Microneedle array structure and method for producing same

Abstract

The present invention relates to a microneedle array structure obviating the need to peel off a support following use, and a method for producing same. The method of the present invention allows a microneedle array structure to be provided without a separate support, and after using on the skin, the inconvenience of having to discard the support can be eliminated.

Description

Microneedle array structure and manufacturing method thereof

[0001] This patent application claims priority to Republic of Korea Patent Application No. 10-2023-0191761, filed with the Korean Intellectual Property Office on December 26, 2023, the disclosure of which is incorporated herein by reference.

[0002] The present invention relates to a microneedle array structure that does not require support peeling after use.

[0003] As efforts continue to improve the convenience of applying cosmetics and pharmaceuticals to subjects in the beauty and medical fields, "microneedles," a next-generation active ingredient delivery technology, have been gaining attention. Microneedles, a replacement for injectable or oral medications, can be simply applied to the skin to produce the same effects as existing cosmetics or pharmaceuticals. In particular, the utility of microneedles is increasing as attempts are being made to integrate them into everyday applications aimed at improving quality of life, such as obesity medications and hair loss treatments.

[0004] Microneedles are typically microscopic needles measuring several hundred nanometers in size. A microneedle array is a transdermal delivery system that consists of a patch containing a collection of multiple microneedles. This patch is applied to the skin to deliver functional cosmetics and / or drugs. Because numerous microneedles are applied to the skin to allow the body to absorb the functional active ingredients, it is often referred to as a "patch injection," and has been primarily used in the cosmetic and plastic surgery fields.

[0005] There are several types of microneedles, and they vary in form, primarily depending on their intended use and manufacturing method. Solid microneedles are microneedles made from a single material and are primarily used to create microscopic holes in the target area, followed by the additional application of functional cosmetic compositions or drugs. They are typically manufactured using materials such as silicone, metal, and polymers. Coated microneedles are microneedles whose surfaces are coated with a specific substance and are used to deliver or detect specific substances into the skin. They are typically manufactured by manufacturing solid microneedles and then coating them with a specific substance. This coating is typically made of a biocompatible material. Dissolving microneedles are microneedles that melt for a specific period of time or under specific conditions. They are primarily used for the delivery of functional cosmetic compositions or drugs. The microneedle body is inserted into the skin and melts, effectively delivering the functional active substance into the skin. Hollow microneedles are microneedles with a hollow space in the center. They are mainly used to inject or extract liquids into the skin while the microneedles are inserted into the skin, and have a shape most similar to a typical syringe.

[0006] Microneedles can be used in a variety of functional cosmetics and pharmaceuticals, depending on their size, strength, and material. In particular, they offer significantly less pain than conventional injections, leading to improved medication compliance and reduced risk of infection. Furthermore, the use of microscopic needles allows for superior delivery of functional active substances even with minimal dosage, and the delivery speed of these active substances can be controlled.

[0007] For microneedle patches with these various advantages, it has been common to provide microneedles by combining them on a non-dissolvable support, and the support must be removed after attachment to the skin. Microneedle patches require a certain amount of time for the microneedles to dissolve after attachment to the skin, and the loss of effective ingredients is inevitable during the support removal process. Furthermore, if the support remains attached to the skin after the microneedle ingredients have completely dissolved, other skin problems may occur.

[0008] The present invention has been derived to solve the above-described problems.

[0009] The present inventors have made extensive research efforts to develop a microneedle array structure in which the microneedles and the base layer form an integral soluble sheet without the need for a separate support or an adhesive component to bind the microneedles to the support, and without the need for peeling after application to the skin. As a result, when the microneedle array structure is manufactured by arranging soluble microneedles on a lattice structure sheet containing a biocompatible polymer material, the structure has flexibility and elasticity suitable for attachment to the skin, and when applied to the skin, both the microneedles and the base layer can be easily absorbed into the skin without the need for a separate process of peeling the support from the skin, thereby completing the present invention.

[0010] Accordingly, an object of the present invention is to provide a microneedle array structure.

[0011] Another object of the present invention is to provide a method for manufacturing a microneedle array structure.

