Microneedle structure and method for producing same

Abstract

A microneedle structure is provided with needle-like parts having a flow path therein. The flow paths open on the surface of the needle-like parts. A coating containing a hydrophilic substance is formed on the inner surface of the flow paths.

Description

Microneedle structure and method for manufacturing the same

[0001] The present invention relates to a microneedle structure and a method for manufacturing the same.

[0002] A microneedle structure is a structure having a fine needle-like structure (hereinafter sometimes referred to as the needle portion). Microneedle structures are used, for example, to collect liquid (such as body fluid) from a target (such as a living organism or the human body) or to inject liquid into a target. In such a microneedle structure, a channel is formed in the needle portion. The needle portion is inserted into the target, and liquid is collected from the target through the channel, or liquid is injected into the target.

[0003] In relation to the above, for example, Patent Document 1 (International Publication No. 2022 / 211059) discloses a microneedle structure in which a needle-shaped portion is provided on one side of a specific substrate, the needle-shaped portion is made of a composition containing a low-melting-point resin having a melting point of 150°C or less, and pores are formed on the surface and inside of the needle-shaped portion.

[0004] For microneedle structures, it is desirable that liquids can be rapidly collected or injected. In other words, high liquid absorption capacity is required for microneedle structures. Therefore, the object of the present invention is to provide a microneedle structure having high liquid absorption capacity.

[0005] The inventors of the present invention discovered that the liquid absorption capacity can be enhanced by coating the inner surface of the channel of the needle-shaped portion with a hydrophilic substance, and thus arrived at the present invention.

[0006] In other words, in one embodiment of the present invention, the microneedle structure comprises a needle-shaped portion having a channel through which a liquid injected into or received from an object flows. This channel is open on the surface of the needle-shaped portion. A coating containing a hydrophilic substance is formed on the inner surface of the channel.

[0007] According to the present invention, a microneedle structure having high liquid absorption properties is provided.

[0008] Figure 1 is a schematic cross-sectional view showing a microneedle structure according to an embodiment. Figure 2 is a schematic cross-sectional view showing an example of a microneedle patch. Figure 3 is a schematic diagram showing an example of the process of forming the needle-shaped portion. Figure 4 is a schematic diagram showing a microneedle patch fabricated in the embodiment. Figure 5 is a schematic diagram showing a method for measuring the liquid absorption rate in the embodiment.

[0009] Embodiments of the present invention will be described below with reference to the drawings.

[0010] (1) Microneedle Structure Figure 1 is a schematic cross-sectional view showing a microneedle structure 1 according to this embodiment. This microneedle structure 1 is used to exchange liquid with an object (e.g., a living organism, the human body).

[0011] As shown in Figure 1, the microneedle structure 1 has a needle-shaped portion 2 and a base portion 3. In the example shown in Figure 1, the needle-shaped portion 2 and the base portion 3 are integral. However, the needle-shaped portion 2 and the base portion 3 may be formed from separate components.

[0012] The base portion 3 is the part that supports the needle-shaped portion 2. The shape of the base portion 3 is not particularly limited. In this embodiment, the base portion 3 is flat.

[0013] The needle-shaped portion 2 is the part that is inserted into the target. Multiple needle-shaped portions 2 are provided. Each needle-shaped portion 2 extends upward from one surface of the base portion 3 (hereinafter sometimes referred to as the needle-shaped portion forming surface). The needle-shaped portions 2 are formed from a needle-shaped portion forming resin.

[0014] A flow channel is formed inside the base portion 3 and the needle-shaped portion 2. In this embodiment, the base portion 3 and the needle-shaped portion 2 have a porous structure. The pores contained in this porous structure function as a flow channel. In the needle-shaped portion 2, the flow channel opens on the surface of the needle-shaped portion 2. Therefore, when the needle-shaped portion 2 is inserted into an object, the liquid injected into the object, or the liquid received from the object, flows through the flow channel. The opening on the surface of the needle-shaped portion 2 is connected to the back surface of the base portion 3 (the surface opposite to the surface on which the needle-shaped portion 2 is formed) via a flow channel provided inside the needle-shaped portion 2 and the base portion 3. Therefore, although not shown in Figure 1, if a functional member (a member that stores the liquid injected into the object, or a member that acts passively on the liquid absorbed from the object) is placed on the back surface of the base portion 3, it becomes possible to exchange liquid between the functional member and the object via the microneedle structure 1.

[0015] Although not shown in the figures, in this embodiment, at least in the needle-shaped portion 2, a coating containing a hydrophilic substance is formed on the inner surface of the flow channel. That is, the inner surface of the flow channel is covered with a layer containing a hydrophilic substance. By forming such a coating, high liquid absorption can be achieved. Furthermore, the high liquid absorption can be maintained over a long period of time due to the formation of the coating. In other words, durability is also improved.

[0016] The above is an overview of the microneedle structure according to this embodiment. Next, the details of each part will be described in detail.

[0017] (2) Needle-shaped part forming resin First, the needle-shaped part forming resin that forms the needle-shaped part 2 will be described. The specific type of needle-shaped part forming resin is not particularly limited. The needle-shaped part forming resin may be formed from one type of resin or from a mixture of multiple resins.

[0018] Preferably, the needle-forming resin contains a resin having a melting point of 130°C or lower (hereinafter referred to as a low-melting-point resin). Using a low-melting-point resin makes it easier to heat and melt the raw material during the manufacture of the microneedle structure 1, and makes it easier to mold the raw material using a mold. In other words, it is preferable from the viewpoint of moldability. The melting point of the low-melting-point resin is preferably 100°C or lower, and more preferably 80°C or lower.

[0019] The low-melting-point resin is preferably solid at room temperature (25°C). Using such a resin makes it easier to maintain the strength of the needle-shaped portion 2 at room temperature. The melting point of the low-melting-point resin is preferably 40°C or higher, more preferably 45°C or higher.

[0020] The low-melting-point resin is preferably a water-insoluble resin. Using a water-insoluble resin makes it less likely for the needle-shaped portion to dissolve due to aqueous liquids present in the target when it is inserted. In other words, the shape of the needle-shaped portion is more easily maintained during insertion.

[0021] Specific examples of low-melting-point resins include, for example, polyester; polyolefin resins such as polyethylene and α-olefin copolymers; olefin copolymer resins such as ethylene-vinyl acetate copolymers and ethylene-ethyl acrylate copolymers; polyurethane elastomers; and derivatives thereof.

