WO2024237204A1 - Microneedle manufacturing method, microneedle, and microneedle unit - Google Patents

Abstract

[Problem] To provide: a microneedle manufacturing method capable of easily manufacturing a microneedle provided with a horizontal hole as a liquid drug discharge port in a penetrating state; a microneedle; and a microneedle unit. [Solution] A microneedle manufacturing method for manufacturing a microneedle provided with a vertical hole as a liquid drug flow channel and a horizontal hole as a liquid drug discharge port connected to the vertical hole, wherein: a slide pin for molding the horizontal hole is formed in a molding die; a core pin for molding the vertical hole is brought into contact with the formed slide pin; a resin is filled in the molding die in the state described above; and after a curing period, the core pin is retracted and the slide pin is pulled out so as to integrally mold the microneedle provided with the vertical hole as the liquid drug flow channel and the horizontal hole as the liquid drug discharge port connected to the vertical hole in a penetrating state.

Description

Microneedle manufacturing method, microneedle, and microneedle unit

The present invention relates to a microneedle manufacturing method, a microneedle, and a microneedle unit, and in particular to a method that is devised to easily manufacture a microneedle having a penetrating horizontal hole that serves as a drug solution discharge port.

General hollow microneedles made of resin have a vertical hole at the center of the tip for injecting a medicinal solution subcutaneously or intradermally. Such conventional hollow microneedles made of resin have a problem in that they have low mechanical strength and are difficult to insert.

In response to this, horizontal-hole type hollow microneedles have been proposed. Examples of documents that disclose the configuration of such hollow microneedles include Patent Document 1 and Patent Document 2.

First, in the case of the microneedle unit according to the invention described in Patent Document 1, it is configured by bonding together a first divided element and a second divided element, and has a configuration in which a drug solution discharge port is provided sideways. This ensures the mechanical strength of the tip, prevents clogging by the skin when puncturing, and enables effective injection of the drug solution into the skin or subcutaneously.
Incidentally, Patent Document 1 was filed by the present applicant.

Next, in the case of the hollow microneedle array according to the invention described in Patent Document 2, the orifice is provided substantially horizontally on the inclined surface of the molded product.

Patent No. 6347960 Special Publication No. 2012-523270

The above conventional configuration has the following problems.
First, in the case of the invention described in Patent Document 1, the first divided element and the second divided element must be precisely bonded together, which makes it difficult to mass-produce them with high precision while ensuring airtightness. In addition, there are problems in that the number of steps is large, resulting in high costs.
There is also a problem that there are limitations on the shape of the liquid medicine discharge hole.
Furthermore, a needle hub is required to attach the microneedle unit to a syringe, but such a needle hub must be molded as a separate part, which causes a further increase in manufacturing costs.

Furthermore, in the case of the invention described in Patent Document 2, since the device is not provided completely horizontally to begin with, there is a problem in that the effect of the horizontal orientation cannot be fully obtained.
Furthermore, similar to the invention described in Patent Document 1, there is a problem in that a plurality of plates is required for manufacturing, and complicated operations and adjustments are required.
In addition, because the openings are formed by the contact between the penetration pin and the cavity, there are problems such as burrs due to breakage or wear, limitations on the needle and hole shapes, and weak parts. As a result, it is extremely difficult to uniformly form the openings of all the needles.

The present invention was made based on these points, and its purpose is to provide a microneedle manufacturing method that can easily manufacture a microneedle that has a penetrating horizontal hole that serves as a drug solution discharge port, as well as a microneedle and a microneedle unit.

In order to solve the above problems, the microneedle manufacturing method according to claim 1 of the present invention is a microneedle manufacturing method for manufacturing a microneedle having a vertical hole as a drug solution flow path and a horizontal hole connected thereto as a drug solution discharge outlet, characterized in that a slide pin for molding the horizontal hole is made to appear in a molding die, a core pin for molding the vertical hole is abutted against the emerged slide pin, resin is filled into the molding die in this state, and after a curing period has elapsed, the core pin is retracted and the slide pin is pulled out, thereby integrally molding a microneedle having a vertical hole as a drug solution flow path and a horizontal hole connected thereto as a drug solution discharge outlet.
A microneedle manufacturing method according to claim 2 is the microneedle manufacturing method according to claim 1, wherein the molding die is composed of a pair of cores arranged so as to be able to come into contact with and separate from one another, the pair of cores are separated and the slide pin is made to appear between them, the pair of cores are brought close to each other to sandwich the slide pin, the core pin is made to appear and abut against the slide pin, resin is filled between the pair of cores in this state, and after a curing period has elapsed, the core pin is retracted and the slide pin is pulled out, thereby integrally molding a microneedle having a vertical hole as a drug solution flow path and a horizontal hole connected thereto as a drug solution discharge outlet in a penetrated state.
Furthermore, the microneedle manufacturing method according to claim 3 is the microneedle manufacturing method according to claim 2, characterized in that the pair of cores are a pair of sliding cores arranged so as to be movable together in a direction perpendicular to the axial direction of the microneedle, and the microneedle is formed from this pair of sliding cores.
Furthermore, the microneedle manufacturing method according to claim 4 is the microneedle manufacturing method according to claim 3, characterized in that a core insert is disposed between the pair of slide cores, and the core pin is adapted to protrude and retract by penetrating through this core insert.
Furthermore, the microneedle manufacturing method according to claim 5 is the microneedle manufacturing method according to claim 4, characterized in that each of the pair of slide cores is formed with a recess for accommodating the slide pin, and a cavity is formed for accommodating the core insert with the core pin exposed.
Furthermore, the microneedle manufacturing method according to claim 6 is the microneedle manufacturing method according to claim 5, characterized in that the pair of slide cores are set to a size sufficient to mold the area from the microneedle to the needle base, and the core insert is also set to a size sufficient to mold the area from the microneedle to the needle base, and the pair of slide cores and core insert are used to integrally mold the area from the microneedle to the needle base as a microneedle unit.
Furthermore, the microneedle manufacturing method according to claim 7 is the microneedle manufacturing method according to claim 4, characterized in that the core insert has a plurality of core pins arranged in a row, and the slide core has a cavity in which the core insert with the plurality of core pins exposed is housed, and the pair of slide cores and core inserts are used to arrange a plurality of microneedles in a row and mold them as a single unit.
Furthermore, the microneedle manufacturing method according to claim 8 is the microneedle manufacturing method according to claim 7, characterized in that the lateral holes of the multiple microneedles are formed in one continuous operation by a single slide pin.
Furthermore, the microneedle manufacturing method according to claim 9 is characterized in that, in the microneedle manufacturing method described in claim 2, the pair of cores are a cabinet nest upper plate and a cabinet nest lower plate arranged so as to be able to be separated from each other in the axial direction of the microneedle, and the microneedle is formed from these cabinet nest upper plate and cabinet nest lower plate.
Furthermore, the microneedle manufacturing method according to claim 10 is the microneedle manufacturing method according to claim 9, characterized in that a core insert is arranged below the cabinet insert lower plate so as to be movable in the axial direction of the microneedle.
The microneedle according to claim 11 is characterized in that it comprises a vertical hole as a drug solution flow path and a horizontal hole connected thereto as a drug solution discharge port, which are formed in a penetrating state, and are integrally molded.
A microneedle according to claim 12 is the microneedle according to claim 11, characterized in that the cross-sectional shape of the transverse hole is circular.
Furthermore, the microneedle according to claim 13 is the microneedle according to claim 11, characterized in that it is composed of a base portion, a neck portion provided at the tip side of the base portion, and a cone portion provided at the tip side of the neck portion, and the horizontal hole is provided in the lower part of the cone portion.
Furthermore, the microneedle according to claim 14 is characterized in that, in the microneedle according to claim 13, the pyramidal portion is a quadrangular pyramidal portion, and the horizontal hole is provided penetrating on a line connecting a pair of edges of the quadrangular pyramidal portion.
A microneedle according to claim 15 is characterized in that in the microneedle according to claim 14, the end of the edge of the quadrangular pyramid portion on the neck side is formed into an outwardly convex arc shape.
Furthermore, the microneedle according to claim 16 is characterized in that, in the microneedle according to claim 13, the lower part of the base portion is formed with a larger diameter than the neck portion, and the diameter gradually decreases from there toward the neck portion.
Furthermore, the microneedle according to claim 17 is characterized in that, in the microneedle according to claim 13, the vertical hole is formed from the base portion to the neck portion and gradually narrows from the base portion to the neck portion.
Furthermore, a microneedle unit according to claim 18 is characterized in comprising a microneedle according to any one of claims 11 to 17, and a needle base which is integrally molded with the base end side of the microneedle and to which the tip of the cylindrical body of a syringe is connected.

