WO2023120808A1

WO2023120808A1 - Method for manufacturing microneedle patch

Info

Publication number: WO2023120808A1
Application number: PCT/KR2022/001927
Authority: WO
Inventors: 전이슬; 이재준; 배태근; 이인덕
Original assignee: 주식회사 페로카
Priority date: 2021-12-20
Filing date: 2022-02-08
Publication date: 2023-06-29
Also published as: KR20230093605A

Abstract

The present invention includes a method for manufacturing a microneedle patch, the method comprising the steps of: injecting a first base material into a first mold; curing the first base material to form a core; inserting the core into a second mold and injecting a second base material into the second mold; and curing the second base material to form a cover disposed outside the core.

Description

Microneedle patch manufacturing method

The present invention relates to a method for manufacturing a microneedle patch.

Drug injection into the human body has traditionally been performed by needle injection, but needle injection causes great pain. Therefore, a non-invasive drug injection method has also been developed, but there is a problem in that the amount of drug required is too large compared to the amount of injection.

Due to these problems, a lot of research has been done on a drug delivery system (DDS), which has made further progress with the development of nanotechnology.

Unlike conventional injection needles, microneedles can be characterized by painless skin penetration and no trauma. In addition, a certain degree of physical hardness may be required because the microneedle must penetrate the stratum corneum of the skin. In addition, an appropriate length may be required in order for the physiologically active material to reach the epidermal layer or the dermal layer of the skin. In addition, in order to effectively deliver the physiologically active substance of hundreds of "micro" needles into the skin, the skin permeability of the "micro" needles must be high and maintained for a certain period of time until they are dissolved after being inserted into the skin.

Accordingly, interest in microneedles capable of delivering a drug in a precise amount and accurately setting a target position is increasing.

The present invention can effectively deliver active ingredients to a target location and can provide a method for manufacturing a microneedle patch having a multi-layered structure in a radial direction.

In one embodiment of the present invention, the steps of injecting a first base material into a first mold, forming a core by curing the first base material, inserting the core into a second mold, and A method for manufacturing a microneedle patch comprising injecting a second base material into a mold and forming a cover disposed outside the core by curing the second base material.

The method for manufacturing a microneedle patch according to the present invention can manufacture a microneedle having a plurality of layers in a radial direction. Since the core is first manufactured and then the cover is formed outside the core, strength and durability of the microneedle can be increased.

In the method for manufacturing a microneedle patch according to the present invention, the adhesive force between the microneedle and the mold is reduced due to the contraction of the microneedle, so that a high-quality microneedle patch can be manufactured.

1 is a perspective view showing a microneedle patch according to an embodiment of the present invention.

FIG. 2 is a cross-sectional view of the microneedle arrangement of FIG. 1 .

FIG. 3 is an enlarged view of a part of FIG. 2 .

4 to 8 are views showing modified examples of FIG. 3 .

9 is a flowchart illustrating a method of manufacturing a microneedle patch according to another embodiment of the present invention.

10 to 12 are diagrams illustrating the method of manufacturing the microneedle patch of FIG. 9 .

13 is a flowchart illustrating a method of manufacturing a microneedle patch according to another embodiment of the present invention.

14 and 15 are views illustrating the method of manufacturing the microneedle patch of FIG. 13 .

In addition, the core may include a first active ingredient, and the cover may include a second active ingredient that is activated together with the first active ingredient or increases the activity of the first active ingredient.

In addition, in the forming of the core, the first base material may shrink and harden so that the adhesive force between the first base material and the surface of the first mold may decrease.

Also, in the forming of the cover, the second base material may shrink and harden, so that the adhesive force between the second base material and the surface of the second mold may decrease.

In addition, the second base material may cover the outside of the core so that it is not exposed to the outside.

Another aspect of the present invention includes the steps of injecting a first base material into a first mold, forming a core by curing the first base material, and injecting a second base material into a second mold; Forming a cover having an insertion groove by curing the second base material; and inserting the core into the insertion groove of the cover.

In addition, the step of inserting the core into the cover may further include applying an intermediate material to an outer surface of the core or an inner surface of the insertion groove.

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

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 accompanying drawings.

