JP2014094171A - Microneedle and microneedle array - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a microneedle and a microneedle array having excellent diffusibility of material.SOLUTION: A microneedle is shaped like a cone, a frustum or a shape of the apex of a cone replaced with a curved surface or a flat surface. The microneedle has a height of 20 μm or more and less than 500 μm, the aspect ratio (h/a) of the height h to the maximum length a of a base is 2 or more, and the microneedle is formed of mesoporous material. A microneedle array includes a plurality of microneedles on a base material. The microneedle is shaped conical, like a truncated cone, pyramidal or like a truncated pyramid.

Description

  The present invention relates to a microneedle and a microneedle array.

  Administration of drugs using transdermal absorption has advantages over oral and injection administration, such as the ability to avoid the first-pass effect in the liver and the need for frequent administration. As a factor inhibiting this transdermal absorption, there is a barrier function of the stratum corneum existing on the skin surface. This barrier function prevents evaporation of water in the body and leakage of body fluids, while inhibiting the administered drug from being absorbed through the skin. This function is mainly due to the low permeability of the stratum corneum material. For this reason, in order to keep the blood concentration of the drug constant by administering the drug using transdermal absorption, it is necessary to improve the efficiency of transdermal absorption which is reduced by the barrier function of the stratum corneum on the skin surface.

  The microneedle method is a barrier function that opens a hole in the stratum corneum without making it reach the nerve, that is, without feeling pain, by applying something like a sword mountain with a needle that passes only through the stratum corneum to the skin. This method can be applied not only to drug administration but also to sample collection. Microneedles used for this are actively researched and developed in the fields of medicine, drug discovery, cosmetics and the like.

  For example, a medical microneedle has been proposed that supplies a drug to the body and collects a body fluid from the body through a through-hole formed in the microneedle. Patent Document 1 discloses a microneedle in which a through hole is formed by a short pulse laser method on a microneedle formed by a thermal imprint method.

JP 2011-72695 A

  However, in the microneedle in which the through hole disclosed in Patent Document 1 is formed, there is a limit to the ratio of the hole to the needle volume that can be set in order to secure the sharpened portion of the needle. For this reason, there is a limit to the diffusibility of the target substance, such as a drug.

  The present invention has been made in view of such a background art, and provides a microneedle and a microneedle array excellent in diffusibility of a substance.

  A microneedle that solves the above problem is a microneedle having a shape in which a cone, a frustum, or the top of a cone is replaced with a curved surface or a flat surface, and has a height of 20 μm or more and less than 500 μm, and a height h The aspect ratio (h / a) of the maximum length a of the base is 2 or more and is made of a mesoporous material.

  A microneedle array that solves the above-described problems has a plurality of microneedles on a substrate.

  ADVANTAGE OF THE INVENTION According to this invention, the microneedle and microneedle array excellent in the diffusibility of the substance can be provided.

It is the schematic which shows one embodiment of the microneedle of this invention. It is a schematic diagram which shows an example of the cross-sectional shape of the microneedle of this invention. It is the schematic which shows one embodiment of the microneedle array of this invention. It is process drawing which shows one embodiment of the manufacturing method of the microneedle of this invention. It is process drawing which shows the other embodiment of the manufacturing method of the microneedle of this invention. It is a figure which shows the calculation result showing the density | concentration distribution of the chemical | medical agent discharge | released from the microneedle. It is the schematic which shows the conventional microneedle.

  Hereinafter, embodiments of the present invention will be described in detail.

  First, the microneedle of the present invention will be described.

  The microneedle according to the present invention is a microneedle having a shape in which a cone, a frustum, or a top of a cone is replaced with a curved surface or a flat surface, and has a height of 20 μm or more and less than 500 μm, and a height h and a base The aspect ratio (h / a) of the maximum length a is 2 or more and is made of a mesoporous material.

  FIG. 1 is a schematic view showing one embodiment of the microneedle of the present invention. The microneedle 11 of the present invention is composed of a mesoporous material 12 having pores that are porous bodies. By transporting a substance such as a drug through the pores 13 of the mesoporous material 12, it is possible to release the substance such as the drug from all positions of the microneedle as indicated by an arrow A.