[0022] Furthermore, the low-melting-point resin is preferably a biodegradable resin. Using a biodegradable resin can reduce the impact of the needle-like structure on living organisms when the target is a living organism. Examples of biodegradable resins include polyester and its derivatives. Aliphatic polyesters and their derivatives are preferably used as polyesters and their derivatives. Examples of aliphatic polyesters and their derivatives include homopolymers or copolymers containing units derived from at least one selected from the group consisting of glycolic acid, lactic acid, and caprolactone. In addition, polybutylene succinate (melting point: 84 to 115°C) and aliphatic aromatic copolyester (melting point: 110 to 120°C) can also be cited as aliphatic polyesters that are biodegradable resins. As a polybutylene succinate, for example, BioPBS provided by Mitsubishi Chemical Corporation can be used. As an aliphatic aromatic copolyester, for example, Ecoflex manufactured by BASF can be used.

[0023] The biodegradable resin is preferably a resin in which the acid dissociation constant of its monomer is 4 or higher. Having an acid dissociation constant of 4 or higher reduces the impact on the body when the microneedle structure is applied to a living organism. The acid dissociation constant of the monomer referred to here is the acid dissociation constant of the hydroxycarboxylic acid formed when the monomer is a cyclic ester. The acid dissociation constant of the monomer is preferably 4.0 or higher, and more preferably 4.5 or higher. Furthermore, the acid dissociation constant of the monomer is preferably 25 or less, and more preferably 15 or less. An example of a monomer constituting such a biodegradable resin with an acid dissociation constant of 4 or higher is caprolactone. In the biodegradable resin, it is preferable that the constituent units derived from monomers with an acid dissociation constant of 4 or higher constitute 70% by mass or more of the total constituent units, more preferably 80% by mass or more, and even more preferably 90% by mass or more.

[0024] In a particularly preferred embodiment, the low-melting-point resin comprises a homopolymer or copolymer containing caprolactone-derived units. Most preferably, the low-melting-point resin comprises polycaprolactone.

[0025] The weight-average molecular weight of the low-melting-point resin is not particularly limited, but is, for example, 5,000 or more, preferably 15,000 or more, more preferably 30,000 or more, and even more preferably 45,000 or more. Within this range, the necessary strength for the needle-shaped portion is easily maintained. The weight-average molecular weight of the low-melting-point resin is the value obtained by the method described in the examples below.

[0026] The upper limit of the weight-average molecular weight of the low-melting-point resin is not particularly limited, but is, for example, 200,000 or less, preferably 150,000 or less, more preferably 100,000 or less, and even more preferably 70,000 or less. Within this range, the processability of the needle-shaped portion is further improved.

[0027] The needle-forming resin may contain components other than low-melting-point resin. However, it is preferable that the main component of the needle-forming resin (the component accounting for 50% or more by mass) is a low-melting-point resin. The content of low-melting-point resin in the needle-shaped portion is, for example, 50% or more by mass, preferably 65% ​​or more by mass, more preferably 70% or more by mass, and even more preferably 90% or more by mass. If low-melting-point resin is included in such an amount, it becomes easier to employ methods such as heating and melting the material or heating the material and molding it in a mold during the manufacture of the microneedle structure 1.

[0028] The resin forming the needle-like structure may be a hydrophobic resin. When the needle-like structure is formed from a hydrophobic material, the liquid absorption tends to be low. However, according to this embodiment, since the inner surface of the channel is coated with a hydrophilic material, the liquid absorption can be improved even if the resin forming the needle-like structure is hydrophobic.

[0029] (3) Hydrophilic substances Next, we will explain the hydrophilic substances included in the coating. Hydrophilic substances are used to enhance liquid absorption. Hydrophilic substances are different from the needle-forming resins. As hydrophilic substances, substances with higher hydrophilicity than the needle-forming resins are used.

[0030] (3-1) In a preferred embodiment of the hydrophilic substance, the hydrophilic substance contains a hydrophilic polymer. As the hydrophilic polymer, those containing carbon atoms and oxygen atoms and having a ratio of the number of oxygen atoms to carbon atoms (hereinafter sometimes referred to as the O / C ratio) of 2 / 5 or more are preferred. By using such a hydrophilic polymer, the liquid absorption property can be further enhanced.

[0031] When the object is a living body, the hydrophilic polymer is preferably a substance having biocompatibility. If it is a substance having biocompatibility, the influence on the living body during the use of the microneedle structure 1 can be reduced. Preferably, since the hydrophilic polymer is a substance having biocompatibility and the needle-like part forming resin is a biodegradable resin, the influence on the living body during the use of the microneedle structure 1 can be significantly reduced.

[0032] Examples of the hydrophilic polymer having an O / C ratio of 2 / 5 or more and having biocompatibility include polysaccharides such as polyethylene glycol, polyvinyl alcohol, cellulose, cellulose derivatives, hyaluronic acid, and polyacrylic acid. Examples of the cellulose derivative include hydroxyalkyl cellulose and carboxymethyl cellulose. Further, examples of other hydrophilic polymers having biocompatibility include polyvinyl pyrrolidone.

[0033] 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.

[0034] 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 100,000.

[0035] Preferably, the hydrophilic polymer is a compound having repeating units with hydroxyl groups. Using such a hydrophilic polymer yields particularly high water absorption. Furthermore, it is preferable that the hydroxyl groups do not bond to carbonyl groups to form carboxyl groups. That is, it is preferable that the hydrophilic polymer is a compound having repeating units with hydroxyl groups but lacking carboxyl groups. By forming hydrogen bonds between hydroxyl groups that are not bonded to carbonyl groups, it is possible to improve the mechanical strength of the needle-like portion and obtain a hydrophilic polymer that is poorly soluble in water. Additionally, hydrophilic polymers with carboxyl groups, such as polyacrylic acid, tend to thicken liquids, which can hinder the passage of liquid through the channel. However, if the compound has repeating units with hydroxyl groups but lacks carboxyl groups, this problem is less likely to occur. When the microneedle structure 1 contains the low-melting-point resin described above, the mechanical strength of the needle-like portion tends to decrease. However, by using a hydrophilic polymer that has repeating units with hydroxyl groups but lacks carboxyl groups, high mechanical strength of the needle-like portion can be maintained.

[0036] From the viewpoint of biosafety, polysaccharides such as polyvinyl alcohol, cellulose, and cellulose derivatives are preferred as compounds having repeating units with hydroxyl groups. Examples of cellulose derivatives include hydroxyalkylcellulose.

[0037] Preferably, the hydrophilic polymer is a resin that is substantially insoluble in water at room temperature (25°C). Using such a substance makes it difficult for the coating to dissolve in liquid when using microneedles. Therefore, the durability of the coating is improved. More preferably, the hydrophilic polymer is a resin that is insoluble in water at room temperature but soluble in hot 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, and preferably 25% or less. Such a polymer can be used to obtain high hydrophilicity, and therefore high liquid absorption.

[0038] Polyvinyl alcohol is a particularly preferred hydrophilic polymer. Polyvinyl alcohol has high hydrophilicity but is almost insoluble in water at room temperature. Therefore, in addition to high liquid absorption, high durability can be obtained. Furthermore, according to the inventors' findings, it is also possible to increase the mechanical strength of the needle-like portion by using polyvinyl alcohol. From the viewpoint of easily obtaining the property of being insoluble in water at room temperature, the degree of saponification of polyvinyl alcohol is preferably 95% or higher, and more preferably 97% or higher.

