Drug delivery device

Abstract

Provided is a drug delivery device capable of improving percutaneous absorption efficiency of a drug.　A drug delivery device (100) has: a drug-containing part (30) that contains a drug; a base material sheet (10); and a first electrode (21) and a second electrode (22) that are disposed on the base material sheet (10). The first electrode (21) and / or the second electrode (22) has a convex part (20) that is convex on the side opposite to the surface facing the base material sheet (10). The potential applied to the first electrode (21) differs from the potential applied to the second electrode (22).

Description

Drug Delivery Devices

[0001] The present invention relates to a drug delivery device.

[0002] One method for administering a drug to the body is transdermal absorption, in which the drug is absorbed into the body through the skin. Iontophoresis, in which a voltage is applied to the skin using electrodes, supplies a drug placed between the electrode and the skin through the skin into the body. For example, Patent Document 1 discloses a transdermal or transmucosal drug delivery device for use in iontophoresis, which is configured to apply a combination of pulse depolarized current and at least one of direct current and pulse current.

[0003] International Publication No. 1999 / 000157

[0004] However, conventional drug delivery devices such as those described in Patent Document 1 have room for improvement in terms of more efficient administration of drugs into the body. Therefore, an object of the present invention is to provide a drug delivery device that can improve the transdermal absorption efficiency of drugs by using electrodes with convex portions.

[0005] The drug delivery device according to the embodiment of the present invention that can solve the above problems is as follows: [1] A drug delivery device comprising: a drug-containing portion containing a drug, a base sheet, and a first electrode and a second electrode disposed on the base sheet, wherein the first electrode and / or the second electrode have a convex portion that is convex on the side opposite to the surface facing the base sheet, and a potential applied to the first electrode and a potential applied to the second electrode are different.

[0006] The drug delivery device is used by placing it on the skin so that the side of the base sheet on which the electrodes are located faces the skin. Since at least one of the first and second electrodes has a convex portion, the first and / or second electrodes can be pressed more firmly into the skin. The drug delivery device applies a current between the first and second electrodes, which are given different potentials, to press the drug in the drug-containing portion into the skin or promote the movement of the drug within the skin. Therefore, the stronger pressing of the first and / or second electrodes into the skin can increase the penetration of the drug into the skin. As a result, the efficiency of transdermal drug absorption can be improved.

[0007] The drug delivery device is preferably any one of the following [2] to [8]. [2] The drug delivery device according to [1], wherein the first electrode has the convex portion that satisfies the following requirement (1), and / or the second electrode has the convex portion that satisfies the following requirement (2). Requirement (1) In the thickness direction of the base sheet, the surface of the base sheet on which the first electrode is arranged is spaced apart from the surface of the base sheet by a height T1 ０ and the maximum height of the first electrode is T1 １００ When the maximum height T1 １００ 95% of the height T1 ９５ The area A1 defined by the outline of the first electrode ９５ is the height T1 ０ The area A1 defined by the outline of the first electrode ０ Requirement (2) In the thickness direction of the base sheet, the surface of the base sheet on which the second electrode is disposed is smaller than a height T2 ０ and the maximum height of the second electrode is T2 １００ When the maximum height T2 １００ 95% of the height T2 ９５ The area A2 defined by the outline of the second electrode ９５ is the height T2 ０ The area A2 defined by the outline of the second electrode ０ [3] When the first electrode satisfies the requirement (1), the area A1 ９５ is the area A1０ and when the second electrode satisfies the requirement (2), the area A2 ９５ is the area A2 ０ [4] The drug delivery device according to any one of [1] to [3], wherein the first electrode and the second electrode have the convex portion. [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 placed on the skin so that the side of the base sheet on which the first electrode and the second electrode are located faces the skin, and the drug-containing portion is located on the surface of the first electrode closest to the skin or the surface of the second electrode closest to the skin, or the drug-containing portion is contained in the first electrode or the second electrode. [7] The drug delivery device according to any one of [1] to [6], further comprising an electrolyte-containing portion containing water, a moisture-retaining substance, and an electrolyte, wherein the drug-containing portion is disposed on a surface of the first electrode closer to the skin or is included in the first electrode, and the electrolyte-containing portion is disposed on a surface of the second electrode closer to the skin, or the drug-containing portion is disposed on a surface of the second electrode closer to the skin or is included in the second electrode, and the electrolyte-containing portion is disposed on the surface of the first electrode closer to the skin. [8] The drug delivery device according to any one of [1] to [7], further comprising a power supply unit and a control unit that controls the flow of electricity from the power supply unit.

[0008] According to the drug delivery device, the first electrode and / or the second electrode are pressed strongly into the skin, thereby increasing the penetration of the drug into the skin, thereby improving the efficiency of transdermal absorption of the drug.

[0009] 2 is a diagram schematically illustrating the basic structure of a drug delivery device according to one embodiment of the present invention. FIG. 3 is a plan view of a drug delivery device according to one embodiment of the present invention. FIG. 4 is a cross-sectional view taken along III-III in FIG. 2. FIG. 5 is a perspective view of a substrate and an electrode of a drug delivery device according to one embodiment of the present invention. FIG. 6 is a perspective view showing a modification of the perspective view of FIG. 4. FIG. 7 is a perspective view showing another modification of the perspective view of FIG. 4. FIG. 8 is a perspective view showing yet another modification of the perspective view of FIG. 4. FIG. 9 is a perspective view showing yet another modification of the perspective view of FIG. 4.

