KR20140006167A - Nano and micro needle using low temperature drawing and fabricating method thereof - Google Patents

Abstract

The present invention comprises the steps of coating the surface of the substrate (mixture) to the mixture (mixture) to have a viscosity by mixing a solvent (solvent) in the polymer (polymer); Contacting a pillar with the surface of the mixture of substrates; Solidifying while drawing the mixture from the substrate by increasing the distance between the pillar and the substrate; And cutting the portion formed by drawing to form a needle, and a nano / micro needle using a low temperature drawing technique and a method of manufacturing the same.
According to the present invention, it is possible to make the manufacturing process at a low temperature so that the drug sensitive to high heat is not affected by heat, thereby to ensure the reliability of the action of the drug, and to easily change the needle shape in the low temperature process do.

Description

Nano / microneedle using low temperature drawing technique and its manufacturing method {NANO AND MICRO NEEDLE USING LOW TEMPERATURE DRAWING AND FABRICATING METHOD THEREOF}

The present invention relates to a nano / micro needle using a low temperature drawing technique and a method for manufacturing the same, and more particularly, the manufacturing process can be made at a low temperature so that high temperature sensitive drugs are not affected by heat, The present invention relates to a nano / micro needle and a method of manufacturing the same using a low temperature drawing technique for easily changing needle shape.

In general, the drug delivery system (DDS) is a series of techniques that control the delivery of substances with pharmacological activity to cells, tissues, organs, and organs for optimal efficacy using various physicochemical techniques. In other words, the most common drug delivery system is the human ingestion of oral drugs, and there are other transdermal permeable drug delivery systems that can be applied topically, for the purpose of efficiently and safely administering pharmaceutical substances such as drugs. Importance has already been recognized for a long time.

In addition, the method of injecting a liquid medicine into the human body using a syringe has been used for a long time, but had the problems of accompanying pain and temporary injection of the drug. Therefore, in order to remedy the disadvantages of such syringes, micro-sized transdermal penetration needles that are much smaller than the needles of syringes have been manufactured and utilized.

Such microneedles are used as a device for injecting drugs for skin beauty or treatment into skin tissue, or as a device for extracting body fluids such as blood from the inside of the skin, and used in many fields, such as treatment of skin diseases or vaccination of diseases. A method of delivering a drug using such a microneedle may include coating a drug on a needle surface and manufacturing a microneedle by mixing a drug and a material of the needle. Needles used in many parts are polymers, except in the case of metals or materials that are insoluble in the human body. 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 a microneedle to deliver the drug in the body.

Conventional microneedle manufacturing method is a "biodegradable solid microneedle and its manufacturing method" of Patent No. 10-0793615 filed with the Republic of Korea Patent Office, which is a biodegradable for forming biodegradable solid microneedle on the surface of the substrate Coating a viscous material; Solidifying while drawing a biodegradable viscous material coated with a frame patterned with pillars; And cutting the drawn biodegradable viscous material.

However, such a conventional method of manufacturing a microneedle requires a phase change process such as a liquid phase (viscous flow region) even when a drug is dissolved in a polymer or molded into a solid microneedle. The supply of heat is essential in the process. In particular, when molding a solid needle using a high temperature, if the drug contained in the needle is sensitive to heat, the effect of the drug is generated in the body, so the high temperature process should be excluded from the molding process of the solid needle. Although a method of manufacturing a needle using sugar has been developed, this is a technique of injecting a liquid phase of sugar using a mold, which reduces the diameter or size of the needle due to the use of a mold or limits the shape deformation. Eggplant had other problems.

In order to solve the conventional problems as described above, the present invention can be a manufacturing process at a low temperature so that the drug sensitive to high heat is not affected by heat, thereby ensuring the reliability of the action of the drug, The purpose is to facilitate needle shape change in low temperature processes.

Other objects of the present invention will be readily understood through the following description of the embodiments.

In order to achieve the above object, according to an aspect of the present invention, the method comprising the steps of: coating a surface of the substrate (mixture) to have a viscosity by mixing a solvent (solvent) in the polymer (polymer); Contacting a pillar with a surface of the mixture of substrates; Solidifying while drawing the mixture from the substrate by increasing the distance between the pillar and the substrate; And cutting a portion formed by the drawing to form a needle, thereby providing a method of manufacturing nano / micro needle using a low temperature drawing technique.

