WO2023190910A1 - Microneedle structure - Google Patents

Abstract

This microneedle structure 10 comprises a needle-shaped part 12 having a hole 13 formed in the interior thereof. The needle-shaped part 12 contains a resin and a filler 21. Such a microneedle structure can be configured to have a needle-shaped part having high strength.

Description

microneedle structure

The present invention relates to a microneedle structure.

In recent years, microneedles have been proposed that supply drugs into the body and collect body fluids from the body through through holes formed in the microneedles. For example, microneedles are known that include a microneedle-shaped biocompatible matrix and porous particles provided on the surface or at least partially inside the biocompatible matrix (Patent Document 1). .

Japanese Patent Application Publication No. 2014-094171

In Patent Document 1, the biocompatible material that makes up the microneedles is swollen within a few seconds to a few hours when inserted into the skin, and is absorbed into living tissue, so the microneedles do not swell in the body. It is assumed that it will be absorbed. However, from the viewpoint of safety, it is desirable to remove the inserted microneedles so that they remain in the skin as little as possible. Here, for example, if a microneedle containing porous particles as shown in Patent Document 1 is inserted and then removed from the skin, there is a problem that the microneedle is damaged due to insufficient strength. Furthermore, if the strength of the needle-like portion of the microneedle is low, it may break when puncturing the skin, reducing the efficiency of drug supply, etc.

The present invention was made in view of the above circumstances, and an object of the present invention is to provide a microneedle structure having a needle-like portion with high strength.

In order to achieve the above object, the present invention first provides a microneedle structure comprising a needle-like part with a hole formed inside the microneedle structure, the needle-like part containing a resin and a filler. A microneedle structure is provided (invention 1).

In the above invention (invention 1), the needle-shaped portion contains not only resin but also filler, so that sufficient strength can be maintained. In other words, if the needle has a structure in which multiple holes are opened on its side, the speed at which fluid is absorbed or released from the needle may be lower than in a structure in which holes are opened only at the top of the needle. Although it is possible to increase the strength, the needle-shaped portion may become brittle and have insufficient strength. However, since the present invention contains a filler, the strength can be increased, and it is possible to prevent the needle-like part from being damaged when, for example, the needle-like part is pierced into the skin.

In the above invention (invention 1), it is preferable that a porous structure is formed in the needle-like part (invention 2).

In the above inventions (Inventions 1 and 2), it is preferable that the resin constituting the needle portion is a low melting point resin having a melting point of 130° C. or lower (Invention 3).

In the above invention (invention 3), it is preferable to include a base material having the needle-shaped portion on one side (invention 4).

In the above invention (invention 4), it is preferable that the base material and the needle-like part are bonded together via a base made of the same material as the needle-like part (invention 5).

In the above inventions (Inventions 1 to 5), the filler is preferably made of resin (Invention 6).

In the above invention (invention 6), the filler is preferably made of a resin whose glass transition temperature is 80° C. or lower (invention 7).

In the above inventions (Inventions 6 and 7), the filler preferably consists of one or more types selected from the group consisting of natural organic polymers or modified products thereof, and biodegradable resins (Invention 8).

In the above inventions (Inventions 1 to 8), the filler is preferably fibrous (Invention 9).

In the above inventions (Inventions 1 to 9), it is preferable that the filler is contained in an amount of 3 to 50% by mass based on the entire mass of the needle-shaped portion (Invention 10).

In the above inventions (Inventions 1 to 10), it is preferable that the resin forming the needle portion is a water-insoluble resin (Invention 11).

In the above inventions (Inventions 1 to 11), it is preferable that the resin forming the needle portion is a biodegradable resin (Invention 12).

They are (1) a schematic cross-sectional view and (2) a partially enlarged view of a needle-like part of the microneedle structure of the present invention. FIG. 1 is a schematic partial cross-sectional view of a test patch using the microneedle structure of the present invention. (a) to (c) are explanatory diagrams showing the steps of a method for manufacturing a microneedle structure according to an embodiment. (a) to (c) are explanatory diagrams showing the steps of a method for manufacturing a microneedle structure according to an embodiment.

Embodiments of the present invention will be described below.
[Microneedle structure]
FIG. 1 shows a microneedle structure 10 according to one embodiment of the present invention. The microneedle structure 10 includes a plurality of needle-shaped parts 12 spaced apart from each other at predetermined intervals on one side of a base material 11. Further, a plurality of holes 13 are formed in each of the needle portions 12 . A through hole 15 is formed in the base material 11 . The microneedle structure 10 is a test patch that absorbs body fluid from within the skin through the hole 13 of the needle-shaped part 12 and performs a test using the body fluid obtained through the base material 11, and the base material 11 and It can be used as a drug administration patch for administering a drug into the body through the skin through the hole 13 of the needle-shaped portion 12. Note that in the present invention, body fluids include blood, lymph fluid, interstitial fluid, and the like.

(1) Needle-shaped portion The shape, size, formation pitch, and number of needle-like portions 12 can be appropriately selected depending on the intended use of the microneedle. Examples of the shape of the needle portion 12 include a cylindrical shape, a prismatic shape, a conical shape, a pyramid shape, and the like, and in this embodiment, it is a pyramid shape. The maximum diameter or maximum cross-sectional dimension of the needle-like portion 12 is, for example, 25 to 1000 μm, and the tip diameter or cross-sectional dimension of the tip is 1 to 100 μm. The height is, for example, 50 to 2000 μm. Furthermore, the needle-shaped parts 12 are provided in a plurality of rows in one direction of the base material 11, and a plurality of needle-like parts 12 are formed in each row and arranged in a matrix.

The needle-shaped portion 12 is made of resin. It is preferable that the resin forming the needle portion 12 is a low melting point resin. The low melting point resin is preferably a material that is solid at room temperature and has a melting point of 130°C or less, particularly preferably a material with a melting point of 40 to 120°C, and most preferably a material with a melting point of 45 to 100°C. . By being solid at room temperature, the shape of the needle-like part 12 can be maintained at room temperature, and when the melting point is 130°C or less, when melting the resin to form the needle-like part 12, the resin is not heated at high temperatures. No need for heating, low cost and excellent workability. In addition, even if the resin is bonded to the base material 11 in a molten state, or the resin is heated while the resin and the base material are bonded, the base material 11 may soften, deform, or burn because it is melted at a low temperature. Therefore, there is a high degree of freedom in selecting the base material 11. Furthermore, for example, even when a nonwoven fabric or a resin film made of synthetic fibers or the like having a low heat resistance temperature is used as the base material 11, deterioration of the base material 11 due to softening of the synthetic fibers can be prevented.