[0039] (3-2) Carboxyl group reactive compound In another preferred embodiment, the hydrophilic substance is derived from a carboxyl group reactive compound. A carboxyl group reactive compound is a compound having a functional group that reacts with and bonds to a carboxyl group.

[0040] In some cases, carboxyl groups may form on the surface of the channel in the needle-shaped portion. For example, if a resin having ester bonds (e.g., polyester such as polycaprolactone) is used as the resin forming the needle-shaped portion, surface modification such as plasma treatment on the channel surface may cause the ester bonds to decompose and carboxyl groups to be generated. If a carboxyl-reactive compound is used as the hydrophilic substance, the hydrophilic substance reacts with the carboxyl groups on the channel surface and bonds to the channel surface. This allows a coating containing a hydrophilic substance derived from the carboxyl-reactive compound to be firmly bonded to the channel surface. As a result, the coating becomes less likely to peel off, and the durability of the coating can be increased.

[0041] Examples of functional groups included in carboxyl-reactive compounds include amino groups, hydroxyl groups, epoxy groups, and isocyanate groups. Amino groups are preferred. In this specification, amino groups are defined as -NH ２ The compound may be a substituted amino group in which one or two hydrogen atoms are further substituted. In the case of a compound having an amino group, the amino group reacts with the carboxyl group formed on the inner surface of the channel to form an amide bond. This allows the coating to be firmly bonded to the surface of the channel.

[0042] The carboxyl group-reactive compound may be a low-molecular-weight compound (a compound without repeating units) or a high-molecular-weight compound (a compound with repeating units). In other words, the carboxyl group-reactive compound may also be a compound that falls under the category of hydrophilic polymers as described above.

[0043] However, preferably, the carboxyl group-reactive compound is a low molecular weight compound. Low molecular weight compounds do not easily thicken liquids, so when liquids pass through the channel, the possibility of obstruction 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. More preferably, it is a low molecular weight organic compound. Specific examples of such carboxyl group-reactive compounds include amino acids. Examples of amino acids include amino acids that make up proteins. A preferred amino acid is arginine. When arginine is used, particularly high liquid absorption can be obtained.

[0044] (3-3) Other hydrophilic substances Hydrophilic substances may also be inorganic substances. Examples of inorganic substances that can be used as hydrophilic substances include silicon dioxide, aluminum oxide, titanium dioxide, zinc oxide, cerium oxide, and kaolin.

[0045] (4) Liquid absorption rate According to the microneedle structure 1 of this embodiment, high liquid absorption is achieved as a result of the coating provided on the surface of the flow path. Specifically, according to this embodiment, a microneedle structure having a liquid absorption rate of 1% or more can be realized by measuring by the method described below. The liquid absorption rate of the microneedle structure 1 is 10% or more in a preferred embodiment, 30% or more in a more preferred embodiment, and 35% or more in an even more preferred embodiment.

[0046] (Method for measuring liquid absorption rate) Prepare a 10 mm diameter copper ammonia rayon nonwoven fabric and determine its mass. Also, prepare a liquid-impermeable, repositionable adhesive tape and attach a liquid-impermeable resin film cut into a circle with a diameter of 10 mm to the adhesive surface of the repositionable adhesive tape. Place the nonwoven fabric in the center of the surface of the microneedle structure where the needle-like portion is not formed. Obtain the sample by attaching the repositionable adhesive tape so that the positions of the nonwoven fabric and the circular resin film coincide. Pierce the needle-like portion of the sample into a 1% agarose gel containing phosphate-buffered saline, then remove the sample from the agarose gel and remove any water droplets attached to the surface where the needle-like portion is located. Then, peel the repositionable adhesive tape from the microneedle structure to separate the microneedle structure from the nonwoven fabric and determine the mass of the microneedle structure. Then, calculate the liquid absorption rate using the following formula 1. (Formula 1) Absorption rate (%) = (Mass of microneedle structure after absorption - Mass of microneedle structure before absorption) ÷ Mass of microneedle structure before absorption × 100

[0047] Furthermore, if the base has a porous structure similar to that of the needle-shaped portion, the mass of the microneedle structure measured in the above measurement method is the combined mass of the needle-shaped portion and the base. In addition, the concentration of the agarose gel is expressed as a percentage of the value obtained by dividing the mass of agarose (g) by the volume of phosphate-buffered saline (ml), which is the solvent.

[0048] (5) Other constituent needle-like parts The shape, size, formation pitch, and number of needle-like parts are not particularly limited. For example, the shape of each needle-like part may be cylindrical, prismatic, conical, pyramidal, or cone-shaped. The maximum diameter or dimension of the cross-section at the base end of each needle-like part is, for example, 25 to 1000 μm. The tip diameter or tip cross-sectional dimension of each needle-like part is, for example, 1 to 100 μm. The height of each needle-like part is, for example, 50 to 2000 μm. Multiple needle-like parts are arranged, for example, in a matrix. The number of needle-like parts included in the microneedle structure is, for example, 10 to 1000, preferably 20 to 100.

[0049] (6) Microneedle Patch The microneedle structure 1 according to this embodiment can be used, for example, as a microneedle patch. Figure 2 is a schematic cross-sectional view showing an example of a microneedle patch 8. This microneedle patch 8 includes the microneedle structure 1, a support tape 9, and a functional member 10. The support tape 9 supports the functional member 10 and the microneedle structure 1.

[0050] The support tape 9 is made of, for example, adhesive tape. The microneedle structure 1 is supported on one surface of the support tape 9. An attachment area is provided on the outer circumference of the support tape 9 to be attached to the target. When the support tape 9 is attached to the target so that the microneedle structure 1 faces the target, the needle-shaped portion 2 of the microneedle structure 1 is inserted into the target.

[0051] The functional member 10 is a member that exchanges liquid with the target via the microneedle structure 1. The functional member 10 is sandwiched between the microneedle structure 1 and the support tape 9. When the needle-shaped portion 2 is inserted into the target, the functional member 10 is connected to the target via the flow path contained in the microneedle structure 1. As a result, liquid is exchanged between the functional member 10 and the target, and the desired function is realized. For example, the functional member 10 may be an inspection sheet for collecting aqueous liquid (such as body fluid) from the target and examining its components. Alternatively, the functional member 10 may be a storage member for storing liquid (medicinal solution) to be injected into the target. Furthermore, the functional member 10 may be an absorbent member for absorbing the aqueous liquid collected from the target. Examples of absorbent members include porous materials with a different structure from the microneedle structure 1, such as nonwoven fabric. As for the nonwoven fabric, copper ammonium rayon nonwoven fabric, which was used in the measurement of the liquid absorption rate described above, can be used.