As described above, according to the microneedle manufacturing method of claim 1 of the present invention, in a microneedle manufacturing method for manufacturing a microneedle having a vertical hole as a drug solution flow path and a horizontal hole as a drug solution discharge outlet connected thereto in a penetrating state, a slide pin for molding the horizontal hole is made to appear in a molding die, a core pin for molding the vertical hole is abutted against the emerged slide pin, resin is filled into the molding die in this state, and after a curing period has elapsed, the core pin is retracted and the slide pin is pulled out, thereby integrally molding a microneedle having a vertical hole as a drug solution flow path and a horizontal hole as a drug solution discharge outlet connected thereto in a penetrating state. Therefore, a microneedle having a vertical hole as a drug solution flow path and a horizontal hole as a drug solution discharge outlet connected thereto in a penetrating state can be easily manufactured by integral molding.
In this case, both ends of the slide pin are firmly held by the molding die, so its rigidity is fully guaranteed, there is no misalignment or deformation, the transverse hole can be formed with high precision, and no burrs are generated at the boundary between the slide pin and the core pin.
In addition, since the core pin is abutted against the slide pin, this also ensures rigidity and prevents misalignment and deformation, allowing the horizontal hole to be formed with high precision, and no burrs are generated at the boundary with the slide pin.
The same is true for the core pin side; by abutting it against the slide pin, misalignment or deformation due to resin pressure can be prevented, the horizontal hole can be molded with high precision, and no burrs are generated at the boundary with the slide pin.
According to a microneedle manufacturing method according to claim 2, in the microneedle manufacturing method according to claim 1, the molding die is composed of a pair of cores arranged so that they can be separated from each other, the slide pin is made to appear between the pair of cores when the pair of cores are separated, the pair of cores are brought close to each other to sandwich the slide pin, the core pin is made to appear and abut against the slide pin, resin is filled between the pair of cores in this state, and after a curing period has elapsed, the core pin is retracted and the slide pin is pulled out, thereby integrally molding a microneedle having a vertical hole as a drug solution flow path and a horizontal hole connected to the vertical hole as a drug solution discharge outlet, which are penetrated therethrough, thereby ensuring the above-mentioned effects.
Furthermore, since the molding die is made up of a pair of cores, the structure is simple.
Furthermore, according to the microneedle manufacturing method of claim 3, in the microneedle manufacturing method of claim 2, the pair of cores are a pair of sliding cores arranged so as to be able to be brought into contact with and separated from each other in a direction perpendicular to the axial direction of the microneedle, and the microneedle is formed from this pair of sliding cores, so that a row of microneedles can be manufactured with high precision.
Furthermore, according to the microneedle manufacturing method of claim 4, in the microneedle manufacturing method of claim 3, a core insert is disposed between the pair of slide cores, and the core pin appears and disappears by penetrating through this core insert, so that the above-mentioned effect can be reliably achieved.
Furthermore, the core pin can be easily inserted and removed, and the degree of contact can be easily adjusted.
Furthermore, according to the microneedle manufacturing method of claim 5, in the microneedle manufacturing method described in claim 4, each of the pair of slide cores is formed with a recess for accommodating the slide pin, and a cavity is formed for accommodating the core insert with the core pin exposed, so that the above-mentioned effect can be reliably achieved.
In this case, both ends of the slide pin are firmly held by the recesses in the slide core, so that its rigidity is fully guaranteed, there is no misalignment or deformation, the transverse hole can be formed with high precision, and no burrs are generated at the boundary between the slide pin and the core pin.
Also, the slide pin can be securely held by the recesses of the pair of slide cores.
Furthermore, according to the microneedle manufacturing method of claim 6, in the microneedle manufacturing method of claim 5, the pair of slide cores are set to a size that molds the range from the microneedle to the needle base, and the core insert is also set to a size that molds the range from the microneedle to the needle base, and the pair of slide cores and core insert are used to integrally mold the range from the microneedle to the needle base as a microneedle unit, thereby ensuring the above-mentioned effects.
Moreover, the area from the microneedle to the needle base can be easily molded as a microneedle unit.
Furthermore, according to the microneedle manufacturing method of claim 7, in the microneedle manufacturing method of claim 5, a plurality of core pins are arranged in a row in the core insert, and a cavity is provided in the slide core in which the core insert with the plurality of core pins revealed is housed, and a plurality of microneedles are arranged in a row and integrally molded using the pair of slide cores and core inserts, thereby ensuring the above-mentioned effects.
Moreover, it is possible to easily mold a plurality of microneedles arranged in a row.
Furthermore, according to the microneedle manufacturing method of claim 8, in the microneedle manufacturing method of claim 6, the lateral holes of the multiple microneedles are formed in one go by a single slide pin, so that the lateral holes can be easily formed in the multiple microneedles.
Furthermore, according to the microneedle manufacturing method of claim 9, in the microneedle manufacturing method of claim 2, the pair of cores are a cabinet nest upper plate and a cabinet nest lower plate that are arranged so as to be able to be separated from each other in the axial direction of the microneedle, and the microneedle is formed from these cabinet nest upper plate and cabinet nest lower plate, so that multiple rows of microneedles can be manufactured with high precision.
Furthermore, according to the microneedle manufacturing method of claim 10, in the microneedle manufacturing method of claim 9, a core nest is arranged below the cabinet nest lower plate so as to be movable in the axial direction of the microneedle, so that microneedles can be manufactured without expanding the space in a direction perpendicular to the axial direction of the microneedle.
Furthermore, according to the microneedle of claim 11, a vertical hole serving as a drug solution flow path and a horizontal hole connected thereto serving as a drug solution outlet are provided in a penetrating state and are molded as a single piece, so that the mechanical strength is high and reliable puncture and drug solution injection is possible.
Furthermore, the opening area is increased, which reduces the injection resistance and allows the drug to penetrate shallowly and widely into the skin efficiently.
According to the microneedle of claim 12, since the cross-sectional shape of the transverse hole in the microneedle of claim 11 is circular, injection of the medicinal solution can be carried out efficiently.
Furthermore, according to the microneedle of claim 13, in the microneedle of claim 11, it is composed of a base portion, a neck portion provided at the tip side of the base portion, and a cone portion provided at the tip side of the neck portion, and the horizontal hole is provided at the bottom of the cone portion, thereby ensuring reliable puncture and injection of medicinal solution.
The weight improves the puncture performance, the base ensures needle strength and improves formability, and the stretching effect of the skin makes it easier to puncture. Also, the puncture stops at the base, so the puncture depth is kept constant.
According to the microneedle of claim 14, the cone portion is a quadrangular pyramid portion in the microneedle of claim 13, and the horizontal hole is provided on a line connecting a pair of edges of the quadrangular pyramid portion, so that the puncture can be performed reliably and the injection of the medicinal solution can be performed reliably. Also, the puncture property can be improved by the edge (ridge line).
Furthermore, according to the microneedle of claim 15, in the microneedle of claim 14, the end of the edge of the quadrangular pyramid portion on the neck side is formed into an outwardly convex arc, thereby preventing damage to the skin when the needle is pulled out after puncturing.
Furthermore, according to the microneedle of claim 16, in the microneedle of claim 13, the lower part of the base portion is formed with a larger diameter than the neck portion, and the diameter gradually decreases from there toward the neck portion, making puncture easier and enabling the puncture depth to be constant.
Furthermore, according to the microneedle of claim 17, in the microneedle of claim 13, the vertical hole is formed from the base portion to the neck portion and gradually narrows from the base portion to the neck portion, thereby enabling efficient injection of medicinal liquid.
Furthermore, according to a microneedle unit according to claim 18, it comprises a microneedle according to any one of claims 11 to 17, and a needle base which is integrally molded with the base end side of the microneedle and to which the tip of the cylindrical body of a syringe is connected, so that the microneedle to the needle base form a single part, thereby simplifying the configuration and facilitating parts management.

