Microneedle structure and microneedle patch

Abstract

This microneedle structure is provided with: a needle-like part to be inserted into a subject; and a flow path that opens on the surface of the needle-like part and through which a liquid to be injected into the subject or a liquid received from the subject flows. The needle-like part is formed of a needle-like part composition. The needle-like part composition contains a first resin which is a water-insoluble hydrophilic resin.

Description

Microneedle structure and microneedle patch

[0001] The present invention relates to a microneedle structure and a microneedle patch.

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

[0003] In relation to the above, for example, Patent Document 1 (WO 2023 / 042525) discloses a microneedle patch comprising a liquid-impermeable substrate having through-holes, an absorbent material capable of absorbing liquid filled in the through-holes, a needle-shaped portion provided on one side of the substrate and having a flow path formed therein, and a functional member provided on the other side of the substrate, wherein the needle-shaped portion and the absorbent material are connected to each other, and the absorbent material and the functional member are connected to each other.

[0004] It is desirable for a microneedle structure to be able to quickly collect or inject a liquid. The liquid handled by the microneedle structure is often aqueous. Therefore, the microneedle structure is required to have high water absorption. Therefore, an object of the present invention is to provide a microneedle structure having high water absorption.

[0005] In one aspect, the microneedle structure according to the present invention comprises a needle-shaped portion to be inserted into a subject and having a flow path opening on its surface, the needle-shaped portion being formed from a needle-shaped portion composition including a first resin that is a water-insoluble hydrophilic resin.

[0006] In another aspect, the present invention relates to a microneedle patch. The microneedle patch includes the above-mentioned microneedle structure, a functional member connected to a flow path, and a liquid-impermeable substrate supporting the microneedle structure and the functional member. The substrate has a through-hole, and the microneedle structure has a water-absorbing portion filling the through-hole, and the water-absorbing portion is connected to the functional member.

[0007] According to the present invention, a microneedle structure having high water absorbency is provided.

[0008] Fig. 1 is a schematic cross-sectional view showing a microneedle patch according to an embodiment. Fig. 2 is a schematic cross-sectional view showing an example of a suitable configuration of a microneedle structure. Fig. 3 is a schematic view showing an example of a method for manufacturing a microneedle structure. Fig. 4 is a graph showing the water absorption rates of Examples 1 to 6 and Comparative Examples 1 to 3.

[0009] Hereinafter, an embodiment of the present invention will be described with reference to the drawings.

[0010] (1) Microneedle Patch Fig. 1 is a schematic cross-sectional view showing a microneedle patch 1 according to this embodiment. This microneedle patch 1 is used by being attached to a target (e.g., a living organism, the human body). The microneedle patch 1 can be, for example, a test patch for collecting an aqueous liquid (such as a body fluid) from a target and testing its components. Alternatively, the microneedle patch 1 can be a drug solution administration patch for administering an aqueous drug solution to a target.

[0011] As shown in FIG. 1 , the microneedle patch 1 has a microneedle structure 2 , a functional member 3 , and an adhesive substrate 4 .

[0012] The adhesive substrate 4 is a substrate having an adhesive surface. The adhesive substrate 4 is, for example, in the form of a sheet (tape). The adhesive substrate 4 can be realized, for example, by an elastic woven fabric having an adhesive layer formed on its surface. The adhesive substrate 4 supports the microneedle structure 2 and the functional member 3. The microneedle structure 2 and the functional member 3 are adhered to the center of the adhesive surface of the adhesive substrate 4. An attachment portion 7, which is an area to be attached to an object, is provided on the outer periphery of the adhesive surface of the adhesive substrate 4.

[0013] The functional member 3 is disposed between the adhesive substrate 4 and the microneedle structure 2. The functional member 3 is a part that realizes the function of the microneedle patch 1. The functional member 3 is configured to receive liquid from a subject or to inject liquid into a subject via the microneedle structure 2. For example, the functional member 3 is a test sheet that changes color depending on the composition of the liquid received from the subject. In this case, the microneedle patch 1 functions as a test patch. Alternatively, the functional member 3 may be a storage member for storing a medicinal liquid to be injected into the subject. In this case, the microneedle patch 1 functions as a medicinal liquid administration patch.

[0014] The microneedle structure 2 is a part that allows a liquid to flow between the functional member 3 and a subject. The microneedle structure 2 has a needle-shaped portion 5, a base portion 6, and a flow path 13.

[0015] The base 6 is generally flat. The outer periphery of the base 6 is adhered to the adhesive substrate 4, and is thereby supported by the adhesive substrate 4. One surface of the base 6 is in contact with the functional member 3.

