KR20200098894A - Apparatus and method for manufacturing of micro niddle - Google Patents

Abstract

The present invention relates to an apparatus and method for manufacturing a microneedle, capable of manufacturing needles with a uniform shape and height by elongating a mixed solution containing a drug via centrifugation into a needle shape. To this end, the apparatus for manufacturing a microneedle comprises: a mixed solution eject unit which ejects a polymer mixture solution onto an upper surface of a patch placed on a first substrate; a substrate assembly unit which assembles the first substrate and a second substrate such that a patch-placed surface of the second substrate is spaced apart at a predetermined gap from the patch-placed surface of the first substrate in a direction facing the same; and a needle forming unit which generates a centrifugal force such that the polymer mixture solution on the first substrate is elongated in a direction of the second substrate, thereby forming a needle shape.

Description

Microneedle manufacturing apparatus and manufacturing method TECHNICAL FIELD [APPARATUS AND METHOD FOR MANUFACTURING OF MICRO NIDDLE}

The present invention relates to a microneedle manufacturing technology, and more particularly, to a microneedle manufacturing apparatus and manufacturing method capable of minimizing changes in properties of drugs or nutrients supplied into the body.

Methods for delivering drugs and bioactive substances into the body include dosage form, ointment, patch attachment, injection, and the like.

The method of taking the formulation has disadvantages such as that drugs and bioactive substances are digested or absorbed in the gastrointestinal tract or lost by the mechanism of the liver.

In the case of using an injection, since the drug is delivered by inserting a needle into the body, the drug effect appears quickly, and the drug is directly delivered to the body tissues such as blood or muscle, thereby enabling effective drug delivery.

However, in the method of using injections, the needle causes strong irritation and wounds on the skin, and pain is accompanied by this. In addition, since there is a possibility that additional infection may occur due to the wound, the procedure can only be performed by a specialist.

Microneedles have been developed as a drug delivery method to solve the problem of the injection method using such a needle.

Microneedles are systems that deliver drugs into the body with minimal invasion using a fine needle, and demand is expanding in that there is no pain, can prevent damage to the skin, can prevent infection, and can be self-administered. Is expected to be.

1 is a view for explaining the operation of a general microneedles, the microneedles are composed of a patch 100 that can be attached to the skin, and a needle 102 formed on one surface of the patch and a drug and a polymer are mixed.

According to this configuration, when the patch 100 on which the needle 102 is formed is attached to the skin, the polymer contained in the needle reacts with the body moisture and body temperature to dissolve and release the drug in the polymer to deliver the drug to the skin mucosa. .

In general, a molding method and a tensile method have been developed as a method for manufacturing microneedles.

Korean Patent No. 1850957 has been proposed as a method for manufacturing a microneedle using a conventional molding method.

Korean Patent Registration No. 1850957 is to form an intaglio structure pattern having a structure corresponding to the shape of a microneedle on the surface of a mold, fill a polymer material containing a chemical solution inside the pattern of the intaglio structure, and put a patch material on the surface of the polymer material. After attaching, microneedles are manufactured by separating the patch material from the mold.

2 and 3 are cross-sectional views for explaining a problem of a microneedle manufacturing method using a conventional molding method.

Referring to FIG. 2, when separating the patch 100 on which the needle 102 is formed from the mold 200, the needle 102 having flexibility is damaged, resulting in a poor production yield of a good product, and a continuous process is difficult.

In order to solve the shortcomings of the process as shown in FIG. 2, a method of solidifying the chemical liquid filled in the mold through a heat drying process after filling a polymer material containing a chemical solution inside the pattern of the intaglio structure as shown in FIG. 3 Although this is applied, there is a problem that the properties of the drug are changed during the heating and drying process.

Meanwhile, Korean Patent No. 1435888 has been proposed as a method for manufacturing a microneedle using a conventional molding method.

Korean Patent No. 1435888 applies a polymer material containing a chemical solution to a first substrate, then contacts the second substrate, and then stretches the polymer material by moving the second substrate relative to the first substrate. Solidify the material.

4 is a cross-sectional view illustrating a method of manufacturing a microneedle using a conventional tensioning method.

However, the tensioning method such as Korean Patent No. 1435888 has a disadvantage in that it is difficult to align the horizontal state during the tensioning process as shown in FIG. 4, and thus, it is difficult to manufacture a needle having a uniform height and shape.

