KR101694314B1 - Manufacturing method of multi layer micro needle - Google Patents

Abstract

The present invention provides a method for producing a multilayer micro-needle. The method comprises the steps of: (a) preparing an intaglio-shaped mold corresponding to a micro-needle to be produced; (b) filling the mold in a chamber, and depressurizing the inside of the chamber; (c) coating a micro-needle first raw material on the mold in the depressurized chamber; (d) hardening the micro-needle first raw material fed in the mold; (e) producing a needle groove on the top surface of the hardened first micro-needle first raw material; (f) depressurizing the inside of the chamber, and coating a micro-needle second raw material on the top surface of the micro-needle first raw material having the needle groove formed thereon in the depressurized chamber; and (g) hardening the micro-needle second raw material fed in the top surface of the micro-needle first raw material.

Description

TECHNICAL FIELD [0001] The present invention relates to a method for manufacturing a microneedle needle,

The present invention relates to a microneedle manufacturing method, and more particularly, to a microneedle microneedle manufacturing method for forming a microneedle shape in a multilayered manner.

Generally, a drug delivery system (DDS) is a series of techniques for controlling the delivery of a substance having pharmacological activity to cells, tissues, organs and organs in order to exhibit optimal effects using various physicochemical techniques The most common drug delivery system for ingesting oral medications is the transdermal drug delivery system that can be applied to localized areas. The importance of effective and safe administration of medicinal substances such as drugs It has long been recognized.

In addition, although a method of injecting a liquid medicine into a human body using a syringe is a method used for a long period of time, it has a problem of accompanied pain and temporary injection of a drug. Therefore, in order to improve the disadvantage of such a syringe, a transcutaneous penetration needle having a micro size much smaller than the needle of a syringe is manufactured and utilized.

Such microneedles are used in many fields such as injecting medicines for skin cosmetics or treatment into skin tissues, or as a device for extracting body fluids such as blood from the inside of skin, and for treating skin diseases or preventing diseases Methods for delivering drugs using these micro needles include coating the drug on the needle surface and mixing the drug and needle materials to prepare the micro needle.

Except for materials that do not dissolve in metal or human body in particular, the needles used in many parts are polymers. When the drug is delivered using the microneedle made of such a polymer, the drug is coated on the needle or the drug is mixed with the polymer to make the micro needle and deliver the drug to the body.

A conventional micro needle manufacturing method is disclosed in Korean Patent No. 10-0793615 entitled " Biodegradable Solid Micro Needle and Method for Manufacturing the Same "filed in the Korean Intellectual Property Office, which is a biodegradable solid micro needle for forming biodegradable solid micro needles Coating a viscous material; Coagulating a biodegradable viscous material coated with a frame patterned with a column while drawing; And cutting the drawn biodegradable viscous material.

However, in this method, it is practically impossible to manufacture a microneedle having a multi-layered structure made of different materials, and thus a method of forming a coating layer on the surface of the microneedle fabricated has been used.

The present invention is to provide a method of manufacturing microneedles having a multi-layer structure having an accurate shape.

An object of the present invention is to provide a microneedle manufacturing method capable of precisely realizing a shape of a microneedle needle using a mold.

Another object of the present invention is to provide a method for manufacturing a microneedle needle which can be mass-produced in a large quantity and can reduce manufacturing cost.

Another object of the present invention is to provide a method of manufacturing a microneedle needle which is easy to manage hygiene.

(A) providing a mold having a negative shape corresponding to a microneedle to be manufactured; (b) applying the microneedle raw material to the mold; (c) curing the microneedle primary material injected into the mold; (d) forming a needle groove on an upper surface of the primary raw material of the cured primary micro needle; (e) applying a microneedle raw material to an upper surface of the microneedle raw material having the needle groove formed therein; And (f) curing the microneedle raw material injected onto the upper surface of the primary raw material of the microneedle.

Between the step (b) and the step (c)

The method may further include a step of charging the mold with the first raw material of the needle into the chamber and pressing the first raw material of the needle using the internal pressure of the chamber.

The step (c) may be performed in the chamber.