[0012] According to one aspect of the present invention, the present invention provides a microneedle array structure comprising a base layer having a lattice shape and a plurality of microneedles formed by protruding in one direction of the base layer; the microneedles are arranged at predetermined intervals at each corner and / or each side of each square unit constituting the lattice shape; and the base layer and the microneedles are both made of a biocompatible biodegradable polymer material.

[0013]

[0014] The present inventors have made extensive research efforts to develop a microneedle array structure in which the microneedles and the base layer form an integral soluble sheet without the need for a separate support or an adhesive component to bind the microneedles to the support, and without the need for peeling after application to the skin. As a result, it was discovered that when a microneedle array structure is manufactured by arranging soluble microneedles on a lattice structure sheet containing a biocompatible polymer material, the structure has flexibility and elasticity suitable for attachment to the skin, and when applied to the skin, both the microneedles and the base layer can be easily absorbed into the skin without the need for a separate process of peeling the support from the skin.

[0015] In one embodiment of the present invention, the height of the microneedle and the maximum diameter of the bottom have a length ratio of 1:5 to 3:1, and the maximum diameter of the bottom of the microneedle and the width of the side of the square unit have a length ratio of 1:1 to 1:5.

[0016] In one embodiment of the present invention, the width of a side of a square unit and the length of each side have a length ratio of 1:5 to 1:30.

[0017] In one embodiment of the present invention, the length of the microneedle is 50 μm to 1000 μm, and the maximum diameter of the bottom of the microneedle is 50 μm to 5000 μm.

[0018] In one embodiment of the present invention, the microneedle has a tip that is conical, pyramidal, or turret-shaped.

[0019] In one embodiment of the present invention, the biocompatible polymer material constituting the microneedle is hyaluronic acid (HA), poly(lactic acid; PLA), poly(ε-caprolactone; PCL), polyhydroxyalkanoate (PHA), polyesteramide (PEA), polyethylene glycol (PEG), poly(p-dioxanone; PPDO), poly(lactic-co-glycolic acid; PLGA), polyglycolic acid (PGA), polyvinyl alcohol (PVA), chitosan, collagen, gelatin, alginic acid, pectin, carrageenan, Chondroitin sulfate, dextran sulfate, polylysine, carboxymethyl chitin, fibrin, agarose, pullulan, cellulose, polyvinylpyrrolidone (PVP);Hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hydroxypropyl methyl cellulose (HPMC), carboxymethyl cellulose, gum arabic, cyclodextrin, dextrin, glucose, fructose, starch, trehalose, glucose, maltose, lactose, lactulose, fructose, turanose, melitose, melezitose, dextran, sorbitol, xylitol, palatinit, polyglycolic acid, polyethylene oxide, At least one selected from the group consisting of polyacrylic acid, polyacrylamide, polymethacrylic acid, and polymaleic acid;

[0020] In one embodiment of the present invention, the biocompatible polymer material constituting the base layer is hyaluronic acid (HA), poly(lactic acid; PLA), poly(ε-caprolactone; PCL), polyhydroxyalkanoate (PHA), polyesteramide (PEA), polyethylene glycol (PEG), poly(p-dioxanone; PPDO), poly(lactic-co-glycolic acid; PLGA), polyglycolic acid (PGA), polyvinyl alcohol (PVA), chitosan, collagen, gelatin, alginic acid, pectin, carrageenan, Chondroitin sulfate, dextran sulfate, polylysine, carboxymethyl chitin, fibrin, agarose, pullulan, cellulose, polyvinylpyrrolidone (PVP);Hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hydroxypropyl methyl cellulose (HPMC), carboxymethyl cellulose, gum arabic, cyclodextrin, dextrin, glucose, fructose, starch, trehalose, glucose, maltose, lactose, lactulose, fructose, turanose, melitose, melezitose, dextran, sorbitol, xylitol, palatinit, polyglycolic acid, polyethylene oxide, Any one selected from the group consisting of polyacrylic acid, polyacrylamide, polymethacrylic acid, and polymaleic acid;

[0021] In one embodiment of the present invention, the microneedles and the base layer are made of the same biocompatible polymer.

[0022] In one embodiment of the present invention, the microneedle array structure additionally includes a predetermined cargo material to be delivered into the skin of a subject.