  FIG. 7 is a schematic view showing a conventional microneedle. The conventional microneedle 71 has a through-hole 72 and discharges a substance such as a drug in one direction as indicated by an arrow B from one place of the through-hole 72. Therefore, since the microneedle of the present invention is composed of a mesoporous material having pores, the diffusibility of the target substance is higher than that of the conventional microneedle.

  The shape of the microneedle of the present invention is a shape in which the cone, the frustum, or the top of the cone is replaced with a curved surface or a flat surface. The shape of the microneedle is preferably a conical shape, a truncated cone shape, a polygonal pyramid shape, or a polygonal frustum shape. The shape of the microneedle may be any of a substantially truncated cone shape, a substantially polygonal pyramid shape, and a substantially polygonal frustum shape. The shape in which the pyramid, the frustum, or the top of the cone is replaced with a curved surface or a flat surface includes those in which the side surfaces are concave or convex.

  FIG. 2 is a schematic diagram showing an example of a cross-sectional shape of the microneedle of the present invention. The microneedle shown in FIG. 2 has a truncated cone shape, h is the height of the microneedle, a is the maximum length of the bottom, p is the bottom surface, and q is the surface. The height h of the microneedle 1 is set to a height that avoids the barrier function of the stratum corneum on the skin surface at the use position, and achieves both the purpose of enhancing the administration effect of the target substance and the purpose of giving no pain to the use target. Is desirable. For that purpose, it is preferable that the thickness of the stratum corneum in the skin is not less than the thickness of the epidermis. The suitable height h varies depending on the place of use, but is preferably 20 μm or more and 500 μm or less, preferably 30 μm or more and 250 μm or less.

  The shape of the microneedle of the present invention is such that the aspect ratio (h / a) between the height h and the maximum length a of the base is 2 or more, preferably 4 or more, more preferably 4 or more, from the viewpoint of penetration into the skin. 50 or less is desirable.

  The microneedle of the present invention is composed of a mesoporous material that is a porous body. Therefore, the microneedle of the present invention has a large number of holes. Moreover, the microneedle of the present invention has a continuous hole between the bottom surface and the surface, and the hole is a hole of a mesoporous material.

  This hole may communicate with the bottom surface (p in FIG. 2) and the surface (q in FIG. 2) of the microneedle. By communicating these holes, the substance can be transported between the bottom surface and the surface. Further, the holes may be arranged with orientation. Particularly, when the pores are aligned in a uniaxial direction and the alignment direction is the longitudinal direction of the microneedle, it is preferable because the substance can be effectively transported between the bottom surface and the surface. . In this case, the orientation in the uniaxial direction means that the orientation distribution of the holes is 45 degrees or less in full width at half maximum. This orientation direction can be verified by rocking curve measurement of in-plane X-ray diffraction measurement and observation with a transmission electron microscope while changing the angle of the cross-sectional sample.

  In the microneedle of the present invention, a drug may be introduced and held in the pores as necessary. The microneedle of the present invention can adsorb a large amount of drug due to the large surface area of the mesoporous material. Here, examples of the drug include pharmaceuticals and cosmetics.

  Next, the microneedle array of the present invention will be described.

  The microneedle array of the present invention has a plurality of the above microneedles on a substrate.

  FIG. 3 is a schematic view showing one embodiment of the microneedle array of the present invention. In FIG. 3, the microneedle 31 of the present invention may be formed on a substrate 30 as necessary. The material used for the substrate 30 is not particularly limited, and examples thereof include a polymer material, an inorganic material, and a metal material.

  Moreover, it is preferable that the base material 30 has a continuous hole, and the hole communicates between the front surface and the back surface of the base material. Since the base material 30 has continuous holes 32 for transporting substances between the front and back surfaces, the back surface of the base material (the surface opposite to the surface on which the microneedle is formed), the microneedle, It is possible to transport materials between the two. Moreover, this base material is comprised from a mesoporous material, and the mesopore may be sufficient as the hole which performs the mass transport between the front and back of a base material. The hole diameter of the continuous hole 32 for transporting the substance between the front and back surfaces of the substrate and the hole diameter of the holes 33 of the mesoporous material constituting the microneedle on the substrate may be different.