[0010] The present invention will be described below based on the embodiments, but the present invention is not limited to the following embodiments and can be implemented with appropriate modifications within the scope of the above and below-described purposes, and all such modifications are included 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, please refer to the specification or 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.

[0011] The drug delivery device according to the embodiment has a drug-containing portion containing a drug, a base sheet, and a first electrode and a second electrode arranged on the base sheet, and the first electrode and / or the second electrode has a convex portion that is convex on the side opposite to the surface facing the base sheet, and the potential applied to the first electrode and the potential applied to the second electrode are different.

[0012] In a drug delivery device, a voltage is applied to the electrodes to pass a weak current through the skin, which causes an electrical repulsive action or electroosmotic flow, which pushes the drug in the drug-containing portion into the skin or promotes the movement of the drug within the skin, thereby allowing the drug to be absorbed transdermally. In this case, the first electrode and / or the second electrode have a convex portion, which allows the first electrode and / or the second electrode, i.e., the electrode having the convex portion, to be more strongly pressed into the skin, thereby increasing the permeability of the drug into the skin. As a result, the efficiency of transdermal drug absorption can be improved.

[0013] Hereinafter, a drug delivery device according to an embodiment of the present invention will be described with reference to FIGS. 1 to 10. FIG. 1 is a diagram illustrating the basic structure of a drug delivery device according to one embodiment. FIG. 1 is a diagram illustrating the drug delivery device placed on the skin surface, but omits the base sheet placed on the opposite side of the skin surface relative to the electrodes. FIG. 2 is a plan view of a drug delivery device according to one embodiment. FIG. 2 shows a plan view of the drug delivery device placed on the skin, viewed from the side opposite the side facing the skin. FIG. 3 is a cross-sectional view taken along III-III in FIG. 2. That is, in FIGS. 1 and 3, the electrode side is drawn downwards on the paper. FIGS. 4 to 10 are perspective views of the base sheet and electrodes of drug delivery devices according to different embodiments, as viewed from the electrode side. That is, in FIGS. 4 to 10, the electrode side is drawn upwards on the paper. Thus, the up-down relationship between the base material and the electrodes on the paper is reversed between FIGS. 1 and 3 and FIGS. 4 to 10.

[0014] 1, 2, 3, and 4, the drug delivery device 100 includes a drug-containing portion 30 containing a drug, a base sheet 10, and a first electrode 21 and a second electrode 22 disposed on the base sheet 10. The first electrode 21 and / or the second electrode 22 has a convex portion 20 that is convex on the side opposite to the surface facing the base sheet 10, and a potential applied to the first electrode 21 is different from a potential applied to the second electrode 22. The first electrode 21 and the second electrode 22 may be collectively referred to as electrodes.

[0015] 3 to 10, the base sheet 10 has a longitudinal direction x and a thickness direction t. In this specification, the thickness direction t is defined as the direction from the base sheet 10 toward the electrodes.

[0016] The phrase "the first electrode 21 and the second electrode 22 are arranged on the base sheet 10" means that the first electrode 21 and the second electrode 22 are arranged so as to be in direct or indirect contact with the base sheet 10, and the phrase "on the base sheet 10" does not refer to an up-down relationship in the vertical direction relative to the base sheet 10. That is, the drug delivery device 100 has a configuration in which the first electrode 21 and the second electrode 22 are arranged on one side of the base sheet 10 in the thickness direction t.

[0017] 1 and 2 , the drug delivery device 100 is placed on the skin surface 201 so that the side of the base sheet 10 on which the first electrode 21 and the second electrode 22 are arranged faces the skin 200. The drug delivery device 100 may be placed on the skin surface 201 so that the base sheet 10 is vertically above the electrodes, or may be placed on the skin surface 201 so that the base sheet 10 is vertically below the electrodes, or the drug delivery device 100 may be placed on the skin surface 201 in any other orientation.

[0018] Preferably, the drug delivery device 100 further includes a power supply unit 50 and a control unit 60 that controls the application of electricity from the power supply unit 50. The drug delivery device 100 also preferably includes a wiring unit 70 that electrically connects each electrode to the power supply unit 50. This allows, for example, a voltage to be applied to the first electrode 21 and the second electrode 22 from the power supply unit 50 via the wiring unit 70 under the control of the control unit 60. This voltage application allows the drug to be delivered from the drug-containing portion 30 to the inside of the skin 202, for example, along the direction of the arrow in FIG. 1 . The power supply unit 50, the control unit 60, and the wiring unit 70 will be described in detail below.

[0019] In the drug delivery device 100, the potentials applied to the first electrode 21 and the second electrode 22 are different. In this specification and claims, "different potentials applied to the electrodes" refers to a state in which voltages are applied to the electrodes with a difference in potential between them. On the other hand, "same potentials applied to the electrodes" refers to a state in which voltages are applied to the electrodes with the same potential between them. That is, regardless of factors that change the equipotential due to the length of the wiring, the potentials applied to the electrodes are used to determine whether the potentials are different or the same. For example, by applying a voltage such that the first electrode 21 is positive and the second electrode 22 is negative, the potentials applied to the first electrode 21 and the second electrode 22 will be different. By applying a voltage to the electrodes in this manner, a drug can be delivered from the drug-containing portion 30 of the drug delivery device 100 to the inside of the skin 202.

