KR102611702B1 - Micro-needle patch and manufacturing method for micro-needle patch - Google Patents

Abstract

The present invention relates to a microneedle patch and a method of manufacturing the microneedle patch, comprising the steps of filling a mold having a plurality of needle grooves with a buffer solution, placing a base material on the needle groove, and applying the base material to the buffer solution. It includes the step of spreading and drying the mold.

Description

Microneedle patch and manufacturing method for microneedle patch {Micro-needle patch and manufacturing method for micro-needle patch}

The present invention relates to a microneedle patch and a method of manufacturing the microneedle patch.

Injection of drugs into the human body has traditionally been done through needle injection, but needle injection causes great pain. Accordingly, non-invasive drug injection methods have also been developed, but there is a problem that the amount of drug required is too large compared to the injection amount.

Due to these problems, much research has been conducted on drug delivery systems (DDS), which has made greater progress possible with the development of nanotechnology.

Micro-needles, unlike conventional injection needles, can feature painless skin penetration and no trauma. Additionally, the micro-needle must penetrate the stratum corneum of the skin, so a certain level of physical hardness may be required. Additionally, an appropriate length may be required for the bioactive substance to reach the epidermal or dermal layer of the skin. In addition, in order for the bioactive substances of hundreds of micro-needles to be effectively delivered into the skin, the micro-needles must have high skin permeability and must be maintained for a certain period of time until dissolution after insertion into the skin.

Accordingly, interest in microneedles that can deliver drugs in precise amounts and accurately set target positions is increasing.

Republic of Korea Patent Publication No. 10-2017-0008183 (2017.01.23.)

The present invention can provide a microneedle patch that can effectively deliver an active ingredient to a target location in a quantitative amount, and a method of manufacturing the microneedle patch.

One aspect of the present invention includes filling a mold with a plurality of needle grooves with a buffer solution, placing a base material on the needle grooves, diffusing the base material into the buffer solution, and forming the mold. Provides a method for manufacturing a microneedle patch including the step of drying.

Additionally, in the step of diffusing the base material into the buffer solution, the base material may be injected into the needle groove.

Additionally, the buffer solution can dissolve the base material.

Additionally, the buffer solution may contain water, and the base material may contain hyaluronic acid.

Additionally, an active ingredient may be disposed inside the base material.

Additionally, in the step of drying the mold, the buffer solution may be removed, and the base material may harden in the needle groove.

Another aspect of the present invention provides a microneedle patch including a base and a plurality of microneedles mounted on the base, wherein the microneedle is dried after the base material is dissolved in the buffer solution.

Additionally, the buffer solution may contain water, and the base material may contain hyaluronic acid.

Additionally, an active ingredient may be disposed inside the base material.

Other aspects, features and advantages in addition to those described above will become apparent from the following drawings, claims and detailed description of the invention.

The microneedle patch manufacturing apparatus and microneedle patch manufacturing method according to the present invention can manufacture high quality microneedle patches. By creating a vacuum in the mold, the residual gas inside the microneedle patch is removed to ensure that the microneedle does not contain foreign substances. By removing the gas between the mold and the base material, a microneedle patch is easy to attach to the target and is effective in drug delivery. It can be manufactured.

Figure 1 is a diagram showing an apparatus for manufacturing a microneedle patch according to an embodiment of the present invention.
Figure 2 is a perspective view showing the microneedle patch manufactured according to Figure 1.
Figure 3 is a flowchart showing a method of manufacturing a microneedle patch according to another embodiment of the present invention.
Figures 4 to 8 are diagrams showing steps for manufacturing microneedles using the microneedle patch manufacturing method of Figure 3.
Figure 9 is a diagram showing the microneedle patch of Figure 2.
Figures 10 to 12 are diagrams showing another embodiment of the microneedle patch of Figure 9.

Hereinafter, the configuration and operation of the present invention will be described in detail with reference to embodiments of the present invention shown in the attached drawings.

Since the present invention can be modified in various ways and can have various embodiments, specific embodiments will be illustrated in the drawings and described in detail in the detailed description. The effects and features of the present invention and methods for achieving them will become clear by referring to the embodiments described in detail below along with the drawings. However, the present invention is not limited to the embodiments disclosed below and may be implemented in various forms.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. When describing with reference to the drawings, identical or corresponding components will be assigned the same reference numerals and redundant description thereof will be omitted. .

In the following embodiments, terms such as first and second are used not in a limiting sense but for the purpose of distinguishing one component from another component.