Since the present invention can apply various transformations and have various embodiments, specific embodiments will be illustrated in the drawings and described in detail in the detailed description. Effects and features of the present invention, and methods for achieving them will become clear with reference to the embodiments described later in detail together 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, and when describing with reference to the drawings, the same or corresponding components are assigned the same reference numerals, and overlapping descriptions thereof will be omitted. .

In the following embodiments, terms such as first and second are used for the purpose of distinguishing one component from another component without limiting meaning.

In the following examples, expressions in the singular number include plural expressions unless the context clearly dictates otherwise.

In the following embodiments, terms such as include or have mean that features or components described in the specification exist, and do not preclude the possibility that one or more other features or components may be added.

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

When an embodiment is otherwise implementable, a specific process sequence may be performed differently from the described sequence. For example, two processes described in succession may be performed substantially simultaneously, or may be performed in an order reverse to the order described.

1 is a perspective view showing a microneedle patch according to an embodiment of the present invention, FIG. 2 is a view showing a cross-section of the microneedle arrangement of FIG. 1, and FIG. 3 is an enlarged view of a portion of FIG. 2 am.

Referring to FIGS. 1 to 3 , the microneedle patch 100 may include a base 110 and a microneedle 120 .

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

The base 110 may be removed when the microneedle 120 is implanted into the skin. For example, the base may be removed from the skin by applying force by the user.

As another example, in the microneedle patch 100, a portion where the base 110 and the microneedle 120 are connected is first dissolved, and the base 110 may be removed after a predetermined time has elapsed after attachment.

As another example, when the microneedle patch 100 is attached for a long time, the base 110 may be dissolved. As another example, the base 110 may be removed by a 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 . For example, the base 110 may include the same material as any one of the core 121 and the cover 122 of the microneedle 120 .

As an alternative embodiment, the base 110 may include a physiologically active material. After attaching the microneedle patch 100 to the skin, an effective drug can be effectively delivered to the patient by the physiologically active substance coming out of the base 110. In addition, the base 110 and the microneedle 120 can be easily separated by the physiologically active substance coming out of the base 110 .

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 (eg, disaccharides). In another embodiment, the base 110 preferably does not contain drugs or active ingredients.

Base 110 may include a biocompatible material. The base 110 may select a biocompatible material selected as a base material of the microneedle 120 to be described later as a base material.

The microneedles 120 protrude from the surface of the base 110 and may be provided in plurality. The microneedle 120 may be formed of a biocompatible material and an additive.

Biocompatible materials include carboxymethyl cellulose (CMC), hyaluronic acid (HA), alginic acid, pectin, carrageenan, chondroitin sulfate, dex Tran 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), carboxymethylcellulose, cyclodextrin (Cyclodextrin), maltose, lactose, trehalose, cellobiose, isomaltose, turanose, and lactulose, or containing at least one of , At least one polymer selected from the group consisting of cellulose and a copolymer of monomers forming such a polymer.

The additives are trehalose, oligosaccharide, sucrose, maltose, lactose, cellobiose, hyaluronic acid, alginic 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 not only hyaluronic acid but also hyaluronic acid salts (eg, sodium hyaluronate, potassium hyaluronate, magnesium hyaluronate and calcium hyaluronate) and mixtures thereof. Hyaluronic acid is used as a meaning including 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) may use 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.

The disaccharide may include sucrose, lactulose, lactose, maltose, trehalose, or cellobiose, and may include sucrose, maltose, or trehalose in particular.

As an optional embodiment, an adhesive may be included. The adhesive is at least one adhesive selected from the group consisting of silicone, polyurethane, hyaluronic acid, physical adhesive (Gecko), poly acrylic, ethyl cellulose, hydroxy methyl cellulose, ethylene vinyl acetate and polyisobutylene.

As an alternative embodiment, the microneedle 120 may additionally include metal, a high molecular weight polymer, or an adhesive.

