KR101983970B1 - The multi-step stuctured microneedle patch and the producing method for the same - Google Patents

Abstract

The present invention relates to an adhesive patch comprising a plurality of needles and an adhesive patch for fixing the needles, each of the needles comprising an effective component flowing into the body and formed in the shape of a quadrangular pyramid of a multilayer structure, And a tip portion formed by sequentially laminating a composition in which at least one active ingredient and a polymer material flowing into the body are mixed, the tip portion of which is sharpened.

Description

TECHNICAL FIELD [0001] The present invention relates to a multi-step micro needle patch and a manufacturing method thereof,

The present invention relates to a multi-stage micro needle patch and its manufacturing method, and more particularly, to a multistage micro needle patch for transcutaneous delivery of an active substance having pharmaceutical, medical or cosmetic efficacy and a method of manufacturing the same.

In 1998, the Micro Needle Company of Georgia Institute of Technology, USA, presented the possibility of applying microneedle arrays as a silicon device using semiconductor processing technology to drug delivery, and many studies have been actively conducted thereon. Microneedles are made in various sizes and shapes based on special needs based on various materials such as metals, polymers, glass, and ceramics as well as silicon.

Most microneedle fabrication methods are based on micromachining techniques that add, remove, and duplicate microstructures using photolithography, silicon etching, laser cutting, metal electroplating, metal electrolytic polishing and microfabrication. There are four known methods for delivering drugs using micro needles.

The first is to insert the micro needle into the skin, drill the hole, and treat the drug at the site where the micro needle is removed, so that the drug spreads through the hole. This method is simple to use and easy to manufacture, but has a disadvantage in that it can not confirm the amount of drug delivery accurately, and thus drugs with limited availability or high price are difficult to use.

The second method is to mount the material to be transferred on the surface of the microneedle through a coating method, insert the coated microneedle into the skin, and dissolve the coated drug in the skin. This method is easy to insert into the skin because metal with excellent mechanical strength is mainly used, but it is suitable for small amount of drug delivery because the amount coated on the micro needle is limited.

Third, as shown in FIG. 1 and FIG. 2, a microneedle is prepared by mixing a substance such as a water-soluble or biodegradable polymer dissolved in the skin together with a drug to be delivered. As shown in the figure, this method is advantageous in that the micro needle itself is dissolved in the skin and the drug is delivered, so that there is no need to treat the micro needle after use, while the micro needle itself is made drug based Therefore, maintaining the proper mechanical strength to penetrate the skin is the key.

The end is similar to the currently used syringe needle in a collapsed form, in which the hollow needle of the micro needle is emptied into the skin by the applied pressure of the liquid drug. In this case, however, it is advantageous to deliver a larger amount of drug than other types of micro needles, but it is necessary to overcome the difficulty of manufacturing micro needles and delivering liquid medicines into the skin, resulting in more pain do.

Since the skin is composed of a viscoelastic layer, when the micro needle is inserted into the skin, the shape of the skin may be deformed, so that the micro needle can not effectively penetrate the skin. Thus, the physical properties of the microneedles, the design of the microneedles, and the insertion method greatly influence the insertion of the microneedles into the skin. When inserting the micro needles into the skin, it is important that the micro needles can be inserted without bending or breaking.

In addition, since the micro needle has a fine structure, it is required to select a suitable material and manufacture a method for maintaining its physical shape. In the case of manufacturing micro needles using a commonly used molding technique, defective microneedles generated per unit area are a problem. Particularly, air pockets generated during solidification of micro needles degrade the quality of microneedle patches Is recognized as a problem.

The most important consideration when using a micro needle is the application advantages that distinguish it from other conventional invasive methods, such as ensuring drug stability, effective drug delivery and pain relief.

The materials loaded on the micro needle, in particular the biopharmaceuticals, must be able to maintain their efficacy when loaded on the micro needle and during storage thereafter. Many studies have confirmed that biological activity is maintained based on pharmacokinetic measurements and pharmacodynamic responses of the materials, and methods are being developed to further enhance the stability of the materials loaded on the micro needle. Among the many drugs, vaccine safety has attracted a lot of attention because if they can be stored for a long period of time without refrigeration, and if they are able to store the vaccine, they will be of great help in using the vaccine in developing countries.

When the solid micro-needles are coated or encapsulated in the soluble micro-needle, the stability of the drug may be impaired due to the drying process. Various studies are being conducted to overcome this problem.

Disclosure of Invention Technical Problem [8] Accordingly, the present invention has been made to solve the above-mentioned problems, and an object of the present invention is to provide a micro needle patch for delivering a drug through a skin, A micro needle patch having a multi-stage structure and a method of manufacturing the same.

