrodes 2 carrying the enzyme 3. This can also be improved, and a desired current can be stably secured.

  As conditions for freeze-drying the enzyme 3 and the electrode 2, it is particularly preferable to impregnate the electrode 2 carrying the enzyme 3 in a 1M trehalose aqueous solution and then freeze-dry the impregnated electrode 3. Under this condition, it is possible to prevent the higher order structure from being destroyed when the enzyme 3 is frozen and thawed, thereby losing the catalytic activity.

  In the biological tissue sticking kit according to the embodiment of the present invention shown in FIGS. 1 to 5 and the biological tissue sticking patch according to the embodiment of the present invention shown in FIGS. 6 to 10, the enzyme 3 (3a, 3b) is used. ) Are dried by freeze drying or the like, but in the biological tissue sticking kit of the present invention and the biological tissue sticking patch of the present invention, the electrode is not limited to this. If 2a and 2b are substantially free of water, it is possible to obtain an effect of preventing the enzyme 3 from being inactivated between the time of manufacture of the kit and the patch and the time of use. “Substantially free of water” means that the weight ratio of water to the electrode is less than 10%. Incidentally, the ratio is preferably less than 5%, and more preferably less than 2%.

-Conductive member-
Examples of the material of the conductive member 4 include carbon materials such as carbon nanotube, ketjen black, glassy carbon, graphene, fullerene, carbon fiber, carbon fabric, and carbon aerogel; polyaniline, polyacetylene, polypyrrole, poly (p-phenylene vinylene), Conductive polymers such as polythiophene and poly (p-phenylene sulfide); semiconductors such as silicone, germanium, indium tin oxide (ITO), titanium oxide, copper oxide, silver oxide; gold, platinum, titanium, aluminum, tungsten, copper, Examples thereof include metals such as iron and palladium, and conductive polymers are particularly preferable from the viewpoints of flexibility and biocompatibility.
Note that, for example, the conductive member 4 may be a circuit formed of a conductive polymer on the surface of the hydrogel using a printing technique.

  The resistance value of the conductive member 4 is preferably 10Ω to 18MΩ, and more preferably 30 kΩ to 200 kΩ. Since the difference of the oxidation-reduction potential due to the enzyme 3 is about 0.3 V to 0.7 V, the above-described effect on the living tissue 1 can be ensured if the resistance value is in the above range.

-Conductive layer-
As the conductive layer 5, one having flexibility and compatibility with the outer surface of the living tissue 1 is preferable.
More specifically, the conductive layer 5 is preferably a hydrogel, and in particular, a hydrogel having a certain regularity is preferable. If such a hydrogel is used, the adhesiveness of the conductive layer 5 to the living tissue 1 when the patch 1 is attached can be enhanced.

  Examples of the hydrogel used for the conductive layer 5 included in the patch 1 include agar, gelatin, agarose, xanthan gum, gellan gum, sclerotia gum, arabic gum, tragacanth gum, caraya gum, cellulose gum, tamarind gum, guar gum, locust bean gum, glucomannan, Chitosan, carrageenan, quince seed, galactan, mannan, starch, dextrin, curdlan, casein, pectin, collagen, fibrin, peptide, chondroitin sulfate such as sodium chondroitin sulfate, hyaluronic acid (mucopolysaccharide) and sodium hyaluronate Gels containing natural polymers such as alginates such as hyaluronate, alginic acid, sodium alginate and calcium alginate, and derivatives thereof; Gels containing cellulose derivatives such as chilled cellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose and their salts; poly (acrylic acid, polymethacrylic acid, poly (acrylic acid / alkyl methacrylate copolymer) Gels containing meth) acrylic acids and salts thereof; polyvinyl alcohol, polyhydroxyethyl methacrylate, polyacrylamide, poly (N-isopropylacrylamide), polyvinyl pyrrolidone, polystyrene sulfonic acid, polyethylene glycol, carboxyvinyl polymer, alkyl-modified carboxyvinyl polymer , Maleic anhydride copolymer, polyalkylene oxide resin, N-vinyl acetate Gels containing synthetic polymers such as crosslinked amides, crosslinked acrylamides, crosslinked starch / acrylate graft copolymers, etc .; silicone hydrogels; interpenetrating network hydrogels and semi-interpenetrating network hydrogels; mixtures of two or more of these In particular, from the viewpoint of load resistance and biocompatibility, gel containing collagen and glucomannan; gel containing carboxymethylcellulose and sodium carboxymethylcellulose; gel containing polyacrylic acid and sodium polyacrylate; interpenetrating network structure Hydrogels and semi-interpenetrating network hydrogels are preferred. In addition, although it does not specifically limit as hydrogel, Usually, the hydrogel containing a polymer is used.

