JP2016007702A - Method for manufacturing microneedle array, and molding die for injection molding used therefor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for manufacturing a microneedle array capable of producing a microneedle array having performance usable in place of an injection syringe, in a large scale at low cost, and a molding die for injection molding used therefor.SOLUTION: In a method for manufacturing a microneedle array 10, the microneedle array 10 having a plurality of tip-pointed resin-made microneedles 12 is manufactured using a molding die 14 for injection molding formed with a plurality of recesses 15 corresponding to forms of the microneedles 12 by filling the recesses 15 with resin while evacuating gas in the recesses 15 from the recesses 15. The molding die 14 for injection molding for manufacturing the microneedle array 10 has the recesses 15 which correspond to forms of the microneedles 12 and which are filled with resin and gas-evacuating means 16 for evacuating gas in the recesses 15 to the outside from the inside of the recesses 15.

Description

  The present invention relates to, for example, a method for producing a microneedle array that can be administered into the body in place of a conventionally used syringe, and an injection mold used therefor.

As the aging society progresses in the future, the proportion of medical care will increase in the social system. For this reason, for example, there is a need to reduce the frequency of outpatients such as elderly people and busy people, and to perform home medication based on doctors' prescriptions for doctors and remote hospitals where there is a shortage of hospitals such as remote or depopulated areas. large.
In the medical practice, in addition to surgical treatments for affected areas such as trauma, in-medicine with a syringe accounts for a large proportion of medication. This syringe is usually administered by a qualified person such as a doctor or nurse at a hospital, but some patients are allowed to do it at home, such as insulin administration for diabetes. There are also things.

The merit of administration by a syringe is that it can be administered directly to the subcutaneous or blood vessels, but the disadvantage is that the pain during injection and the wound remains or swells as the number of doses increases.
Therefore, it is considered to use a resin-made microneedle array having a plurality of microneedles (microneedles) on a flat plate instead of a syringe. The use of this microneedle array is painless because the microneedles have a length that can reach the depth of the subcutaneous painless point, and it is only necessary to apply the patch to the epidermis so that the patient himself can The ability to do medication at home greatly reduces the burden on the patient.

In this way, microneedle arrays have various advantages and will have great needs in society in the future, so if they are put to practical use, it is considered that they can greatly contribute to an aging society in the future. .
The above-described microneedle array can be manufactured by injection molding using, for example, a mold disclosed in Patent Document 1, specifically, a mold in which a recess corresponding to the shape of the microneedle is formed. Thereby, the microneedle array can be mass-produced at low cost.

JP 2012-217653 A

However, when the microneedle array is manufactured with the above-described mold, the gas in the recesses cannot be exhausted to the outside when the resin is filled in the recesses, and a gas pool is generated in the recesses. There was a problem that the resin did not spread sufficiently and the tip of the manufactured microneedle was not sharp.
For this reason, the microneedle array manufactured by the conventional method did not have sufficient performance for use as a substitute for a syringe.

  The present invention has been made in view of such circumstances, and a method of manufacturing a microneedle array capable of mass-producing a microneedle array having performance that can be used in place of a syringe at low cost, and injection molding used therefor The purpose is to provide a metal mold.

According to a first aspect of the present invention, there is provided a microneedle array manufacturing method comprising: a microneedle array having a plurality of resin-made microneedles having a sharp tip; an injection having a plurality of recesses corresponding to the shape of the microneedle; In a method of manufacturing using a molding die,
The resin is filled into the recess while exhausting the gas in the recess from the recess.

  In the method for manufacturing a microneedle array according to the first invention, it is preferable that the gas in the recess is exhausted from the bottom of the recess where the tip of the microneedle is formed.

  In the method of manufacturing the microneedle array according to the first invention, it is preferable to forcibly exhaust the gas in the recess.

An injection mold according to the second invention that meets the above-mentioned object is an injection mold for manufacturing a microneedle array having a plurality of resin-made microneedles with a sharp tip.
Corresponding to the shape of the microneedle, it has a plurality of recesses in which resin is filled, and gas exhaust means for letting gas in the recesses escape from the recesses to the outside.

