Microneedle patch and analysis method

Abstract

A microneedle patch 1 comprises: a liquid absorbent layer 20 that absorbs liquid; needle-shaped parts 11 each including a flow path 13 formed therein, the flow path 13 in each needle-shaped part 11 being connected to one surface side of the liquid absorbent layer 20; and a cover layer disposed detachably on the other surface side of the liquid absorbent layer 20 and covering the liquid absorbent layer 20. Such a microneedle patch has adequate strength and enables a sufficient amount of body fluid to be drawn from a subject and analyzed. The present invention also provides an analysis method using the microneedle patch, with which a sufficient amount of body fluid can be drawn from a subject and analyzed.

Description

Microneedle patch and analysis method

[0001] The present invention relates to a microneedle patch and an analytical method.

[0002] In recent years, microneedle patches have been proposed that use microneedle structures that supply drugs to the body or collect body fluids from the body through through-holes formed in micro-sized needle-shaped portions. Examples of microneedle patches include a liquid-impermeable substrate having through-holes, a liquid-absorbing absorbent material filled in the through-holes, a needle-shaped portion provided on one side of the substrate and having a flow path formed therein, and a functional member provided on the other side of the substrate, where the needle-shaped portion and the absorbent material are connected to each other, and the absorbent material and the functional member are connected to each other (Patent Document 1).

[0003] International Publication No. 2023 / 042525

[0004] Currently, there is a demand for analytical methods for collecting and analyzing body fluids that are less painful and less stressful on the human body, and the use of microneedle patches as analytical tools is being considered. Microneedle patches are preferable for testing and providing medicinal solutions because they cause less pain and strain on the human body. However, conventional microneedle patches are configured to deliver interstitial fluid from the needle-shaped portion to the functional component through through-holes in the substrate. However, because the substrate is liquid-impermeable, even when attempting to obtain the amount of interstitial fluid required for analysis, the interstitial fluid may flow in the opposite direction, i.e., toward the skin, from the connection between the needle-shaped portion and the substrate. On the other hand, if a microneedle structure is formed without a substrate, the strength of the microneedle structure itself cannot be maintained.

[0005] The present invention has been made in consideration of the above-mentioned circumstances, and aims to provide a microneedle patch that can extract and analyze a sufficient amount of body fluid from a subject while maintaining strength, and an analytical method that can extract and analyze a sufficient amount of body fluid from a subject using the microneedle patch.

[0006] In order to achieve the above-mentioned object, firstly, the present invention provides a microneedle patch comprising a liquid-absorbing layer that absorbs liquid and a needle-shaped portion having a flow path formed therein, the flow path of the needle-shaped portion being connected to one side of the liquid-absorbing layer, and the other side of the liquid-absorbing layer being provided with a covering layer that covers the liquid-absorbing layer and is separable from the other side (Invention 1).

[0007] In the above invention (Invention 1), the flow path of the needle-shaped portion is connected to one side of the liquid-absorbent layer, and the other side of the liquid-absorbent layer has a covering layer that covers the liquid-absorbent layer. Therefore, the covering layer maintains strength without using a substrate, and the liquid-absorbent layer allows for the extraction of a sufficient amount of body fluid from a subject. However, if only the covering layer is used without a substrate, and the covering layer adheres to the liquid-absorbent layer and becomes inseparable, there is a risk that the liquid-absorbent layer cannot be separated from the covering layer, making it impossible to extract the extracted body fluid. Therefore, in the present invention, the covering layer is further provided so that it can be separated from the other side, allowing the extracted body fluid to be extracted by separating the liquid-absorbent layer from the covering layer. Therefore, the microneedle patch of the present invention maintains strength while allowing the extraction of a sufficient amount of body fluid from a subject for analysis.

[0008] In the above invention (Invention 1), it is preferable that the liquid-absorbing layer has compressive deformability (Invention 2).

[0009] In the above invention (Invention 1), it is preferable that the liquid-absorbing layer is made of a hard porous material (Invention 3).

[0010] In the above invention (Invention 1), it is preferable that the needle-shaped portion contains a water-insoluble hydrophilic resin (Invention 4).

[0011] In the above invention (Invention 1), it is preferable that a coating containing a hydrophilic substance is formed on the inner surface of the flow channel (Invention 5).

[0012] In the above invention (Invention 1), it is preferable that a first region of the surface of the cover layer facing the liquid absorbent layer, which faces the liquid absorbent layer, does not have adhesiveness (Invention 6).

[0013] In the above invention (Invention 6), a base on which the needle-shaped portion is provided is provided between the liquid absorbent layer and the needle-shaped portion, and the base is exposed to a greater extent than the liquid absorbent layer in a planar view, and it is preferable that a second region facing the exposed base on the surface of the covering layer facing the liquid absorbent layer has adhesiveness (Invention 7).

[0014] In the above invention (Invention 7), it is preferable that a third region other than the first region and the second region on the surface of the cover layer facing the liquid-absorbent layer has adhesiveness (Invention 8).

[0015] In the above invention (Invention 1), it is preferable that a base on which the needle-shaped portion is provided is provided between the liquid absorbent layer and the needle-shaped portion, and that the covering layer is provided with at least a recess into which the base portion fits (Invention 9).

[0016] In the above invention (Invention 9), it is preferable that a hollow portion be provided between the liquid-absorbing layer and the covering layer (Invention 10).

[0017] The above invention (Invention 10) is preferably characterized by having a pressure reducing means for reducing the pressure inside the liquid absorbent layer (Invention 11).

[0018] Secondly, the present invention provides an analytical method using a microneedle patch comprising a liquid-absorbing layer that absorbs liquid and a needle-shaped portion having a flow path formed therein, the needle-shaped portion being connected to one side of the liquid-absorbing layer, and a liquid-impermeable coating layer on the other side of the liquid-absorbing layer, the coating layer being detachable from the other side, the analytical method comprising the steps of: puncturing the needle-shaped portion of the microneedle patch into a subject and absorbing liquid from the subject; separating the liquid-absorbing layer from the coating layer; and recovering the liquid from the separated liquid-absorbing layer (Invention 12).

[0019] The above invention (Invention 112) includes a step of separating the liquid absorbent layer from the covering layer and a step of recovering the liquid from the separated liquid absorbent layer, thereby ensuring strength while allowing a sufficient amount of body fluid to be extracted from the subject and analyzed.

[0020] (a) A schematic cross-sectional view of a microneedle patch according to embodiment 1 of the present invention, (b) a schematic plan view of a microneedle structure according to embodiment 1 of the present invention. A partially enlarged cross-sectional view of a needle-shaped portion of a microneedle patch according to embodiment 1 of the present invention. (a) to (c) Explanatory diagrams showing the steps of a method for manufacturing a microneedle patch according to an embodiment. (a) to (c) Explanatory diagrams showing the steps of a method for manufacturing a microneedle patch according to an embodiment. (a) to (b) Explanatory diagrams showing the steps of a method for manufacturing a microneedle patch according to an embodiment. A schematic cross-sectional view of a microneedle patch according to embodiment 2 of the present invention. A schematic cross-sectional view of a microneedle patch according to embodiment 3 of the present invention. A schematic cross-sectional view of a microneedle patch according to embodiment 4 of the present invention. A schematic cross-sectional view of a microneedle patch according to embodiment 4 of the present invention.