As will be described later, in the case of a structure in which a plurality of holes 13 are opened on the side surface of the needle-like part 12, fluid is absorbed or released from the needle-like part 12 compared to a structure in which holes are opened only at the top of the needle-like part. Although it is possible to increase the speed, the needle-shaped portion 12 becomes brittle and its strength tends to decrease. However, in this embodiment, as described later, the filler is contained in the needle-shaped portion 12, so that the strength of the needle-shaped portion 12, particularly the strength of the tip of the needle-shaped portion 12, can be increased. It is possible to prevent the needle-like part 12 from being damaged when the needle-like part 12 is pierced into the skin.

The resin constituting the needle portion 12 may further be a water-insoluble resin. Being water-insoluble, it is possible to maintain the shape of the microneedle structure 10 for a desired application time without being dissolved by body fluids when applied to a living body, and as will be described later. A minute hole 13 can be easily formed. Examples of water-insoluble resins include polyolefin resins such as polyethylene and α-olefin copolymers, olefin copolymer resins such as ethylene-vinyl acetate copolymer resins, polyurethane elastomers, and ethylene-ethyl acrylate copolymers. Examples include acrylic copolymer resins.

Furthermore, the resin constituting the needle-shaped portion 12 may be a biodegradable resin. Here, biodegradable resin is a plastic that is completely decomposed into _CO2 and water by the action of microorganisms that exist in nature after use. can reduce the impact of As such biodegradable resins, aliphatic polyesters and derivatives thereof are preferably used, and further, homocopolymers of at least one monomer selected from the group consisting of glycolic acid, lactic acid, and caprolactone, or Examples include copolymers made of two or more types of monomers. In addition, polybutylene succinate (melting point: 84-115°C), aliphatic aromatic copolyester (melting point: 110-120°C), etc. can also be used as low-melting point biodegradable resins. As the butylene succinate, BioPBS provided by Mitsubishi Chemical Corporation, etc. can be used, and as the aliphatic aromatic copolyester, Ecoflex manufactured by BASF, etc. can be used.

Furthermore, the biodegradable resin may be a resin whose monomer has an acid dissociation constant of 4 or more. When the acid dissociation constant of the monomer is 4 or more, the influence on the living body when the microneedle structure 10 is applied to the living body can be reduced. Note that, when the monomer is a cyclic ester, the acid dissociation constant of the monomer referred to herein is the acid dissociation constant of the hydroxycarboxylic acid in which the cyclic ester is ring-opened. The acid dissociation constant of the monomer is preferably 4.0 or more, more preferably 4.5 or more. Further, the acid dissociation constant of the monomer is preferably 25 or less, more preferably 15 or less. An example of such a monomer constituting the biodegradable resin and having an acid dissociation constant of 4 or more is caprolactone. In the biodegradable resin having a low melting point, the constituent units of the monomers from which the acid dissociation constant is 4 or more preferably account for 70% by mass or more, and preferably 80% by mass or more of the total constituent units. The content is more preferably 90% by mass or more.

Further, the molecular weight of the resin constituting the needle-shaped portion 12 is usually 5,000 to 300,000, preferably 7,000 to 200,000, and more preferably 8,000 to 150,000.

Most preferably, the resin constituting the needle portion 12 is polycaprolactone or caprolactone, which is a water-insoluble low-melting resin, a biodegradable resin, and has a monomer acid dissociation constant of 4 or more. and copolymers of other polymers.

The needle portion 12 further contains filler 21. It is possible to improve the mechanical strength of the needle-like part 12 because the needle-like part 12 contains the filler 21. The filler 21 is preferably contained in a dispersed state in the resin of the needle-shaped portion 12.

The filler 21 is preferably made of resin, and is preferably made of one selected from the group consisting of natural organic polymers or modified products thereof, and biodegradable resins. The filler 21 made of resin can also be one containing an inorganic component, such as an organic/inorganic hybrid filler in which an inorganic substance is attached to the surface of resin particles. It is preferable to consist only of organic components and, more preferably, it consists only of resin. Examples of natural organic polymers include cellulose, and fillers made of natural organic polymers or modified products thereof include cellulose fibers, cellulose acetate true spherical particles, and the like.

As the biodegradable resin, those mentioned above can be used, but when a biodegradable resin is used as the resin constituting the needle-like part 12, a biodegradable resin different from this biodegradable resin is used. From the viewpoint of further improving the mechanical strength of the filler 21 as described later, a biodegradable resin having a melting point exceeding 130° C. or having no melting point is preferable. Such biodegradable resins include polylactic acid (melting point: 170°C), polyglycolic acid (melting point: 218°C), polyhydroxybutyric acid (melting point: 175°C), and cellulose acetate diacetate (melting point: 230-300°C). ) etc. Note that biodegradable resins such as cellulose acetate diacetate also fall under the category of modified natural organic polymers.

From the viewpoint of further improving the mechanical strength of the needle-shaped portion 12, the filler 21 is preferably made of a resin with a melting point exceeding 130° C. or having no melting point. If the resin has a melting point exceeding 130° C., it will be difficult to soften at a temperature near the room temperature at which the microneedle structure 10 is used. Therefore, when the filler 21 is made of a resin having a melting point exceeding 130° C., it is easy to obtain sufficient strength of the microneedle structure 10. In addition, when the filler 12 is made of a resin with a melting point exceeding 130°C, by adding such a hard-to-melt resin in the form of a filler, the hard-to-melt resin can be added when mixed with a low-melting point resin. This is preferred because it can be produced by dispersing the filler in the composition and kneading it at a low temperature without melting it. Other than the biodegradable resins mentioned above, examples of resins with a melting point exceeding 130°C or no melting point include polypropylene (melting point: 155°C), polybutylene terephthalate (223°C), polyethylene terephthalate (melting point: 260°C), Examples include polytetrafluoroethylene (melting point: 327°C), melamine resin (melting point: none), unmodified cellulose (melting point: none).

It is preferable that the filler 21 is made of a resin having a glass transition temperature of 80° C. or lower. Since the filler 21 is made of a resin with a glass transition temperature of 80° C. or less, the filler tends to soften during melting even when melting the resin constituting the needle portion 12 at a low temperature. It becomes easily compatible with the resin forming the shaped portion 12. This makes it easier to improve the strength of the needle-shaped portion 12 to be manufactured. Note that when the resin contained in the filler 21 is crosslinked, the polymer before crosslinking has a glass transition temperature of 80° C. or lower. Examples of resins having a glass transition temperature of 80°C or lower include polypropylene (Tg: 0°C), polybutylene terephthalate (Tg: 50°C), polyethylene terephthalate (Tg: 69°C), polymethyl methacrylate (Tg: 60°C), Examples include polylactic acid (Tg: 60°C), polyglycolic acid (Tg: 40°C), polyhydroxybutyric acid (Tg: 15°C), etc. Among these, as mentioned above, those that are biodegradable resins Preferably, it is polylactic acid, polyglycolic acid, polyhydroxybutyric acid, or a copolymer of these polymeric monomers. It is also preferable that the filler 21 is made of a resin having a glass transition temperature of −10° C. or higher, from the viewpoint of further improving the mechanical strength of the needle-shaped portion 12. The filler 21 is more preferably made of a resin having a glass transition temperature of 10 to 80°C, and even more preferably made of a resin having a glass transition temperature of 30 to 75°C.