  In the injection mold according to the second invention, the gas exhaust means has a gas escape hole communicating with the bottom of the recess where the tip of the microneedle is formed, and the recess of the gas escape hole and It is preferable that the inner width of the communication portion is 100 μm or less.

  In the injection mold according to the second invention, it is preferable that the gas exhaust means has a function of forcibly exhausting the gas in the recess.

The manufacturing method of the microneedle array according to the present invention and the injection mold used for the method are as follows. Resin filling into the recess corresponding to the shape of the microneedle is exhausted (released) from the recess. Therefore, the occurrence of gas accumulation in the recess can be suppressed and further prevented. Thereby, since resin can be spread over every corner in a recessed part, the front-end | tip of the microneedle produced by injection molding can be sharpened.
Therefore, a microneedle array having performance that can be used instead of a syringe can be mass-produced at low cost.

  In particular, when the gas in the recess is forcibly exhausted, the gas in the recess can be reliably exhausted, so that a higher quality microneedle array can be provided.

It is a partial expanded explanatory view of the injection mold used for the manufacturing method of the microneedle array which concerns on one embodiment of this invention. It is a perspective view of the microneedle array manufactured with the same injection mold. It is a partial expansion explanatory view of the injection mold concerning a modification.

Next, embodiments of the present invention will be described with reference to the accompanying drawings for understanding of the present invention.
First, a microneedle array 10 obtained by a method of manufacturing a microneedle array according to an embodiment of the present invention will be described with reference to FIGS. The microneedle array 10 is a device for medical administration (medical device) instead of a conventionally used syringe. However, the microneedle array 10 is not limited to this, and the cosmetic liquid to the skin and scalp is not limited to this. It can also be used for administration.

The microneedle array 10 is made of resin, and includes a flat plate 11 and a plurality of microneedles (also referred to as needles or microneedles) 12 with a sharp tip disposed on the flat plate 11. Note that the entire microneedle array is not necessarily made of resin, and at least the microneedles need only be made of resin. Moreover, a plating layer can be formed on the surface of the microneedle as necessary.
Here, as the resin, for example, a biodegradable plastic (biodegradable resin) or a thermoplastic resin can be used.

Biodegradable plastics are plastics that are decomposed by microorganisms, and examples include polylactic acid, polycaprolactone, polyhydroxyalkanoate, polyglycolic acid, modified polyvinyl alcohol, casein, and modified starch, with polylactic acid being particularly preferred. .
This polylactic acid is made from corn, and is characterized by being decomposed into carbon dioxide and oxygen in the human body and in the natural environment. For this reason, if the microneedle is made of polylactic acid, even if the microneedle is broken in the body, it is decomposed and absorbed in the body, which is safe for the human body.

  Examples of the thermoplastic resin include polycarbonate resin, polyethylene resin, polypropylene resin, AS resin, ABS resin, methacrylic acid resin, polyvinyl chloride resin, polyacetal resin, polyamide resin, modified polyphenylene ether resin, polybutylene terephthalate resin, Polyethylene terephthalate resin or the like can be used, but polycarbonate resin is preferred.

The shape of the flat plate 11 is rectangular (may be square) in plan view, but is not particularly limited, and may be, for example, a circle, an ellipse, or a polygon (regular polygon).
The shape of the microneedle 12 is a conical shape, but may be, for example, an elliptical cone shape or a polygonal pyramid shape (triangular pyramid shape, quadrangular pyramid shape, etc.), and the size thereof is, for example, the base end diameter on the flat plate 11 side. The (base end width) is about 0.1 to 0.5 mm, the height is about 0.2 to 2.0 mm, and the tip diameter is about 0.1 mm or less. Here, the base diameter is considered in consideration of difficulty in bending (suppressing and further preventing damage), and the height is considered in consideration of the length that can be administered to the dermis by breaking the epidermis of the skin. The tip diameter is set in consideration of the fact that pain is not felt during use (makes it difficult to feel).