[0020] 1 and 3, the drug-containing portion 30 is preferably adjacent to the first electrode 21 or the second electrode 22. This makes it easier for the drug to be delivered from the drug-containing portion 30 to the inside of the skin 202 when a voltage is applied. The degree of penetration of the drug into the inside of the skin 202 can be adjusted, for example, by controlling the potential applied to the electrodes. The configuration of the drug-containing portion 30 will be described in detail later.

[0021] 4 to 10 , at least one of the first electrode 21 and the second electrode 22 has a convex portion 20 that is convex on the side opposite to the surface facing the base sheet 10. Because at least one of the first electrode 21 and the second electrode 22 has the convex portion 20, the electrode having the convex portion 20 is pressed more strongly into the skin 200 even with the same pressing force. This makes it easy to increase the contact area between the drug-containing portion 30 adjacent to the electrode and the skin surface 201, thereby increasing the permeability of the drug into the interior of the skin 202.

[0022] An electrode being convex means that the electrode has a shape in which the area defined by the outline of the electrode in a plane parallel to the base sheet 10 decreases along the thickness direction t of the base sheet 10. Conversely, an electrode being not convex means that the electrode has a shape in which the area defined by the outline of the electrode in a plane parallel to the base sheet 10 does not decrease along the thickness direction t of the base sheet 10, such as a cylindrical or polygonal prism-shaped electrode having a central axis parallel to the thickness direction t.

[0023] As shown in FIG. 4 , the convex portion 20 may have a hemispherical convex shape. Also, as shown in FIG. 5 , the convex portion 20 may have a hemispherical shell convex shape. By having the convex portion 20 be hemispherical or hemispherical shell-shaped, the surface of the electrode that connects to the skin surface 201 can be curved, allowing the electrode to be pressed in while reducing damage to the skin 200. While FIGS. 4 and 5 show a configuration in which the outline shape of the portion where the electrode connects to the base sheet 10 is circular, the shape of this portion is not limited to circular and may be any shape, such as a triangle, a polygon such as a rectangle, a polygon with rounded corners, an ellipse, a partial circle, or an irregular shape. Furthermore, the convex portion 20 does not need to be a perfect hemispherical or hemispherical shell-shaped portion; it need only be convex on the side opposite the surface facing the base sheet 10.

[0024] As shown in Figures 6 and 7, the convex portion 20 may be formed on a base and have a proximal end such that the area defined by the contour of the electrode in a plane parallel to the base sheet 10 is smaller than that of the base. It is preferable that the area defined by the contour of the electrode in a plane parallel to the base sheet 10 does not change along the thickness direction t of the base sheet 10. By forming a convex shape on the base with a proximal end smaller than that of the base, the base stably connects the electrode to the base sheet 10, while the convex shape with a proximal end smaller than that of the base can easily and strongly press the electrode into the skin 200. Examples of convex shapes formed on the base include hemispheres, hemispherical shells, cylinders, polygonal prisms, and rounded polygonal prisms, but the shape is not particularly limited. While Figures 6 and 7 illustrate a cylindrical shape as the shape of the base, the shape of the base may be any shape, such as a polygonal prism, a rounded polygonal prism, a portion of a cylinder, or an irregular shape.

[0025] As shown in Figure 8, the convex portion 20 may be an arched convex shape in which an arch is formed so that the area defined by the contour of the electrode in a plane perpendicular to the longitudinal direction x of the base sheet 10 does not change along the longitudinal direction x. Since the area defined by the contour of the electrode in a plane perpendicular to the longitudinal direction x does not change along the longitudinal direction x, it is easy to increase the contact area between the drug-containing portion 30 adjacent to the electrode and the skin surface 201. Furthermore, the degree of indentation can be controlled by adjusting the curvature of the arch shape, such that a stronger curvature of the arch shape results in a stronger indentation, and a gentler curvature of the arch shape results in a weaker indentation. While Figure 8 shows a configuration in which the contour shape of the portion where the electrode connects to the base sheet 10 is rectangular, the shape of this portion is not limited to a rectangle and may be any shape, such as a triangle, a hexagon, or other polygon, a rounded polygon, an ellipse, a circle, a portion of a circle, or an irregular shape.

[0026] As shown in Figure 9, the convex portion 20 may be a plurality of protrusions formed on a base. It is preferable that the area of ​​the base defined by the contour of the electrode in a plane parallel to the base sheet 10 does not change along the thickness direction t of the base sheet 10. The phrase "the area of ​​the base defined by the contour of the electrode in a plane parallel to the base sheet 10 does not change along the thickness direction t" includes the area at the largest position in the thickness direction t being 1 to 1.2 times the area at the smallest position in the thickness direction t. Forming multiple protrusions on the base allows the base to stably connect the electrode to the base sheet 10 while the multiple protrusions can easily and strongly press the electrode into the skin 200. While Figure 9 illustrates a cylindrical shape as the shape of the base, the shape of the base may be any shape, such as a polygonal prism, a polygonal prism with rounded corners, a portion of a cylinder, or an irregular shape. 9 shows an embodiment in which the area defined by the outline of each of the multiple protrusions on the base decreases along the thickness direction t in a plane parallel to the base sheet 10, but the area defined by the outline of each of the multiple protrusions on the base may have a needle-like shape that does not decrease along the thickness direction t. Furthermore, while FIG. 9 shows an example in which the convex portion 20 is a plurality of protrusions formed on a base, the convex portion 20 may also be a plurality of protrusions without a base. In this case, it is preferable that the area defined by the outline of each of the multiple protrusions in a plane parallel to the base sheet 10 decreases along the thickness direction t. Note that, "the area defined by the outline of the protrusion decreases along the thickness direction t" means that, in the case of multiple protrusions, the area defined by the outline of each of the multiple protrusions decreases along the thickness direction t.