[0021] (Embodiment 1) A microneedle patch 1 according to one embodiment of the present invention comprises a microneedle structure 10 having needle-shaped portions 11 and a liquid-absorbing layer 20, and a sheet 30 as a covering layer.

[0022] 1 and 2 show a microneedle structure 10 according to one embodiment of the present invention. The microneedle structure 10 comprises a plurality of needle-shaped portions 11. Each of the needle-shaped portions 11 has a plurality of holes 12 formed therein, and the holes 12 open on the surface of the needle-shaped portion 11. The microneedle structure 10 is capable of absorbing body fluids from within the skin through the holes 12 of the needle-shaped portions 11. In the present invention, body fluids include blood, lymph, interstitial fluid, etc.

[0023] The shape of the needle-like portion 11 may be cylindrical, prismatic, conical, pyramidal, or the like, and in this embodiment, it is conical. The maximum diameter or maximum cross-sectional dimension of the needle-like portion 11 may be, for example, 25 to 1000 μm, and the tip diameter or cross-sectional dimension of the tip may be, for example, 1 to 100 μm. The height of the needle-like portion 11 may be, for example, 50 to 2000 μm. The spacing between the needle-like portions 11 (the distance from the center of the maximum cross-section) may be, for example, 200 to 3000 μm, and preferably 400 to 2000 μm. When the region where the needle-like portions 11 are present is rectangular, the distance between the tip of the needle located at one end of the needle-like portion 11 and the tip of the needle located at the other end is preferably 3 to 20 mm, and more preferably 5 to 10 mm. Furthermore, the area of ​​the region where the needle-like portions 11 are present may be, for example, 9 to 400 mm. ２ It is preferable that the thickness is 25 to 100 mm. ２ In addition, it is preferable that the number of needles of the needle-shaped portion 11 in the region where the needle-shaped portion 11 exists is about 10 to 100, and more preferably about 25 to 75.

[0024] One or more holes 12 are formed in one needle-shaped portion 11, and one or more holes 12 open on the surface of the needle-shaped portion 11. The needle-shaped portion 11 has multiple holes 12 formed therein. In this embodiment, the needle-shaped portion 11 is made of a porous material. By using a porous material, it is not necessary to mechanically form fine flow paths, which is preferable. Furthermore, bodily fluids or medicinal fluids can flow through multiple flow paths 13 (described below) formed in the needle-shaped portion 11, which is preferable because the flow rate can be increased compared to when a single, simple, communicating hole is formed. Furthermore, since the needle-shaped portion 11 is made of a porous material, multiple holes 12 open on the side surface of the needle-shaped portion 11, which increases the rate at which fluid is absorbed or released from the needle-shaped portion 11 compared to a structure in which holes open only at the top of the needle-shaped portion.

[0025] Porous materials that can be used for the needle-shaped portion 11 include foamed molding materials formed by foaming a resin, sintered porous bodies formed by sintering resin particles, and porous materials with a porous structure formed by removing a pore-forming material. In this embodiment, the needle-shaped portion 11 is formed by a so-called salt leaching method, in which a protrusion is made from a composition obtained by mixing a pore-forming material with a material constituting the needle-shaped portion, and the pore-forming material is removed in a removal step to form the pores 12, while the material constituting the needle-shaped portion 11 remains, forming the needle-shaped portion 11 with a porous structure (details will be described later). Forming the needle-shaped portion 11 by such a salt leaching method is preferable because it allows the pore diameter of the pores 12 to be increased, thereby improving the absorbency of body fluids.

[0026] The needle-shaped portion 11 can be made of a water-insoluble material. Considering ease of handling during the manufacturing process, the water-insoluble material is preferably a water-insoluble resin. Examples of the water-insoluble resin include polyolefin resins such as polyethylene and α-olefin copolymers, olefin copolymer resins such as ethylene-vinyl acetate copolymer resins, polyurethane elastomers, and acrylic copolymer resins such as ethylene-ethyl acrylate copolymers.

[0027] Furthermore, such a water-insoluble resin is preferably a water-insoluble biodegradable resin that is less likely to affect the human body. As the biodegradable resin, aliphatic polyesters and their derivatives are preferably used, and at least one selected from the group consisting of polylactic acid, polyglycolic acid, polycaprolactone, and copolymers obtained by copolymerizing the monomers constituting these resins may also be used. A mixture of two or more of these biodegradable resins may also be used. For example, a copolymer of polycaprolactone or caprolactone with a monomer constituting another biodegradable resin may be used.

[0028] From the viewpoint of ease of heat processing, the water-insoluble resin is preferably a water-insoluble resin having a melting point of 130° C. or lower. Examples of water-insoluble resins having a melting point of 130° C. or lower include polycaprolactone, which is a biodegradable resin, and copolymers of caprolactone and other monomers constituting biodegradable resins, and a homopolymer of polycaprolactone is preferred.

[0029] The needle-shaped portion 11 may contain a second resin different from the water-insoluble resin (first resin) described above. The second resin is a water-insoluble hydrophilic resin (hereinafter, sometimes simply referred to as a hydrophilic resin). The second resin may be composed of one type of hydrophilic resin, or may be composed of multiple hydrophilic resins.

[0030] The water-insoluble hydrophilic resin is a polymeric substance that is insoluble in water and has hydrophilic functional groups. The use of a hydrophilic resin improves the water absorption of the needle-shaped portion 11. As a result, the flow of liquid between the target and the liquid-absorbent layer 20 via the flow path 13 can be promoted. Furthermore, the use of a water-insoluble resin reduces the solubility of the needle-shaped portion 11 in water. This makes it difficult for the needle-shaped portion 11 to dissolve in the liquid contained in the target even after the needle-shaped portion 11 is inserted into the target. Therefore, the shape of the needle-shaped portion 11 is more likely to be maintained. In addition, as will be described in detail below, the use of a water-insoluble hydrophilic resin makes it easier to manufacture a needle-shaped portion 11 with a porous structure. Therefore, it is easier to form fine flow paths 13 in the needle-shaped portion 11.

[0031] Examples of hydrophilic functional groups include hydroxyl groups, carboxyl groups, sulfonic acid groups, amine groups, and acetamide groups. Among these, hydroxyl groups and carboxyl groups are preferred. The hydrophilic functional groups are preferably present in the main chain or side chain of the second resin. The carboxyl groups may be in the form of carboxylate salts in the presence of counter ions such as metal ions.

[0032] The second resin may be a resin having both a repeating unit having a hydrophilic functional group and a repeating unit not having a hydrophilic functional group. In this case, however, it is preferable that the mass of the repeating unit having the hydrophilic functional group accounts for at least half of the mass of the resin. More preferably, the second resin includes a resin in which all repeating units have a hydrophilic functional group.

[0033] The equivalent weight of the hydrophilic functional group in the second resin is, for example, 1500 or less, preferably 1100 or less, more preferably 900 or less, and even more preferably 50 or less.

[0034] Specific examples of the second resin include polyvinyl alcohol and polysaccharides. Among these, polysaccharides with low water solubility are preferred. Examples of polysaccharides include cellulose, calcium alginate, chitin, cross-linked hyaluronic acid, and derivatives thereof. As polyvinyl alcohol, fully saponified polyvinyl alcohols with a higher degree of water insolubility are preferred.

[0035] When the target is a living body, the first resin preferably contains a biologically derived polysaccharide from the viewpoint of affinity with the living body. Furthermore, from the viewpoint of keeping raw material costs low, cellulose or a derivative thereof is preferred, and cellulose is more preferred.