For example, about 10 to 2000 microneedles 12 (preferably, the lower limit is 50 and the upper limit is 1000) are arranged upright in the range of about 1 cm ^{2 of the} flat plate 11. Therefore, the size of the flat plate 11 only needs to have an area where the microneedles 12 can be arranged.
Here, the arrangement region on the flat plate 11 of the microneedle group 13 composed of a plurality of microneedles 12 is rectangular (may be square) in plan view, but is, for example, circular, elliptical, or polygonal However, the long side is rectangular if it is a rectangle, the diameter is circular if it is a circle, the long axis is elliptical, and if it is a polygon (regular polygon), one side is about 5 to 50 mm, for example. . In addition, although each microneedle 12 is arrange | positioned on the flat plate 11 by plane view, it can also arrange | position in zigzag form or at random, for example.

Since the microneedle is a part that administers to the human body, if necessary, grooves and depressions can be formed on the surface side of the microneedle, and further, a hole (penetration) that opens toward the front side of the microneedle. A hole may be formed).
The shape, size and number of the microneedles 12 described above, and the conditions of the arrangement and the range of the arrangement of the microneedles 12 on the flat plate 11 depend on the intended use of the microneedle array (for example, the dosage required for the human body). ) Is not particularly limited, and various modifications can be made.

Next, an injection mold (hereinafter simply referred to as a mold) 14 according to an embodiment of the present invention will be described with reference to FIGS. 1 and 2.
The mold 14 is made of metal used for injection molding.
Here, when manufacturing the mold 14, when a recess (needle hole corresponding to the shape of the microneedle) is directly carved in the mold member, the metal constituting the mold member may be, for example, carbon steel, stainless steel, Heat-resistant steel, superalloy, alloy tool steel, tool steel, alloy steel, high-speed tool steel, cemented carbide, copper alloy, aluminum alloy, zinc alloy, silicon, etc., for example, coating treatment with fluorine, titanium, etc. Although general-purpose metals can be used, it is preferable to use hard carbon steel or the like in view of the durability (life) of the mold.
Further, when the mold 14 is manufactured, a convex portion (master mold) having a microneedle shape is once formed, and this is transferred by electroforming to form a main mold (concave mold). As the metal, a metal that can be electroformed, such as Ni, Co, or Cu, or an alloy of these metals can be used.

The mold 14 corresponds to the contour shape of the surface of the microneedle 12, and a plurality of recesses 15 in which a molten resin (hereinafter also referred to as a molten resin) is filled, and the gas in the recesses 15 from the recesses 15. And gas exhaust means 16 for escaping to the outside.
Here, the recesses 15 are formed in the mold 14 in the same number as the number of microneedles 12 to be formed. The concave portion 15 is configured such that the bottom 17 position forms the tip of the microneedle 12. Therefore, the upper side of the recess 15, that is, the side forming the base of the microneedle 12 (PL surface side) is open.
The gas exhaust means 16 includes a gas escape hole 18 that communicates with the bottom 17 of the recess 15.

The gas escape hole 18 is a through-hole having a circular cross section formed such that its axial center is located on the axial center of the recess 15, and a small diameter portion 19 serving as a communication portion with the recess 15, and the small diameter portion 19. And a large diameter portion 20 having an inner diameter larger than that of the small diameter portion 19. Note that the upper end (one end) of the small diameter portion 19 communicates with the bottom 17 of the recess 15, and the lower end (other end) of the large diameter portion 20 opens to the outside (outside the mold 14).
Here, the inner diameter (inner width) of the small diameter portion 19 is small, for example, preferably 100 μm (0.1 mm) or less. The inner diameter of the microneedle 12 formed is suppressed while preventing or preventing the resin from flowing into the gas escape hole 18 when the recess 15 is filled with molten resin (injection molding is performed). It can be set by sharpening the tip or considering the physical properties of the resin used.