  By positively changing the hole diameters of the holes and the holes and controlling the surface energy of the base material and the mesoporous material, the transport direction of the substance in the holes can be controlled. For example, by using a material having a large surface energy for the base material, a material having a large pore diameter (the base material 30 having relatively large holes 32 in FIG. 3) (relatively small in specific surface area) A substance can be transported toward a material having a small pore diameter (in FIG. 3, a mesoporous material of the microneedle 31 having a relatively small hole 33) having a large surface area. Here, as an example, the case where the hole of the substrate is larger than the hole of the mesoporous material is shown, but the opposite hole of the substrate is made of the mesoporous material depending on the transport direction of the desired substance. A configuration smaller than the holes can also be selected. Thus, it is possible to provide a function of controlling the direction of transport of the substance, for example, introducing a drug into the body and collecting a body fluid from the body.

  The pores of the mesoporous material used in the present invention have a pore diameter of 2 nm to 50 nm, preferably 3 nm to 50 nm. The pores of the substrate have a pore diameter of 2 nm to 50 nm, preferably 3 nm to 50 nm. The pore size can be calculated by measuring an isothermic adsorption line such as nitrogen and using a BJH (Barrett-Joyner-Halenda) method or the like.

  Moreover, this base material may have a dense surface layer 34 on the surface as necessary. By having a dense surface layer, it is possible to prevent leakage of the drug from sites other than the microneedles. The dense surface layer is not particularly limited. For example, it is preferable to form a barrier layer as the surface layer 34 shown in FIG. As the barrier layer, for example, a polymer coating film can be used.

  It is preferable to place a drug holding layer on the back surface of the base material as necessary. The drug holding layer holds the drug, the substance containing the drug, stores it, and supplies it through the microneedle. On the contrary, it plays a role of storing a substance (such as a body fluid) collected through the microneedle. Here, the base material may also serve as the drug holding layer. Although this medicine holding layer is not particularly limited, for example, a polymer material can be used.

  It is preferable to arrange a plurality of microneedles on this substrate to form a microneedle array. By using a microneedle array, it becomes possible to administer more drugs and collect more body fluids.

  The mesoporous material used in the present invention is a porous material having a pore diameter of 2 nm to 50 nm. The porosity is preferably 10% or more and 80% or less. The mesoporous material is formed mainly by using a molecular assembly as a template, and removing the template from a mesostructure in which the wall material has fixed the structure of the molecular assembly. An example of a material forming this molecular assembly is a surfactant.

  Although it does not specifically limit as a wall material of a mesoporous material, An oxide, a high molecular compound, a metal, etc. can be mentioned. The oxide means an inorganic oxide and an organic substance inside and outside the skeleton of the inorganic oxide. Examples of the inorganic oxide include silicon oxide, tin oxide, zirconia oxide, titanium oxide, niobium oxide, tantalum oxide, aluminum oxide, tungsten oxide, hafnium oxide, and zinc oxide. Of these, silicon oxide is most preferred. Examples of the inorganic oxide containing an organic substance in the skeleton include those in which atoms other than oxygen constituting the inorganic oxide are bonded to an organic molecule, such as silicon. The oxide is formed from an oxide precursor. Examples of oxide precursors include silicon and metal element alkoxides, chlorides, and the like. Examples of the polymer compound include polycarbonate, ABS resin, phenol resin and the like. Examples of the metal include nickel, iron, and alloys thereof.

  The template material for the mesoporous material is not particularly limited, but a surfactant is preferably used. Examples of the surfactant include ionic and nonionic surfactants. Examples of the ionic surfactant include a halide salt of trimethylalkylammonium ion. As an example of a nonionic surfactant, what contains polyethyleneglycol as a hydrophilic group can be mentioned. Specific examples of the surfactant containing polyethylene glycol as a hydrophilic group include polyethylene glycol alkyl ether and polyethylene glycol-polypropylene glycol-polyethylene glycol block copolymers. It is possible to change the structural period by changing the molecular weight of the hydrophobic part and the hydrophilic part of the surfactant. In general, it is possible to enlarge the pore size by making the hydrophobic part and the hydrophilic part large. In addition to the surfactant, an additive for adjusting the structural period may be added. Examples of the additive for adjusting the structure period include hydrophobic substances. Examples of this hydrophobic substance include alkanes, aromatic compounds that do not contain a hydrophilic group, and specific examples include octane.

  Although the manufacturing method of a mesoporous material is not specifically limited, For example, it can manufacture with the following method. A precursor of the wall material is added to a surfactant solution in which the aggregate functions as a template to obtain a desired shape, and a wall material generation reaction is performed. Thereafter, the template molecule is removed to obtain a mesoporous material. The mesostructure to be formed can be selected depending on the combination of the template molecule and the wall material.

