Microneedle array

Abstract

To provide a microneedle array that allows naratriptan to be impregnated into the subcutis of a person quickly by piercing a microneedle into a human skin.SOLUTION: A microneedle array includes: a microneedle array 11; an adhesive sheet 12 provided on the reverse face of the microneedle array 11 beyond the periphery of the microneedle array 11; and a protective release sheet 13 provided on the surface of the adhesive sheet 12 in the periphery of the microneedle array 11. The microneedle array 11 includes a plurality of dissoluble microneedles 11a pierced into the human skin. The microneedle 11a contains, as a medicinal component, naratriptan with water-soluble polymer as a base material.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a microneedle array for penetrating medicinal ingredients into human skin. [Background technology]

[0002] Conventionally, topical preparations have been used that are applied to human skin and that exert their effects on local or systemic disease sites with specific medicinal ingredients. As topical preparations, for example, so-called patches such as poultices and tapes are known, and by attaching these to human skin, the medicinal ingredients penetrate the skin.

[0003] However, with these topical preparations, it sometimes takes a long time for the medicinal ingredients to penetrate the skin (particularly the stratum corneum), or the medicinal ingredients do not penetrate sufficiently into the subcutaneous tissue or systemic blood flow.

[0004] In recent years, a formulation (hereinafter, microneedle array) has been proposed that uses a water-soluble polymer as a base and an array of numerous fine needles (hereinafter, microneedles) containing specific medicinal ingredients as a base to solve the shortcomings of such topical preparations.

[0005] When the microneedle array is attached to human skin, the microneedles inserted into the human skin dissolve, allowing the medicinal ingredients contained in the microneedles to easily and reliably penetrate into the skin and subcutaneously. Furthermore, the inserted microneedle part dissolves and disappears in the skin. Since the microneedles of the needle part of such a microneedle array are very fine and have a shape that is highly penetrable, even if they are inserted into the skin, there is no pain or bleeding, and the puncture wound is quickly closed, making it extremely effective as a method for supplying medicinal ingredients into the skin and subcutaneously.

[0006] Recently, microneedle arrays have been proposed that contain, as an active ingredient, a triptan drug (particularly sumatriptan), which is a selective serotonin receptor agonist drug, for the purpose of alleviating migraines (see, for example, Patent Documents 1 to 12).

[0007] Triptan drugs are usually taken orally, but oral medications have the disadvantages of low bioavailability due to their absorption from the small intestine and metabolism in the liver, and large single doses. Therefore, microneedle arrays, which can easily administer drugs intradermally or subcutaneously and are expected to have a faster effect than existing oral medications, are attracting attention as a new option for migraine drug administration. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] Patent Publication No. 2022-177280 [Patent Document 2] JP 2023-29328 A [Patent Document 3] JP 2022-71044 A [Patent Document 4] JP 2021-121339 A [Patent Document 5] Special Publication No. 2021-528155 [Patent Document 6] Special Publication No. 2020-536634 [Patent Document 7] JP 2020-73023 A [Patent Document 8] Special Publication No. 2020-500173 [Patent Document 9] WO2017-104491 publication [Patent Document 10] Special Publication No. 2018-511438 [Patent Document 11] Special Publication No. 2017-517295 [Patent Document 12] WO2015-129807 publication Summary of the Invention [Problem to be solved by the invention]

[0009] However, among the triptan drugs, many microneedle arrays containing sumatriptan or zolmitriptan have been proposed as described above, but no microneedle arrays containing naratriptan have been proposed at all. This is presumably because sumatriptan and zolmitriptan have a property of being easily soluble in water, and therefore have a high affinity with the water-soluble polymer base that constitutes the microneedle, while naratriptan has a property of being poorly soluble in water, and therefore has a low affinity with the water-soluble polymer of the microneedle, and has been considered to be unsuitable for addition to microneedles based on water-soluble polymers.

[0010] Of course, even triptan drugs other than naratriptan, such as sumatriptan and zolmitriptan, have a certain pharmacological effect when used with microneedles, but the other triptan drugs have a shorter half-life in the body (the time it takes for the drug to be reduced by half in the body) than naratriptan, so the pharmacological effect was not sufficient. In this regard, it is possible to increase the dosage of the triptan drug to fully exert its pharmacological effect, but since microneedles must be formed very finely in order to be inserted into human skin, there is a limit to how much the dosage of the triptan drug can be increased.