[0023] In one embodiment of the present invention, the cargo material is at least one selected from the group consisting of low molecular weight compounds, peptides, proteins, nucleic acids, polysaccharides, viruses, and liposomes.

[0024]

[0025] According to another aspect of the present invention, the present invention provides a method for manufacturing a microneedle array structure, comprising the following steps:

[0026] (a) a step of filling a biocompatible polymer material into a negative mold including a base layer in a lattice shape and a plurality of microneedle-shaped filling portions formed by protruding in one direction of the base layer; and

[0027] (b) A step of separating the microneedle array structure formed by solidifying the biocompatible polymer material filled through step (a) from the negative mold.

[0028] In one embodiment of the present invention, the negative mold is manufactured through a step of filling a curable resin or a biocompatible polymer into a positive mold including the base layer and the microneedle shape and curing the curable resin or biocompatible polymer.

[0029] The features and advantages of the present invention are summarized as follows:

[0030] (a) The present invention provides a microneedle array structure.

[0031] (b) The present invention provides a method for manufacturing a microneedle array structure.

[0032] (c) When the microneedle array structure of the present invention is used, it can be provided without the need for a separate support, and the inconvenience of having to remove the support after application to the skin can be eliminated.

[0033] FIG. 1 illustrates a microneedle array structure including a grid-shaped base layer according to one embodiment of the present invention.

[0034] Figure 2 is a schematic diagram showing a microneedle array structure (1) and a cross-sectional shape according to one embodiment of the present invention.

[0035] Figure 3 shows an example of a cross-sectional shape of a base layer (20) according to one embodiment of the present invention.

[0036] Figure 4 shows an example of the shape of a microneedle (10) according to one embodiment of the present invention.

[0037] FIG. 5 shows a dimensional drawing of a microneedle array structure according to one embodiment of the present invention.

[0038] FIG. 6 illustrates an example of a positive mold for manufacturing a microneedle array structure according to one embodiment of the present invention.

[0039] Hereinafter, with reference to the attached drawings, embodiments of the microneedle array structure of the present invention will be described in detail so that those skilled in the art can easily practice the present invention. The terms used in this specification have been selected from currently widely used general terms as much as possible while considering the functions of the present invention, but these may vary depending on the intention of engineers working in the related field, precedents, the emergence of new technologies, etc. Unless otherwise defined, the technical and scientific terms used may have the meaning commonly understood by those skilled in the art to which this invention pertains.

[0040] As used herein and in the appended claims, the singular expression "singular" includes the plural expression unless the context clearly dictates otherwise. Furthermore, the plural expression "singular" includes the singular expression unless the context clearly dictates otherwise.

[0041] In this specification and the appended claims, the terms “include” or “have” mean that a feature or component described in the specification is present, and unless specifically limited, does not preclude the possibility that one or more other features or components may be added.

[0042] Additionally, the numerical ranges used herein include lower and upper limits and all values ​​within that range, increments logically derived from the shape and width of the defined range, all doubly defined values, and all possible combinations of upper and lower limits of numerical ranges defined in different shapes. Unless otherwise specifically defined in the specification of the present invention, values ​​outside the numerical range that may arise due to experimental error or rounding of values ​​are also included in the defined numerical range.

[0043] The term “about” or the like used in this specification and the appended claims is used to encompass the tolerance when an tolerance exists.

[0044] The term “biocompatibility” as used herein means the property of being substantially non-toxic, chemically inert and non-immunogenic to the human body.

[0045] The term “biodegradability” in this specification refers to the property of being self-decomposed in response to environmental factors within the human body, such as temperature, moisture, and microorganisms.

[0046] “Microneedle” according to one embodiment of the present invention refers to a dissolving microneedle, which is a microneedle that has the property of dissolving when inserted into the skin.

[0047] “Microneedle array structure” according to one embodiment of the present invention means a microneedle assembly in which a plurality of microneedles are arranged in a predetermined manner.

[0048] Conventional microneedle arrays are provided with a support (patch) to which the microneedles are attached. When a support is included, a separate adhesive is applied during the manufacturing process to bond the microneedles to the support. Furthermore, effective attachment to areas with significant skin flexion is challenging, and removal of the support after a certain period of time after application to the skin is essential.