Wherein the step (a) comprises the steps of: preparing a metal embossed metal; duplicating a metal intaglio mold from the metal embossed metal; duplicating the resin embossed mold using the UV hardening resin from the metal intaglio metal; (D) forming a needle groove by using the resin negative embossing mold as the mold, and using the resin embossing mold as the step (d), wherein the resin embossing mold is copied from the resin positive embossing mold using a UV curable resin .

A protrusion having a height equal to or higher than a coating height of the raw material of the microneedle may be attached to the edge of the resin intaglio mold to be used as a mold.

After the step (f), a step of attaching a protective sheet having adhesion to the surface of the cured micro needle and having a waterproof function may be further carried out.

Meanwhile, it is preferable that the mold is made of a material having a relatively small coefficient of thermal expansion as compared with the microneedle raw material.

The method of manufacturing a microneedle needle according to the present invention produces a microneedle having an accurate shape by manufacturing a microneedle needle using a mold.

In addition, the method for manufacturing a microneedle microneedle according to the present invention can reduce the manufacturing cost of the microneedle because the mold can be used repeatedly.

In addition, the method of manufacturing a microneedle micro needle according to the present invention facilitates hygiene management by allowing injection and curing of the raw material of the needle in the sealed chamber.

FIG. 1 is a process diagram showing a method of manufacturing a microneedle micro needle according to an embodiment of the present invention.
FIG. 2 is a view showing a process up to primary raw material curing in a method of manufacturing a microneedle microneedle according to an embodiment of the present invention.
3 is a view showing a process after the primary raw material curing in the method of manufacturing the multi-layer micro needle according to the embodiment of the present invention.
4 is a process diagram illustrating a process of manufacturing a mold used in a method of manufacturing a micro needle according to an embodiment of the present invention.

The terms and words used in the present specification and claims should not be construed as limited to ordinary or preliminary meaning and the inventor shall properly define the concept of the term in order to describe its invention in the best possible way It should be construed in accordance with the meaning and concept consistent with the technical idea of the present invention. It should be noted that the embodiments described in the present specification and the configurations shown in the drawings are only the most preferred embodiments of the present invention and do not represent all the technical ideas of the present invention, It should be understood that various equivalents and modifications are possible.

The skin consists of stratum corneum (<20 μm), epidermis (<100 μm), and dermis (300-2,500 μm) from the epidermis.

In order to deliver medicines and skin cosmetic ingredients without pain to a specific skin layer, it is necessary that the microneedle having a diameter of the upper end of the microneedle in the range of 10 to 100 mu m, an effective length of 250 to 3,000 mu m, Layer microneedle manufacturing method of the present invention.

2 is a view illustrating a process up to primary raw material curing in a method of manufacturing a microneedle microneedle according to an embodiment of the present invention, and Fig. 2 3 is a view showing a process after the primary raw material curing in the method of manufacturing the multi-layer microneedle according to the embodiment of the present invention.

The method of manufacturing a micro needle according to the present invention is for improving microneedle shape reproducibility and mass productivity, and is capable of manufacturing a micro needle using a mold.

As shown in the drawing, a method of manufacturing a microneedle according to the present invention includes a mold preparing step S110, a mold charging and depressurizing step S120, a first raw material applying step S130, a chamber pressing step S140, , A first raw material curing step S150, a needle groove forming step S160, a chamber reducing step S170, a second raw material applying step S180, a chamber pressing step S190, a secondary raw material curing A step S200, and a protective sheet attaching step S210.

The microneedles have problems in that the raw material is not completely injected into the shape of the engraved needle when the mold is used for manufacturing the needle because of the shape characteristic of the fine needle having the fine size.

In the present invention, the microneedle raw material is injected in the chamber, and then the chamber is pressed so that the microneedle raw material applied to the mold can be completely and precisely injected into the needle-like needle shape.

In addition, the present invention provides a method for manufacturing a microneedle microneedle capable of sequentially injecting different kinds of drugs by making the microneedles have a multilayered structure using different kinds of raw materials.

The mold preparing step (S110) is a step of preparing a mold with an angular shape corresponding to the microneedles to be manufactured. The mold can be manufactured by various methods, and the material is not particularly limited either. However, since the microneedle must penetrate the skin, it is preferable that the material of the mold is made of a material harmless to the human body when the skin is contacted. This is because dust or the like of the mold can be adsorbed on the surface of the micro needle when the micro needle is manufactured from the mold.