[0036] The content of the second resin in the needle-shaped portion 11 is, for example, 3 to 50% by mass, preferably 4 to 40% by mass, and more preferably 10 to 30% by mass. Within this range, the water absorption of the needle-shaped portion is further improved. Furthermore, the needle-shaped portion 11 can be easily prepared when forming the needle-shaped portion. The second resin may be present in the needle-shaped portion 11 in the form of a filler.

[0037] The needle-shaped portion 11 may further contain a filler. By containing a filler in the needle-shaped portion 11, the mechanical strength of the needle-shaped portion 11 can be improved. The filler is preferably contained so as to be in a dispersed state in the resin of the needle-shaped portion 11. The filler is preferably made of a resin, and is preferably made of one type selected from the group consisting of natural organic polymers or modified products thereof, and biodegradable resins. An example of a natural organic polymer is cellulose, and examples of fillers made of natural organic polymers or modified products thereof include cellulose fiber and spherical cellulose acetate microparticles.

[0038] In this embodiment, as described above, the hole 12 is a void formed by removing the pore-forming material from a protrusion made of the material constituting the needle-shaped portion 11 and the pore-forming material. Body fluids and medicinal solutions pass through the flow path 13 formed by these hole 12 communicating with each other. As shown in the cross section of the needle-shaped portion 11, the flow path 13 is formed by the removal of the pore-forming material, forming a plurality of voids that communicate with each other. The size of the opening of the hole 12 is determined depending on the analysis method using the microneedle structure 10, but from the viewpoint of facilitating the passage of liquid, the opening is preferably 0.1 to 50.0 μm, more preferably 0.5 to 25.0 μm, and even more preferably 1.0 to 10.0 μm.

[0039] In this embodiment, a coating containing a hydrophilic substance may be formed on the inner surface of the flow channel 13 of the needle-shaped portion 11. That is, the inner surface of the flow channel 13 may be covered with a layer containing a hydrophilic substance. By forming such a coating, high liquid absorption can be achieved. Furthermore, by forming the coating, high liquid absorption can be maintained for a long period of time. That is, durability is also improved.

[0040] Next, the hydrophilic substance contained in the coating will be described. The hydrophilic substance is used to enhance the liquid absorption. The hydrophilic substance is a substance different from the first resin. The hydrophilic substance used has higher hydrophilicity than the first resin.

[0041] In a preferred embodiment, the hydrophilic substance includes a hydrophilic polymer. The hydrophilic polymer preferably contains carbon atoms and oxygen atoms, and has a ratio of the number of oxygen atoms to the number of carbon atoms (hereinafter sometimes referred to as the O / C ratio) of 2 / 5 or more. The use of such a hydrophilic polymer can further enhance the liquid absorbency.

[0042] When the subject is a living organism, the hydrophilic polymer is preferably a biosafe substance. A biosafe substance will have less of an effect on the living organism when using the microneedle patch 1. Preferably, the hydrophilic polymer is a biosafe substance and the needle-shaped portion-forming resin is a biodegradable resin, thereby significantly reducing the effect on the living organism when using the microneedle patch 1.

[0043] Examples of biosafe hydrophilic polymers having an O / C ratio of 2 / 5 or more include polyethylene glycol, polyvinyl alcohol, cellulose, cellulose derivatives, polysaccharides such as hyaluronic acid, polyacrylic acid, etc. Examples of cellulose derivatives include hydroxyalkyl cellulose, carboxymethyl cellulose, etc. Other biosafe hydrophilic polymers include polyvinylpyrrolidone, etc.

[0044] When polyethylene glycol is used as the hydrophilic polymer, its weight average molecular weight is, for example, 1,000 to 10,000, preferably 2,000 to 6,000.

[0045] When polyvinyl alcohol is used as the hydrophilic polymer, its weight average molecular weight is, for example, 5,000 to 200,000, preferably 10,000 to 10,000.

[0046] Preferably, the hydrophilic polymer is a compound having a repeating unit with a hydroxyl group. Using such a hydrophilic polymer results in particularly high water absorption. Furthermore, it is preferable that the hydroxyl group does not bond to a carbonyl group to form a carboxyl group. That is, the hydrophilic polymer is preferably a compound having a repeating unit with a hydroxyl group without a carboxyl group. Hydroxy groups not bonded to carbonyl groups form hydrogen bonds, resulting in a hydrophilic polymer that is less soluble in water. Furthermore, hydrophilic polymers with carboxyl groups, such as polyacrylic acid, tend to thicken liquids, potentially hindering their passage through the flow channel 13. However, such problems are less likely to occur if the hydrophilic polymer is a compound having a repeating unit with a hydroxyl group without a carboxyl group. By using a hydrophilic polymer that is a compound having a repeating unit with a hydroxyl group without a carboxyl group, it is possible to maintain the high mechanical strength of the needle-shaped portion.

[0047] From the viewpoint of biological safety, compounds having a repeating unit having a hydroxy group are preferably polysaccharides such as polyvinyl alcohol, cellulose, and cellulose derivatives. Examples of cellulose derivatives include hydroxyalkyl cellulose.

[0048] Preferably, the hydrophilic polymer is a resin that is substantially insoluble in water at room temperature (25°C). Using such a substance makes the coating less likely to dissolve in liquid when the microneedle is in use. This improves the durability of the coating. More preferably, the hydrophilic polymer is a resin that is insoluble in water at room temperature but dissolves in warm water (40°C or higher). Here, "insoluble in water at room temperature" means that the solubility in water at 20°C is 50% or less, preferably 25% or less. Such a polymer can achieve high hydrophilicity and therefore high liquid absorption.

[0049] A particularly preferred hydrophilic polymer is polyvinyl alcohol. Polyvinyl alcohol has high hydrophilicity but is hardly soluble in water at room temperature. Therefore, in addition to high liquid absorption, high durability is obtained. Furthermore, according to the findings of the present inventors, the use of polyvinyl alcohol also makes it possible to increase the mechanical strength of the needle-shaped portion. From the viewpoint of easily obtaining the property of being insoluble in water at room temperature, the saponification degree of polyvinyl alcohol is preferably 95% or more, and more preferably 97% or more.

[0050] In another preferred embodiment, the hydrophilic substance is derived from a carboxyl group-reactive compound. The carboxyl group-reactive compound is a compound having a functional group that reacts with and bonds to a carboxyl group.

[0051] Carboxyl groups may be formed on the surface of the flow channel 13 in the needle-shaped portion 11. For example, if a resin having an ester bond (e.g., a polyester such as polycaprolactone) is used as the resin forming the needle-shaped portion, surface modification such as plasma treatment of the surface of the flow channel 13 may decompose the ester bond and generate carboxyl groups. If a carboxyl group-reactive compound is used as the hydrophilic substance, the hydrophilic substance reacts with the carboxyl group on the surface of the flow channel 13 and bonds to the surface of the flow channel 13. This allows a coating containing a hydrophilic substance derived from the carboxyl group-reactive compound to be firmly bonded to the surface of the flow channel 13. As a result, the coating is less likely to fall off, and the durability of the coating can be improved.

[0052] Examples of functional groups contained in the carboxyl group-reactive compound include an amino group, a hydroxy group, an epoxy group, and an isocyanate group. An amino group is preferred. In this specification, the amino group is defined as -NH ２ Alternatively, one or two hydrogen atoms in the formula (I) may be further substituted to form a substituted amino group. In the case of a compound having an amino group, the amino group reacts with a carboxyl group formed on the inner surface of the flow channel 13 to form an amide bond. This allows the coating to be firmly bonded to the surface of the flow channel 13.