In order to solve this disadvantage, Japanese Patent Application Laid-Open No. 2012-504034 applies a polymer material on a substrate, contacts a contact protrusion of a lifting support with an electric viscous composition, and then heat-treats and blows a microneedle.

However, the microneedle manufacturing method applying the heat treatment and blowing process has a problem in that the properties of the drug are changed by the heat treatment as in the case of heating and drying during the molding process described above.

Korean Patent No. 1850957 "Medical mesh formed with microneedles and its manufacturing method" Korean Patent No. 1435888 "Method for manufacturing biodegradable microneedles using hyaluronic acid" Japanese Patent Laid-Open Publication No. 2012-504034 "Method of manufacturing solid microstructures by blowing and solid microstructures manufactured from now on"

An object of the present invention for solving the disadvantages of the background technology is a microneedle manufacturing apparatus capable of manufacturing a needle having a uniform shape and height by tensioning a mixed solution containing a drug in a needle shape by centrifugation, and To provide a manufacturing method.

In addition, the present invention is to provide a microneedle manufacturing apparatus and a manufacturing method capable of minimizing changes in drug properties by manufacturing a uniform needle without performing a separate heat treatment process.

In order to solve the problem, the microneedle manufacturing apparatus of the present invention has a mixed solution discharge part for discharging a polymer mixed solution on an upper surface of a patch mounted on a first substrate, and a patch mounting surface of the second substrate faces the patch mounting surface of the first substrate. A substrate assembly unit for assembling the first substrate and the second substrate so as to be spaced apart from each other by a predetermined distance, and a needle forming unit for forming a needle shape by generating a centrifugal force so that the polymer mixed solution on the first substrate is stretched in the direction of the second substrate. do.

In this case, it may further include a plasma treatment unit installed in the front end of the mixed solution discharge unit for surface treatment of the patch.

In addition, the needle forming portion is provided with an insertion hole for inserting the substrate assembly assembled in the substrate assembly portion in a vertical direction, and air discharge portions may be formed at both ends of the insertion hole.

The microneedle manufacturing method of the present invention comprises the steps of discharging a polymer mixed solution on the upper surface of the patch of the first substrate, and the patch seating surface of the second substrate is constant in a direction opposite to the patch seating surface of the first substrate from which the polymer mixed solution is discharged. Assembling the second substrate and the first substrate so as to be spaced apart from each other, and forming a needle shape by generating a centrifugal force so that the polymer mixture solution on the first substrate assembled by the substrate assembly unit is stretched in a direction of the second substrate.

In addition, a process of plasma-processing the patch of the first substrate before discharging the polymer mixture solution to the first substrate and the patch of the second substrate before the substrate assembly step may be further included.

The microneedles manufactured according to the present invention have a uniform height and shape, and as the change in properties of the drug is minimized, the duration of the drug or nutrient may be increased, thereby improving treatment and health improvement effects.

1 is a view for explaining the operation of a general microneedle.
2 and 3 are cross-sectional views for explaining a problem of a microneedle manufacturing method using a conventional molding method.
Figure 4 is a cross-sectional view for explaining a microneedle manufacturing method using a conventional tensile method.
5 is a block diagram illustrating a configuration of a microneedle manufacturing apparatus according to an embodiment of the present invention.
6 is a conceptual diagram showing a method of manufacturing a microneedle according to an embodiment of the present invention.
7 is a cross-sectional view of a substrate assembly having a microneedle structure manufactured according to an embodiment of the present invention.
8 is a perspective view of a substrate having a microneedle structure manufactured according to an embodiment of the present invention.
9 is a graph showing changes in EGF activity of a drug according to a process time for a microneedle manufactured according to an embodiment of the present invention and a microneedle manufactured by a conventional method.
10 is a graph showing changes in the activity of ascorbic acid of a drug according to processing time for a microneedle manufactured according to an embodiment of the present invention and a microneedle manufactured by a conventional method.

Hereinafter, a preferred embodiment of the present invention will be described in detail with reference to the accompanying drawings.

5 is a block diagram illustrating a configuration of a microneedle manufacturing apparatus according to an exemplary embodiment of the present invention, and FIG. 6 is a conceptual diagram illustrating a method of manufacturing a microneedle according to an exemplary embodiment of the present invention.