[0052] (7) Uses of the microneedle structure or microneedle patch Preferably, the microneedle structure 1 or microneedle patch is used to absorb liquid from a living body. Examples of liquids include blood and interstitial fluid. For example, if the functional member 10 is an inspection sheet for inspecting interstitial fluid, the components of the interstitial fluid absorbed by the microneedle structure 1 or microneedle patch are inspected by the inspection sheet. Alternatively, if the functional member 10 is an absorbent member that absorbs interstitial fluid, the interstitial fluid absorbed by the microneedle structure 1 or microneedle patch and further absorbed by the absorbent member can be extracted in a test solution and the components of the interstitial fluid can be analyzed.

[0053] (8) Method for manufacturing the microneedle structure Next, the method for manufacturing the microneedle structure 1 will be described.

[0054] In general terms, the method for manufacturing the microneedle structure 1 according to this embodiment includes a step of forming a needle-shaped portion having a channel inside (step S1), and a step of forming a coating by bringing a hydrophilic material into contact with the inner surface of the channel after the step of forming the needle-shaped portion (step S3). In a preferred embodiment, a plasma irradiation step (step S2) is further performed between steps S1 and S3. Plasma irradiation before coating formation makes it easier for the coating to adhere to the inner surface of the channel. This makes it possible to bond the coating more firmly to the surface of the channel.

[0055] The following provides a detailed explanation of each step, using an example.

[0056] (Step S1) Formation of the needle-like portion First, the needle-like portion is formed. Specifically, a microneedle structure (hereinafter referred to as an intermediate) is fabricated before the coating is formed. Figure 3 is a schematic diagram showing an example of the process of forming the needle-like portion (intermediate).

[0057] (A) Step S1-1: Preparation of base material (Figures 3(a) to 3(d)) First, the base material of the microneedle structure is prepared. More specifically, as shown in Figure 3(a), a dispersion is prepared by mixing the pore-forming agent with a solvent. In this embodiment, the pore-forming agent contains water-soluble particles. The water-soluble particles are incompatible with both the solvent and the needle-forming resin, but dissolve in water. Details of the water-soluble particles will be described later.

[0058] As a solvent, one that does not dissolve the water-soluble particles contained in the pore-forming agent can be used. For example, organic solvents such as IPA (isopropyl alcohol), ethyl acetate, ethanol, dichloromethane, dimethylformamide, and toluene can be used as solvents. The amount of solvent used is, for example, 50 to 150 parts by mass, preferably 80 to 120 parts by mass, when the total amount of the pore-forming agent and the needle-shaped resin is 100 parts by mass.

[0059] Next, as shown in Figure 3(b), the needle-shaped resin 12 is added to the dispersion, heated and melted, and stirred. This yields a mixture. If the pore-forming agent contains water-soluble particles, the water-soluble particles remain dispersed in the mixture in particulate form without dissolving.

[0060] Next, as shown in Figure 3(c), the obtained mixture is poured into the mold 13 for base material molding. The mold 13 for base material molding is provided with recesses corresponding to the size of the microneedle structure. The mixture is poured into these recesses. Then, the mixture is heated to remove the solvent. The mixture is also compressed and molded by pressing or other means.

[0061] Next, as shown in Figures 3(c) to 3(d), the molded mixture is cooled and solidified. The solidified mixture is then removed as the base material 14. If the pore-forming agent contains water-soluble particles, the water-soluble particles exist in a particulate state (dispersed state) within the obtained base material 14.

[0062] (B) Step S1-2: Molding (Figure 3(e)) Next, as shown in Figure 3(e), the base material 14 is filled into the mold 15. The mold 15 used has recesses that correspond to the shape of the needle-shaped portion. Then, heating and pressing are performed. Heating causes the base material 14 to become fluid and is molded to the shape of the mold. That is, the base material 14 is molded to have a shape with a needle-shaped portion.

[0063] (C) Step S1-3: Solidification (Figure 3(f)) Next, the molded base material 14 is cooled and solidified. Then, as shown in Figure 3(f), the molded base material is removed from the mold as the molded product 16.

[0064] (D) Step S1-4: Treatment with water (Figures 3(g) to 3(h)) Next, as shown in Figure 3(g), the molded product 16 is treated with water. This removes the pore-forming agent present in the molded product 16. As a result, a porous structure is formed in the molded product 16, and voids that function as flow channels are formed. After removing the pore-forming agent, the molded product is dried as shown in Figure 3(h). This yields a molded product having needle-shaped portions containing a porous structure, which serves as an intermediate 17 for the microneedle structure.

[0065] (Step S2) Plasma irradiation Although not shown in the diagram, after the creation of the intermediate 17, the needle-shaped portion 2 is subjected to plasma irradiation. Plasma irradiation excites the inner surface of the flow channel. Plasma treatment makes it easier to fix the hydrophilic material to the inner surface of the flow channel in the next step S3.

[0066] Plasma irradiation is preferably performed on both the surface where the needle-like portion is formed and the back surface. The plasma irradiation time for each surface is, for example, 5 to 120 seconds.

[0067] (Step S3) Coating Formation Subsequently, a coating is formed by bringing a hydrophilic substance into contact with the surface of the channel in the needle-shaped portion. This gives rise to a microneedle structure.

[0068] Specifically, a hydrophilic substance-containing liquid (including a liquid containing a substance that reacts with the surface of the channel in the needle-shaped portion to form a hydrophilic substance; the same applies hereinafter) is prepared. Then, an intermediate of the microneedle structure is immersed in the hydrophilic substance-containing liquid. This forms a coating containing the hydrophilic substance on the surface of the channel in the needle-shaped portion. It is preferable to reduce the surrounding environment pressure while the intermediate of the microneedle structure is immersed. This makes it easier for the hydrophilic substance-containing liquid to penetrate deep into the channel of the microneedle intermediate. The reduced pressure condition is, for example, about 0.01 MPa to 0.5 MPa. The time for maintaining the reduced pressure environment is, for example, about 15 minutes to 3 hours.

[0069] The concentration of the hydrophilic substance in the hydrophilic substance-containing solution is appropriately selected depending on the type of hydrophilic substance.

[0070] 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.

[0071] When the hydrophilic substance is a compound derived from arginine, the concentration of arginine in the hydrophilic substance-containing solution 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.

[0072] 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.

[0073] The solvent used in the hydrophilic substance-containing liquid is not particularly limited. For example, water and isopropyl alcohol can be used as solvents. Preferably, water is used as the solvent.

[0074] Furthermore, the coating does not necessarily have to be formed by a hydrophilic substance-containing liquid. For example, it is possible to form a coating on the inner surface of the channel by using a film-forming method such as plasma CVD. For instance, if the hydrophilic substance is an inorganic substance such as silicon dioxide, plasma CVD can be used.

