Microneedle device

Abstract

The present invention is a microneedle device comprising: a needle array including a base part and a needle part protruding from the base part; and a pressing member that presses a surface of the base part on the opposite side from a surface on which the needle part is provided. The needle part has a bottom end on the base part side, a tip positioned on the opposite side from the base part, and a side surface connecting the bottom end and the tip. When the needle part is viewed from the side, a distance X1 from the bottom end to the tip of the needle part in a protrusion direction of the needle part is 500-4000 μm. The ratio (B / A) of the an area B of a pressing surface of the pressing member that presses the base part of the needle array to an area A of a region of the base part where the needle part is present is 1.0 or more, and when the needle part is viewed from the side, the ratio (W2 / W1) of a width dimension W2 at the bottom end of the needle part to a width dimension W1 of the needle part at a position bisecting the distance X1 is 1.8-80.

Description

Microneedle device

[0001] The present invention relates to a microneedle device.

[0002] Conventionally, as a method for grasping a health condition, a method of collecting and analyzing body fluids such as blood and interstitial fluid is known. Since the collection of body fluids and the like is usually performed by a syringe, it is accompanied by strong pain. From such a viewpoint, a minimally invasive method is required as a method for analyzing body fluids. For example, in Patent Document 1, a device for analyzing body fluids using fine microneedles has been studied.

[0003] Japanese Patent No. 7256821

[0004] The microneedle should be as small as possible from the viewpoint of minimal invasiveness. However, if it is too small, it will bend when piercing the skin due to insufficient strength, and it will not be able to reach the dermis, and it may become impossible to analyze because it cannot contact body fluids such as blood and interstitial fluid which are the analysis targets. On the other hand, if the size of the microneedle is increased in consideration of strength, strong pain may be felt when piercing the skin, which is not preferable from the viewpoint of minimal invasiveness. Thus, the viewpoint of ensuring the strength of the microneedle (preventing bending) and reliably reaching the dermis, and the viewpoint of suppressing pain when piercing the skin are in a trade-off relationship with each other.

[0005] An object of the present invention is to provide a microneedle device in which the needle portion of the needle array is difficult to bend when piercing the skin, can surely reach the dermis, and can suppress pain.

[0006] The inventors of this invention have diligently studied and investigated the above problems, and as a result have arrived at the present invention. In other words, the present invention is a microneedle device comprising a needle array having a base and needle portions protruding from the base, and a pressing member that presses the surface of the base opposite to the surface on which the needle portions are provided, wherein the needle portion has a bottom end on the base side, a tip located on the opposite side of the base, and a side surface connecting the bottom end and the tip, and when the needle portion is viewed from the side, the distance X1 from the bottom end to the tip of the needle portion in the direction of protrusion of the needle portion is 500 μm to 4000 μm, the ratio (B / A) of the area B of the pressing surface of the pressing member that presses the base of the needle array to the area A of the region of the base where the needle portion exists is 1.0 or more, and when the needle portion is viewed from the side, the ratio (W2 / W1) of the width dimension W2 at the bottom end of the needle portion to the width dimension W1 of the needle portion at a position that bisects the distance X1 is 1.8 to 80.

[0007] According to the present invention, it is possible to provide a microneedle device in which the needle portion of the needle array is less likely to bend when punctured into the skin, can reliably reach the dermis, and can suppress pain.

[0008] This is a schematic cross-sectional view showing an example of the microneedle device of the present invention. This is a schematic perspective view showing an example of the microneedle device of the present invention. This is a schematic top view showing an example of the microneedle device of the present invention. This is a schematic perspective view showing an example of a needle array. This is a cross-sectional view taken along line A-A in Figure 2A. This is an enlarged view of the dashed line in Figure 2B. This is a step diagram showing an example of a method for manufacturing a needle array. This is a step diagram showing an example of a method for manufacturing a needle array. This is a step diagram showing an example of a method for manufacturing a needle array. This is a step diagram showing an example of a method for manufacturing a needle array. This is a step diagram showing an example of a method for manufacturing a needle array. This is a step diagram showing an example of a method for manufacturing a needle array. This is an explanatory diagram of an example of a use of the microneedle device of the present invention. This is an explanatory diagram of an example of a use of the microneedle device of the present invention.

[0009] The microneedle device of the present invention will be described in detail below. However, the present invention is not limited to the following embodiments and can be modified and applied as appropriate without altering the essence of the invention.

