Microneedle array

Abstract

The purpose of the present invention is to provide a microneedle array with which it is possible to quickly penetrate Naratriptan into the subcutaneous tissue of a person by inserting microneedles into the skin of the person. The present invention comprises: a microneedle array 11; an adhesive sheet 12 provided on the back surface of the microneedle array 11 in a manner extending beyond the periphery of the microneedle array 11; and a protective release sheet 13 provided around the microneedle array 11 on the surface of the adhesive sheet 12. The microneedle array 11 includes a plurality of dissolvable microneedles 11a to be inserted into the skin of a person. The microneedles 11a contain a water-soluble polymer as a base agent and Naratriptan as an active pharmaceutical ingredient.

Description

Microneedle Array

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

[0002] Conventionally, topical preparations have been used that are applied to human skin and deliver a specific medicinal ingredient to exert its effect locally or at a systemic disease site. Known topical preparations include so-called patches such as poultices and tapes, which are applied to human skin to allow the medicinal ingredient to penetrate the skin.

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

[0004] Therefore, in recent years, a technology has been proposed to solve the drawbacks of such topical preparations, which uses a water-soluble polymer as a base and an array of many fine needles (hereinafter referred to as microneedles) containing a specific medicinal ingredient (hereinafter referred to as microneedle array).

[0005] When the microneedle array is attached to human skin, the microneedles inserted into the skin dissolve, allowing the medicinal ingredients contained in the microneedles to easily and reliably penetrate into and under the skin. Furthermore, the inserted microneedle portions dissolve and disappear within the skin. Such microneedle arrays are extremely effective as a method for delivering medicinal ingredients into and under the skin, since the microneedles in the needle portion are formed to be extremely fine and have a shape that allows for easy penetration. Therefore, even if the microneedles are inserted into the skin, no pain or bleeding occurs, and the puncture wound closes quickly.

[0006] In recent years, microneedle arrays containing triptan drugs (particularly sumatriptan), which are selective serotonin receptor agonists, as active ingredients have been proposed 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 disadvantages such as low bioavailability due to their absorption from the small intestine and metabolism in the liver, and a large single dose. 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 medication administration.

[0008] Japanese Patent Application Laid-Open No. 2022-177280 Japanese Patent Application Laid-Open No. 2023-29328 Japanese Patent Application Laid-Open No. 2022-71044 Japanese Patent Application Laid-Open No. 2021-121339 Special Publication No. 2021-528155 Special Publication No. 2020-536634 Japanese Patent Application Laid-Open No. 2020-73023 Special Publication No. 2020-500173 WO2017-104491 Special Publication No. 2018-511438 Special Publication No. 2017-517295 WO2015-129807

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

[0010] Of course, 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 was possible to increase the dose 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 was a limit to how much the dose of the triptan drug could 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.

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

[0013] Specifically, the microneedle array of the present invention is a microneedle array comprising a plurality of dissolvable microneedles to be inserted into human skin, 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 pieces per unit area.

[0015] Furthermore, the microneedle array preferably has as its base 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 into a water-soluble polymer substrate as a medicinal ingredient, if the amount of naratriptan relative to the water-soluble polymer is small (the content of naratriptan relative to the water-soluble polymer substrate is less than 10 mg / ml), the temperature of the water-soluble polymer substrate is set to 25°C to 30°C, if the amount of naratriptan relative to the water-soluble polymer is medium (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 is 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 relative to the water-soluble polymer substrate is 175 mg / ml to 250 mg / ml), the temperature of the water-soluble polymer substrate is set to 70°C to 80°C.

[0018] Furthermore, 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 the naratriptan may be 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 apart from each other to stretch the microneedle-forming components dripped onto the surfaces of both substrates to a predetermined length and solidifying them at room temperature in this state; and a fifth step of cutting the portion of the microneedle-forming component 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.

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

[0021] Fig. 2 is a cross-sectional view and a plan view showing a microneedle patch according to an embodiment of the present invention. Fig. 3 is a diagram showing a process for manufacturing the microneedle patch of Fig. 1. Fig. 4 is a diagram showing specifications of microneedle samples (MAP1, MAP2) according to Example 1 of the present invention, and a diagram showing specifications of test groups (G1, G2, G3) according to Example 1 of the present invention. Fig. 5 is a diagram showing the results of an animal experiment for Example 1 of the present invention. Fig. 6 is a diagram showing the results of a dissolution experiment for Example 2 of the present invention.

[0022] Next, a microneedle patch 1 according to an embodiment of the present invention will be described with reference to FIGS. 1 and 2. FIG.

[0023] As shown in Figure 1, this microneedle patch 1 comprises a microneedle array 11 having a plurality of microneedles 11a, an adhesive sheet 12 provided on the back 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 in the vertical and horizontal directions on a substrate 11b, and is formed as a thin film having a horizontal width of approximately 65 mm and a vertical width of 30 mm. Note that in Fig. 1, the microneedles 11a are shown enlarged to clarify their shapes, but in reality they are finer than what is shown.

[0025] The microneedles 11a 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 The density is set to about 120 to 600 pieces per square meter. The cone shape is a so-called volcano shape, in which the side surface of a truncated cone is curved inward.