[0053] The carboxyl group-reactive compound may be a low molecular weight compound (a compound having no repeating units) or a high molecular weight compound (a compound having repeating units). That is, the carboxyl group-reactive compound may also be a compound that corresponds to the above-mentioned hydrophilic polymer.

[0054] However, the carboxyl group-reactive compound is preferably a low molecular weight compound. Since low molecular weight compounds are less likely to thicken the liquid, when the liquid passes through the flow channel 13, the possibility of the passage being hindered due to thickening is reduced. The formula weight of the low molecular weight compound is usually 2,000 or less, preferably 1,000 or less, and more preferably 600 or less. A low molecular weight organic compound is more preferably used. Specific examples of such carboxyl group-reactive compounds include amino acids. Examples of amino acids include amino acids that constitute proteins. A preferred amino acid is arginine. When arginine is used, particularly high liquid absorption properties are obtained.

[0055] The hydrophilic substance may be an inorganic substance, such as silicon oxide, aluminum oxide, titanium oxide, zinc oxide, cerium oxide, or kaolin.

[0056] The needle-like portions 11 are provided at predetermined intervals on the sheet-like base 21. In this embodiment, the needle-like portions 11 are provided in a plurality of rows in one direction, and a plurality of needle-like portions 11 are formed in each row and arranged in a matrix on the base 21.

[0057] The base 21 is formed simultaneously with the needle-shaped portion 11 during the manufacturing process. Therefore, the base 21 is formed with the same structure and composition as the needle-shaped portion 11. That is, like the needle-shaped portion 11, the base 21 is also made of a porous material, and the base 21 also has holes 12 and flow paths 13 formed therein. Therefore, the base 21 can absorb liquid, but when its thickness is 300 μm or more, it also functions as a liquid-absorbent layer 20. The base 21 can fix the needle-shaped portion 11 to prevent it from falling off, and the flow paths 13 of the needle-shaped portion 11 can communicate with the liquid-absorbent layer 20 via the flow paths 13 of the base 21. Furthermore, when a separate liquid-absorbent layer 20 is provided on a thin base 21 with a thickness of less than 300 μm, the flow paths 13 through which liquid reaches the liquid-absorbent layer 20 can be shortened, allowing the liquid-absorbent layer 20 to absorb biological liquids more quickly.

[0058] (Liquid-absorbing layer) In the microneedle structure 10 of this embodiment, the needle-shaped portion 11 is provided on one surface of the base 21, and the liquid-absorbing layer 20 is directly laminated on the other surface. The liquid-absorbing layer 20 has a circular shape that is smaller than the base 21 in a plan view. That is, as shown in Figure 1 (2), the central portion of the base 21 is covered with the liquid-absorbing layer 20 in a plan view, and the outer portions are exposed.

[0059] The liquid-absorbent layer 20 preferably has compressive deformability. By having compressive deformability, when the liquid-absorbent layer 20 is pressed through the sheet 30, air is pushed out between the liquid-absorbent layer 20 and the skin, and the sheet 30 returns to its original shape, creating a state of negative pressure between the liquid-absorbent layer 20 and the skin. This allows liquid derived from the living body to be drawn into the liquid-absorbent layer 20 through the flow paths 13 of the needle-shaped portions 11, thereby increasing the speed or amount of liquid absorption by the microneedle patch 1. Examples of absorbent materials that have compressive deformability include foam molding materials such as sponge, nonwoven fabrics, cotton, paper, woven fabrics, knitted fabrics, etc.

[0060] The liquid absorbent layer 20 may also contain a resin that has hydroxyl groups and is insoluble in water. The inclusion of such a resin can enhance the hydrophilicity of the liquid absorbent layer 20. Furthermore, the water-insolubility of the resin can prevent the resin from leaching out when storing biological fluids. Examples of such resins include fully saponified polyvinyl alcohol and polysaccharides. Examples of polysaccharides include cellulose, calcium alginate, chitin, cross-linked hyaluronic acid, and derivatives thereof. From the perspective of keeping raw material costs low, cellulose or its derivatives are preferred as polysaccharides, with cellulose being even more preferred. In the case of a compressively deformable liquid absorbent layer 20, nonwoven fabrics, cotton, paper, woven fabrics, or knitted fabrics may be formed from cellulose fibers. Examples of cellulose fibers include natural cellulose fibers such as cotton, and regenerated cellulose fibers such as viscose rayon and cuprammonium rayon.

[0061] The liquid-absorbent layer 20 may be fixed to the base 21, or may simply be placed thereon. In this embodiment, the liquid-absorbent layer 20 is simply placed on the base 21, but a sheet 30 (described later) is adhered to the base 21 around the liquid-absorbent layer 20 via an adhesive layer, so that the liquid-absorbent layer 20 is held between the base 21 and the sheet 30. In this embodiment, only one layer of the liquid-absorbent layer 20 is provided, but the liquid-absorbent layer 20 may be configured to have multiple layers. If the needle-shaped portion 11 contains a water-insoluble hydrophilic resin or if a coating containing a hydrophilic substance is formed on the inner surface of the flow path 13 in the needle-shaped portion 11, the liquid-absorbent layer 20 has increased liquid absorption. Therefore, even if the liquid-absorbent layer 20 is simply placed on the base 21 without being adhered thereto, rapid liquid absorption can be expected in the liquid-absorbent layer 20.

[0062] (Sheet) In this embodiment, the sheet 30 has a rectangular shape that is larger than the base 21 in a plan view. Therefore, the sheet 30 covers the microneedle structure (the liquid absorbent layer 20 and the base 21), and the portion of the sheet 30 that is outside the base 21 is directly attached to the skin. In consideration of the ability of the sheet 30 to conform to the skin to which it is attached, it is preferable that the sheet 30 be made of a flexible and stretchable material, but the sheet 30 is not limited to such materials.

[0063] The sheet 30 is preferably liquid-impermeable. Liquid-impermeable sheets 30 do not spread from the liquid-absorbent layer 20 toward the sheet 30, allowing the liquid to be efficiently absorbed by the liquid-absorbent layer 20. Examples of liquid-impermeable sheets 30 include those based on resin films, and examples of resins used for resin films include polyester resins such as polyethylene terephthalate, polyolefin resins such as polyethylene, and polyurethane resins. Furthermore, the base material of the sheet 30 may be, for example, a stretchable nonwoven fabric, woven fabric, or knitted fabric, taking into consideration the conformability when applied to the living body, and conventionally known materials can be used. Nonwoven fabric, woven fabric, or knitted fabric may be impregnated with a resin to impart liquid-impermeability. In this embodiment, a polyethylene terephthalate film is used as the sheet 30.

[0064] On the surface of the sheet 30 facing the liquid absorbent layer 20, the area facing the liquid absorbent layer 20 is referred to as the first area A1, the area facing only the exposed base 21 is referred to as the second area A2, and the other area is referred to as the third area A3.

