KR20230024668A - Micro-needle patch - Google Patents

Abstract

The present invention relates to a microneedle patch having a plurality of microneedles, wherein the microneedles include: a first needle part in which crosslinked hyaluronic acid and non-crosslinked hyaluronic acid are mixed and which has a sharpened tip; and a second needle part which is in contact with the first needle part and in which the crosslinked hyaluronic acid and the non-crosslinked hyaluronic acid are mixed. Accordingly, the microneedle patch with improved skin improvement effect and user convenience can be provided.

Description

Microneedle patch {Micro-needle patch}

The present invention relates to 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 provide a microneedle patch with improved skin improvement effect and improved user convenience.

In one embodiment of the present invention, in the microneedle patch having a plurality of microneedles, the microneedle is a mixture of cross-linked hyaluronic acid and non-cross-linked hyaluronic acid. and a first needle part having a sharpened tip, and a second needle part contacting the first needle part and mixing crosslinked hyaluronic acid and non-crosslinked hyaluronic acid.

In addition, based on the total weight of the hyaluronic acid in the first needle part, the cross-linked hyaluronic acid has a content (w/w) in a first range, and the total weight of the hyaluronic acid in the second needle part Based on , the cross-linked hyaluronic acid may have a content in a second range different from the content (w/w) in the first range.

In addition, the content of the cross-linked hyaluronic acid in the first needle portion may be greater than that in the second needle portion.

In addition, the first needle part of the microneedle may have greater rigidity than the second needle part.

In addition, the height of the first needle portion may be equal to or less than the height of the second needle portion.

Also, a dissolution rate of the second needle portion may be different from a dissolution rate of the first needle portion.

In addition, the dissolution rate of the second needle portion of the microneedle may be higher than the dissolution rate of the first needle portion.

In addition, at least one of the first needle part and the second needle part may have an active ingredient.

In addition, the microneedle may further include an adhesive layer disposed between the first needle part and the second needle part.

Another aspect of the present invention includes a base and a microneedle protruding from the surface of the base, in which cross-linked hyaluronic acid and non-cross-linked hyaluronic acid are mixed, , The microneedle provides a microneedle patch having a higher content (w/w) of the crosslinked hyaluronic acid than the uncrosslinked hyaluronic acid based on the total weight of the hyaluronic acid.

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

The microneedle patch according to the present invention includes crosslinked hyaluronic acid and non-crosslinked hyaluronic acid, and can effectively improve skin wrinkles. In particular, the content of cross-linked hyaluronic acid based on the total weight of hyaluronic acid is set to be greater than the content of non-cross-linked hyaluronic acid, thereby enhancing the skin wrinkle improvement effect.

The microneedle patch according to the present invention contains a relatively high content of cross-linked hyaluronic acid at the tip of the microneedle, so that when attached to the skin, the stiffness of the tip tip easily and effectively punctures the skin and can be implanted into the skin. .

In the microneedle patch according to the present invention, since each layer of the microneedle has a different dissolution rate, the retention time of hyaluronic acid may be set differently according to the thickness of the skin.

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 and 5 are diagrams showing modified examples of FIG. 2 .
6 is a cross-sectional view showing a microneedle patch according to another embodiment of the present invention.
FIG. 7 is an enlarged view of a portion of FIG. 6 .
8 to 12 are diagrams showing modified examples of FIG. 7 .
13 and 14 are cross-sectional views of a microneedle patch according to another embodiment of the present invention.
15 to 17 are flowcharts illustrating a method of manufacturing a microneedle patch according to another embodiment of the present invention.
18 and 19 are enlarged pictures of a microneedle patch and microneedles manufactured according to an embodiment of the present 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 4 is an enlarged view of region A of FIG. 3 .

Referring to FIGS. 1 to 4 , the microneedle patch 100 may include a base 110 and microneedles 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 plurality of layers 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 have a lower solubility than the layer most adjacent to the microneedle 120, that is, the layer most spaced apart from the tip of the microneedle 120. Since a 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 (eg, disaccharides). In addition, the base 110 preferably does not contain drugs or active ingredients.

The base 110 may include a biocompatible material. The base 110 may select a biocompatible material selected as a base material as a base material. In addition, the base 110 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, and 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 , to form these polymers It is at least one polymer selected from the group consisting of copolymers of monomers and cellulose.