[0011] The present invention has been made in consideration of the above-mentioned technical background, and aims to provide a microneedle array that can incorporate naratriptan, a migraine medication, into microneedles based on a water-soluble polymer and that can rapidly penetrate naratriptan subcutaneously by inserting the microneedles into human skin. [Means for solving the problem]

[0012] The applicant has conducted research and experiments into the application of naratriptan, a triptan drug, in microneedle patches and has discovered that naratriptan can also be contained in microneedles based on a water-soluble polymer.

[0013] Specifically, the microneedle array of the present invention is a microneedle array comprising a plurality of soluble microneedles to be inserted into human skin, and is characterized in that the microneedles have a water-soluble polymer base and contain naratriptan as an active ingredient.

[0014] The microneedles are formed in a cone or truncated cone shape with a tip diameter of 5 to 100 μm (preferably smaller than the pore diameter of 20 to 50 μm), a base diameter of 120 to 800 μm, and a height of 30 to 1000 μm, a strength of 0.4 to 0.6 N, a distance between adjacent needles of 100 μm to 1800 μm, and a length of 1 cm. 2 It is preferable that the density is set to about 120 to 600 per unit.

[0015] In addition, the microneedle array is preferably based on a water-soluble polymer consisting of at least one of hyaluronic acid, chondroitin sulfate, glycogen, dextrin, dextran, dextran sulfate, hydroxypropyl methylcellulose, alginic acid, chitin, chitosan, pullulan, collagen, gelatin, polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acid, carboxyvinyl polymer, polylactic acid, polyglycolic acid, and lactic acid-glycolic acid copolymer.

[0016] Furthermore, the microneedle patch according to the present invention is characterized by comprising the above-mentioned microneedle array, an adhesive sheet provided on the back surface of the microneedle array in a manner that extends beyond the periphery of the microneedle array, and a protective release sheet provided on the surface of the adhesive sheet around the periphery of the microneedle array.

[0017] Furthermore, in the method for manufacturing microneedles according to the present invention, when naratriptan is incorporated as a medicinal ingredient into the water-soluble polymer base material, if the amount of naratriptan relative to the water-soluble polymer is small (the content of naratriptan in the water-soluble polymer base material is less than 10 mg / ml), the temperature of the water-soluble polymer base material should be set to 25°C to 30°C, if the amount of naratriptan relative to the water-soluble polymer is medium (the content of naratriptan in the water-soluble polymer base material is 20 mg / ml to 30 mg / ml), the temperature of the water-soluble polymer base material should be set to 60°C to 65°C, and if the amount of naratriptan relative to the water-soluble polymer is large (the content of naratriptan in the water-soluble polymer base material is 175 mg / ml to 250 mg / ml), the temperature of the water-soluble polymer base material should be set to 70°C to 80°C.

[0018] In addition, in the method for producing microneedles according to the present invention, naratriptan may be micronized to reduce the particle size of the naratriptan, and then uniformly dispersed in a water-soluble polymer base material.

[0019] Furthermore, the method for manufacturing microneedles according to the present invention may include a first step of preparing a substrate for forming a plurality of microneedles on its surface; a second step of dripping microneedle-forming components in the form of spots onto the surface of the substrate; a third step of stacking the substrates onto which the microneedle-forming components have been dripped one above the other to bring the microneedle-forming components of both substrates into contact with each other; a fourth step of pulling the substrates away from each other to stretch the microneedle-forming components dripped onto the surfaces of both substrates to a predetermined length and allowing them to solidify in this state at room temperature; and a fifth step of cutting the portions of the microneedle-forming components with the smallest diameter on the surfaces of both substrates after the microneedle-forming components on the surfaces of both substrates have completely solidified, thereby forming microneedles of a predetermined shape and size on the surfaces of both substrates. Effect of the Invention

[0020] According to the present invention, naratriptan as a migraine drug can be contained in a microneedle based on a water-soluble polymer, and by inserting the microneedle into human skin, naratriptan can be rapidly penetrated into and under the skin of a human. As a result, naratriptan in particular has a longer half-life in the body (the time it takes for the drug to be halved in the body) than other triptan drugs, and the dosage required to exert its pharmacological effect is smaller than that of other triptan drugs, so that a sufficient dosage can be contained in a finely formed microneedle, and the pharmacological effect of naratriptan can be exerted for a long period of time. [Brief description of the drawings]

[0021] [Figure 1] 1A and 1B are cross-sectional and plan views showing a microneedle patch according to an embodiment of the present invention. [Diagram 2] FIG. 2 is a diagram showing the steps for manufacturing the microneedle patch of FIG. 1. [Diagram 3] FIG. 2 is a diagram showing the specifications of the microneedle samples (MAP1, MAP2) according to Example 1 of the present invention. [Figure 4] FIG. 2 is a diagram showing the specifications of test groups (G1, G2, G3) according to the first embodiment of the present invention. [Diagram 5] FIG. 1 shows the results of an animal experiment in Example 1 of the present invention. [Figure 6] FIG. 1 shows the results of a dissolution experiment in Example 2 of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] Next, a microneedle patch 1 according to an embodiment of the present invention will be described with reference to FIGS.