Coating the mixture may control the viscosity and glass transition temperature (Tg) of the polymer solution including the drug by adjusting the content of the polymer and the solvent.

In the coating of the mixture, the hardness of the needle may be adjusted by adjusting the content ratio of the solvent to the polymer.

The coating of the mixture may include mixing the drug or the genetic material with the polymer and the solvent, and after removing the solvent, the weight ratio of the drug or the genetic material to the polymer is 1: 0.0001. It may be ~ 9.

In the drawing of the mixture, the degree of fineness of the needle may be adjusted by adjusting the feeding speed of the pillar or the substrate.

The mixture may be maintained at 50 ° C. or lower through the content control of the solvent.

The drawing step of the mixture can shorten the manufacturing time of the needle by forcibly cooling or solidifying the temperature of the polymer solution.

The drawing step of the mixture may control the fabrication time of the needle by heating or cooling the mixture through the substrate.

According to another aspect of the present invention, there is provided a nano / micro needle using a low temperature drawing technique prepared according to the nano / micro needle manufacturing method using a low temperature drawing technique as described above.

According to the nano / microneedle using the low-temperature drawing technique and the method for manufacturing the same, the manufacturing process can be performed at a low temperature so that the drug sensitive to high temperature is not affected by heat, thereby resulting in reliability of the action of the drug. It is ensured, and to facilitate the needle shape change in low temperature process.

1 is a view for sequentially explaining a method for manufacturing a nano / micro needle using a low temperature drawing technique according to a first embodiment of the present invention,
FIG. 2 is a diagram illustrating an apparatus used in a method of manufacturing nano / microneedle using a low temperature drawing technique according to a first embodiment of the present invention.
3 is a view for sequentially explaining a method of manufacturing a nano / micro needle using a low temperature drawing technique according to a second embodiment of the present invention,
FIG. 4 is a view showing an apparatus used in a method of manufacturing nano / microneedle using a low temperature drawing technique according to a second embodiment of the present invention.
5 and 6 are views and images for explaining a method of manufacturing a nano / micro needle using a low temperature drawing technique according to a third embodiment of the present invention,
FIG. 7 is a view for explaining a method of manufacturing nano / micro needle using a low temperature drawing technique according to a fourth embodiment of the present invention;
8 and 9 are images showing the needle of the micro-size manufactured by the nano / micro needle manufacturing method using a low temperature drawing technique according to the present invention,
10 to 12 are images showing the needle of the nano-size manufactured by the method for manufacturing nano-micro needle using a low temperature drawing technique according to the present invention.

While the invention is susceptible to various modifications and alternative forms, specific embodiments thereof are shown by way of example in the drawings and will herein be described in detail. It is to be understood, however, that the invention is not to be limited to the specific embodiments, but is to be understood to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention, And the scope of the present invention is not limited to the following examples.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings, wherein like or corresponding elements are denoted by the same reference numerals, and redundant explanations thereof will be omitted.

The nano / micro needles 12 (shown in FIGS. 1 and 3) using the low temperature drawing technique according to the present invention are nano or micro size needles used for in vivo drug delivery, detection of analytes in the body, and biopsy. As a solvent, a mixture of a solvent and a polymer may be prepared by using a low temperature drawing technique, and may be prepared by mixing a drug or a genetic material with a polymer. There is no limitation on the material of the polymer. A polymer having the same may be used, and as the biodegradable substance having such viscosity, for example, various substances such as hydrogel, maltose, a therapeutic agent for skin diseases, cosmetic cosmetics, water-soluble substance, and polymer protein may be used. The method will be described in detail together with a method for manufacturing nano / microneedle using a low temperature drawing technique according to the present invention. .

1 is a view for sequentially explaining a method for manufacturing nano / micro needle using a low temperature drawing technique according to a first embodiment of the present invention.

As shown in FIG. 1, the nano / microneedle manufacturing method using the low temperature drawing technique according to the first embodiment of the present invention includes coating a mixture, contacting a pillar with the mixture, and drawing the mixture. And forming the needle by cutting.