The filler 21 is preferably contained in an amount of 3 to 50% by mass, more preferably 5 to 43% by mass, and even more preferably 10 to 35% by mass, based on the mass of the entire needle portion 12. It is. When the content is 50% by mass or less, it becomes easy to maintain the shape of the needle-shaped portion 12, and workability during manufacturing also improves. When the content is 3% by mass or more, it becomes easier to increase the strength. By containing the filler 21 in a content within this range, the strength of the needle-like part 12 due to the filler 21 can be increased while forming the needle-like part 12 with a desired porosity and maintaining liquid permeability. It becomes easier. Further, two or more kinds of fillers 21 described above may be contained. Even in this case, it is preferable to include the filler 21 in the resin constituting the needle portion 12 so that the total amount of the filler 21 falls within the above content range.

The shape of the filler 21 may be plate-like (flake-like), fibrous, spherical, amorphous, etc., but fibrous is preferable. It is preferable that the shape of the filler 21 is fibrous because it easily adapts to the melted resin constituting the needle-like part 12 and easily improves the strength of the obtained needle-like part 12. Examples of fillers having a fibrous shape include metal fiber fillers, carbon fibers, carbon nanofibers, and cellulose fibers. When the filler 21 has a shape other than fibrous, for example, when it has a spherical or amorphous shape, the filler 21 can be made of a resin having a glass transition temperature of 80° C. or lower, as described above. becomes more compatible with low melting point resins. The particle size of the filler 21 is 0.3 to 150 μm, preferably 0.5 to 125 μm, and more preferably 1 to 100 μm. By setting the particle size of the filler 21 to 0.3 to 150 μm, the filler 21 can be easily dispersed in a composition containing a low melting point resin, and the strength of the obtained microneedle structure 10 can be further improved. I can do it. The particle diameter of the filler 21 is the average of 7 values obtained by observing the filler 21 in the microneedle structure 10 with a scanning electron microscope (SEM) and measuring the length of the longest part of the particle. When the filler 21 is fibrous, the particle diameter refers to the fiber length.

In this way, the strength at the tip of the needle portion 12 obtained by having the filler 21 is usually 40 mN or more, preferably 60 mN or more, and more preferably 85 mN or more. By setting the force to 40 mN or more, it is possible to prevent the needle-like portion 12 from breaking even if the skin is punctured, and the microneedle structure 10 can be used, for example, as a test patch. The tip strength of the needle-shaped portion 12 is a value measured by the procedure described in Examples described later.

The needle-shaped portion 12 has a hole 13 formed therein as a flow path through which liquid flows. One or more holes 13 are formed in one needle-like section 12 and open at least one on the surface of the needle-like section 12 . The hole 13 may be formed in any way, for example, a single communicating hole may be provided mechanically, but it is preferable that the needle-shaped portion 12 has a porous structure as in this embodiment. . If the needle-shaped part 12 is formed so that at least a part thereof has a porous structure, body fluids or medical fluids can pass through the pores 13 of the porous structure, so it is not necessary to mechanically form a nano-order flow path. It is preferable that there is no such thing. In addition, since body fluids or medical fluids can flow through all the flow paths in the porous structure of the needle part 12, the amount of flow can be reduced compared to when a single communicating hole is formed. It is possible to increase it. Furthermore, when the needle-like part 12 is formed so that at least a part thereof has a porous structure, if the porous structure is not covered on a part or all of the side surface of the needle-like part, the needle-like part 12 A hole 13 is also opened on the side surface. In this case, the amount of liquid flowing can be increased compared to the case where only the tip of the needle portion 12 is opened.

However, in such a case, the needle-shaped portion 12 may become brittle, but in this embodiment, since the needle-shaped portion 12 is formed by adding a filler to a low-melting resin, the needle-shaped portion 12 may become brittle. The needle-shaped portion 12 with high strength can be formed without becoming.

The method for forming the porous structure will be described in detail later, but the porous structure may be formed simultaneously with the formation of the needle-shaped portion 12, or the protrusion 32 (not shown in FIG. 1, which will be described later) in which no porous structure is formed. A method of forming a porous structure in the projection 32 after the formation of the hole 13 is preferable from the viewpoint of making the hole 13 have a continuous structure. In the latter case, for example, the protrusion 32 is formed by mixing two or more different materials, and then at least one material is removed to form the hole 13, thereby obtaining the porous needle-shaped part 12. That's fine. According to such a method of forming a porous structure, the filler 21 is contained in a dispersed state in the resin of the needle-shaped part 12. In this embodiment, the needle-shaped part 12 is made of polycaprolactone and the filler 21, and as described later, the protrusion part 32 is made of polycaprolactone, which is a water-insoluble resin, the filler 21, and a water-soluble material. In the removal process, the water-soluble material is removed to form the pores 13, and the water-insoluble resin and filler 21 remain, forming the porous needle-shaped part 12. .

As described above, the hole 13 is a void formed by removing a water-soluble material from the protrusion 32 made of a water-insoluble resin and a water-soluble material, and body fluids and medical solutions pass through the hole 13 as a flow path. . As shown in the cross section of the needle-shaped portion 12, a plurality of voids are formed by removing the water-soluble material and are communicated with each other. Depending on the hole 13 , a flow path is formed that communicates from the surface of the needle-shaped portion 12 to one side of the base material 11 . The size of the opening of the hole 13 is determined depending on the intended use of the microneedle structure 10, such as a test patch, but from the viewpoint of making it easier for liquid to pass through, the size of the opening is 0.1 to 50 mm. It is preferably 0.0 μm, more preferably 0.5 to 25.0 μm, and even more preferably 1.0 to 10.0 μm. The water-soluble material and its content are appropriately selected in the manufacturing process so as to have such an opening diameter.

In addition, in this embodiment, the needle-like part 12 is formed by removing the water-soluble material from the protrusion part 32 made of a water-insoluble resin and a water-soluble material to form a porous structure, but the present invention is not limited to this, and the porous structure Forming the needle-shaped portion 12 using a resin, forming a porous structure simultaneously with the formation of the needle-shaped portion 12 using a foamed material, or sintering a particulate composition containing a low-melting point resin. It is also possible to form a porous structure. Even in this case, it is possible to increase the strength of the needle portion 12 by incorporating the filler 21 into the porous resin.