[0075] (9) Other characteristics of the manufacturing method The manufacturing method of the microneedle structure has been described above with reference to an example.

[0076] In the above example, in step S1 (formation of needle-shaped parts, see Figures 3(a) to (b)), the case in which a dispersion is prepared by mixing the pore-forming agent with a solvent and then adding the needle-shaped part-forming resin 12 to the dispersion to obtain the mixture was described. However, the mixture may also be obtained by adding the pore-forming agent to the heated and melted needle-shaped part-forming resin 12 without using a solvent. Furthermore, the mixing order of the pore-forming agent, solvent, and needle-shaped part-forming resin 12 is not particularly limited. For example, the pore-forming agent may be added after mixing the solvent and the needle-shaped part-forming resin 12.

[0077] Furthermore, according to the inventors' findings, the pore-forming agent affects the porous structure of the needle-like portion. Therefore, by using a suitable pore-forming agent, a needle-like portion with a desired porous structure can be realized, and liquid absorption can be enhanced. This point will be described in detail below.

[0078] (Water-soluble particles as pore-forming agent) As previously described, the pore-forming agent preferably includes water-soluble particles. More preferably, the water-soluble particles include first particles having an average particle size of 17 μm or less. The average particle size here refers to the 50% diameter of the particle size measured by laser diffraction particle size measurement. Laser diffraction particle size measurement is performed by wet measurement using anhydrous ethanol. An example of a device for performing laser diffraction particle size measurement is the "MacroTrac Particle Size Analyzer MT3300" manufactured by Nikkiso Co., Ltd. By using first particles of this size, numerous openings are more easily formed on the surface of the needle-shaped part. As a result, it becomes possible to further increase the liquid absorption rate.

[0079] More preferably, the water-soluble particles have second particles in addition to the first particles. The second particles are water-soluble particles having an average particle diameter exceeding 17 μm. When the second particles are used in addition to the first particles, the pores are likely to be continuous inside the needle-like portions. As a result, the internal pore area of the needle-like portions is likely to increase. Thereby, it becomes possible to further enhance the liquid absorption property.

[0080] The amount of the water-soluble particles used (when the first particles and the second particles are used, the total amount thereof) is, for example, 50 to 90 parts by mass, preferably 60 to 80 parts by mass, when the total of the pore-forming agent and the needle-like portion-forming resin is 100 parts by mass.

[0081] The amount of the first particles used is, for example, 20 to 90 parts by mass, preferably 30 to 70 parts by mass, when the total of the pore-forming agent and the needle-like portion-forming resin is 100 parts by mass.

[0082] The amount of the second particles used is, for example, 1 to 40 parts by mass, preferably 3 to 30 parts by mass, when the total of the pore-forming agent and the needle-like portion-forming resin is 100 parts by mass.

[0083] The first particles and the second particles may be the same substance or different substances.

[0084] From the viewpoint of being incompatible with both the solvent and the needle-like portion-forming resin, it is preferable to use an inorganic salt as the water-soluble particles.

[0085] Examples of the inorganic salt include cations such as Na ＋ , Mg ２＋ , Ca ２＋ , Al ３＋ , and H ＋ etc., or anions such as Cl <00000​​​​​​​​​​​​​​​​​​​​​​Examples include compounds that dissociate into anions such as NaCl, KCl, and Na. Specifically, inorganic salts include NaCl, KCl, and Na ２ SO ４ CaCl ２ AlCl ３ Al ２ (SO ４ ) ３ These can be used. A preferred inorganic salt is NaCl.

[0086] (Water-soluble resin as pore-forming agent) In a more preferable approach, a water-soluble resin is used as a pore-forming agent in addition to the water-soluble particles mentioned above. By using a water-soluble resin in combination, the liquid absorption rate can be further increased. The water-soluble resin is preferably one that is readily soluble in water, and examples include polyalkylene glycol, polyvinylpyrrolidone, polyacrylamide, polyvinyl methyl ether, and cellulose derivatives such as carboxymethylcellulose. Among these, polyalkylene glycol is preferred from the viewpoint of ease of availability, solubility in water, and safety. Examples of polyalkylene glycols include polyethylene glycol and polypropylene glycol.

[0087] The amount of water-soluble resin used as a pore-forming agent is, for example, 0.5 to 20 parts by mass, preferably 1 to 15 parts by mass, based on a total of 100 parts by mass of the pore-forming agent and the needle-shaped resin.

[0088] The weight-average molecular weight of the water-soluble resin used as a pore-forming agent is, for example, 1,000 to 10,000, preferably 2,000 to 8,000.

[0089] By using both water-soluble particles and water-soluble resin as pore-forming agents, the liquid absorption capacity of the microneedle structure 1 can be improved. Water-soluble particles form pores that easily open on the surface of the needle-like structure, while water-soluble resins easily form pores inside the needle-like structure. Therefore, it is presumed that the pores opening on the surface of the needle-like structure function as entry and exit points for fluid to and from the outside of the needle-like structure, while these pores connect to the internal pores formed by the water-soluble resin, thereby forming an efficient flow path.

[0090] To further illustrate the present invention, the inventors will now describe some examples they have implemented. However, the present invention should not be limited to the following examples.

[0091] Microneedle structures for Examples 1 to 16 and Comparative Examples 1 to 2 were obtained according to the conditions shown in Table 1. Specifically, the microneedle structures were obtained by the following procedure.

[0092] (Example 1) 3.0 g of pelletized PCL (polycaprolactone, weight-average molecular weight 50,000, melting point 60°C; the method for measuring weight-average molecular weight will be described later) was prepared as the needle-shaped resin. This was placed in a 100 ml beaker. Next, 6.0 g of ethyl acetate was added as the solvent. The beaker was placed on a hot plate heated to 65°C and stirred with a stirrer bar at a rotation speed of 300 rpm for 60 minutes. Next, 6.5 g of NaCl (corresponding to the first particle: Naikai Salt Industry Co., Ltd., Nacle UM-10) with an average particle size of 10 μm and 0.5 g of PEG (polyethylene glycol, weight-average molecular weight 4,000, melting point 40°C) were added as pore-forming agents. Next, 2.0 g of ethyl acetate, prepared separately, was added dropwise along the edge of the beaker. While maintaining a temperature of 65°C, the rotation speed of the magnetic stirrer was increased to 500 rpm, and the mixture was stirred for another 10 minutes to obtain a mixture for forming the base material.

[0093] Next, a mold made of polydimethylsiloxane was prepared for forming the base material. The mold used for forming the base material had a recess (with an opening that was square in shape, with sides of 20 mm x 20 mm, and a depth of 0.25 mm). The base material forming mixture, which had been returned to room temperature, was dropped into the recess of this base material forming mold using a dropper with a cut tip. Any portion of the dropped mixture that did not fit into the recess was scraped off with a spatula. The base material forming mold was left to stand on a hot plate heated to 120°C for 10 minutes to remove the solvent.