In the following examples, singular terms include plural terms unless the context clearly dictates otherwise.

In the following embodiments, terms such as include or have mean that the features or components described in the specification exist, and do not exclude in advance the possibility of adding one or more other features or components.

In the drawings, the sizes of components may be exaggerated or reduced for convenience of explanation. For example, the size and thickness of each component shown in the drawings are shown arbitrarily for convenience of explanation, so the present invention is not necessarily limited to what is shown.

In cases where an embodiment can be implemented differently, a specific process sequence may be performed differently from the described sequence. For example, two processes described in succession may be performed substantially at the same time, or may be performed in an order opposite to that in which they are described.

Figure 1 is a diagram showing an apparatus for manufacturing a microneedle patch according to an embodiment of the present invention.

Referring to FIG. 1, the microneedle patch manufacturing apparatus 1 may include a first injection module 10, a second injection module 20, and a drying module 30.

In the drawing, the microneedle patch manufacturing device 1 shows a first injection module 10, a second injection module 20, and a drying module 30 each sequentially disposed, but the microneedle patch manufacturing device 1 is not limited to this. The needle patch may be modified in various ways depending on the manufacturing process.

As an example, the microneedle patch manufacturing device 1 may be provided with a plurality of at least one of the first injection module 10, the second injection module 9), and the drying module 30. As another example, in the microneedle patch manufacturing device 1, the drying module 30 may be disposed prior to the second injection module 20.

In one embodiment, the first injection module 10 may inject the buffer solution (BS) into the mold (M), and the second injection module 20 may place the base material (BM) into the mold (M). . As shown in FIG. 1, the first injection module 10 and the second injection module 20 may be provided, respectively.

In another embodiment, the first injection module 10 may inject both the buffer solution (BS) and the base material (BM) into the mold (M). The first injection module 10 may be integrated to inject both the buffer solution (BS) and the base material (BM).

The drying module 30 dries the mold (M) after the mold (M) is mounted inside. When the drying module 30 is driven, the buffer solution BS may be removed.

Figure 2 is a perspective view showing the microneedle patch manufactured according to Figure 1.

Referring to FIG. 2, the microneedle patch 100 manufactured in the microneedle patch manufacturing apparatus 1 may have a plurality of microneedles 120 disposed on the base 110. The microneedle patch 100 can be attached to an object and deliver drugs or cosmetic substances.

The base 110 supports the microneedles 120, and may be provided with a plurality of microneedles 120 on one surface. One side of the base 110 may be in contact with the skin, and the opposite side may be exposed to the outside.

The base 110 can be removed when the microneedle 120 is implanted into the skin. In one example, the base may be removed from the skin by the user applying force. As another example, the portion where the base 110 and the microneedle 120 are connected to the microneedle patch 100 is dissolved first, and the base 110 can be removed after a certain period of time has elapsed after attachment. As another example, the base 110 of the microneedle patch 100 may dissolve when attached for a long time. As another example, the base 110 may be removed by the user applying a material for dissolution.

In one embodiment, the base 110 may include any one of the materials included in the microneedle 120. The base 110 may include a biodegradable material like the microneedle 120.

In alternative embodiments, base 110 may include a biologically active material. After attaching the microneedle patch 100 to the skin, the active ingredient can be effectively delivered to the patient by the biologically active substance emitted from the base 110. Additionally, the base 110 and the microneedle 120 can be easily separated by the physiologically active material coming from the base 110.

In one embodiment, the base 110 may have a slower solubility than the layer closest to the microneedle 120, that is, the layer disposed furthest from the tip of the microneedle 120. Since the portion of the microneedle 120 adjacent to the base 110 dissolves the fastest, the base 110 can be easily separated from the microneedle 120.

In one embodiment, the base 110 may include a water-soluble polymer. The base 110 may be composed of a water-soluble polymer or may contain other additives (for example, disaccharides, etc.). Additionally, the base 110 preferably does not contain drugs or active ingredients.

Base 110 may include a biocompatible material. The base 110 may be made of a biocompatible material selected as the base material of the microneedle 120, which will be described later.

Microneedles 120 protrude from the surface of the base 110 and may be provided in plural numbers. The microneedle 120 is formed of a base material (BM), and the base material (BM) may include biocompatible materials and additives.