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.

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.

The microneedle 120 may include cross-linked hyaluronic acid and non-cross-linked hyaluronic acid. The microneedle 120 may be prepared by mixing crosslinked hyaluronic acid (HA1) and non-crosslinked hyaluronic acid (HA2). The physical properties of uncrosslinked hyaluronic acid (HA2) and crosslinked hyaluronic acid (HA1) are compared as follows.

Cross-linked hyaluronic acid (HA1) is a water-insoluble polymer, has a network structure in water, and has a solid gel state. The cross-linked hyaluronic acid (HA1) may have a hydrogel state. Cross-linked hyaluronic acid (HA1) has an amorphous (heterogeneous) state in water, and the particle size in water ranges from tens to hundreds of micrometers (um). Cross-linked hyaluronic acid (HA1) has higher elasticity than viscosity and has swelling properties in water. In addition, it has a hyaluronic acid degrading enzyme inhibitory effect.

Non-crosslinked hyaluronic acid (HA2) is a water-soluble polymer and has a liquid sol state in water. Non-crosslinked hyaluronic acid (HA2) maintains a homogenized state of particles in water, and the size of the particles in water has a range of nanometers (nm). Non-crosslinked hyaluronic acid (HA2) has higher viscosity than elasticity, and has a weak swelling effect in water. In addition, there is no inhibitory effect on hyaluronic acid degrading enzyme. For example, uncrosslinked hyaluronic acid (HA2) can be degraded by hyaluronidase.

Cross-linked hyaluronic acid (HA1) can be prepared by adding a cross-linking agent to uncross-linked hyaluronic acid (HA2). For example, hyaluronic acid having an average molecular weight of 360 kDa (molecular weight range of 240-490 kDa), which is a biocompatible polymer, is completely dissolved in alkaline water (0.25 N NaOH), and then butanediol diglycidyl ether is used as a cross-linking agent to achieve cross-linking. (BDDE, 1, 4-Butanediol diglycidyl ether) can be added to produce cross-linked hyaluronic acid.

In one embodiment, the weight of the cross-linked hyaluronic acid (HA1) in the microneedle 120 may be greater than the weight of the uncross-linked hyaluronic acid (HA2). Preferably, the crosslinked hyaluronic acid (HA1) is 50% to 95% based on the total weight, and the non-crosslinked hyaluronic acid (HA2) may be 5% to 50%. Preferably, the weight ratio of uncrosslinked hyaluronic acid (HA2) to crosslinked hyaluronic acid (HA1) may range from 1:1 to 1:19. More preferably, the weight ratio of uncrosslinked hyaluronic acid (HA2) to crosslinked hyaluronic acid (HA1) may range from 1:8 to 1:12.

Since the content of cross-linked hyaluronic acid (HA1) relative to the total weight of the microneedle 120 is greater than that of uncross-linked hyaluronic acid (HA2), the microneedle 120 can be used for wrinkle treatment. Cross-linked hyaluronic acid (HA1) has a network structure in vivo and has swelling properties, so it can fill the space in vivo. In addition, since cross-linked hyaluronic acid (HA1) has an inhibitory effect on hyaluronic acid degrading enzyme, it can maintain a long-term state in the skin and increase the period of wrinkle treatment. In addition, the cross-linked hyaluronic acid (HA1) increases the strength of the microneedle 120, so that the microneedle patch 100 can be easily inserted without breaking when attached to the skin.

Since the uncrosslinked hyaluronic acid (HA2) of the microneedle 120 has a higher decomposition rate than the crosslinked hyaluronic acid (HA1), the base 110 can be easily separated from the microneedle patch 100. That is, when the microneedle patch 100 is inserted into the skin, the non-crosslinked hyaluronic acid (HA2) is decomposed at a relatively faster rate, and the overall strength of the microneedle 120 may decrease due to the decomposed portion. Therefore, the user can easily remove the base 110 and keep the microneedle 120 inserted into the skin.

As an alternative embodiment, the microneedle 120 may include a disaccharide additive. The disaccharide may include sucrose, lactulose, lactose, maltose, trehalose, or cellobiose, and may include sucrose, maltose, or trehalose in particular.