[0094] Furthermore, the surface of the mixture for base material formation was flattened. Specifically, a SUS plate (2 mm thick, 80 mm short side, 100 mm long side, rectangular) was prepared, and a release film was attached to one side of this SUS plate with double-sided tape so that the release treatment surface faced outwards, creating a jig. Immediately after the heating of the mold for base material formation was completed, this jig was positioned so that the release treatment surface was in contact with the mixture injected into the mold for base material formation. Then, using a heating press machine (AH-1T, manufactured by AS ONE Corporation) without a temperature setting, the mixture was pressurized at 10 MPa for 10 minutes. After the pressure was released, the mold for base material formation with the jig and mixture injected was placed between two SUS plates (2 mm thick, 80 mm short side, 100 mm long side, rectangular) that had been cooled to 3°C beforehand, the four corners were fixed with alligator clips, and the mixture was cooled for 10 minutes to solidify.

[0095] Next, the solidified mixture was removed from the mold used for forming the base material. The base material was then left to stand in a drying oven (30°C) for 24 hours to dry. This resulted in a base material in which water-soluble particles were dispersed.

[0096] A mold for heat pressing was prepared. The mold used was made of polydimethylsiloxane and had multiple recesses for forming needle-like structures. The recesses used for forming needle-like structures had the following characteristics: • Recess shape: Conical shape with a circular cross-section • Maximum cross-sectional diameter of the recess: 300 μm • Height of the recess: 600 μm • Pitch of the recesses: 1000 μm • Number of recesses: 3 in rows 1 and 7, 5 in rows 2 and 6, and 7 in rows 3, 4 and 5, for a total of 37 • Size of the area where the recesses are formed: 6.3 mm square • Arrangement of the recesses: Regular octagonal shape

[0097] A mold was placed on the lower stage of a heating press machine (AH-1T, manufactured by AS ONE Corporation). The base material was then placed on the recess for forming the needle-like portion. A 30 mm square sheet (lid) made of polydimethylsiloxane was then placed on top. As a preliminary step, the base material was pressed at 2 MPa for 1 minute and 30 seconds while heating the lower stage at a set heating temperature of 120°C and the upper stage at a set heating temperature of 110°C. Then, as the main step, the base material was pressed at 3 MPa for 30 seconds with the lower and upper stages heated to the same temperatures as the preliminary step. The molten base material contained in the lid and mold was then refrigerated at 3°C ​​for 5 minutes to solidify. This resulted in obtaining a sample (molded product) with a needle-like portion and a base. The sample was then removed from the mold. Finally, the sample was immersed in purified water at room temperature for 1 hour and stirred with a stirrer bar. At this stage, the sample was secured to the beaker wall with double-sided tape to prevent contact with the stirrer bar. Next, the sample was immersed in purified water and stirred with the stirrer bar at 200 rpm for 30 minutes. Then, it was immersed again in purified water and stirred once more with the stirrer bar at 200 rpm for 30 minutes to dissolve and remove the pore-forming agent. After that, the sample was left to stand in a drying oven (30°C) for 24 hours to evaporate the moisture and dry it. This yielded an intermediate for the microneedle structure.

[0098] Next, as a pretreatment for hydrophilic coating the intermediate, plasma irradiation was performed on both the needle-shaped surface and the opposite surface of the dried intermediate. Plasma irradiation was performed for 30 seconds on each surface using a tabletop vacuum plasma device (YHS-R, manufactured by Kai Semiconductor Co., Ltd.).

[0099] As a hydrophilic substance, powdered PEG (polyethylene glycol, weight-average molecular weight 4,000) was prepared. The prepared PEG was diluted with purified water to obtain a 1.0 mass% PEG aqueous solution. The plasma-irradiated intermediate was immersed in the 1.0 mass% PEG aqueous solution and left for 1 hour under a reduced pressure of 0.09 MPa at 25°C. This allowed the 1.0 mass% PEG solution to penetrate the porous structure (channel) of the needle-shaped portion. After that, the intermediate was removed and left to stand in a drying oven (30°C) for 24 hours to evaporate the moisture and dry, forming a coating of the hydrophilic substance. This obtained the microneedle structure according to Example 1.

[0100] (Example 2) The amount of NaCl with an average particle size of 10 μm was changed to 6.3 g, and the amount of PEG used as a pore-forming agent was changed to 0.7 g. The microneedle structure according to Example 2 was fabricated in the same manner as in Example 1.

[0101] (Example 3) L(+)-arginine (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., formula weight: 174.2 g / mol) was diluted with purified water to prepare a 0.1 M (mol / l) arginine aqueous solution (hydrophilic substance-containing solution). This 0.1 M (mol / l) arginine aqueous solution was used instead of the 1.0 mass% PEG aqueous solution. The microneedle structure according to Example 3 was fabricated in the same manner as in Example 2.

[0102] (Example 4) The concentration of the arginine aqueous solution was changed to 0.25 M. The microneedle structure according to Example 4 was fabricated in the same manner as in Example 3.

[0103] (Example 5) The arginine aqueous solution was modified to a concentration of 0.5 M. The microneedle structure according to Example 5 was fabricated in the same manner as in Example 3.

[0104] (Example 6) Instead of purified water, a mixture of purified water and isopropyl alcohol (mass ratio 3:1) was used as the solvent for diluting L(+)-arginine. The microneedle structure according to Example 6 was prepared in the same manner as in Example 3.

[0105] (Example 7) The arginine solution was modified to a concentration of 0.25 M. The microneedle structure according to Example 7 was fabricated in the same manner as in Example 6.

[0106] (Example 8) PVA (polyvinyl alcohol, manufactured by ALDRICH, weight-average molecular weight: 35,000, degree of saponification: 98-99%) as a hydrophilic substance was sealed in a centrifuge tube and purified water was injected. The centrifuge tube containing the PVA and purified water was immersed in warm water heated to 90°C to dissolve the PVA and obtain a 1.0 mass% PVA aqueous solution. A microneedle structure according to Example 8 was prepared in the same manner as in Example 2, except that this 1.0 mass% PVA aqueous solution was used instead of a 1.0 mass% PEG aqueous solution.

[0107] (Example 9) The concentration of the PVA aqueous solution was changed to 3.0% by mass. The microneedle structure according to Example 9 was fabricated in the same manner as in Example 8.

[0108] (Example 10) The concentration of the PVA aqueous solution was changed to 5.0% by mass. The microneedle structure according to Example 10 was fabricated in the same manner as in Example 8.

[0109] (Example 11) The amount of NaCl with an average particle size of 10 μm was changed to 6.3 g, and 0.7 g of NaCl (sodium chloride, corresponding to the second particle, manufactured by Naikai Salt Industry Co., Ltd., Nakuru UM) with an average particle size of 35 μm was used as a pore-forming agent. On the other hand, PEG was not used as a pore-forming agent. The microneedle structure according to Example 11 was fabricated in the same manner as in Example 1 in other respects.