An interpenetrating network hydrogel refers to a gel in which other network structures are uniformly entangled with the base network structure, resulting in the formation of a plurality of network structures throughout the gel, and a semi-interpenetrating network structure. The hydrogel refers to a gel in which other linear structures are uniformly entangled with a base network structure, and as a result, a plurality of network structures are formed throughout the gel. Here, the network structure and / or the linear structure is formed from a plurality of types of polymers. In particular, when the number of the network structure and / or the linear structure is 2, the (semi) interpenetrating network hydrogel is a double It is called a network gel (DN gel). These gels are known as hydrogels having very high mechanical strength (see WO2003 / 093337).
Here, in the (semi) interpenetrating network structure hydrogel, 10 mol% or more of the first monomer component is a charged monomer, and 60 mol% or more of the second monomer component is electrically neutral. The molar ratio of the amount of the first monomer component to the amount of the second monomer component in the hydrogel is 1: 2 to 1: 100 (preferably 1: 3 to 1:50). More preferably, the crosslinking degree when polymerizing and crosslinking the second monomer component is higher than the crosslinking degree when polymerizing and crosslinking the first monomer component. Small points are essential.
Examples of the first monomer include olefins having an acidic group (for example, a carboxyl group, a phosphoric acid group and a sulfonic acid group) and a basic group (for example, an amino group), such as 2-acrylamido-2-methyl. Examples thereof include propanesulfonic acid, acrylic acid, methacrylic acid, and salts thereof. Examples of the second monomer include acrylamide, N-isopropylacrylamide, vinyl pyridine, styrene, methyl methacrylate, fluorine-containing olefin (for example, trifluoroethyl acrylate), hydroxyethyl acrylate, vinyl acetate, and the like.
An example of a method for producing a (semi) interpenetrating network structure hydrogel is as follows. First, a first monomer component is polymerized and crosslinked to form a network structure (first network structure) in which a certain amount or more of charged groups (for example, a carboxyl group) are present, and then electrically The second monomer component, which is electrically neutral, is introduced into the first network structure by polymerizing and crosslinking the second monomer component which is neutral.

Further, the tensile stress at break of the hydrogel is preferably 1 kPa to 100 MPa, more preferably 10 kPa to 20 MPa.
When the tensile breaking stress is within the above range, the mechanical strength of the conductive layer 5 can be increased. Even when the patch 1 is affixed to the skin or when the user of the patch 1 moves the body, the hydrogel is prevented from being destroyed, and the patch 1 is adhered to the living tissue 1 while maintaining the regularity of the patch 1. Can continue to.
The “tensile breaking stress” can be measured by measuring the stress at which the hydrogel breaks by a tensile load using a load cell. As a measuring device, for example,
Examples thereof include a tensile tester 5960 series manufactured by Instron.

  Furthermore, the water content of the hydrogel used for the conductive layer 5 is preferably 10% to 99.99%, and more preferably 80% to 99.99%. If it is the said range, about a patch, effects, such as an improvement in electric power generation performance and an increase in inclusion amount of an enzyme substrate, a medicine, etc., can be acquired.

  Furthermore, the pH of the hydrogel used for the conductive layer 5 is preferably 3 to 9, and more preferably 4 to 8. If it is the said range, it can be set as the optimal pH of an enzyme, activity can be improved, and the inflammation by the contact with the conductive layer 5 of the biological tissue 1 can be suppressed.

  As described above, the conductive layer 5 may include a substrate of the enzyme 3 (3a, 3b); water; at least one selected from the group consisting of drugs, cosmetics, and formulations; an electrolyte. Hereinafter, each detail is further described.

--Substrate--
The substrate of enzyme 3 (3a, 3b) can be determined according to the enzyme used.

--- Water--
Examples of water include ultrapure water.

--- Drugs, etc .--
The definitions of “drug”, “cosmetics”, and “formulation” in the term “at least one selected from the group consisting of drugs, cosmetics, and formulations” used in the present specification are shown below.
“Drug” refers to the active ingredient itself. “Cosmetics” refers to those that are applied to living tissue 1 such as skin for the purpose of cleansing the body or making it look beautiful. , Quasi drugs, cosmetics). The “formulation” refers to a product that is made into a dosage form convenient for use by blending an additive or the like with a drug, filling, molding, and / or the like, and / or a product obtained as a result thereof.