Biocompatible materials include Carboxymethyl cellulose (CMC), Hyaluronic acid (HA), alginic acid, Pectin, Carrageenan, Chondroitin Sulfate, and Dex. Dextran Sulfate, Chitosan, polylysine, carboxymethyl chitin, fibrin, Agarose, pullulan, polyanhydride , polyorthoester, polyetherester, polyesteramide, poly butyric acid, poly valeric acid, polyacrylate, Ethylene-vinyl acetate polymer, acrylic substituted cellulose acetate, polyvinyl chloride, polyvinyl fluoride, polyvinyl imidazole, chlorosulphonate polyolefins , polyethylene oxide, polyvinylpyrrolidone (PVP), hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC), hydroxypropylcellulose (HPC), carboxymethyl cellulose, cyclodextrin. Contains at least one of (Cyclodextrin), Maltose, Lactose, Trehalose, Cellobiose, Isomaltose, Turanose, and Lactulose; , one or more polymers selected from the group consisting of cellulose and copolymers of monomers that form such polymers.

Additives include trehalose, oligosaccharide, sucrose, maltose, lactose, cellobiose, hyaluronic acid, and arginine. Alginic acid, pectin, carrageenan, chondroitin sulfate, dextran sulfate, chitosan, polylysine, collagen, gelatin, carboxymethyl chitin ( carboxymethyl chitin), fibrin, agarose, polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polymethacrylate, hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC), Hydroxypropylcellulose (HPC), carboxymethyl cellulose, cyclodextrin, gentiobiose, alkyltrimethylammonium bromide (Cetrimide), hexadecyltrimethylammoniumbromide (CTAB) , Gentian Violet, benzethonium chloride, docusate sodium salt, a SPAN-type surfactant, polysorbate (Tween), Lauryl It may include at least one of sodium dodecyl sulfate (SDS), benzalkonium chloride, and glyceryl oleate.

Hyaluronic acid is used to include both hyaluronic acid as well as hyaluronic acid salts (e.g., sodium hyaluronate, potassium hyaluronate, magnesium hyaluronate, and calcium hyaluronate) and mixtures thereof. Hyaluronic acid is used to include cross-linked hyaluronic acid and/or non-cross-linked hyaluronic acid.

According to one embodiment of the present invention, the hyaluronic acid of the present invention has a molecular weight of 2 kDa to 5000 kDa.

According to another embodiment of the present invention, the hyaluronic acid of the present invention has a molecular weight of 100-4500, 150-3500, 200-2500 kDa, 220-1500 kDa, 240-1000 kDa or 240-490 kDa.

Carboxymethyl cellulose (CMC) can be used as CMC of various known molecular weights. For example, the average molecular weight of CMC used in the present invention is 90,000 kDa, 250,000 kDa, or 700,000 kDa.

Disaccharides may include sucrose, lactulose, lactose, maltose, trehalose, or cellobiose, and may particularly include sucrose, maltose, and trehalose.

In an optional embodiment, an adhesive may be included. The adhesive is one or more adhesives selected from the group consisting of silicone, polyurethane, hyaluronic acid, physical adhesive (Gecko), polyacrylic, ethyl cellulose, hydroxy methyl cellulose, ethylene vinyl acetate and polyisobutylene.

In an optional embodiment, the microneedle 120 may additionally include metal, high molecular weight polymer, or adhesive.

The microneedle 120 may contain an active ingredient (EM). At least a portion of the microneedle 120 may contain a pharmaceutical, medical, or cosmetic active ingredient (EM). For example, as a non-limiting example, active ingredients include, but are not limited to, protein/peptide drugs, hormones, hormone analogs, enzymes, enzyme inhibitors, signal transduction proteins or parts thereof, antibodies or parts thereof, single chain antibodies, and conjugates. It includes at least one of a protein or its binding domain, an antigen, an attachment protein, a structural protein, a regulatory protein, a toxin protein, a cytokine, a transcriptional regulatory factor, a blood coagulation factor, and a vaccine. More specifically, the protein/peptide medicine contains insulin, insulinlike growth factor 1 (IGF-1), growth hormone, erythropoietin, granulocyte-colony stimulating factors (G-CSFs), and granulocyte/macrophage-CSFs (GM-CSFs). colony stimulating factors), interferon alpha, interferon beta, interferon gamma, interleukin-1 alpha and beta, interleukin-3, interleukin-4, interleukin-6, interleukin-2, epidermal growth factors (EGFs), calcitonin , ACTH (adrenocorticotropic hormone), TNF (tumor necrosis factor), atobisban, buserelin, cetrorelix, deslorelin, desmopressin , dynorphin A (1-13), elcatonin, eleidosin, eptifibatide, GHRHII (growth hormone releasing hormone-II), gonadorelin ), goserelin, histrelin, leuprorelin, lypressin, octreotide, oxytocin, pitressin, secretin ), sincalide, terlipressin, thymopentin, thymosine, triptorelin, bivalirudin, carbetocin, Cyclosporine, exedine, lanreotide, LHRH (luteinizing hormone releasing hormone), nafarelin, parathyroid hormone, pramlintide, T-20 (enfuvirtide), thimalfacin ( thymalfasin) and ziconotide. Additionally, the active ingredient (EM) may be a cosmetic ingredient such as whitening, filler, anti-wrinkle, or antioxidant.