[0110] (Example 12) A microneedle structure according to Example 12 was prepared in the same manner as in Example 11, except that 0.35 g of PEG (polyethylene glycol, weight-average molecular weight 4,000, melting point 40°C) was further used as a pore-forming agent.

[0111] (Example 13) A microneedle structure according to Example 13 was prepared in the same manner as in Example 12, except that the amount of PEG was changed to 0.5 g.

[0112] (Example 14) A microneedle structure according to Example 14 was prepared in the same manner as in Example 11, except that the amount of NaCl with an average particle size of 10 μm was changed to 4.9 g and the amount of NaCl with an average particle size of 35 μm was changed to 2.1 g.

[0113] (Example 15) A microneedle structure according to Example 15 was prepared in the same manner as in Example 14, except that 0.35 g of PEG (polyethylene glycol, weight-average molecular weight 4,000, melting point 40°C) was further used as a pore-forming agent.

[0114] (Example 16) A microneedle structure according to Example 16 was prepared in the same manner as in Example 14, except that the amount of PEG (weight-average molecular weight 4,000, melting point 40°C) used as a pore-forming agent was changed to 0.5 g.

[0115] (Comparative Example 1) A microneedle structure according to Comparative Example 1 was prepared in the same manner as in Example 11, except that the microneedle structure was not treated with a hydrophilic substance. Specifically, plasma irradiation and immersion in polyethylene glycol solution were not performed.

[0116] (Comparative Example 2) A microneedle structure according to Comparative Example 2 was prepared in the same manner as in Example 14, except that the microneedle structure was not subjected to hydrophilic treatment. Specifically, plasma irradiation and immersion in polyethylene glycol solution were not performed.

[0117] (Measurement of water absorption rate) The water absorption rate of the microneedle structures according to the examples and comparative examples was measured according to the measurement method described in the embodiments above. Specifically, first a microneedle patch having the structure shown in Figure 4 was made. More specifically, a nonwoven fabric 4 was placed in the center of the back surface (the surface opposite to the surface where the needle-like part is formed at the base) of the microneedle structure 1. The nonwoven fabric 4 was circular in shape and had a size of 10 mm in diameter. Specifically, a nonwoven fabric made of cupro (copper ammonia rayon) (manufactured by Asahi Kasei Corporation, Cupro continuous long fiber nonwoven fabric Benliese, SN-140, thickness: 70 μm) was used. In addition, a re-peelable adhesive sheet 6 was prepared in which the adhesive layer was partially sealed with polyethylene terephthalate (PET) film 5. This adhesive sheet 6 was a square with sides of 20 mm, similar in shape to the outer edge of the microneedle structure. A polyethylene terephthalate film 5 (thickness: 25 μm) with the same shape as the nonwoven fabric 4 was laminated to the center of the adhesive layer of the adhesive sheet 6. This adhesive sheet 6 was laminated to the surface of the base of the microneedle structure 1, on which the nonwoven fabric 4 was placed in the center, to obtain a microneedle patch. The re-peelable adhesive sheet 6 used was one that could be peeled off from the surface of the microneedle structure 1. Furthermore, the adhesive layer of the adhesive sheet 6 does not adhere to the nonwoven fabric 4 due to the presence of the PET film 5. Therefore, the microneedle patch was configured so that the nonwoven fabric 4 could be safely removed by peeling off the adhesive sheet 6 after the liquid had been stored in the nonwoven fabric 4.

[0118] Next, 300 mg of agarose gel (NE-AG01, Fast Gene) was placed in a petri dish. Furthermore, 27 ml of purified water and 3 ml of phosphate-buffered saline (PBS) (Dulbecc's phosphate-buffered saline (10x concentrated): D-PBS(-)(10x), manufactured by Nacalai Tesque Co., Ltd.) were mixed in a graduated cylinder to prepare a 10-fold dilution, which was then poured into the petri dish containing the agarose gel. The petri dish containing this mixture was placed on a hot plate heated to 120°C, and the agarose gel was dissolved while stirring with a spoon. It was then allowed to cool to room temperature to obtain a 1% agarose gel containing PBS. Using this agarose gel, a microneedle patch was absorbed according to the procedure shown in Figure 5. That is, as shown in Figures 5(a) to (b), the needle portion of the microneedle patch was punctured into the agarose gel 7 and left to stand for 5 minutes. Subsequently, as shown in Figure 5(c), the microneedle patch was lifted from the agarose gel 7, and any droplets adhering to the needle-shaped portion were blown off and removed using an air blow gun. Then, as shown in Figures 5(d) to (e), the adhesive sheet 6 was peeled off the microneedle patch after absorption, and the nonwoven fabric 4 was removed. The mass of the microneedle structure 1 after absorption was then measured. The mass before absorption was also measured in advance before the absorption test. The absorption rate was then calculated according to the following formula.

[0119] (Equation 1) Absorption rate (%) = (Mass of microneedle structure after absorption - Mass of microneedle structure before absorption) ÷ Mass of microneedle structure before absorption × 100

[0120] For each example and comparative example, three microneedle patches were prepared, and the average value of the absorption rate was used as the result.

[0121] (Measurement of Strength) For the microneedle structures of the examples and comparative examples, the stress was measured by crushing each needle-shaped part one by one using a force gauge (manufactured by IMADA). Specifically, the microneedle structure was placed on a stage with the needle-shaped part facing upward, observed with a microscope, and one needle-shaped body with a sharp tip shape was selected. The attachment was then brought close to the microneedle, aligning it with the position of the selected needle-shaped body. At this time, care was taken to ensure that the attachment did not come into contact with adjacent microneedles. The vertical position of the attachment was moved to a position where it contacted the tip of the needle-shaped body but no force was applied to the needle-shaped body. From there, it was raised by 0.1 mm, and then the attachment was lowered at a descent rate of 5 mm / min to begin measuring the force applied to the attachment. Ten needle-shaped parts were measured, and from the measured stress, the stress at the needle tip was set to 0.0 mm, and the stress for every 0.02 mm displacement was extracted up to 0.3 mm. Of these, the average of the stress measured at the 0.2 mm displacement point across 10 needle-shaped sections was calculated and used as the strength of the microneedle structure.

