Drug delivery device

Abstract

A drug delivery device (1) comprising a base material sheet (2), a first electrode (11), a second electrode (12), and a third electrode (13) disposed on the base material sheet (2), and a drug-containing part (19) containing a drug, wherein: the potential applied to the first electrode (11) and the potential applied to the second electrode (12) are the same; the potential applied to the first electrode (11) and the potential applied to the third electrode (13) are different; and, on the base material sheet 2, the separation distance between the first electrode (11) and the third electrode (13) is shorter than the separation distance between the second electrode (12) and the third electrode (13).

Description

Drug Delivery Devices

[0001] The present invention relates to a drug delivery device, and more particularly to a drug delivery device that can deliver a drug into the body transdermally by electrical action.

[0002] Iontophoresis is a known technique for transdermally delivering a drug placed between an electrode and the skin into the body by applying a voltage to the skin using an electrode. Patent Document 1, for example, discloses a transdermal or transmucosal drug delivery device that combines pulse depolarized current and at least one of direct current and pulse current.

[0003] International Publication No. 1999 / 000157

[0004] A drug delivery device can allow a drug to penetrate into the skin from a drug-containing portion by applying a voltage between electrodes. However, when using the drug delivery device, it is desirable to be able to arbitrarily adjust the penetration of the drug into the skin. For example, if the drug could penetrate the skin stepwise rather than all at once, or if the penetration of the drug into the skin could be adjusted depending on the type of drug, various uses of the drug delivery device would be possible, which would be desirable. The present invention has been made in consideration of the above circumstances, and its object is to provide a drug delivery device that can adjust the penetration of the drug.

[0005] The drug delivery device of the present invention, which has been able to solve the above problems, is as follows: [1] A drug delivery device comprising a base sheet, a first electrode, a second electrode, and a third electrode arranged on the base sheet, and a drug-containing portion containing a drug, wherein a potential applied to the first electrode is the same as a potential applied to the second electrode, a potential applied to the first electrode is different from a potential applied to the third electrode, and a distance between the first electrode and the third electrode on the base sheet is shorter than a distance between the second electrode and the third electrode. [2] The drug delivery device according to [1], further comprising a fourth electrode arranged on the base sheet, a potential applied to the third electrode is the same as a potential applied to the fourth electrode, and a distance between the first electrode and the fourth electrode on the base sheet is shorter than a distance between the second electrode and the fourth electrode, and a distance between the first electrode and the third electrode is shorter than a distance between the first electrode and the fourth electrode. [3] The drug delivery device of [1], wherein an electrode group A consisting of a plurality of electrodes including the first electrode and the second electrode is arranged on the base sheet, the electrodes constituting the electrode group A are supplied with the same potential, and the electrode group A is arranged on the base sheet so as to be surrounded by a convex polygon that does not include the third electrode. [4] The drug delivery device of [2], wherein an electrode group A consisting of a plurality of electrodes including the first electrode and the second electrode and an electrode group B consisting of a plurality of electrodes including the third electrode and the fourth electrode are arranged on the base sheet, the electrodes constituting the electrode group A are supplied with the same potential, the electrodes constituting the electrode group B are supplied with the same potential, the electrode group A and the electrode group B are each surrounded by a convex polygon on the base sheet, and the area formed by the convex polygon surrounding the electrode group A and the area formed by the convex polygon surrounding the electrode group B are arranged so as not to overlap each other. [5] The drug delivery device according to any one of [1] to [4], wherein the drug-containing portion further contains water and a moisture-retaining substance, and the drug is ionized.[6] The drug delivery device according to any one of [1] to [5], wherein the drug delivery device is disposed in epithelial tissue, and the drug-containing portion is disposed on the surfaces of the first electrode and the second electrode that are closer to the epithelial tissue and / or the surface of the third electrode that is closer to the epithelial tissue. [7] The drug delivery device according to any one of [1] to [5], wherein the drug delivery device is disposed in epithelial tissue, and the drug-containing portion is disposed on the surfaces of the first electrode and the second electrode that are closer to the epithelial tissue. [8] The drug delivery device according to any one of [1] to [5], wherein the drug delivery device is disposed in epithelial tissue, and the first electrode, the second electrode, and the third electrode are disposed on the surfaces of the base sheet that are closer to the epithelial tissue, and the drug-containing portion is contained in the first electrode and the second electrode and / or the third electrode. [9] The drug delivery device according to any one of [1] to [5], wherein the drug delivery device is disposed in epithelial tissue, the first electrode, the second electrode, and the third electrode are disposed on a surface of the base sheet closer to the epithelial tissue, and the drug-containing portion is contained in the first electrode and the second electrode.

[10] The drug delivery device according to any one of [1] to [9], wherein the drug delivery device further includes an electrolyte-containing portion containing water, a moisture-retaining substance, and an electrolyte, the electrolyte-containing portion being disposed on a surface of the third electrode closer to the epithelial tissue or being contained in the third electrode disposed on a surface of the base sheet closer to the epithelial tissue.

[11] The drug delivery device according to any one of [1] to

[10] , further including a power supply unit and a control unit that controls the flow of electricity from the power supply unit.

[0006] The drug delivery device of the present invention has a base sheet on which multiple electrodes, including a first electrode, a second electrode, and a third electrode, are arranged. The potential applied to the first electrode is the same as the potential applied to the second electrode, and the potential applied to the first electrode is different from the potential applied to the third electrode. The separation distance between the first electrode and the third electrode on the base sheet is shorter than the separation distance between the second electrode and the third electrode. By arranging the electrodes in this manner, the potential gradient between the first electrode and the third electrode is greater than the potential gradient between the second electrode and the third electrode. The drug retained in the drug-containing portion penetrates into the skin using the potential gradient along the electric field lines between the electrodes as a driving force, thereby promoting drug penetration between the first electrode and the third electrode more than drug penetration between the second electrode and the third electrode. This allows, for example, rapid drug delivery between the first electrode and the third electrode and delayed drug delivery between the second electrode and the third electrode, thereby enabling sustained drug delivery to the skin over an extended period of time. Alternatively, it is possible to adjust the drug penetration into the skin depending on the type of drug. The drug delivery device of the present invention can adjust the penetration of the drug by arranging the first electrode, second electrode, and third electrode in this manner.

[0007] 1 shows an example of a cross-sectional configuration of a drug delivery device of the present invention, illustrating the state in which the drug delivery device is placed on the skin. 1 shows an example of a configuration of a drug delivery device of the present invention, illustrating a cross-sectional view of the drug delivery device. 2 shows a plan view of the drug delivery device shown in FIG. 2 as seen from the bottom. 3 shows another example of a configuration of a drug delivery device of the present invention, illustrating a cross-sectional view of the drug delivery device. 4 shows a plan view of the drug delivery device shown in FIG. 4 as seen from the bottom. 4 shows another example of a configuration of a drug delivery device of the present invention, illustrating a cross-sectional view of the drug delivery device. 5 shows a plan view of the drug delivery device shown in FIG. 6 as seen from the bottom. 6 shows another example of a configuration of a drug delivery device of the present invention, illustrating a plan view of the drug delivery device as seen from the bottom. 7 shows another example of a configuration of a drug delivery device of the present invention, illustrating a plan view of the drug delivery device as seen from the bottom. 8 shows another example of a configuration of a drug delivery device of the present invention, illustrating a cross-sectional view of the drug delivery device. 9 shows a plan view of the drug delivery device shown in FIG. 11 as seen from the bottom.

[0008] The drug delivery device of the present invention will be specifically described below based on the following embodiments. However, the present invention is not limited to the following embodiments, and appropriate modifications can be made within the scope of the above and below-described purposes, and all such modifications are within the technical scope of the present invention. In addition, hatching and component symbols may be omitted in each drawing for convenience. In such cases, reference should be made to the specification and other drawings. Furthermore, the dimensions of various components in the drawings may differ from the actual dimensions, as priority is given to helping understand the features of the present invention.