[0027] 10 , in the drug delivery device 100, it is preferable that the first electrode 21 has a convex portion 20 that satisfies the following requirement (1), and / or the second electrode 22 has a convex portion 20 that satisfies the following requirement (2): (1) In the thickness direction t of the base sheet 10, the surface on which the first electrode 21 of the base sheet 10 is disposed is spaced apart from the surface at a height T1 ０ The maximum height of the first electrode 21 is T1 １００ When this is done, the maximum height T1 １００95% of the height T1 ９５ The area A1 defined by the outline of the first electrode 21 in ９５ is the height T1 ０ The area A1 defined by the outline of the first electrode 21 in ０ (2) In the thickness direction t of the base sheet 10, the surface on which the second electrode 22 of the base sheet 10 is disposed is set at a height T2 ０ The maximum height of the second electrode 22 is T2 １００ When this is done, the maximum height T2 １００ 95% of the height T2 ９５ Area A2 defined by the outline of the second electrode 22 ９５ is the height T2 ０ Area A2 defined by the outline of the second electrode 22 ０ is smaller than.

[0028] The part of the electrode at 95% of its maximum height is the part that is closest to the skin 200 when the drug delivery device 100 is placed on the skin 200. If at least one of the first electrode 21 and the second electrode 22 satisfies the above requirements, the area of ​​the part of the electrode that is closest to the skin 200 can be reduced, making it easier to press the electrode firmly into the skin 200. ９５ and area A1 ０ When comparing, if there are multiple protrusions as the convex portion 20, the area A1 ９５ and area A1 ０ It is preferable to compare the area A2 ９５ and area A2 ０ The same applies when comparing the areas at different heights, such as 70% height.

[0029] Figure 10 shows a configuration in which only the first electrode 21 has a convex portion 20 and satisfies requirement (1), but it is also possible that both the first electrode 21 and the second electrode 22 have a convex portion 20, with the first electrode 21 satisfying requirement (1) and the second electrode 22 satisfying requirement (2), or that only the second electrode 22 has a convex portion 20 and satisfies requirement (2).

[0030] When the first electrode 21 satisfies the requirement (1), the area A1 ９５ is the area A1０ If the second electrode 22 satisfies the requirement (2), the area A2 ９５ is the area A2 ０ It is preferable that the area of ​​the part at 95% of the maximum height of the electrode is ½ or less of the area of ​​the outline of the electrode on the surface of the base sheet 10. When the area of ​​the part at 95% of the maximum height of the electrode is ½ or less of the area of ​​the outline of the electrode on the surface of the base sheet 10, the convex portions 20 can be easily pressed into the skin 200. Furthermore, when the convex portions 20 have a protrusion or needle shape, when the drug delivery device 100 is placed on the skin 200, a force from the base side of the convex portions 20, i.e., the side closer to the base sheet 10, is easily transmitted to the tip side of the convex portions 20, i.e., the side in contact with the skin 200.

[0031] When the first electrode 21 satisfies the requirement (1), the area A1 ９５ is the area A1 ０ It is more preferable that the area is 1 / 3 or less, even more preferable that the area is 1 / 4 or less, and even more preferable that the area is 1 / 8 or less. ０ Area A1 for ９５ The lower limit of the area A2 is not particularly limited, but may be, for example, 1 / 100 or more. ９５ is the area A2 ０ It is more preferable that the area is 1 / 3 or less, even more preferable that the area is 1 / 4 or less, and even more preferable that the area is 1 / 8 or less. ０ Area A2 ９５ The lower limit of is not particularly limited, but may be, for example, 1 / 100 or more. When the area of ​​the portion at 95% of the maximum height of the electrode is within the above range relative to the area of ​​the outline of the electrode on the surface of the base sheet 10, the convex portions 20 can be easily pressed into the skin 200.

[0032] The height of the electrode at which the area defined by the outline of the electrode is smaller than the area of ​​the outline of the electrode on the surface of the base sheet 10 may be 90%, 80%, 60%, 50%, or 30% of the maximum height. That is, in the thickness direction t of the base sheet 10, the area defined by the outline of the first electrode 21 at 90%, 80%, 60%, 50%, or 30% of the maximum height of the first electrode 21 is preferably smaller than the area defined by the outline of the first electrode 21 on the surface of the base sheet 10 on which the first electrode 21 is disposed. Furthermore, in the thickness direction t of the base sheet 10, the area defined by the outline of the second electrode 22 at 90%, 80%, 60%, 50%, or 30% of the maximum height of the second electrode 22 is preferably smaller than the area defined by the outline of the second electrode 22 on the surface of the base sheet 10 on which the second electrode 22 is disposed. The area defined by the outline of the electrode at the height is smaller than the area defined by the outline of the electrode on the surface of the base sheet 10, so that the convex portion 20 can be easily formed. For example, in the thickness direction t of the base sheet 10, the area defined by the outline of the first electrode 21 at a height that is 70% of the maximum height of the first electrode 21 is area A1 ０ The area defined by the outline of the first electrode 21 at a height that is 50% of the maximum height of the first electrode 21 is preferably equal to or less than the area A1 ０ For example, the area defined by the outline of the second electrode 22 at a height that is 70% of the maximum height of the second electrode 22 in the thickness direction t of the base sheet 10 is area A2 ０ The area defined by the outline of the second electrode 22 at a height that is 50% of the maximum height of the second electrode 22 is preferably equal to or less than the area A2 ０ It is preferable that the value is 75% or less of the above.