--- Drug ---
Examples of the drug that can be used in the patch for attaching a biological tissue of the present invention include the following.
Examples of anti-aging effects include uric acid, glutathione, metonin, polyphenol, melanoidin, astaxanthin, kinetin, epigallocatecaterate, coenzyme Q10, vitamins, superoxide dismutase, mannitol, quercetin, catechin and derivatives thereof, rutin And derivatives thereof, button pi extract, yashajitsu extract, melissa extract, rakan fruit extract, dibutylhydroxytoluene, butylhydroxyanisole and the like.
Examples of those having a whitening effect include whitening agents and anti-inflammatory agents. The whitening agent has the effect of preventing the darkening of the skin caused by sunburn and the like, and the occurrence of spots and freckles caused by pigmentation. For example, arbutin, ellagic acid, linoleic acid, vitamin C and derivatives, kojic acid , Tranexamic acid, placenta extract, chamomile extract, licorice extract, geese extract, oxon extract, seaweed extract, cucumber extract, caquette extract, gokahi extract, rice bran extract, wheat germ extract, saicin Extract, Hawthorn extract, Sunpens extract, Shirayuri extract, Peonies extract, Sempukuka extract, Soybean extract, Tea extract, Molasses extract, Byaclen extract, Grape extract, Hop extract, Mikaika extract , Mokka extract, saxifrage extract and the like. The anti-inflammatory agent has an action of suppressing inflammation such as hot flashes and erythema on the skin after sunburn. For example, sulfur and its derivatives, glycyrrhizic acid and its derivatives, glycyrrhetinic acid and its derivatives, Altea extract , Ashitaba extract, Arnica extract, Ginseng extract, nettle extract, Duckweed extract, Hypericum extract, Chamomile extract, Snapdragon extract, Watercress extract, Comfrey extract, Salvia extract, Bamboo extract, Examples include perilla extract, birch extract and gentian extract.
As what has a peeling and brightening effect, (alpha) -hydroxy acid, a salicylic acid, sulfur, urea etc. are mentioned, for example.
Examples of the slimming effect include plant extracts such as ginger, chili pepper tincture, and clara root, carbon dioxide, vitamin E, and derivatives thereof that have an effect of promoting blood circulation.
Examples of those having a moisturizing effect include proteins such as elastin and keratin and derivatives thereof and hydrolysates thereof, salts thereof, amino acids such as glycine, serine, asoaraginic acid, glutamic acid, arginine and theanine, and derivatives thereof, sorbitol Erythritol, trehalose, inositol, glucose, sucrose and derivatives thereof, dextrin and derivatives thereof, saccharides such as honey, D-pantenol and derivatives thereof, sodium lactate, sodium pyrrolidonecarboxylate, sodium hyaluronate, mucopolysaccharide, urea, Phospholipids, ceramides, oren extract, ginger extract, gentian extract, genus oyster extract, gypsophila extract, gypsophila extract, dokudami extract, hamamelis extract, bodaiju extract, maronier extract Things, quince extract, and the like.
As what has a hair repair effect, phospholipid polymer, hydrolyzed collagen, 18-MEA, hydrolyzed wheat protein, hydrolyzed rice protein, phytic acid, inositol etc. are mentioned, for example.
Examples of those having a hair-growth effect include isopropylmethylphenol, ginkgo biloba extract, L-menthol, carpronium chloride, diphenhydramine hydrochloride, kash (what necklace), glycyrrhizic acid (dipotassium), salicylic acid, dialkylmonoamine derivatives, gyoza, cephalanthin, senkyu , Assembly, chixetsu carrot, ginseng, capsicum tincture, toki, trehalose, nicotinic acid / nicotinic acid amide, vitamin E (tocopherol), hinokitiol, placenta extract, pentadecanoic acid glyceride and the like.
As those having skin conditioning effects, for example, ceramides, cholesterols, amine derivatives, caffeine, chicken crown extract, shell extract, royal jelly, for the purpose of improving rough skin such as barrier function improvement and damage healing Silk protein and its degradation products and derivatives thereof, lactoferrin and its degradation products, chondroitin sulfate, mucopolysaccharides such as hyaluronic acid and their salts, collagen, yeast extract, lactic acid bacteria extract, bifidobacteria extract, fermentation metabolic extraction , Ginkgo biloba extract, barley extract, sea cucumber extract, sea squirrel extract, carrot extract, arnica extract, turmeric extract, eucalyptus extract, cattail, bonito extract, rosemary extract, glycolic acid, citric acid , Lactic acid, malic acid, tartaric acid, succinic acid and the like.
Examples of those having a relaxing effect include lavender, rosemary, sandalwood, oris, bitter orange, cypress, orange oil and the like.
In addition, these chemical | medical agents may be used individually by 1 type, and may be used in combination of 2 or more type.

--- Cosmetics ---
Examples of cosmetics include lotion, milky lotion, beauty essence, cream, cream pack, massage cream, cleansing cream, cleansing gel, facial cleansing foam, sunscreen, styling gel, shampoo, body shampoo, hair setting gel, fragrance, dyeing Examples include hair materials.
According to these cosmetics, effects such as anti-aging, whitening, peeling / brightening, slimming, moisturizing, hair repair, hair growth, skin conditioning, relaxation, UV protection, etc. can be obtained.
In addition, these cosmetics may be used individually by 1 type, and may be used in combination of 2 or more type.