[0065] In the first region A1, the sheet 30 is configured to have no adhesiveness. In this case, the first region A1 may be configured to have no adhesiveness by not providing an adhesive layer therein, or alternatively, an adhesive layer may be provided in the first region A1 and a film 31 (described later) may be provided thereon to prevent adhesiveness, as in the present embodiment. When the liquid-absorbent layer 20 is made of a compressively deformable material such as sponge, nonwoven fabric, or cotton, if the first region A1 of the sheet 30 has adhesiveness, the liquid-absorbent layer 20 may easily adhere to the liquid-absorbent layer 20, making it difficult to peel the liquid-absorbent layer 20 from the sheet 30. Therefore, in the present embodiment, the sheet 30 is configured to have no adhesiveness in the first region A1, thereby making it possible to easily peel the liquid-absorbent layer 20 from the sheet 30.

[0066] When the adhesive layer and the film 31 are provided in the first region A1, the adhesive layer may be the same as the adhesive layer used in the second region described below. By forming them in this manner, the manufacturing process becomes easier.

[0067] An adhesive layer (not shown) having a weak adhesive strength that allows for re-peelability is provided in the second region A2 facing the base 21. By providing such a weak adhesive strength that allows for re-peelability, the sheet 30 is fixed to the base 21, and when performing an analysis, the base 21 can be peeled off from the sheet 30 to remove the liquid absorbent layer 20 and extract the extracted liquid.

[0068] The adhesive layer formed in the second region A2 may be an adhesive layer made of, for example, an acrylic adhesive, a rubber adhesive, a urethane adhesive, an olefin adhesive, or the like.

[0069] An adhesive layer (not shown) is provided in the third region A3 of the liquid-absorbing layer 20. This adhesive layer is preferably a biosafe adhesive because it is attached to the skin. The adhesive layer in the third region A3 may be more adhesive than the adhesive layer in the second region A2, from the viewpoint of not affecting adhesion to the skin and removal of the microneedle structure 10. In this regard, the adhesive layer in the third region A3 may use a different adhesive than the adhesive layer in the second region A2, or the same adhesive may be provided in a thicker layer than in the second region A2.

[0070] A film 31 is provided between the liquid absorbent layer 20 and the first region A1 of the sheet 30 to prevent the pressure-sensitive adhesive layer of the sheet 30 from coming into direct contact with the liquid absorbent layer 20. The film 31 may be provided in advance in the first region A1 of the sheet 30. In this case, the film 31 may be a release sheet for the sheet 30.

[0071] A liquid-impermeable film is preferable as the film 31. As the liquid-impermeable film, the same material as the base material of the above-described liquid-impermeable sheet 30 can be used. In this embodiment, a PET film is used.

[0072] Furthermore, a plurality of through holes 32 serving as ventilation means are formed at intervals around the liquid absorbent layer 20 of the sheet 30, and are configured so that air can be pushed out through the through holes 32 when the sheet 30 is attached. When the air inside the liquid absorbent layer 20 is pushed out by pressing the liquid absorbent layer 20 via the sheet 30, only a limited amount of air is pushed out through the flow paths 13 of the needle-like portions 11, so it is preferable to provide the sheet 30 with the above-mentioned through holes 32 for ventilation.

[0073] The microneedle patch 1 includes the sheet 30, ensuring the strength of the microneedle structure 10, while the liquid-absorbing layer 20 allows for the acquisition of a sufficient amount of interstitial fluid. Furthermore, the microneedle structure 10 can be separated from the sheet 30. Once separated, the liquid-absorbing layer 20 is simply placed on the base 21, allowing for easy removal of the liquid-absorbing layer 20. If the microneedle structure 10 is adhered to the sheet 30 and cannot be separated, extraction of the liquid in the liquid-absorbing layer 20 may be hindered during analysis. Forcible peeling may result in damage to the microneedle structure 10, resulting in fragments being mixed with the liquid in the liquid-absorbing layer 20. Therefore, if the liquid-absorbing layer 20 can be separated from the sheet 30 as in this embodiment, sufficient liquid can be extracted, problems due to damage to the microneedle structure 10 can be prevented, and the desired analysis can be performed. Furthermore, if the base 21 is made of a porous material, the base 21 is brittle and more likely to be damaged when the sheet 30 is peeled off.

[0074] (Analysis Method) An analysis method using the microneedle patch 1 including the microneedle structure 10 including the needle-shaped portion 11 and the liquid-absorbing layer 20 described above, and the sheet 30 will be described.

[0075] First, the needle-shaped portion 11 of the microneedle patch 1 is placed on the surface of the target and punctured. In this state, pressure is applied to the microneedle patch 1 at a position corresponding to the microneedle structure 10 to promote liquid absorption from the target. After a predetermined time has elapsed in this state, the microneedle patch 1 is peeled off from the target surface. Thereafter, the sheet 30 is peeled off from the microneedle patch 1. Next, the liquid-absorbing layer 20 is separated from the microneedle structure 10. The liquid is recovered from the separated liquid-absorbing layer 20. The recovered liquid is used to perform the desired analysis.

[0076] In this way, in this embodiment, the microneedle patch 1 is configured so that its sheet 30 can be re-peelable, so that the liquid-absorbing layer 20 can be removed without being destroyed, and a sufficient amount of extracted body fluid can be obtained for analysis.

[0077] The liquid may be collected from the microneedle structure 10 as well as the liquid-absorbing layer 20. This method is preferable when the liquid-absorbing layer 20 is fixed to the microneedle structure 10 so that it cannot be separated from the microneedle structure 10.

[0078] The analysis method according to this embodiment can also be carried out using microneedle patches 2 to 4 according to the second or third embodiment described below.

[0079] 3 to 5 show a method for manufacturing the microneedle patch 1 according to an embodiment of the present invention. In this embodiment, as shown in Fig. 3(a), a mixture 41 containing a needle-shaped portion material and a pore-forming material is prepared (preparation step), and as shown in Fig. 3(b) and (c), a predetermined process is carried out to give the mixture 41 a desired shape, thereby obtaining a solid composition 42 (composition formation step).

[0080] Thereafter, as shown in Figures 4(a) and (b), the solid composition 42 is heated and pressurized to form protrusions 43 (protrusion formation process), and then, as shown in Figure 4(c), the pore-forming material is dissolved and removed from the protrusions 43 to form needle-shaped portions 11 (removal process).

[0081] Through these steps, a microneedle structure 10 is obtained in which the protrusions 43 have become needle-shaped portions 11, as shown in Fig. 5(a). Thereafter, a sheet 30 is provided, which is a removable adhesive sheet in which the adhesive layer is sealed with a polyethylene terephthalate film, as shown in Fig. 5(b), to obtain a microneedle patch 1.

[0082] (Preparation step) First, a mixture 41 of the material constituting the needle-shaped portion 11 and the pore-forming material is prepared. The above-mentioned materials can be used as the material constituting the needle-shaped portion 11. In order to make it easier for the pore-forming material to diffuse into the material constituting the needle-shaped portion 11, the material constituting the needle-shaped portion 11 may be heated and melted before use.

[0083] Examples of pore-forming materials include water-soluble materials with melting points higher than room temperature. The water-soluble material may be organic or inorganic, and examples include sodium chloride, potassium chloride, sodium sulfate, sodium carbonate, potassium nitrate, alum, sugar, and water-soluble resins. The water-soluble resin is preferably a thermoplastic water-soluble resin, preferably one with a melting point higher than room temperature. Examples of thermoplastic water-soluble resins include the biodegradable resins described below, as well as hydroxypropyl cellulose and polyvinylpyrrolidone. Furthermore, considering the effects on the human body, it is more preferable that the thermoplastic water-soluble resin be biodegradable. Examples of such biodegradable and thermoplastic water-soluble resins include at least one selected from the group consisting of polyalkylene glycols such as polyethylene glycol and polypropylene glycol, polyvinyl alcohol, collagen, and mixtures thereof, with polyalkylene glycol being particularly preferred.