The microneedle 120 may contain an active ingredient (EM). At least a portion of the microneedle 120 may include a pharmaceutical, medical or cosmetic active ingredient (EM). For example, as non-limiting examples, active ingredients include, but are not limited to, protein/peptide drugs, hormones, hormone analogues, enzymes, enzyme inhibitors, signaling proteins or parts thereof, antibodies or parts thereof, single chain antibodies, binding It includes at least one of proteins or binding domains thereof, antigens, adhesion proteins, structural proteins, regulatory proteins, toxin proteins, cytokines, transcriptional regulators, blood coagulation factors, and vaccines. More specifically, the protein / peptide drug is insulin, IGF- 1 (insulinlike growth factor 1), growth hormone, erythropoietin, G-CSFs (granulocyte-colony stimulating factors), GM-CSFs (granulocyte / macrophage- 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 , adrenocorticotropic hormone (ACTH), tumor necrosis factor (TNF), atobisban, buserelin, cetrorelix, deslorelin, desmopressin , dynorphin A (1-13), elcatonin, eleidosin, eptifibatide, growth hormone releasing hormone-II (GHRHII), gonadorelin ), goserelin, histrelin, leuprorelin, lypressin, octreotide, oxytocin, pitressin, secretin ), sincalide, terlipressin, thymopentin, thymosine, triptorelin, bivalirudin, carbetocin, cyclosporine, exedine, lanreotide, luteinizing hormone releasing hormone (LHRH), nafarelin, parathyroid hormone, pramlintide, T-20 (enfuvirtide), tymalfacin ( thymalfasin) and ziconotide. In addition, the active ingredient (EM) may be a cosmetic ingredient such as whitening, filler, wrinkle removal or antioxidant.

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

In one embodiment, the active ingredient (EM) may be intensively distributed in a partial area of the microneedle 120 . That is, since the active ingredient EM is disposed at a specific height or a specific depth in the microneedle 120, the active ingredient EM can be effectively delivered.

In another embodiment, the active ingredient (EM) may be dissolved in the microneedle 120 . The active ingredient (EM) may be dissolved in a base material of the microneedle 120 such as the aforementioned biodegradable materials to form the microneedle 120 . The active ingredient (EM) may be dissolved in the base material at a uniform concentration and may be intensively distributed at a specific height or depth 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) according to regions. Among the plurality of microneedles, a microneedle of a first group contains a first active ingredient among the plurality of active ingredients, and a microneedle of a second group different from the first group contains a second active ingredient among the plurality of active ingredients. can 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, a portion of the coating layer of the microneedle 120 may be coated with the first active ingredient, and the other portion may be coated with the second active ingredient.

In one embodiment, the microneedle 120 may be elongated. Since the microneedle 120 has a predetermined length, the drug can be delivered to a deep location in the skin.

The microneedle 120 may have a core 121 and a cover 122 . Since the cover 122 is disposed outside the core 121, the microneedle 120 may have a multi-layered structure in the radial direction.

The core 121 extends along the central axis of the microneedle 120 and may have a predetermined length. The core 121 may have various shapes. For example, the core 121 may have a cylindrical or polygonal column shape as shown in FIG. 3 .

Since the core 121 extends in the insertion direction of the microneedle 120 and has a predetermined rigidity, it is stably inserted when inserted into the skin, and the microneedle patch 100 can be maintained in an attached state.

In one embodiment, the core 121 may be disposed such that one end contacts the base 110 and the other end faces a sharpened tip (ST) of the core. In another embodiment, although not shown in the drawings, the core may be disposed such that one end is inserted into the base and the other end faces the tip ST. In another embodiment, although not shown in the drawings, the core may be disposed in an inner space of the cover with one end spaced apart from the base.

The cover 122 may cover the outside of the core 121 . The cover 122 may cover the outside so that the core 121 is not exposed to the outside.

The cover 122 may have an extension portion 122A extending along the core 121 and a tip portion 122B disposed at an end of the extension portion 122A to form a tip tip ST.

The core 121 may be formed of a first base material that is a biocompatible material, and the cover 122 may be formed of a second base material that is a biocompatible material. The first base material and the second base material may be selected from the aforementioned biocompatible materials.

In one embodiment, the first base material and the second base material may be different biocompatible materials. Since the first base material and the second base material are different from each other, the core 121 and the cover 122 may have different physical and pharmaceutical properties.