[0122] (Weight-average molecular weight of polycaprolactone) The weight-average molecular weight (Mw) of polycaprolactone (PCL) used in the examples was measured using gel permeation chromatography (GPC) under the following conditions (GPC measurement), and is the value converted to a standard polystyrene. The sample for GPC measurement was prepared in the following procedure. First, 1 g of polycaprolactone (PCL) and 9 g of tetrahydrofuran (THF, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) were added to a screw tube, shaken, and completely dissolved to prepare a 10% PCL solution. 1 ml of the obtained solution and 9 ml of THF were added dropwise to a separately prepared screw tube to prepare a 1% PCL solution. This 1% PCL solution was filtered through a GD / X syringe filter (manufactured by Whatman) and added dropwise to the GPC apparatus. (Measurement conditions) • Measuring device: Tosoh Corporation, HLC-8320 • GPC column (passed in the following order): Tosoh Corporation TSK gel superH-H, TSK gel superHM-H, TSK gel superH2000 • Solvent: Tetrahydrofuran • Measurement temperature: 40°C

[0123] (Results and Discussion) Table 1 shows the results for liquid absorption rate and strength.

[0124] Comparing the liquid absorption rates of Comparative Example 1 and Example 11, Example 11 showed a higher liquid absorption rate than Comparative Example 1. This result indicates that the liquid absorption rate can be increased by forming a coating with a hydrophilic substance (polyethylene glycol). This trend can also be confirmed by comparing Comparative Example 2 and Example 14.

[0125] Furthermore, comparing the liquid absorption rates of Example 2 with those of Examples 3-10, Examples 3-10 showed higher liquid absorption rates than Example 2. This indicates that when arginine solution and polyvinyl alcohol aqueous solution are used as the hydrophilic substance-containing liquid, even higher liquid absorption rates can be obtained than when polyethylene glycol aqueous solution is used.

[0126] Furthermore, when examining the strength, Examples 8 to 10, which used PVA (polyvinyl alcohol) as the hydrophilic substance, showed higher strength than the other examples and comparative examples. This indicates that using polyvinyl alcohol as the hydrophilic substance can increase not only the liquid absorption rate but also the strength.

[0127] Furthermore, comparing the liquid absorption rates of Example 11 with those of Examples 12-13, the liquid absorption rates of Examples 12-13 are higher than those of Example 11. From this, it can be understood that the liquid absorption rate is further increased by using water-soluble particles (sodium chloride) and PEG (polyethylene glycol) in combination as pore-forming agents. This trend can also be observed from the comparison of the liquid absorption rates of Example 14 with those of Examples 15-16.

[0128] (Incorporation by Reference) This application claims priority under Japanese Patent Application No. 2024-171020, filed September 30, 2024, the disclosures of which are incorporated herein by reference.

[0129] 1... Microneedle structure, 2... Needle-shaped part, 3... Base part, 4... Nonwoven fabric, 5... PET film, 6... Removable adhesive tape, 7... Agarose gel, 8... Microneedle patch, 9... Tape, 10... Functional component, 12... Needle-shaped part forming resin, 13... Mold for base material molding, 14... Base material, 15... Mold, 16... Molded product, 17... Intermediate

Claims

1. A microneedle structure comprising a needle-shaped portion for insertion into a target, wherein a channel is provided inside the needle-shaped portion for the flow of a liquid injected into or received from the target, and the inner surface of the channel is coated with a hydrophilic substance.

2. The microneedle structure according to claim 1, wherein the needle-shaped portion has a porous structure, and the flow channel is formed by pores contained in the porous structure.

3. The microneedle structure according to claim 1 or 2, wherein the hydrophilic substance comprises a hydrophilic polymer.

4. The microneedle structure according to claim 3, wherein the hydrophilic polymer comprises carbon atoms and oxygen atoms, and the ratio of the number of oxygen atoms to carbon atoms in the hydrophilic polymer is 2 / 5 or more.

5. The microneedle structure according to claim 4, wherein the hydrophilic polymer has repeating units having hydroxyl groups.

6. The microneedle structure according to claim 5, wherein the hydrophilic polymer does not have carboxyl groups and has repeating units having hydroxyl groups.

7. The microneedle structure according to claim 3, wherein the hydrophilic polymer is a compound insoluble in water at room temperature.

8. The microneedle structure according to claim 7, wherein the hydrophilic polymer is polyvinyl alcohol.

9. The microneedle structure according to claim 1 or 2, wherein the hydrophilic substance is derived from a carboxyl-reactive compound having a functional group that reacts with and binds to a carboxyl group.

10. The microneedle structure according to claim 9, wherein the functional group comprises an amino group.

11. The microneedle structure according to claim 10, wherein the carboxyl group-reactive compound comprises an amino acid.

12. The microneedle structure according to claim 11, wherein the amino acid comprises arginine.

13. The microneedle structure according to claim 1 or 2, wherein the needle-shaped portion is formed of a needle-shaped portion forming resin, and the needle-shaped portion forming resin contains a low-melting-point resin having a melting point of 130°C or lower.

14. The microneedle structure according to claim 1 or 2, wherein the needle-shaped portion is formed of a needle-shaped portion forming resin, and the needle-shaped portion forming resin contains polyester.

15. The needle-shaped portion is formed from a needle-shaped portion forming resin, and the needle-shaped portion forming resin is a biodegradable resin, the microneedle structure according to claim 1 or 2.

16. The microneedle structure according to claim 1 or 2, wherein the liquid absorption rate of the needle-shaped portion, as measured by the following test method, is 1% or more. (Test method) Prepare a 10 mmφ copper ammonia rayon nonwoven fabric and determine its mass. Prepare a liquid-impermeable, repositionable adhesive tape and attach a liquid-impermeable resin film cut into a circle with a diameter of 1 cm to the adhesive surface of the repositionable adhesive tape. Place the nonwoven fabric in the center of the surface of the microneedle structure where the needle-shaped portion is not formed. Obtain a sample by attaching the repositionable adhesive tape so that the positions of the nonwoven fabric and the circular resin film coincide. Pierce the needle-shaped portion of the sample into a 1% agarose gel containing phosphate-buffered saline, then remove the sample from the agarose gel and remove any water droplets attached to the surface where the needle-shaped portion is provided. Then, peel the repositionable adhesive tape from the microneedle structure to separate the microneedle structure from the nonwoven fabric and determine the mass of the microneedle structure. Then, the absorption rate is calculated using the following formula 1. (Formula 1) Absorption rate (%) = (Mass of microneedle structure after absorption - Mass of microneedle structure before absorption) ÷ Mass of microneedle structure before absorption × 100 17. A microneedle structure according to claim 1 or 2, used for absorbing liquid from a living organism.

18. A microneedle patch comprising a microneedle structure according to claim 1 or 2 and a functional member which is a member that exchanges liquid with a target via the microneedle structure.

19. A method for manufacturing a microneedle structure according to claim 1 or 2, comprising: a step of forming a needle-shaped portion having a channel inside; and a step of forming the coating by bringing the hydrophilic substance into contact with the inner surface of the channel after the step of forming the needle-shaped portion.

20. A manufacturing method according to claim 19, further comprising the step of irradiating the needle-shaped portion with plasma between the step of forming the needle-shaped portion and the step of forming the coating.

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