[0049] In order to solve the above-described problem, the present inventors have developed a microneedle array structure in which the microneedles and the base layer form an integral body by filling a biocompatible soluble microneedle raw material into a negative mold and then filling a biocompatible soluble base layer raw material on top of the microneedle filling portion and molding it into a lattice shape after the molding process, thereby having flexibility suitable for attachment to curved parts of the skin and improving usability by eliminating the need for a separate process of removing the support after application to the skin.

[0050] A microneedle array structure (1) according to one embodiment of the present invention is characterized in that the microneedles (10) are provided in a state of being bonded to a base layer having a lattice shape.

[0051] As illustrated in FIG. 1, a microneedle array structure according to one embodiment of the present invention has a plurality of microneedles arranged on one surface of a base layer such as a lattice shape or a mesh structure.

[0052] In the case of conventional general microneedle patches, a flat support made of a non-biodegradable material has been used, and microneedles have been attached to one surface of the support. However, in the case of the microneedle array structure according to an embodiment of the present invention, a lattice-shaped biodegradable polymer is used as a base layer, and microneedles (10) are positioned on one surface of the lattice-shaped base layer (20), thereby imparting flexibility to the microneedle array structure, and providing a microneedle array structure that does not require removing the non-dissolvable support after attachment to the skin.

[0053] Fig. 2 shows a cross-section of a microneedle array structure (1) according to one embodiment of the present invention. The 'parallel cross-section plane (1b)', which cuts the microneedle array structure along a vertical plane that passes through the center of a lattice point, which is a point where the horizontal and vertical sides constituting the lattice shape intersect, and is parallel to the horizontal or vertical sides, and the 'vertical cross-section plane (1a)', which cuts the microneedle array structure along a vertical plane that is parallel to the horizontal or vertical sides but does not pass through the center of the lattice point, are shown. By examining the vertical cross-section plane (1a), a cross-section perpendicular to the longitudinal direction of the horizontal and vertical sides constituting the base layer can be confirmed, and through this, a vertical cross-sectional shape of a base layer portion of a negative mold for manufacturing the microneedle array structure according to one embodiment of the present invention can be confirmed.

[0054] The microneedles (10) protruding on the above base layer (20) can be arranged on the base layer according to a predetermined size, shape, number, and spacing depending on the purpose and use. The size, number, and spacing of the microneedles can be determined depending on the amount of biodegradable polymer material and / or additional effective ingredient to be administered through the skin of the subject. In one embodiment of the present invention, both the microneedles (10) and the base layer (20) are biocompatible biodegradable polymer materials. The microneedles (10) must have a rigidity that can penetrate the skin, and the base layer (20) must have a flexibility that can be attached to curved skin. In order to achieve these characteristics, the inventors of the present invention manufactured the base layer (20) in a lattice shape.

[0055] In addition, in one embodiment of the present invention, the length (h) of the microneedle (10) and the maximum diameter (dm) of the bottom of the microneedle have a length ratio of 1:5 to 3:1. In other specific examples, the length (h) and the diameter (dm) have a length ratio of 1:4 to 3:1, 1:3 to 3:1, 1:2 to 3:1, 1:1 to 3:1, 1:1 to 2.5:1, or 1:1 to 2:1. The maximum diameter of the bottom surface of the microneedle (10) described above is, for example, if the shape of the bottom surface of the microneedle (10) is an equilateral triangle, the length of one side becomes the maximum diameter, if it is a circle, the length of the diameter becomes the maximum diameter, if it is a regular polygon with an even number of vertices, the length from one vertex to the opposite vertex becomes the maximum diameter, and if it is a regular polygon with an odd number of vertices, the length from one vertex to either of the two vertices of the opposite side becomes the maximum diameter.

[0056] In a specific embodiment of the present invention, the width (w) of the side of each square unit of the base layer (20) means the maximum width that the base layer has among the vertical cross-sections (1a) of the side, as shown in FIG. 2. In addition, the length (dt) of the side of each square unit means the length from one grid point to the adjacent grid point, or in other words, the distance from the intersection point where the central axis of any horizontal side forming the grid shape intersects the central axis of the vertical side to the other closest adjacent intersection point. The width (w) of the side of the square unit and the length (dt) of each side have a length ratio of 1:5 to 1:30. In other specific embodiments, the length ratio may be from 1:5 to 1:25, from 1:5 to 1:20, from 1:5 to 1:19, from 1:5 to 1:18, from 1:5 to 1:17, from 1:5 to 1:16, from 1:5 to 1:15, from 1:6 to 1:14, from 1:7 to 1:13, or from 1:8 to 1:12.