[0016] The needle-shaped portion 5 is the portion that is inserted into the target. The needle-shaped portion 5 extends so as to protrude from the other surface of the base portion 6 (the surface opposite to the surface that contacts the functional member 3). A plurality of needle-shaped portions 5 are provided. When the adhesive base material 4 is attached to the target at the attachment portion 7, each needle-shaped portion 5 is inserted into the target.

[0017] The flow channel 13 is provided to allow liquid to circulate between the subject and the functional member 3. One end of the flow channel 13 is connected to the surface of the needle-shaped portion 5. That is, one end of the flow channel 13 opens at the surface of the needle-shaped portion 5. The other end of the flow channel 13 is connected to the functional member 3. Due to the presence of the flow channel 13, when the needle-shaped portion 5 is inserted into the subject, liquid flows from the subject to the functional member 3, or liquid is injected from the functional member 3 into the subject.

[0018] (2) Needle-Shaped Portion In this embodiment, the composition of the material (hereinafter referred to as the needle-shaped portion composition) that constitutes the needle-shaped portion 5 is devised. The composition of the needle-shaped portion composition will be described in detail below.

[0019] (2-1) First Resin The needle-shaped portion composition contains a first resin. The first resin is a water-insoluble hydrophilic resin (hereinafter, sometimes simply referred to as a hydrophilic resin). The first resin may be composed of one type of hydrophilic resin, or may be composed of multiple hydrophilic resins.

[0020] The water-insoluble hydrophilic resin is a polymeric substance that is insoluble in water and has hydrophilic functional groups. The use of a hydrophilic resin improves the water absorption of the needle-shaped portion 5. As a result, the flow of liquid between the target and the functional member 3 via the flow path 13 can be promoted. Furthermore, the use of a water-insoluble resin reduces the solubility of the needle-shaped portion 5 in water. This makes it difficult for the needle-shaped portion 5 to dissolve in the liquid contained in the target even after the needle-shaped portion 5 is inserted into the target. Therefore, the shape of the microneedle structure 2 is more easily maintained. In addition, as will be described in detail later, the use of a water-insoluble hydrophilic resin makes it easier to manufacture a needle-shaped portion 5 with a porous structure. Therefore, it is easier to form a fine flow path 13 in the needle-shaped portion 5.

[0021] Examples of hydrophilic functional groups include hydroxyl groups, carboxyl groups, sulfonic acid groups, amine groups, and acetamide groups. Among these, hydroxyl groups and carboxyl groups are preferred. The hydrophilic functional groups are preferably present in the main chain or side chain of the first resin. The carboxyl groups may be in the form of carboxylate salts in the presence of counter ions such as metal ions.

[0022] The first resin may be a resin having both a repeating unit having a hydrophilic functional group and a repeating unit not having a hydrophilic functional group. In this case, however, it is preferable that the mass of the repeating unit having the hydrophilic functional group accounts for at least half of the mass of the resin. More preferably, the first resin includes a resin in which all repeating units have a hydrophilic functional group.

[0023] The equivalent weight of the hydrophilic functional group in the first resin is, for example, 1500 or less, preferably 1100 or less, more preferably 900 or less, and even more preferably 500 or less.

[0024] Specific examples of the first resin include polyvinyl alcohol and polysaccharides. Among these, polysaccharides with low water solubility are preferred. Examples of polysaccharides include cellulose, calcium alginate, chitin, cross-linked hyaluronic acid, and derivatives thereof. As polyvinyl alcohol, fully saponified products with a higher degree of water insolubility are preferred.

[0025] When the target is a living body, the first resin preferably contains a biologically derived polysaccharide from the viewpoint of affinity with the living body. Furthermore, from the viewpoint of keeping raw material costs low, cellulose or a derivative thereof is preferred, and cellulose is more preferred.

[0026] The content of the first resin in the needle-shaped portion composition is, for example, 3 to 50% by mass, preferably 4 to 40% by mass, and more preferably 10 to 30% by mass. Within such a range, the water absorption of the needle-shaped portion 5 is further improved. Furthermore, the needle-shaped portion composition can be easily prepared when forming the needle-shaped portion 5.