Further, the needle-like portion 12 may have a base portion 14 provided over at least a region in which the needle-like portion 12 is formed between the needle-like portion 12 and one side of the base material 11 . In this embodiment, the base 14 is provided in a layered manner over the entire one side of the base material 11 . The base portion 14 serves as a base for each needle-like portion 12 and has a hole 13 similarly to each needle-like portion 12 . The base portion 14 is formed to have a thickness of, for example, 0.1 to 500 μm. By having such a thickness, the strength of the base material 11 is increased, and preferable adhesiveness is obtained between the needle-shaped portion 12, the base portion 14, and the base material 11.

It is preferable that the base part 14 also has a porous structure like the needle part 12, and it is more preferable to use the same resin so that it has the same porous structure as the needle part 12. When a porous structure is used for the base 14, there is a channel formed therein through which the liquid flows, so there is no need to mechanically form the holes 13, and the liquid from the needle-like part 12 flows through the base 14. It is preferable that it can pass through the hole 13 and fill the through hole 15. In this embodiment, the base 14 is made of the same resin as the needle-like part 12 and is formed by the same process, so it is not only easy to manufacture, but also the needle-like part 12 and the base material 11 can be easily made. is preferable because better adhesion can be obtained through the base portion 14. Furthermore, in the present embodiment, the base 14 is provided over the entire one side of the base 11, so that the base 14 is provided even in the part of the base 11 where the needle-shaped part 12 is not formed. 11, the strength of the microneedle structure 10 as a whole is further improved.

(2) Base material The needle-like part 12 has a hole 13 formed therein as a flow path through which liquid flows. The strength of the shaped portion 12 will be reduced. When the needle-shaped portion 12 has a porous structure, the strength of the needle-shaped portion 12 tends to further decrease. Therefore, in this embodiment, in order to support the needle-like part 12 from the root side of the needle-like part 12 and improve the strength of the microneedle structure 10, the microneedle structure 10 supports the needle-like part 12 from one side. A base material 11 is provided.

It is preferable that the base material 11 is configured so that liquid can pass through it in the thickness direction. Being able to pass a liquid in the thickness direction of the base material 11 means that the base material 11 itself may be made of a liquid-permeable material, or the base material 11 may be made of a liquid-impermeable material. The liquid may be allowed to pass through the through hole 15 formed in the base material 11 in the thickness direction of the base material 11.

The base material 11 made of a liquid-permeable material has a plurality of voids that communicate with each other, so that the back surface (the surface where the needle-shaped portion 12 is provided) is moved from one side (the surface where the needle-shaped portion 12 is provided) to the back surface (the surface where the needle-like portion 12 is provided). Examples of porous substrates include microscopic substrate pores formed therethrough on the opposite side of the substrate. When a low melting point resin is used as the resin forming the needle portion 12, the composition containing the low melting point resin can be processed at a low temperature, thereby making it possible to avoid exposing the base material 11 to high temperatures. . Therefore, it is possible to select various base materials as the base material 11 depending on the purpose. The base material 11 made of such a liquid-permeable material may be in the form of a plate, but is preferably in the form of a sheet, which has a high ability to follow the skin. As the base material 11, preferably, a base material made of a fibrous material that is easy to handle is used. Here, the fibrous material in the present invention means fibers such as natural fibers and chemical fibers. Examples of the base material made of fibrous substances include nonwoven fabrics, woven fabrics, knitted fabrics, and paper made of these fibers.

When the base material 11 is made of a liquid-impermeable material and allows liquid to pass through the through-holes 15 in the thickness direction, liquid absorption of the base material 11 can be suppressed. Therefore, liquid can pass only through the through holes 15 in the base material 11. Therefore, the body fluid obtained from the needle-like part 12 or the drug solution transported to the needle-like part 12 does not seep into the base material 11, and the entire amount can be allowed to flow through the through-hole 15. As a result, when the microneedle structure 10 is used as a test patch, body fluid can immediately pass through the base material 11, allowing for rapid analysis. Even when used as a drug administration patch, the drug solution does not seep out and the entire amount of the drug solution can be quickly supplied to the skin.

Examples of such liquid-impermeable materials include resin films, metal-containing sheets, glass films, and the like. Examples of the metal-containing sheet include metal foil. Moreover, among resin films, a metal layer may be formed on a resin film having low water resistance by vapor deposition or the like to improve water resistance and may be used as the metal-containing sheet. Alternatively, it may be a material that is not liquid-impermeable, such as a nonwoven fabric or paper, or a laminated resin film made by laminating a water-insoluble resin on these materials so that the entire film is impermeable to liquid.

In this embodiment, the base material 11 is made of a liquid-impermeable resin film. Examples of resins used in such resin films include polybutylene terephthalate, polyethylene terephthalate, polyethylene, polypropylene, ethylene-vinyl acetate copolymer, vinyl chloride, acrylic resin, polyurethane, polylactic acid, and the like. When a low melting point resin is used as the resin forming the needle portion 12, the composition containing the low melting point resin can be processed at a low temperature, thereby making it possible to avoid exposing the base material 11 to high temperatures. . Therefore, even with resin films using these resins, problems such as deformation of the base material are unlikely to occur.

Furthermore, the base material 11 may be a single layer or may have a structure in which multiple layers are laminated. The base material 11 may be formed by laminating a porous base material 11 such as a nonwoven fabric and a liquid-impermeable base material 11 in which through-holes are formed. Further, the resin film may be a composite film obtained by impregnating a nonwoven fabric or a cloth with a resin. The thickness of the base material 11 is preferably 3 to 200 μm, more preferably 10 to 140 μm, and still more preferably 30 to 115 μm. When the thickness is 3 μm or more, it is easy to maintain the strength as the base material 11, and when the thickness is 200 μm or less, the followability to the skin is improved and the liquid transport time can be shortened. It is possible.

An adhesive layer 16 is provided on one side of the base material 11 on which the needle-shaped portion 12 is formed. Thereby, the adhesiveness between the needle-shaped portion 12 and the base material 14 and the base material 11 can be improved. As such an adhesive layer, a pressure sensitive adhesive is preferable, and examples thereof include an acrylic adhesive, a silicone adhesive, a rubber adhesive, and more preferably an acrylic adhesive. Further, by providing the adhesive layer 16 on the base material 11, in the method for manufacturing a microneedle structure described below, the solid composition 31 is bonded to the base material 11 in advance, and the solid composition 31 is bonded to the base material 11 in advance. The microneedle structure 10 can be easily obtained by putting the object 31 into a mold and heating and pressing it in a heating and pressing step. When the adhesive layer 16 is provided on the base material 11, a gap may be created between the base material 11 and the needle-like part 12, and liquid may leak out, or the adhesive layer may cause the base material 11 and the needle-like part 12 to There is a concern that the passage of liquid between the two may be obstructed. Therefore, it is preferable to provide the adhesive layer 16 so as to surround the region through which the liquid should pass in the base material 11, while providing a region in which the adhesive layer 16 is not formed in the central portion. Although such an effect cannot be obtained, a first primer layer (not shown) may be used instead of the adhesive layer 16 for the purpose of improving the adhesiveness between the needle-shaped portion 12 and the base material 11. It may be provided. Further, even when the base material 11 has the adhesive layer 16, a first primer layer as an intermediate layer may be provided between the base material 11 and the adhesive layer 16. Examples of the primer layer include an acrylic primer layer, a polyester primer layer, and the like.