In addition, the mold should be manufactured in an appropriate manner in consideration of mass production performance and manufacturing cost in mass production. A concrete manufacturing method of the mold proposed by the present invention will be described later with reference to Fig.

Referring to FIGS. 1 and 2, a mold loading and depressurizing step S120 is performed by filling a mold provided in a chamber C capable of adjusting internal pressure and internal temperature, .

At this time, the pressure inside the chamber C is preferably reduced to 0.1 atm or less, and it is more preferable that the pressure in the chamber C is reduced to a vacuum state.

The decompression of the inside of the chamber C charged with the mold to a vacuum state is intended to prevent the presence of air bubbles in the applied raw material when the raw material of the microneedle is applied to the surface of the mold. The mold has recesses corresponding to microneedles having a diameter of several tens to several hundreds of micrometers. If bubbles are present in the grooves of the recesses, the shape of the microneedles can not be reproduced, resulting in defects. There is a problem that the leading end portion is not formed in a sharp manner.

Since there is no gas inside the chamber C in which the mold is loaded, no air bubbles are generated inside the microneedle raw material when the microneedle raw material is applied.

The raw material applying step S130 is preferably a continuous process in the same chamber C as the mold charging and depressurizing step S120.

The raw material applying step S130 is a step of applying the microneedle raw material 300 on the mold in the decompressed chamber C.

At this time, an additional step such as pressing with the roller after application of the first raw material 300 of the microneedle is not required, and merely a step of pouring the raw material of the microneedle according to a certain amount can be performed.

This is because the inside of the chamber C in which the mold is loaded is in a vacuum state or sufficiently decompressed state so that the microneedle primary raw material 300 is poured onto the mold by simply pouring the fluidity- (UV2). &Lt; / RTI &gt;

The chamber pressurization step S140 is performed in the same chamber C as the preceding processes.

Since the chamber pressurization step S140 raises the pressure inside the chamber rather than the pressure inside the chamber at the time of performing the raw material applying step (S130), which is a previous process, the pressure inside the pressurized chamber does not have to be higher than the atmospheric pressure.

For example, if the mold charging and depressurizing step S120 and the primary raw material applying step S130 are performed in a vacuum state, the chamber pressurizing step S140 simply releases the vacuum inside the chamber so that the inside of the chamber is at atmospheric pressure Can be.

Of course, the pressure inside the chamber in the chamber pressurization step S140 may be pressurized to a level higher than the atmospheric pressure.

The surface of the primary raw material of the microneedle applied on the mold is pressurized by the pressure inside the chamber in the chamber pressurization step S140 so that the flow of the microneedle primary raw material 330 is completely injected into the mold UV2 .

The micro needle curing step S150 is a step of hardening the microneedle raw material.

It is preferable that the micro needle curing step (S150) is performed continuously in the interior of the chamber. This is because decompression and pressurization must be carried out in the subsequent process of inputting the second raw material.

The micro needle curing step (S150) is a step of curing the micro needle raw material through heating and blowing.

If the microneedle curing step (S150) is performed inside the chamber, both the step of applying the microneedle raw material and the step of hardening are carried out in the chamber, so that the produced microneedle product is contaminated with bacteria or foreign matter There is an effect that can be blocked.

Next, the steps after the primary raw material curing step (S150) will be described with reference to Figs. 1 and 3. Fig.

The needle groove forming step S160 is a step of forming a needle groove 312 on the upper surface of the hardened primary raw material so that a needle using a secondary raw material can be formed.

In this case, it is preferable that the needle groove 310 is formed to be aligned with the hardened primary raw material needle 310 so that the needle groove 312 can be formed up to the inside of the primary raw material needle 310. This allows the needles to be constructed of heterogeneous materials in a multi-layered structure, enabling sequential delivery of different drugs.

The needle groove 312 may be formed by using a resin embossing mold UV1 having a shape corresponding to the mold UV2.

The mold (UV2) corresponds to a resin intaglio mold and is copied from the resin positive mold (UV1). Therefore, the mold UV2 and the resin positive mold UV1 have a concave shape and a convex shape corresponding to each other. This portion will be described later with reference to FIG.