[0023] As shown in Figure 1, the microneedle patch 1 comprises a microneedle array 11 having a plurality of microneedles 11a, an adhesive sheet 12 provided on the back surface of the microneedle array 11, and a protective release sheet 13 provided on the surface of the adhesive sheet 12 around the microneedle array 11.

[0024] As shown in Fig. 1, the macroneedle array 11 has a plurality of microneedles 11a arranged vertically and horizontally on a substrate 11b, and is formed into a thin film having a horizontal width of about 65 mm and a vertical width of 30 mm. Note that in Fig. 1, the microneedles 11a are shown enlarged to clarify their shape, but in reality they are finer than what is shown.

[0025] The microneedles 11a are formed in a cone shape or truncated cone shape with a tip diameter of 5 to 100 μm (preferably smaller than the pore diameter of 20 to 50 μm), a base diameter of 120 to 800 μm, and a height of 30 to 1000 μm, a strength of 0.4 to 0.6 N, a distance between adjacent ones of 100 μm to 1800 μm, and a length of 1 cm. 2 The density is set to about 120 to 600 per square meter. The cone shape is a so-called volcano shape, and is a truncated cone shape with the side surface curved inward.

[0026] The microneedle 11a is a solid needle of uniform texture based on a water-soluble polymer and containing naratriptan as an active ingredient, and is designed to dissolve when inserted into human skin.

[0027] Naratriptan is a type of triptan drug used as a migraine medication, as described below.

[0028] Generic name: Naratriptan Generic name: Naratriptan hydrochloride ·European common name Naratriptan Hydrochloride Product name: Naratriptan hydrochloride tablets Drug Classification Number 2160 ATC code N02CC02

[0029] In order to use the microneedle 11a as a medicine, it is necessary to make the content of naratriptan contained in the microneedle 11a constant, and for that purpose, it is necessary to uniformly include naratriptan in the components forming the microneedle 11a. In this regard, since many cosmetic ingredients are water-soluble substances, the components can be homogenized by mixing, but since naratriptan is not hydrophilic among pharmaceutical ingredients, it is difficult to uniformly disperse it in the components forming the microneedle 11a, and since there is a particle size distribution of naratriptan granules, there is a risk that the content of naratriptan in the microneedle 11a will differ. Therefore, for example, naratriptan can be finely divided to adjust the particle size of naratriptan, and then naratriptan can be mixed and uniformly dispersed in the water-soluble polymer base material of the microneedle 11a. Since naratriptan finely divided in this way is expected to improve cell permeability, it is possible to deliver naratriptan in the required amount to the required place when needed.

[0030] In addition, the water-soluble polymer used in the base is preferably a biocompatible substance that is non-toxic to the human body, chemically inactive, and biodegradable so that it can be decomposed in the body by body fluids, enzymes, or microorganisms, etc. Examples of such polymers include polysaccharides such as hyaluronic acid, chondroitin sulfate, glycogen, dextrin, dextran, dextran sulfate, hydroxypropylmethylcellulose, alginic acid, chitin, chitosan, and pullulan; proteins such as collagen, gelatin, and hydrolysates thereof; and synthetic polymer compounds such as polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acid, carboxyvinyl polymer, polylactic acid, polyglycolic acid, and lactic acid-glycolic acid copolymer.

[0031] Furthermore, the substrate 11b of the microneedle array 11 is not particularly limited as long as it is a film or sheet on which the microneedles 11a can be formed, and may have the same composition as the microneedles 11a or a different composition. Examples of substrates with a different composition from the microneedles 11a include polymethyl methacrylate, cellulose acetate, ethyl cellulose, polyethylene resin, polypropylene resin, ethylene-propylene copolymer, ethylene-vinyl acetate copolymer, vinyl chloride resin, vinylidene chloride resin, vinyl acetate-vinyl chloride copolymer, polyamide resin, polyester resin, acrylonitrile-butadiene-styrene copolymer, styrene-isoprene-styrene copolymer, styrene-ethylene-butylene-styrene copolymer, urethane resin, silicone resin, and aluminum.