[0027] The first resin may be present in the needle-shaped portion 5 in the form of a filler. Specifically, the first resin may be present in the needle-shaped portion 5 in a state separated from other components. The filler may be, for example, spherical, amorphous, rod-like, flake-like, fibrous, etc., but fibrous filler is preferred from the viewpoint of ease of mixing with the second resin described below. The average particle size of the filler is, for example, 1 to 50 μm, preferably 2 to 30 μm, and more preferably 3 to 20 μm. The average particle size of the filler can be determined by observing the filler in the microneedle structure 2 with a scanning electron microscope (SEM) and measuring the length of the longest part of the particle, taking a seven-point average. When the filler is fibrous, the average particle size refers to the fiber length.

[0028] Preferably, the first resin includes cellulose fibers.

[0029] (2-2) Second Resin The needle-shaped portion composition may further contain a second resin that is different from the first resin. The second resin is a resin that is less hydrophilic than the first resin. By using the second resin, properties other than water absorbency (for example, strength) can be adjusted. A water-insoluble resin is used as the second resin. The second resin may be one type of resin or may be composed of multiple types of resins. From the viewpoint of processability of the needle-shaped portion composition, it is preferable that the second resin is a thermoplastic resin.

[0030] The melting point of the second resin is, for example, 250°C or lower, preferably 200°C or lower, and more preferably 130°C or lower. If the melting point is 130°C or lower, the processability of the needle-shaped portion composition is improved. In other words, when creating the needle-shaped portion 5, the needle-shaped portion composition can be molded without heating to a high temperature. Therefore, when the needle-shaped portion composition is used in combination with other materials, the amount of heat applied to the other materials during molding can be reduced. This makes it easier to combine the needle-shaped portion composition with other materials that have low heat resistance. On the other hand, it is preferable that the second resin is solid at room temperature (25°C). By using such a resin, the strength of the needle-shaped portion 5 is more easily maintained at room temperature. The melting point of the second resin is preferably 40°C or higher, more preferably 45°C or higher.

[0031] As the second resin, for example, a resin that is incompatible with the first resin is used.

[0032] As the second resin, for example, a resin that does not have a hydroxyl group, a carboxyl group, a sulfonic acid group, an amine group, or an acetamide group in a portion other than the terminals can be used.

[0033] When the first resin is a polysaccharide, the second resin may be, for example, a resin other than a polysaccharide.

[0034] Specific examples of the second resin include polyester; polyolefin-based resins such as polyethylene and α-olefin copolymers; olefin copolymer-based resins such as ethylene-vinyl acetate copolymer-based resins and ethylene-ethyl acrylate copolymers; polyurethane-based elastomers; and derivatives thereof.

[0035] The second resin is preferably a biodegradable resin. By using a biodegradable resin, the impact on living organisms can be reduced. Examples of such biodegradable resins include polyesters and their derivatives. As polyesters and their derivatives, aliphatic polyesters and their derivatives are preferably used. 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. Other examples of biodegradable aliphatic polyesters include polybutylene succinate (melting point: 84-115°C) and aliphatic-aromatic copolyesters (melting point: 110-120°C). Examples of polybutylene succinate that can be used include BioPBS, available from Mitsubishi Chemical Corporation. Examples of aliphatic-aromatic copolyesters that can be used include Ecoflex, available from BASF.

[0036] The biodegradable resin is preferably a resin in which the acid dissociation constant of the monomer is 4 or more. By having the acid dissociation constant of the monomer be 4 or more, the impact on the living body when the microneedle structure is applied to the living body can be reduced. In addition, when the monomer is a cyclic ester, the acid dissociation constant of the monomer referred to here 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. Furthermore, the acid dissociation constant of the monomer is preferably 25 or less, more preferably 15 or less. An example of a monomer constituting such a biodegradable resin and having an acid dissociation constant of 4 or more is caprolactone. In the second resin, the constituent units derived from a monomer having an acid dissociation constant of 4 or more preferably account for 70% by mass or more of all constituent units, more preferably 80% by mass or more, and even more preferably 90% by mass or more.

[0037] In a particularly preferred embodiment, the second resin comprises a homopolymer or copolymer containing units derived from caprolactone. Most preferably, the second resin comprises polycaprolactone.

[0038] The weight-average molecular weight of the second resin is not particularly limited, but from the viewpoint of water absorption, it is, for example, 5,000 or more, preferably 15,000 or more, more preferably 40,000 or more, even more preferably 45,000 or more, and most preferably 60,000 or more. Furthermore, within such a range, it is easy to maintain the strength required for the needle-shaped portion 5. Furthermore, as the weight-average molecular weight of the second resin increases, the water absorption of the microneedle structure 2 tends to improve.

[0039] The upper limit of the weight average molecular weight of the second resin is not particularly limited, but is, for example, 200,000 or less, preferably 150,000 or less.Within this range, the processability of the needle-shaped portion composition is unlikely to be impaired.