[0009] The drug delivery device of the present invention includes a base sheet, multiple electrodes arranged on the base sheet, and a drug-containing portion containing a drug. The drug delivery device of the present invention can be applied to the skin and a voltage applied between the electrodes to deliver the drug contained in the drug-containing portion into the body through the skin. Iontophoresis is a known technique for transdermally delivering drugs into the body using electrical action. Iontophoresis applies a voltage from electrodes to the skin, generating a potential gradient across the skin, and then uses this potential gradient to deliver the drug transdermally into the body. The potential gradient across the skin serves as a driving force, causing the drug to penetrate into the skin through electrical repulsion between the drug and the electrodes. Alternatively, the potential gradient across the skin can generate an electroosmotic flow within the skin, which then transports the drug from the epithelial tissue into the subcutaneous tissue or blood vessels. The drug delivery device of the present invention can be used in such iontophoresis devices.

[0010] The drug delivery device of the present invention includes a base sheet and a plurality of electrodes, including a first electrode, a second electrode, and a third electrode, arranged on the base sheet. The potentials applied to the first electrode and the second electrode are the same, while the potentials applied to the first electrode and the third electrode are different. The distance between the first electrode and the third electrode on the base sheet is shorter than the distance between the second electrode and the third electrode. By providing a plurality of electrodes, including the first electrode, the second electrode, and the third electrode, in this manner, it is possible to adjust the penetration of the drug into the skin. For example, it is possible to allow the drug to penetrate the skin gradually rather than all at once, or to adjust the penetration of the drug into the skin depending on the type of drug. Below, a drug delivery device according to an embodiment of the present invention is described in detail with reference to the drawings.

[0011] 1 to 5 show examples of the configuration of a drug delivery device provided with a first electrode, a second electrode, and a third electrode as electrodes. Fig. 1 shows an example of the cross-sectional configuration of the drug delivery device of the present invention, showing the drug delivery device placed on the skin. Fig. 2 shows a cross-sectional view of a drug delivery device according to one embodiment of the present invention. Fig. 3 shows a plan view of the drug delivery device shown in Fig. 2, viewed from the bottom. Fig. 4 shows a cross-sectional view of a drug delivery device according to another embodiment of the present invention. Fig. 5 shows a plan view of the drug delivery device shown in Fig. 4, viewed from the bottom.

[0012] As shown in Figure 1, drug delivery device 1 is a device placed on skin 31 and can transdermally deliver a drug into the body. Drug delivery device 1 includes a base sheet 2, a plurality of electrodes including a first electrode 11, a second electrode 12, and a third electrode 13 arranged on base sheet 2, and a drug-containing portion 19 containing a drug. Each electrode is preferably electrically connected to a power supply unit 21. By placing drug delivery device 1 on epithelial tissue 32 and applying a voltage between the electrodes from power supply unit 21, a potential gradient is generated within the skin tissue, and this potential gradient can be used to transdermally deliver a drug.

[0013] The drug delivery device 1 has a planar direction in which the base sheet 2 extends and a thickness direction in which the electrodes are laminated on the base sheet 2. An upper side and a lower side are defined in the thickness direction, and the lower side refers to the side that faces the skin (epithelial tissue) when the drug delivery device 1 is placed on the skin for use, and the upper side refers to the opposite side.

[0014] The base sheet 2 is a sheet on which electrodes including a first electrode 11, a second electrode 12, and a third electrode 13 are arranged, and these electrodes are arranged on the base sheet 2. The electrodes are arranged on the lower surface of the base sheet 2, i.e., the surface closer to the epithelial tissue, and are preferably fixed to the lower surface of the base sheet 2. "Electrodes including a first electrode 11, a second electrode 12, and a third electrode 13" arranged on the base sheet 2 means that these electrodes are arranged on the surface (main surface) of the base sheet 2, and does not refer to the hierarchical relationship between the base sheet 2 and the electrodes in the thickness direction.

[0015] The base sheet 2 can be made of an insulator, and is preferably electrically insulated from the electrodes arranged on the base sheet 2. At least the area of ​​the base sheet 2 where the electrodes are arranged needs to be made of an insulator, but it is preferable that the entire base sheet 2 is made of an insulator. The base sheet 2 can be made of, for example, a resin sheet, a cloth material such as a nonwoven fabric, a woven fabric, or a knitted fabric, or paper. The base sheet 2 may be an elastic body, and may be made of, for example, a rubber sheet, which is a type of resin sheet.

[0016] The shape (planar shape) of the base sheet 2 is not particularly limited, and examples thereof include polygons such as squares, hexagons, and octagons, polygons with rounded corners, circles, ellipses, dumbbell shapes, and irregular shapes.

[0017] The electrodes, including the first electrode 11, the second electrode 12, and the third electrode 13, may be any known electrodes. The electrodes may be made of a conductor and electrically connected to a power supply unit 21. The electrodes are preferably connected to the power supply unit 21 via a wiring unit 23. The first electrode 11, the second electrode 12, and the third electrode 13 may be connected to either the positive or negative pole of the power supply unit 21. The electrode connected to the positive pole serves as an anode, and the electrode connected to the negative pole serves as a cathode. The drug delivery device 1 also preferably has a control unit 22 for controlling the flow of electricity between the electrodes. Details of the power supply unit 21, the wiring unit 23, and the control unit 22 will be described later.

[0018] As long as the electrode is electrically connected to the power supply unit 21, only a portion of the electrode may be made of a conductor, or the entire electrode may be made of a conductor. Examples of conductors constituting the electrode include metals such as gold, silver, copper, platinum, zinc, lead, tin, titanium, aluminum, nickel, and alloys thereof, as well as silver halides and carbon. A silver / silver halide electrode may also be used. A silver / silver halide electrode is formed by coating the surface of silver with silver halide. Metals include preferably silver, zinc, gold, platinum, and titanium, with silver and zinc being more preferred. Examples of silver halides include silver fluoride, silver chloride, silver bromide, and silver iodide, with silver chloride being preferred. Examples of carbon include carbon fiber, graphite, ketjen black, fullerene, carbon nanotube, carbon nanohorn, and furnace black.

[0019] The shape of the conductor used in the electrode is not particularly limited, and examples thereof include plate-shaped, thin film-shaped, fibrous, and particulate shapes. Examples of plate-shaped electrodes include metal plates. Thin film electrodes can be formed, for example, by printing ink containing a conductive substance on the base sheet 2, by disposing a thin metal film on the base sheet 2, or by etching. When the conductor is fibrous or particulate, the electrode is preferably composed of a fiber aggregate (e.g., a fiber mass) or a particle aggregate (e.g., an agglomerated particle mass).

[0020] Of the multiple electrodes, the electrode functioning as the anode preferably contains silver, zinc, gold, platinum, titanium, carbon, etc. from the viewpoint of biocompatibility, and more preferably contains silver or zinc from the viewpoint of reducing pH changes. Of the multiple electrodes, the electrode functioning as the cathode preferably contains silver / silver chloride, gold, platinum, titanium, carbon, etc. from the viewpoint of biocompatibility, and more preferably contains silver / silver halide from the viewpoint of reducing pH changes. By reducing pH changes, skin irritation during use of the drug delivery device 1 can be reduced.

[0021] The shape (planar shape) of the electrode is not particularly limited, and examples thereof include polygons such as squares, hexagons, and octagons, polygons with rounded corners, circles, ellipses, and irregular shapes.

[0022] The drug-containing portion 19 contains at least a drug. Examples of drugs contained in the drug-containing portion 19 include low-molecular-weight ionic drugs, high-molecular-weight drugs such as peptides, proteins, and oligonucleotides, antibody drugs, and nucleic acid drugs. The drug is preferably ionized, i.e., is preferably an ionic substance.