[0010] The microneedle device of the present invention comprises a needle array having a base and needle portions protruding from the base, and a pressing member that presses the surface of the base opposite to the surface on which the needle portions are provided, wherein the needle portion has a bottom end on the base side, a tip located on the opposite side of the base, and a side surface connecting the bottom end and the tip, and when the needle portion is viewed from the side, the distance X1 from the bottom end to the tip of the needle portion in the direction of protrusion of the needle portion is 500 μm to 4000 μm, the ratio (B / A) of the area B of the pressing surface of the pressing member that presses the base of the needle array to the area A of the region of the base where the needle portion exists is 1.0 or more, and when the needle portion is viewed from the side, the ratio (W2 / W1) of the width dimension W2 at the bottom end of the needle portion to the width dimension W1 of the needle portion at a position that bisects the distance X1 is 1.8 to 80.

[0011] Figure 1A is a schematic cross-sectional view showing an example of the microneedle device of the present invention. Figure 1B is a schematic perspective view showing an example of the microneedle device of the present invention. Figure 1C is a schematic top view showing an example of the microneedle device of the present invention. The microneedle device 1 shown in Figure 1A comprises a needle array 10 having a base and needle portions protruding from the base, and a pressing member 6 that presses the surface of the base opposite to the surface on which the needle portions are provided. It also comprises a cylindrical housing 5, a rod-shaped pressure ring 2 disposed inside the housing 5, a spring 3 for moving the pressure ring 2 up and down within the housing 5, and a needle fixing jig 4 disposed at the tip of the pressure ring 2 so as to be exposed from the lower end of the housing 5 when the contracted spring 3 is released. Although not shown, the needle array 10 is fixed to the needle fixing jig 4.

[0012] In the microneedle device 1, the pressure ring 2, spring 3, needle fixing jig 4, housing 5, and pressing member 6 are holding members for holding the needle array 10, and the needle array 10 is detachable.

[0013] In the microneedle device 1, by contracting the spring 3, the needle fixing jig 4 to which the needle array 10 is fixed can be pulled upward into the housing 5, with the pressure ring 2 located at its tip. By releasing the contracted spring 3, the pressure ring 2 is moved downward into the housing 5, and the pressing member 6 presses the base of the needle array 10 on the side opposite to the side with the needle portion. As a result, the needle fixing jig 4 to which the needle array 10 is fixed is exposed from the lower end of the housing 5, allowing the needle portion of the needle array 10 to penetrate the skin.

[0014] Figure 2A is a schematic perspective view showing an example of a needle array. Figure 2B is a cross-sectional view taken along line A-A in Figure 2A. Figure 2C is an enlarged view of the dashed line in Figure 2B.

[0015] The needle array 10 shown in Figures 2A and 2B comprises a base portion 20 and needle portions 30 protruding from the base portion 20. The surface of the base portion 20 is flat, and the needle portions 30 protrude in a first direction perpendicular to the surface of the base portion 20 (indicated by arrow Z in Figures 2A and 2B).

[0016] The needle array 10 may have only one needle portion 30 or may have multiple needle portions 30. The surfaces of the base portion 20 of the needle array 10 (the surface on which the needle portion 30 is provided and the surface opposite to the surface on which the needle portion 30 is provided) may be flat or curved, but flat surfaces are preferred. Furthermore, the direction in which the needle portion 30 of the needle array 10 protrudes may be perpendicular to the surface of the base portion 20 or oblique to the surface of the base portion 20. When the direction in which the needle portion 30 protrudes is oblique to the surface of the base portion 20, the direction in which the needle portion 30 protrudes may be, for example, 30° or more and less than 90° with respect to the surface of the base portion 20.

[0017] As shown in Figures 2A to 2C, the needle portion 30 of the needle array 10 has a bottom end 31 on the base 20 side, a tip 32 located on the opposite side of the base 20, and a side surface 33 connecting the bottom end 31 and the tip 32. The needle portion 30 is also shaped to gradually taper from the bottom end 31 to the tip 32. In the needle array 10 shown in Figures 2A to 2C, the tip 32 is planar and formed parallel to the surface of the base 20. That is, the needle portion 30 has a frustoconical shape.