[0032] The adhesive sheet 12 is provided on the back surface of the microneedle array 11, and is formed in an oval shape that is slightly larger than the microneedle array 11. The adhesive sheet 12 is made of a material that is impermeable to drugs or physiologically active substances and has excellent moisture permeability and elasticity, and may be, for example, a film made of one or more materials selected from paper, nonwoven fabric, woven fabric, natural or synthetic rubber, polyethylene terephthalate, polyvinyl chloride, polypropylene, polyurethane, polystyrene, polycarbonate, polyethylene terephthalate glycol, ethylene vinyl alcohol, polyethylene, polyester, and nylon.

[0033] The adhesive sheet 12 has an adhesive 12a on the surface. The adhesive 12a is a medically usable pressure sensitive adhesive (PSA). The adhesive 12a may be a rubber adhesive, an acrylic adhesive, a silicone adhesive, or a water-based emulsion adhesive. These adhesives may be used alone or in combination.

[0034] For example, when a rubber-based adhesive is used, a tackifier and a softener are generally added to a rubber-based elastomer. Examples of the rubber-based elastomer include styrene-isoprene-styrene block copolymers, styrene-butadiene-styrene block copolymers, styrene-isoprene rubber, styrene-butadiene rubber, polyisobutylene, polyisoprene, and natural rubber. When an acrylic-based adhesive is used, examples of the acrylic polymer compound include copolymers of at least one type of (meth)acrylic acid alkyl ester, such as 2-ethylhexyl acrylate, methyl acrylate, butyl acrylate, hydroxyethyl acrylate, and 2-ethylhexyl methacrylate. When a silicone-based adhesive is used, a mixture or partial condensate of silicone rubber and silicone resin can be used as the silicone-based adhesive. Examples of the silicone rubber include linear polydiorganosiloxane, and examples of the silicone resin include polyorganosiloxane.

[0035] The protective release sheet 13 is formed in a rectangular shape with a width of 120 mm and a length of 70 mm, and has a hole 13a in the center for exposing the microneedle array 11. The protective release sheet 13 is formed thinner than the height of the microneedle array 11, and is formed large enough to extend beyond the adhesive sheet 12. A gap is formed between the inner edge of the hole 13a of the protective release sheet 13 and the outer edge of the microneedle array 11, and a part of the adhesive 12a of the adhesive sheet 12 is exposed in the gap. Furthermore, cutting lines 13b extending laterally are formed on both sides of the protective release sheet 13, and when the microneedle patch 1 is used, the release protective sheet can be easily peeled off from the adhesive sheet 12 along the cutting lines 13b.

[0036] Next, an example of a method for producing the microneedle patch 1 (DEN: Droplet-Extension method) will be described with reference to FIG.

[0037] First, a component for forming a microneedle is prepared in advance by incorporating a predetermined amount of naratriptan as a medicinal ingredient into a water-soluble polymer base material. At this time, the temperature of the water-soluble polymer base material may be adjusted according to the desired content of naratriptan to dissolve the naratriptan. In addition, the naratriptan may be finely divided to reduce the particle size of the naratriptan, and then uniformly dispersed in the water-soluble polymer base material.

[0038] 2(a), a substrate 11b for forming a plurality of microneedles 11a on its surface is prepared (first step). At this time, the substrate 11b may be the substrate 11b itself, or the substrate 11b may be provided with the above-mentioned adhesive sheet 12 or protective release sheet 13 in advance.

[0039] 2(b), components for forming the microneedles 11a are dropped in spots on the surface of the substrate 11b by a dropping device K (second step). At this time, as a preliminary step to dropping the components for forming the microneedles 11a, in order to maximize the absorption rate of the naratriptan contained in the microneedles 11a into the skin, a predetermined viscous substance may be dropped, and then the components for forming the microneedles 11a may be dropped on the surface of the viscous substance.

[0040] Next, as shown in FIG. 2(c), the substrates 11b onto which the components for forming the microneedles 11a have been dropped are stacked one on top of the other, so that the components for forming the microneedles 11a of both substrates 11b come into contact with each other (third step).

[0041] Next, as shown in FIG. 2(d), the two substrates 11b are pulled away from each other, so that the components forming the microneedles 11a dropped onto the surfaces of the two substrates 11b are stretched to a predetermined length and solidified at room temperature in this state (fourth step).