--- Formulation ---
The preparation is not particularly limited as long as it contains an active ingredient such as a drug. In the case of a hydrophilic active ingredient, it is sufficient that the active ingredient is dispersed or dissolved in an aqueous medium. In the case of a lipophilic active ingredient, the active ingredient may be dispersed or dissolved in an oily medium. . Specific examples include skin external preparations, foods, tablets, and pharmaceuticals.

  The dosage form of the above-described cosmetics or preparations is not particularly limited, and is an aqueous type, a solubilized type, a multilayer type, an oil-in-water type, a water-in-oil type, an oily type, a water-in-oil-in-water type, an oil Examples include oil-in-water type. Moreover, it can also be expected that both hydrophilic and lipophilic active ingredients are allowed to act effectively by using liposomes, vesicles and the like.

--- Electrolyte--
The electrolyte is not particularly limited as long as it has an effect of enhancing the conductivity of the conductive layer, and examples thereof include organic acids and / or inorganic acids and derivatives thereof and salts thereof.
Examples of the anionic species constituting the electrolyte include amino acid ions (natural amino acid ions, non-natural amino acid ions), chloride ions, citrate ions, lactate ions, succinate ions, phosphate ions, malate ions, pyrrolidone carboxylic acids. Ion, sulfococolic acid ion, sulfate ion, nitrate ion, phosphate ion, carbonate ion, perchlorate ion, etc., where natural amino acids include glycine, alanine, valine, leucine, isoleucine, phenylalanine, tyrosine, Threonine, serine, proline, tryptophan, methionine, cysteine, aspartic acid, glutamic acid, asparagine, glutamine, lysine, arginine, histidine, and natural amino acids include hydroxyproline, cystine, thyroxine, etc. It is.
Examples of the cation species constituting the electrolyte include K ⁺ , Na ⁺ , Ca ²⁺ , Mg ^{2+ and the} like.
Specific examples of the electrolyte include, for example, sodium salts of amino acids, sodium chloride, calcium chloride, magnesium chloride, sodium citrate, sodium lactate, calcium lactate, sodium succinate, sodium malate, sodium pyrrolidonecarboxylate, zinc sulfocolate, Examples include potassium aluminum sulfate (alum), and sodium citrate, sodium lactate, sodium monohydrogen phosphate, sodium dihydrogen phosphate, and sodium phosphate are particularly preferable from the viewpoint of biocompatibility.
In addition, these electrolytes may be used individually by 1 type, and may be used in combination of 2 or more type.

  The concentration of the electrolyte in the conductive layer is preferably 1 mM or more, and more preferably 50 mM or more. If it is the said range, resistance of a conductive layer can be reduced (for example, to 3 k (ohm) or less), and an electric current can be increased.

-Frame-
The material of the frame 6 is preferably a material that can be adapted to the shape of the living tissue 1 (for example, skin), for example, a plastic material. Specific examples include resins such as silicone, polydimethylsiloxane, polyisoprene, polyurethane, polyethylene, latex, and nitrile rubber. In particular, from the viewpoint of water repellency, flexibility, and workability, polydimethylsiloxane (PDMS) is used. preferable.

-Outer cover-
The outer cover 7 is preferably waterproof.
Providing the waterproof outer surface cover 7 can prevent the water contained in the conductive layer 5 from evaporating, so that the conditions for the oxidation-reduction reaction by the enzyme 3 (3a, 3b) are ensured in the assembly system. The service life of kits and patches can be extended.
Examples of the outer cover 7 include a waterproof spray paste, a waterproof tape, and a waterproof bandage.

  The outer cover 7 preferably has air permeability. If the outer surface cover 7 having air permeability is provided, an enzyme using a substance contained in the atmosphere as a substrate (for example, BOD using oxygen as a reduction reaction substrate) can be used for the enzyme 3a supported on the anode 2a. Costs associated with enzyme substrates can be reduced.

-Isolation member-
Examples of the material of the separating member 8 include plastics such as polyethylene, polypropylene, polyethylene terephthalate, acrylic resin, polycarbonate, and polyamide, cellophane made of elastomer, rubber, cellulose, polymer resin, quartz, glass, and the like. From the viewpoint of flexibility, cellophane and plastic are preferred.

-Inner cover-
As the material of the inner surface cover 9, the same material as that of the isolation member 8 can be used.

  In addition, the isolation member 8 and the inner surface cover 9 may be integrated (not shown). According to this configuration, the separating member 8 and the inner surface cover 9 can be removed simultaneously. For example, the separating member 8 and the inner surface cover 9 can be removed at the same time by connecting them at one end in the longitudinal direction and pulling them out from one end side during use.