[0018] The tip 32 of the needle portion 30 may be sharp and pointed or flat, but it is preferable that it be sharp and pointed. In this specification, the tip 32 of the needle portion 30 being sharp and pointed means that the width dimension W3 of the tip 32 of the needle portion 30 is greater than 0 μm and 50 μm or less. If the tip 32 of the needle portion 30 is flat, the tip 32 may be formed parallel to the surface of the base portion 20 or at an angle to the surface of the base portion 20.

[0019] The needle portion 30 of the needle array 10 may be frustoconical, frustoconical, conical, or pyramidal. It may also have a flared shape from the tip 32 to the base 20.

[0020] In the needle array 10, when the needle portion 30 is viewed from the side, the distance X1 from the bottom end 31 to the tip 32 of the needle portion 30 in the protruding direction Z is 500 μm to 4000 μm. If the distance X1 is less than 500 μm, the needle portion 30 may not be able to reach the dermis when puncturing the skin, and may not be able to come into contact with the body fluids to be analyzed, such as blood and interstitial fluid. If the distance X1 exceeds 4000 μm, the strength of the needle portion 30 may be insufficient, causing the needle portion 30 to bend when puncturing the skin, and preventing it from reaching the dermis. Furthermore, from the viewpoint of reducing pain when the needle portion 30 is inserted into the skin and making the needle portion 30 less prone to bending, the distance X1 is preferably 600 μm to 4000 μm, more preferably 1000 μm to 3000 μm, and even more preferably 1500 μm to 2000 μm.

[0021] In the needle array 10, when the needle portion 30 is viewed from the side, the ratio of the width dimension W2 at the bottom end 31 of the needle portion 30 to the width dimension W1 at position H1, which bisects the distance X1 from the bottom end 31 to the tip 32 of the needle portion 30 in the protruding direction Z of the needle portion 30, is 1.8 to 80. If the ratio of the width dimension W2 to the width dimension W1 (W2 / W1) is less than 1.8, the strength of the needle portion 30 will be insufficient, and the needle portion 30 may bend when puncturing the skin, preventing it from reaching the dermis. If the ratio of the width dimension W2 to the width dimension W1 (W2 / W1) exceeds 80, the needle portion 30 may easily slip out of the skin when puncturing the skin, preventing it from reaching the dermis. The ratio of the width dimension W2 to the width dimension W1 (W2 / W1) is preferably 5.0 to 15.

[0022] In the needle array 10, when the needle portion 30 is viewed from the side, the width dimension W1 of the needle portion at position H1 that bisects the distance X1 from the bottom end 31 to the tip 32 of the needle portion 30 in the protruding direction Z of the needle portion 30 is preferably 50 μm to 500 μm, more preferably 50 μm to 400 μm, even more preferably 50 μm to 350 μm, and particularly preferably 150 μm to 250 μm. It is preferable that the width dimension W1 is within the above range because it can further reduce pain when the needle portion 30 is inserted into the skin.

[0023] In the needle array 10, when the needle portion 30 is viewed from the side, the width dimension W2 at the bottom end 31 of the needle portion 30 is preferably 300 μm to 4000 μm, more preferably 750 μm to 3000 μm, and even more preferably 1000 μm to 2000 μm.

[0024] In the needle array 10, when the needle portion 30 is viewed from the side, the width dimension W3 of the tip 32 of the needle portion 30 is preferably greater than 0 μm and 100 μm or less, and more preferably greater than 0 μm and 50 μm or less. It is preferable that the width dimension W3 is within the above range, as this can further reduce pain when the needle portion 30 is inserted into the skin.

[0025] When the needle array 10 has multiple needle portions 30, the arrangement of the needle portions 30 is not particularly limited. For example, when the needle array 10 is viewed from above, the needle portions 30 may be arranged at the vertices of a square grid, at the vertices of a rectangular grid, or at each vertex when triangles or other polygons are used to tile a plane. Also, when the needle array 10 is viewed from above, the needle portions 30 may be arranged in a circular or elliptical shape.

[0026] In the needle array 10, the area A of the region where the needle portion 30 of the base portion 20 is located is not particularly limited. In this specification, "area A of the region where the needle portion of the base portion is located" means the area of ​​a square formed by the four sides tangent to the outer circumference of the base end 31 of the needle portion 30 when the needle array 10 has only one frustoconical needle portion 30. Also, when the needle array 10 has multiple frustoconical needle portions 30 arranged at the vertices of a square or rectangular grid, it means the area of ​​a square or rectangle formed by the four sides tangent to the outer circumference of the base end 31 of the needle portion 30 arranged on the outermost edge of the square or rectangular grid, and which encloses all the needle portions 30. For example, in the case of the needle array 10 shown in Figure 1C, it means the area of ​​the portion enclosed by the dotted line.