According to an aspect of the present invention, there is provided a multi-needle micro-needle patch comprising a plurality of needles and an adhesive patch for fixing the needles, each of the needles including an effective component flowing into the body A tip portion formed in a conical shape of a multilayer structure and formed by sequentially laminating a base portion contacting with the adhesive patch, a composition containing at least one effective ingredient and a polymer material flowing into the body, and a sharp tip portion .

According to an embodiment of the present invention, the polymer material may be selected from the group consisting of trehalose, carboxymethyl cellulose NA, lecithin, phenoxyethanol, disodium EDTA, Sodium chloride, and distilled water.

According to an embodiment of the present invention, the height of the tip portion may be 0.1-0.8 mm, and the height of the base portion may be 0.05-0.2 mm.

According to an aspect of the present invention, there is provided a method of manufacturing a micro needle patch of a multi-stage structure, the method including sequentially forming a composition including at least one active ingredient in the engraved portion of a mold including a plurality of needle- Forming a microstructure of a multi-stage structure by injection and drying; Applying an adhesive patch on top of the mold; And removing the adhesive patch from the mold to attach the micro needle to the adhesive patch and separate it from the mold.

According to an embodiment of the present invention, the step of forming the micro-needle of the multi-stage structure comprises sequentially injecting and drying a composition containing at least one active ingredient into the engraved portion to form a tip portion; And a step of injecting a composition containing a polymer material and drying to form a base end portion.

According to an embodiment of the present invention, the composition containing the active ingredient is prepared by mixing the active ingredient with a polymer material, and the polymer material may be selected from the group consisting of Trehalos, Carboxymethyl cellulose NA, It is preferably characterized by comprising Lecithin, Phenoxyethanol, Disodium EDTA, Sodium Chloride and distilled water.

As described above, the present invention can deliver a plurality of active substances to be delivered to the body without causing pain, and can effectively deliver a sufficient amount of the active substance to the body. In addition, the micro needle composition and the manufacturing method according to the present invention have the effect of significantly reducing the incidence of air pockets that occur normally during manufacture.

1 is a view showing a drug delivery action by inserting a general micro needle patch into the skin.
2 is a view showing a manufacturing process of a general micro needle patch.
3 is a cross-sectional view illustrating a multi-step structure in a multi-step micro needle patch according to an embodiment of the present invention.
4 is a view illustrating a process of manufacturing a micro needle patch according to an embodiment of the present invention.
FIG. 5 is a view showing a manufacturing process of forming a multi-stage micro needle according to an embodiment of the present invention by injecting a tip portion composition of a micro needle patch.
6 is a perspective view of a general micro needle patch and a micro needle patch according to an embodiment of 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 should be understood, however, that the invention is not intended to be limited to the particular embodiments, but includes all modifications, equivalents, and alternatives falling within the spirit and scope of the invention.

Terms including ordinals such as first, second, etc. may be used to describe various elements, but the elements are not limited by such terms. These terms are used only to distinguish one component from another.

When an element is referred to as being "connected" or "connected" to another element, it may be directly connected or connected to the other element, but other elements may be present in between . On the other hand, when an element is referred to as being "directly connected" or "directly connected" to another element, it should be understood that there are no other elements in between.

The terminology used in this application is used only to describe a specific embodiment and is not intended to limit the invention. The singular expressions include plural expressions unless the context clearly dictates otherwise. In this application, the terms "comprises", "having", and the like are used to specify that a feature, a number, a step, an operation, an element, a component, or a combination thereof, But do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, or combinations thereof.

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

FIG. 3 is a cross-sectional view illustrating a multi-step structure in a multi-stage micro needle patch according to an embodiment of the present invention, and FIGS. 4 and 5 are views illustrating a process of manufacturing a micro needle patch according to an embodiment of the present invention.

A multi-layer micro needle patch of the present invention includes a plurality of needles and an adhesive patch for fixing the needles, each needle including a drug that flows into the body, is formed in the shape of a quadrangular pyramid of a multi-layer structure, A proximal portion formed by laminating a composition including a proximal portion contacting the patch, a plurality of effective components flowing into the body, and a polymer material.

More specifically, the micro needle patch has a plurality of needles spaced at regular intervals and pointedly protruded. Each of the needles is formed by laminating a proximal end portion, which is a lower end portion in contact with the patch, and a composition in which an effective ingredient to be injected into the body is mixed with a polymeric material, to form a tip portion. For example, when the effective components to be injected into the body are A, B, and C, a composition layer comprising a mixture of A and a polymer substance, a composition layer comprising a mixture of B and a polymer substance, and a composition layer comprising a mixture of C and a polymer substance While being sequentially stacked, they are narrowed to form a tip end portion so as to have a quadrangular pyramid shape. The polymeric material mixed with the drug can flow into the body and can be dissolved together with the drug and can maintain the strength of the micro needle so that the micro needle penetrates into the body without interfering with the inflow of the drug into the body , And is a material capable of forming microneedles without introducing air.