  Examples of the biological tissue 1 to which the kit and the patch can be attached include keratin-containing tissues mainly composed of keratin such as the skin of the face, fingers, arms, body, hair, nails, lips, and inner surface of the oral cavity. Without limiting to, any tissue that forms the outer surface of a living body can be used.

  In the biological tissue sticking kit of the embodiment of the present invention shown in FIGS. 1 to 5 and the biological tissue sticking patch of the embodiment of the present invention shown in FIGS. 6 to 10, the anode (cathode) 2a and the present invention are used. The two electrodes 2 composed of the cathode (anode) 2b of the present invention are included, but the biological tissue application kit and the biological tissue application patch of the present invention are not limited thereto, and are not limited thereto, and at least one anode (cathode), and A plurality of electrodes including at least one cathode (anode) may be included.

  Moreover, in the biological tissue sticking kit of the embodiment of the present invention shown in FIGS. 1 to 5 and the biological tissue sticking patch of the embodiment of the present invention shown in FIGS. 6 to 10, the enzyme 3a is supported on the anode 2a. In addition, the enzyme 3b is supported on the cathode 2b. However, in the biological tissue sticking kit and the biological tissue sticking patch of the present invention, the enzyme 3b that catalyzes the oxidation reaction is not limited to this. It may be supported. In this case, as the anode 2a, an inorganic catalyst such as platinum, a platinum alloy, gold, copper, etc., and those obtained by nano-particulate these inorganic catalysts supported on a carbon electrode obtained by solidifying activated carbon can be used.

  Furthermore, the biological tissue sticking kit of the embodiment of the present invention shown in FIGS. 1 to 5 and the biological tissue sticking patch of the embodiment of the present invention shown in FIGS. 6 to 10 are suitable for sticking to the skin or the like. However, the biological tissue affixing kit and the biological tissue affixing patch of the present invention are not limited to this, and can have any shape depending on the biological tissue 1 to be attached. .

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to the following Example at all.

Example 1
A. Production of electrode A-1. Electrode Material In this example, a carbon fiber fabric (product number: TCC-3250, manufactured by Toho Tenax) for modifying carbon nanotubes was used as an electrode material. In addition, fructose dehydrogenase (D-fructose dehydrogenase (FDH), derived from Gluconobacter, EC number: 1.1.99.11, 20 U / mg, Mw: about 140000, manufactured by Toyobo Co., Ltd.) is used for the cathode (anode). As the anode (cathode), bilirubin oxidase (BOD, derived from Myrothecium, EC number: 1.3.3.5, Mw: about 68000, 2.39 U / mg, manufactured by Amano Enzyme) was used.

A-2. Pretreatment of carbon nanotubes Carbon nanotubes (product number: C 70 P, manufactured by Bayer MaterialScience) (hereinafter also referred to as CNT) are heated to 400 ° C. over 11 hours using an oven, and then naturally cooled. The CNTs were heat treated. By this heat treatment, defects were generated in the CNT.
Distilled water, nitric acid, and sulfuric acid were mixed in a beaker at a volume ratio of 1: 3: 1, and the mixed solution was allowed to cool for several tens of minutes. Then, CNT was acid-processed by adding CNT to this acidic mixed solution, and ultrasonically treating for about 30 minutes using an ultrasonic bath.
The CNT mixed solution was allowed to cool for about 5 hours, and then this solution was neutralized using an aqueous sodium hydroxide solution. The neutralized CNT mixed solution was filtered under reduced pressure conditions to collect CNTs. The collected CNTs were frozen at −80 ° C. for 1 hour, and then dried at room temperature and 10 Pa using a freeze dryer.

A-3. Enzyme support and freeze-drying of enzyme support electrode A-3-1. Production of Cathode (Anode) A CNT suspension adjusted to 10 mg / mL was purified using a 0.5% Triton X-100 aqueous solution. In order to improve the dispersibility of CNTs, this CNT suspension was sonicated for 5 minutes using an ultrasonic homogenizer. 10 μL of the CNT suspension was dropped onto a 5 mm × 5 mm carbon fiber fabric and dried at 70 ° C. for about 5 minutes. This dripping and drying operation was repeated, and a total of 40 to 50 μL of the CNT suspension was added onto the carbon fiber fabric.
A carbon fiber fabric modified with CNTs was impregnated with 50 mM citrate buffer, and washed for 1 hour or more with stirring under reduced pressure. This electrode was immersed in an FDH solution adjusted to 5 mg / mL at 4 ° C. for 8 hours or more to fix the FDH to the electrode. The FDH electrode was immersed in a 50 mM citrate buffer at room temperature for 5 minutes to remove unadsorbed FDH. The FDH electrode was immersed in a 50 mM citrate buffer solution in which 1 M trehalose was dissolved. The FDH electrode was snap frozen by immersing in liquid nitrogen. Finally, it was put into a freeze dryer (product number: ALPHA 2-4 LSC, manufactured by CHRiST (Kubota Corp.)) to prepare a dried FDH electrode.