[0023] The drug is preferably a pharmaceutical. Pharmaceuticals are drugs used for the diagnosis, treatment, or prevention of diseases. Examples of pharmaceuticals include anti-inflammatory agents, antipyretic and anti-inflammatory analgesics, antibiotics, local anesthetics, antiallergic agents, anti-Alzheimer's agents, anti-Parkinson's disease agents, psychoneurotic agents, anti-rheumatic agents, smoking cessation aids, and circulatory organ agents.

[0024] The molecular weight of the drug is preferably from 100 to 1,000,000, more preferably from 500 to 50,000, even more preferably from 700 to 15,000, and even more preferably from 1,000 to 8,000. In particular, if the molecular weight of the drug is 8,000 or less, the permeability of the drug into the skin can be increased.

[0025] The drug-containing portion 19 preferably contains water and a moisture-retaining substance in addition to the drug. This allows the drug to be held in the drug-containing portion 19 in a water-dissolved state, facilitating the drug's penetration into the skin. The drug is preferably impregnated in the moisture-retaining substance as a drug solution. The moisture-retaining substance is not particularly limited as long as it is a substance that can retain moisture, and examples thereof include cloth, paper, porous materials, and hydrogels, with hydrogels being particularly preferred.

[0026] Examples of fabric materials include nonwoven fabrics, woven fabrics, knitted fabrics, etc., and among these, knitted fabrics are preferred. Examples of constituent fibers of fabric materials include natural fibers such as cotton, linen, and silk, recycled fibers such as rayon, semi-synthetic fibers such as acetate, and synthetic fibers formed from polyester (e.g., PET), polyolefin (e.g., polypropylene, polyethylene), polyurethane, polyamide (e.g., nylon), etc. Paper materials preferably contain pulp, and examples thereof include tissue paper.

[0027] The porous body preferably has voids inside, and the voids preferably have a structure in which they are connected to the outside of the porous body. For example, the porous body preferably contains air bubbles, and the air bubbles preferably have interconnected open cells. The porous body may be made of a resin, ceramic, or metal. However, it is preferably made of a resin in order to improve the conformability of the drug delivery device 1 to the skin when attached to the skin. Examples of resins that constitute the porous body include fluororesins such as PTFE, PFA, and ETFE; polyolefin resins such as polyethylene and polypropylene; polyester resins such as polyethylene terephthalate and polybutylene terephthalate; silicone resins such as polydimethylsiloxane; polyamide resins such as nylon; and cellulose derivatives such as hydroxyethyl cellulose and hydroxypropyl cellulose. The porous body may also be a porous membrane.

[0028] The hydrogel is not particularly limited as long as it is a gel-like substance containing water, and preferably contains a water-soluble polymer. The water-soluble polymer preferably has a crosslinked structure, which makes the water-soluble polymer more likely to function as a gel and improves the shape retention of the hydrogel. The water-soluble polymer may have hydrophobic groups in addition to hydrophilic groups. The hydrogel may have a crystalline structure.

[0029] The water-soluble polymer can be composed of a polysaccharide or a synthetic resin. Examples of polysaccharides include gelatin, agar, agarose, dextran, carboxy starch, dextrin, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, chitosan, alginic acid and its salts, and hyaluronic acid and its salts. Examples of synthetic resins include polyvinyl alcohol, polyethylene oxide, polyvinyl methyl ether, polyvinyl ether-maleic anhydride copolymer, methoxyethylene-maleic anhydride copolymer, isobutylene-maleic anhydride copolymer, silicone-containing copolymer, polyvinylpyrrolidone, polyacrylamide, carboxyvinyl polymer, polyacrylic acid and its salts. The silicone-containing copolymer preferably has a siloxane structure and one or both of an ether structure and an ester structure. The salt may be either a partially neutralized salt or a fully neutralized salt.

[0030] The drug-containing portion 19 may contain an electrolyte. Suitable examples of the electrolyte include halide salts such as calcium chloride, potassium chloride, and sodium chloride. This facilitates the formation of an electroosmotic flow within the skin when a voltage is applied between the electrodes. Among halide salts, chloride salts are more preferred.

[0031] Drug-containing portion 19 may contain a pH adjuster (pH buffer). Examples of pH adjusters include acetic acid, phosphoric acid, citric acid, carbonate, and salts thereof. This can suppress pH fluctuations in drug-containing portion 19 and prevent deterioration of the drug contained in drug-containing portion 19.

[0032] The drug-containing portion 19 may contain additives such as a crosslinking agent, a filler, an adhesive, a preservative, a moisturizer, an antioxidant, a colorant, a fragrance, an oil, an ultraviolet absorber, a cooling agent, a warming agent, a transdermal absorption enhancer, and a conductive substance. If the drug-containing portion 19 contains an adhesive, it becomes easier to attach the drug-containing portion 19 to the skin. If the drug-containing portion 19 contains a transdermal absorption enhancer, it promotes the penetration of the drug into the skin. Examples of transdermal absorption enhancers include hydrophilic polyethers such as polyethylene glycol and polypropylene glycol, organic acid esters such as isopropyl myristate and isopropyl palmitate, fatty acids having 6 to 20 carbon atoms such as oleic acid, stearic acid, and palmitic acid, squalane, castor oil, anionic surfactants, cationic surfactants, and amphoteric surfactants. If the drug-containing portion 19 contains a conductive substance, the conductivity of the drug-containing portion 19 can be increased. Examples of conductive substances include conductive fibers and conductive fillers. The conductive filler preferably contains conductive particles.

[0033] The drug-containing portion 19 is preferably provided adjacent to at least one electrode selected from the first electrode 11, the second electrode 12, and the third electrode 13, or is included in at least one electrode selected from the first electrode 11, the second electrode 12, and the third electrode 13. In the former case, the drug-containing portion 19 is preferably disposed on the underside of the electrode, i.e., the surface closest to the epithelial tissue. For example, a moisture-retaining substance containing a drug solution is preferably disposed on the underside of the electrode. In the latter case, the electrode is composed of an aggregate of conductive fibers or an aggregate of conductive particles, and the drug solution is retained within the aggregate of conductive fibers or the aggregate of conductive particles, thereby allowing the drug-containing portion 19 to be contained in the electrode. Various configuration examples of the drug delivery device 1 are shown in FIGS. 2 to 5. In FIGS. 2 and 3, the drug-containing portion 19 is provided adjacent to the first electrode 11 and the second electrode 12, and in FIGS. 4 and 5, the drug-containing portion 19 is provided adjacent to the third electrode 13.

[0034] The drug-containing portion 19 may be provided on either the anode electrode or the cathode electrode depending on whether the ionized substance functioning as the medicinal ingredient becomes a cation or anion when the drug ionizes. If the ionized substance functioning as the medicinal ingredient is a cation, it is preferably provided on the anode electrode. If the ionized substance functioning as the medicinal ingredient is an anion, it is preferably provided on the cathode electrode. Note that if the ionized substance has both a functional group that dissociates into a cation and a functional group that dissociates into an anion, the drug-containing portion 19 may be provided on either the anode electrode or the cathode electrode depending on whether the ionized substance is positively or negatively charged overall. The ionization state of the drug is determined based on the pH conditions of the drug-containing portion 19.

[0035] 2, drug-containing portion 19 is provided on first electrode 11 and second electrode 12, and first electrode 11 and second electrode 12 are connected to the positive pole of power supply 21, so that first electrode 11 and second electrode 12 serve as anodes. Therefore, it is preferable that the drug contained in drug-containing portion 19 be such that, when ionized, the medicinal component becomes a cation, or the drug as a whole becomes a positively charged ionized product.