[0040] The content of the second resin in the needle-shaped portion composition is, for example, 50% by mass or more, preferably 65% ​​by mass or more, and more preferably 70% by mass or more. When the second resin is contained in such an amount, good processability can be achieved.

[0041] (3) Other Next, the configuration of other parts of the microneedle structure 2 will be described.

[0042] The needle-shaped portion 5 is not particularly limited in configuration, but preferably has a porous structure. In this case, the pores in the porous structure function as part of the flow path 13. A porous structure of the needle-shaped portion 5 allows liquid to flow between the needle-shaped portion 5 and the subject via multiple pathways. This further facilitates liquid flow. Furthermore, when the needle-shaped portion 5 has a porous structure, the surface area within the pores with which the aqueous liquid comes into contact inside the needle-shaped body is large. Therefore, by including a hydrophilic first resin in the needle-shaped portion, the hydrophilicity of the surface within the pores is enhanced, making it easier to achieve the effect of improving the water absorption of the needle-shaped portion 5. When the needle-shaped portion 5 has a porous structure, the pores in the porous structure may also open to the side of the needle-shaped body. In this case, the amount of aqueous liquid absorbed or released from the needle-shaped portion can be increased compared to when the flow path is open only to the tip of the needle-shaped portion.

[0043] The porous structure can be easily produced, for example, by using a pore-forming material during molding. Alternatively, the porous structure may be formed by fusing fine pieces of resin or by using a foaming agent. By using the porous structure as a flow path, the manufacturing process becomes easier than when nano-order flow paths are mechanically formed after molding the resin. Note that portions other than the needle-shaped portion 5 of the microneedle structure 2, such as the base 6 and the water-absorbing portion 9 described below, may also have a porous structure.

[0044] The shape, size, formation pitch, and number of the needle-like portions 5 are not particularly limited. Examples of the shape of the needle-like portions 5 include cylindrical, prismatic, conical, and pyramidal shapes. The maximum diameter or maximum dimension of the cross section at the base end of the needle-like portion 5 is, for example, 25 to 1000 μm. The tip diameter or tip cross-sectional dimension of the needle-like portion 5 is, for example, 1 to 100 μm. The height of the needle-like portion 5 is, for example, 50 to 2000 μm. The multiple needle-like portions 5 are arranged, for example, in a matrix. The number of needle-like portions 5 is, for example, 10 to 1000, preferably 30 to 500, and more preferably 50 to 300.

[0045] The base 6 and the needle-shaped portion 5 may be integrally formed from the same composition, or may be formed from separate members. Also, at least a portion of the base 6 and at least a portion of the needle-shaped portion 5 may be integrally formed.

[0046] FIG. 2 is a schematic cross-sectional view showing an example of a microneedle structure 2 different from the example shown in FIG. 1 . In the example shown in FIG. 2 , the microneedle structure 2 has a substrate 8 and a water-absorbing portion 9 supported by the substrate 8. The base 6 is formed by the substrate 8 and a portion of the water-absorbing portion 9. Specifically, a through-hole is provided in the substrate 8. The water-absorbing portion 9 fills the through-hole of the substrate 8 and is disposed on one surface of the substrate 8. The water-absorbing portion 9 contacts the functional member 3 above the through-hole. The needle-shaped portion 5 extends so as to protrude from the surface of the water-absorbing portion 9 opposite the functional member 3. The water-absorbing portion 9 is formed as an integral body using a needle-shaped portion composition. Both the needle-shaped portion 5 and the water-absorbing portion 9 have a porous structure. As a result, the pores in the water-absorbing portion 9 also function as flow paths 13 (omitted in FIG. 2 ), and the surface of the needle-shaped portion 5 and the functional member 3 are connected via the water-absorbing portion 9.

[0047] The substrate 8 is liquid-impermeable. If the substrate 8 is liquid-impermeable, the liquid will only pass through the through-holes. This prevents the liquid from seeping into the substrate 8. As a result, the liquid can be efficiently circulated between the functional member 3 and the target. For example, when the microneedle patch 1 is used as a test patch, the test can be performed quickly. Furthermore, when the microneedle patch is used as a drug solution administration patch, the drug solution can be administered quickly. The material of the substrate 8 is not particularly limited, and examples thereof include a resin film, a metal-containing sheet, and a glass film. Furthermore, the substrate 8 may be a base film on which an adhesive layer is formed.

[0048] The thickness of the substrate 8 is, for example, 3 to 200 μm, preferably 10 to 170 μm, and more preferably 50 to 150 μm.