  For the microneedle of the present invention, one having a mesostructure having continuous holes is advantageous. In the microneedle of the present invention, the holes may be uniaxially oriented as necessary. This alignment method is not particularly limited, and for example, production and formation of a mesoporous material can be performed in a strong magnetic field.

  Next, the manufacturing method of the microneedle of this invention is demonstrated.

  A method for producing a microneedle made of the mesoporous material of the present invention is not particularly limited, and examples thereof include (1) a method of etching after forming a mask and (2) a micromold method. Below, the specific example of a manufacturing method is demonstrated using drawing.

(1) Method of Etching After Forming Mask FIG. 4 is a process diagram showing one embodiment of the method for producing a microneedle of the present invention. In the microneedle manufacturing method of the present invention, first, a mesoporous film 40 is produced (FIG. 4A), and a mask layer 41 is formed thereon (FIG. 4B). As the mask layer 41, a photosensitive resin, a metal, a metal compound, an oxide, or the like can be used, and it is preferable to select an appropriate material according to the material of the mesoporous film.

  Next, patterning is performed on the mask layer to form a mask 42 (FIG. 4C). When the mask layer is a photosensitive resin, patterning is performed by a lithography method to form the mask 42. When the mask layer is made of metal or the like, the mask layer is patterned by lithography, and then the mask layer is etched to form a mask by patterning the mask layer.

  Next, the microneedles 43 are formed by etching the mesoporous film on which the mask is formed (FIG. 4D). If the mask remains even after the formation of the microneedles, the mask is removed by using a resist stripping solution or the like as required (FIG. 4E).

(2) Micromold Method FIG. 5 is a process diagram showing another embodiment of the method for producing microneedles of the present invention. In the microneedle manufacturing method of the present invention, first, a mold 50 such as PDMS (polydimethylsiloxane) having good releasability is prepared (FIG. 5A), and a precursor 51 of a mesoporous material is introduced into the mold 50. (FIG. 5B). After the precursor of the mesoporous material is solidified to become the mesoporous material, the mold 50 is separated to obtain the microneedles 52 (FIG. 5C).

  In the microneedle of the present invention, a drug may be introduced and held in the pores as necessary. The introduction of the drug into the microneedle is not particularly limited, and examples thereof include a method of applying a liquid containing the drug to the microneedle and drying. Here, examples of the drug include pharmaceuticals and cosmetics.

  The present invention will be described in more detail with reference to the following examples. However, the method of the present invention is not limited to these examples.

Example 1
In this example, the high diffusibility characteristic of the microneedle of the present invention is described by calculation, specifically, the concentration profile when the drug diffuses from the microneedle.

FIG. 6 shows a calculation result representing the concentration distribution of the drug released from the microneedle. In the figure, x represents a direction parallel to the bottom of the microneedle, and y represents a direction perpendicular to the bottom of the microneedle. FIG. 6 (a) shows that a substance (testosterone) is transferred from a tetragonal pyramid mesoporous microneedle (porosity 50%) having a height of 200 μm and a bottom of 50 μm square impregnated with testosterone into an aqueous solution. The concentration distribution of the substance in the case of diffusion (diffusion coefficient D = 7.5 × 10 ⁻⁶ cm ² s ⁻¹ ) is shown. The state after 1 h has been shown. In the figure, white means high density and black means low density, and the location of the microneedle is indicated by a dotted line. From this, it was confirmed that the microneedles using the mesoporous material diffuse widely in all directions.

(Comparative Example 1)
A comparative example 1 with respect to the example 1 is shown in FIG. Here, from a through-hole microneedle in which a hole is impregnated with a substance (testosterone), a square pyramid having a height of 200 μm and a bottom having a square shape of 50 μm and having one through-hole having a square cross section of 10 μm on a side, to an aqueous solution. The concentration distribution of the substance when the substance diffuses is shown. FIG. 6B shows a state after 1 hour has elapsed, and in the comparative example of FIG. 6B, the diffusion of the substance remained in a narrow range compared to FIG. 6A.

  From the comparison between Example 1 and Comparative Example 1, it was confirmed that the microneedle using the mesoporous material of the present invention has high diffusibility.

(Example 2)
In this example, a method of manufacturing a mesoporous microneedle array formed by etching after forming a mask will be described.