[0036] 4, drug-containing portion 19 is provided on third electrode 13, and third electrode 13 is connected to the negative electrode of power supply 21, so that third electrode 13 serves as a cathode. Therefore, it is preferable that the drug contained in drug-containing portion 19 be such that, upon ionization, the medicinal component becomes an anion, or the drug as a whole becomes a negatively charged ionized product.

[0037] The drug delivery device 1 preferably has an electrolyte-containing portion 20. The electrolyte-containing portion 20 preferably contains water and an electrolyte, and preferably further contains a moisture-retaining substance. By providing the electrolyte-containing portion 20, the electrical resistance between the electrode provided with the electrolyte-containing portion 20 and the skin is reduced, thereby reducing the power consumption of the drug delivery device 1. Furthermore, when a voltage is applied between the electrodes, an electroosmotic flow is more likely to be formed inside the skin. The electrolyte-containing portion 30 is preferably a portion that does not contain a drug.

[0038] The electrolyte-containing portion 20 is preferably provided on at least one electrode selected from the first electrode 11, the second electrode 12, and the third electrode 13, which does not have the drug-containing portion 19. In this case, the electrode not having the drug-containing portion 19 means an electrode that does not have the drug-containing portion 19 adjacent thereto and does not include the drug-containing portion 19. The electrolyte-containing portion 20 is preferably provided adjacent to the electrode not having the drug-containing portion 19, or is preferably included in the electrode not having the drug-containing portion 19. In the former case, the electrolyte-containing portion 20 is preferably disposed on the underside of the electrode, i.e., the surface closer to the epithelial tissue. For example, a water-retaining substance containing an electrolyte solution is preferably disposed on the underside of the electrode. In the latter case, the electrode is composed of an aggregate of conductive fibers or an aggregate of conductive particles, and the electrolyte solution is retained within the aggregate of conductive fibers or the aggregate of conductive particles, thereby allowing the electrolyte-containing portion 20 to be contained in the electrode. 2 and 3, electrolyte-containing portion 20 is provided adjacent to third electrode 13, and in Figures 4 and 5, electrolyte-containing portion 20 is provided adjacent to first electrode 11 and second electrode 12. Hereinafter, "drug-containing portion 19 or electrolyte-containing portion 20 is provided on an electrode" means both that drug-containing portion 19 or electrolyte-containing portion 20 is provided adjacent to an electrode and that drug-containing portion 19 or electrolyte-containing portion 20 is included in the electrode.

[0039] For details of the electrolytes and water-retaining substances in the electrolyte-containing portion 20, please refer to the explanation of the electrolytes and water-retaining substances in the drug-containing portion 19 above. The electrolytes contained in the electrolyte-containing portion 20 may be the same as or different from the electrolytes contained in the drug-containing portion 19. The water-retaining substances contained in the electrolyte-containing portion 20 may be the same as or different from the water-retaining substances contained in the drug-containing portion 19. The electrolyte-containing portion 20 may further contain a pH adjuster, and may also contain additives such as crosslinkers, fillers, adhesives, preservatives, humectants, antioxidants, colorants, fragrances, oils, UV absorbers, cooling agents, warming agents, transdermal absorption enhancers, and conductive substances. For details of these pH adjusters and various additives, please refer to the explanation of the pH adjusters and additives in the drug-containing portion 19 above.

[0040] Drug delivery device 1 can cause a drug to penetrate into the skin from drug-containing portion 19 by applying a voltage between the electrodes, but it is desirable to be able to adjust the penetration of the drug into the skin as desired when using drug delivery device 1. For example, if the drug could penetrate the skin stepwise rather than all at once, or if the penetration of the drug into the skin could be adjusted depending on the type of drug, this would enable various uses of drug delivery device 1 and be desirable.

[0041] From the above viewpoint, the drug delivery device 1 has at least a first electrode 11, a second electrode 12, and a third electrode 13 as electrodes, wherein the potential applied to the first electrode 11 is the same as the potential applied to the second electrode 12, and the potential applied to the first electrode 11 is different from the potential applied to the third electrode 13, and the distance between the first electrode 11 and the third electrode 13 on the base sheet 2 is shorter than the distance between the second electrode 12 and the third electrode 13. By providing the electrodes in this manner, the potential gradient between the first electrode 11 and the third electrode 13 is greater than the potential gradient between the second electrode 12 and the third electrode 13. The drug held in the drug-containing portion 19 penetrates into the skin using the potential gradient along the electric field lines between the electrodes as a driving force, and therefore, the penetration of the drug between the first electrode 11 and the third electrode 13 is more promoted than the penetration of the drug between the second electrode 12 and the third electrode 13. This allows, for example, a drug to be rapidly delivered into the skin between the first electrode 11 and the third electrode 13, and slowly delivered into the skin between the second electrode 12 and the third electrode 13, thereby enabling the drug to be continuously delivered to the skin for a long period of time. By arranging the first electrode 11, the second electrode 12, and the third electrode 13 in this manner, the drug delivery device 1 can arbitrarily adjust the penetration of the drug. Note that the separation distance between the electrodes means the shortest separation distance between the electrodes.

[0042] In the drug delivery device 1 shown in Figures 2 and 3, drug-containing portions 19 are provided on the first electrode 11 and the second electrode 12, and an electrolyte-containing portion 20 is provided on the third electrode 13. By providing drug-containing portions 19 in this manner, the penetration of the drug into the skin from drug-containing portion 19 provided on the first electrode 11 is promoted more than the penetration of the drug into the skin from drug-containing portion 19 provided on the second electrode 12. As a result, the drug is supplied into the skin quickly from drug-containing portion 19 provided on the first electrode 11, and the drug is supplied into the skin slowly from drug-containing portion 19 provided on the second electrode 12. This makes it possible, for example, to continuously supply the drug to the skin over a long period of time.

[0043] The drug contained in the drug-containing portion 19 provided on the first electrode 11 and the drug contained in the drug-containing portion 19 provided on the second electrode 12 may be the same or different. The charge number of the drug contained in the drug-containing portion 19 provided on the first electrode 11 and the charge number of the drug contained in the drug-containing portion 19 provided on the second electrode 12 may be the same or different. The charge number of the drug refers to the charge number of the ionized substance that functions as a medicinal ingredient when the drug is ionized. When the drug is positively charged overall, the charge number is a positive value, and when the drug is negatively charged overall, the charge number is a negative value. When the drug is supplied from the drug-containing portion 19 provided on the first electrode 11 in a fast-acting manner and from the drug-containing portion 19 provided on the second electrode 12 in a delayed-acting manner as described above, it is preferable that the charge number of the drug contained in the drug-containing portion 19 provided on the first electrode 11 and the charge number of the drug contained in the drug-containing portion 19 provided on the second electrode 12 are the same. Alternatively, it is preferable that the drug contained in the drug-containing portion 19 provided in the first electrode 11 and the drug contained in the drug-containing portion 19 provided in the second electrode 12 are the same.

[0044] On the other hand, the charge number of the drug contained in the drug-containing portion 19 provided on the second electrode 12 may be greater than the charge number of the drug contained in the drug-containing portion 19 provided on the first electrode 11. For example, when the potential gradient between the first electrode 11 and the third electrode 13 is the same as the potential gradient between the second electrode 12 and the third electrode 13, a drug with a higher charge number penetrates the skin more rapidly than a drug with a lower charge number. However, in the drug delivery device 1 shown in FIGS. 2 and 3, the potential gradient between the first electrode 11 and the third electrode 13 is greater than the potential gradient between the second electrode 12 and the third electrode 13, so the skin penetration of a drug with a lower charge number contained in the drug-containing portion 19 provided on the first electrode 11 can be made to be approximately the same as the skin penetration of a drug with a higher charge number contained in the drug-containing portion 19 provided on the second electrode 12. In other words, it is possible to allow multiple drugs with different charge numbers to penetrate the skin effectively.