For the reasons described above, the smaller the inner diameter of the small-diameter portion 19, the more desirable. Therefore, it is preferably 50 μm or less, more preferably 30 μm or less, and particularly preferably 10 μm or less (several μm).
On the other hand, the lower limit value of the inner diameter of the small-diameter portion 19 is not particularly limited for the reason described above, but is considered to be about 1 μm if judged from the limit of technical processing.
Moreover, since the large diameter part 20 is a part which made the internal diameter larger than the small diameter part 19 for the reason on a process, if the whole gas escape hole can be formed in a small diameter part, it is not necessary to provide.
As described above, when the gas escape hole 18 is constituted by the small diameter portion 19 and the large diameter portion 20, the length (depth) of the small diameter portion 19 in the axial direction is prevented in order to prevent damage to the bottom 17 of the concave portion 15. ) Is preferably 1.5 times (more preferably 2.5 times) the inner diameter of the small-diameter portion 19 or more.

With the above-described configuration, the gas escape hole 18 (that is, the gas exhaust means 16) is used for the gas (including the gas in the molten resin) in the recess 15 during injection molding (when the molten resin is filled in the recess 15). The gas in the recess 15 can be forcibly exhausted by, for example, an injection mold (hereinafter also simply referred to as a mold) 21 shown in FIG. The mold 21 is different from the above-described mold 14 only in part of the configuration of the gas exhaust means, and therefore the same components are denoted by the same reference numerals and detailed description thereof is omitted.
The mold 21 has a plurality of recesses 15 corresponding to the contour shape of the surface of the microneedle 12, and a gas exhaust means 22 for escaping the gas in the recesses 15 from the recesses 15 to the outside.

The gas exhaust means 22 includes a gas escape hole 23 communicating with the bottom 17 of the recess 15 and an ejector portion 24 (forcing the gas in the recess 15 to the outside (outside the mold 21) through the gas escape hole 23 ( Ejector function).
The gas escape hole 23 communicates the aforementioned small diameter portion 19, the bottomed large diameter portion 25 having an inner diameter larger than that of the small diameter portion 19, and the adjacent large diameter portion 25, and the downstream end is external (mold). 21) and an exhaust hole 26 opened to the outside.
As a result, by constantly supplying air from an air source (not shown) to the ejector portion 24, the gas in the recess 15 is released from the gas escape holes 23 (small diameter portion 19, large diameter portion 25, and exhaust hole 26). The air can be forcibly exhausted (gas vented) through the.

For example, a strip or engraved mold can be applied to the mold 14 or the mold 21 described above.
Here, the strip type is a divided type in which a plurality of thin plates are laminated in the thickness direction, and a gold plate in which the concave portion 15 corresponding to the shape of the microneedle 12 and the gas escape holes 18 and 23 are formed by the thin plates bonded together. It is a type. The engraving mold is a mold in which the above-described recess 15 and gas escape holes 18 and 23 are formed on a single thick plate.
The concave portion 15 and the gas escape holes 18 and 23 are formed by a method used when producing an injection mold, for example, 1) a concave portion (a needle corresponding to the shape of the microneedle) directly on the mold member. A method of carving holes), 2) a method of once forming a convex mold (master mold) having the shape of a microneedle, and transferring this by electroforming to form a main mold (concave mold).
Here, for the method 1), for example, engraving using a micro drill, laser processing, electric discharge processing, or the like can be used.
The method 2) can be used when, for example, the shape of the microneedle is complicated and the method 1) cannot be applied. In addition, a convex type can be manufactured with a sintered material using a 3D printer, for example.

Then, the manufacturing method of the microneedle array which concerns on one embodiment of this invention is demonstrated, referring FIG. 1, FIG.
First, an injection mold 14 is prepared.
This mold 14 can be manufactured by the method described above. The mold is preferably made of a hard material in consideration of durability (number of shots). For example, when the fluidity of the resin constituting the microneedle array 10 is improved, injection molding is performed. Since the pressure can be reduced, it can be made of a material other than a hard material (for example, a material having good thermal conductivity).

Next, injection molding is performed using the mold 14.
Here, molten resin is filled in each recess 15 of the mold 14. At this time, the gas in the molten resin or the gas in the recess 15 passes through the gas release holes 18 formed in the bottom 17 of the recess 15. Then, the air is exhausted from the inside of the recess 15 to the outside. In particular, when the mold 21 shown in FIG. 3 is used, when the molten resin is filled in the recess 15, the gas in the recess 15 is supplied via the gas escape hole 23 by always supplying air to the ejector portion 24. Can be forced to the outside.
Thereby, since molten resin can be spread to every corner in the recessed part 15, the front-end | tip of the produced microneedle 12 can be sharpened.