[0027] In one embodiment of the present invention, the needle array 10 may or may not have through holes penetrating the needle portion 30 and the base portion 20, but from the viewpoint of the strength of the needle portion 30, it is preferable that it does not have through holes.

[0028] The material of the needle portion 30 of the needle array 10 is not particularly limited, but is preferably an organic polymer compound, a metal such as aluminum or stainless steel alloy, silicon, carbon, ceramic, or various inorganic materials including calcium-based minerals. These materials may be used individually or in combination of two or more.

[0029] As organic polymer compounds, known compounds (synthetic polymers and natural polymers) can be used. For example, bioabsorbable polymers, polyethylene terephthalate (PET), polyethylene (PE), polypropylene (PP), acrylic resins, epoxy resins, polystyrene, and other plastic materials can be used.

[0030] As bioabsorbable polymers, known compounds (synthetic polymers and natural polymers) can be used, such as ester compounds like polylactic acid, polyglycolic acid, poly-ε-caprolactone, poly-p-dioxanone, and polymalic acid; acid anhydrides like polyacid anhydrides; orthoester compounds like polyorthoesters; carbonate compounds like polycarbonates; phosphazene compounds like polydiaminophosphazenes; peptide compounds like synthetic polypeptides; phosphate ester compounds like polyphosphoesterurethanes; carbon-carbon compounds like polycyanoacrylates; poly-β-hydroxybutyric acid; polyamino acids; chitin; chitosan; hyaluronic acid; and sodium hyaluronate. Examples include pectin, galactan, starch, dextran, dextrin, alginic acid, sodium alginate, cellulose compounds (ethylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose), agar, keltrol, leozan, xanthan gum, pullulan, gum arabic, and other glycoside compounds (polysaccharides), collagen, gelatin, fibrin, gluten, peptide compounds (peptides, proteins) such as serum albumin, phosphate ester compounds (nucleic acids) such as deoxyribonucleic acid and ribonucleic acid, and vinyl compounds such as polyvinyl alcohol.

[0031] The base portion 20 of the needle array 10 can be made of the same material as the needle portion 30 described above.

[0032] In the needle array 10, it is preferable that the material of the base portion 20 and the material of the needle portion 30 are the same.

[0033] Furthermore, the needle array 10 may be formed by integrally molding the base portion 20 and the needle portion 30, or by connecting separately molded base portion 20 and needle portion 30, but it is preferable that the base portion 20 and needle portion 30 are integrally molded.

[0034] The needle portion 30 of the needle array 10 is preferably equipped with a sensor portion such as an electrode. When the needle portion 30 is equipped with a sensor portion, it is possible to analyze the target of analysis in the body fluid using the sensor portion. The location of the sensor portion is not particularly limited as long as the sensor portion and the body fluid can come into contact when the needle portion 30 is inserted into the skin, and it may be installed on the surface of the needle portion 30 (the tip 32 or side surface 33 of the needle portion 30), or the needle portion 30 itself may be a needle-shaped sensor. Furthermore, if the needle array 10 has a through hole that penetrates the needle portion 30 and the base portion 20, the sensor portion may be installed on the inner surface of the through hole.

[0035] When the needle portion 30 of the needle array 10 includes a sensor portion such as an electrode, the material of the sensor portion is not particularly limited, and materials used for electrodes of conventionally known sensors can be used, such as gold, silver, copper, copper alloy, indium tin oxide (ITO), carbon, polyethylene dioxythiophene (PEDOT), and iron. These materials may be used individually or in combination of two or more. The material of the sensor portion is preferably gold.

[0036] Furthermore, if the needle portion 30 of the needle array 10 is equipped with a sensor portion such as an electrode, the appearance of the needle array 10 may be opaque, semi-transparent, or transparent, but it is preferable that it be opaque. In this specification, "opaque" means that when the color difference with respect to a color difference reference color (black) is measured using a color difference meter (CR-200, manufactured by Minolta Corporation) with the lightness index value L* as an indicator, the lightness index value L* exceeds 60. For example, if the needle portion 30 of the needle array 10 is equipped with an electrode made of gold, the appearance of the needle array 10 will be opaque.