[0049] The diameter of the through-holes provided in the substrate 8 is, for example, 1 to 50 mm, preferably 2 to 30 mm, and more preferably 5 to 20 mm.

[0050] When the microneedle structure 2 is composed solely of a porous structure, such as when both the needle-shaped portion 5 and the base portion 6 of the microneedle structure 2 in FIG. 1 have a porous structure, it is preferable that the water absorption rate of the microneedle structure 2 measured by the following method be 10% or more, from the viewpoint of increasing the liquid flow rate inside the microneedle structure 2. (Method for measuring water absorption rate) The microneedle structure is immersed in 10 ml of purified water in an environment of 25°C. The immersed microneedle structure is placed in a reduced pressure environment of 0.09 MPa for 1 hour, allowing water to penetrate into the interior of the porous structure. The microneedle structure is then removed from the purified water, and water droplets adhering to the surface are removed. Water droplets on the surface of the microneedle structure on which the needle-shaped portion is formed are removed by blowing them off with an air blow gun, and water droplets on the surface of the microneedle structure on the base side are removed by placing the base on a glass plate and allowing the water droplets to be pushed around the base by the weight of the microneedle structure. After leaving it to stand for 5 seconds, the microneedle structure is then removed from the glass plate. Thereafter, the weight of the sample after absorbing water is measured. Then, the water absorption rate (the ratio of absorbed water to the weight of the sample) is calculated using the following formula: Water absorption rate (%) = (weight of sample after absorbing water - weight of sample before absorbing water) / weight of sample before absorbing water x 100 The water absorption rate measured by this method is more preferably 13% or more, even more preferably 20% or more, and even more preferably 28% or more. There are no particular restrictions on the upper limit of the water absorption rate, but it is usually about 50% or less.

[0051] Furthermore, for a microneedle structure 2 having a substrate 8 as shown in Figure 2, the substrate 8 (and other components that do not have a porous structure) can be removed, leaving the structure consisting only of a porous structure, and the water absorption rate can be measured using the same measurement method.

[0052] (4) Manufacturing Method There is no particular limitation on the manufacturing method of the microneedle structure 2. Hereinafter, the manufacturing method of the microneedle structure 2 will be described using as an example a method for manufacturing the microneedle structure 2 having the configuration shown in Fig. 2 .

[0053] FIG. 3 is a schematic diagram showing an example of a method for manufacturing the microneedle structure 2.

[0054] First, as shown in Fig. 3(a), a mixture 10 that will be the precursor of the water absorbing portion 9 is prepared. Specifically, the first resin, the second resin, and the pore-forming material are heated and kneaded, for example, at a temperature at which the second resin melts.

[0055] The pore-forming material is used to form a porous structure. The pore-forming material is a substance that is removed in a subsequent process. This forms pores in the area where the pore-forming material was present. A water-soluble material is used as the pore-forming material. The pore-forming material may be an organic or inorganic substance. In a preferred embodiment, a water-soluble thermoplastic resin is used as the pore-forming material. Furthermore, the pore-forming material is preferably a biodegradable resin. A particularly preferred pore-forming material is polyalkylene glycol. The weight-average molecular weight of the polyalkylene glycol is, for example, 200 to 4,000,000, preferably 600 to 500,000, and particularly preferably 1,000 to 100,000. Among polyalkylene glycols, polyethylene glycol is preferably used.

[0056] The pore-forming material is used in an amount of, for example, 10 to 90 parts by mass, preferably 15 to 70 parts by mass, and more preferably 20 to 55 parts by mass, per 100 parts by mass of the needle-shaped portion composition (excluding volatile components such as the solvent). With such an amount, the needle-shaped portion 5 can be formed with a favorable porosity in terms of water absorbency.

[0057] Next, as shown in Fig. 3(b), the mixture 10 is molded. Specifically, a base material mold having a recess is prepared, and the mixture 10 is poured into the recess. After pouring, the surface of the mixture 10 is flattened as necessary. As a result, the mixture 10 is molded into a roughly sheet-like shape, and the base material 11 is obtained.

[0058] 3(c), degassing and refrigeration for solidification are performed as necessary, and the base material 11 is removed. Next, although not shown, a base material 8 having through holes formed therein is prepared, and the base material 8 is bonded to the base material 11. The base material 8 is bonded to the base material 11 via, for example, an adhesive.