In one embodiment, the active ingredient (EM) may be a colloid dispersed in a solvent that forms the microneedles 120 in the form of fine particles. The microparticles may themselves be an active ingredient (EM) or may include a coating material carrying the active ingredient (EM).

The active ingredient (EM) may be intensively distributed in a partial layer of the microneedle 120. That is, since the active ingredient (EM) is placed at a specific height in the microneedle 120, the active ingredient (EM) can be effectively delivered.

In another embodiment, the active ingredient (EM) may be dissolved within the microneedle 120. The active ingredient (EM) may be dissolved in the base material of the microneedle 120, such as the biodegradable materials described above, to form the microneedle 120. The active ingredient (EM) may be dissolved in the base material at a uniform concentration, and may be concentratedly distributed at a specific height of the microneedle 120, like the above-described fine particles.

In one embodiment, the microneedle patch 100 may have a plurality of active ingredients (EM) depending on the zone. Among the plurality of microneedles, a first group of microneedles contains a first active ingredient among the plurality of active ingredients, and a second group of microneedles different from the first group contains a second active ingredient among the plurality of active ingredients. may include.

In one embodiment, a pharmaceutical, medical, or cosmetic active ingredient (EM) may be coated on the microneedle 120. The active ingredients (EM) may be coated on the entire microneedle 120 or only a portion of the microneedle 120. Alternatively, in the microneedle 120, part of the coating layer may be coated with the first active ingredient, and another part may be coated with the second active ingredient.

Microneedles 120 may have various shapes. The microneedles 120 may have a cone shape. For example, the microneedles 120 may have a polygonal shape such as a cone shape, a triangular pyramid shape, or a square pyramid shape.

Microneedles 120 may have a layered structure. Microneedles 120 may have a plurality of stacked layers. The number of layers forming the microneedle 120 is not limited to a specific number.

Figure 3 is a flowchart showing a microneedle patch manufacturing method according to another embodiment of the present invention, and Figures 4 to 8 are diagrams showing steps for manufacturing microneedle using the microneedle patch manufacturing method of Figure 3.

3 to 8, the microneedle patch manufacturing method includes filling a mold with a plurality of needle grooves with a buffer solution (S10), placing a base material on the needle groove (S20), and placing the base material on the needle groove. It includes a step of diffusing into the buffer solution (S30) and a step of drying the mold (S40).

Hereinafter, the buffer solution (BS) is defined as a solution capable of dissolving the base material (BM). The buffer solution (BS) is a substance that can dissolve the base material (BM) forming the microneedle. The buffer solution (BS) is soluble in the base material (BM) and depends on the type of the base material (BM).

For example, the buffer solution (BS) may be set as a solution capable of dissolving the base material of A. Additionally, the buffer solution (BS) may be set to solution B, which can dissolve the base material of B.

In one embodiment, if the base material (BM) is set to hyaluronic acid, the buffer solution (BS) may be set to water, especially purified water.

In one embodiment, the buffer solution (BS) may not dissolve the active ingredient (EM). The active ingredient (EM) is disposed inside the base material (BM), and the base material (BM) is dissolved in the buffer solution (BS), but the active ingredient (EM) is not dissolved in the buffer solution (BS). However, the active ingredient (EM) may be injected into the needle groove (NG) together with the base material (BM) and placed inside the microneedle.

In another example, the buffer solution (BS) may dissolve the active ingredient (EM). The active ingredient (EM) is disposed inside the base material (BM), and both the base material (BM) and the active ingredient (EM) are dissolved in the buffer solution (BS). For example, when the buffer solution (BS) is water and the active ingredient (EM) is water-soluble, the active ingredient (EM) may be dissolved in the buffer solution (BS).