For example, the core 121 may have greater rigidity than the cover 122 . Since the core 121 has relatively high rigidity, the elongated microneedle 120 can be stably inserted into the skin.

In another embodiment, the first base material and the second base material may be the same biocompatible material. Since the core 121 and the cover 122 are formed of the same base material, a strong bond can be maintained at the connected portion.

The microneedle 120 may have the above-described active ingredient (EM). The cover 122 includes an active ingredient (EM), and when the microneedle 120 is attached to the skin, the active ingredient (EM) can be activated while the cover 122 is decomposed.

The microneedle patch 100 according to the present invention has a core 121 extending along the longitudinal direction, so that the microneedle 120 can be implanted deep into the skin. Since the core 121 has a predetermined rigidity, the user can effectively attach the microneedle patch 100 to the skin without damaging the microneedle 120 when attaching it to the skin.

Since the microneedle patch 100 according to the present invention has the active ingredient (EM) in the microneedle 120, the active ingredient (EM) can be delivered to the skin. In particular, since the microneedles 120 have a layered structure in the radial direction, the same active ingredient can be delivered to the skin during a set time during which the microneedles 120 are implanted into the skin and the cover 122 is disassembled.

4 to 8 are views showing modified examples of FIG. 3 .

Referring to FIG. 4 , the microneedle patch 100A may have a base 110 and microneedles 120A. The microneedle 120A may have a core 121A and a cover 122A. Compared to the above-described microneedle 120, the microneedle 120A has a characteristic of an active ingredient, and hereinafter, this will be mainly described.

The core 121A may be formed of a first base material, and the first active ingredient EM1 may be disposed therein. In one embodiment, the first active ingredient EM1 may be evenly distributed in the core 121A. In another embodiment, the first active ingredient EM1 may be densely disposed at a specific height of the core 121A.

The cover 122A may be formed of a second base material, and the second active ingredient EM2 may be disposed therein. In one embodiment, the second active ingredient EM2 may be evenly distributed on the cover 122A. In another embodiment, the second active ingredient EM2 may be densely disposed at a specific height of the cover 122A or densely disposed at the apical tip.

As the cover 122A is disassembled, the second active ingredient EM2 is delivered into the skin. When the decomposition of the cover 122A ends, the decomposition of the core 121A starts, and the first active ingredient EM1 can be delivered into the skin.

In one embodiment, the first active ingredient (EM1) may be activated together with the second active ingredient (EM2). While the second active ingredient (EM2) remains in the skin, the first active ingredient (EM1) can be activated together with the second active ingredient (EM2).

In another embodiment, the activity of the first active ingredient EM1 may be increased by the second active ingredient EM2. That is, when the first active ingredient EM1 is delivered into the skin while the second active ingredient EM2 remains in the skin, the activity of the first active ingredient EM1 can be amplified.

In detail, the second active ingredient (EM2) may be a substance that promotes the activity of the first active ingredient (EM1). The second active ingredient (EM2) may be any one of various enzymes that degrade the extracellular matrix (ECM).

Accordingly, when the microneedle patch 100 is attached to the skin, the second active ingredient EM2 flows into the body from the cover 122A and decomposes the extracellular matrix in the body, so that the first active ingredient EM1 is effectively absorbed into the body. can be absorbed into That is, the absorption rate of the first active ingredient (EM1) can be increased by decomposing the extracellular matrix in the body of the second active ingredient (EM2). For example, the activity-promoting substance (APM) may be hyaluronidase, an enzyme that degrades or cleaves hyaluronic acid as an extracellular matrix.

In one embodiment, at least one of the mass per unit volume, the number of moles per unit volume, and the volume per unit volume of the second active ingredient (EM2) may be smaller than that of the first active ingredient (EM1). Here, the unit volume may refer to a unit volume of an area where the first active ingredient EM1 and the second active ingredient EM2 are disposed in the microneedle patch 100, for example, the microneedle 120.

The mass per unit volume, the number of moles per unit volume, and the volume per unit volume mean the mass, number of moles, and volume of the first active ingredient EM1 and the second active ingredient EM2 per unit volume of the microneedle 120, respectively.