As the acrylic pressure-sensitive adhesive, one containing an acrylic polymer obtained by polymerizing a monomer whose main component is an acrylic acid alkyl ester can be used. The acrylic polymer may be a copolymer of an acrylic acid alkyl ester and other monomers. Other monomers include acrylic esters other than alkyl acrylates, such as acrylic esters having a hydroxyl group, acrylic esters having a carboxyl group, and acrylic esters having an ether group, as well as vinyl acetate, styrene, etc. Examples include monomers other than acrylic esters.

The acrylic polymer may be crosslinked by a reaction between a functional group derived from the above-mentioned acrylic ester having a hydroxyl group, acrylic ester having a carboxyl group, etc., and a crosslinking agent.

In addition to the above-mentioned components, the acrylic pressure-sensitive adhesive may contain a tackifier, a plasticizer, an antistatic agent, a filler, a curable component, and the like.

As a coating liquid for obtaining an acrylic pressure-sensitive adhesive, either a solvent type or an emulsion type can be used.

The shape of the through-holes 15 formed in the base material 11 is not particularly limited, but a structure in which a plurality of through-holes with small diameters are provided is preferable from the viewpoint of ensuring sufficient flow rate while generating capillary action. . The diameter of the through hole is, for example, 2 mm or less, preferably 0.05 to 1 mm, and more preferably 0.1 to 0.8 mm. The method for forming the through hole is not particularly limited, and it can be formed, for example, by punching or laser drilling. In this embodiment, when transporting the liquid from the needle-like part 12 , since the base material 11 has liquid impermeability, the liquid does not seep into the base material 11 and can be transported through the through hole 15 . Since the liquid is distributed in the thickness direction of the base material 11, the transportation distance is short, and when configured as a detection patch, detection can be performed at a high analysis speed, and when configured as a drug administration patch, , it is possible to administer the drug solution early.

The total area of each through hole 15 (total area) is preferably 0.05 to 15% in total, more preferably 0.05 to 15% of the area of the area on the base material 11 in which the through hole 15 is provided. is 0.75 to 10%, more preferably 1 to 5%. When the total area of the through holes 15 is 15% or less of the area of the above region of the base material 11, the rigidity of the base material 11 can be easily ensured. Further, when the total area of the through holes 15 is 0.05% or more of the area of the above region of the base material 11, body fluid can be more efficiently acquired via the base material 11.

When the base 14 is formed in the microneedle structure 10, the base 14 is directly adhered to one side of the base material 11, and the base 14 is formed integrally with the needle-like part 12, so that the needle-like part 12 is provided on the base material 11 without using an adhesive or the like, the holes 13 have good communication, and liquid can easily pass through. In the microneedle structure 10 having such a configuration, even if the adhesive layer 16 is not provided on the base material 11, the solid composition 31 can be heated in the formation step of the microneedle structure manufacturing method described below. It can be obtained by adhering to the base material 11 or by a similar adhesion method using heat. Note that in this embodiment, the base portion 14 is provided over the entire surface of the base material 11, but the present invention is not limited thereto. It is preferable that the base portion 12 is formed at least in the region where the needle-like portion 12 is formed. Even if the base 14 is directly adhered to one side of the base material 11, the first primer layer is provided on the base material 11 instead of the adhesive layer 16 as described above, and the base material 14 may be adhered to the base material 11 through the first primer layer, or through another layer other than the adhesive layer 16 and the first primer layer.

The microneedle structure 10 formed in this manner can be used as a test patch or a drug administration patch. For example, in the test patch 2 shown in FIG. 2, the analysis sheet 17 is arranged so as to face the needle-like part 12 at a position covering the region in which the through-hole 15 of the base material 11 of the obtained microneedle structure 10 is formed. A tape 18 is laminated to cover the analysis sheet 17. In the case of a drug administration patch, a drug administration member is placed instead of the analysis sheet 17 so as to face the needle portion 12 at a position covering the region in which the through holes 15 of the base material 11 of the obtained microneedle structure 10 are formed. may be arranged, and the tape 18 may be laminated to cover the drug administration member. In such test patches 2 and drug administration patches, the strength of the needle parts 12 is high, so it is possible to penetrate the skin without damaging the needle parts 12, and it is possible to insert the needle parts 12 into the body. This is preferable because it can prevent the constituent materials from remaining. Note that the tape 18 for fixing the analysis sheet 17 or the drug administration member onto the base material 11 may be an adhesive tape provided with an adhesive layer.

[Method for manufacturing microneedle structure]
3 and 4 show a method for manufacturing the microneedle patch 1 according to the embodiment of the present invention. In this embodiment, a water-insoluble low melting point resin is used as the resin constituting the needle portion 12. A solid composition 31 containing the water-insoluble low-melting resin, the filler 21, and a water-soluble material for forming the holes 13 is adhered to the base material 11 (adhesion step), and then the solid composition 31 is heated. The protrusions 32 are formed by applying pressure (forming step), and then the water-soluble material is removed from the protrusions 32 (removal step) to form the protrusions 32 into the needle-like portions 12. This will be explained in detail below.

(Adhesion process)
First, the preparation of the base material 11 and the solid composition 31 will be explained. First, a mixture 33 is prepared by heating and melting and mixing a water-insoluble low-melting resin, a filler 21, a water-soluble material, and optional components. In preparing the mixture 33, it is preferable to heat at 40°C or more and 180°C or less, more preferably 55 to 140°C, and more preferably 70 to 180°C, so that the viscosity can be reduced when the resin is melted. It is more preferable to heat at 120°C. Also in the preparation of the mixture 33, since a water-insoluble low melting point resin is used as the resin constituting the needle portion 12 in this embodiment, the heating temperature can be set low. Therefore, in the subsequent formation process, even if the base material 11 is heated together with the solid composition 31 to form the protrusions 32, it is heated at a low temperature. The base material 11 does not soften, deform, or burn, and there is a high degree of freedom in selecting the base material 11. Note that the mixture 33 is preferably in a molten state. If heating at a lower temperature is important, the mixture 33 may be softened to the extent that it adheres to the base material 11, but in order to reduce the manufacturing time, it is preferable to melt the water-insoluble material as described above. It is preferable to heat at a temperature higher than the melting point of the low melting point resin to be started.