[0057] In one embodiment of the present invention, the length (h) of the microneedle (10) can be variously adjusted by various factors such as changes in the strength of the microneedle (10) due to changes in the purpose of use or raw materials, and specifically, for example, the length (h) of the microneedle (10) can be 50 μm to 1000 μm. In other specific examples, the length (h) of the microneedle (10) can be 50 μm to 800 μm, 50 μm to 700 μm, 50 μm to 600 μm, 50 μm to 500 μm, or 100 μm to 500 μm, and can be variously adjusted. In addition, in one embodiment of the present invention, the maximum diameter (dm) of the bottom surface of the microneedle (10) may be appropriately selected by a person skilled in the art in relation to the length (h) of the microneedle (10) so as to form a minimum tip angle of the microneedle (10) that can penetrate the skin. Specifically, for example, the maximum diameter (dm) of the bottom surface of the microneedle (10) may be 50 μm to 5000 μm. In other specific embodiments, the maximum diameter (dm) is 50 μm to 4500 μm, 50 μm to 4000 μm, 50 μm to 3500 μm, 50 μm to 3000 μm, 50 μm to 2500 μm, 50 μm to 2000 μm, 50 μm to 1500 μm, 50 μm to 1400 μm, 50 μm to 1300 μm, 50 μm to 1200 μm, 50 μm to 1100 μm, 50 μm to 1000 μm, 50 μm to 950 μm, 50 μm to 900 μm, 50 μm to 850 μm, 50 μm to 800 μm, 50 μm to 750 μm, 50 μm to 700 μm, 50 μm to 650 μm, 50 μm to 600 μm, 50 μm to 550 μm, or 50 μm to 500 μm, and can be variously adjusted.

[0058] In one embodiment of the present invention, the thickness of the base layer (20) is measured as the distance from the bottom surface of the microneedle to the bottom surface of the base layer (20), and may be, for example, 50 μm to 1000 μm. In other specific examples, the thickness of the base layer (20) may be 50 μm to 800 μm, 50 μm to 700 μm, 50 μm to 600 μm, 50 μm to 500 μm, or 100 μm to 500 μm, and may be variously adjusted.

[0059] In one embodiment of the present invention, referring to FIG. 3, the shape of the vertical cross-section of the base layer (20) is not particularly limited, and can be manufactured in various shapes such as polygons, trapezoids, and semicircles. However, in the case of manufacturing by a molding method using a negative mold, in consideration of the convenience of separating the manufactured product from the negative mold, it is preferable to design a shape that gradually narrows or at least does not become larger from the portion exposed to the outside toward the inside of the negative mold when filling the raw material onto the negative mold.

[0060] In one embodiment of the present invention, the microneedle (10) may have a tip shape of a cone, a polygonal pyramid, or a bell tower shape (see FIG. 4), and any shape of the tip that can penetrate the skin is sufficient, but is not necessarily limited thereto. The polygonal pyramid shape includes a triangular pyramid, a square pyramid, and various polygonal pyramid shapes including a hexagonal pyramid, an octagonal pyramid, a dodecagonal pyramid, etc., and is not particularly limited. The bell tower shape refers to a shape illustrated on the far right of FIG. 4, and the shape of the microneedle (10) is not particularly limited as long as it has a tip shape suitable for penetrating the skin.

[0061] The plurality of microneedles (10) included in one microneedle array structure (1) do not need to all have the same shape, and may be a collection of various shapes. However, in order to uniformly apply the microneedle array structure (1) to the entire area of ​​the application site, it is preferable that the microneedles (10) included in one microneedle array structure (1) be designed to have the same shape.