[0026] The microneedles 11a are solid needles of uniform structure that are based on a water-soluble polymer and contain naratriptan as an active ingredient, and are 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 ・English generic name: Naratriptan Hydrochloride ・Product name: Naratriptan hydrochloride tablets ・Therapeutic classification number: 2160 ・ATC code: N02CC02

[0029] In order to use this microneedle 11a as a pharmaceutical, it is necessary to uniformly align the content of naratriptan contained in the microneedle 11a, and to achieve this, it is necessary to uniformly incorporate naratriptan into 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 among pharmaceutical ingredients, naratriptan is not hydrophilic, so it is difficult to uniformly disperse it in the components forming the microneedle 11a. In addition, due to the particle size distribution of naratriptan granules, there is a risk of differences in the content of naratriptan in the microneedle 11a. Therefore, for example, naratriptan can be micronized to adjust the particle size of naratriptan, and then mixed with naratriptan and uniformly dispersed in the water-soluble polymer matrix of the microneedle 11a. Since such micronized naratriptan is expected to have improved cell permeability, it is possible to deliver naratriptan when needed, to the needed place, and in the needed amount.

[0030] In addition, the water-soluble polymer used as the base material is preferably a biocompatible material that is not toxic to the human body, is chemically inert, and has biodegradability that can be decomposed in vivo by body fluid, enzymes or microorganisms etc. For example, include polysaccharides such as hyaluronic acid, chondroitin sulfate, glycogen, dextrin, dextran, dextran sulfate, hydroxypropylmethylcellulose, alginic acid, chitin, chitosan, pullulan etc.; proteins such as collagen, gelatin and their hydrolysates etc.; synthetic polymer compounds such as polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acid, carboxyvinyl polymer, polylactic acid, polyglycolic acid, lactic acid-glycolic acid copolymer etc.

[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 microneedles 11a can be formed, and may have the same composition as or a different composition from the microneedles 11a. 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 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 may be used.

[0033] The adhesive sheet 12 has an adhesive 12a on its surface. This adhesive 12a is a medically acceptable pressure-sensitive adhesive (PSA). Examples of adhesives that can be used include rubber-based adhesives, acrylic-based adhesives, silicone-based adhesives, and aqueous emulsion adhesives. These adhesives may be used alone or in combination.

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

[0035] The protective release sheet 13 is formed in the shape of a rectangle 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. This 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. Furthermore, a gap is left between the inner edge of the hole 13a in the protective release sheet 13 and the outer edge of the microneedle array 11, and a portion of the adhesive 12a of the adhesive sheet 12 is exposed in this gap. Furthermore, cutting lines 13b extending laterally are formed on both sides of the protective release sheet 13, so that the release protective sheet can be easily peeled off from the adhesive sheet 12 along the cutting lines 13b when using the microneedle patch 1.

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

[0037] First, a microneedle forming component is prepared in advance by incorporating a predetermined amount of naratriptan as a medicinal ingredient into a water-soluble polymer base material. The temperature of the water-soluble polymer base material is adjusted according to the desired naratriptan content to dissolve the naratriptan. Furthermore, the naratriptan is micronized to reduce its particle size, and then uniformly dispersed in the water-soluble polymer base material.

[0038] Next, as shown in Fig. 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 itself may be used, or the substrate 11b may be provided with the adhesive sheet 12 or protective release sheet 13 in advance.

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

[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 on both substrates 11b come into contact with each other (third step).

[0041] Next, as shown in Figure 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 then solidified at room temperature in this state (fourth step).

[0042] Next, as shown in Figure 2 (e), after the components forming the microneedles 11a on the surfaces of both substrates 11b have completely solidified, the part (central part) where the diameter of the components forming the microneedles 11a is smallest 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 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 microneedles 11a dissolve and disappear under the skin. Because the microneedles 11a of this microneedle patch 1 are formed to be extremely thin and flexible, there is no pain or bleeding when they are penetrated into the skin, and the puncture wound closes quickly, making it an extremely effective method for delivering naratriptan subcutaneously.

[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.

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

[0046] As shown in Figure 4, the experimental method involved injecting test groups G1 (tablet), G2 (MAP1), and G3 (MAP2) into rats and measuring the amount of naratriptan detected in the blood of the rats. Specifically, 8-week-old male rats were used, and tablets were injected orally, while MAP1 and MAP2 were injected through the skin. 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 sharply immediately after injection, and then gradually decreased over time.

[0048] Specifically, in the G1 (tablet) group, the detected 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 gradually declined until the detected 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 detected amount of naratriptan reached a maximum (246.2289 ng / ml) 30 minutes after the start of infusion, 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, G1 (tablet) has a higher maximum detectable amount of naratriptan than G2 and G3, but it takes time to reach the maximum, and then the detectable amount of naratriptan remaining in the body decreases rapidly. In contrast, G2 and G3 have a shorter time to reach the maximum detectable amount of naratriptan, and then the detectable amount of naratriptan remaining in the body decreases gradually, and after 12 hours, twice as much naratriptan remains as G1 (tablet). This confirms that naratriptan is more effective 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 substrate of the microneedles (water was used in the experiment) will be described with reference to FIG. 6 .

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

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

[0056] DESCRIPTION OF SYMBOLS 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 soluble microneedles to be inserted into human skin, the microneedles being based on a water-soluble polymer and containing naratriptan as an active ingredient.

2. The microneedle is formed in a cone or 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, 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 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 as described in 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 manufacturing a microneedle array as described in claim 1, characterized in that when naratriptan is incorporated as an active ingredient into the water-soluble polymer base material, the temperature of the water-soluble polymer base material is set to 25°C to 30°C when 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 is set to 60°C to 65°C when 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), and the temperature of the water-soluble polymer base material is set to 70°C to 80°C when 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).

6. A method for producing a microneedle array as described in claim 1, comprising micronizing naratriptan to reduce the particle size thereof, and then uniformly dispersing the naratriptan in a water-soluble polymer substrate.

7. A method for producing a microneedle array as claimed in claim 1, comprising: a first step of preparing a substrate for forming a plurality of microneedles on its surface; a second step of dropping 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 dropped 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 dropped 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.

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