In one embodiment, in the total weight of the microneedle 120, the first active ingredient (EM1) may occupy a greater weight than the second active ingredient (EM2). For example, the weight of the first active ingredient (EM1) may be 5 to 20 times the weight of the second active ingredient (EM2). Preferably, the weight of the first active ingredient (EM1) may be 10 to 12 times the weight of the second active ingredient (EM2).

If the weight of the first active ingredient (EM1) is less than 5 times that of the second active ingredient (EM2), the second active ingredient (EM2) may excessively degrade the patient's extracellular matrix and damage the user's cells. , may interfere with the absorption of the first active ingredient (EM1). If the weight of the first active ingredient (EM1) is greater than 20 times that of the second active ingredient (EM2), the second active ingredient (EM2) cannot degrade hyaluronic acid in the extracellular matrix, so that the first active ingredient (EM1) not activated effectively.

In one embodiment, the second active ingredient (EM2) may be activated before the first active ingredient (EM1). That is, in a state where the microneedle 120 is inserted into the body, the second active ingredient EM2 may be delivered into the body before the first active ingredient EM1. Alternatively, in a state where the first active ingredient (EM1) and the second active ingredient (EM2) are delivered into the body, the first active ingredient (EM1) decomposes the extracellular matrix in the body, in particular, after degrading hyaluronic acid. , the first active ingredient (EM1) may react.

The microneedle patch 100A according to the present invention has a core 121A extending along the longitudinal direction, so that the microneedle 120A can be implanted in a deep location. Since the core 121A has a predetermined rigidity, the user can effectively attach the microneedle patch 100A to the skin without damaging the microneedle patch 120A.

Since the microneedle patch 100A according to the present invention has an active ingredient in each of the core 121A and the cover 122A, the active ingredient can be sequentially delivered into the skin. The second active ingredient EM2 included in the cover 122A may be delivered into the skin first, and then the first active ingredient EM1 included in the core 121A may be delivered into the skin.

Referring to FIG. 5 , the microneedle patch 100B may have a base 110 and microneedles 120B. The microneedle 120B may have a core 121B, a cover 122B and an intermediate layer 123B. Compared to the above-described microneedle 120, the microneedle 120B has a characteristic in the middle layer 123B, and hereinafter, this will be mainly described.

The intermediate layer 123B may be disposed between the core 121B and the cover 122B to enhance bonding strength between the core 121B and the cover 122B. The intermediate layer 123B may be formed of a third base material having biocompatibility, adhered to the first base material of the core 121B, and adhered to the second base material of the cover 122B. The middle layer 123B may enhance durability and strength of the microneedle 120B by strengthening the bonding force between the core 121B and the cover 122B.

Referring to FIG. 6 , the microneedle patch 100C may have a base and microneedles. The microneedle may have a core 121C, a cover 122C and an intermediate region 123C. Compared to the above-described microneedle 120B, the microneedle has a characteristic in the middle region 123C, and hereinafter, this will be mainly described.

The middle region 123C may be formed by mixing the first base material BM1 of the core 121C and the second base material BM2 of the cover 122C.

In one embodiment, the first base material BM1 has a higher ratio than the second base material BM2 in the middle region 123C closer to the core 121C, and closer to the cover 122C the second base material. (BM2) may have a higher ratio than that of the first base material (BM1).

Since the middle region 123C is formed by mixing the first base material BM1 and the second base material BM2, the bonding force between the core 121C and the cover 122C is strengthened to increase durability and strength of the microneedle. can

Referring to FIG. 7 , the microneedle patch 100D may have a base 110 and microneedles 120D. The microneedle 120D may have a core 121D and a cover 122D. Compared to the aforementioned microneedle 120, the microneedle 120D is characterized by the layered structure of the cover 122D, which will be mainly described below.

The cover 122D may have a multi-layered structure in the radial direction. The cover 122D may be formed of at least two or more layers, and a base material and an active material may be disposed on each layer. However, hereinafter, for convenience of description, an embodiment in which the cover 122D includes a first cover layer 1221D and a second cover layer 1222D will be mainly described.

The first cover layer 1221D may be disposed to cover the outside of the core 121D, and the second cover layerer 122D may be disposed to cover the outside of the first cover layer 1221D. After disassembly of the outermost second cover layer 1222D is finished, the first cover layer 1221D is disassembled, and then disassembly of the core 121D starts.