As the water-soluble material, a water-soluble material having at least a melting point higher than room temperature is preferable. The water-soluble material may be organic or inorganic, and includes sodium chloride, potassium chloride, mirabilite, sodium carbonate, potassium nitrate, alum, sugar, and water-soluble resins. The water-soluble resin is preferably a water-soluble thermoplastic resin, and preferably has a melting point higher than room temperature. Examples of water-soluble thermoplastic resins include hydroxypropylcellulose, polyvinylpyrrolidone, and the like, in addition to the biodegradable resins described below. The water-soluble thermoplastic resin is more preferably a biodegradable resin in consideration of its effect on the human body. Such biodegradable 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 glycols being particularly preferred. The molecular weight of the polyalkylene glycol is, for example, preferably 200 to 4,000,000, more preferably 600 to 500,000, and particularly preferably 1,000 to 100,000. Among polyalkylene glycols, it is preferable to use polyethylene glycol.

In addition, in order to easily melt both the low-melting point resin and the water-soluble material at the same heating temperature when preparing the mixture 33, the difference between the melting point of the low-melting point resin and the water-soluble material is The temperature is preferably 40°C or lower, more preferably 30°C or lower.

The water-insoluble material and the water-soluble material are preferably mixed at a mass ratio of 9:1 to 1:9, more preferably 8.5:1.5 to 3:7, and 8:1 to 1:9. Particularly preferred is a mixing ratio of 2 to 5:5. By configuring the mixture 33 in this proportion, the needle-shaped portion 12 can be formed with a desired porosity, and it becomes easier to achieve both liquid permeability and strength of the needle-shaped portion 12.

The filler 21 included in the mixture 33 can be the same as that described for the microneedle structure 10.

The filler 21 is preferably contained in an amount of 1 to 30 parts by mass, more preferably 2 to 27.5 parts by mass, and 3 to 25 parts by mass, based on 100 parts by mass of the water-insoluble resin and water-soluble material. It is particularly preferred that parts by weight are mixed. When the amount is 30 parts by mass or less, it is easy to maintain the shape of the needle-shaped portion 12 and maintain workability during manufacturing. Further, it is easy to maintain a desired porosity of the needle-shaped portion 12. If the amount is 1 part by mass or more, it is easy to increase the strength.

The mixture 33 is injected into a solid composition recess 42 formed in a solid composition mold 41, as shown in FIG. 3(a). It is sufficient that the solid composition recess 42 has a shape and capacity that can store a desired amount of the mixture 33.

The material of the solid composition mold 41 is not particularly limited, but it should be made of, for example, a silicone compound that is easy to make an accurate mold and easy to peel off the solidified composition 31. is preferable, and in this embodiment it is made of polydimethylsiloxane.

With the mixture 33 stored in the solid composition recess 42, a layer of, for example, polydimethylsiloxane (PDMS) is applied to the upper surface of the solid composition recess 42 in order to flatten the surface of the obtained solid composition 31. A solid composition sheet 43 consisting of the following is placed as a lid. By holding the entire mold 41 for solid composition at -10 to 3°C for 1 to 60 minutes, the molten mixture 33 solidifies and becomes solid, so that the solid composition can be removed from the mold 41 for solid composition. The material sheet 43 is peeled off, and then the solid composition sheet 43 is peeled off. As a result, a solid composition 31 shown in FIG. 3(b) is obtained.

Prepare the base material 11. The base material 11 has an adhesive layer 16 in this embodiment, and the adhesive layer 16 may be formed by coating or application, but in this embodiment, the base material 11 has an adhesive layer 16 in a predetermined area. Adhesive tape is used as the base material 11. Then, a through hole 15 is formed in the base material 11. The method of forming the through hole 15 is not particularly limited, and may be formed by punching or laser drilling, for example.

Then, as shown in FIG. 3(c), the solid composition 31 is attached to the adhesive layer 16 of the base material 11 to integrate the base material 11 and the solid composition 31. In this way, by having the first adhesive layer 16, the solid composition 31 is adhered to the base material 11 in advance, and the base material 11 and the solid composition 31 are placed in a mold and heated as described below. By heating and pressing in the pressurizing process, the microneedle structure 10 can be easily obtained. Further, since the base material 11 and the solid composition 31 are integrated, handling such as transportation becomes easier.

(Formation process)
Next, as shown in FIG. 4(a), the solid composition 31 including the base material 11 is placed in the recess 51 of the mold 52 having the recess 51. A protrusion forming recess 53 is also provided at the center of the bottom surface of the recess 51 . The solid composition 31 is placed on the bottom surface of the recess 51, that is, on the protrusion forming recess 53. The protrusion forming recess 53 is for forming the needle-like part 12 and is formed in a shape and size corresponding to the needle-like part 12. Then, the lid 54 of the mold 52 is installed on the other side (back side) of the base material 11. This lid 54 is also made of polydimethylsiloxane.

Next, a heating step shown in FIG. 4(b) is performed. The heating process is for forming the protrusions 32 and the like in a desired shape, and heating and pressing may be performed all at once, but as in the present embodiment, the solid composition is heated in the recess 51 of the mold 52. 31, a preliminary process for starting melting of the solid composition 31 including the base material 11, and a book for sufficiently filling the recesses 51 etc. with the molten solid composition 31. It is preferable that it consists of a step.

First, in the preliminary step and the main step, as shown in FIG. 4(b), with the solid composition 31 placed in the recess 51, the mold 52 and the lid 54 are placed between the base material 11 and the solid composition. An object 31 is held between the two. Then, in this state, the mold 52 and the lid 54 are placed on the lower stage 56, and the upper stage 57 is installed on the mold 52 and the lid 54.

As for the heating conditions in the preliminary step and the main step, it is sufficient to heat at 40° C. or higher and 180° C. or lower, which has a small effect on the base material 11, preferably at 55 to 140° C., and 70 to 120° C. It is more preferable to heat at ℃. In this embodiment, the solid composition 31 is heated at a temperature at which it can be melted. In addition, in order to heat the solid composition 31, 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.

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 MP. With the pressure within this range, the solid composition 31 can be melted in a short time, and the molten solid composition 31 can be quickly filled into the recesses 51 and the like. Then, by holding it for 10 seconds to 10 minutes, the solid composition 31 becomes in a molten state. Note that the pressurizing conditions may be changed between the preliminary step and the main step. For example, in this step, pressurization can be performed at a higher pressure or for a longer time than in the preliminary step.