[0042] Next, as shown in FIG. 2(e), after the components forming the microneedles 11a on the surfaces of both substrates 11b have completely solidified, the part (central part) of the components forming the microneedles 11a with the smallest diameter is cut to form microneedles 11a of a predetermined shape and size on the surfaces of both substrates 11b (fifth step).

[0043] Thus, when the microneedle patch 1 is attached to human skin, the microneedles 11a penetrate the human skin and then dissolve, allowing the naratriptan contained in the microneedles 11a to easily and reliably penetrate into and under the skin, and the inserted microneedle 11a portion dissolves under the skin and disappears. Since the microneedles 11a of this type are formed to be very thin and flexible, even if they are inserted into the skin, there is no pain or bleeding, and the puncture wound closes quickly, making this a highly effective method for supplying naratriptan subcutaneously. EXAMPLES

[0044] <Example 1> As Example 1 of the microneedle array according to the present invention, an animal experiment for verifying the effect of the microneedles will be described with reference to Figs. 3 to 5.

[0045] As the microneedle according to the present invention, samples of MAP1 and MAP2 were prepared as shown in FIG. 3. MAP1 has a microneedle height of 748.3 μm, a diameter of the tip of the microneedle of 88.8 μm, a diameter of the base of the microneedle of 765.3 μm, a strength of 0.425 N, and a naratriptan content of the entire microneedle of 2.25 mg. MAP2 has a microneedle height of 718.3 μm, a diameter of the tip of the microneedle of 98.8 μm, a diameter of the base of the microneedle of 567.4 μm, a strength of 0.557 N, and a naratriptan content of the entire microneedle of 1.69 mg. As a comparative example for the samples of MAP1 and MAP2, a tablet containing 2.5 mg of naratriptan was prepared.

[0046] Next, as shown in Figure 4, the experimental method was to inject the test groups G1 (tablet), G2 (MAP1), and G3 (MAP2) into rats and measure the amount of naratriptan detected in the blood of the rats. Specifically, 8-week-old male rats were used, and the tablets were injected orally, while MAP1 and MAP2 were injected through the skin. The sampling times were 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, and 12 hours, and the sampling site was the jugular vein.

[0047] Next, as the experimental results, as shown in FIG. 5, in all groups G1 to G3, the detected amount of naratriptan rose rapidly immediately after injection, and then gradually decreased over time.

[0048] Specifically, in the G1 (tablet) group, the detectable amount of naratriptan reached a maximum (410.391 ng / ml) 55 minutes after the start of infusion, then declined steeply from 4 to 6 hours, and then declined more gradually until the detectable amount reached 50 ng / ml 12 hours later.

[0049] On the other hand, in the G2 (MAP1) group, the detected amount of naratriptan reached a maximum (226.1895 ng / ml) 25 minutes after the start of injection, and then gradually decreased to 100 ng / ml 12 hours later.

[0050] In the G3 (MAP2) group, the detectable amount of naratriptan reached a maximum (246.2289 ng / ml) 30 minutes after the start of injection, and then gradually decreased to 100 ng / ml 12 hours later.

[0051] In addition, "AUC" in FIG. 5 means the blood drug concentration, which is the total amount of active drug that reaches the systemic circulation (area under the time curve), and indicates the degree of bioabsorption rate of the drug.

[0052] Thus, in G1 (tablet), the maximum detectable amount of naratriptan is higher than in G2 and G3, but it takes time to reach the maximum, and the amount of naratriptan remaining in the body decreases rapidly after that. In contrast, in G2 and G3, the time to reach the maximum detectable amount of naratriptan is short, and the amount of naratriptan remaining in the body decreases slowly after that, and after 12 hours, twice as much naratriptan remains as in G1 (tablet). From this, it was confirmed that the effect of naratriptan is faster and lasts longer when injected with a microneedle than when injected with a tablet.

[0053] <Example 2> As Example 2 of the microneedle array according to the present invention, a dissolution experiment for verifying the optimal content of naratriptan in the water-soluble polymer base material of the microneedles (water was used in the experiment) will be described with reference to FIG.

[0054] As shown in Figure 6, in the case of water at room temperature (25°C), naratriptan was sufficiently dissolved up to a content (mg) of 10 mg / ml of water-soluble polymer base material (ml), but was not sufficiently dissolved at 20 mg / ml. In addition, in the case of water at 60°C, naratriptan was sufficiently dissolved up to a content (mg) of 20 mg / ml to 30 mg / ml of water-soluble polymer base material (ml). In addition, in the case of water at 70 to 80°C, naratriptan was sufficiently dissolved up to a content (mg) of 175 mg / ml to 250 mg / ml of water-soluble polymer base material (ml).