  In performing the above-described injection molding, the material of the microneedle 12 (type of resin), the number, shape, dimensions, etc. are taken into consideration, the material of the mold to be used, and the injection molding conditions (for example, , Injection molding pressure and temperature). Further, as described above, when forming a groove, a recess, a hole opened toward the front side, or the like in the microneedle, a mold having a plurality of recesses corresponding to this shape is used.

After injection molding by the method described above, the microneedle array 10 as a molded product is taken out from the mold 14.
The microneedle array 10 can be used as a product by further applying a drug according to the purpose to the surface of the microneedle 12.

  As described above, by using the microneedle array manufacturing method of the present invention and the injection mold used therefor, a plurality of one part (mold) is incorporated into one mold, and hot By applying a device such as a runner, more efficient mass production becomes possible, and the microneedle array 10 having performance that can be used instead of a syringe can be mass-produced at low cost.

As described above, the present invention has been described with reference to the embodiment. However, the present invention is not limited to the configuration described in the above embodiment, and the matters described in the scope of claims. Other embodiments and modifications conceivable within the scope are also included. For example, the right scope of the present invention also includes the case where the manufacturing method of the microneedle array of the present invention and the injection mold used for the same are configured by combining some or all of the above-described embodiments and modifications. It is.
For example, in the above-described embodiment, the case where the gas escape hole is formed so that its axis is located on the axis of the recess has been described. However, gas accumulation at the tip of the recess is suppressed and further prevented. If possible, a gas escape hole can be formed at another position of the concave portion (for example, a ridge line portion on the front end side).

In the above embodiment, the inner diameter of the small diameter portion of the gas escape hole communicating with the bottom of the concave portion is the same in the axial direction. However, depending on the processing method, the diameter may be reduced toward the bottom of the concave portion. May be. Note that the shape of the small diameter portion is not limited to a circular cross section as long as it can communicate with the bottom of the recess. In this case, it is preferable that the inner width of the communication portion (the bottom of the recess) is 100 μm or less.
The configuration for forcibly exhausting the gas in the recess is not limited to the ejector section, and for example, a suction pump or the like (suction means) can be used.
Further, the above-described injection mold can be used as an insert incorporated in an existing mold.

10: Microneedle array, 11: Flat plate, 12: Microneedle, 13: Microneedle group, 14: Mold for injection molding, 15: Recess, 16: Gas exhaust means, 17: Bottom, 18: Gas escape hole, 19 : Small diameter part, 20: Large diameter part, 21: Injection mold, 22: Gas exhaust means, 23: Gas escape hole, 24: Ejector part, 25: Large diameter part, 26: Exhaust hole

Claims (6)

In a method for manufacturing a microneedle array having a plurality of resin-made microneedles with a sharp tip using an injection mold having a plurality of recesses corresponding to the shape of the microneedle,
A method of manufacturing a microneedle array, wherein filling of the resin into the recess is performed while exhausting the gas in the recess from the recess.   2. The method of manufacturing a microneedle array according to claim 1, wherein the gas in the recess is exhausted from the bottom of the recess where the tip of the microneedle is formed.   3. The method of manufacturing a microneedle array according to claim 1, wherein the gas in the recess is forcibly exhausted. In an injection mold for producing a microneedle array having a plurality of resin-made microneedles with sharp tips,
An injection mold characterized by having a plurality of recesses corresponding to the shape of the microneedles and filled with resin, and gas exhaust means for escaping the gas in the recesses from the recesses to the outside.   5. The injection mold according to claim 4, wherein the gas exhaust means has a gas escape hole communicating with a bottom of the recess in which a tip of the microneedle is formed, and the gas escape hole is connected to the recess. An injection mold characterized in that the inner width of the communicating portion is 100 μm or less.   The injection mold according to claim 4 or 5, wherein the gas exhaust means has a function of forcibly exhausting the gas in the recess.

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