In the step (S10) of filling a mold with a plurality of needle grooves with a buffer solution (S10), the mold (M) is filled with the buffer solution (BS), and the needle groove (NG) is filled with the buffer solution (BS) (see FIG. 4). Through the first injection module 10, the buffer solution BS can be filled into the mold M.

The mold (M) may have a base groove (BG) and a needle groove (NG). The base 110 may be formed in the base groove (BG), and the microneedle 120 may be formed in the needle groove (NG).

The buffer solution (BS) may fill the entire needle groove (NG).

In one embodiment, the buffer solution (BS) may be filled only in a plurality of needle grooves (NG). In order to first mold the microneedle 120 and then mold the base 110, the buffer solution (BS) is injected only into the needle groove (NG).

In another embodiment, the buffer solution (BS) may be fully filled in both the needle groove (NG) and the base groove (BG). In order to manufacture the microneedle patch 100 in which the base 110 and the microneedle 120 are integrated, the buffer solution (BS) is filled into both the needle groove (NG) and the base groove (BG), and the base material (BM) is filled. can fill the entire mold (M).

In another embodiment, the buffer solution (BS) may be filled only in part of the needle groove (NG). In order to manufacture the microneedle 120 having a multi-layer structure, the buffer solution (BS) is injected into only a portion of the needle groove (NG), and then the buffer solution (BS) is further filled to sequentially manufacture the microneedle (120). It can be manufactured. This will be explained in detail below.

In the step of placing the base material on the needle groove (S20), the base material (BM) is placed in the mold (M) (see FIG. 5).

By placing the base material (BM) on the needle groove (NG), the base material (BM) is set to be easily dissolved in the buffer solution (BS) stored in the needle groove (NG). The base material BM may be injected into the base groove BG through the nozzle 21 of the second injection module 20.

Since the base material (BM) has a certain viscosity, it is difficult to inject directly into the needle groove (NG). However, when the base material (BM) is dissolved in the buffer solution (BS), the fluidity increases, so the base material (BM) can be filled in the needle groove (NG).

In one embodiment, the base material (BM) is injected into the base groove (BG) of the mold (M). In order for the base material BM to sufficiently fill the needle groove NG, the base material BM may fill the base groove BG or may be formed to be convex beyond the capacity of the base groove BG.

In the step of diffusing the base material into the buffer solution (S30), the base material (BM) may be dissolved in the buffer solution (BS).

The base material (BM) is dissolved in the buffer solution (BS) and injected into each needle groove (NG).

As shown in FIG. 6, the base material BM initially spreads from the upper part of the needle groove NG, and gradually the base material BM spreads to the tip of the needle groove NG.

Afterwards, as shown in FIG. 7, the base material (BM) is entirely filled into the mold (M). When all of the base material (BM) is dissolved in the buffer solution (BS), the concentration of the base material (BM) decreases and the viscosity decreases.

Since the buffer solution (BS) is completely filled in the needle groove (NG), the base material (BM) dissolves in the buffer solution (BS) and completely fills the needle groove (NG). Since the base material BM completely fills the needle groove NG, the microneedle 120 can be manufactured in the shape of the needle groove NG.

In one embodiment, when the base material (BM) is hyaluronic acid, water, especially purified water, is stored in the needle groove (NG) as a buffer solution (BS). Since hyaluronic acid dissolves in water, hyaluronic acid is filled into the needle groove (NG). Since hyaluronic acid is a viscous material, there is a limit to filling the needle groove (NG) with hyaluronic acid alone. However, hyaluronic acid dissolved in water has weak viscosity and high fluidity, so it can be filled in the needle groove (NG).

In one embodiment, the active ingredient (EM) may be placed inside the base material (BM). The base material (BM) and the active ingredient (EM) exist in a mixed form, and as the base material (BM) is dissolved in the buffer solution (BS), the active ingredient (EM) can be injected together into the needle groove (NG). there is.

At this time, the active ingredient (EM) is not dissolved in the buffer solution (BS). Therefore, the active ingredient (EM) mixed in the base material (BM) when injected into the mold (M) and the active ingredient (EM) inside the finally manufactured microneedle 120 are the same. Since the active ingredient (EM) does not react with the buffer solution (BS), the effectiveness of the active ingredient (EM) does not change during the manufacturing process.