[0033] 4 to 9, it is preferable that both the first electrode 21 and the second electrode 22 have a convex portion 20. It is preferable that a drug-containing portion 30 is disposed adjacent to one of the first electrode 21 and the second electrode 22, and an electrolyte-containing portion 40 (described later) is disposed adjacent to the other, but by having both the first electrode 21 and the second electrode 22 have the convex portion 20, it is possible to easily increase the contact area between the drug-containing portion 30 and the electrolyte-containing portion 40 and the skin surface 201, and therefore it is possible to more easily increase the permeability of the drug into the interior of the skin 202.

[0034] 10, either the first electrode 21 or the second electrode 22 may have a convex portion 20. When either the first electrode 21 or the second electrode 22 has a convex portion 20, it is preferable that the electrode adjacent to the drug-containing portion 30 has a convex portion 20. This makes it possible to easily increase the contact area between the drug-containing portion 30 and the skin surface 201, thereby increasing the permeability of the drug into the interior of the skin 202.

[0035] The drug delivery device 100 may be placed on the surface 201 of the skin 200 that forms the body surface, or on a cell layer that covers the mucous membrane on the surface of a body cavity or the surface of the lumen of an organ. The drug delivery device 100 is preferably placed on the skin surface 201 or the mucous membrane surface. This makes it easier to attach the drug delivery device 100 to a living body and transdermally absorb the drug.

[0036] The drug delivery device 100 is preferably placed on the skin surface 201 of the hand, arm, foot, leg, back, abdomen, chest, face, head, or the mucosal surface of the oral cavity, and more preferably attached to the skin surface 201 of a joint such as the elbow, shoulder, or wrist or in the vicinity thereof.

[0037] The drug delivery device 100 is preferably attached to the body part by adhering, wrapping, adhering, or placement, and is more preferably attached by adhering. Examples of attachment include attachment using an adhesive or a pressure-sensitive adhesive. Examples of wrapping include wrapping using an elastic band. Examples of adhering include adhering using a porous sheet, which will be described later. Examples of placement include placement using a medical clip. The drug delivery device 100 is preferably used for humans, but may also be used for animals other than humans, such as dogs, cats, horses, and cows.

[0038] The drug-containing section 30 contains a drug. The drug is preferably a pharmaceutical. A pharmaceutical is a drug used for the diagnosis, treatment, or prevention of a disease. The pharmaceutical preferably includes, for example, an anti-inflammatory agent, an antipyretic / anti-inflammatory analgesic, an antibiotic, a local anesthetic, an anti-allergic agent, an anti-Alzheimer's agent, an anti-Parkinson's disease agent, a psychotropic agent, an anti-rheumatic agent, a smoking cessation aid, a circulatory agent, or a combination thereof. The pharmaceutical may also include a low-molecular-weight ionic compound, a peptide, a protein, an oligonucleotide, an antibody drug, a nucleic acid drug, or a combination thereof.

[0039] 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 particularly preferably from 1,000 to 8,000. When the molecular weight of the drug is 8,000 or less, the drug can easily penetrate into the skin 202.

[0040] Preferably, the drug-containing portion 30 further contains water and a moisture-retaining substance, and the drug is ionized, so that the drug can be held in the drug-containing portion 30 in a water-dissolved state, and can be easily delivered to the inside of the skin 202 when a voltage is applied.

[0041] The drug is preferably impregnated in the form of a drug solution into a moisture-retaining substance. Examples of moisture-retaining substances include cloth materials, paper materials, porous materials, and hydrogels, with hydrogels being preferred.

[0042] Examples of fabric materials include nonwoven fabrics, woven fabrics, knitted fabrics, etc., among which knitted fabrics are preferred. Examples of constituent fibers of fabric materials include natural fibers such as cotton, linen, and silk, regenerated 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.

[0043] The paper material preferably contains pulp, and examples thereof include tissue paper.

[0044] 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 conformability to the skin surface 201 when the drug delivery device 100 is attached to the skin 200. 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.

[0045] 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.

[0046] 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.

[0047] The drug-containing portion 30 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 inside the skin 202 when a voltage is applied between the electrodes. Among halide salts, chloride salts are more preferred.

[0048] The drug-containing portion 30 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 the drug-containing portion 30 and prevent deterioration of the drug contained in the drug-containing portion 30.

[0049] The drug-containing portion 30 may contain additives such as crosslinking agents, fillers, adhesives, preservatives, moisturizers, antioxidants, colorants, fragrances, oils, ultraviolet absorbers, cooling agents, warming agents, transdermal absorption promoters, and conductive substances.

[0050] If the drug-containing portion 30 contains an adhesive, it becomes easier to attach the drug-containing portion 30 to the skin 200.

[0051] If the drug-containing portion 30 contains a transdermal absorption enhancer, it will promote the penetration of the drug into the inside of the skin 202. 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.