FIG. 1 is a diagram showing a first embodiment of the present invention, and is a perspective view showing a configuration of a microneedle unit. FIG. 2 is an enlarged perspective view of a portion II in FIG. 1 according to the first embodiment of the present invention. FIG. FIG. 1 is a diagram showing a first embodiment of the present invention, and is a front view of a microneedle unit. FIG. 4 is an enlarged perspective view of a portion IV in FIG. 3 according to the first embodiment of the present invention. FIG. 1 is a diagram showing a first embodiment of the present invention, and is a side view of a microneedle unit. FIG. 6 is an enlarged side view of a portion VI in FIG. 5 , showing the first embodiment of the present invention. FIG. 1 is a diagram showing a first embodiment of the present invention, and is a front view of a microneedle. FIG. 1 is a perspective view of a microneedle according to a first embodiment of the present invention. FIG. 1 is a diagram showing a first embodiment of the present invention, and is a longitudinal sectional view of a microneedle. FIG. 1 is a diagram showing a first embodiment of the present invention, and is a longitudinal sectional view of a microneedle. 11(a) is a perspective view showing a state in which a slide pin is inserted, FIG. 11(b) is a perspective view showing a state in which a pair of slide cores are brought close to each other, and FIG. 11(c) is a perspective view showing a state in which a core pin has emerged and is abutting against the slide pin. 12(a) is a perspective view showing the state after resin has been filled, FIG. 12(b) is a perspective view showing the state after the core pin has been retracted, FIG. 12(c) is a perspective view showing the state after the slide pin has been retracted, and FIG. 12(d) is a perspective view showing the state after a pair of slide cores have been separated. FIG. 2 is a perspective view of the main part showing a state in which a core pin is pressed against a slide pin and resin is filled, according to the first embodiment of the present invention. FIG. 14 is an enlarged view of a portion XIV in FIG. 13, showing the first embodiment of the present invention. FIG. 11 is a plan view of a microneedle according to a second embodiment of the present invention. FIG. 13 is a side view of a microneedle according to a second embodiment of the present invention. FIG. 13 is a plan view of a microneedle according to a third embodiment of the present invention. FIG. 13 is a side view of a microneedle according to a third embodiment of the present invention. FIG. 13 is a plan view of a microneedle according to a fourth embodiment of the present invention. FIG. 13 is a side view of a microneedle according to a fourth embodiment of the present invention. FIG. 13 is a plan view of a microneedle according to a fifth embodiment of the present invention. FIG. 13 is a side view of a microneedle according to a fifth embodiment of the present invention. FIG. 13 is a plan view of a microneedle according to a sixth embodiment of the present invention. FIG. 13 is a side view of a microneedle according to a sixth embodiment of the present invention. FIG. 13 is a front view of the upper part of the microneedle unit according to the seventh embodiment of the present invention. 26A is an electron microscope photograph showing a part of a microneedle unit, and FIG. 26B is an optical microscope photograph showing a microneedle, showing the first embodiment of the present invention. 27A and 27B are diagrams showing a first embodiment of the present invention. FIG. 27(a) is a photograph showing the manufactured microneedle unit attached to a Luer lock syringe, and FIG. 27(b) is a microscopic photograph showing water being uniformly ejected from the side hole. FIG. 13 is a perspective view illustrating the eighth embodiment of the present invention, for explaining the manufacturing process for manufacturing microneedles arranged in multiple rows. FIG. 13 is a perspective view illustrating the eighth embodiment of the present invention, for explaining the manufacturing process for manufacturing microneedles arranged in multiple rows. FIG. 13 is a perspective view illustrating the eighth embodiment of the present invention, for explaining the manufacturing process for manufacturing microneedles arranged in multiple rows. FIG. 13 is a perspective view illustrating the eighth embodiment of the present invention, for explaining the manufacturing process for manufacturing microneedles arranged in multiple rows. FIG. 13 is a perspective view illustrating the eighth embodiment of the present invention, for explaining the manufacturing process for manufacturing microneedles arranged in multiple rows. FIG. 13 is a perspective view illustrating the eighth embodiment of the present invention, for explaining the manufacturing process for manufacturing microneedles arranged in multiple rows. FIG. 13 is a perspective view illustrating the eighth embodiment of the present invention, for explaining the manufacturing process for manufacturing microneedles arranged in multiple rows. FIG. 13 is a perspective view illustrating the eighth embodiment of the present invention, for explaining the manufacturing process for manufacturing microneedles arranged in multiple rows. FIG. 13 is a perspective view illustrating the eighth embodiment of the present invention, for explaining the manufacturing process for manufacturing microneedles arranged in multiple rows. FIG. 13 is a perspective view of a microneedle unit according to an eighth embodiment of the present invention. FIG. 13 is a perspective view of a microneedle unit according to the ninth embodiment of the present invention. FIG. 13 is a perspective view showing the relationship between a microneedle unit and a guide pin according to the ninth embodiment of the present invention. FIG. 23 is a perspective view of a microneedle unit according to a tenth embodiment of the present invention. FIG. 23 is a perspective view showing the relationship between a microneedle unit and a guide pin according to the tenth embodiment of the present invention.