[0084] The material constituting the needle-shaped portions 11 and the pore-forming material are preferably mixed at a mass ratio of 8:2 to 2:8, and more preferably 7:3 to 3:7. By forming the mixture 41 at this ratio, needle-shaped portions 11 with the desired porosity can be formed, and it becomes easier to achieve both liquid permeability and strength for the needle-shaped portions 11.

[0085] The pore-forming material may be mixed with a solvent, such as isopropyl alcohol, ethyl acetate, ethanol, dichloromethane, dimethylformamide, or toluene.

[0086] The mixture 41 may contain not only the material constituting the needle-shaped portion 11 and the pore-forming material, but also other materials, such as a water-insoluble hydrophilic resin or a filler.

[0087] (Composition Forming Step) The mixture 41 is poured into a recess 45 for a solid composition formed in a mold (die) 44 for a solid composition. The recess 45 for a solid composition may be formed with a shape and volume that allows a desired amount of the mixture 41 to be stored therein.

[0088] The material of the mold 44 for the solid composition is not particularly limited, but it is preferable that it be made of a silicone compound or the like, which makes it easy to make an accurate mold and makes it easy to peel off the solidified solid mixture 41, and in this embodiment it is made of polydimethylsiloxane.

[0089] With the mixture 41 stored in the recess 45 for the solid composition, unnecessary mixture 41 is removed with a spatula or the like, and the surface of the resulting solid composition 42 is flattened. In this case, heating may be performed to partially remove the solvent contained in the mixture 41. The solid composition mold 44 is then pressurized at 2 to 20 MPa, and after the pressure is released, the mixture is held at −10 to 15°C for 1 to 60 minutes, whereby the molten mixture 41 solidifies and becomes solid. When the mixture is held in a cooled state, it may be sandwiched between, for example, cooled SUS plates. The mixture is then heated at 35 to 70°C to evaporate the remaining solvent from the solid mixture 41, and the mixture is dried to obtain the solid composition 42.

[0090] 4( a), the solid composition 42 is placed in a recess 51 of a mold 52 having a recess 51. As with the mold 44 for the solid composition, the material of the mold 52 is not particularly limited, but it is preferable that the mold 52 be made of a silicone compound or the like that makes it easy to form an accurate mold and to peel off the solid composition 42, and in this embodiment, it is made of polydimethylsiloxane.

[0091] A protrusion-forming recess 53 is formed in the center of the bottom surface of the recess 51. The protrusion-forming recess 53 is for forming the needle-like portion 11 and is formed in a shape and size corresponding to the needle-like portion 11. A lid 54 of the mold 52 is then placed on the other surface side (rear side). This lid 54 is also made of polydimethylsiloxane. The solid composition 42 is placed on the protrusion-forming recess 53.

[0092] Next, a heating and pressurizing treatment is carried out to form the desired shapes of protrusions 43, etc. In this case, the heating and pressurizing treatment may be carried out all at once, but as in the present embodiment, it is preferable to carry out the heating and pressurizing treatment in two steps: a preliminary step of starting to melt the solid composition 42 so that the solid composition 42 is sufficiently filled into the recesses 51 and the protrusion-forming recesses 53 of the mold 52; and a main step of sufficiently filling the recesses 51 and the protrusion-forming recesses 53 of the mold 52 with the molten solid composition 42.

[0093] 4(b), in the preliminary step and the main step, the solid composition 42 is placed in the recess 51 and sandwiched between the mold 52 and the lid 54. Then, in this state, the mold 52 and the lid 54 are placed on the lower stage 56, and the upper stage 57 is placed on the mold 52 and the lid 54.

[0094] The heating conditions in the preliminary step and this step may be any temperature higher than the melting point of the material constituting the needle-shaped portion 11, and in this embodiment, heating is performed at a temperature at which the solid composition 42 can melt. Note that, to heat the solid composition 42, at least one of the lower stage 56 and the upper stage 57 may be heated, or both may be heated. In this step, heating may be maintained after the preliminary step, and the temperature may be changed as appropriate.

[0095] In this state, the mold 52 is pressed (pressurized) between the upper stage 57 and the lower stage 56. The pressure in this preliminary step is preferably 0.1 to 5.0 MPa. By using a pressure in this range, the solid composition 42 can be melted in a short time, and the molten solid composition 42 can be quickly filled into the recesses 51, etc. Then, by maintaining this state for 10 seconds to 10 minutes, the solid composition 42 becomes molten. Note that the pressurizing conditions may be different between the preliminary step and the main step. For example, in the main step, pressurization can be performed under conditions of higher pressure or for a longer time than in the preliminary step.

[0096] By carrying out the preliminary step and the main step as in this embodiment, the solid composition 42 is sufficiently melted and filled into the recesses 51 and the protrusion-forming recesses 53 .

[0097] Thereafter, the mold 52 is removed from the lower stage 56, and the molten solid composition 42 is refrigerated and solidified by being held at −10 to 15° C. for 1 to 60 minutes, thereby forming the protrusions 43 and the like having a shape corresponding to the protrusion-forming recesses 53 and having high transferability.

[0098] (Removing Step) Then, the solid composition 42 on which the solidified protrusions 43 have been formed is separated from the mold 52 and left to stand in a liquid, thereby performing the removing step of removing the pore-forming material and forming the needle-shaped portions 11 .

[0099] The cleaning solution used in this removal step contains water, and the removal step is performed by placing the solid composition 42 on which the protrusions 43 have been formed in a cleaning solution 58, as shown in FIG. 4(c). By placing the solid composition 42 in a cleaning solution containing water, the pore-forming material contained in the protrusions 43, etc., that is exposed to the outside or that is connected to the exposed portions dissolves and flows into the water, where it is removed. The cleaning solution 58 may contain water, and may be, for example, a mixed solvent of water and alcohol. This removal forms holes 12 in the protrusions 43, etc., and forms needle-shaped portions 11 made of a water-insoluble component, as shown in FIG. 5(a). In addition to the needle-shaped portions 11, the pore-forming material is also removed from the molten solid composition 42 that had adhered to the recesses 51 by filling them, and the base 21 is also formed with the same porous structure.

[0100] (Plasma Irradiation Step) After the needle-shaped portion 11 and the base portion 21 are fabricated, the needle-shaped portion 11 may be irradiated with plasma and coated with a hydrophilic substance (not shown). Plasma irradiation excites the inner surface of the flow channel 13. By performing the plasma irradiation treatment, it becomes easier to fix the hydrophilic substance to the inner surface of the flow channel 13 in the subsequent coating step.

[0101] The plasma irradiation is preferably performed on both the needle-shaped portion 11 side and the base portion 21 side. The plasma irradiation time for each side is, for example, 5 to 120 seconds.

[0102] (Coating Step) Subsequently, a hydrophilic substance is brought into contact with the inner surface of the flow channel 13 in the needle-shaped portion 11 to form a coating.