After the resin positive embossing mold UV1 is aligned with the mold, the upper surface of the primary raw material cured by the resin positive embossing mold UV1 is pressed to form the needle groove 310.

The needle groove forming step S160 is illustrated as being performed inside the chamber C in the drawing, but may be performed outside the chamber C.

Next, a chamber depressurization step (S170), a secondary raw material application step (S180), a chamber pressurization step (S190), and a secondary raw material curing step (S200) are performed to apply and cure the second raw material.

The chamber depressurization step S170 is a preparation step for allowing the secondary raw material to be completely injected into the needle groove 312. [ At this time, the pressure to be depressurized is preferably 0.1 atm or less, and the bubbles can be further suppressed as it is closer to a vacuum state.

The first raw material applying step S180, the chamber pressurizing step S190 and the second raw material curing step S200 are the same as the first raw material applying step S130 except that the raw material to be coated is the second raw material 320. [ The chamber pressurization step S140, and the primary raw material curing step S150, and thus a duplicate description will be omitted.

If the raw material hardening step S150 and the second raw material hardening step S200 take a relatively long time to harden the raw materials, the hardening process is performed to some extent inside the chamber, As shown in Fig. This is to improve the productivity of the product through efficient use of the chamber.

Lastly, a step S210 of attaching the protective sheet 320 to the back surface of the micro needle having completed the hardening of the second raw material 320 may be performed.

The protective sheet 320 is preferably made of a material having an adhesive force on the surface and having a waterproof function.

Since the microneedle raw material is made of a biodegradable material, it is very vulnerable to moisture. Therefore, a protective sheet having a waterproof function is attached to the back surface of the dried micro needles to prevent the micro needle products from being damaged by moisture.

4 is a process diagram illustrating a process of manufacturing a mold used in a method of manufacturing a micro needle according to an embodiment of the present invention.

As shown in the drawing, the mold used in the method of manufacturing the microneedle according to the present invention is formed by sequentially forming a metallic embossing mold M2, a resin embossing mold UV1, and a resin embossing mold UV2 in this order from the metal embossing mold M1 And after the duplication, the resin negative-tone metal mold (UV2) is used as a mold.

The metal embossed metal mold M1 is manufactured so as to correspond to the shape of the microneedle through the precision machining of the metal. The metal embossed mold (M1) can be made of copper (Cu) material which does not cause an allergic reaction to skin contact.

A metal embossing die M1 corresponding to the shape of a microneedle is manufactured through a metal precise processing technique, and then a mold is manufactured through a multi-step replication process.

A metal intaglio mold M2 having an engraved shape corresponding to the metal emboss mold M1 is copied from the metal emboss mold M1 using an electroforming method.

A plurality of metal intaglio molds (M2) can be duplicated using one metal embossing mold (M1), but there is a limit to the number of copies. This is because the number of times that replication can be performed at a reliable level is limited because there is a possibility that the shape of the microneedle may be deformed as the number of times of replication is repeated even if the copying is performed through the electrophoresis process.

Next, a resin embossed mold (UV1) made of a UV-curable resin material is copied from the metal intaglio mold (M2). The resin positive embossing mold (UV1) is formed by applying a UV curing resin to a metal negative embossing mold (M2), attaching a base film, and uniformly applying UV curing resin by using a roller, Followed by curing and then separating.

At this time, the application of the UV curable resin is carried out by charging the metal intaglio mold M2 into the chamber, applying the UV curable resin in the depressurized state or the vacuum state, and then applying the pressure inside the chamber to the metallic intaglio mold M2 After the UV curable resin is completely injected, the base film may be attached and cured by irradiation with UV light.

Next, the resin negative embossing mold (UV2) made of UV curable resin is replicated from the resin positive embossing mold (M1). The resin intaglio mold (UV2) is obtained by applying a UV curable resin to the resin positive mold (M1), attaching a base film, and uniformly applying a UV curable resin using a roller, A method of curing and then separating can be used.

Meanwhile, the resin intaglio mold M2 manufactured by this method can be used as a mold for manufacturing micro needles. However, as shown in the figure, at the edge of the resin negative mold M2, (110 in Fig. 2) having a height can be attached to the mold and used as a mold.