Below, a first embodiment of the present invention will be described with reference to Figs. 1 to 14. Fig. 1 is a perspective view of a microneedle unit 1 according to this embodiment, and the microneedle unit 1 is composed of a needle base 3 and a plurality of microneedles 5 (three in this embodiment) provided at the tip of the needle base 3. The microneedle unit 1 is made of resin and is molded as a single unit.

The needle base 3 is composed of a first cylindrical portion 11, a second cylindrical portion 13 that is integral with the tip side of the first circular head portion 11 and has a smaller diameter than the first cylindrical portion 11, and a microneedle base portion 15 that is integral with the tip side of the second cylindrical portion 13. The first cylindrical portion 11 has flange portions 21, 21 at the base end thereof, which are 180° opposed to each other. These flange portions 21, 21 act as a prevention against coming off when the microneedle unit 1 is connected to a screw-in type syringe (not shown) (a so-called "Luer lock type" syringe). If the syringe is not a screw-in type (a so-called "Luer taper type"), the flange portions 21, 21 are not necessary. The first cylindrical portion 11 has a hollow portion (not shown) inside, into which the tip of the syringe barrel of the syringe is detachably inserted.

A pair of protrusions 23, 23 protrude from the bottom of the second cylindrical portion 13 to the top of the first cylindrical portion 11. The pair of protrusions 23, 23 are perpendicular to the pair of flanges 21, 21 and are provided at positions that are 180° opposed to each other. A cap (not shown) is placed on the microneedle 5 side of the microneedle unit 1. When the cap is gripped and screwed into the syringe, the protrusions 23, 23 come into contact with a rib inside the cap and function as a rotation stopper.

The microneedle base 15 has a tapered shape that gradually reduces in diameter toward the tip. That is, the cross-sectional shape of the lower end 15a of the microneedle base 15 is circular, and the cross-sectional shape of the upper end 15b is elliptical. The microneedle base 15 has a tapered shape that linearly connects the circular lower end 15a and the elliptical upper end 15b. Above the upper end 15b there is an elliptical upper end surface 15d via an inclined surface 15c, and the three microneedles 5 already mentioned are integrally provided on this upper end surface 15d.

As shown in Figures 7 to 10, the microneedle 5 is composed of a base portion 41, a neck portion 43 provided on the base portion 41, and a cone portion 45 provided on the neck portion 43. In this embodiment, the cone portion 45 has an approximately quadrangular pyramid shape.

The base portion 41 has a cross-sectional shape of a square with four arc-shaped corners in a range of a specified height from the lowest end. It does not necessarily have to be a square, and can be a circle, etc. The diameter is tapered from the top of the specified height range to the lowest end of the neck portion 43. The neck portion 43 also has a cross-sectional shape of a square with four arc-shaped corners, and the square is offset by 45° from the square of the base portion 41. A horizontal hole 51 is provided at the bottom of the cone portion 45, and this horizontal hole 51 is penetrating, with both end openings serving as drug solution discharge outlets 53, 53.

As shown in FIG. 9, a vertical hole 61 is formed inside the base portion 41 and the neck portion 43 as a drug flow path, and this vertical hole 61 is formed so as to gradually narrow in the range from the base portion 41 to the neck portion 43.