In one embodiment, the first cover layer 1221D and the second cover layer 1222D may each have a base material and an active ingredient.

When the core 121D, the first cover layer 1221D, and the second cover layer 1222D each have different active ingredients, the microneedle patch 100D sequentially delivers the active ingredients into the skin over time. can do. Since decomposition progresses gradually from the outermost to the center of the microneedle 120D, various drugs can be delivered by adjusting the decomposition rate of the microneedle 120D.

In another embodiment, the first cover layer 1221D may have a base material, and the second cover layer 1222D may have a base material and an active ingredient.

If the core 121D and the second cover layer 1222D each contain an active ingredient and the first cover layer 1221D does not contain the active ingredient, the microneedle patch 100D may have a rest period in the middle of drug delivery. .

In detail, after the active ingredient of the second cover layer 1222D is delivered into the skin, the active ingredient of the core 121D is not delivered into the skin until decomposition of the first cover layer 1221D is completed. Since the active ingredient is not additionally transferred during the decomposition process of the first cover layer 1221D, absorption time of the active ingredient of the second cover layer 1222D can be secured.

Referring to FIG. 8 , the microneedle patch 100E may have a base 110 and microneedles 120E. The microneedle 120E may have a core 121E and a cover 122E. Compared to the above-described microneedle 120, the microneedle 120E has a characteristic shape, and hereinafter, this will be mainly described.

The microneedle 120E may be formed in a cone shape. A cover 122E is disposed outside the core 121E, and the cover 122E may cover a surface of the cone-shaped core 121E so that the core 121E is not exposed to the outside.

In the microneedle 120E, an active ingredient may be disposed on at least one of the core 121E and the cover 122E. Also, in the microneedle 120E, an intermediate layer or an intermediate region may be formed between the core 121E and the cover 122E.

FIG. 9 is a flowchart illustrating a method for manufacturing a microneedle patch according to another embodiment of the present invention, and FIGS. 10 to 12 are diagrams illustrating the method for manufacturing a microneedle patch of FIG. 9 .

9 to 12, the method of manufacturing a microneedle patch includes injecting a first base material into a first mold (S1), curing the first base material to form a core (S2), and forming a core (S2). in a second mold, injecting a second base material into the second mold (S3), and curing the second base material to form a cover disposed outside the core (S4). can include

In the step of injecting the first base material into the first mold ( S1 ), the first base material BM1 may be injected into the first groove MG1 of the first mold MD1 to form the core 121 . there is. At this time, a base material may be injected to form the base 110 on the top of the first groove MG1 as well.

In order to inject the first base material BM1 to the bottom of the first groove MG1, a worker may form a vacuum in the first mold MD1. For example, a suction device (not shown) is disposed under the porous first mold MD1 and the suction device is driven to suck the first base material BM1 to the bottom of the first groove MG1. can As another example, the first base material BM1 may be filled up to the bottom of the first groove MG1 by centrifugal force by rotating the first mold MD1.

In step S2 of forming a core by curing the first base material, the first base material BM1 may be cured.

In one embodiment, the first base material BM1 is contracted and cured, so that the adhesive force between the first base material BM1 and the surface of the first mold MD1 may decrease.

In detail, the first base material BM1 may be dried to form the core 121 . When the volume of the first base material BM1 decreases due to drying, the outer surface of the core 121 moves. Referring to FIG. 10 , the first base material BM1 having fluidity contacts the surface of the first groove MG1 before drying, but when drying proceeds, the first base material BM1 shrinks. The outer surface of the core 121 moves from the 1A surface 121-S1 to the 2A surface 121-S2 by the first contractive force CF1 of the first base material BM1. Since the adhesive force between the dried core 121 and the first mold MD1 decreases, the core 121 can be easily separated from the first mold MD1.

In the step of inserting the core into a second mold and injecting a second base material into the second mold (S3), the core 121 formed in the first mold MD1 is inserted into the second mold MD2. . At this time, the second base material BM2 may be injected into the second groove MG2 of the second mold MD2 to fill the outside of the core 121 with the second base material BM2.