A-3-2. Preparation of anode (cathode) Pretreated CNTs were added to a 1.0% Triton X-100 aqueous solution and ethanol, and 10 mg / mL CNT suspension (water) and 4 mg / mL CNT suspension, respectively. (Ethanol) was prepared. In order to improve the dispersibility of CNTs, this CNT suspension was sonicated for 5 minutes using an ultrasonic homogenizer. 12.5 μL of the CNT suspension (water) was dropped on a 5 mm × 5 mm carbon fiber fabric and dried at 70 ° C. for about 10 minutes. This dripping and drying operation was repeated 4 times, and a total of 50 μL of the CNT suspension (water) was added onto the carbon fiber fabric. This electrode was washed with stirring in a solution of ethanol.
A BOD solution adjusted to 10 mg / mL was dropped onto a 1 mL electrode and dried at 35 ° C. for about 6 hours under reduced pressure. This dripping and drying operation was repeated twice, and a total of 50 μL of CNT suspension (ethanol) was added onto the electrode to produce a BOD air electrode. As a solution for dissolving BOD, 50 mM PBS (pH 7.0) or 50 mM PBS (pH 7.0) added with 1 M trehalose was used.

B. Production of Conductive Member In this example, a commercially available conductive polymer sheet (product number: ORGACON (registered trademark) EL350 / 630, manufactured by Agfa) was used as the conductive member.

C. Production of Conductive Layer A 0.4 g / mL acrylamide aqueous solution and a 0.02 g / mL bisacrylamide aqueous solution were prepared using a 50 mM citrate buffer. Then, 250 μL of a 0.4 g / mL aqueous acrylamide solution, 120 μL of a 0.02 g / mL aqueous bisacrylamide solution, and 630 μL of a 50 mM citrate buffer were mixed, and this mixture was further treated with Irgacure as a radical photopolymerization initiator. 1 mg of (registered trademark) 2959 was added to prepare a photopolymerization reaction solution. This reaction solution was irradiated with UV for 1 minute to prepare an acrylamide gel as a conductive layer.
The acrylamide gel used on the cathode side was impregnated with a 200 mM fructose aqueous solution prepared using a 50 mM citrate buffer for 1 day. For the acrylamide gel used on the anode side, the photopolymerization reaction product was used as it was.

D. Production of Frame In this example, a frame made of polydimethylsiloxane (hereinafter also referred to as PDMS) was used as the frame. The frame was provided with a hole for embedding the anode side conductive layer and the cathode side conductive layer, a bridge part separating the hole part, and a communication part communicating between the hole parts. In Example 1, a frame having a hole penetrated, that is, a frame having no bottom surface was used.

E. Production of Outer Cover In this example, a commercially available medical tape (3M, manufactured by Nexcare) was used as the outer cover.

F. Preparation of Patch The medical tape was placed with its adhesive surface facing up, and the frame prepared on the adhesive surface was placed with its bridge portion facing up. Subsequently, a conductive member, an anode and a cathode, an anode-side conductive layer, and a cathode-side conductive layer were added to the hole of the frame in this order to prepare a biological tissue patch. FIG. 11A is an exploded perspective view of the patch, and FIG. 11B is a cross-sectional view of the assembled patch.

G. Output Performance Measurement The potential difference (cell voltage) between the anode and cathode of the prepared patch was measured using a potentiostat. The results are shown in FIG. 12 (the vertical axis indicates the patch current density (white square) and the output density (white circle), and the horizontal axis indicates the cell voltage). The open circuit voltage of the patch was 0.71 V, and the maximum power density was 172 μW / cm ² . Since the resistance value of the skin surface is about 100 kΩ, it was found that a current of about 7 μA can be passed through the tissue on the skin surface according to this patch. The magnitude of this current was strong enough for electrical stimulation to living tissue.

H. Durability Performance Measurement For the patch prepared in the above “F. Preparation of Patch” and the control patch prepared in F above without using a medical tape, as in the above “G. Output Performance Measurement”, between the anode and cathode of the patch The potential difference was measured over time using a potentiostat. In the patch of the example using the medical tape, the drying of the acrylamide gel as the conductive layer was prevented for a long time, whereas in the control patch not using the medical tape, the acrylamide as the conductive layer as time passed. When the drying of the gel progressed and the time exceeded 10,000 seconds, the gel broke.
The results are shown in FIG. 13 (the vertical axis indicates the patch output as an index, and the horizontal axis indicates the time. Note that the patch output indicates an output standardized by the initial output). The produced patch was able to maintain about 80% output even at 10,000 seconds. This is considered to be because an excessive increase in the salt concentration in the gel could be suppressed by preventing the gel from drying. The slight decrease in output over time is thought to be due to the fact that protons are generated when fructose is oxidized at the cathode, and local changes occur in the pH near the cathode, resulting in a decrease in the activity of fructose dehydrogenase. . On the other hand, the output of the control patch decreased to about 20% at the time of 10,000 seconds. This is considered to be because the salt concentration in the gel increased excessively as the gel dried.
In this test, in order to connect the potentiostat lead to the electrode, it was necessary to make a hole in a part of the medical tape, but in the actual use of the patch, a more sealed environment was created. be able to. Therefore, it is considered that the durability performance is higher than the result in this test.