The cone section 45 has a square cross section and has edge sections 63, 63, 63, 63 along four orthogonal directions. The horizontal hole 51 already described is provided on the ridge of the cone section 45, i.e., on a line connecting a pair of opposing edge sections 63, 63 of the four edge sections 63, 63, 63, 63, and both ends serve as the drug solution discharge ports 53, 53. The lower parts of the edge sections 63, 63, 63, 63 are formed in an outwardly convex arc shape.

The length of the microneedle 5 is preferably 0.2 to 2.0 mm, more preferably 0.5 to 1.5 mm, in terms of puncture performance, moldability, drug permeability, etc. The needle thickness of the microneedle 5 (thickness of the neck portion 43) is preferably 0.05 to 0.3 mm, more preferably 0.1 to 0.25 mm, in terms of strength, skin damage, moldability, etc. The size of the vertical hole 61 and horizontal hole 51 is preferably 0.03 to 0.2 mm in diameter, more preferably 0.05 to 0.1 mm. The pitch of the microneedle 5 is preferably 0.5 to 3.0 mm.

The microneedle unit 1 having the above configuration is manufactured by a microneedle manufacturing apparatus 71 shown in Fig. 11. In the microneedle manufacturing apparatus 71, as shown in Fig. 11(a), a pair of slide cores 73, 73 are arranged so as to be movable toward and away from each other in a horizontal direction perpendicular to the axial direction of the microneedle 5, and a slide pin drive mechanism and other mechanical parts (not shown) are also provided. The slide cores 73, 73 are arranged in a size that allows the needle base 3 and the microneedle 5 to be integrally molded.
11 and 12, one slide core 73 is shown by a solid line, and the other slide core 73 is shown by a virtual line.

As shown in FIG. 11(a), a core nest 81 is disposed between the pair of slide cores 73, 73, and a plurality of (three in this embodiment) core pins 83, 83, 83 are provided at the upper end of the core nest 81 so that they can be projected and retracted. As shown in FIG. 13 and FIG. 14, the upper end of the core pin 83 forms an engagement recess 83a, and the cross-sectional shape of the engagement recess 83a is semicircular. The pair of slide cores 73, 73 are disposed so that they can be separated from each other with the core nest 81 in between. The core nest 81 is also disposed in a size that allows the needle hub 3 and the microneedle 5 to be integrally molded.

As shown in FIG. 11(a), the slide core 73 is provided with a cavity 73a for molding the microneedle 5 and a cavity 73b for molding the needle base 3. A slide pin 85 is disposed between the pair of slide cores 73, 73 on the core insert 81 so that it can be moved in and out by the slide pin drive mechanism. The slide cores 73, 73 are formed with recesses 73c, 73c into which the slide pin 85 fits. The slide pin 85 has a circular cross-sectional shape.

A microneedle manufacturing method using the microneedle manufacturing apparatus 71 will be described below.
11A, the pair of slide cores 73, 73 are separated from each other, and the three core pins 83, 83, 83 are retracted into the core insert 81. Next, a slide pin 85 appears between the pair of slide cores 73, 73 as indicated by the arrow a by the slide pin drive mechanism.

Next, as shown in FIG. 11(b), the pair of slide cores 73, 73 are brought close together as indicated by arrow b to clamp the slide pin 85 and surround the core insert 81 with a gap remaining. As a result, the slide pin 85 is held by the recesses 73c, 73c of the pair of slide cores 73, 73, ensuring its rigidity and preventing bending. Also, the core insert 81 is clamped by the cavities 73b, 73b of the pair of slide cores 73, 73 with a gap of a specified thickness remaining.

Next, as shown in FIG. 11(c), three core pins 83, 83, 83 emerge from the core insert 81 toward the top. The fitting recesses 83a, 83a, 83a at the tips of the emerged core pins 83, 83, 83 are fitted into the slide pin 85. This positions the core pins 83, 83, 83, and prevents the slide pin 85 from shifting or deforming due to pressure applied during resin filling, which will be described later. The same is true for the core pins 83, 83, 83, which come into contact with the slide pin 85, preventing them from shifting or deforming.

Next, as shown in FIG. 12(a), after the mold is completely closed, resin is injected from the molding machine. First, resin 87 flows into the gap between the cavity 73b and the core insert 81. Next, resin 87 flows toward the tip, and forms the vertical hole 61 by flowing into the gap between the core pins 83, 83, 83 and the cavity 73a. After that, resin flows into the gap between the slide pin 83 and the cavity 73a, forming the horizontal hole 51, and finally the resin reaches the tip and the injection process is completed.

Next, after a predetermined curing time (period) for cooling has elapsed, the core pins 83, 83, 83 are retracted into the uncored insert 81 as shown in FIG. 12(b).

Next, as shown in FIG. 12(c), the slide pin 85 is retracted into the slide pin drive mechanism as indicated by arrow c.

Next, as shown in FIG. 12(d), the pair of slide cores 73, 73 are separated as indicated by arrow d to remove the molded product, the microneedle unit 1 according to this embodiment.

The state of resin filling shown in FIG. 12(a) will be described in detail. FIG. 13 is an enlarged cross-sectional view showing the state of resin filling, and FIG. 14 is a further enlarged cross-sectional view showing part XIV of FIG. 13. The slide pin 85 is held by the recesses 73c, 73c of the pair of slide cores 73, 73, ensuring its rigidity. In this state, resin 87 is pressurized and filled with a predetermined molding pressure. At that time, the core pin 83 is pressed against the slide pin 85, so it can resist the molding pressure, and neither the core pin 83 nor the slide pin 85 are displaced or deformed. As a result, the occurrence of burrs at the contact portion between the slide pin 85 and the core pin 83 can be suppressed.

In this embodiment, the upper part of the core pin 83 is a fitting recess 83a with a semicircular cross section to match the outer diameter of the slide pin 85, but this is not limited to this, and other modifications are also possible, such as a V-shape, flat surfaces, or other shapes. It is also possible to increase adhesion by plating or coating the surface of the pin.