[0059] Next, as shown in FIG. 3( d ), the base material 11 to which the substrate 8 is adhered is placed on a mold 12 in which recesses for forming needle-shaped portions are formed. The base material 11 is then molded by hot pressing. Hot pressing may be performed multiple times under different conditions. For example, a preliminary process under milder conditions may be followed by a main process under relatively harsh conditions. The temperature condition for the hot pressing is preferably equal to or higher than the melting point of the second resin. For example, when using polycaprolactone with a melting point of 60°C, a temperature of approximately 90 to 160°C is preferred. This results in the formation of needle-shaped portions 5 in the base material 11. Furthermore, the base material 11 is embedded in the through-holes of the base material 8. This results in a structure having the base material 8 and the water-absorbing portion 9 (derived from the base material 11).

[0060] 3( e) and 3( f), the structure is removed from the mold 12, immersed in water, and washed. For example, the structure is immersed at 40° C. for 24 hours and then dried at 40° C. for 24 hours. This removes the pore-forming material contained in the water absorption section 9, and a porous structure is formed in the water absorption section 9.

[0061] Subsequently, a drying process is carried out as shown in Fig. 3(g), thereby completing the microneedle structure 2.

[0062] A microneedle patch 1 can be obtained by attaching a functional member 3 and an adhesive substrate 4 to the obtained microneedle structure 2. In the method for manufacturing the microneedle structure 2 according to this embodiment, the step of adhering the substrate 8 to the base material 11 may be omitted to obtain a microneedle structure 2 without the substrate 8.

[0063] Next, examples carried out by the present inventors will be described in order to explain the present invention in more detail, but the present invention should not be construed as being limited to the following examples.

[0064] [Measurement Method] The method for measuring the weight average molecular weight (Mw) of polycaprolactone (PCL) and the water absorption rate of the microneedle structure used in the examples is described below. (Weight Average Molecular Weight Mw) 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 the value was converted to a standard polystyrene standard. The sample for GPC measurement was prepared as follows. 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 dropped into 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 device. (Measurement conditions) Measurement device: HLC-8320, manufactured by Tosoh Corporation GPC columns (passed in the following order): TSK gel super H-H, TSK gel super HM-H, TSK gel super H2000, manufactured by Tosoh Corporation Measurement solvent: tetrahydrofuran Measurement temperature: 40°C

[0065] (Water Absorption Rate) The weight of the sample microneedle structure before water absorption was measured. Next, the sample was placed in a tray (non-charged balance dish manufactured by AS ONE Corporation) in an environment of 25°C, and 10 ml of purified water was poured into the sample to immerse it. The tray was then placed in a reduced pressure environment of 0.09 MPa for 1 hour to allow water to penetrate into the porous structure of the sample. Next, the sample was removed from the tray, and water droplets adhering to the surface were removed. Specifically, water droplets on the surface on which the needle-shaped portion of the microneedle structure was formed were removed by blowing them off with an air blow gun. In addition, water droplets on the surface on the base side of the microneedle structure were removed by placing the base on a glass plate and allowing the water droplets to be pushed around the base by the weight of the microneedle structure. After leaving it for 5 seconds, the microneedle structure was removed from the glass plate. Thereafter, the weight of the sample after water absorption was measured. The water absorption rate (the ratio of absorbed water to the weight of the sample) was calculated using the following formula.

[0066] (Formula 1) Water absorption rate (%) = (weight of sample after water absorption - weight of sample before water absorption) ÷ weight of sample before water absorption × 100

[0067] [Example 1] A microneedle structure according to Example 1 was produced according to the method shown in Fig. 3. However, the substrate 8 was not used. Table 1 shows the composition of the microneedle structure.

[0068] Specifically, first, 3 g of polyethylene glycol (PEG) (weight average molecular weight 4,000) as a pore-forming material, 7 g of pellet-shaped (cross-sectional diameter 3.5 mm) polycaprolactone (weight average molecular weight 80,000, melting point 60°C) as a second resin, and 0.5 g of a cellulose filler (ARBOCEL Ultrafine Cellulose, average particle size = 6-12 μm, manufactured by Rettenmeyer Japan) as a first resin were heated and kneaded at 170°C using a kneader (Laboplastomill 4C150, Toyo Seiki Seisakusho Co., Ltd.). This prepared a mixture.

[0069] Next, a base material forming mold made of polydimethylsiloxane was prepared. A recess (a square opening measuring 15 mm x 15 mm on each side and 1.5 mm deep) was formed in the base material forming mold. The prepared mixture was poured into the recess of this base material forming mold. Next, a sheet made of polydimethylsiloxane was placed on the base material forming mold, and the surface of the mixture was flattened. In this state, it was refrigerated at 3°C ​​for 5 minutes to solidify the molten mixture. This yielded a base material. The obtained base material was removed from the base material forming mold.