As an optional embodiment, the microneedle 120 may include an adhesive. The adhesive is at least one adhesive selected from the group consisting of silicone, polyurethane, hyaluronic acid, physical adhesive (Gecko), polyacrylic, ethyl cellulose, hydroxy methyl cellulose, ethylene vinyl acetate and polyisobutylene.

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

The microneedle patch 100 according to the present invention includes crosslinked hyaluronic acid (HA1) and non-crosslinked hyaluronic acid (HA2) with microneedle 120, and can effectively improve skin wrinkles. In particular, the content of cross-linked hyaluronic acid (HA1) based on the total weight of hyaluronic acid is set higher than that of non-cross-linked hyaluronic acid (HA2), thereby increasing the skin wrinkle improvement effect. In addition, the microneedle patch 100 can be attached to the skin by non-crosslinked hyaluronic acid (HA2), the base 110 can be easily and simply separated, and the skin wrinkle improvement period by the microneedle 120 can be extended.

4 and 5 are diagrams showing modified examples of FIG. 2 .

Referring to FIG. 4 , the microneedle patch 100A may include a base 110 and microneedles 120A.

The microneedle 120A may include crosslinked hyaluronic acid (HA1) and non-crosslinked hyaluronic acid (HA2). The content of the cross-linked hyaluronic acid (HA1) may vary according to the height of the microneedle 120A.

In one embodiment, the area adjacent to the base 110 (ie, the upper end of the microneedle) in the microneedle 120A may have a smaller amount of cross-linked hyaluronic acid (HA1) than the apical tip area. A relatively higher content of cross-linked hyaluronic acid (HA1) may be set in the tip (ST) of the microneedle (120A) than in other areas.

In one embodiment, in the microneedle 120A, the content of the cross-linked hyaluronic acid (HA1) may increase along the tip (ST) from the base (110).

Since the strength of the tip of the microneedle 120A piercing the skin is set high, the microneedle patch 100A can be easily attached. Since the cross-linked hyaluronic acid (HA1) increases the strength of the microneedle (120A), the tip (ST) of the microneedle (120A) has a relatively strong strength. When the user attaches the microneedle patch 100A to the skin, the microneedle 120A can be easily and simply inserted into the skin.

The microneedle patch 100A can easily separate the base 110. Since the content of non-crosslinked hyaluronic acid (HA2) is relatively small in the area adjacent to the base 110, the non-crosslinked hyaluronic acid (HA2) is decomposed at a relatively high speed, and the user can easily separate the base 110. there is.

Referring to FIG. 5 , the microneedle patch 100B may include a base 110 and microneedles 120B.

The microneedle 120B may include crosslinked hyaluronic acid (HA1) and non-crosslinked hyaluronic acid (HA2). In addition, the microneedle 120B may include an active ingredient (EM).

The microneedle 120B may include a pharmaceutical, medical or cosmetic active ingredient (EM) in at least a portion thereof. 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), nafarerin ( nafarelin), parathyroid hormone, pramlintide, T-20 (enfuvirtide), thymalfasin, and ziconotide. In addition, the active ingredient (EM) may be a cosmetic ingredient such as a whitening agent or antioxidant.

In one embodiment, the active ingredient (EM) may be a colloid dispersed in a solvent forming microneedles (120B) 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).

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

In another embodiment, the active ingredient (EM) may be dissolved in the microneedle (120B). The active ingredient (EM) may be dissolved in a base material of the microneedle 120B, such as the aforementioned biodegradable materials, to configure the microneedle 120B. The active ingredient (EM) may be dissolved in the base material at an even concentration, and may be intensively distributed at a specific height of the microneedle 120B like the above-described fine particles.

In another embodiment, the microneedle patch 100B 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 another embodiment, a pharmaceutical, medical or cosmetic active ingredient (EM) may be coated on the microneedle 120B. The active ingredients (EM) may be coated on the entire microneedle 120B or only a portion of the microneedle 120B. Alternatively, a portion of the coating layer of the microneedle 120B may be coated with the first active ingredient, and the other portion may be coated with the second active ingredient.

6 is a cross-sectional view showing a microneedle patch according to another embodiment of the present invention, and FIG. 7 is an enlarged view of a portion of FIG. 6 .