[0045] In the drug delivery device 1 shown in Figures 4 and 5, a drug-containing portion 19 is provided on the third electrode 13, and an electrolyte-containing portion 20 is provided on the first electrode 11 and the second electrode 12. In this case, the drug contained in the drug-containing portion 19 provided on the third electrode 13 permeates toward the first electrode 11 and the second electrode 12, but the permeation of the drug into the skin from the third electrode 13 toward the first electrode 11 along the electric field lines between the third electrode 13 and the first electrode 11 is more accelerated than the permeation of the drug from the third electrode 13 toward the second electrode 12 along the electric field lines between the third electrode 13 and the second electrode 12. Therefore, the drug is rapidly supplied from the drug-containing portion 19 provided on the third electrode 13 to the first electrode 11, and the drug is slowly supplied from the drug-containing portion 19 provided on the third electrode 13 to the second electrode 12. This enables the drug to be continuously supplied to the skin for a long period of time.

[0046] Although not shown in the drawings, drug-containing portions 19 may be provided on first electrode 11, second electrode 12, and third electrode 13. In this case, it is preferable that the drug in drug-containing portions 19 provided on first electrode 11 and second electrode 12 and the drug in drug-containing portion 19 provided on third electrode 13 have a positive charge on one side and a negative charge on the other side of the medicinal component.

[0047] As shown in Figures 2 and 3, drug-containing portion 19 is preferably provided in first electrode 11 and second electrode 12. That is, drug-containing portion 19 is preferably disposed on the surfaces of first electrode 11 and second electrode 12 that are closer to the epithelial tissue, or is preferably included in first electrode 11 and second electrode 12 that are disposed on the surfaces of base sheet 2 that are closer to the epithelial tissue. By providing drug-containing portion 19 in first electrode 11 and second electrode 12, the flow of drug into the skin is more easily ensured both between first electrode 11 and third electrode 13 and between second electrode 12 and third electrode 13. Furthermore, the drug contained in drug-containing portion 19 provided in first electrode 11 can be made different from the drug contained in drug-containing portion 19 provided in second electrode 12, and various variations in drug use can be achieved.

[0048] The electrolyte-containing portion 20 is preferably provided on the third electrode 13. That is, the electrolyte-containing portion 20 is preferably disposed on the surface of the third electrode 13 closer to the epithelial tissue, or is preferably included in the third electrode 13 disposed on the surface of the base sheet 2 closer to the epithelial tissue. This can promote the penetration of the drug into the skin from the drug-containing portion 19 provided on the first electrode 11 and the second electrode 12. The electrolyte-containing portion 20 can contain an electrolyte with a lower molecular weight than the drug and which more easily penetrates the skin. Therefore, by providing the electrolyte-containing portion 20 on one of the electrodes functioning as an anode and the electrode functioning as a cathode, when a voltage is applied between the electrodes, ions having an opposite charge to the charge of the ionized substance functioning as the medicinal ingredient can be rapidly penetrated into the skin. This generates a diffusion potential due to the ions within the skin, promoting the penetration of the ionized substance functioning as the medicinal ingredient into the skin.

[0049] The drug delivery device 1 may be provided with other electrodes in addition to the first electrode 11, the second electrode 12, and the third electrode 13. Figures 6 and 7 show configuration examples of a drug delivery device provided with a first electrode, a second electrode, a third electrode, and a fourth electrode. Figure 6 shows a cross-sectional view of the drug delivery device, and Figure 7 shows a plan view of the drug delivery device shown in Figure 6 as seen from the bottom.

[0050] As shown in Figures 6 and 7, the drug delivery device 1 may have a first electrode 11, a second electrode 12, a third electrode 13, and a fourth electrode 14 arranged on a base sheet 2. In the drug delivery device 1 shown in Figures 6 and 7, the potential applied to the first electrode 11 is the same as the potential applied to the second electrode 12, the potential applied to the third electrode 13 is the same as the potential applied to the fourth electrode 14, and the potential applied to the first electrode 11 is different from the potential applied to the third electrode 13. On the base sheet 2, the separation distance between the first electrode 11 and the third electrode 13 is shorter than the separation distance between the second electrode 12 and the third electrode 13, the separation distance between the first electrode 11 and the fourth electrode 14 is shorter than the separation distance between the second electrode 12 and the fourth electrode 14, and the separation distance between the first electrode 11 and the third electrode 13 is shorter than the separation distance between the first electrode 11 and the fourth electrode 14. The drug delivery device 1 may be provided with multiple electrodes functioning as anodes and multiple electrodes functioning as cathodes, and multiple potential gradients are formed between the anodes and cathodes, achieving the same effect as the drug delivery device 1 described above.

[0051] 6 and 7, the first electrode 11 and the second electrode 12 are connected to the positive pole of the power supply unit 21, the first electrode 11 and the second electrode 12 are provided with drug-containing portions 19, the third electrode 13 and the fourth electrode 14 are connected to the negative pole of the power supply unit 21, and the third electrode 13 and the fourth electrode 14 are provided with electrolyte-containing portions 20. However, various variations are possible in the connection between the power supply unit 21 and each electrode, the arrangement of the drug-containing portions 19 or electrolyte-containing portions 20 on each electrode, the type of drug contained in the drug-containing portions 19, etc. For details, see the above explanation.

[0052] The drug delivery device 1 may be provided with more electrodes, which will be described with reference to Figures 8 and 9. Figures 8 and 9 show plan views of the drug delivery device as viewed from the bottom. Note that the power supply, control unit, and wiring unit are omitted in Figures 8 and 9.

[0053] As shown in FIG. 8 , an A-electrode group 15 consisting of a plurality of electrodes including a first electrode 11 and a second electrode 12 is disposed on a base sheet 2. The electrodes constituting the A-electrode group 15 are applied with the same potential. The A-electrode group 15 is preferably disposed on the base sheet 2 so as to be surrounded by a convex polygon 17 that does not include the third electrode 13. The convex polygon 17 is a polygon in which all interior angles of the vertices are less than 180°, and is formed so that all vertices protrude toward the outside of the polygon when viewed from the inside. The number of vertices of the convex polygon 17 is not particularly limited as long as it is three or more, and may be infinite. The convex polygon 17 may be triangular, quadrilateral, or substantially circular. The A-electrode group 15 includes all electrodes that are equipotential with the first electrode 11. The number of electrodes included in the A-electrode group 15 is not particularly limited as long as it is two or more. In FIG. 8 , the A-electrode group 15 is shown surrounded by a convex rectangle.

[0054] In the drug delivery device 1 shown in Figure 8, drug-containing portions 19 are preferably provided on multiple electrodes constituting electrode group A 15. This facilitates the flow of drug into the skin from drug-containing portions 19 provided on multiple electrodes constituting electrode group A 15 toward third electrode 13, making it easier to continuously supply drug to the skin over a long period of time, for example. Electrode group A 15 may include multiple electrodes spaced from third electrode 13 by the same distance. An electrolyte-containing portion 20 is preferably provided on third electrode 13.

[0055] In FIG. 8 , only one electrode having the same potential as the third electrode 13 is provided, i.e., a plurality of anodes or cathodes are provided and only one of the other is provided. However, when a plurality of electrodes having the same potential as the third electrode 13 are provided, i.e., when a plurality of anodes and a plurality of cathodes are provided, it is preferable to provide the electrodes as follows. As shown in Figure 9, an A electrode group 15 consisting of a plurality of electrodes including a first electrode 11 and a second electrode 12, and a B electrode group 16 consisting of a plurality of electrodes including a third electrode 13 and a fourth electrode 14 are arranged on a base sheet 2, the same potential is applied to each electrode constituting the A electrode group 15, and the same potential is applied to each electrode constituting the B electrode group 16, and on the base sheet 2, the A electrode group 15 can be surrounded by a convex polygon 17, and the B electrode group 16 can be surrounded by a convex polygon 18, and it is preferable that they are arranged so that the area formed by the convex polygon 17 surrounding the A electrode group 15 and the area formed by the convex polygon 18 surrounding the B electrode group 16 do not overlap each other. The B electrode group 16 includes all electrodes at the same potential as the third electrode 13. The number of electrodes included in the B electrode group 16 is not particularly limited as long as it is two or more.