As described above, according to this embodiment, the following effects can be obtained.
First, the microneedle 5 having the vertical hole 61 as a drug solution flow path and the horizontal hole 51 connected thereto as a drug solution discharge port in a penetrating state can be easily manufactured by integral molding. This is because a pair of slide cores 73, 73 are arranged so as to be able to come into contact with and separate from each other, a core insert 81 having a retractable core pin 83 is arranged between them, and a slide pin 85 is further arranged so as to be able to retract in order to form the horizontal hole 51.
Furthermore, since the slide pin 85 is clamped between the recesses 73c, 73c of the pair of slide cores 73, 73, its rigidity is guaranteed and the slide pin 85 will not shift in position or deform due to the pressure applied when filling the resin 87, so that the horizontal hole 51 can be molded with high precision and the occurrence of burrs can be eliminated.
In particular, both sides immediately adjacent to the recess 73b forming the microneedle 5 are strongly supported at an extremely short distance like a double-supported beam, thereby further increasing the rigidity.
Furthermore, since the core pin 83 is brought into close contact with the slide pin 85, this also makes it possible to prevent the slide pin 85 from shifting in position or deforming, and the microneedle 5 can be molded with high precision.
In particular, the cross-sectional shape of the fitting recess 83a of the core pin 83 is semicircular, which matches the outer periphery of the circular cross-sectional shape of the slide pin 85, and therefore the above-mentioned effect is enhanced.
Furthermore, since the position of the core pin 83 itself is maintained, the core pin 83 does not shift position or deform during molding, and the microneedle 5 can be molded with high precision.
In particular, the core pin 83 has a fitting recess 83a having a semicircular cross section at its tip, and the fitting recess 83a matches the outer shape of the slide pin 85, so that the above-mentioned effect is even greater.
Moreover, the pair of slide cores 73, 73 are set to a size that allows the microneedle 5 and the needle base 3 to be integrally molded, and the core insert 81 is also set to a size that allows the microneedle 5 and the needle base 3 to be integrally molded, so that it is possible to easily mold the microneedle unit 1 in which the microneedle 5 and the needle base 3 are integrated. This eliminates the need to prepare a separate needle base 3 as a separate part.
Furthermore, because it is molded as a single piece, it is completely airtight compared to separate parts.
Furthermore, the microneedles 5 are not bonded but are integrally molded, and therefore have high mechanical strength.
Furthermore, in comparison with conventional bonding methods, airtightness of the drug flow path is perfectly guaranteed.
In addition, a pyramidal portion 45 having a quadrangular pyramid shape and four edge portions 63 are provided at the tip, so that the skin can be sharply cut and punctured.
Furthermore, since the lower portion of the edge portion 63 is rounded, the skin is not damaged when the needle is removed from the skin after puncturing.
Furthermore, since the cross-sectional shape of the horizontal hole 51 is circular, resistance during injection of the liquid medicine is small.
Further, a neck portion 43 is provided below the cone portion 45, and this neck portion 43 is in close contact with the skin when the needle is punctured, so that leakage of the injected medicinal liquid can be prevented.
In addition, since the base portion 41 is provided below the neck portion 43 and the space between them is in an arc shape, the mechanical strength of the microneedle 5 can be increased.
Furthermore, the base portion 41 tensions the skin when puncturing, making it easier to puncture and enabling the puncture depth to be constant.
Furthermore, since the vertical hole 61 is formed so as to be gradually narrowed from the bottom to the top, the drug solution can be efficiently injected.

Next, a second embodiment of the present invention will be described with reference to Figures 15 and 16. In the second embodiment, the R-shape of the lower part of the edge portion 63 of the pyramid portion 45 having a quadrangular pyramid shape is eliminated.
The other configurations are the same as those of the first embodiment, and the same parts in the drawings are given the same reference numerals and their explanation is omitted.
Therefore, the same effects as those of the first embodiment can be achieved.

Next, a third embodiment of the present invention will be described with reference to Figures 17 and 18. In the third embodiment, the cross-sectional shape of the neck portion 43 in the configuration of the second embodiment is changed to a square.
The other configurations are the same as those of the second embodiment, and the same parts in the drawings are given the same reference numerals and their explanation is omitted.
Therefore, the same effects as those of the second embodiment can be achieved.

Next, a fourth embodiment of the present invention will be described with reference to Figures 19 and 20. In the fourth embodiment, the tip portion is a cone portion 91, and the cross-sectional shape of the neck portion 43 is a circle.
The other configurations are the same as those of the first embodiment, and the same parts in the drawings are given the same reference numerals and their explanation is omitted.
Therefore, the same effects as those of the first embodiment can be achieved.

Next, a fifth embodiment of the present invention will be described with reference to Figures 21 and 22. In the case of the fifth embodiment, a cone portion 93 is provided instead of the tapered portion and neck portion in the first embodiment.
The other configurations are the same as those of the first embodiment, and the same parts in the drawings are given the same reference numerals and their explanation is omitted.
Therefore, the same effects as those of the first embodiment can be achieved.
In addition, the tip is thinner and sharper, making it easier to pierce the skin and reducing damage to the skin.

Next, a sixth embodiment of the present invention will be described with reference to Figures 23 and 24. In the sixth embodiment, each side of the quadrangular pyramid portion 45 in the first embodiment is formed concave, and each side of the neck portion 43 is also formed concave.
The other configurations are the same as those of the first embodiment, and the same parts in the drawings are given the same reference numerals and their explanation is omitted.
Therefore, the same effects as those of the first embodiment can be achieved.

Next, the seventh embodiment of the present invention will be described with reference to FIG. 25. In the first to sixth embodiments, the horizontal holes 51 are provided in a straight line for the three microneedles 5, 5, 5, and are molded using one slide pin 85. In contrast, in the seventh embodiment, as shown in FIG. 25, the horizontal holes 51 are provided for the three microneedles 5, 5, 5, and are oriented in a direction parallel to each other. For this reason, one slide pin 85 and one core pin 83 are arranged for each of the three microneedles 5, 5, 5 (a total of three slide pins 85 and three core pins 83), and the same operation as in the first embodiment is performed for each of them.
Other configurations are the same as those in the first to sixth embodiments, and the same parts in the drawings are given the same reference numerals and their explanation is omitted.

Therefore, the same effects can be achieved as in the first to sixth embodiments.