In another example, the buffer solution (BS) may dissolve the active ingredient (EM). The active ingredient (EM) is disposed inside the base material (BM), and both the base material (BM) and the active ingredient (EM) are dissolved in the buffer solution (BS). For example, when the buffer solution (BS) is water and the active ingredient (EM) is water-soluble, the active ingredient (EM) may be dissolved in the buffer solution (BS). Even if the active ingredient (EM) is dissolved in the buffer solution (BS), the effect of the active ingredient (EM) does not change.

In an alternative embodiment, the diffusion of the base material (BM) can be controlled by controlling the environment.

For example, the diffusion rate of the base material (BM) can be increased by controlling the temperature or humidity inside the chamber where the mold (M) is located.

As another example, the diffusion rate of the base material (BM) can be increased by injecting an additive (not shown) that increases the diffusion rate into the buffer solution (BS).

As another example, the mold M may be mounted on a stirrer (not shown), and the diffusion rate of the base material BM may increase due to vibration generated by driving the stirrer.

In the step of drying the mold (S40), the microneedle 120 can be manufactured by drying the buffer solution (BS) (see FIG. 8).

The mold (M) is mounted on the drying module 30, and the drying module 30 is driven to dry the mold (M). By the drying module 30, the buffer solution (BS) stored in the base mold (M) can be removed.

When the buffer solution (BS) dries, the concentration of the base material (BM) increases. Afterwards, the buffer solution (BS) is completely removed and the moisture contained in the base material (BM) is also removed, thereby creating the microneedle 120 made of the base material (BM).

Since the buffer solution (BS) is completely removed, only the base material (BM) can be effectively stored in the needle groove (NG). The base material (BM) changes into a solid, and the microneedle 120 has a predetermined rigidity.

The microneedle 120, which is molded from a solid, contains an active ingredient (EM) inside. The active ingredient (EM) remains contained in the base material (BM).

A base material (BM) suitable for forming microneedles has a certain viscosity. Since the needle grooves (NG) of the mold (M) are manufactured very finely, it is difficult to completely fill the needle grooves (NG) with the viscous base material (BM).

If the base material (BM) is not completely filled in the needle groove (NG), the tip of the microneedle is formed bluntly. Since the microneedle 120 must be inserted through the skin of the subject, the end of the microneedle 120 must be manufactured in the shape of a sharpened tip. However, the viscous base material BM does not completely fill the needle groove NG, and the microneedle 120 is formed bluntly due to the empty space, making it difficult for the microneedle 120 to be attached to the object. Decreases the drug delivery effect.

In addition, the viscous base material (BM) may be stored in the form of a gas such as air in the form of a bubble (BU) during the manufacturing process of the microneedle patch 100. Even if the base material BM is squeezed and injected into the needle groove NG, internal bubbles may still exist in the needle groove NG. Gas remaining in the internal bubbles of the base material (BM) may seriously deteriorate the quality of the microneedle 120. Since the microneedle 120 is a part that is implanted into the subject's skin, it should not contain foreign substances including gas. If the gas (g) in the bubble (BU) is injected into the object, the safety of the object may be threatened.

The method for manufacturing a microneedle patch according to the present invention can manufacture a microneedle patch with an elaborate shape and improved quality by completely filling a mold with a base material. Since the base material is completely filled in the needle groove by the buffer solution, the microneedle is manufactured in the shape of a sharpened tip, so that it can be easily attached to the skin of the subject. Additionally, since foreign substances such as air are not injected into the needle groove during the manufacturing process, a high quality microneedle patch can be manufactured.

In detail, in order to manufacture microneedles with high rigidity, 1.4 MDa 10% HA, a polymer, must be selected as the base material. However, the polymer 1.4MDa 10%HA has a relatively high viscosity, making it difficult to completely inject into the mold. According to the method of manufacturing a microneedle patch according to the present invention, purified water, a buffer solution, is injected into the mold, and 1.4 MDa 10% HA, a polymer, is dissolved in the buffer solution, so that the base material is completely injected into the needle groove. Afterwards, when the purified water is dried, microneedles with the shape of the needle groove are manufactured.

The method for manufacturing a microneedle patch according to the present invention can manufacture a microneedle patch with a complex and detailed needle shape. When the base material is diffused into the buffer solution during the manufacturing process of the microneedle patch, the viscosity of the base material is lowered and the fluidity is increased. Even if the shape of the needle groove is complex and very precise, the base material can completely fill the needle groove due to its fluidity.

Figure 9 is a diagram showing the microneedle patch of Figure 2.