[0062] In one specific example of the present invention, the biocompatible polymer material constituting the microneedle (10) is hyaluronic acid (HA), poly(lactic acid; PLA), poly(ε-caprolactone; PCL), polyhydroxyalkanoate (PHA), polyesteramide (PEA), polyethylene glycol (PEG), poly(p-dioxanone; PPDO), poly(lactic-co-glycolic acid; PLGA), polyglycolic acid (PGA), polyvinyl alcohol (PVA), chitosan, collagen, gelatin, alginic acid, pectin, carrageenan, Chondroitin sulfate, dextran sulfate, polylysine, carboxymethyl chitin, fibrin, agarose, pullulan, cellulose, polyvinylpyrrolidone (PVP);Hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hydroxypropyl methyl cellulose (HPMC), carboxymethyl cellulose, gum arabic, cyclodextrin, dextrin, glucose, fructose, starch, trehalose, glucose, maltose, lactose, lactulose, fructose, turanose, melitose, melezitose, dextran, sorbitol, xylitol, palatinit, polyglycolic acid, polyethylene oxide, Any one selected from the group consisting of polyacrylic acid, polyacrylamide, polymethacrylic acid, and polymaleic acid;

[0063] In addition, as a biocompatible polymer material constituting the base layer (20) of the microneedle array structure (1) according to one specific example of the present invention, the biocompatible polymer material constituting the microneedle (10) can be used in the same manner, and hyaluronic acid (HA), poly(lactic acid; PLA), poly(ε-caprolactone; PCL), polyhydroxyalkanoate (PHA), polyesteramide (PEA), polyethylene glycol (PEG), poly(p-dioxanone; PPDO), poly(lactic-co-glycolic acid; PLGA), polyglycolic acid (PGA), polyvinyl alcohol (PVA), chitosan, collagen, gelatin, Alginic acid, pectin, carrageenan, chondroitin sulfate, dextran sulfate, polylysine, carboxymethyl chitin, fibrin, agarose, pullulan, cellulose, polyvinylpyrrolidone (PVP);Hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hydroxypropyl methyl cellulose (HPMC), carboxymethyl cellulose, gum arabic, cyclodextrin, dextrin, glucose, fructose, starch, trehalose, glucose, maltose, lactose, lactulose, fructose, turanose, melitose, melezitose, dextran, sorbitol, xylitol, palatinit, polyglycolic acid, polyethylene oxide, Any one or more selected from the group consisting of polyacrylic acid, polyacrylamide, polymethacrylic acid, and polymaleic acid may be used.;

[0064] In one embodiment of the present invention, the microneedles (10) and the base layer (20) may be made of the same biocompatible polymer. When the microneedle array structure (1) of the present invention is manufactured using a negative mold, if the microneedles (10) and the base layer (20) are designed to be formed of the same biocompatible polymer, the microneedle array structure (1) can be manufactured through a single raw material filling and molding process in a single negative mold in which the shapes of the microneedles (10) and the base layer (20) are engraved. This means that there may be a great advantage in the manufacturing process compared to the conventional technology including a separate non-biodegradable support. Meanwhile, considering the characteristics of the microneedles (10) that penetrate the skin immediately when the microneedle array structure (1) is applied to the skin and the base layer (20) that is expected to be gradually absorbed into the skin after being attached to the skin, the microneedle (10) layer and the base layer (20) may be selected from different biocompatible and biodegradable polymers depending on the intended use. This means that different raw materials can be selected from among the biocompatible polymer materials described above to form the microneedle (10) and base layer (20).

[0065] In one embodiment of the present invention, the microneedle array structure (1) may additionally include a predetermined cargo material to be delivered into the skin of a subject. The term “cargo” material in this embodiment refers to a biocompatible material suitable for injection into a living body, and an effective material expected to exhibit a desired effect by the user, and is not particularly limited. Specifically, for example, the cargo material may be at least one selected from the group consisting of low-molecular-weight compounds, peptides, proteins, nucleic acids, polysaccharides, viruses, and liposomes. The nucleic acids described above may include oligonucleotides, plasmid DNA, siRNA, PNAs (peptide nucleic acids), and the like. Specifically, for example, the cargo material of the present invention may be selected without limitation from conventionally known pharmaceutical compositions or functional cosmetic compositions.