Next, a microneedle unit 1 actually manufactured according to the first embodiment is shown in Figs.
FIG. 26( a ) is an electron microscope photograph showing a portion of three microneedles 5 , 5 , 5 of an actually produced microneedle unit 1 , and FIG. 26( b ) is an optical microscope photograph showing one microneedle 5 .
FIG. 27( a ) is a photograph showing the manufactured microneedle unit 1 attached to a Luer lock syringe 101 , and FIG. 27( b ) is a microscope photograph showing water 103 being uniformly discharged from the lateral hole 51 .
In this example, the material was polyglycolic acid (PGA), and the molding conditions were: mold temperature 120° C., resin temperature 240° C., resin pressure 110 MPa, mold clamping force 10 t, and approximately 40 s cycle.
It was possible to integrally mold a microneedle unit 1 having a clean through-hole 51 of φ80 μm. The tip of the microneedle 5 and the edge of the quadrangular pyramid are formed sharply. In addition, the needle pitch is 1.3 mm, the needle length (effective puncture length) is 0.65 mm, and the needle width is 0.22 mm.

Next, an eighth embodiment of the present invention will be described with reference to Figures 28 to 37. In the first embodiment, an example of manufacturing a microneedle unit 1 in which a plurality of microneedles 5 (three in the first embodiment) are arranged in a row will be described, but in this eighth embodiment, an example of manufacturing a microneedle unit 1' in which the microneedles 5 are arranged in multiple rows will be described.

In the first embodiment, a pair of slide cores 73, 73 are arranged in the microneedle manufacturing apparatus 71 so that they can be brought into contact with each other in a direction perpendicular to the axial direction of the microneedle (horizontal direction in the first embodiment), but in the eighth embodiment, a cabinet nest upper plate 103 and a cabinet nest lower plate 105, which correspond to a pair of slide cores, are arranged in the microneedle manufacturing apparatus 101 so that they can be brought into contact with each other in the axial direction of the microneedle (vertical direction in this embodiment), and a core nest 107 is arranged below the cabinet nest lower plate 105 so that it can be raised and lowered in the vertical direction. This will be described in detail below.

The cabinet insert upper plate 103 is formed with a plurality of recesses 109 for forming the tips of the microneedles (in this embodiment, 4 recesses x 4 rows = 16 recesses), and also with a plurality of recesses 111 for slide pins (in this embodiment, 4 recesses). The cross-sectional shape of the recesses 111 for slide pins is a downward-facing semicircle.

The cavity insert lower plate 105 has a cavity 113 formed therein, and also has a plurality of (four in this embodiment) slide pin recesses 115 formed therein. The cavity 113 is formed of a base cavity 113a corresponding to the base 3' of the microneedle unit 1', and 16 microneedle cavities 113b corresponding to a total of 16 microneedles 5 (four in four rows). The cross-sectional shape of the slide pin recesses 115 is an upward-facing semicircle.

As shown in FIG. 30, four slide pins 121 are arranged so that they can be extended and retracted horizontally, and the four slide pins 121 are clamped by the slide pin recesses 111 and 115. The slide pins 121 are driven by a slide pin drive device 123.

The core insert 107 has a protruding portion 131 for forming the base 3' of the microneedle 1, and this protruding portion 131 has 16 through holes 133 drilled therein, corresponding to a total of 16 microneedles 5, arranged in 4 rows x 4 columns. As shown in FIG. 32, a core pin 141 is disposed so as to pass through each of the 16 through holes 133 and be capable of ascending and descending.

The manufacturing steps will be described below in order.
FIG. 28 shows the state before operation where the slide pin 121, the core pin 131, and the resin are not inserted.
Next, as shown in FIG. 29, the cabinet insert upper plate 103 is raised in order to insert the slide pin 121.
Next, as shown in FIG. 30, the slide pin 121 is inserted between the cabinet insert upper plate 103 and the cabinet insert lower plate 105.
Next, as shown in FIG. 31 , the cabinet nest upper plate 103 is lowered so that the slide pin 121 is sandwiched between the cabinet nest upper plate 103 and the cabinet nest lower plate 105 .

Next, as shown in FIG. 32, the core pin 131 is raised and the fitting recess at the tip of the core pin 123 is fitted into the slide pin 121. This positions the slide pin 121 and prevents it from shifting or deforming due to pressure applied during resin filling.

Next, as shown in FIG. 33 , resin 151 is injected to fill the cavity 109 of the cavity insert upper plate 103, between the cavity 113 of the cavity insert lower plate 105 and the protrusion 131 of the core insert 107, and between the cavity 113 of the cavity insert lower plate 105 and the core pin 141.
Next, as shown in FIG. 34, after a predetermined curing period has elapsed, the core pin 141 is retracted.
Next, as shown in FIG. 35, the slide pin 121 is retracted.
Next, as shown in FIG. 36, the core insert 107 is lowered to expose and remove the molded microneedle unit 1'.

The microneedle unit 1' has a configuration as shown in Figure 37.

Therefore, the same effects as those in the first to seventh embodiments can be achieved.
Furthermore, by using such a multi-row microneedle unit 1', it becomes possible to inject a drug or collect interstitial fluid over a wider area.

Next, a ninth embodiment of the present invention will be described with reference to Figures 38 and 39. In this case, the base 3 of the microneedle unit 1' is circular in plan view, and multiple microneedles 5 (10 in this embodiment) are arranged circumferentially. The horizontal holes 51 of each microneedle 5 are oriented in the same direction, and as shown in Figure 39, they are formed using five slide pins 121.

Next, a tenth embodiment of the present invention will be described with reference to Figures 40 and 41. In this case, the base 3' of the microneedle unit 1' is circular in plan view, and multiple microneedles 5 (six in this embodiment) are arranged in pairs along the radial direction at 120° positions. The horizontal holes 51 of each microneedle 5 are oriented in the radial direction, and are formed using three slide pins 121, as shown in Figure 41.