[0037] Next, a method for manufacturing the needle array 10 will be described. The needle array 10 may be formed, for example, by injection molding using a mold, by using a cast mold, or by using a 3D printer.

[0038] The following describes a method for manufacturing a needle array 10 using a mold, as an example of such a method.

[0039] Figures 3A to 3H are process diagrams showing, in order, an example of a method for manufacturing a needle array.

[0040] In the method for manufacturing a needle array using a mold, first, as shown in Figure 3A, a microneedle resin 50 is coated onto the substrate S using a spin coater.

[0041] Next, as shown in Figure 3B, a lifting member 60 is prepared, on which pillars 61 are formed in a predetermined arrangement. The lifting member 60 can be manufactured using a 3D printer or the like. Then, the microneedle resin 50 is made fluid, and the lifting member 60 is positioned so that the pillars 61 are in contact with the microneedle resin 50. Making the microneedle resin 50 fluid means, for example, if the microneedle resin 50 is a thermoplastic resin, raising its temperature to its melting point.

[0042] Next, the microneedle resin 50 is made fluid, and the pillar 61 of the lifting member 60 is brought into contact with the microneedle resin 50. Then, as shown in Figure 3C, the lifting member 60 is pulled upward. This causes the microneedle resin 50 to be stretched by the lifting member 60. After that, the microneedle resin 50 is hardened, and the constricted portion of the microneedle resin 50 is cut off.

[0043] This makes it possible to fabricate the microneedle 51 shown in Figure 3D.

[0044] The dimensions and shape of the micro needle 51 can be adjusted by changing the shape of the pillar 61, the viscosity of the resin 50 for the micro needle, the pulling speed, the pulling distance, etc. when pulling up the resin 50 for the micro needle. By adjusting the dimensions and shape of the micro needle 51, the dimensions and shape of the needle part 30 of the needle array 10 obtained through subsequent processes can be adjusted.

[0045] Next, as shown in FIG. 3E, the micro needle 51 is inverted up and down, placed in the container 70, the mold resin 80 is poured into the container 70, and the mold resin 80 is cured.

[0046] Next, as shown in FIG. 3F, the mold 81 is produced by removing the micro needle 51.

[0047] Next, as shown in FIG. 3G, the resin 10a for the needle array is put into the mold 81.

[0048] Thereafter, the resin 10a for the needle array is cured and taken out from the mold 81, whereby the needle array 10 in which the base part 20 and the needle part 30 are integrally formed as shown in FIG. 3H can be produced.

[0049] When the needle array 10 has a through hole penetrating the needle part 30 and the base part 20, after forming the needle part 30 in which the through hole is not formed, the through hole may be formed by laser processing or the like, or the needle part 30 in which the through hole is formed may be formed at once.

[0050] The micro needle device of the present invention includes a pressing member that presses the surface of the base of the needle array on the side opposite to the surface provided with the needle part. The shape of the pressing member is not particularly limited, and may be, for example, a prismatic shape such as a cylindrical shape or a quadrangular prism shape. The pressing surface (bottom surface) of the pressing member may be a flat surface or a curved surface, but a flat surface is preferable. The central axis of the pressing member is preferably perpendicular to the pressing surface (bottom surface) of the pressing member. In this specification, the pressing surface of the pressing member refers to the surface (bottom surface of the pressing member) that presses the surface of the base of the needle array on the side opposite to the surface provided with the needle part. For example, when the shape of the pressing member is cylindrical, it refers to the circular portion corresponding to the bottom surface of the pressing member.

[0051] In a pressing member, the area B of the pressing surface of the pressing member that presses the surface of the base of the needle array opposite to the surface on which the needles are provided is not particularly limited. In this specification, "area B of the pressing surface of the pressing member" refers to the area of ​​the surface (bottom surface of the pressing member) that presses the surface of the base of the needle array opposite to the surface on which the needles are provided. For example, if the shape of the pressing member is cylindrical, it refers to the area of ​​the circle corresponding to the bottom surface of the pressing member. For example, in the case of the needle array 10 shown in Figure 1C, it refers to the area of ​​the outer circumference of the pressing member 6.