Referring to FIGS. 6 and 7 , the microneedle patch 200 may have a plurality of stacked layers. The microneedle patch 200 may include a base 210 and microneedles 220 . The base 210 may be substantially the same as the base 110 of the above-described embodiment.

The number of layers forming the microneedle 220 is not limited to a specific number. However, hereinafter, for convenience of description, the microneedle 220 having two layers will be mainly described.

The microneedle 220 may include a first needle part 221 disposed at an end and a second needle part 222 stacked on the first needle part 221 .

The first needle part 221 may form a sharpened tip of the microneedle 220 . The first needle part 221 may be formed by mixing crosslinked hyaluronic acid (HA1) and non-crosslinked hyaluronic acid (HA2).

The second needle part 222 contacts the first needle part 221 and may be formed by mixing cross-linked hyaluronic acid (HA1) and non-cross-linked hyaluronic acid (HA2).

The first needle part 221 and the second needle part 222 may have different hyaluronic acid contents. Based on the total weight of hyaluronic acid in the first needle portion 221, the cross-linked hyaluronic acid (HA1) may have a content (w/w) within a first range. In addition, based on the total weight of hyaluronic acid in the second needle portion 222, the cross-linked hyaluronic acid (HA1) may have a content (w/w) in a second range different from the content (w/w) in the first range.

In one embodiment, the microneedle 220 may have a higher content (w/w) of cross-linked hyaluronic acid (HA1) in a portion adjacent to the apical tip than in a portion adjacent to the base 210. The first range of the first needle unit 221 may be set larger than the second range of the second needle unit 222 . That is, the content of cross-linked hyaluronic acid (HA1) in the first needle part 221 may be set higher than that in the second needle part 222 .

Since the first needle part 221 has a high content of cross-linked hyaluronic acid (HA1), its rigidity is relatively increased. Since the content of the cross-linked hyaluronic acid (HA1) in the second needle portion 222 is lower than that of the first needle portion 221, the stiffness of the second needle portion 222 may be set relatively lower than that of the first needle portion 221.

In detail, when the microneedle patch 200 is attached to the skin, the first needle part 221 punctures the skin, and the first needle part 221 and the second needle part 222 are implanted into the skin. Since the first needle part 221 has a smaller volume than the second needle part 222, the weight of the cross-linked hyaluronic acid (HA1) is smaller in the first needle part 221 than in the second needle part 222. However, since the content of the first range of the first needle portion 221 is greater than the content of the second range of the second needle portion 222, the first needle portion 221 of the microneedle 220 punctures the skin. be strong enough to do so.

In addition, when the microneedle 220 is inserted into the skin, the cross-linked hyaluronic acid (HA1) of the second needle part 222 has a sufficient content, so that after being implanted into the skin, it has a swelling property and a mesh structure to improve skin wrinkles. can have an effect.

In one embodiment, the dissolution rate of the first needle portion 221 and the dissolution rate of the second needle portion 222 may be set to be different from each other. Since the first content of the first needle portion 221 and the second content of the second needle portion 222 are different, each layer may have a different dissolution rate.

In one embodiment, the dissolution rate of the first needle portion 221 may be set to be slower than the dissolution rate of the second needle portion 222 . Since the first content of the first needle portion 221 is set higher than the second content of the second needle portion 222, the dissolution rate of the second needle portion 222 is greater than the dissolution rate of the first needle portion 221. can be set up quickly.

In one embodiment, the first needle part 221 may be formed of crosslinked hyaluronic acid (HA1), and the second needle part 222 may be formed of uncrosslinked hyaluronic acid (HA2). Since only crosslinked hyaluronic acid (HA1) is formed in the first needle part 221 and non-crosslinked hyaluronic acid (HA2) is formed in the second needle part 222, the first needle part 221 is formed only with the second needle part 221. It may have higher rigidity than the needle part 222 .

The microneedle patch 200 according to the present invention includes a relatively high content of cross-linked hyaluronic acid (HA1) in the tip of the microneedle 220, so that when attached to the skin, the stiffness of the tip helps the skin easily and effectively. It can be punctured and implanted into the skin.