[0052] If the drug-containing portion 30 contains a conductive substance, it is possible to increase the conductivity of the drug-containing portion 30. Examples of the conductive substance include conductive fibers and conductive fillers. The conductive filler preferably contains conductive particles.

[0053] The drug delivery device 100 is placed on the skin 200 so that the side of the base sheet 10 on which the first electrode 21 and the second electrode 22 are arranged faces the skin 200, and it is preferable that the drug-containing portion 30 is arranged on the side of the first electrode 21 closer to the skin 200 or the side of the second electrode 22 closer to the skin 200, or that the drug-containing portion 30 is included in the first electrode 21 or the second electrode 22.

[0054] When the drug-containing portion 30 is arranged on the surface of the first electrode 21 closer to the skin 200 or the surface of the second electrode 22 closer to the skin 200, it is preferable that the drug-containing portion 30 is arranged so that the moisture-retaining substance containing the drug solution is located close to the skin surface 201.

[0055] When the drug-containing portion 30 is included in the first electrode 21 or the second electrode 22, the electrode is composed of an aggregate of conductive fibers or an aggregate of conductive particles, and the drug solution is held inside the aggregate of conductive fibers or the aggregate of conductive particles, thereby allowing the drug-containing portion 30 to be included in the electrode, thereby reducing the thickness of the drug delivery device 100.

[0056] 1 and 3, drug-containing portion 30 is disposed on the side of first electrode 21 closer to skin 200, i.e., on the surface of first electrode 21 opposite to the side facing base sheet 10. For example, when first electrode 21 is an anode and the drug in drug-containing portion 30 is positively charged, if drug-containing portion 30 is disposed on the side of first electrode 21 closer to skin 200, it is thought that the drug will be more easily delivered to inside skin 202 due to the electrical repulsion between the drug and the cathode and the electroosmotic flow from the anode to the cathode.

[0057] Although not shown, drug-containing portion 30 may be disposed on the side of second electrode 22 closer to skin 200, i.e., on the surface of second electrode 22 opposite to the side facing base sheet 10. For example, when second electrode 22 is a cathode and the drug in drug-containing portion 30 is negatively charged, if drug-containing portion 30 is disposed on the side of second electrode 22 closer to skin 200, it is thought that the drug will be more easily delivered to inside skin 202 due to the electrical repulsion between the drug and the cathode.

[0058] Although the above example illustrates a configuration in which the first electrode 21 is an anode and the second electrode 22 is a cathode, the first electrode 21 may be a cathode and the second electrode 22 may be an anode. Alternatively, for example, the anode and cathode may be switched by changing the direction of the current at predetermined intervals.

[0059] That is, the drug-containing portion 30 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 30 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 30.

[0060] The shape of the drug-containing portion 30 may be different from the shape of the adjacent electrode. For example, the outer edge of the drug-containing portion 30 may be located further outward than the outer edge of the adjacent electrode. This allows the area of ​​the drug-containing portion 30 to be increased, thereby increasing the amount of drug that the drug-containing portion 30 can store. Furthermore, it is possible to reduce irritation to the skin 200 when a voltage is applied. The shape of the outer edge of the drug-containing portion 30 may or may not be similar to the shape of the outer edge of the adjacent electrode.

[0061] As shown in FIGS. 1 and 3 , the drug delivery device 100 further includes an electrolyte-containing portion 40 containing water, a moisture-retaining substance, and an electrolyte. Preferably, the drug-containing portion 30 is disposed on the surface of the first electrode 21 closest to the skin 200, or is included in the first electrode 21 and the electrolyte-containing portion 40 is disposed on the surface of the second electrode 22 closest to the skin 200. Alternatively, the drug-containing portion 30 is disposed on the surface of the second electrode 22 closest to the skin 200, or is included in the second electrode 22 and the electrolyte-containing portion 40 is disposed on the surface of the first electrode 21 closest to the skin 200. The inclusion of the electrolyte-containing portion 40 in the drug delivery device 100 reduces electrical resistance between the electrode having the electrolyte-containing portion 40 and the skin 200, thereby reducing the power consumption of the drug delivery device 100. Furthermore, when a voltage is applied between the electrodes, electroosmotic flow is more likely to occur within the skin 202. The electrolyte-containing portion 40 is preferably a portion that does not contain a drug.

[0062] That is, the electrolyte-containing portion 40 is preferably provided in an electrode that is not provided with the drug-containing portion 30. In this case, an electrode that is not provided with the drug-containing portion 30 means an electrode that is not provided adjacent to the drug-containing portion 30 and does not include the drug-containing portion 30. The electrolyte-containing portion 40 is preferably disposed on the surface of the electrode that is closer to the skin 200, and for example, a moisture-retaining substance containing an electrolyte solution is preferably disposed on the surface of the electrode that is closer to the skin 200.

[0063] Alternatively, the electrolyte-containing portion 40 may be included in the first electrode 21 or the second electrode 22. For example, the electrode may be composed of an aggregate of conductive fibers or an aggregate of conductive particles, and an electrolyte solution may be held inside the aggregate of conductive fibers or the aggregate of conductive particles, thereby allowing the electrolyte-containing portion 40 to be included in the electrode. This allows the thickness of the drug delivery device 100 to be reduced.