[0056] When multiple electrodes are arranged as shown in Figures 8 and 9, the area on the base sheet 2 where the electrode(s) functioning as anodes are arranged and the area where the electrode(s) functioning as cathodes are arranged are not mixed and are arranged separately, and can be separated, for example, by a straight line. By arranging the A electrode group 15 and the third electrode 13 or the A electrode group 15 and the B electrode group 16 in this manner, the separation distance between the electrodes included in the A electrode group 15 and the third electrode 13 or the B electrode group 16 can be greatly changed without requiring a large area of ​​the base sheet 2. In other words, the difference between the shortest separation distance and the longest separation distance between the electrodes included in the A electrode group 15 and the third electrode 13 or the B electrode group 16 can be made large. This makes it easier to adjust the penetration of the drug from the drug-containing portion 19 into the skin.

[0057] In the drug delivery device 1 shown in FIG. 9 , drug-containing portions 19 are provided on multiple electrodes constituting the A electrode group 15, and electrolyte-containing portions 20 are provided on multiple electrodes constituting the B electrode group 16, but the arrangement of the drug-containing portions 19 and the electrolyte-containing portions 20 is not limited to this. In the drug delivery device 1 shown in FIG. 8 , drug-containing portions 19 are provided on multiple electrodes constituting the A electrode group 15, and electrolyte-containing portions 20 are provided on the third electrode 13, but the arrangement of the drug-containing portions 19 and the electrolyte-containing portions 20 is not limited to this. In the drug delivery device 1 shown in FIGS. 8 and 9 , various variations are possible regarding the connection between the power supply unit 21 and each electrode, the arrangement of the drug-containing portions 19 or electrolyte-containing portions 20 on each electrode, the type of drug contained in the drug-containing portions 19, etc. For details, please refer to the above explanation.

[0058] The separation distance between the A electrode group 15 and the third electrode 13 is preferably the same as or longer than the separation distance between the electrodes included in the A electrode group 15. Furthermore, the separation distance between the A electrode group 15 and the B electrode group 16 is preferably the same as or longer than the separation distance between the electrodes included in the A electrode group 15 and the separation distance between the electrodes included in the B electrode group 16. The separation distance between the A electrode group 15 and the third electrode 13 refers to the shortest separation distance between the electrodes included in the A electrode group 15 and the third electrode 13. The separation distance between the A electrode group 15 and the B electrode group 16 refers to the shortest separation distance between the electrodes included in the A electrode group 15 and the electrodes included in the B electrode group 16. In the drug delivery device 1 shown in Figures 2 to 5, the separation distance between the first electrode 11 and the third electrode 13 is preferably the same as or longer than the separation distance between the first electrode 11 and the second electrode 12. In the drug delivery device 1 shown in Figures 6 and 7, the separation distance between the first electrode 11 and the third electrode 13 is preferably equal to or longer than the separation distance between the first electrode 11 and the second electrode 12 and the separation distance between the third electrode 13 and the fourth electrode 14. This arrangement of the electrodes eliminates any combination of an electrode functioning as an anode and an electrode functioning as a cathode in which the separation distance between the two electrodes is extremely short. This prevents current from flowing unevenly between specific electrodes, facilitating the delivery of drugs from the drug-containing portion 19 into the skin between multiple electrodes. The separation distance between electrodes included in electrode group A 15 (or electrode group B 16) refers to the separation distance between each electrode included in electrode group A 15 (or electrode group B 16) and its nearest neighboring electrode.

[0059] The separation distance between the A electrode group 15 and the third electrode 13 may be 1.0 times or more, 1.2 times or more, or 1.5 times or more the separation distance between the electrodes included in the A electrode group 15. On the other hand, if the separation distance between the A electrode group 15 and the third electrode 13 is too large, there is a risk of increasing electrical resistance via skin tissue between the A electrode group 15 and the third electrode 13. Therefore, the separation distance between the A electrode group 15 and the third electrode 13 is preferably 5.0 times or less, more preferably 4.0 times or less, and even more preferably 3.0 times or less the separation distance between the electrodes included in the A electrode group 15. From the same perspective, the separation distance between the A electrode group 15 and the B electrode group 16 may be 1.0 times or more, 1.2 times or more, or 1.5 times or more the separation distance between the electrodes included in the A electrode group 15 and the electrodes included in the B electrode group 16. Furthermore, the separation distance between electrode group A 15 and electrode group B 16 is preferably 5.0 times or less, more preferably 4.0 times or less, and even more preferably 3.0 times or less of the separation distance between the electrodes included in electrode group A 15 and the electrodes included in electrode group B 16.

[0060] The arrangement of the electrodes included in the A electrode group 15 and the third electrode 13 is not limited to the form described above, and for example, the third electrode 13 may be arranged within the arrangement area of ​​the electrodes included in the A electrode group 15. The arrangement of the electrodes included in the A electrode group 15 and the electrodes included in the B electrode group 16 is also not limited to the form described above, and for example, the arrangement area of ​​the electrodes included in the A electrode group 15 and the arrangement area of ​​the electrodes included in the B electrode group 16 may overlap.

[0061] Among the electrodes arranged on the base sheet 2, electrodes with the same potential can be determined by whether or not the electrodes are connected to the power supply unit 21 by the wiring unit 23. Electrodes that are connected to the power supply unit 21 by the wiring unit 23 can be determined to have the same potential. On the other hand, two electrodes with different potentials can be determined by whether one electrode is connected to the positive pole of the power supply unit 21 and the other electrode is connected to the negative pole of the power supply unit 21.

[0062] It is preferable that at least one electrode included in electrode group A 15 be separated from third electrode 13 at the shortest distance at multiple locations. By arranging the electrode in electrode group A 15 and the third electrode 13 in this manner, more current flows easily between the electrode in electrode group A 15 and the third electrode 13, promoting drug penetration from drug-containing portion 19 into the skin. In the drug delivery device 1 shown in Figures 3, 5, and 7, the edge of first electrode 11 facing third electrode 13 is parallel to the edge of third electrode 13 facing first electrode 11, so that first electrode 11 is separated from third electrode 13 at the shortest distance at multiple locations. Furthermore, the edge of second electrode 12 facing third electrode 13 is parallel to the edge of third electrode 13 facing second electrode 12, so that second electrode 12 is separated from third electrode 13 at the shortest distance at multiple locations.

[0063] At least one electrode included in electrode group A 15 is preferably separated at a minimum distance from at least one electrode included in electrode group B 16 at multiple locations, and at least one electrode included in electrode group B 16 is preferably separated at a minimum distance from at least one electrode included in electrode group A 15 at multiple locations. By arranging the electrode in electrode group A 15 and the electrode in electrode group B 16 in this manner, more current flows more easily between the electrode in electrode group A 15 and the electrode in electrode group B 16, and the penetration of the drug from drug-containing portion 19 into the skin is promoted.

[0064] Of the electrodes included in electrode group A 15, at least one electrode, excluding the electrode arranged closest to third electrode 13, may be arranged so that no other electrodes are located on the straight line segment that forms the shortest distance between that electrode and third electrode 13. If multiple straight line segments that form the shortest distance can be set, it is sufficient that the electrodes are arranged so that no other electrodes are located on at least one of the straight line segments. By arranging that electrode in electrode group A 15 and third electrode 13 in this manner, a large potential gradient can be achieved between that electrode in electrode group A 15 and third electrode 13, making it easier for electricity to flow between that electrode in electrode group A 15 and third electrode 13, and promoting the penetration of the drug from drug-containing portion 19 into the skin.