[0070] Next, a mold for hot pressing was prepared. The mold used was made of polydimethylsiloxane and had a plurality of recesses for forming needle-shaped portions. The recesses for forming needle-shaped portions had the following characteristics: Shape of recesses for forming needle-shaped portions: quadrangular pyramid shape with a square cross section Length of one side of the largest cross section of the recesses for forming needle-shaped portions: 500 μm Height of recesses for forming needle-shaped portions: 900 μm Pitch of recesses for forming needle-shaped portions: 1000 μm Number of recesses for forming needle-shaped portions: 13 in a vertical column, 13 in a row, a total of 169 Size of the area where the recesses for forming needle-shaped portions were formed: 15 mm square Arrangement of recesses for forming needle-shaped portions: square lattice

[0071] Next, the mold was placed on the lower stage of a heating press (AH-1T, manufactured by AS ONE Corporation). Furthermore, a base material was placed on the recess for forming the needle-shaped portion. Furthermore, a 30 mm square polydimethylsiloxane sheet (lid) was placed on top of it. Then, as a preliminary step, the base material was pressed at 2 MPa for 1 minute 30 seconds while heating at a lower stage setting temperature of 115°C and an upper stage setting temperature of 105°C. Thereafter, as the main step, the base material was pressed at 4 MPa for 30 seconds while the lower and upper stages were heated to the same temperature as in the preliminary step. Furthermore, the molten base material contained in the lid and mold was refrigerated at 3°C ​​for 5 minutes to solidify the base material. This formed a needle-shaped portion and the like. The sample was then peeled from the mold and immersed in purified water at 40°C for 24 hours to dissolve and remove the pore-forming material. Thereafter, the sample was left to stand in a drying oven (40°C) for 24 hours to evaporate the water and dry it, thereby obtaining a microneedle structure according to Example 1.

[0072] Example 2 A microneedle structure according to Example 2 was obtained in the same manner as in Example 1 except that the amount of filler (first resin) added was changed to 2.0 g.

[0073] Example 3 A microneedle structure according to Example 3 was obtained in the same manner as in Example 1, except that the molecular weight of PCL (second resin) was changed to 40,000.

[0074] Example 4 A microneedle structure according to Example 4 was obtained in the same manner as in Example 3, except that the amount of filler (first resin) added was changed to 2.0 g.

[0075] Example 5 A microneedle structure according to Example 5 was obtained in the same manner as in Example 1, except that the molecular weight of PCL (second resin) was changed to 10,000.

[0076] Example 6 A microneedle structure according to Example 6 was obtained in the same manner as in Example 5, except that the amount of filler (first resin) added was changed to 2.0 g.

[0077] Comparative Example 1 A microneedle structure according to Comparative Example 1 was obtained in the same manner as in Example 1, except that no filler (first resin) was added.

[0078] Comparative Example 2 A microneedle structure according to Comparative Example 2 was obtained in the same manner as in Example 3, except that the filler (first resin) was not blended.

[0079] Comparative Example 3 A microneedle structure according to Comparative Example 3 was obtained in the same manner as in Example 5, except that the filler (first resin) was not blended.

[0080] [Results and Discussion] The water absorption rate was measured by the method described above for the microneedle structures according to Examples 1 to 6 and Comparative Examples 1 to 3. The measurement results are shown in Table 1 and Fig. 4. In Fig. 4, the numerical values ​​written above each Example and Comparative Example indicate the amount (g) of filler (first resin) added.

[0081] Comparing Examples 1, 2, and Comparative Example 1, in which the weight-average molecular weight of the second resin was 80,000, the water absorption rates of Examples 1 and 2 were all higher than that of Comparative Example 1. This indicates that the addition of the first resin, which is a water-insoluble hydrophilic resin, improves the water absorption rate. A similar trend was also confirmed when the weight-average molecular weight of the second resin was 40,000 (comparison between Examples 3, 4, and Comparative Example 2) and when the weight-average molecular weight of the second resin was 10,000 (comparison between Examples 5, 6, and Comparative Example 3).

[0082] Furthermore, when comparing Example 1, Example 3, and Example 5, Example 1 had a higher water absorption rate than Examples 3 and 5. Furthermore, when comparing Example 2, Example 4, and Example 6, Example 2 had a higher water absorption rate than Examples 4 and 6. From this, it was found that microneedle structures in which the weight average molecular weight of the second resin is 45,000 or more tend to have improved water absorption. Although the reason for this is unclear, it is presumed that when the weight average molecular weight of the second resin is high, the porous structure changes and a porous structure with increased water absorption is obtained.