In the microneedle patch 200 according to the present invention, since each layer of the microneedle 220 has a different dissolution rate, the holding time of hyaluronic acid can be set differently according to the thickness of the skin. In addition, since the dissolution rate of the portion adjacent to the base is faster than that of the end, the base 210 can be quickly separated after the microneedle patch 200 is attached.

8 to 12 are diagrams showing modified examples of FIG. 7 .

Referring to FIG. 8 , the microneedle patch 200A may include a base 210 and microneedles 220A. The microneedle 220A may have a plurality of layered structures and include a first needle portion 221A and a second needle portion 222A.

The first needle portion 221A and the second needle portion 222A may have different hyaluronic acid contents. Based on the total weight of hyaluronic acid in the first needle portion 221A, the cross-linked hyaluronic acid (HA1) may have a content (w/w) within a first range. In addition, based on the total weight of hyaluronic acid in the second needle portion 222A, the cross-linked hyaluronic acid (HA1) may have a content (w/w) in a second range different from the content (w/w) in the first range.

The first needle portion 221A and the second needle portion 222A are similar to the first needle portion 221 and the second needle portion 222 of the above-described embodiment, and have a technical feature in height, which is centered on them. to be explained by

The first needle portion 221A may have a first height h1, and the second needle portion 222A may have a second height h2. The first height h1 may be set lower than the second height h2.

The first needle portion 221A may have a lower height than the second needle portion 222A, and the first range of the first needle portion 221A may be set greater than the second range of the second needle portion 222A. . Since the content of cross-linked hyaluronic acid (HA1) is high in the first needle portion 221A, rigidity is relatively increased. In particular, since the first needle part 221A has a relatively low first height h1 and a high first content of cross-linked hyaluronic acid (HA1), it may have a strongly aggregated structure, and the microneedle 220A The first needle portion 221A of ) can effectively puncture the skin and insert the microneedle 220A into the skin.

The microneedle patch (200A) according to the present invention includes a relatively high content of cross-linked hyaluronic acid (HA1) in the tip of the microneedle (220A), so that when attached to the skin, the stiffness of the tip helps the skin easily and effectively. It can be punctured and implanted into the skin.

Referring to FIG. 9 , the microneedle patch 200B may include a base 210 and microneedles 220B. The microneedle 220B has a plurality of layered structures and may include a first needle part 221 , a second needle part 222 and a third needle part 223B. The first needle portion 221B and the second needle portion 222B are similar to the first needle portion 221 and the second needle portion 222 of the above-described embodiment, and thus a detailed description thereof will be omitted.

The third needle portion 223B is disposed adjacent to the base 210 . The third needle unit 223B may connect the microneedle 220B to the base 210 . The dissolution rate of the third needle portion 223B may be set higher than that of the first needle portion 221B and the second needle portion 222B.

The height of the third needle portion 223B is set lower than the height of the first needle portion 221B or the height of the second needle portion 222B, but the dissolution rate of the third needle portion 223B is higher than that of the first needle portion 221B. ) or the second needle part 222B, so it is rapidly decomposed. The third needle part 223B is a part connected to the base 210, and when the third needle part 223B is disassembled, the user can easily separate the base 210 from the microneedle 220B.

Referring to FIG. 10 , a microneedle patch 200C may include a base 210 and microneedles 220C. The microneedle 220C has a plurality of layered structures and may include a first needle portion 221C and a second needle portion 222C.

The first needle portion 221C and the second needle portion 222C may have different hyaluronic acid contents. Based on the total weight of hyaluronic acid in the first needle part 221C, the cross-linked hyaluronic acid (HA1) may have a content (w/w) within a first range. In addition, based on the total weight of hyaluronic acid in the second needle portion 222C, the cross-linked hyaluronic acid (HA1) may have a content (w/w) in a second range different from the content (w/w) in the first range.

The first needle part 221C and the second needle part 222C may be loaded with other active ingredients EM. For example, the first active ingredient EM1 loaded on the first needle part 221C is a drug targeting the dermis, and the second active ingredient EM2 loaded on the second needle part 222C targets the epidermis. It may be a drug that At this time, the delivery rate of the first active ingredient and the second active ingredient may be adjusted by adjusting the biodegradation rate of the first needle portion 221C and the second needle portion 222C.