[0103] Specifically, a hydrophilic substance-containing liquid (including a liquid containing a substance that reacts with the inner surface of the flow path 13 in the needle-shaped portion 11 to form a hydrophilic substance; the same applies hereinafter) is prepared. Then, the needle-shaped portion 11 and the base portion 21 are immersed in the hydrophilic substance-containing liquid. As a result, a coating containing a hydrophilic substance is formed on the inner surface of the flow path 13 in the needle-shaped portion 11. While the needle-shaped portion 11 and the base portion 21 are immersed, it is preferable to reduce the pressure of the surrounding environment. This makes it easier for the hydrophilic substance-containing liquid to penetrate deep into the flow path 13 of the microneedle structure. The reduced pressure condition is, for example, about 0.01 MPa to 0.5 MPa. The reduced pressure environment is maintained for, for example, about 15 minutes to 3 hours.

[0104] The concentration of the hydrophilic substance in the hydrophilic substance-containing liquid is appropriately selected depending on the type of hydrophilic substance.

[0105] For example, when the hydrophilic substance is polyethylene glycol, the concentration of polyethylene glycol in the hydrophilic substance-containing liquid is preferably 0.1 to 15% by mass, more preferably 0.3 to 10% by mass, and even more preferably 0.5 to 8% by mass.

[0106] When the hydrophilic substance is a compound derived from arginine, the concentration of arginine in the hydrophilic substance-containing liquid is, for example, 0.01 to 3 mol / L, preferably 0.03 to 2 mol / L, and more preferably 0.05 to 1 mol / L.

[0107] When the hydrophilic substance is polyvinyl alcohol, the concentration of polyvinyl alcohol in the hydrophilic substance-containing liquid is, for example, 0.1 to 15% by mass, preferably 0.3 to 10% by mass, and more preferably 0.5 to 8% by mass.

[0108] The solvent used for the hydrophilic substance-containing liquid is not particularly limited. For example, water, isopropyl alcohol, etc. can be used as the solvent. Preferably, water is used as the solvent.

[0109] The coating does not necessarily have to be formed from a hydrophilic substance-containing liquid. For example, a film-forming method such as plasma CVD can be used to form a coating on the inner surface of the flow channel 13. For example, when the hydrophilic substance is an inorganic substance such as silicon oxide, plasma CVD can be used.

[0110] 5(b), the liquid-absorbing layer 20 is placed at a predetermined position on the back side of the obtained base 21. Thereafter, a sheet 30 having a film 31 as a release layer is laminated so as to cover the liquid-absorbing layer 20, thereby manufacturing a microneedle patch 1 having the microneedle structure 10 of this embodiment that is capable of extracting a desired amount of liquid.

[0111] Next, the sheet 30 is prepared. First, an adhesive is applied to the entire base material of the sheet 30. Next, the adhesive is again applied to the area that will become the third area A3. As a result, an adhesive layer with weak adhesiveness is formed in the first area A1 and the second area A2, and an adhesive layer with stronger adhesiveness than the first area A1 and the second area A2 is formed in the third area A3. Next, a film 31 is provided as a release layer in the area that will become the first area A1. Eight through holes 32 are opened at equal intervals in the sheet 30 along the outer edge of this film 31. In this way, the sheet 30 is obtained.

[0112] Thereafter, by laminating a sheet 30 having a film 31 as a release layer so as to cover the liquid absorbing layer 20, it is possible to manufacture a microneedle patch 1 capable of extracting the desired amount of liquid.

[0113] (Embodiment 2) The microneedle patch 2 according to this embodiment shown in Figure 6 differs from Embodiment 1 in that a hard porous material is used as the liquid-absorbent layer 20. The liquid-absorbent layer 20 made of a hard porous material does not have compressive deformation properties, and therefore is less likely to leak absorbed liquid due to impact or the like. Therefore, as shown in Figure 6, only the upper surface of the liquid-absorbent layer 20 is covered with a sheet 30, and the sides are not covered with the sheet 30 and are exposed. Note that in the following Embodiments 2 to 5, the same reference numerals are used for components similar to those of Embodiment 1, and only the parts that differ from any of the comparative embodiments will be described.

[0114] Hard porous materials that can be used for the liquid-absorbent layer 20 of this embodiment include porous materials obtained by the salt leaching method described in the method for forming the needle-shaped portions 11, as well as sintered porous bodies obtained by sintering resin particles. When the liquid-absorbent layer 20 is made of a material other than a porous material, for example, a polymeric water-absorbing material such as polyacrylate particles can be used. Forming the liquid-absorbent layer 20 from a porous material is preferable because it facilitates separation of the stored biological liquid. Note that these porous materials can also be used in the above-mentioned embodiment 1.

[0115] Furthermore, the liquid absorbent layer 20 preferably contains a resin whose molecular structure contains carbon atoms and oxygen atoms, with the ratio of the number of oxygen atoms to carbon atoms being 1 / 2 or more. Even if such a resin does not itself have pores, it can be made porous by the salt leaching method described above. The hydrophilicity of the liquid absorbent layer 20 can be enhanced by using a resin whose molecular structure contains carbon atoms and oxygen atoms, with the ratio of the number of oxygen atoms to carbon atoms being 1 / 2 or more, as the liquid absorbent layer 20. When the resin is a biodegradable resin, examples of such hydrophilic resins include polylactic acid, whose molecular structure contains a ratio of the number of oxygen atoms to carbon atoms of 2 / 3, polyglycolic acid, whose molecular structure contains a ratio of 1 / 1, and copolymers of lactic acid and glycolic acid.

[0116] Furthermore, as in the first embodiment, the liquid-absorbing layer 20 may contain a resin that has hydroxyl groups and is insoluble in water. As described in the first embodiment, the resin that has hydroxyl groups and is insoluble in water may be mixed in particulate form as a filler into the base resin of the porous material. For example, the porous material may be formed using a composition in which cellulose fiber is mixed as a filler into a polycaprolactone-based base.

[0117] In this embodiment, the base 21 is made of the same biodegradable resin as the needle-shaped portions 11, and the liquid-absorbent layer 20 is made of a sintered porous body formed by sintering resin particles. By making the base 21, the needle-shaped portions 11, and the liquid-absorbent layer 20 out of different materials in this way, the amount of liquid that can be absorbed by the liquid-absorbent layer 20 can be increased by using a material for the liquid-absorbent layer 20 that is more liquid-absorbent than the base 21. Alternatively, for example, the base 21 may be made of the same biodegradable resin as the needle-shaped portions 11, and the liquid-absorbent layer 20 may be made of a biodegradable resin in which a pore-forming material has been prepared so that the pore area of ​​each layer is larger than that of the needle-shaped portions 11. Even in this case, the amount of liquid that can be absorbed by the liquid-absorbent layer 20 can be increased by using a material for the liquid-absorbent layer 20 that is more liquid-absorbent than the base 21.

[0118] When such a hard liquid-absorbent layer 20 is used, unlike in Embodiment 1, the base 21 and the liquid-absorbent layer 20 are formed to be the same size, and the base 21 and the liquid-absorbent layer 20 are fixed together, and then the sheet 30 is adhered to the liquid-absorbent layer 20. In this case, the adhesive layer in the first region A1 of the sheet 30 is removably adhesive. Because the adhesive is easily peeled from the hard liquid-absorbent layer 20, there is little need to provide the first region A1 without adhesive, as in Embodiment 1, and the microneedle patch 1 can be easily manufactured. When the base 21 and the liquid-absorbent layer 20 are fixed together, the solid composition 42 is placed on the mold 52 in the protrusion formation step, and then this porous body is placed on the solid composition 42 and subjected to a heating treatment. This results in a microneedle structure 10 in which the base 21 and the liquid-absorbent layer 20 made of a porous body are adhered and fixed together.