[0052] The microneedle device of the present invention has a ratio (B / A) of area B (area of ​​the pressing surface of the pressing member that presses the base of the needle array) to area A (area of ​​the region where the needle portion is located at the base of the needle array) of 1.0 or more. If the ratio of area B to area A (B / A) is less than 1.0, the needle portion may not reach the dermis when it is inserted into the skin. The ratio of area B to area A (B / A) is preferably 1.1 to 80, and more preferably 4 to 20.

[0053] In the microneedle device of the present invention, it is preferable that the center point of the needle array when the needle array is viewed in plan and the central axis of the pressing member are on the same line.

[0054] Next, the method of using the microneedle device of the present invention will be described. Figures 4A and 4B are explanatory diagrams illustrating examples of the use of the microneedle device of the present invention.

[0055] When using the microneedle device 1, first, as shown in Figure 4A, the spring 3 is compressed and the pressure ring 2 is pulled upward. Then, the end of the housing 5 on the side where the needle array 10 is located is pressed against the skin.

[0056] Subsequently, the spring 3 is released as shown in Figure 4B. This causes the pressing surface of the pressing member 6 to press against the base of the needle array on the side opposite to the side with the needle portion, causing the needle array 10 to move downward and puncture the skin. If the needle portion of the needle array 10 has a through hole, the pressure ring 2 is pushed in, and body fluid can be collected by pressurizing the area around the needle array 10.

[0057] This specification describes the following inventions:

[0058] (1) The present invention relates to a microneedle device comprising a needle array having a base and needle portions protruding from the base, and a pressing member that presses the surface of the base opposite to the surface on which the needle portions are provided, wherein the needle portion has a bottom end on the base side, a tip located on the opposite side of the base, and a side surface connecting the bottom end and the tip, and when the needle portion is viewed from the side, the distance X1 from the bottom end to the tip of the needle portion in the direction of protrusion of the needle portion is 500 μm to 4000 μm, the ratio (B / A) of the area B of the pressing surface of the pressing member that presses the base of the needle array to the area A of the region of the base where the needle portion exists is 1.0 or more, and when the needle portion is viewed from the side, the ratio (W2 / W1) of the width dimension W2 at the bottom end of the needle portion to the width dimension W1 of the needle portion at a position that bisects the distance X1 is 1.8 to 80.

[0059] The present invention (2) is a microneedle device according to the present invention (1), wherein the width dimension W1 is 50 μm to 500 μm.

[0060] The present invention (3) is a microneedle device according to the present invention (1) or (2), wherein the width dimension W2 is 300 μm to 4000 μm.

[0061] The present invention (4) is a microneedle device according to any one of the present inventions (1) to (3), wherein, when the needle portion is viewed from the side, the width dimension W3 at the tip of the needle portion is greater than 0 μm and less than or equal to 100 μm.

[0062] The present invention will now be specifically described with reference to examples, but the present invention is not limited to these examples unless it deviates from the spirit of the invention.

[0063] (Example 1) An epoxy resin (SU-8 3050, manufactured by Nippon Kayaku Co., Ltd.) was coated onto a glass substrate (26 x 76 mm, 1.5 mm thick) as a resin for microneedles using a spin coater (Opticoat MS-A100, manufactured by MIKASA) at a speed of 1000 rpm for 30 seconds.

[0064] A lifting component with pillars formed on it was fabricated using a 3D printer (Anycubic Photon M3 Plus, manufactured by Anycubic). The lifting component was made of a 10 x 10 mm, 1 mm thick flat plate, with cylindrical pillars with a diameter of 0.45 mm arranged at the vertices of a square grid at 2 mm intervals.

[0065] The epoxy resin on the glass substrate was held at 120°C for 15 minutes to achieve a fluid state. Then, the outermost surface of the pillar of the lifting member was brought into contact with the epoxy resin, and it was cooled at a rate of 20°C / min. When it reached 60°C, it was lifted 2000 μm perpendicular to the glass substrate at a speed of 25 μm / second. After that, it was allowed to stand at 25°C for 20 minutes to cure, and then the constricted portion of the epoxy resin was cut to create microneedles.

[0066] Next, the obtained microneedles were placed in a glass petri dish, and polydimethylsiloxane (PDMS) (SYLGARD 184, manufactured by DAW SILICONES) was poured in as a molding resin in a ratio of main agent to hardener of 10:1. The resin was then cured at 100°C for 30 minutes. After that, the microneedles were removed, and a mold was prepared from the PDMS with the shape of the microneedles transferred onto it.