[0065] The above will be described with reference to FIG. 10 , where a first electrode 11 and a second electrode 12 are provided as electrode group A 15. In FIG. 10 , among the electrodes included in electrode group A 15, first electrode 11 is arranged closest to third electrode 13, and second electrode 12 is arranged farther from third electrode 13 than first electrode 11. However, first electrode 11 does not exist on the line segment defining the shortest distance between second electrode 12 and third electrode 13. That is, the line segment defining the shortest distance between second electrode 12 and third electrode 13 can be set without intersecting with first electrode 11. By arranging second electrode 12 in this manner, the electric field lines between second electrode 12 and third electrode 13 extend linearly, thereby increasing the potential gradient between second electrode 12 and third electrode 13. This facilitates penetration of the drug from drug-containing portion 19 into the skin between second electrode 12 and third electrode 13.

[0066] From the same viewpoint as above, at least one of the electrodes included in the A electrode group 15, excluding the electrode arranged closest to the B electrode group 16, may be arranged so that no other electrode is located on the straight line segment that forms the shortest distance between the electrode included in the A electrode group 15 and the B electrode group 16. Furthermore, at least one of the electrodes included in the B electrode group 16, excluding the electrode arranged closest to the A electrode group 15, may be arranged so that no other electrode is located on the straight line segment that forms the shortest distance between the electrode included in the B electrode group 16 and the A electrode group 15.

[0067] The power supply unit 21, the control unit 22, and the wiring unit 23 will now be described. The power supply unit 21 is electrically connected to the electrodes. The power supply unit 21 can be disposed on the base sheet 2, for example. The power supply unit 21 includes a battery and has a positive electrode and a negative electrode. One of the positive electrode and the negative electrode is connected to an electrode included in the A electrode group 15 (e.g., the first electrode 11 and the second electrode 12), and the other is connected to an electrode included in the B electrode group 16 (e.g., the third electrode 13 or even the fourth electrode 14). When a drug ionizes to form cations or ionized substances that are positively charged overall, it is preferable that the positive electrode be connected to the electrode on which the drug-containing portion 19 is provided. When a drug ionizes to form an anion or ionized substances that are negatively charged overall, it is preferable that the negative electrode be connected to the electrode on which the drug-containing portion 19 is provided.

[0068] The battery used in the power supply unit 21 may be a primary battery or a secondary battery. The primary battery is preferably a lithium battery, and more preferably a coin-type lithium battery. This reduces costs and is particularly suitable when the drug delivery device 1 is disposable. The power supply unit 21 may have multiple batteries, for example, two coin-type lithium batteries connected in series. The applied voltage of the power supply unit 21 is preferably 0.1 V or more and 6 V or less. The current density is 0.01 mA / cm. ２ 0.4mA / cm or more ２ It is preferable that:

[0069] The drug delivery device 1 preferably includes a control unit 22 that controls the current flow from the power supply unit 21. The control unit 22 can set the type of current flow between the electrodes. The control unit 22 can be disposed on, for example, the base sheet 2. Examples of current flow include direct current (DC), pulsed current, and pulse depolarized current. DC current is a type of current flow that applies a predetermined direct current between the electrodes. Pulse current is a type of current flow that applies predetermined repetitive pulses between the electrodes. Pulse depolarized current is a type of current flow that applies predetermined repetitive pulses between the electrodes and forcibly discharges residual charge during pulse pauses. Therefore, the control unit 22 preferably includes a DC output circuit, a pulse output circuit, or a pulse depolarized output circuit. The control unit 22 may include only one of these circuits or two or more of them. Among these, pulsed current or pulse depolarized current is preferred as the type of current flow from the viewpoint of efficient drug delivery. Therefore, the control unit 22 preferably includes at least a pulse output circuit or a pulse depolarized output circuit.

[0070] The pulse frequency when applying pulsed or pulse depolarized current is preferably 0.5 Hz or more and 50 Hz or less. This ensures skin permeability of the drug while reducing irritation of epithelial tissue caused by voltage application. The pulse frequency of the pulse voltage is not limited to the above range, and may be, for example, 0.5 Hz or more and 5,000 kHz or less, 0.5 Hz or more and 50 kHz or less, or 0.5 Hz or more and 5 kHz or less. The pulse frequency refers to the frequency of the pulse voltage applied between the electrodes.

[0071] The pulse width is preferably 10 ms or more and 1000 ms or less. The pulse width corresponds to the time during which the output is on within one cycle of pulsed or pulse depolarized current. The pulse width is preferably 40% or more of one cycle, more preferably 45% or more, and is preferably 60% or less, more preferably 55% or less.

[0072] The waveform of the pulse voltage is not particularly limited, and examples thereof include a square wave, a triangular wave, a sawtooth wave, a sine wave, and any combination thereof. Among these, the waveform of the pulse voltage is preferably a square wave.

[0073] The control unit 22 preferably controls the voltage to output the pulses, but may also control the current to output the pulses.

[0074] The control unit 22 may have a processor and a memory. For example, the control unit 22 may be configured to switch between DC output, pulse output, and pulse depolarization output using the processor in accordance with a program stored in the memory. Examples of the memory include an SSD, HDD, and ROM.

[0075] The control unit 22 may have a circuit capable of changing the direction of current. For example, the control unit 22 may be configured such that a processor changes the direction of current using the circuit in accordance with a program stored in memory. This allows for alternating switching between anodes and cathodes. For example, the drug delivery device 1 may be configured such that the control unit 22 can switch from a mode in which a voltage is applied so that the electrodes in the A electrode group 15 serve as anodes and the electrodes in the B electrode group 16 serve as cathodes to a mode in which a voltage is applied so that the electrodes in the A electrode group 15 serve as cathodes and the electrodes in the B electrode group 16 serve as anodes. When the electrodes in the A electrode group 15, the electrodes in the B electrode group 16, or both are active electrodes, this switching of electrodes can regenerate consumed electrodes.

[0076] Each function of the control unit 22 may be realized by, for example, a processor, an application specific integrated circuit (ASIC), a digital signal processor (DSP), a field programmable gate array (FPGA), or a combination thereof. The control unit 22 may also include a constant voltage diode or a constant current diode.

[0077] The drug delivery device 1 preferably has a wiring unit 23 that electrically connects each electrode to the power supply unit 21. The wiring unit 23 preferably electrically connects the power supply unit 21 to the control unit 22 and also electrically connects the control unit 22 to the electrodes. This allows the control unit 22 to control the flow of electricity from the power supply unit 21 to the electrodes. The control unit 22 may be provided so as to be electrically connected to at least one of the electrodes that function as an anode and the electrodes that function as a cathode.

[0078] The wiring portion 23 may have a thin film, plate, or cable shape. Examples of thin film wiring include printed wiring produced by printing, etching, or the like. Examples of printing include screen printing, offset printing, and inkjet printing, and the wiring portion 23 can be formed by printing using ink containing a conductive material. Examples of cable wiring include metal wires coated with an insulating film. The wiring portion 23 is preferably made of a conductor, and for details of the conductor that constitutes the wiring portion 23, see the description of the conductor that constitutes the electrode above.

[0079] The wiring portion 23 is disposed, for example, on the base sheet 2. In this case, the wiring portion 23 is preferably disposed inside or on the upper surface of the base sheet 2. The wiring portion 23 can be provided on the base sheet 2 by, for example, printing. The wiring portion 23 may also be fixed to the base sheet 2 by an adhesive.