[0064] For details of the electrolytes and water-retaining substances in the electrolyte-containing portion 40, please refer to the explanation of the electrolytes and water-retaining substances in the drug-containing portion 30 above. The electrolytes contained in the electrolyte-containing portion 40 may be the same as or different from the electrolytes contained in the drug-containing portion 30. The water-retaining substances contained in the electrolyte-containing portion 40 may be the same as or different from the water-retaining substances contained in the drug-containing portion 30. The electrolyte-containing portion 40 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 30 above.

[0065] Each electrode preferably contains a conductive material, more preferably is made of a conductive material. The conductive material preferably contains a metal, carbon, or a mixture thereof, more preferably contains a metal. The metal preferably contains, for example, gold, silver, silver halide, copper, platinum, zinc, tin, titanium, aluminum, nickel, or an alloy thereof, more preferably contains silver, silver halide, or zinc, and even more preferably contains silver chloride or zinc. By containing an electrochemically active metal, the electrodes can easily reduce pH changes primarily caused by the electrolysis of water. For example, by containing zinc in the first electrode 21 and silver chloride in the second electrode 22, pH changes can be easily reduced. Reducing pH changes can reduce skin irritation. The metal is preferably in the form of a plate, fiber, or particle, more preferably a plate. The carbon preferably contains carbon fiber, graphite, ketjen black, fullerene, carbon nanotube, carbon nanohorn, furnace black, or a mixture thereof. The carbon is preferably in the form of a plate, fiber, or particle, and more preferably in the form of a plate. For example, the first electrode 21 may contain carbon, and the second electrode 22 may contain silver chloride.

[0066] The base sheet 10 can be made of an insulator, and is preferably electrically insulated from the electrodes arranged on the base sheet 10. At least the area of ​​the base sheet 10 where the electrodes are arranged needs to be made of an insulator, but it is preferable that the entire base sheet 10 is made of an insulator. The base sheet 10 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 10 may be an elastic body, and may be made of, for example, a rubber sheet, which is a type of resin sheet.

[0067] The shape (planar shape) of the base sheet 10 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.

[0068] Preferably, the base sheet 10 directly or indirectly supports electrodes. For example, it is preferable that the electrodes are fixed to the surface of the base sheet 10 closer to the skin 200, and that the power supply unit 50, the control unit 60, or both are fixed to the surface of the base sheet 10 farther from the skin 200.

[0069] The power supply unit 50 is electrically connected to the electrodes. The power supply unit 50 includes a battery and has a positive electrode and a negative electrode. It is preferable that one of the positive electrode and the negative electrode is connected to the first potential electrode 20A, and the other is connected to the second potential electrode 20B. When the drug ionizes, if cations or ionized substances that are positively charged overall become the medicinal component, it is preferable that the positive electrode is connected to the electrode provided with the drug-containing portion 30. When the drug ionizes, if anions or ionized substances that are negatively charged overall become the medicinal component, it is preferable that the negative electrode is connected to the electrode provided with the drug-containing portion 30.

[0070] The battery used in the power supply unit 50 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 for disposable drug delivery devices 100. The power supply unit 50 may have multiple batteries, for example, two coin-type lithium batteries connected in series. The applied voltage of the power supply unit 50 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:

[0071] The drug delivery device 100 preferably includes a control unit 60 that controls the application of current from the power supply unit 50. The control unit 60 can set the type of current application between the electrodes. Examples of current application include direct current (DC) application, pulsed current application, and pulse depolarized current application. DC application is a type in which a predetermined direct current is applied between the electrodes. Pulse application is a type in which a predetermined repetitive pulse is applied between the electrodes. Pulse depolarized current is a type in which a predetermined repetitive pulse is applied between the electrodes and residual charge is forcibly discharged during pulse pauses. Therefore, the control unit 60 preferably includes a DC output circuit, a pulse output circuit, or a pulse depolarized output circuit. The control unit 60 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 application from the viewpoint of efficient drug delivery. Therefore, the control unit 60 preferably includes at least a pulse output circuit or a pulse depolarized output circuit.

[0072] The pulse frequency when applying pulsed current 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 due to 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.

[0073] 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.

[0074] 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.

[0075] The control unit 60 preferably controls the voltage to output the pulses, but may also control the current to output the pulses.

[0076] The control unit 60 may have a processor and a memory. For example, the control unit 60 may be configured to switch between DC output, pulse output, and pulse depolarization output using the processor in accordance with a program recorded in the memory. Examples of the memory include an SSD, HDD, and ROM.

[0077] The control unit 60 may have a circuit capable of redirecting the current. For example, the control unit 60 may be configured such that a processor redirects the current using the circuit in accordance with a program stored in memory. This allows the anode and cathode to be alternately switched. When the first electrode 21, the second electrode 22, or both, are active electrodes, this switching of the electrodes can regenerate consumed power.

[0078] Each function of the control unit 60 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 60 may also include a constant voltage diode or a constant current diode.

[0079] The drug delivery device 100 preferably includes a wiring unit 70 that electrically connects each electrode to the power supply unit 50. The wiring unit 70 preferably electrically connects the power supply unit 50 to the control unit 60 and also electrically connects the control unit 60 to the electrodes. This allows the control unit 60 to control the flow of electricity from the power supply unit 50 to the electrodes. The control unit 60 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.