[0067] As the resin for the needle array, 1 g of polylactic acid (manufactured by Musashino Chemical Co., Ltd.) was placed in a mold, and the temperature was controlled to 240°C using a nanoimprint apparatus (manufactured by SCIVAX Corporation), after which a load of 10 N was applied for 5 minutes. After that, it was cooled to 25°C to cure the polylactic acid. The cured material was removed from the mold, and a needle array was fabricated in which the base and needle parts were integrally molded.

[0068] The needle array was manufactured through the above process. The obtained needle array was mounted on a microneedle device. The pressing member of this microneedle device has a pressing surface area B of 2.3 cm² that presses against the base of the needle array. ２ The central axis of the pressing member was made perpendicular to the pressing surface (bottom surface) of the pressing member. In addition, the center point of the needle array when viewed from above and the central axis of the pressing member were made to be on the same line. In this way, the microneedle device according to Example 1 was fabricated. For the obtained microneedle device, the dimensions of the needle portion of the needle array (distance X1, width dimensions W1 to W3, ratio of width dimension W2 to width dimension W1 (W2 / W1)), and the ratio of area B to area A (B / A) are shown in Table 1.

[0069] (Examples 2-12 and Comparative Examples 1-5) Microneedle devices according to Examples 2-12 and Comparative Examples 1-5 were fabricated in the same manner as in Example 1, except that the dimensions of the needle portion of the needle array (distance X1, width dimensions W1-W3, ratio of width dimension W2 to width dimension W1 (W2 / W1)), and the ratio of area B to area A (B / A) were adjusted to the values ​​shown in Table 1.

[0070] Using the microneedle devices obtained in Examples 1 to 12 and Comparative Examples 1 to 5, the needle portion was inserted into the skin of the posterior forearm (back of the hand) of one subject under conditions of a puncture pressure of 9 N and a puncture speed of 240 mm / sec. The following were evaluated using the methods described below: (1) pain when the needle portion of the needle array was inserted, (2) bending of the needle portion after puncture, (3) whether the needle portion reached the dermis, (4) the amount of body fluid leakage from the puncture site, and (5) blood contamination of the leaked interstitial fluid.

[0071] (1) Pain upon puncture of the needle array needles A total of three punctures were performed on different days on the skin of the posterior forearm (back of the hand) of one subject using the needle array needles, under the conditions of a puncture pressure of 9N and a puncture speed of 240 mm / sec. The presence and degree of pain during each puncture were evaluated based on the following criteria. The needle array was replaced after each puncture, and the puncture site was shifted to avoid puncturing the same location on the skin. The average of the scores from the three punctures was recorded as the evaluation result in the "Pain" column of Table 1. 1: No pain 2: Some pain 3: Severe pain

[0072] (2) Bending of the needle after puncture After evaluating (1) above, the needle was visually inspected after removal, and the presence and degree of bending of the needle was evaluated based on the following criteria. The evaluation was performed a total of three times, and the average of the scores from the three evaluations was recorded as the evaluation result in the "Bending of the needle" column of Table 1. 1: No bending 2: Bent to an angle of less than 90° from the position before puncture 3: Bent to an angle of 90° or more from the position before puncture

[0073] (3) Whether the needle reaches the dermis After evaluating (1) above, the needle was withdrawn, a resin ring with an outer diameter of 9 mm, an inner diameter of 7 mm, and a height of 10 mm was placed around the puncture hole, and a load of 10 N was applied to the ring for 30 seconds to pressurize the area around the puncture hole. It was visually confirmed whether or not body fluid leaked out of the puncture hole due to the pressurization. If body fluid leaked out, it was evaluated that the needle had reached the dermis, and if no body fluid leaked out, it was evaluated that the needle had not reached the dermis. The evaluation was performed a total of three times, and the degree to which the needle reached the dermis each time was scored according to the following criteria, and the average of the three scores was recorded as the evaluation result in the "Dermis Reach" column of Table 1. 1: Needle reached the dermis 2: Needle did not reach the dermis