[0080] As shown in Figures 11 and 12, the drug delivery device 1 may have a cover sheet 3 and a shape-retaining sheet 4. Figures 11 and 12 show configuration examples in which a cover sheet and a shape-retaining sheet are further provided in the drug delivery device shown in Figures 2 and 3, where Figure 11 shows a cross-sectional view of the drug delivery device and Figure 12 shows a plan view of the drug delivery device shown in Figure 11 as seen from the bottom side.

[0081] The cover sheet 3 is preferably placed on the upper side of the base sheet 2, and is provided so as to cover the entire base sheet 2 and be larger than the base sheet 2. The cover sheet 3 preferably extends outward beyond the outer edge of the base sheet 2. By providing the cover sheet 3, the drug delivery device 1 can be protected by the cover sheet 3, and the drug delivery device 1 can be stably attached to the skin.

[0082] The shape-retaining sheet 4 is disposed below the base sheet 2, and an opening 5 is provided in the portion where the drug-containing portion 19 or the electrolyte-containing portion 20 is disposed. The drug-containing portion 19 and the electrolyte-containing portion 20 are disposed so as to be exposed from the opening 5 of the shape-retaining sheet 4. By providing the shape-retaining sheet 4, the drug-containing portion 19 and the electrolyte-containing portion 20 can be more easily held stably.

[0083] The cover sheet 3 and the shape-retaining sheet 4 are preferably made of an insulating material and can be made of a sheet that can be used for the base sheet 2. The sheets that make up the drug delivery device 1 are preferably fixed to each other with an adhesive. However, only one of the cover sheet 3 and the shape-retaining sheet 4 may be provided.

[0084] The drug delivery device 1 preferably has an adhesive portion on the underside, which allows the drug delivery device 1 to be attached to the skin and stably attached to the skin. The adhesive portion is an exposed portion on the underside of the drug delivery device 1, and can be provided on the underside of the base sheet 2, the underside of the cover sheet 3, or the underside of the shape-retaining sheet 4.

[0085] The drug delivery device 1 can be placed in epithelial tissue for use. The epithelial tissue on which the drug delivery device 1 is placed may be epithelial tissue of the skin or epithelial tissue of the mucosa, but is preferably epithelial tissue of the skin. The drug delivery device 1 is preferably attached to epithelial tissue of the arm, hand, leg, foot, back, abdomen, chest, face, head, or oral cavity, and more preferably to epithelial tissue of or near a joint such as an elbow, shoulder, or wrist. Furthermore, the drug delivery device 1 is preferably configured to allow the drug to penetrate at least the tight junctions of the epithelial tissue. The penetration of the drug into the epithelial tissue can be adjusted, for example, by controlling the voltage.

[0086] The drug delivery device 1 is preferably attached to the epithelial tissue by adhesion, wrapping, adsorption, or placement, and more preferably attached to the epithelial tissue by adhesion. Examples of attachment include adhesion using an adhesive portion. Examples of wrapping include wrapping using a band. Examples of adsorption include adsorption using a porous body. Examples of placement include placement using a medical clip. The drug delivery device 1 is preferably placed in the epithelial tissue of humans, but may also be placed in the epithelial tissue of animals other than humans, such as dogs, cats, horses, and cows.

[0087] Although various embodiments of the drug delivery device of the present invention have been described above, the configurations of the drug delivery device described above can be implemented by arbitrarily combining or substituting multiple embodiments. For example, the configurations of providing a cover sheet or a shape-retaining sheet shown in Figures 11 and 12 can be applied to any of the embodiments described above.

[0088] This application claims the benefit of priority based on Japanese Patent Application No. 2024-051371, filed on March 27, 2024. The entire contents of the specification of Japanese Patent Application No. 2024-051371, filed on March 27, 2024, are incorporated herein by reference.

[0089] 1: Drug delivery device 2: Base sheet 3: Cover sheet 4: Shape-retaining sheet 5: Opening 11: First electrode 12: Second electrode 13: Third electrode 14: Fourth electrode 15: Electrode group A 16: Electrode group B 17: Convex polygon surrounding electrode group A 18: Convex polygon surrounding electrode group B 19: Drug-containing portion 20: Electrolyte-containing portion 21: Power supply portion 22: Control portion 23: Wiring portion 31: Skin 32: Epithelial tissue

Claims

1. A drug delivery device comprising: a base sheet; a first electrode, a second electrode, and a third electrode arranged on the base sheet; and a drug-containing portion containing a drug, wherein the potential applied to the first electrode is the same as the potential applied to the second electrode, the potential applied to the first electrode is different from the potential applied to the third electrode, and the separation distance between the first electrode and the third electrode on the base sheet is shorter than the separation distance between the second electrode and the third electrode.

2. A drug delivery device as described in claim 1, wherein a fourth electrode is further disposed on the base sheet, the potential applied to the third electrode and the potential applied to the fourth electrode are the same, and the separation distance between the first electrode and the fourth electrode on the base sheet is shorter than the separation distance between the second electrode and the fourth electrode, and the separation distance between the first electrode and the third electrode is shorter than the separation distance between the first electrode and the fourth electrode.

3. A drug delivery device as described in claim 1, wherein an A electrode group consisting of a plurality of electrodes including the first electrode and the second electrode is arranged on the base sheet, the same potential is applied to each electrode constituting the A electrode group, and the A electrode group is arranged on the base sheet so as to be surrounded by a convex polygon that does not include the third electrode.

4. The drug delivery device of claim 2, wherein an A electrode group consisting of a plurality of electrodes including the first electrode and the second electrode, and a B electrode group consisting of a plurality of electrodes including the third electrode and the fourth electrode are arranged on the base sheet, the same potential is applied to each of the electrodes constituting the A electrode group, and the same potential is applied to each of the electrodes constituting the B electrode group, and on the base sheet, the A electrode group and the B electrode group can each be surrounded by a convex polygon, and the area formed by the convex polygon surrounding the A electrode group and the area formed by the convex polygon surrounding the B electrode group are arranged so as not to overlap each other.

5. A drug delivery device according to any one of claims 1 to 4, wherein the drug-containing portion further contains water and a moisture-retaining substance, and the drug is ionized.

6. A drug delivery device according to any one of claims 1 to 4, wherein the drug delivery device is placed in epithelial tissue, and the drug-containing portion is placed on the surfaces of the first electrode and the second electrode that are closer to the epithelial tissue, and / or on the surface of the third electrode that is closer to the epithelial tissue.

7. A drug delivery device according to any one of claims 1 to 4, which is placed in epithelial tissue, and the drug-containing portion is placed on the surface of the first electrode and the second electrode that is closer to the epithelial tissue.

8. A drug delivery device according to any one of claims 1 to 4, wherein the drug delivery device is placed in epithelial tissue, the first electrode, the second electrode and the third electrode are placed on the surface of the base sheet closer to the epithelial tissue, and the drug-containing portion is contained in the first electrode and the second electrode and / or the third electrode.

9. A drug delivery device according to any one of claims 1 to 4, wherein the drug delivery device is placed in epithelial tissue, the first electrode, the second electrode and the third electrode are placed on the surface of the base sheet that is closer to the epithelial tissue, and the drug-containing portion is contained in the first electrode and the second electrode.

10. The drug delivery device of claim 7, further comprising an electrolyte-containing portion containing water, a moisture-retaining substance, and an electrolyte, the electrolyte-containing portion being disposed on the surface of the third electrode closer to the epithelial tissue, or being included in the third electrode disposed on the surface of the base sheet closer to the epithelial tissue.

11. The drug delivery device of claim 9, further comprising an electrolyte-containing portion containing water, a moisture-retaining substance, and an electrolyte, the electrolyte-containing portion being disposed on the surface of the third electrode closer to the epithelial tissue, or being included in the third electrode disposed on the surface of the base sheet closer to the epithelial tissue.

12. The drug delivery device according to any one of claims 1 to 4, further comprising a power supply unit and a control unit that controls the flow of electricity from the power supply unit.

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