As described above, since the present invention is manufactured by pouring a predetermined amount of microneedle raw material into a mold, the protrusion (110 of FIG. 2) is attached to prevent the microneedle raw material being injected from overflowing.

On the other hand, it is preferable that the resin intaglio mold M2 used as the mold of the micro needle is made of a material having a relatively large thermal expansion coefficient as compared with the microneedle raw material.

This is for the purpose of allowing the micro needle material and the mold to be heated and dried together to cure the micro needle at the time of micro needle curing, so that the hardened micro needle can be easily separated from the mold.

If the thermal expansion coefficient of the mold is smaller than the thermal expansion coefficient of the needle raw material, the shrinkage rate of the mold becomes larger than the shrinkage rate of the needle, so that the needle is pressed against the mold and the needle may be damaged when the micro needle is separated.

As described above, the resin embossing mold UV1 to be copied of the resin intaglio mold UV2 can be used in the process of forming the needle grooves 312 on the back side of the cured primary raw material.

As described above, according to the method of manufacturing a microneedle microneedle according to the present invention, it is possible to mass-produce a microneedle with a microneedle structure using a resin intaglio mold and a resin embossed mold, .

In addition, by using the engraved metal mold, it is possible to reduce the occurrence of defects due to bubbles during manufacture, thereby providing an effect of manufacturing a microneedle needle of excellent quality.

It is to be understood that the above-described embodiments are to be considered in all respects as illustrative and not restrictive, and the scope of the present invention will be indicated by the appended claims rather than by the foregoing detailed description. It is intended that all changes and modifications that come within the meaning and range of equivalency of the claims, as well as any equivalents thereof, be within the scope of the present invention.

10: metal plate
12: Needle
110: projection
300: Micro needle primary material
310: Needle
312: Needle home
320: Microneedle Secondary raw material
330: Protective sheet
C: chamber
M1: Metal embossed mold
M2: Metal intaglio mold
UV1: Resin embossed mold
UV2: Resin embossed mold
S110: mold preparing step
S120: Mold charging and decompression step
S130: First raw material application step
S140: chamber pressurization step
S150: Primary raw material curing step
S160: needle groove forming step
S170: chamber depressurization step
S180: Second raw material application step
S190: chamber pressurization step
S200: Secondary raw material curing step
S210: Step of attaching protective sheet

Claims (7)

(a) providing a mold having a depressed shape corresponding to a microneedle to be manufactured;
(b) applying the microneedle raw material to the mold;
(c) curing the microneedle primary material injected into the mold;
(d) pressing the upper surface of the primary raw material of the microneedle cured in the step (c) with a mold having a projection to form needle grooves on the upper surface of the primary raw material of the primary microneedle;
(e) applying a microneedle raw material to an upper surface of the microneedle raw material having the needle groove formed therein; And
(f) curing the microneedle secondary raw material injected onto the upper surface of the primary raw material of the microneedle.
The method according to claim 1,
Between the step (b) and the step (c)
Further comprising a pressurizing step of charging the mold with the needle first raw material applied thereto into the chamber and pressing the needle raw material using the internal pressure of the chamber.
3. The method of claim 2,
Wherein the step (c) is performed in the chamber.
The method according to claim 1,
The step (a)
Providing a metal embossing die;
Duplicating a metal intaglio mold from the metal emboss mold,
Duplicating a resin embossed metal mold using the UV hardening resin from the metal intaglio mold;
Forming a needle groove in the step (d) by using the resin negative-angle mold as the mold, and using the resin positive-angle mold as a step of forming the needle groove in the step (d) Wherein the micro needle is manufactured by a method of manufacturing a micro needle.
5. The method of claim 4,
Wherein a projection having a height equal to or higher than a coating height of the raw material of the microneedle is attached to an edge of the resin negative-angle metal mold and used as a mold.
The method according to claim 1,
After the step (f)
Further comprising the step of attaching a protective sheet having adhesion to the surface and having a waterproof function on the back surface of the cured micro needle.
The method according to claim 1,
Wherein the mold is made of a material having a thermal expansion coefficient relatively lower than that of the microneedle raw material.

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