Referring to FIG. 11 , the microneedle patch 200D may include a base 210 and microneedles 220D. The microneedle 220D has a plurality of layered structures and may include a first needle portion 221D and a second needle portion 222D.

The first needle portion 221D and the second needle portion 222D may have different hyaluronic acid contents. Based on the total weight of hyaluronic acid in the first needle part 221D, the cross-linked hyaluronic acid (HA1) may have a content (w/w) within a first range. In addition, based on the total weight of hyaluronic acid in the second needle portion 222D, the cross-linked hyaluronic acid (HA1) may have a content (w/w) in a second range different from the content (w/w) in the first range.

A curvature CS may be formed in a region where the first needle portion 221D and the second needle portion 222D contact each other.

The microneedle 220D may have a curvature CS that is convex downward toward the tip. In an area where the first needle portion 221D and the second needle portion 222D contact each other, a portion adjacent to the tip may have a downwardly convex shape. The curvature CS may be symmetrical on both sides of the central axis in the longitudinal direction of the microneedle 220D.

Since the microneedle 220D has a layered structure having a curvature, each layer can be easily separated. A contact portion between the first needle portion 221D and the second needle portion 222D is thinly formed at the edge of the microneedle 220D. In detail, the distance between the outer surface of the first needle portion 221D and the boundary surface is relatively short. When the microneedle 220D is inserted into the skin, the outer surface starts to biodegrade. Since the first needle part 221D is easily peeled off by the curved surface, the first needle part 221D and the second needle part 222D are can be easily disassembled.

Referring to FIG. 12 , the microneedle patch 200E may include a base 210 and microneedles 220E. The microneedle 220E has a plurality of layered structures, and may include a first needle portion 221E, a second needle portion 222E, and an adhesive layer ADL.

The first needle portion 221E and the second needle portion 222E may have different hyaluronic acid contents. Based on the total weight of hyaluronic acid in the first needle portion 221E, the cross-linked hyaluronic acid (HA1) may have a content (w/w) within a first range. In addition, based on the total weight of hyaluronic acid in the second needle portion 222E, the cross-linked hyaluronic acid (HA1) may have a content (w/w) in a second range different from the content (w/w) in the first range.

In the microneedle 220E, an adhesive layer ADL may be disposed between the first needle portion 221E and the second needle portion 222E. The microneedle 220E may be manufactured by forming the first needle portion 221E, adding an adhesive material to form the adhesive layer ADL, and forming the second needle portion 222E on the adhesive layer ADL. can

In one embodiment, the adhesive layer ADL may be formed of a material capable of increasing adhesive strength between the first needle portion 221E and the second needle portion 222E. Also, the adhesive layer ADL may be formed of a biocompatible material or a biodegradable material.

For example, the adhesive layer ADL may be formed of a moisture layer. Moisture is applied to the upper surface of the first needle part 221E to melt the upper surface of the first needle part 221E, and then the second needle part 222E is attached to the first needle part 221E and the second needle part 221E. Section 222E may be coupled.

In one embodiment, the adhesive layer ADL may be formed of a material having a higher biodegradation rate than the first needle portion 221E and the second needle portion 222E. When the microneedle 220E is inserted into the skin, since the adhesive layer ADL is first decomposed, the first needle portion 221E and the second needle portion 222E may be separated.

In the drawings, the adhesive layer ADL is shown as dividing the first needle portion 221E and the second needle portion 222E, but is not limited thereto. For example, the adhesive layer ADL may have a mixed shape of the first needle portion 221E and the second needle portion 222E.

Since the microneedle 220E includes the adhesive layer ADL, bonding strength between the first needle portion 221E and the second needle portion 222E may be increased. When the microneedle 220E is inserted into the skin, the first needle portion 221E and the second needle portion 222E are not easily separated by an external force applied to the microneedle patch. Meanwhile, after the microneedle 220E is inserted into the skin, the adhesive layer ADL is easily decomposed, and the first needle portion 221E and the second needle portion 222E may be separated.

13 and 14 are cross-sectional views of a microneedle patch according to another embodiment of the present invention.

Referring to FIG. 13 , the microneedle patch 300 may include a base 310 , microneedles 320 and a shaft 330 .

As the microneedle 320, the microneedles 120, 120A, and 120B of the above-described embodiment may be applied.