Referring to FIG. 9, the microneedle patch 100 may be provided with a base 110 and a single-layer microneedle 120 using the above-described microneedle patch manufacturing apparatus 1 or the microneedle patch manufacturing method. The microneedle 120 may contain an active ingredient (EM) therein.

The microneedle 120 is formed by dissolving the base material (BM) in the buffer solution and then drying the buffer solution (BS). At this time, the buffer solution (BS) can be completely removed.

In one embodiment, the buffer solution may include water, and the base material (BM) may include hyaluronic acid.

In one embodiment, the active ingredient (EM) is disposed inside the base material (BM), and the active ingredient (EM) may not be dissolved in the buffer solution.

Figures 10 to 12 are diagrams showing another embodiment of the microneedle patch of Figure 9.

Referring to FIG. 10, the microneedle patch 200 can be manufactured using the above-described microneedle patch manufacturing apparatus 2 or the microneedle patch manufacturing method. The microneedle patch 200 may have a base 210 and microneedles 220 having a multi-layer structure.

By operating the above-described microneedle patch manufacturing apparatus 1 multiple times or performing the microneedle patch manufacturing method multiple times, the microneedle patch 200 with a multilayer structure can be manufactured.

In detail, the first buffer solution is injected into the needle groove (NG). The first buffer solution does not completely fill the needle groove (NG).

As an example, the first buffer solution is filled to have a volume larger than the volume of the first layer 221. The first buffer solution may be filled to a height h1' greater than h1 in FIG. 10.

The first base material BM1 is placed in the mold M, and the first base material BM1 is diffused into the first buffer solution BS. Since the first base material BM1 is dissolved in the first buffer solution, the tip of the needle groove NG is filled with the first base material BM1.

In the subsequent process, the mold (M) filled with the first buffer solution and the first base material (BM1) is dried to remove the first buffer solution. Accordingly, the first layer 221 is formed at the tip of the needle groove NG with the first base material BM1. When the first buffer solution is removed through the drying process, the height of the first layer 221 is formed to h1.

Afterwards, the second buffer solution (BS) is injected into the needle groove (NG). The second buffer solution is filled on top of the first layer 221 in the needle groove NG.

The second base material (BM2) is placed in the mold (M), and the second base material (BM2) is diffused into the second buffer solution (BS). Since the second base material BM2 is dissolved in the second buffer solution, the first layer 221 is filled with the second base material BM2.

In the subsequent process, the mold (M) filled with the second buffer solution and the second base material (BM2) is dried to remove the second buffer solution. As a result, the second layer 222 is formed on the first layer 221 with the second base material BM2, so the microneedle 220 has a multi-layer structure.

At least one of the first layer 221 and the second layer 222 may have an active ingredient. As shown in the drawing, the first active ingredient (EM1) may be disposed on the first layer 221, and the second active ingredient (EM2) may be disposed on the second layer 222. However, it is not limited to this, and may have only the first active ingredient (EM1) or only the second active ingredient (EM2). Additionally, multiple types of active ingredients may be mixed in each layer.

The first layer 221 may be formed to have greater strength than the second layer 222. The first layer 221 undergoes an additional drying process during the manufacturing process of the second layer 222. The strength of the first layer 221 can be strengthened by an additional drying process. When the strength of the first layer 221 is strengthened, the microneedle patch 200 can be easily attached to the skin of the subject.

In one embodiment, the second buffer solution may dissolve only the second base material (BM2) and not the first base material (BM1). After the first layer 221 composed of the first base material BM1 is formed, even if the second buffer solution is injected into the needle groove NG, the first layer 221 is formed by the second buffer solution BS. It may not melt. Therefore, since the boundaries between the first layer 221 and the second layer 222 are clearly distinguished, the target positions of the first layer 221 and the second layer 222 can be clearly distinguished.

The microneedle patch 200 has a multi-layer structure in which the microneedles 220 disposed on one surface of the base 210 can accurately deliver the active ingredient (EM) to the target point. Since the microneedle 220 has a plurality of layered structures, active ingredients can be loaded on each layer. For example, the first active ingredient (EM1) may be loaded on the first layer 221, and the second active ingredient (EM2) may be loaded on the second layer 222. Thus, the microneedle patch 200 can adjust the activation depth of each active ingredient depending on the height of the layer. That is, the microneedle patch 200 can deliver active ingredients to any one of the epidermis, dermis, subcutaneous fat, and muscle.