Referring to FIG. 11 , the second base material BM2 fills the second groove MG2 to a predetermined height. The second base material BM2 may be filled up to a preset height in consideration of the volume of the core 121 . When the core 121 is inserted into the second groove MG2, the cover 122 is disposed outside the cover 122, so that the core 121 is not exposed to the outside.

In step S4 of curing the second base material to form a cover disposed outside the core, the second base material BM2 may be cured.

In one embodiment, the adhesive force between the second base material and the surface of the second mold MD2 may decrease as the second base material shrinks and hardens.

In detail, the cover 122 may be formed by drying the second base material BM2 . When the volume of the second base material BM2 is reduced by drying, the outer surface of the cover 122 moves. Referring to FIG. 12 , the second base material BM2 having fluidity comes into contact with the surface of the second groove MG2 before drying, but when drying proceeds, the second base material BM2 shrinks. The outer surface of the cover 122 moves from the 1B surface 122-S1 to the 2B surface 122-S2 by the second contractive force CF2 of the second base material BM2. Since the adhesive force between the dried cover 122 and the second mold MD2 decreases, the cover 122 can be easily separated from the second mold MD2.

As an alternative embodiment, an intermediate material may be applied to the surface of the core 121 before inserting the core 121 into the second mold MD2 . The core 121 coated with the intermediate material may be inserted into the second mold MD2 , and the second base material BM2 may be disposed outside the intermediate material. Thus, the intermediate material may be disposed between the core 121 and the cover 122 to form an intermediate layer.

The method for manufacturing a microneedle patch according to the present invention may manufacture a microneedle having a plurality of layers in a radial direction. Since the core 121 is first manufactured and then the cover 122 is formed outside the core 121, strength and durability of the microneedle 120 can be increased.

The elongated microneedle is manufactured by injecting a base material into a groove of a mold in order to manufacture a core or a cover. Since the size of the groove of the mold is very small, there is a high risk of damage to the manufactured microneedle patch when it is separated from the groove. A high-quality microneedle patch can be manufactured.

13 is a flowchart illustrating a method for manufacturing a microneedle patch according to another embodiment of the present invention, and FIGS. 14 and 15 are diagrams illustrating the method for manufacturing a microneedle patch of FIG. 13 .

13 to 15, the method of manufacturing a microneedle patch includes injecting a first base material into a first mold (S10), curing the first base material to form a core (S20), and Injecting a second base material into a mold (S30), curing the second base material to form a cover having an insertion groove (S40), and inserting the core into the insertion groove of the cover (S50). ) may be included.

The step of injecting the first base material into the first mold (S10) and the step of curing the first base material to form a core (S20) are the same as the microneedle manufacturing method of the above-described embodiment, so descriptions thereof are omitted. do it with

In the step of injecting the second base material into the second mold ( S30 ), the second base material BM2 may be injected into the space between the second mold MD2 and the third mold MD3 .

The second mold MD2 may have a second groove MG2, and the third mold MD3 may have a protruding pin MP. The protruding plate MP may have a shape and volume corresponding to that of the core 121 . The second base material BM2 is filled up to a predetermined height in the second groove MG2, and the third mold MD3 is assembled to the second mold MD2.

In the step of curing the second base material to form a cover having an insertion groove (S40), the second base material BM2 disposed between the second mold MD2 and the third mold MD3 is cured. can do. The outer shape of the cover 122 may be formed by the second groove MG2, and the insertion groove 122-CH may be formed by the protruding pin MP.

The cover 122 can be easily separated from the mold by the contractility of the second base material BM2. Since the second base material BM2 shrinks during curing, the adhesive force between the surface of the second groove MG2 and the second base material BM2 decreases. Also, the adhesive force between the surface of the protruding pin MP and the second base material BM2 is reduced.

In the step of inserting the core into the insertion groove of the cover (S50), the microneedle 120 may be formed by inserting the core 121 into the cover 122.

The core 121 may have a diameter of D1, and the insertion groove 122-CH may have an inner diameter of D2. In one embodiment, D1 and D2 are set to be substantially the same, and the core 121 may be coupled to the insertion groove 122-CH by an interference fit.