By performing the preliminary step and the main step as in this embodiment, the solid composition 31 is sufficiently melted and filled into the recesses 51 and the protrusion forming recesses 53. Furthermore, if the obtained needle-like part 12 or base part 14 has a porous structure, the adhesion area of the needle-like part 12 or base part 14 to the base material 11 becomes small, which is disadvantageous for the adhesion between them. By heating in the forming step in a state where the base material 11 and the solid composition 31 are adhered to each other, the adhesion between the needle-shaped portion 12 or the base portion 14 and the base material 11 can be improved.

Thereafter, the mold 52 is removed from the lower stage 37, and the molten solid composition 31 is held at -10 to 3°C for 1 to 60 minutes (refrigeration solidification step) to solidify it by refrigeration. As a result, the protrusions 32 and the like having a shape corresponding to the protrusion forming recess 53 and having high transferability are formed.

(Removal process)
After the adhesion process is completed, the solidified protrusion 32 and the base material 11 bonded together are separated from the mold 52 and left standing in a liquid to remove the water-soluble material, thereby forming the needle-like part 12. A removal process is performed to form a .

The cleaning liquid in this removal process contains water, and in the removal process, as shown in FIG. This is done by letting it stand still. When left standing in a cleaning solution containing water, the portions of the water-soluble material contained in the protrusions 32, etc. that are exposed to the outside or that are in communication with the exposed portions are dissolved and flowed out into the water. removed. Note that the cleaning liquid 58 only needs to contain water, and may be a mixed solvent of water and alcohol, for example. By this removal, holes 13 are formed in the protrusions 32 and the like, and needle-shaped parts 12 made of the remaining low melting point resin and filler are formed. Furthermore, in addition to the needle-shaped portion 12, water-soluble material is also removed from the molten solid composition 31 that had adhered to one side of the base material 11 by filling the recess 51, so that the base portion 14 is also removed. formed as the same porous structure. Thereby, the microneedle structure 10 of this embodiment is obtained.

(Method for manufacturing test patches, etc.)
Although not shown, the analysis sheet 17 is placed at a predetermined position on the back side of the base material 11 of the obtained microneedle structure 10, and the tape 18 is laminated to cover the analysis sheet 17 (installation step). It is possible to manufacture test patches. The lamination method can be a conventionally known method. For example, after placing the analysis sheet 17 on the back side of the base material 11, a commonly used rubber adhesive, acrylic adhesive, silicone A test patch can be manufactured by laminating adhesive tapes 18 in which an adhesive layer such as a type adhesive is formed on a tape base material. Drug delivery patches can also be manufactured by similar methods.

(Modified example)
In this embodiment, the solid composition 31 contains a water-soluble material, a water-soluble low melting point resin, and the filler 21. However, the solid composition 31 contains at least the resin and the filler 21. There are no particular limitations as long as it is. When using the solid composition 31 as in this embodiment, the composition does not contain a solvent, so discoloration and deformation of the base material 11 can be suppressed, which is preferable. Furthermore, in this embodiment, the order of the adhesion process and the formation process may be changed, and the adhesion process may be performed in parallel with the formation process. That is, the concave portion 42 may be filled with the mixture 33, and before the mixture 33 is solidified, the base material 11 may be placed on the mixture 33 and an adhesion step may be performed to obtain a solid composition with a base material.

In this embodiment, the needle-like part 12 is formed using a water-insoluble material in order to easily form the hole 13 by removing the water-soluble material, but the method for producing the needle-like part 12 is not particularly limited. For example, in the forming step, a liquid composition containing a water-soluble material, a water-insoluble material, and a solvent is formed, the solvent is evaporated, a composition other than the solvent is filled into the protrusion-forming recess, and the composition is dried. Alternatively, a method of forming a protrusion may be used. Further, for example, in the forming step, a liquid composition containing a water-soluble material and a water-insoluble material is prepared to have a viscosity of 0.1 to 1000 mP·s on the base material 11 using a dispenser or the like. A method may also be used in which the needle-like portion 12 is formed by dropping the liquid dropwise.

Hereinafter, the present invention will be explained in more detail with reference to Examples.

〔Example〕
(Example 1)
While heating 3 g of polyethylene glycol (PEG) (weight average molecular weight: 4,000, melting point 40°C) and 7 g of polycaprolactone (PCL) (weight average molecular weight: 10,000) as water-soluble materials at 110°C, The mixture was heated and stirred. Furthermore, 0.5 g of ARBOCEL Natural Cellulose Fibers (average fiber length: 45 μm, manufactured by Rettenmeyer Japan Co., Ltd., containing 10% by mass of ignition residue other than cellulose fibers at 850° C. for 4 hours) was added and stirred again. . In this way, mixture 33 was prepared. A solid composition mold 42 made of polydimethylsiloxane is prepared, and a recess 42 with a square opening of 15 mm x 15 mm on each side and a depth of 1.5 mm is formed in the solid composition mold 41. It had been. The mixture 33 was injected so as to fill the concave portions 42 of the mold 41 for solid composition.

A sheet 43 for a solid composition made of polydimethylsiloxane was used as a lid and placed on a mold 41 for a solid composition into which the mixture 33 had been injected, and the surface of the solid composition 31 was flattened. This state was maintained at 3° C. for 5 minutes, and the molten mixture 33 solidified into a solid, and was separated from the solid composition mold 41 to obtain a solid composition 31. Next, the adhesive layer 16 of the base material 11, which is an adhesive tape (an acrylic adhesive layer (25 μm thick) formed on a polyethylene terephthalate (PET) base material (100 μm thick)), is attached to one side of the solid composition 31. It was pasted on the surface and glued. As a result, a solid composition 31 including a base material 11 was obtained.

In order to perform the forming process, a mold 52 having a concave portion 53 for forming a protrusion was prepared. The mold 52 was made of polydimethylsiloxane, and had a protrusion-forming recess 53 formed on its surface having a recess 51 as described in detail below.
・Shape of the recess for forming a protrusion: Square pyramid shape with a square cross section ・Length of one side of the maximum cross section of the recess for forming a protrusion: 500 μm
・Height of recess for forming protrusion: 900μm
・Pitch of recesses for forming protrusions: 1000μm
・Number of recesses for forming protrusions: 13 columns and 13 rows, total 169 ・Size of area where recesses for forming protrusions are formed: 15 mm square ・Arrangement of recesses for forming protrusions: Square grid pattern

The mold 52 is placed on the lower stage 56 of a heating press machine (AH-1T, manufactured by As One Corporation), and the solid composition 31 with the base material 11 is placed on the mold 52 so as to face the recess 51. Then, a 30 mm square polydimethylsiloxane sheet (lid 54) was placed on top of it, and while heating at the lower stage setting heating temperature of the heating press machine: 100°C and the upper stage setting heating temperature: 90°C. A preliminary step was performed by pressing at 2 MPa for 1 minute and 30 seconds. Thereafter, this step was carried out by pressing at 4 MPa for 30 seconds while maintaining the temperature of the hot press machine and heating it. Further, the base material 11 and the molten composition contained in the lid 54 and the mold 52 were stored in a refrigerator at 3° C. for 5 minutes to solidify the composition, and the protrusions 32 and the like were formed. Thereafter, the base material 11 was peeled off from the mold 52, and the base material 11 and the formed projections 32 and the like were immersed in purified water at 23° C. for 24 hours to dissolve and remove the water-soluble material. Thereafter, the base material 11 and the molded solid composition 31 were left in a drying oven (30° C.) for 5 hours to evaporate water and dry, thereby obtaining the microneedle structure 10.