(2-1) Production of mesostructured film 8.7 g of tetraethoxysilane, 3 g of cetylpyridinium chloride, 2.2 g of 0.1 M hydrochloric acid, 25.9 g of ethanol and 27.7 g of n-heptane mixed solvent And reflux for 1 hour. The solution is concentrated using an evaporator and cast on a silicon substrate. A mesostructured film having a thickness of 250 μm is obtained by drying the substrate in a petri dish.

(2-2) Formation of microneedle Formation of microneedle will be described with reference to FIG. A mask in which a mask layer 41 of a photoresist is applied to the mesostructured film 40 formed in the section (2-1) by a spin coating method, and a dot pattern having a diameter of 50 μm is arranged 10 vertically and 10 horizontally by a photolithography method. 42 is formed. Thereafter, dry etching with CF ₄ gas is performed to form a conical microneedle having a bottom diameter of 50 μm and a height of 250 μm. Furthermore, in order to remove the template in the mask and the mesostructured film, the mesoporous microneedle array is fabricated by baking in the atmosphere at 400 ° C. for 12 hours. Thereafter, an ethanol solution of testosterone is dropped onto the microneedles and dried to produce microneedles holding the drug in the pores of the mesoporous material.

(2-3) Release test of substance from mesoporous microneedle A water-soluble cyanine dye serving as a marker is supported in the pores of the prepared mesoporous microneedle. The microneedle is brought into contact with physiological saline, and the release test is performed by observing the release of the marker with an optical microscope.

  As a result of the test, the release of the dye from the entire surface of the microneedle is confirmed, and the high diffusibility of the microneedle using the mesoporous material is confirmed.

(Example 3)
In this embodiment, a method for manufacturing a mesoporous microneedle array in which vacancies in a mesoporous material are uniaxially oriented in the longitudinal direction of the microneedles will be described using a method of forming a mask and performing subsequent etching.

(3-1) Production of mesostructured film 5.2 g of tetraethoxysilane, 2.7 g of 0.01 M hydrochloric acid, 6 g of ethanol were stirred for 20 minutes, and then 1.38 g of polyethylene glycol (20) -polypropylene glycol. (70) -Polyethylene glycol (20) (Numbers in parentheses are the number of repeated blocks) 4.0 g of ethanol is added and stirred for 3 hours to prepare a precursor solution. A precursor solution is cast on a silicon substrate on which a PDMS (polydimethylsiloxane) film is formed, and the substrate is left in a magnetic field of 12 Tesla for 1 hour so that the magnetic field is perpendicular to the substrate surface. A mesostructured film having a thickness of 60 μm is prepared in which the holes filled with the surfactant are oriented perpendicular to the substrate surface. The orientation of the pores filled with the surfactant of the mesostructured film is confirmed by cross-sectional transmission microscope observation.

(3-2) Formation of microneedles Photoresist is applied to the mesostructured film formed in the item (3-1) by a spin coating method, and a dot pattern having a diameter of 7 μm is vertically 10 by 10 by photolithography. The arranged mask is formed. Thereafter, dry etching with CF ₄ gas is performed to form a microneedle array having 100 conical microneedles on the mesostructured film having a diameter of the lower portion of 7 μm and a height of 30 μm. Then, after baking at 400 degreeC in air | atmosphere for 12 hours, a mesoporous microneedle is produced by peeling the film | membrane in which the microneedle array was formed from a board | substrate. The back surface of the microneedle array (the surface opposite to the surface on which the microneedles are formed) is soft wet etched with dilute sodium hydroxide solution to make the mesoporous film slightly thinner so that the holes communicate from the front to the back. Let

  In this way, only a part of the mesoporous film in the thickness direction is microneedled, and wet etching is performed with the mesoporous film remaining on the entire back surface of the microneedles, whereby the mesoporous film is obtained. A mesoporous microneedle array in which holes were communicated to the back surface of was obtained.

(3-3) Release Test of Substance from Mesoporous Microneedle A polymer drug holding layer containing a water-soluble cyanine dye solution serving as a marker on the back surface (the surface without the needle structure) of the prepared mesoporous microneedle Install. Then, physiological saline is brought into contact with the microneedles on the surface, and the release of the marker is observed with a microscope. As a result, high-efficiency dye release from the entire needle surface is confirmed, and the high permeability and diffusivity of the microneedle using a mesoporous material with pores oriented perpendicular to the substrate surface are confirmed.