5, a microneedle manufacturing apparatus according to an embodiment of the present invention includes a plasma processing unit 300, a substrate transfer unit 302, a mixed solution discharge unit 304, a substrate assembly unit 306, and a needle forming unit 308. ).

The plasma processing unit 300 is for improving the adhesion characteristics of the patch through surface modification of the patch, and the plasma processing unit 300 includes a process before discharging the mixed solution to the first substrate 400 and the second substrate 500. Plasma treatment is performed on the patches 402 and 502 on the upper surface of each of the substrates before bonding to the first substrate.

The substrate transfer unit 302 includes a first substrate transfer unit 302a that transfers the plasma-treated first substrate 400 to the mixed solution discharge unit 304 and the plasma-treated second substrate 500. It may be composed of a second substrate transfer unit 302b transferred to the substrate assembly unit 306.

Each of the substrate transfer units 302a and 302b may be driven in the X-Y-Z axis direction to transfer each substrate in the X-Y-Z axis direction, and a gantry type transfer unit may be used.

The mixed solution discharge unit 304 discharges the viscous polymer mixed solution onto the surface of the patch mounted on the first substrate 400 and arranges it in a spot shape.

In this case, the polymer mixture solution may be a polymer solution in which a biocompatible or biodegradable material is mixed.

The substrate assembly unit 306 includes the first substrate 400 and the second substrate 500 so that the patch 402 of the first substrate 400 and the patch of the second substrate 500 from which the mixed solution is discharged are opposed to each other. As a combination, the second substrate 500 is assembled so that the second substrate 500 is positioned above the first substrate 400.

The needle forming unit 308 is a device that provides a centrifugal force by rotation while the substrate assembly 600 is inserted, and the polymer on the first substrate 400 by the centrifugal force generated by the needle forming unit 308 is rotated. The mixed solution is stretched.

That is, the tip of the polymer mixed solution on the first substrate 400 is pulled in the direction of the second substrate 500 to form a needle shape.

To this end, an insertion hole 308a for inserting the substrate assembly 600 in the vertical direction is formed in the needle forming part 308.

However, when the insertion hole 308a has the same shape as the substrate assembly 600, air resistance according to the internal pressure of the insertion hole 308a occurs in the process of inserting the substrate assembly 600 into the insertion hole 308a, and as a result, assembly of the substrate assembly The state can be transformed.

In this way, if the assembly state of the substrate assembly is deformed, the separation distance between the first substrate and the second substrate may become non-uniform, and the polymer mixed solution may not be stretched evenly, resulting in a uniform height and shape. Of the needle becomes impossible to form.

Accordingly, the present invention prevents an increase in the air pressure inside the insertion hole 308a when the substrate assembly 600 is inserted into the insertion hole 308a by forming the air discharge portions 308b at both ends of the insertion hole 308a.

That is, when the substrate assembly 600 is inserted into the insertion hole 308a, as air flows through the air outlet 308b, an increase in pressure inside the insertion hole 308a is prevented, thereby preventing deformation of the assembly state of the substrate assembly. do.

Hereinafter, a method of manufacturing a microneedle according to an embodiment of the present invention will be described.

5 and 6, the first substrate 400 loaded on the substrate loading unit (not shown) is transferred to the plasma processing unit 300 (step a), and the adhesion properties of the patch 402 are improved. To do this, the first substrate 400 is plasma-treated (step b).

Subsequently, the first substrate transfer unit 302a transfers the plasma-treated first substrate 400 to the mixed solution discharge unit 304.

The mixed solution discharge unit 304 discharges the polymer mixed solution onto the surface of the transferred first substrate 402 to form a spot-shaped polymer mixed solution array 404 (step c).

Next, the second substrate 500 loaded on the substrate loading unit (not shown) is transferred to the plasma processing unit 300, and the fifth substrate 500 is plasma treated to improve the adhesion characteristics of the patch 502. (Step d).

Next, after transferring the first substrate 400 and the second substrate 500 from which the polymer mixed solution was discharged to the substrate assembly unit 306, the second substrate 500 is fixed above the first substrate 400. Assemble to be spaced apart (step e).