[0119] In this case, for example, the sheet 30 may be made of an elastically deformable material such as silicone rubber instead of a stretchable woven fabric. Also, the liquid absorbent layer 20 may be a thick base (300 μm or more).

[0120] (Embodiment 3) The microneedle patch 3 of this embodiment shown in Fig. 7 differs in that a covering member 60 is used as the covering layer, rather than the sheet 30 shown in embodiments 1 and 2. The covering member 60 can be made of an elastically deformable material, specifically, urethane foam, styrene rubber, silicone rubber, etc. In this embodiment, it is made of silicone rubber.

[0121] In this embodiment, the covering member 60 has a fitting recess 61 formed on one surface thereof into which at least the base 21 fits, so that the covering member 60 has a shape corresponding to the shape (shape of the base 21) of the microneedle structure 10. As in embodiment 1, the microneedle structure 10 has a base 21 that is larger than the liquid-absorbing layer 20, and the base 21 is exposed from the liquid-absorbing layer 20 in plan view. Although any of the materials shown in embodiments 1 and 2 can be used for the materials of the components of the microneedle structure 10 of this embodiment, in this embodiment, the liquid-absorbing layer 20 is made of nonwoven fabric.

[0122] Since the covering member 60 is made of silicone rubber, it is elastically deformable, and when the covering member 60 around the fitting recess 61 is spread and the microneedle structure 10 is inserted, the covering member 60 elastically deforms and the microneedle structure 10 fits into the fitting recess 61. This fixes the liquid absorbent layer 20 and the base 21 to the covering member 60.

[0123] In the microneedle patch 3 shown in embodiment 3, the covering member 60 is made of silicone rubber, which allows the microneedle structure 10 to be fixed in place, and after the microneedle patch 3 is inserted into the subject, the microneedle structure 10 can be easily separated from the covering member 60 without breaking.

[0124] (Embodiment 4) In the microneedle patch 4 of this embodiment shown in Figure 8, a covering member 60 similar to that of embodiment 3 is used as the covering layer, but it differs from embodiment 3 in that a space 63 is provided between the covering recess 62 of the covering member 60 and the microneedle structure 10.

[0125] In this embodiment, the microneedle structure 10 has a base 21 that is larger than the liquid-absorbing layer 20, and in plan view, the base 21 is exposed from the liquid-absorbing layer 20. Although any of the materials shown in Embodiments 1 and 2 can be used for the materials of each component of the microneedle structure 10 of this embodiment, in this embodiment, the liquid-absorbing layer 20 is made of nonwoven fabric.

[0126] A covering recess 62 is formed on one surface of the covering member 60. The covering recess 62 consists of an opening side 64 close to the opening side and a bottom side 65 on the bottom side of the covering recess 62. The opening side 64 has a shape corresponding to the base 21, and the bottom side 65 is configured to be larger than the liquid absorbent layer 20 but smaller than the opening side 64. Therefore, when the microneedle structure 10 is placed in the covering recess 62, the side surface and peripheral edge of the base 21 are fitted together and fixed at the opening side 64, but a space 63 is formed between the bottom side 65 and the microneedle structure 10.

[0127] In the microneedle patch 4 shown in the fourth embodiment, the covering member 60 is made of silicone rubber, and the opening side portion 64 has a shape corresponding to the base portion 21, so that the microneedle structure 10 can be fixed, and after the microneedle patch 3 is inserted into the subject, the microneedle structure 10 can be easily separated from the covering member 60 without breaking. Furthermore, the formation of the space 63 makes it possible to press the covering member 60 to push out air within the space and create a negative pressure state inside the liquid-absorbent layer 20. This makes it even easier for the liquid-absorbent layer 20 to absorb liquid, and it is possible to shorten the time required to collect bodily fluids.

[0128] 9, a through-hole 66 may be provided in the covering member 60, communicating with the top surface of the covering recess 62 and a pressure reducing means 67 may be inserted into the through-hole to directly remove air from inside the liquid-absorbent layer 20 and reduce the pressure. Examples of the pressure reducing means 67 include a syringe and a vacuum pump.

[0129] 1, 2, 3, 4 Microneedle patch 10 Microneedle structure 11 Needle-shaped portion 12 Hole portion 13 Flow path 20 Liquid-absorbing layer 21 Base portion 30 Sheet 31 Film 32 Through-hole 41 Mixture 42 Solid composition 43 Protrusion portion 44 Mold for solid composition 45 Recess for solid composition 51 Recess 52 Mold 53 Recess for forming protrusion portion 54 Lid 56 Lower stage 57 Upper stage 58 Cleaning liquid 60 Covering member 61 Fitting recess 62 Covering recess 63 Space 64 Opening side portion 65 Bottom side portion 66 Through-hole 67 Pressure reducing means

Claims

1. A microneedle patch comprising a liquid absorbent layer that absorbs liquid and a needle-shaped portion having a flow path formed therein, the flow path of the needle-shaped portion being connected to one side of the liquid absorbent layer, and a covering layer being provided on the other side of the liquid absorbent layer, the covering layer being separable from the other side.

2. The microneedle patch according to claim 1, characterized in that the liquid absorbent layer has compressive deformability.

3. The microneedle patch according to claim 1, characterized in that the liquid absorbing layer is made of a hard porous material.

4. The microneedle patch according to claim 1, characterized in that the needle-shaped portion contains a water-insoluble hydrophilic resin.

5. The microneedle patch according to claim 1, wherein a coating containing a hydrophilic substance is formed on the inner surface of the flow channel.

6. The microneedle patch according to claim 1, characterized in that a first region of the covering layer facing the liquid absorbent layer on the surface facing the liquid absorbent layer is not adhesive.

7. The microneedle patch described in claim 6, characterized in that a base on which the needle-shaped portion is provided is provided between the liquid absorbent layer and the needle-shaped portion, the base is exposed to a greater extent than the liquid absorbent layer in a planar view, and a second region facing the exposed base on the surface of the covering layer facing the liquid absorbent layer has adhesive properties.

8. The microneedle patch described in claim 7, characterized in that a third region other than the first region and the second region on the surface of the covering layer facing the liquid absorbent layer has adhesiveness.

9. The microneedle patch described in claim 1, characterized in that a base on which the needle-shaped portion is provided is provided between the liquid absorbent layer and the needle-shaped portion, and the covering layer is provided with at least a recess into which the base portion fits.

10. The microneedle patch according to claim 9, characterized in that it has a hollow space between the liquid absorbing layer and the covering layer.

11. The microneedle patch according to claim 10, further comprising a pressure reducing means for reducing the pressure inside the liquid absorbing layer.

12. An analytical method using a microneedle patch comprising a liquid absorbing layer that absorbs liquid and a needle-shaped portion having a flow path formed therein, the needle-shaped portion being connected to one side of the liquid absorbing layer, and a coating layer that covers the liquid absorbing layer on the other side of the liquid absorbing layer and is non-permeable to liquid and is provided so as to be detachable from the other side, the analytical method comprising the steps of: puncturing the needle-shaped portion of the microneedle patch into a target and absorbing liquid from the target; separating the liquid absorbing layer from the coating layer; and recovering the liquid from the separated liquid absorbing layer.

Images