The microneedle patch 200 has a multi-layer structure, so the biodegradation rate of each layer can be set differently. The microneedle 220 sets the decomposition speed of the first layer 221 and the second layer 222 to be different, so that the first active ingredient (EM1) and the second active ingredient (EM2) can have different activation times. there is.

The microneedle patch 200 has a multi-layer structure, so the strength of each layer can be set differently. By setting the intensity of the first layer 221 to be higher than the intensity of the second layer 222, the microneedle 220 can be easily injected into the skin.

Referring to FIG. 11, the microneedle patch 200A may have a base 210 and a microneedle 220A.

The microneedle 220A may be formed with a first layer 221A, a second layer 222A, and a transition layer 223A between the first layer 221 and the second layer 222. The transition layer 223A may have a mixed form of the first base material BM1 and the second base material BM2.

The second buffer solution (BS) may dissolve both the second base material (BM2) and the first base material (BM1). After the first layer 221A made of the first base material BM1 is formed, when the second buffer solution is injected into the needle groove NG, the upper surface of the first layer 221A may be partially dissolved.

Afterwards, when the second base material BM2 is injected into the upper surface of the first layer 221A, a transition layer 223A may be formed in the boundary area between the first layer 221A and the second layer 222A. , It may have a mixed form of the first base material (BM1) dissolved in the first layer (221A) and the additionally injected second base material (BM2).

The transition layer 223A can increase the bonding strength of the first layer 221A and the second layer 222A, thereby increasing the strength of the microneedle 220A. The properties of the first layer 221A and the second layer 222A do not change drastically due to the transition layer 223A, and the bonding force between the first layer 221A and the second layer 222A can be increased.

Referring to FIG. 12, the microneedle patch 200B can be manufactured using the above-described microneedle patch manufacturing apparatus 1 or the microneedle patch manufacturing method. The microneedle patch 200B may have a base 210B and a multi-layered microneedle 220B.

The microneedle 220B may include a first layer 221B and a second layer 222B having a layered structure.

First, the first base material (BM1) is injected into the mold (M) filled with the first buffer solution. As the first buffer solution is removed during the drying process, the first layer 221B made of the first base material BM1 may have a curved surface.

Thereafter, the mold M is filled with the second buffer solution, and the second base material BM2 is spread into the second buffer solution. As the second buffer solution is removed during the drying process, a second layer 222B may be formed on the first layer 221B.

As such, the present invention has been described with reference to the embodiments shown in the drawings, but these are merely illustrative, and those skilled in the art will understand that various modifications and equivalent other embodiments are possible therefrom. . Therefore, the true scope of technical protection of the present invention should be determined by the technical spirit of the attached patent claims.

Specific implementations described in the embodiments are examples and do not limit the scope of the embodiments in any way. Additionally, if there is no specific mention such as “essential,” “important,” etc., it may not be a necessary component for the application of the present invention.

In the specification of the embodiment (particularly in the claims), the use of the term “above” and similar referential terms may refer to both the singular and the plural. In addition, when a range is described in an example, the invention includes the application of individual values within the range (unless there is a statement to the contrary), and is the same as describing each individual value constituting the range in the detailed description. . Lastly, unless the order of the steps constituting the method according to the embodiment is clearly stated or there is no description to the contrary, the steps may be performed in an appropriate order. The embodiments are not necessarily limited by the order of description of the steps above. The use of any examples or illustrative terms (e.g., etc.) in the embodiments is merely for describing the embodiments in detail, and unless limited by the claims, the scope of the embodiments is not limited by the examples or illustrative terms. That is not the case. Additionally, those skilled in the art will recognize that various modifications, combinations and changes may be made depending on design conditions and factors within the scope of the appended claims or their equivalents.

1: Manufacturing device of microneedle patch
10: first injection module
20: second injection module
30: drying module
100, 200: Microneedle patch
110, 210: Base
120, 220, 220A, 220B: Microneedle

Claims (9)

Filling a mold having a base groove and a plurality of needle grooves with a buffer solution;
Injecting a base material, which is a raw material for microneedles, into the base groove;
dissolving the base material in the buffer solution and injecting it into the needle groove; and
It includes: drying the mold,
The step of drying the mold is,
A method of manufacturing a microneedle patch, wherein the buffer solution is removed and the base material hardens in the needle groove. delete delete According to claim 1,
The buffer solution includes water, and the base material includes hyaluronic acid. According to claim 1,
A method of manufacturing a microneedle patch, wherein an active ingredient that can be dissolved in the buffer solution is disposed inside the base material. delete delete delete delete

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