[0055] Therefore, when the amount of naratriptan is small relative to the water-soluble polymer substrate (the content of naratriptan relative to the water-soluble polymer substrate is 10 mg / ml or less), the temperature of the water-soluble polymer substrate should be 25°C or higher (preferably 30°C or lower to save energy). When the amount of naratriptan is medium relative to the water-soluble polymer substrate (the content of naratriptan relative to the water-soluble polymer substrate is 20 mg / ml to 30 mg / ml), the temperature of the water-soluble polymer substrate should be 60°C or higher (preferably 65°C or lower to save energy), and when the amount of naratriptan is large relative to the water-soluble polymer substrate (the content of naratriptan relative to the water-soluble polymer substrate is 175 mg / ml to 250 mg / ml), the temperature of the water-soluble polymer substrate should be 70°C or higher (preferably 80°C or lower because water evaporates when the temperature approaches 100°C). [Explanation of symbols]

[0056] 1. Microneedle patch 11. Microneedle array 11a…Microneedle 11b...Substrate 12...Adhesive sheet 12a...Adhesive 13...Protective release sheet 13a…hole 13b…cutting line

Claims

1. A microneedle array comprising a plurality of dissolvable microneedles for insertion into human skin, The microneedle array is characterized in that the microneedles are based on a water-soluble polymer and contain naratriptan as an active ingredient.

2. The microneedle is formed in a cone shape or a truncated cone shape with a tip diameter of 5 to 100 μm, a base diameter of 120 to 800 μm, and a height of 30 to 1000 μm. The strength is 0.4 to 0.6 N, the distance between adjacent needles is 100 μm to 1800 μm, and the length is 1 cm. ２ The microneedle array according to claim 1, wherein the density is set to about 120 to 600 needles per microneedle.

3. The microneedle array of claim 1, wherein the microneedle array is based on a water-soluble polymer consisting of at least one of hyaluronic acid, chondroitin sulfate, glycogen, dextrin, dextran, dextran sulfate, hydroxypropyl methylcellulose, alginic acid, chitin, chitosan, pullulan, collagen, gelatin, polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acid, carboxyvinyl polymer, polylactic acid, polyglycolic acid, and lactic acid / glycolic acid copolymer.

4. A microneedle patch comprising: a microneedle array according to any one of claims 1 to 3; an adhesive sheet provided on the back surface of the microneedle array in an area that extends beyond the periphery of the microneedle array; and a protective release sheet provided on the surface of the adhesive sheet around the periphery of the microneedle array.

5. A method for producing a microneedle array according to claim 1, When naratriptan is contained as a medicinal ingredient in a water-soluble polymer substrate, the temperature of the water-soluble polymer substrate is set to 25°C to 30°C when the amount of naratriptan is small relative to the water-soluble polymer (the content of naratriptan in the water-soluble polymer substrate is less than 10 mg / ml), the temperature of the water-soluble polymer substrate is set to 60°C to 65°C when the amount of naratriptan is medium relative to the water-soluble polymer (the content of naratriptan in the water-soluble polymer substrate is 20 mg / ml to 30 mg / ml), and the temperature of the water-soluble polymer substrate is set to 70°C to 80°C when the amount of naratriptan is large relative to the water-soluble polymer (the content of naratriptan in the water-soluble polymer substrate is 175 mg / ml to 250 mg / ml). This is a method for producing a microneedle array.

6. A method for producing a microneedle array according to claim 1, A method for producing a microneedle array, comprising micronizing naratriptan to reduce the particle size of the naratriptan, and then uniformly dispersing the resulting particles in a water-soluble polymer base material.

7. A method for producing a microneedle array according to claim 1, A first step of providing a substrate for forming a plurality of microneedles on a surface thereof; A second step of dropping a component for forming microneedles onto the surface of the substrate in a spot form; a third step of stacking the substrates onto which the components for forming microneedles have been dropped, so that the components for forming microneedles on both substrates are brought into contact with each other; A fourth step of stretching the components for forming the microneedles dropped on the surfaces of both substrates to a predetermined length by separating the two substrates from each other, and solidifying the components at room temperature in this state; A method for manufacturing a microneedle array, comprising a fifth step of cutting the portion of the microneedle-forming component with the smallest diameter after the components forming the microneedles on the surfaces of both substrates have completely solidified, thereby forming microneedles of a predetermined shape and size on the surfaces of both substrates.

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