Subsequently, the substrate assembly 600 is transferred to the needle forming part 308, and the substrate assembly 600 is inserted into a centrifugal separator and then rotated to apply a centrifugal force to the substrate assembly 600 (step f).

7 is a cross-sectional view of a substrate assembly having a microneedle structure manufactured according to an exemplary embodiment of the present invention, and FIG. 8 is a perspective view of a substrate having a microneedle structure manufactured according to an exemplary embodiment of the present invention.

In the present invention, by rotating the substrate assembly 600 in the needle forming part 308 to apply a centrifugal force, the polymer mixed solution 404 on the first substrate having a spherical shape is stretched in the direction of the second substrate, and thus the first substrate ( The tip of the polymer mixed solution on 400) has a sharp needle 406 shape.

In addition, according to the present invention, as two of the needles are formed by stretching the polymer solution by centrifugal force between the substrates as shown in FIGS. 7 and 8, the needles have a uniform height and shape.

9 is a graph illustrating changes in EGF activity of a drug according to processing time for a microneedle manufactured according to an embodiment of the present invention and a microneedle manufactured by a conventional method.

Referring to FIG. 9, in the case of the microneedle (a) manufactured using the centrifugal separation method, which is an embodiment of the present invention, it was found that the EGF activity did not change significantly by process time, but the microneedle using the conventional heating blowing method In the case of (b), it was found that the EGF activity significantly decreased as the process time passed.

10 is a graph showing changes in the activity of ascorbic acid of a drug according to a process time for a microneedle manufactured according to an embodiment of the present invention and a microneedle manufactured by a conventional method.

Referring to FIG. 10, in the case of the microneedle (a) manufactured using the centrifugal separation method, which is an embodiment of the present invention, it was found that the activity of ascorbic acid did not change significantly for each process time, but the conventional heating and blowing method was used. In the case of the microneedle (b), it was found that the activity of ascorbic acid significantly decreased as the processing time passed.

As described above, in the conventional microneedle manufacturing process, it can be seen that the EGF activity or ascorbic acid activity of the drug changes significantly as the process time elapses as the heating and blowing process is performed to prevent the deformation of the needle.

On the other hand, in the present invention, as the polymer mixture solution is stretched by centrifugal force to form a needle without performing a heating and blowing process, a change in the properties of the drug can be prevented, and a high molecular weight substance can be contained regardless of oil-soluble or water-soluble substances. .

Although the present invention has been described in connection with the above-mentioned preferred embodiments, it is possible to make various modifications or variations without departing from the spirit and scope of the invention. Accordingly, the scope of the appended claims will include such modifications or variations that fall within the gist of the present invention.

100: patch 102: needle
200: mold
300: plasma processing unit 302: substrate transfer unit
304: mixed solution discharge part 306: board assembly part
308: needle formation portion 400: first substrate
402: patch 404: discharge mixed solution
406: needle 500: second substrate
502: needle 600: substrate assembly

Claims (5)

A mixed solution discharge unit for discharging a polymer mixed solution on an upper surface of the patch mounted on the first substrate;
A substrate assembly unit for assembling the first substrate and the second substrate so that the patch mounting surface of the second substrate is spaced apart from the patch mounting surface of the first substrate by a predetermined distance;
And a needle forming unit configured to form a needle shape by generating a centrifugal force so that the polymer mixed solution on the first substrate is stretched in a direction of the second substrate.
The method of claim 1,
And a plasma processing unit installed at a front end of the mixed solution discharge unit and surface-treated the patch.
The method of claim 1,
The needle forming unit is provided with an insertion hole for inserting the substrate assembly assembled in the substrate assembly in a vertical direction, and an air discharge unit is formed at both ends of the insertion hole.
Discharging a polymer mixed solution onto the upper surface of the patch of the first substrate;
Assembling the second substrate and the first substrate so that the patch seating surface of the second substrate is spaced apart by a predetermined distance in a direction opposite to the patch seating surface of the first substrate from which the polymer mixed solution is discharged;
And forming a needle shape by generating a centrifugal force so that the polymer mixed solution on the first substrate assembled by the substrate assembly unit is stretched in the direction of the second substrate.
The method of claim 4,
And performing plasma treatment of the patch of the first substrate before discharging the polymer mixture solution to the first substrate and the patch of the second substrate before the substrate assembly step.

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