The present invention is not limited to the first to tenth embodiments.
First, in the case of the first to seventh embodiments, an example is given in which the entire part from the microneedle to the needle base is molded as a single unit, and in the case of the eighth to tenth embodiments, an example is given in which the microneedle and the base are molded as a single unit, but various other cases are also possible.
In addition, in the first to seventh embodiments, an example has been described in which three microneedles are molded in a row, but the number of microneedles is not limited to three, and may be one, two, four or more.
In addition, in the eighth to tenth embodiments, the microneedles are arranged in multiple rows, and a square array, a circular array, and a radial array have been given as examples, but the present invention is not limited to these, and other arrangements such as a staggered arrangement are also contemplated.
Furthermore, the direction of the slide pin does not necessarily have to be one direction, but it may be inserted from a plurality of directions and the direction of the resulting horizontal hole may be adjusted.
In the first to seventh embodiments, the microneedle is disposed in the center in the left-right direction in Fig. 5, but it may be offset to either the left or right side, which makes it easier to perform oblique puncture.
Furthermore, when multiple microneedles are molded, it is also possible to make the lengths of the microneedles non-uniform.
In addition, in the first to tenth embodiments, the cross-sectional shape of the horizontal hole is circular, but this is not limited to this and may be rectangular or another shape.
The position of the horizontal hole may be, for example, in the neck portion 43 in FIG.
In the first embodiment, the horizontal holes are provided on the ridges of the quadrangular pyramid, but this is not limiting, and a configuration in which the horizontal holes are provided on a plane between the ridges is also possible.
Additionally, the configurations shown in the drawings are merely examples.

The present invention relates to a microneedle manufacturing method, a microneedle, and a microneedle unit, and in particular to a method that is devised to easily manufacture microneedles that have a penetrating horizontal hole that serves as a drug solution discharge port, and is suitable for manufacturing microneedles for vaccine injections, for example.

REFERENCE SIGNS LIST 1 Microneedle unit 1' Microneedle unit 3 Needle base 3' Base 5 Microneedle 41 Base portion 43 Neck portion 45 Taper portion 51 Horizontal hole 53 Drug solution discharge port 61 Vertical hole 73 Slide core 73a Cavity 73b Cavity 73c Recess 81 Core insert 83 Core pin 85 Slide pin

Claims (18)

A microneedle manufacturing method for manufacturing a microneedle having a vertical hole as a drug solution flow path and a horizontal hole as a drug solution discharge port connected thereto in a penetrating state,
A slide pin for forming the horizontal hole is caused to appear in the mold;
A core pin for forming the vertical hole is brought into contact with the emerged slide pin,
In this state, the resin is filled into the molding die,
After the curing period has elapsed, the core pin is retracted and the slide pin is pulled out.
A method for manufacturing a microneedle, comprising the steps of integrally molding a microneedle having a vertical hole as a drug solution flow path and a horizontal hole connected thereto as a drug solution discharge port, the vertical hole penetrating the vertical hole. The method for producing a microneedle according to claim 1,
The mold is composed of a pair of cores arranged so as to be movable together,
The slide pin is caused to appear between the pair of cores while the pair of cores is separated from each other,
The pair of cores are brought close to each other to sandwich the slide pin therebetween,
The core pin is caused to emerge and come into contact with the slide pin,
In this state, resin is filled between the pair of cores,
After the curing period has elapsed, the core pin is retracted and the slide pin is pulled out.
A method for manufacturing a microneedle, comprising the steps of integrally molding a microneedle having a vertical hole as a drug solution flow path and a horizontal hole connected thereto as a drug solution discharge port, the vertical hole penetrating the vertical hole. The method for producing a microneedle according to claim 2,
The method for manufacturing a microneedle, characterized in that the pair of cores are a pair of sliding cores arranged so as to be movable together in a direction perpendicular to the axial direction of the microneedle, and the microneedle is formed from this pair of sliding cores. The method for producing a microneedle according to claim 3,
A core insert is disposed between the pair of slide cores,
A method for manufacturing a microneedle, characterized in that the core pin is made to protrude and retract by penetrating through the core insert. The method for producing a microneedle according to claim 4,
A microneedle manufacturing method, characterized in that each of the pair of slide cores has a recess for accommodating the slide pin and a cavity for accommodating the core insert with the core pin exposed. The method for producing a microneedle according to claim 5,
The pair of slide cores are set to a size that can mold the range from the microneedle to the needle base,
The core insert is also set to a size that can mold the area from the microneedle to the needle base.
A method for manufacturing a microneedle, characterized in that the range from the microneedle to the needle base is integrally molded as a microneedle unit using the pair of slide cores and core inserts. The method for manufacturing a microneedle according to claim 4,
The core insert has a plurality of core pins arranged in a row,
the slide core is provided with a cavity in which the core insert is housed with the plurality of core pins exposed,
A method for manufacturing microneedles, comprising arranging a plurality of microneedles in a line and integrally molding them using the pair of slide cores and core inserts. The method for producing a microneedle according to claim 7,
A method for manufacturing a microneedle, characterized in that the lateral holes of the plurality of microneedles are formed in one go by a single slide pin. The method for producing a microneedle according to claim 2,
The method for manufacturing a microneedle is characterized in that the pair of cores are a cabinet nest upper plate and a cabinet nest lower plate that are arranged so as to be able to be separated from each other in the axial direction of the microneedle, and the microneedle is formed from these cabinet nest upper plate and cabinet nest lower plate. The method for producing a microneedle according to claim 9,
A method for manufacturing a microneedle, characterized in that a core insert is arranged below the cabinet insert lower plate so as to be movable in the axial direction of the microneedle. A microneedle that is molded as a single unit and has a vertical hole that serves as a drug flow path and a horizontal hole that connects to the vertical hole and serves as a drug discharge port. The microneedle according to claim 11,
A microneedle characterized in that the cross-sectional shape of the horizontal hole is circular. The microneedle according to claim 11,
The nozzle is composed of a base portion, a neck portion provided at a tip side of the base portion, and a cone portion provided at a tip side of the neck portion,
The microneedle is characterized in that the horizontal hole is provided in a lower part of the weight portion. The microneedle according to claim 13,
The pyramidal portion is a quadrangular pyramidal portion,
The microneedle is characterized in that the horizontal hole is provided penetrating on a line connecting a pair of edges of the quadrangular pyramid portion. The microneedle according to claim 14,
The microneedle is characterized in that the end of the edge of the quadrangular pyramid portion on the neck portion side is formed into an outwardly convex arc shape. The microneedle according to claim 13,
The microneedle is characterized in that the lower part of the base part is formed with a larger diameter than the neck part, and the diameter gradually decreases from there toward the neck part. The microneedle according to claim 13,
The microneedle is characterized in that the vertical hole is formed from the base portion to the neck portion and is gradually narrowed from the base portion to the neck portion. A microneedle according to any one of claims 11 to 17,
a needle base that is integrally molded on a base end side of the microneedle and has a tip end of a cylindrical body of a syringe connected to the base end side;
A microneedle unit comprising:

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