(Example 2)
A microneedle structure 10 was obtained in the same manner as in Example 1 except that 2.0 g of ARBOCEL Natural Cellulose Fibers as the filler 21 was added.

(Example 3)
A microneedle structure was prepared in the same manner as in Example 1, except that 0.5 g of ARBOCEL Ultrafine Cellulose (average particle size: 6-12 μm, manufactured by Rettenmeyer Japan) was added as filler 21 instead of ARBOCEL Natural Cellulose Fibers. Got 10.

(Example 4)
A microneedle structure was prepared in the same manner as in Example 1, except that 2.0 g of ARBOCEL Ultrafine Cellulose (average particle size: 6-12 μm, manufactured by Rettenmeyer Japan) was added as filler 21 instead of ARBOCEL Natural Cellulose Fibers. Got 10.

(Example 5)
Same as Example 1 except that 0.5 g of lactic acid polymer (PLA) particles (glass transition temperature: 60°C, irregular shape, average particle shape: 53.4 μm) was added as filler 21 instead of ARBOCEL Natural Cellulose Fibers. A microneedle structure 10 was obtained in the same manner.

(Example 6)
As the filler 21, instead of ARBOCEL Natural Cellulose Fibers, Techpolymer SSX (manufactured by Sekisui Plastics Co., Ltd., true spherical cross-linked polymethyl methacrylate (PMMA) fine particles, glass transition temperature of PMMA: 100°C, particle size: 1. A microneedle structure 10 was obtained in the same manner as in Example 1 except that 0.5 g of 5 μm) was added.

(Comparative example 1)
A microneedle structure was obtained in the same manner as in Example 1 except that ARBOCEL Natural Cellulose Fibers as a filler was not added.

The microneedle structures obtained in Examples 1 to 6 and Comparative Example 1 were evaluated for microneedle array transferability and microneedle tip strength as described below.

(Microneedle array transferability evaluation)
In each Example and Comparative Example, protrusions were formed by cooling the composition, and after peeling from the mold and before being immersed in purified water, the protrusions were observed under an optical microscope (magnification: 50x and 100x). , the number of protrusions remaining on the base material was counted. The ratio of this remaining number to the total number of designed protrusions was calculated and determined as the transfer rate. When the transfer rate was 50% or more and 100% or less, it was evaluated as "A", and when it was 0% or more and less than 50%, it was evaluated as "B".

(Microneedle tip strength evaluation)
The microneedle structures obtained in Examples and Comparative Examples were placed on a stage with the needle side facing upward, observed with a microscope, and one needle with a sharp tip was selected. In line with the position of the needle, attach the attachment (made of iron, 2mmφ) of the measuring instrument (digital force gauge (manufactured by Imada Co., Ltd.)) to the needle, being careful not to let the attachment touch the adjacent needle. I brought it closer. Move the attachment up and down to a position where it contacts the tip of the needle but no force is applied to the needle, raise it 0.1 mm from there, and then lower the attachment at a descending speed of 5 mm/min. Measurement of the force applied to the attachment (measurement range: 1 to 5000 mN) was started. At this time, the measurement temperature was 23° C. and the relative humidity was 50%. On the graph where the measured force is output, at the point when a drop in force is first observed, read the maximum value of the force indicated at the position before the drop in force, and calculate that value as the tip strength of the needle. And so. When the tip strength was 60 mN or more, it was evaluated as "A," when the tip strength was less than 60 mN and 40 mN or more, it was evaluated as "B," and when the tip strength was less than 40 mN, it was evaluated as "C." In the transferability evaluation, for Examples or Comparative Examples in which the transfer rate was less than 100%, one needle-shaped portion that remained without falling off the base material was selected for evaluation.

The evaluation results are shown in Table 1.
(Table 1)

As shown in Table 1, in Comparative Example 1, the microneedle tip strength was less than 40 mN and the evaluation was C, but in Examples 1 to 6, it was A or B. The strength was increased due to the inclusion of filler 21. In Examples 1 to 6, the microneedle array transferability evaluation was A or B, but in Examples 1 to 5, the adhesiveness of the interface between the resin constituting the needle portion 12 and the filler 21 was The transferability was high because the resin and filler 21 blended well.

The microneedle structure of the present invention can be used as a test patch, for example, by placing an analysis sheet on the back side and laminating it with tape.

10 Microneedle structure 11 Base material 12 Acicular portion 13 Hole portion 14 Base portion 15 Through hole 16 Adhesive layer 21 Filler 31 Solid composition 32 Projection portion 33 Mixture

Claims (12)

1. A microneedle structure comprising a needle-like part with a hole formed inside the microneedle structure,
   The microneedle structure is characterized in that the needle-like portion includes a resin and a filler.
2. The microneedle structure according to claim 1, wherein a porous structure is formed in the needle-like part.
3. The microneedle structure according to claim 1, wherein the resin forming the needle portion is a low melting point resin having a melting point of 130° C. or lower.
4. The microneedle structure according to claim 3, further comprising a base material having the needle-like portion on one side.
5. The microneedle structure according to claim 4, wherein the base material and the needle-like part are bonded to each other via a base made of the same material as the needle-like part.
6. The microneedle structure according to claim 1, wherein the filler is made of resin.
7. The microneedle structure according to claim 6, wherein the filler is made of a resin whose glass transition temperature is 80° C. or lower.
8. The microneedle structure according to claim 6, wherein the filler comprises one or more types selected from the group consisting of natural organic polymers or modified products thereof, and biodegradable resins.
9. The microneedle structure according to claim 1, wherein the filler is fibrous.
10. The microneedle structure according to claim 1, wherein the filler is contained in an amount of 3 to 50% by mass based on the entire mass of the needle-shaped portion.
11. The microneedle structure according to claim 1, wherein the resin forming the needle-like part is a water-insoluble resin.
12. The microneedle structure according to claim 1, wherein the resin forming the needle-like part is a biodegradable resin.

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