According to the step of coating the mixture, the mixture 10 is mixed on the surface of the substrate 1 to have a viscosity by mixing a solvent with a polymer. Here, the coating is a process of applying to the surface of the substrate 1 using the viscosity of the mixture 10, it may be made by an applicator.

Coating the mixture may control the viscosity and glass transition temperature (Tg) of the polymer solution including the drug by controlling the polymer and solvent content. Here, the glass transition temperature will be described later. In addition, coating the mixture may adjust the content ratio of the solvent to the polymer so that the hardness of the needle 12 may be adjusted in the forming of the needle by cutting, and the mixture 10 may be mixed with the polymer and the solvent. It can be made by mixing the drug or genetic material together, and after removing the solvent so that the needle (12) can be used to treat diseases such as skin diseases or to prevent or diagnose the disease, the weight ratio of the drug or genetic material to the polymer This 1: 0.0001-9 may be.

According to the step of contacting the pillar with the mixture, when the mixture 10 is coated on the surface of the substrate 1, the pillar 2 is brought into contact with the surface of the mixture 10 of the substrate 1. Here, the pillars 2 may have an area or shape for the ends to contact the surface of the mixture 10.

According to the step of drawing the mixture, the mixture 10 is solidified while drawing the mixture 10 from the substrate 1 by increasing the distance between the pillar 2 and the substrate 1. In this case, as in the present embodiment, the distance between the pillar 2 and the substrate 1 may be increased by vertical transfer of the pillar 2, and the needle forming apparatus for this may be, for example, as illustrated in FIG. 2. On the XY stage 3 and the XY stage 3 for feeding the substrate 1 in the X-axis and Y-axis directions, for example, left and right, and back and forth, and the pillars 2 in the Z-axis, for example, up-down directions. Z stage (4) to be transferred to the second stage and the pressing cylinder (5) for moving the pillar (2) installed in the Z stage (4) to be in contact with the surface of the mixture 10 on the substrate (1) can do. Here, the XY stage 3 may have a respective motor and each stage for linearly conveying in the X-axis direction and the Y-axis direction, the rotational force transmitting member for converting the rotational force of the motor into a linear motion to transmit to each of the stages For example, it may have a ball screw and a lead screw, and may have a linear motor or a linear motion guide or the like in place of the torque transmission member and the motor.

Meanwhile, as shown in FIG. 3, the distance between the pillar 2 and the substrate 1 may be increased by vertical transfer of the substrate 1 in the drawing of the mixture. As shown in FIG. 4, the substrate 1 is provided on the XY stage 3 and the substrate 1 for conveying the substrate 1 in the X-axis and Y-axis directions, for example, left and right, and back and forth. ) Is included in the vertical member (3a) which is provided to be perpendicular to the XY stage (3) including a Z stage (6) for transferring the Z axis, for example in the vertical direction, the pillar (2) A pressing cylinder 5 is installed between the pillar 2 and the vertical member 3a to be installed above the substrate 1 and to bring the pillar 2 into contact with the surface of the mixture 10 on the substrate 1. Can be.

According to the step of forming the needle by cutting, the part 11 formed by the drawing is cut to form the needle 12. For example, after confirming that the solvent evaporates to harden the drawing part, which is a nano / micro structure, By narrowing the pillar 2 and the substrate 1, the narrow portion where the neck is formed may be broken to form the needle 12.

On the other hand, as shown in Figures 5 and 6, the drawing step of the mixture can be adjusted to adjust the degree of fineness of the needle 12 by adjusting the conveying speed of the pillar (2) or the substrate (1). For example, the needle 12 thickens as the feed rate of the pillar 2 or substrate 1 is reduced.

In addition, the drawing step of the mixture forces the manufacturing time of the needle 12 to be shorter than the needle manufacturing time at room temperature by forcibly cooling or solidifying the temperature of the polymer solution, and drawing the mixture 10 through the substrate 1. The production time of the needle 12 can be adjusted by heating or cooling.

In the nano / microneedle manufacturing method using a low temperature drawing technique according to the present invention, the mixture 10 may be maintained below 50 ℃ through the control of the content of the solvent.

As shown in FIG. 7, the use of a plurality of pillars 2 may enable the manufacture of a plurality of needles 12 simultaneously. At this time, the plurality of pillars 2 may be arranged one-dimensionally in the width direction or the longitudinal direction to the frame 2a, alternatively, two-dimensionally arranged in the width and length directions or various directions.