(Example 4)
This example shows a mesoporous microneedle array using a micromold method, in which the hole diameters of continuous holes for transporting substances between the front and back surfaces of the substrate and the hole diameters of the holes of the mesoporous material constituting the microneedles are different. explain.

(4-1) Preparation of Precursor Solution 8.7 g of tetraethoxysilane, 2.3 g of polyethylene glycol (20) -polypropylene glycol (70) -polyethylene glycol (20) (the numbers in parentheses are the number of repeated blocks) 4.5 g of 0.01 M hydrochloric acid is dissolved in 21.7 g of ethanol and 22.6 g of n-heptane mixed solvent and refluxed for 1 hour. The solvent is concentrated using an evaporator to prepare a precursor solution.

(4-2) Formation of double-layered mesoporous microneedles A PDMS mold having 10 × 10 quadrangular pyramid-shaped recesses with an opening diameter of 25 μm and a depth of 100 μm was prepared in the same manner as in (2-1). The precursor solution is applied by spin coating, the recesses are filled, and dried. Thereby, a needle part is formed.

  Furthermore, after casting the precursor solution prepared in the item (4-1), the mesostructured film is obtained by drying in a petri dish. Thereby, a base material part having a thickness of 20 μm is formed.

  A mesoporous microneedle array having a quadrangular pyramid shape formed on a mesoporous substrate is manufactured by separating the mesostructured film from the mold, firing, and wet-etching the front and back surfaces with a dilute aqueous sodium hydroxide solution.

(4-3) Evaluation From the two types of precursor solutions used in the production process, a reference sample is produced, and the BJH method is applied to the nitrogen isothermal adsorption measurement results to obtain the average of the substrate part and the microneedle part. The pore diameter is determined to be 4.7 nm and 2.2 nm.

  A polymer drug holding layer containing a water-soluble cyanine dye solution serving as a marker is placed on the surface of the base material portion of the prepared mesoporous microneedle. And a marker is observed with a microscope in a microneedle site | part. As a result, it is confirmed that the dye solution is sucked up at the needle site, and by using a microneedle or a material with a different pore size as its base material, a substance is directed from a material with a large pore size toward a material with a small pore size. It is confirmed that it can be transported.

  Since the microneedle of the present invention is excellent in diffusibility of a substance, it can be used in fields such as medical use, drug discovery, and cosmetics.

11, 31, 43, 52 Microneedle 12 Mesoporous material 13, 33 Pore 30 Base material 32 Hole 34 Surface layer 40 Mesoporous film 41 Mask layer 42 Mask 50 Mold 51 Precursor of mesoporous material 71 Microneedle 72 Through hole

Claims (11)

  A microneedle having a shape in which a cone, a frustum, or a top of a cone is replaced with a curved surface or a plane, the height is 20 μm or more and 500 μm or less, and the aspect ratio of the height h and the maximum length a of the base A microneedle characterized in that (h / a) is 2 or more and is made of a mesoporous material.   The microneedle according to claim 1, wherein the microneedle has a conical shape, a truncated cone shape, a polygonal pyramid shape, or a polygonal frustum shape.   The microneedle according to claim 1 or 2, wherein the height is 30 µm or more and 250 µm or less, and an aspect ratio (h / a) is 4 or more.   The microneedle according to any one of claims 1 to 3, wherein the microneedle has a continuous hole between a bottom surface and a surface of the microneedle, and the hole is a hole of a mesoporous material. .   The microneedle according to any one of claims 1 to 4, wherein pores of the mesoporous material are oriented in a uniaxial direction, and the orientation direction is a longitudinal direction of the microneedle.   The microneedle according to claim 5, wherein the continuous pores transport a substance.   The microneedle according to any one of claims 1 to 6, wherein a drug is held in pores of the mesoporous material.   A microneedle array comprising a plurality of the microneedles according to any one of claims 1 to 7 on a substrate.   The microneedle array according to claim 8, wherein the substrate has continuous holes, and the holes communicate between the front surface and the back surface of the substrate.   The microneedle array according to claim 9, wherein the continuous holes transport a substance.   The microneedle array according to any one of claims 8 to 10, wherein the hole diameter of the hole of the base material is different from the hole diameter of the hole of the mesoporous material of the microneedle on the base material.