[0080] The wiring portion 70 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 70 can be formed by printing using ink containing a conductive material. Examples of cable-shaped wiring include metal wires coated with an insulating film. The wiring portion 70 is preferably made of a conductor, and for details of the conductor that constitutes the wiring portion 70, see the description of the conductor that constitutes the electrode above.

[0081] As shown in FIG. 3, the drug delivery device 100 may have a cover sheet 11 and a shape-retaining sheet 12 .

[0082] The cover sheet 11 is preferably arranged on the surface of the base sheet 10 opposite to the surface on which the electrodes are arranged, and is larger than the base sheet 10 so as to cover the entire base sheet 10. The cover sheet 11 preferably extends outward beyond the outer edge of the base sheet 10. By providing the cover sheet 11, the drug delivery device 100 can be protected by the cover sheet 11, and the drug delivery device 100 can be stably attached to the skin 200.

[0083] The shape-retaining sheet 12 is arranged on the surface of the base sheet 10 opposite to the surface on which the cover sheet 11 is arranged, and preferably has an opening 12A in the portion where the drug-containing portion 30 or the electrolyte-containing portion 40 is arranged. The drug-containing portion 30 and the electrolyte-containing portion 40 are preferably arranged so as to be exposed from the opening 12A of the shape-retaining sheet 12. By providing the shape-retaining sheet 12, the drug-containing portion 30 and the electrolyte-containing portion 40 can be more easily held stably.

[0084] The cover sheet 11 and the shape-retaining sheet 12 are preferably made of an insulating material and can be made of a sheet that can be used for the base sheet 10. The sheets that make up the drug delivery device 100 are preferably fixed to each other with an adhesive. However, only one of the cover sheet 11 and the shape-retaining sheet 12 may be provided.

[0085] The drug delivery device 100 preferably has an adhesive portion on the surface facing the skin 200. This allows the drug delivery device 100 to be attached to the skin 200 and to be stably attached to the skin 200. The adhesive portion can be provided on the surface of the base sheet 10, the cover sheet 11, or the shape-retaining sheet 12 facing the skin 200.

[0086] This application claims the benefit of priority based on Japanese Patent Application No. 2024-051369, filed on March 27, 2024. The entire contents of the specification of Japanese Patent Application No. 2024-051369, filed on March 27, 2024, are incorporated herein by reference.

[0087] DESCRIPTION OF SYMBOLS 10: Base sheet 11: Cover sheet 12: Shape-retaining sheet 12A: Opening 20: Convex portion 21: First electrode 22: Second electrode 30: Drug-containing portion 40: Electrolyte-containing portion 50: Power supply portion 60: Control portion 70: Wiring portion 100: Drug delivery device 200: Skin 201: Skin surface 202: Inside of skin t: Thickness direction x: Longitudinal direction

Claims

1. A drug delivery device comprising: a drug-containing portion containing a drug; a base sheet; and a first electrode and a second electrode disposed on the base sheet, wherein the first electrode and / or the second electrode have a convex portion that is convex on the side opposite to the surface facing the base sheet, and wherein a potential applied to the first electrode and a potential applied to the second electrode are different.

2. The drug delivery device according to claim 1, wherein the first electrode has the convex portion that satisfies the following requirement (1), and / or the second electrode has the convex portion that satisfies the following requirement (2): Requirement (1) In the thickness direction of the base sheet, the surface of the base sheet on which the first electrode is arranged is spaced apart from the surface of the base sheet by a height T1 ０ and the maximum height of the first electrode is T1 １００ When the maximum height T1 １００ 95% of the height T1 ９５ The area A1 defined by the outline of the first electrode ９５ is the height T1 ０ The area A1 defined by the outline of the first electrode ０ Requirement (2) In the thickness direction of the base sheet, the surface of the base sheet on which the second electrode is disposed is smaller than a height T2 ０ and the maximum height of the second electrode is T2 １００ When the maximum height T2 １００ 95% of the height T2 ９５ The area A2 defined by the outline of the second electrode ９５ is the height T2 ０ The area A2 defined by the outline of the second electrode ０ is smaller than.

3. When the first electrode satisfies the requirement (1), the area A1 ９５ is the area A1 ０ and when the second electrode satisfies the requirement (2), the area A2 ９５ is the area A2 ０ 3. The drug delivery device of claim 2, wherein the viscosity is 1 / 2 or less.

4. A drug delivery device according to claim 1 or 2, wherein the first electrode and the second electrode have the convex portion.

5. A drug delivery device according to claim 1 or 2, wherein the drug-containing portion further contains water and a moisture-retaining substance, and the drug is ionized.

6. The drug delivery device is placed on the skin so that the side of the base sheet on which the first electrode and the second electrode are located faces the skin, and the drug-containing portion is located on the surface of the first electrode closest to the skin or the surface of the second electrode closest to the skin, or the drug-containing portion is included in the first electrode or the second electrode. A drug delivery device as described in claim 1 or 2.

7. A drug delivery device as described in claim 6, further comprising an electrolyte-containing portion containing water, a moisture-retaining substance, and an electrolyte, wherein the drug-containing portion is disposed on the surface of the first electrode closest to the skin or is included in the first electrode, and the electrolyte-containing portion is disposed on the surface of the second electrode closest to the skin, or the drug-containing portion is disposed on the surface of the second electrode closest to the skin or is included in the second electrode, and the electrolyte-containing portion is disposed on the surface of the first electrode closest to the skin.

8. The drug delivery device according to claim 1 or 2, 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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