The shaft 330 may connect between the base 310 and the microneedle 320 . The shaft 330 may extend a predetermined length in the longitudinal direction of the microneedle 320 . The microneedle 320 may be deeply inserted by the shaft 330 .

The shaft 330 is decomposed in vivo, and the base 310 can be easily separated. The width of the shaft 330 is set smaller than the width of the upper end of the microneedle 320 . Since the shaft 330 has a smaller volume than the microneedle 320, it may first be dissolved in vivo. When the shaft 330 is dissolved, the microneedle 320 remains inserted into the skin of the subject, and the base 310 can be easily removed.

The shaft 330 may degrade faster in vivo than the microneedle 320 . The base material constituting the shaft 330 may be formed of a material that is well decomposed in vivo faster than the microneedle 320 . Thus, when the microneedle patch 300 is inserted into the skin of a subject, the shaft 330 is quickly dissolved and the base 310 can be easily removed.

In one embodiment, the microneedle 320 may be formed of crosslinked hyaluronic acid (HA1), and the shaft 330 may be formed of non-crosslinked hyaluronic acid (HA2). Since the microneedle 320 is formed only of crosslinked hyaluronic acid (HA1) and the shaft 330 is formed only of non-crosslinked hyaluronic acid (HA2), the microneedle 320 has relatively higher rigidity than the shaft 330. , and the microneedle 320 can easily puncture the skin.

Referring to FIG. 14 , the microneedle patch 300A may include a base 310, microneedles 320A, and a shaft 330.

The microneedle 320A may have a layered structure of a first needle portion 321A and a second needle portion 322A. As the microneedle 320A, the microneedles 220 and 220A to 220E of the above-described embodiment may be applied.

In one embodiment, the microneedle 320A may be formed of only cross-linked hyaluronic acid (HA1), or as described above, the content range of cross-linked hyaluronic acid (HA1) may be set differently in each layer. The shaft 330 may be formed only of non-crosslinked hyaluronic acid (HA2). Since the shaft 330 is formed of only non-crosslinked hyaluronic acid (HA2), the microneedle 320A may have a relatively higher rigidity than the shaft 330, and the microneedle 320A may easily puncture the skin. .

15 to 17 are flowcharts illustrating a method of manufacturing a microneedle patch according to another embodiment of the present invention.

Referring to FIG. 15, in the method for manufacturing a microneedle patch according to the present invention, after preparing a base material by mixing cross-linked hyaluronic acid and non-cross-linked hyaluronic acid, A microneedle is prepared from the material (S1).

In the microneedle, crosslinked hyaluronic acid (HA1) has a higher content (w/w) than non-crosslinked hyaluronic acid (HA2) based on the total weight of hyaluronic acid.

Referring to FIG. 16 , the microneedle patch may have a multi-layered structure.

First, cross-linked hyaluronic acid (HA1) in the total weight of hyaluronic acid forms a first needle part having a content in a first range (S10), and cross-linked hyaluronic acid (HA1) in a content in a second range in the total weight of hyaluronic acid To form a second needle portion having (S20). The first range is different from the second range, and preferably the first range is set larger than the second range.

Referring to FIG. 17 , the microneedle patch can precisely and precisely manufacture microneedles even if the weight of the cross-linked hyaluronic acid (HA1) is large.

Crosslinked hyaluronic acid (HA1) has a network structure and is water insoluble, so it is difficult to cast in a mold. In particular, since the tip of the microneedle has a very small volume, there is a limit to increasing the content of crosslinked hyaluronic acid (HA1) in the tip.

According to the method for manufacturing a microneedle patch according to the present invention, the content of cross-linked hyaluronic acid (HA1) can be increased even at the end of a microneedle by using a low-pressure atmosphere and centrifugal force.

The method includes filling a mold having a plurality of needle grooves with a base material in which crosslinked hyaluronic acid (HA1) and uncrosslinked hyaluronic acid (HA2) are mixed (S110), forming a pressure lower than atmospheric pressure in the mold ( S120), rotating the mold about the rotation axis (S130), and drying the base material filled in the needle groove (S130).