[0066]

[0067] A microneedle array structure (1) according to one embodiment of the present invention can be manufactured by a microneedle array structure manufacturing method including the following steps:

[0068] (a) a step of filling a biocompatible biodegradable polymer material into a negative mold including a base layer in a grid shape and a plurality of microneedle-shaped filling portions formed by protruding in one direction of the base layer; and

[0069] (b) A step of separating the microneedle array structure formed by solidifying the biocompatible biodegradable polymer material filled through step (a) from the negative mold.

[0070] In one embodiment of the present invention, the negative mold may be manufactured through a step of filling a curable resin or a biocompatible biodegradable polymer into a positive mold including the base layer and the microneedle shape and curing the curable resin.

[0071] In one embodiment of the present invention, as the curable resin, a thermosetting resin, such as phenol resin (PF), melamine resin (MF), epoxy resin (EP), urea resin, alkyd resin, polyisoprene, which is a natural rubber, styrene butadiene rubber (SBR), nitrile butadiene rubber (NBR), polychloroprene, and silicone rubber, which are synthetic rubbers, may be used. However, any material that has the property of being able to fill a positive mold mold to form a negative array mold may be used without limitation.

[0072] In one embodiment of the present invention, any one or more of the biocompatible polymers listed as being usable for manufacturing the microneedle (10) and base layer (20) described above may be appropriately selected and used as a biocompatible biodegradable polymer for manufacturing the negative array mold.

[0073]

[0074] (Example)

[0075] Fabrication of lattice-type microneedle array structures

[0076] Squares measuring 6 mm × 6 mm are assembled to form a grid measuring 246 mm × 168 mm in total size, and on a base layer with a width of each horizontal and vertical side of the grid of 0.6 mm, microneedles are formed at the corners (grid points) of each square and at each point where each side of the square is divided into three equal parts, and each microneedle is an octagonal pyramid-shaped positive mold having a base width of 0.24 mm and a height of 0.32 mm (see Figs. 1 and 2).

[0077] A certain amount of silicone was filled into the top of the prepared positive mold mold until the positive mold mold was submerged, and after curing, the polymer resin was separated to manufacture a negative array mold.

[0078] Hyaluronic acid was filled into not only the microneedle portion of the above-mentioned negative array mold but also the lattice-shaped base layer portion, and then dried with hot air. The molded microneedle array was separated from the negative array mold to manufacture a microneedle array structure. The average height of the microneedle was 0.3 mm, and the average height of the lattice-shaped base layer was also 0.3 mm.

[0079]

[0080] (Comparative Example)

[0081] Fabrication of patch-type microneedle array structures

[0082] Unlike the lattice-shaped base layer of the lattice-shaped microneedle array structure of Example 1, a patch-shaped microneedle array structure was manufactured in which microneedles of the same size and arrangement were formed on a two-dimensional, flat, sheet-shaped base layer that does not form a lattice.

[0083]

[0084] In the case of the lattice-type microneedle array structure manufactured according to one embodiment of the present invention, compared to the patch-type microneedle array structure according to the comparative example, it was easy to attach to curved skin, and after a certain period of time, the components remaining on the skin were minimized, so that a separate washing process was not required.

[0085]

[0086] Although some embodiments of the present invention have been described in detail based on some embodiments of the present invention as described above, the spirit of the present invention is not limited to the embodiments and examples presented in this specification, and a person having ordinary knowledge in the technical field to which the present invention pertains can easily propose other embodiments and examples by adding, changing, deleting, or adding components within the scope of the same spirit, and this is also included within the scope of the present invention.

[0087] [Explanation of symbols]

[0088] 1: Microneedle array structure

[0089] 10: Microneedles

[0090] 20: Base layer

[0091] h: microneedle length

[0092] dm: maximum diameter of the bottom of the microneedle

[0093] w: width of each square unit of the base layer (20) (w)

[0094] dt: side length (dt) of each square unit of the base layer (20)

Claims

1. Comprising a base layer having a grid shape and a plurality of microneedles formed by protruding in one direction of the base layer; The above microneedles are arranged at a predetermined interval at each corner and / or each side of each square unit forming the grid shape; A microneedle array structure in which both the base layer and the microneedles are made of a biocompatible, biodegradable polymer material.