For example, the polymeric material may be selected from the group consisting of Trehalos, Carboxymethyl cellulose NA, Lecithin, Phenoxyethanol, Disodium EDTA, Sodium Chloride, And distilled water. Such compositions can form microneedles having a strength enough to be introduced into the body and dissolve without adverse effects in the body, so that they do not interfere with the absorption of the active ingredient drug, so that a soluble micro needle patch (DMN: Dissolvable MicroNeedle) It is suitable for manufacturing.

 The height of the tip portion of the micro needle patch of the multi-stage structure may be 0.1-0.8 mm, and the height of the base end portion may be 0.05-0.2 mm.

Since the plurality of drugs have a laminated structure at the tip, the height of each layer may vary depending on the type of drug to be injected into the body and the amount of the drug.
Referring to FIGS. 3 and 6, the microneedle patch of one embodiment of the present invention includes a proximal portion 34, and proximal portions 31, 32, and 33 that are sequentially stacked on the proximal portion 34. The microneedle patch according to an embodiment of the present invention is a pyramid shape having a quadrangular pyramid shape as a whole. The first end 31 of the tip end portion is formed into a quadrangular pyramid shape with its end portion sharp, 31). Fig. 3 is a cross section of the microneedles. It can be seen that the second stage 32 is formed concavely as a whole.
The third end 33 is formed to extend from the lower portion of the second end 32 to be convex and the base end 34 can be formed to extend from the lower portion of the third end 33 to be concave.
That is, the microneedle patch of the embodiment of the present invention is formed in a pyramid shape as a whole, but has a concave-convex-concave shape in cross section from the second stage 32.
In the microneedle patch of the embodiment of the present invention, the height of the first end 31 of the tip portion is larger than the height of the second end 32, the third end 33, and the base end 34 of the tip portion.

A method of manufacturing a micro needle patch of a multi-stage structure according to an embodiment of the present invention includes sequentially injecting and drying a composition including a plurality of drugs in a recessed portion of a mold including a plurality of needle- Forming a micro needle; Applying an adhesive patch to the top of the mold, and removing the adhesive patch from the mold to attach the micro needles to the adhesive patch and separate from the mold.

The mold is a mold for manufacturing the micro needle, and the shape of the multi needle micro needles is formed in a negative shape. Such a composition in which a drug and a polymer substance to be introduced into a mold are mixed with a mold is injected into a recessed portion of the mold and dried, and a composition in which a plurality of drugs are mixed is formed in a layered structure.

For example, when a drug to be introduced into the body is A, B and C, a composition comprising a mixture of A and a polymer substance is injected and dried, a composition comprising B and a polymer substance is injected and dried, A composition in which a material is mixed is injected and dried to form a microneedle having a structure in which A, B, and C are sequentially laminated. By injecting each composition and drying and then injecting the next composition, it is possible to prevent air pockets of microneedles from being formed.

A micro needle can be manufactured in this manner, an adhesive patch is applied to the top of the mold, and a needle is separated from the mold to produce a multi-stage micro needle patch

Conventionally, when a plurality of drugs are to be injected, the needles are made of a composition in which different drugs are mixed. As shown in the figure on the left side of FIG. 6, the needles include a different composition for each needle, The needle patches are made of the same material so that a plurality of drugs can be injected into the body.

 In other words, the combination of the unique biodegradable microneedle manufacturing method (DFT: DMN Formulation Technology) and Correlate Ingredient Absorb Technology (CIAT) that deeply penetrates the active ingredient into the dermis enables effective delivery of the essential ingredients through the skin.

While the invention has been shown and described with reference to certain preferred embodiments thereof, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention as defined by the appended claims. Accordingly, the true scope of the present invention should be determined by the following claims.

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Claims (6)

In a mold in which a plurality of microneedles having a multi-stage structure composed of a tip portion and a proximal end of the first to third stages are formed in an engraved shape, the polymeric material including the first drug is injected so that the first end is filled Drying;
Injecting and drying the polymeric material including the second drug so that the second end is filled in the upper portion of the first end;
Injecting and drying the polymeric material including the third drug so that the third stage is filled on the second stage, respectively;
Injecting and drying a polymer material including a fourth drug, respectively, on the upper portion of the third end so as to fill the proximal end portion;
Applying an adhesive patch on top of the mold and the base end; And
Separating the microneedles from the mold,
Wherein the first end is a quadrangular pyramid having a sharp end and the second end is formed to be concave extending from a lower portion of the first end and the third end is formed in a shape of a pyramid, And the proximal end portion is formed to be concave extending from a lower portion of the third end.
The method according to claim 1,
The method according to claim 1,
Characterized by comprising Trehalos, Carboxymethyl cellulose NA, Lecithin, Phenoxyethanol, Disodium EDTA, Sodium Chloride and Distilled Water. Of the micro needle patch.
A microneedle patch produced by the manufacturing method of claim 1 or 2.
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