As an alternative embodiment, the intermediate material (M) may be injected into the outer surface of the core 121 or the insertion groove 122-CH of the cover 122. The intermediate material M may be sprayed using the nozzle 20 . The intermediate material M may be disposed between the core 121 and the cover 122 to form an intermediate layer or an intermediate region.

For example, the intermediate material M may melt the first base material BM1 or the second base material BM2. When the intermediate material M comes into contact with the core 121, the size of D1 may be reduced by melting the first base material BM1. Also, when the intermediate material M is injected into the insertion groove 122-CH, the size of D2 may be increased by melting the second base material BM2. Since the intermediate material M melts the first base material BM1 or the second base material BM2, the core 121 can be easily inserted into the insertion groove 122-CH.

As another example, the intermediate material M may have adhesion to the first base material BM1 and the second base material BM2. Thus, the intermediate material (M) is disposed and cured between the core 121 and the cover 122, it is possible to strengthen the bonding force between the core 121 and the cover 122.

The method for manufacturing a microneedle patch according to the present invention may manufacture a microneedle having a plurality of layers in a radial direction. Since the core 121 and the cover 122 are assembled after each manufacturing, the microneedle 120 can be manufactured simply and accurately.

In this way, the present invention has been described with reference to the embodiments shown in the drawings, but this is only exemplary, and those skilled in the art will understand that various modifications and equivalent other embodiments are possible therefrom. . Therefore, the true technical scope of protection of the present invention should be determined by the technical spirit of the appended claims.

Specific executions described in the embodiments are examples, and do not limit the scope of the embodiments in any way. In addition, if there is no specific reference such as "essential" or "important", it may not necessarily be a component necessary for the application of the present invention.

In the specification of the embodiments (particularly in the claims), the use of the term "above" and similar indicating terms may correspond to both singular and plural. In addition, when a range is described in the examples, it includes the invention to which individual values belonging to the range are applied (unless there is no description to the contrary), and it is as if each individual value constituting the range is described in the detailed description. . Finally, if there is no explicit description or description of the order of steps constituting the method according to the embodiment, the steps may be performed in an appropriate order. Examples are not necessarily limited according to the order of description of the steps. The use of all examples or exemplary terms (eg, etc.) in the embodiments is simply to describe the embodiments in detail, and the scope of the embodiments is limited due to the examples or exemplary terms unless limited by the claims. It is not. In addition, those skilled in the art can appreciate that various modifications, combinations and changes can be made according to design conditions and factors within the scope of the appended claims or equivalents thereof.

Claims

injecting a first base material into a first mold;

curing the first base material to form a core;

inserting the core into a second mold and injecting a second base material into the second mold; and

And curing the second base material to form a cover disposed outside the core.
According to claim 1,

the core comprises a first active ingredient;

The method of manufacturing a microneedle patch, wherein the cover includes a second active ingredient that is activated together with the first active ingredient or increases the activity of the first active ingredient.
According to claim 1,

Forming the core

The method of manufacturing a microneedle patch, wherein the first base material shrinks and hardens, thereby reducing the adhesive force between the first base material and the surface of the first mold.
According to claim 1,

Forming the cover

The method of manufacturing a microneedle patch, wherein the second base material shrinks and hardens, thereby reducing the adhesive force between the second base material and the surface of the second mold.
According to claim 1,

The second base material covers the outside of the core so that it is not exposed to the outside, the microneedle patch manufacturing method.
injecting a first base material into a first mold;

curing the first base material to form a core;

injecting a second base material into a second mold;

forming a cover having an insertion groove by curing the second base material; and

A method for manufacturing a microneedle patch, comprising: inserting the core into the insertion groove of the cover.
According to claim 6,

Inserting the core into the cover

The method of manufacturing a microneedle patch, further comprising applying an intermediate material to an outer surface of the core or an inner surface of the insertion groove.
According to claim 6,

the core comprises a first active ingredient;

The method of manufacturing a microneedle patch, wherein the cover includes a second active ingredient that is activated together with the first active ingredient or increases the activity of the first active ingredient.
According to claim 6,

The second base material covers the outside of the core so that it is not exposed to the outside, the microneedle patch manufacturing method.