The operation of the nano / microneedle and its manufacturing method using the low temperature drawing technique according to the present invention will be described.

According to the nano / microneedle using the low temperature drawing technique of the present invention and a method for manufacturing the same, a micro or nano-sized needle by all polymers is made of a solvent that allows the polymer to be melted without using a conventional mold. I can make it.

That is, as shown in Equation 1 below, the conventional phase change (glass transition temperature (Tg) is changed according to the solvent content) by adjusting the content of the solvent, so that the conventional rubbery flow or viscous flow Temperature changes), and such a phase change results in a change in viscosity, so adjusting the change in viscosity can produce a needle.

[Equation 1]

,

,

Here, Tgp is glass transition temperature of polymer, Tgs is glass transition temperature of solvent, and Φp is volume fraction of polymer.

The solvent is evaporated to make the solution more viscous, and as the solvent is removed, the solution's Tg approaches the polymer's Tg, resulting in most of the polymer remaining and breaking or cutting.

Since the existing low temperature process is manufactured using a mold, the shape of the needle can be changed only by changing the shape of the mold. However, in the case of the present invention, a filler (pillar) 2 is used to pull up the polymer, and the solvent is heated at a low temperature, such as 50 ° C. or lower. By evaporating at, the desired shape, such as base diameter, tip diameter, aspect ratio, can be determined, and in particular the shape of the needle can be changed by changing the speed of pulling during the forming process. Therefore, if the needle is made by mixing a high temperature sensitive drug with a polymer solution from the beginning, the heat sensitive drug can be delivered to the body without having to undergo a high temperature process.

Although the present invention has been described with reference to the accompanying drawings, it is to be understood that various changes and modifications may be made without departing from the spirit of the invention. Therefore, the scope of the present invention should not be limited to the described embodiments, but should be determined by the equivalents of the claims, as well as the following claims.

1: Substrate 2: Pillar
2a: Frame 3: XY stage
4,6 Z stage 5: Pressing cylinder
10: mixture 11: drawing part
12: needle

Claims (9)

Coating a surface of the substrate with a mixture that is mixed with a solvent to render it viscous;
Contacting a pillar with a surface of the mixture of substrates;
Solidifying while drawing the mixture from the substrate by increasing the distance between the pillar and the substrate; And
And forming a needle by cutting a portion formed by the drawing. The method of claim 1, wherein the coating of the mixture comprises:
A method of manufacturing nano / microneedle using a low temperature drawing technique, characterized by controlling the viscosity and glass transition temperature (Tg) of a polymer solution including a drug by controlling the content of the polymer and the solvent. The method of claim 1, wherein the coating of the mixture comprises:
The method of manufacturing a nano / microneedle using a low temperature drawing technique characterized in that to control the hardness of the needle, by adjusting the content ratio of the solvent to the polymer. The method of claim 3, wherein the coating of the mixture comprises:
The mixture is made by mixing a drug or a genetic material with the polymer and the solvent, and after removing the solvent, the weight ratio of the drug or the genetic material to the polymer is 1: 0.0001-9 Nano / Micro Needle Manufacturing Method Using Drawing Technique. The method of claim 1, wherein the drawing of the mixture comprises:
The method of manufacturing a nano / microneedle using a low temperature drawing technique, characterized in that to adjust the degree of fineness of the needle by adjusting the feed rate of the pillar or the substrate. The method of claim 1, wherein the mixture,
Nano / microneedle manufacturing method using a low-temperature drawing technique, characterized in that to maintain below 50 ℃ by controlling the content of the solvent. The method of claim 1, wherein the drawing of the mixture comprises:
A method for manufacturing nano / microneedle using a low temperature drawing technique, characterized by shortening the time required for manufacturing the needle by forcibly cooling or solidifying a temperature of a polymer solution. The method of claim 1, wherein the drawing of the mixture comprises:
A method of manufacturing nano / microneedle using a low temperature drawing technique, characterized in that to control the manufacturing time of the needle by heating or cooling the mixture through the substrate. A nano / micro needle using a low temperature drawing technique, characterized in that it is prepared according to the method of any one of claims 1 to 8.

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