[0074] (4) Amount of body fluid leakage from the puncture site In the evaluation in (3) above, if the needle reached the dermis (visual confirmation of body fluid leakage from the puncture site), the amount of body fluid leakage from the puncture site was quantified. Specifically, in the evaluation in (3) above, the entire amount of body fluid leaked from the puncture site was absorbed by a moisture test strip (manufactured by Advantec Toyo Co., Ltd.), and then the amount of body fluid leakage from the puncture site was quantified using a pre-prepared calibration curve based on the relationship between the amount of body fluid absorbed by the moisture test strip (unit: μL) and the degree of color change of the moisture test strip. The amount of body fluid leakage from the puncture site was measured in each of the three evaluations in (3) above, and the average value of these measurements was recorded as the evaluation result in the "Amount of body fluid leakage from the puncture site" column of Table 1. For Comparative Examples 1 to 5, in the evaluation in (3) above, the needle did not reach the dermis (visual confirmation of body fluid leakage from the puncture site was not possible), so the amount of body fluid leakage from the puncture site was set to 0 μL.

[0075] (5) Contamination of leaked bodily fluids with blood In the evaluation in (3) above, if the needle reached the dermis (visual confirmation of leakage of bodily fluids from the puncture site), the color of the bodily fluids leaked from the puncture site was visually inspected to determine whether the leaked bodily fluids were a mixture of interstitial fluid and blood, thereby confirming whether or not there was blood contamination in the leaked bodily fluids. If the leaked bodily fluids were colorless to pale yellow, it was determined that there was no blood contamination in the bodily fluids and that interstitial fluids had leaked. If the color was pale red to reddish, it was determined that a mixture of interstitial fluids and blood had leaked. In the "Presence or Absence of Blood Contamination" column of Table 1, "None" was written if interstitial fluids were leaked, and "Present" was written if a mixture of interstitial fluids and blood was leaked. In addition, if blood was found in even one of the three evaluations in (3) above, it was determined that there was blood contamination in that example. In addition, when interstitial fluid is the target of analysis, it is preferable that there is no blood contamination, as the contamination of bodily fluids with blood can reduce the accuracy of the analysis. In comparative examples 1 to 5, the needle did not reach the dermis in the evaluation described in (3) above (no leakage of bodily fluids from the puncture site could be visually confirmed), therefore, the presence or absence of blood contamination in the bodily fluids was not evaluated.

[0076]

[0077] As shown in Table 1, the microneedle devices according to Examples 1 to 12 were found to have the ability to reliably reach the dermis and suppress pain when the needle portion of the needle array is inserted into the skin.

[0078] According to the present invention, it is possible to provide a microneedle device in which the needle portion of the needle array is less likely to bend when punctured into the skin, can reliably reach the dermis, and can suppress pain. Furthermore, if the needle portion of the needle array is equipped with a sensor portion such as an electrode, the sensor portion can be used to analyze the target substance in bodily fluids, and the device can be used as a biosensor.

[0079] 1 Microneedle device 2 Pressure ring 3 Spring 4 Needle fixing jig 5 Housing 6 Pressing member 10 Needle array 10a Resin for needle array 20 Base 30 Needle part 31 Bottom end 32 Tip 33 Side 50 Resin for microneedle 51 Microneedle 60 Pulling member 61 Pillar 70 Container 80 Resin for molding 81 Mold S Substrate

Claims

1. A microneedle device comprising: a needle array having a base and needle portions protruding from the base; and a pressing member that presses the surface of the base opposite to the surface on which the needle portions are provided, wherein the needle portion has a bottom end on the base side, a tip located on the opposite side of the base, and a side surface connecting the bottom end and the tip; when the needle portion is viewed from the side, the distance X1 from the bottom end to the tip of the needle portion in the direction of protrusion of the needle portion is 500 μm to 4000 μm; the ratio (B / A) of the area B of the pressing surface of the pressing member that presses the base of the needle array to the area A of the region of the base where the needle portion exists is 1.0 or more; and when the needle portion is viewed from the side, the ratio (W2 / W1) of the width dimension W2 at the bottom end of the needle portion to the width dimension W1 of the needle portion at a position that bisects the distance X1 is 1.8 to 80.

2. The microneedle device according to claim 1, wherein the width dimension W1 is 50 μm to 500 μm.

3. The microneedle device according to claim 1 or 2, wherein the width dimension W2 is 300 μm to 4000 μm.

4. The microneedle device according to claim 1 or 2, wherein, when the needle portion is viewed from the side, the width dimension W3 at the tip of the needle portion is greater than 0 μm and less than or equal to 100 μm.

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