KR20200094856A - Liquid injected micro-needle of three or more layers structure and method for preparation thereof - Google Patents

Abstract

The present invention relates to a tree-shaped liquid injection-type microneedle with a three or more layered structure, and a method of manufacturing the same, wherein the microneedle comprises: a middle portion containing a chemical liquid that penetrates the skin and melts in a cavity; a lower portion supporting the middle portion; and an upper portion positioned at an upper end of the middle portion to facilitate penetration. The present invention enhances storage of the chemical liquid.

Description

Liquid injection type microneedle with a three-layer or higher structure and its manufacturing method {LIQUID INJECTED MICRO-NEEDLE OF THREE OR MORE LAYERS STRUCTURE AND METHOD FOR PREPARATION THEREOF}

The present invention relates to a liquid injection type microneedle and a method for manufacturing the same, and more particularly, to a three or more layer structure liquid injection type microneedle having a tree shape formed with a middle portion including a chemical solution, and a method of manufacturing the same.

In the case of injecting a physiologically active substance into human skin, an existing injection needle may be used, but pain at the injection site, damage to the skin, bleeding, and disease infection due to the injection needle may occur.

Accordingly, recently, a method of delivering a physiologically active substance into the skin using a microneedle (or ultra-fine needle) has been actively studied. The microneedles may have a diameter of tens to hundreds of micrometers to penetrate the stratum corneum of the skin, which is the main barrier layer.

Unlike conventional injection needles, microneedles can be characterized by painless skin penetration and no trauma. In addition, since the microneedles must penetrate the stratum corneum of the skin, a certain degree of physical hardness may be required. In addition, an appropriate length may be required for the physiologically active substance to reach the epidermal layer or the dermal layer of the skin. In addition, in order for the physiologically active substances of hundreds of microneedles to be effectively delivered into the skin, the microneedles must have a high skin transmittance and must be inserted into the skin and maintained for a certain time until dissolution.

Existing methods of manufacturing such microneedles include a mold manufacturing method and a tensile manufacturing method.

The microneedle manufacturing method using the mold method is difficult to perforate the skin because the aspect ratio of the microneedle is low due to the characteristics of the mold, and the number density of the microneedles is low.

The microneedle manufacturing method using the tensile method is a method in which a material is dropped on a patch, stretched, dried, and then cut out and thinned. Due to this characteristic, the length of the microneedle is not constant, and the shape of the microneedle is not constant. There is this.

In addition, since both the mold method and the tensile method are expensive, they are acting as an obstacle to the growth of the market, and since it is not possible to arrange a high-density microneedle, it is inconvenient to be attached for about 2 hours. Moreover, since it is difficult to increase the number density of microneedles in both methods, it is recommended to attach a microneedle patch manufactured by both methods for at least 2 hours, which is longer than a general patch that recommends attaching about 20 minutes. There is a downside to being long.

The reason why the attachment time is long is that the number density of needles is low. Since the number density of microneedles is low, the overall surface area of the microneedles included in the patch is narrow and the contact area with the skin is narrow, so the reaction speed with the skin is inevitably slow. However, since it is difficult to increase the number density further with the two existing methods, the reaction speed with the skin cannot be accelerated.

When the manufacturing of medical microneedles, not for cosmetic purposes, is in mind, the limitations of the two existing methods are further revealed. When mixing vaccines or drugs in both existing methods, the entire needle must be made into a homogeneous mixture of the same concentration. However, since it is difficult to make the needle size constant, and the degree of penetration into the skin cannot be controlled due to the drug remaining in the interface between the patch and the skin or in the injection passage, quantitative administration is almost impossible.

Accordingly, the need for a microneedle having a multi-layered structure has begun to be raised, and for example, in the case of insulin quantitative administration, it has been argued that such a multi-layered microneedle is necessary (Ito et al. al., Diabetes Technology & Therapeutics, 2012, 14, 10).

The present invention manufactures a three or more layered liquid injection type microneedle having a tree shape including a middle portion including a chemical solution melted in the cavity, a lower end supporting the middle portion, and an upper end positioned at the upper end of the middle portion, We propose a microneedle that enhances the preservation of the skin, facilitates penetration into the skin, and can administer liquid chemicals.