I. Optimization of enzyme lyophilization conditions Tripolar electrochemical measurements using a potentiostat were performed. Specifically, the measurement was performed by cyclic voltammetry (hereinafter also referred to as CV) (potential sweep rate 10 mVs ⁻¹ ) using Ag / AgCl (saturated KCl) as a reference electrode and a platinum electrode as a counter electrode. The cathode side was a citric acid aqueous solution in which fructose was dissolved, and the anode side was a citric acid aqueous solution.

I1. Optimization of cathode lyophilization conditions In "A-3-1. Production of cathode (anode)", the final concentration of trehalose was changed (1 M, 100 mM, 10 mM, none), and a cathode was produced by lyophilization. Moreover, the final concentration of trehalose was 1 M, and a cathode was produced by air drying. And the said electrochemical measurement was performed about these cathodes.

  CV was performed on the cathode having each final trehalose concentration before drying, immediately after drying, 1 day after drying, 2 days after and 7 days after drying. The results for samples other than the sample before drying are shown in Fig. 14 (the vertical axis indicates the FDH activity ratio (after drying / before drying) (%), and the horizontal axis indicates the number of days after drying. Is an index of the current value normalized by the current value before drying when a potential of 0.6 V (vs. Ag / AgCl) is applied. In a sample prepared by air drying with a final trehalose concentration of 1M, the output immediately after drying was 14%. This is presumably because the salt concentration of the enzyme solution increased excessively with drying and the higher-order structure of the enzyme was destroyed. A sample prepared by freeze-drying without using trehalose had 53% activity immediately after drying and 21% activity 7 days after drying. This is presumably because lyophilization that rapidly sublimates water suppresses the destruction of the higher-order structure of the enzyme. In contrast, a sample prepared by freeze-drying with a final trehalose concentration of 1 M retained the activity before drying immediately after drying, and had about 90% activity even after 7 days of drying. This is because the hydroxyl group of trehalose is responsible for hydrogen bonding with the enzyme instead of hydration during the sublimation of water, preventing the destruction of the higher-order structure of the enzyme, and is also concentrated during the sublimation process of water. This is probably because the enzyme was protected by trehalose molecules. In the sample prepared by freeze-drying with the final concentration of trehalose being 100 mM and 10 mM, the effect of trehalose is considered to be small.

I2. Optimization of anode lyophilization conditions In "A-3-2. Production of anode (cathode)", the final concentration of trehalose was changed (1M, none), and an anode was produced by lyophilization. An anode was prepared by lyophilization. And the said electrochemical measurement was performed about these cathodes. CV was performed on the cathode having each final trehalose concentration immediately after drying, 1 day, 2 days, and 7 days after drying, as in (Reference Test 1-1). The results for samples other than the sample before drying are shown in FIG. 15 (the vertical axis shows the BOD activity ratio (after drying / before drying) (%), and the horizontal axis shows the number of days after drying. Is an index of the current value normalized with the current value before drying when a potential of 0.7 V (vs. Ag / AgCl) is applied. Both when the final concentration of trehalose was 1 M and when trehalose was not used, it had high activity (> 80%) from immediately after drying to 7 days after drying.

(Example 2)
The enzyme used for the cathode was glucose dehydrogenase (glucose dehydrogenase (GDH), derived from Microorganism, EC number: 1.1.1.1.47, 250 U / mg, Mw: about 101,000, manufactured by Toyobo Co., Ltd.) The experiment was conducted in the same manner as in Example 1 described above. In the following, only experiments corresponding to “A-3-1. Production of cathode (anode)” and “G. Output performance measurement” will be described.