[0083]

[0084] REFERENCE SIGNS LIST 1 Microneedle patch 2 Microneedle structure 3 Functional member 4 Adhesive substrate 5 Needle-shaped portion 6 Base portion 7 Adhesion surface 8 Substrate 9 Water-absorbing portion 10 Mixture 11 Base material 12 Mold 13 Flow path

Claims

1. A microneedle structure comprising: a needle-shaped portion to be inserted into a subject; and a flow path opening on the surface of the needle-shaped portion through which a liquid to be injected into the subject or a liquid received from the subject flows, wherein the needle-shaped portion is formed from a needle-shaped portion composition, and the needle-shaped portion composition contains a first resin which is a water-insoluble hydrophilic resin.

2. The microneedle structure according to claim 1, wherein the first resin is a polysaccharide.

3. The microneedle structure according to claim 1 or 2, wherein the needle-shaped portion has a porous structure.

4. The microneedle structure according to claim 3, wherein the microneedle structure has a base from which the needle-like portion extends, and the water absorption rate of the microneedle structure, when composed only of the porous structure, is 10% or more as measured by the following measurement method. (Method of measuring water absorption rate) The microneedle structure is immersed in 10 ml of purified water in an environment of 25°C. The immersed microneedle structure is placed in a reduced pressure environment of 0.09 MPa for 1 hour to allow water to penetrate into the inside of the porous structure. The microneedle structure is then removed from the purified water, and water droplets attached to the surface are removed. The water droplets on the surface of the microneedle structure on the side where the needle-like portion is formed are removed by blowing them off with an air blow gun, and the water droplets on the surface of the base side of the microneedle structure are removed by placing the base on a glass plate and pushing the water droplets around the base by the weight of the microneedle structure, and the microneedle structure is left to stand for 5 seconds, and then the microneedle structure is removed from the glass plate. The weight of the sample after water absorption is then measured. Then, the water absorption rate (the ratio of absorbed water to the weight of the sample) is calculated by the following formula: Water absorption rate (%) = (weight of sample after water absorption - weight of sample before water absorption) / weight of sample before water absorption x 100 5. The microneedle structure according to claim 1 or 2, wherein the content of the first resin in the needle-shaped portion composition is 3 to 50 mass %.

6. The microneedle structure according to claim 1 or 2, wherein the needle-shaped portion composition further contains a second resin which is a resin different from the first resin.

7. The microneedle structure according to claim 6, wherein the second resin has a weight average molecular weight of 45,000 or more.

8. The microneedle structure according to claim 6, wherein the second resin is a thermoplastic resin.

9. A microneedle patch comprising: a microneedle structure as defined in claim 1 or 2; a functional member connected to the flow path; and a liquid-impermeable substrate supporting the microneedle structure and the functional member, wherein the substrate has a through hole, the microneedle structure has a water-absorbing portion filling the through hole, and the water-absorbing portion is connected to the functional member.

10. A microneedle structure comprising a needle-shaped portion to be inserted into a target, and a flow path opening on the surface of the needle-shaped portion and through which a liquid to be injected into the target or a liquid received from the target flows, wherein the needle-shaped portion has a porous structure, the microneedle structure has a base from which the needle-shaped portion extends from one surface, and the microneedle structure has a water absorption rate of 10% or more when the microneedle structure is composed only of the porous structure, as measured by the following measurement method. (Method of measuring water absorption rate) The microneedle structure is immersed in 10 ml of purified water in an environment of 25°C. The immersed microneedle structure is placed in a reduced pressure environment of 0.09 MPa for 1 hour, and water is allowed to penetrate into the inside of the porous structure. Next, the microneedle structure is taken out of the purified water, and water droplets adhering to the surface are removed. Water droplets on the surface of the microneedle structure on which the needle-shaped portion is formed are removed by blowing them off with an air blow gun, and water droplets on the surface of the base side of the microneedle structure are removed by placing the base on a glass plate and allowing the weight of the microneedle structure to push the water droplets around the base, and then leaving it to stand for 5 seconds, and then removing the microneedle structure from the glass plate. Thereafter, the weight of the sample after water absorption is measured. The water absorption rate (the ratio of absorbed water to the sample's own weight) is then calculated using the following formula: Water absorption rate (%) = (weight of sample after water absorption - weight of sample before water absorption) ÷ weight of sample before water absorption x 100

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