2. In paragraph 1, A microneedle array structure, characterized in that the height of the microneedle and the maximum diameter of the bottom have a length ratio of 1:5 to 3:1, and the maximum diameter of the bottom of the microneedle and the width of the side of the square unit have a length ratio of 1:1 to 1:

5.

3. In paragraph 1, A microneedle array structure, characterized in that the width of the side of the square unit and the length of each side have a length ratio of 1:5 to 1:

30.

4. In paragraph 1, A microneedle array structure, characterized in that the length of the microneedles is 50 μm to 1000 μm, and the maximum diameter of the bottom of the microneedles is 50 μm to 5000 μm.

5. In paragraph 1, A microneedle array structure, characterized in that the microneedles have a tip having a cone shape, a polypyramid shape, or a bell shape.

6. In paragraph 1, The biocompatible biodegradable polymer materials constituting the above microneedles are hyaluronic acid (HA), poly(lactic acid; PLA), poly(ε-caprolactone; PCL), polyhydroxyalkanoate (PHA), polyesteramide (PEA), polyethylene glycol (PEG), poly(p-dioxanone; PPDO), poly(lactic-co-glycolic acid; PLGA), polyglycolic acid (PGA), polyvinyl alcohol (PVA), chitosan, collagen, gelatin, alginic acid, pectin, carrageenan, Chondroitin sulfate, dextran sulfate, polylysine, carboxymethyl chitin, fibrin, agarose, pullulan, cellulose, polyvinylpyrrolidone (PVP);Hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hydroxypropyl methyl cellulose (HPMC), carboxymethyl cellulose, gum arabic, cyclodextrin, dextrin, glucose, fructose, starch, trehalose, glucose, maltose, lactose, lactulose, fructose, turanose, melitose, melezitose, dextran, sorbitol, xylitol, palatinit, polyglycolic acid, polyethylene oxide, A microneedle array structure, wherein at least one material is selected from the group consisting of polyacrylic acid, polyacrylamide, polymethacrylic acid, and polymaleic acid.

7. The biocompatible biodegradable polymer material constituting the above base layer is hyaluronic acid (HA), poly(lactic acid); PLA, poly(ε-caprolactone; PCL), polyhydroxyalkanoate (PHA), polyesteramide (PEA), polyethylene glycol (PEG), poly(p-dioxanone; PPDO), poly(lactic-co-glycolic acid); PLGA, polyglycolic acid (PGA), polyvinyl alcohol (PVA), chitosan, collagen, gelatin, alginic acid, pectin, carrageenan, Chondroitin sulfate, dextran sulfate, polylysine, carboxymethyl chitin, fibrin, agarose, pullulan, cellulose, polyvinylpyrrolidone (PVP);Hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hydroxypropyl methyl cellulose (HPMC), carboxymethyl cellulose, gum arabic, cyclodextrin, dextrin, glucose, fructose, starch, trehalose, glucose, maltose, lactose, lactulose, fructose, turanose, melitose, melezitose, dextran, sorbitol, xylitol, palatinit, polyglycolic acid, polyethylene oxide, A microneedle array structure characterized by being any one selected from the group consisting of polyacrylic acid, polyacrylamide, polymethacrylic acid, and polymaleic acid.; 8. A microneedle array structure according to claim 1, characterized in that the microneedles and the base layer are made of the same biocompatible biodegradable polymer.

9. In any one of paragraphs 1 to 8, A microneedle array structure characterized in that the above structure additionally includes a specific cargo material to be delivered into the skin of a subject.

10. In paragraph 9, A microneedle array structure, wherein the cargo material is at least one selected from the group consisting of low molecular weight compounds, peptides, proteins, nucleic acids, polysaccharides, viruses, and liposomes.

11. A method for manufacturing a microneedle array structure comprising the following steps: (a) a step of filling a biocompatible biodegradable polymer material into a negative mold including a base layer in a lattice shape and a plurality of microneedle-shaped filling portions formed by protruding in one direction of the base layer; and (b) A step of separating the microneedle array structure formed by hardening the biocompatible biodegradable polymer material filled through step (a) from the negative mold.

12. A method for manufacturing a microneedle array structure according to claim 11, characterized in that the negative mold is manufactured through a step of filling a curable resin or a biocompatible biodegradable polymer into a positive mold including the base layer and the microneedle shape and curing the curable resin.

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