A-3-1. Production of Cathode (Anode) As in Example 1, 40-50 μL of CNT suspension was added onto the carbon fiber fabric.
Carbon fiber fabric modified with CNTs was impregnated in distilled water and washed for about 30 minutes with stirring. This electrode was immersed in a Nile blue solution prepared to 100 μM in 50 mM phosphate buffer, and stirred at 4 ° C. for 1 hour or more under reduced pressure.
Then, Nile blue was electropolymerized on the electrode by performing CV for 10 cycles in the voltage range of −0.8 to 1.2 V at a potential sweep rate of 10 mVs ⁻¹ . After the electropolymerization, the electrode was washed with distilled water for about 1 to 2 hours, and further impregnated overnight at room temperature with stirring in 1-pyrenebutyric acid N-hydroxysuccinimide ester solution prepared to 1 mM in dimethyl sulfoxide. . The electrode was impregnated with distilled water, washed for 1 hour with stirring, and then impregnated overnight at 4 ° C. with stirring in a poly L-lysine (PLL) solution adjusted to 10 mM in a phosphate buffer. Finally, this electrode was washed with distilled water, and then impregnated with glucose dehydrogenase (GDH) solution adjusted to 1 mg / mL in a phosphate buffer solution at 4 ° C. for 3 hours or more with stirring, and GDH was deposited on the electrode. Immobilized to.

G. Output Performance Measurement Output performance measurement was performed by cyclic voltammetry (hereinafter also referred to as CV) (potential sweep rate 10 mVs ⁻¹ ). For the measurement sample, a glucose solution prepared to 200 mM in a phosphate buffer solution was used, and for the reference sample, a phosphate buffer solution not containing glucose was used. The results are shown in FIG. 16 (the vertical axis shows current density and the horizontal axis shows potential). The maximum current density was 2.93 mA / cm ² . From this result, even when the enzyme used for the cathode (anode) is GDH, by including glucose as a substrate of GDH in the conductive layer, a current that can give sufficiently strong electrical stimulation to the living tissue. It was found that can be generated.

  According to the biological tissue sticking kit of the present invention and the biological tissue sticking patch of the present invention, a current can be passed through the biological tissue while realizing high safety and low environmental load. The biological tissue sticking kit of the present invention and the biological tissue sticking patch of the present invention are particularly preferably used in the beauty and medical fields.

1 Living tissue (skin)
2 electrode 2a anode (cathode)
2b Cathode (anode)
3 Enzyme 3a Enzyme that catalyzes reduction reaction 3b Enzyme that catalyzes oxidation reaction 4 Conductive member 5 Conductive layer 5a Anode-side conductive layer 5b Cathode-side conductive layer 5h Conductive layer holder 5ha Conductive layer mounting portion 5hf Frame mounting portion 6 Frame 6a Conductive Layer attachment part 6b Bridge part 6h Hole part 6t Communication part 7 Outer cover 8 Separating member 9 Inner cover 10 Biological tissue sticking kit 10a assembly 20 of the first embodiment 20a Biological tissue sticking kit 20a assembly 30 of the second embodiment Biological tissue sticking kit 30a assembly 40 of the third embodiment 40 Biological tissue sticking kit 40a assembly 60 of the fourth embodiment 70 Biological tissue sticking patch 70 of the first embodiment 70 Biological tissue sticking patch 80 of the second embodiment 80 Patch for sticking a living tissue according to the third embodiment 90 Patch for sticking a living tissue according to the fourth embodiment

Claims (11)

  A biological tissue affixing kit for producing a biological tissue affixing patch used by being affixed to a biological tissue, comprising a plurality of electrodes including an electrode carrying an enzyme that catalyzes a redox reaction, and the plurality of electrodes A kit for attaching a living tissue, comprising: a conductive member for electrically connecting a conductive layer; and a conductive layer substantially free of water. The biological tissue sticking kit according to claim 1, wherein the conductive layer includes the enzyme substrate.   The biological tissue sticking kit according to claim 1 or 2, wherein the plurality of electrodes and the conductive layer are in contact with each other when the kit is used.   The living tissue patch kit according to any one of claims 1 to 3, wherein the conductive layer further includes at least one selected from the group consisting of a drug, a cosmetic, and a preparation.   The biological tissue affixing kit according to any one of claims 1 to 4, wherein the plurality of electrodes substantially do not contain water.   The biological tissue sticking kit according to any one of claims 1 to 5, further comprising an outer surface cover for sealing the plurality of electrodes, the conductive member, and the conductive layer.   A patch for attaching a living tissue to be used by attaching to a living tissue, a plurality of electrodes including an electrode carrying an enzyme that catalyzes a redox reaction, and a conductive member that electrically connects the plurality of electrodes A patch for attaching a living tissue, comprising a conductive layer substantially free of water. The patch for biological tissue sticking of Claim 7 with which the said conductive layer contains the substrate of the said enzyme, and the said conductive layer is provided in the state which contacted with respect to these electrodes. The patch for biological tissue sticking according to claim 7 or 8 , wherein the conductive layer further includes at least one selected from the group consisting of drugs, cosmetics, and preparations. The patch for biological tissue sticking according to any one of claims 7 to 9 , wherein the plurality of electrodes substantially does not contain water. Wherein the plurality of electrodes, the conductive member, and further includes an outer surface cover sealing the conductive layer, a living tissue sticking patch according to any one of claims 7-10.

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