In the step of filling a mold having a plurality of needle grooves with a base material in which cross-linked hyaluronic acid (HA1) and uncross-linked hyaluronic acid (HA2) are mixed (S110), the cross-linked hyaluronic acid (HA1) is mixed with uncross-linked hyaluronic acid (HA2). A base material having a higher content is prepared and injected into the needle groove.

In the step of forming a pressure lower than atmospheric pressure in the mold (S120), after the mold filled with the base material is placed in a chamber (not shown), a low-pressure atmosphere is formed in the chamber by using a pressure pump or the like. At this time, the gas between the needle groove and the base material is discharged to the outside due to the pressure difference with the outside, and the base material completely fills the needle groove.

In the step of rotating the mold with respect to the rotation axis (S130), centrifugal force is formed on the mold so that the base material can be completely filled in the needle groove by the centrifugal force. In particular, since the base material is filled in the empty space where the gas is removed in the previous step, it is possible to prevent the empty space from being created inside the microneedle.

In the step of drying the base material filled in the needle groove (S130), the microneedle may be formed by drying the base material.

18 and 19 are enlarged pictures of a microneedle patch and microneedles manufactured according to an embodiment of the present invention. In FIGS. 18 and 19 , methylene blue was added to the microneedle to distinguish the microneedle from the shaft.

Referring to FIG. 18, the microneedle was made of 2.4% crosslinked hyaluronic acid, and the shaft was made of uncrosslinked hyaluronic acid.

Since the microneedle that punctures the skin is made of cross-linked hyaluronic acid, the microneedle can be easily implanted into the skin.

Referring to FIG. 19 , the microneedle was made of 2.4% crosslinked hyaluronic acid and 1% uncrosslinked hyaluronic acid, and the shaft was made of uncrosslinked hyaluronic acid.

The tip of the microneedle may be formed sharp and delicate, including crosslinked hyaluronic acid and non-crosslinked hyaluronic acid. In addition, since the cross-linked hyaluronic acid in the microneedle has a higher content than non-crosslinked hyaluronic acid, the microneedle can be easily implanted into the skin.

The microneedle manufacturing method according to the present invention removes gas present inside the base material and applies centrifugal force to the mold, so that sophisticated and detailed microneedles can be manufactured. In particular, even if the content of cross-linked hyaluronic acid (HA1) in the base material is higher than that of uncross-linked hyaluronic acid (HA2), the base material is completely filled in the needle groove by low pressure and centrifugal force, so the quality of the microneedle is improved. It can be.

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.

100: microneedle patch
110: base
120: microneedle
121: first needle part
122: second needle part

Claims (10)

In the microneedle patch having a plurality of microneedles,
The microneedle
A first needle portion in which cross-linked hyaluronic acid and non-cross-linked hyaluronic acid are mixed and having a sharpened tip; and
A microneedle patch comprising: a second needle portion in contact with the first needle portion and in which crosslinked hyaluronic acid and non-crosslinked hyaluronic acid are mixed. According to claim 1,
Based on the total weight of the hyaluronic acid in the first needle part, the cross-linked hyaluronic acid has a content (w/w) in a first range, based on the total weight of the hyaluronic acid in the second needle part. The cross-linked hyaluronic acid has a content in a second range different from the content (w / w) in the first range, the microneedle patch. According to claim 1,
The first needle part has a greater content of the cross-linked hyaluronic acid than the second needle part, the microneedle patch. According to claim 1,
The microneedle patch, wherein the first needle part has a greater rigidity than the second needle part. According to claim 1,
The height of the first needle part is equal to or less than the height of the second needle part, microneedle patch. According to claim 1,
The dissolution rate of the second needle part is different from the dissolution rate of the first needle part, microneedle patch. According to claim 6,
The microneedle
The microneedle patch, wherein the dissolution rate of the second needle portion is faster than the dissolution rate of the first needle portion. According to claim 1,
At least one of the first needle part and the second needle part has an active ingredient, the microneedle patch. According to claim 1,
The microneedle
The microneedle patch further comprising an adhesive layer disposed between the first needle part and the second needle part. Base; and
A microneedle protruding from the surface of the base and in which cross-linked hyaluronic acid and non-cross-linked hyaluronic acid are mixed; includes,
The microneedle patch has a higher content (w / w) of the cross-linked hyaluronic acid than the non-cross-linked hyaluronic acid based on the total weight of the microneedle.

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