In the liquid injection type microneedle having a three or more layer structure according to an embodiment of the present invention, a middle portion including a chemical solution that penetrates into the skin and melts in a cavity, a lower end portion supporting the middle portion, and the It is located at the top of the middle portion and includes an upper end to facilitate penetration.

The middle portion may include a cavity having a predetermined size in the shape of a groove, and may include the chemical liquid in a liquid state in the cavity.

The stopping part may block the upper end of the cavity containing the chemical solution to seal the chemical solution.

The surface of the cavity in contact with the chemical solution may be coated with a waterproof material that does not react with the chemical solution.

The upper end and the middle portion may have a pyramidal or conical shape, and the lower end may have a prismatic or cylindrical shape.

A bottom diameter of the middle portion may be greater than a bottom diameter of the upper end or a bottom diameter of the lower end, and the bottom diameter of the upper end may be greater than a bottom diameter of the lower end.

The lower end portion is located in the lowermost layer of the three or more layers structure and is coupled to the diameter of a pyramid or a bottom of the cone of the middle portion, and may be formed with a diameter capable of supporting the upper end portion and the middle portion including the chemical solution.

The lower end portion is formed of a melting material connecting the base portion and the liquid injection type microneedle, so that the liquid injection type microneedle may be separated from the base portion.

The upper part, the middle part, and the lower part may be formed of different materials.

The method of manufacturing a liquid-injected microneedle according to an embodiment of the present invention includes forming a lower end, forming an initial interruption in a cavity shape on the lower end, and penetrating the cavity into the interior of the skin. Injecting a molten chemical solution, forming the middle portion by blocking an upper end of the cavity into which the chemical solution was injected, and forming an upper end portion on the middle portion.

In the forming of the initial stopping part, a waterproof material that does not react with the chemical may be coated on the surface of the cavity in contact with the chemical.

In the forming of the stopping part, the chemical liquid may be sealed by blocking an upper end of the cavity containing the chemical liquid.

Injecting the chemical solution may inject the chemical solution formed of a biocompatible material.

The liquid injection type microneedle may be manufactured using a 3D printing method to manufacture the liquid injection type microneedle at the lower end, the middle and upper ends.

In the method of manufacturing the liquid injection type microneedle, the liquid injection type microneedle having a three or more layer structure may be manufactured by forming the lower part, the middle part, and the upper part of different materials.

Microneedle patch comprising a liquid injection type microneedle manufactured by the method of manufacturing a liquid injection type microneedle according to an embodiment of the present invention.

According to an embodiment of the present invention, by manufacturing a liquid-injectable microneedle having a three or more layer structure, it is possible to strengthen the storage of the chemical solution, facilitate penetration into the skin, and enable the administration of the liquid chemical solution. .

In addition, according to an embodiment of the present invention, by manufacturing a liquid-injected microneedle having a three or more layer structure using 3D printing technology, skin perforation, presence of pain, needle count density, attachment time, precision, price, expandability, etc. It has advantages over the existing method in terms of technology and economy.

In addition, when manufacturing a liquid-injected microneedle according to the present invention, it is possible to secure high competitiveness in the wrinkle-improving cosmetic market and the medical market.

That is, the present invention is suitable for medical use because it is possible to manufacture a liquid injection type microneedle having a three or more layer structure including an upper end, a middle end, and a lower end of different shapes.

1 is a perspective view showing a liquid injection type microneedle according to an embodiment of the present invention.
2A and 2B are cross-sectional views of a liquid injection type microneedle including a cavity and a chemical solution according to an embodiment of the present invention.
3 is a cross-sectional view of a liquid injection type microneedle having a three or more layer structure according to an embodiment of the present invention.
4 shows an exemplary view comparing the microneedle manufactured by the method according to the present invention and the conventional method.
5 is a perspective view showing a liquid injection type microneedle patch manufactured according to an embodiment of the present invention.
6 is a flowchart illustrating an operation of a method for manufacturing a liquid injection type microneedle according to an embodiment of the present invention.
7 is a diagram illustrating a step of manufacturing a liquid injection type microneedle by a method of manufacturing a liquid injection type microneedle according to an embodiment of the present invention.

Hereinafter, embodiments according to the present invention will be described in detail with reference to the accompanying drawings. However, the present invention is not limited or limited by the embodiments. In addition, the same reference numerals shown in each drawing denote the same members.

In addition, terms used in the present specification are terms used to properly express a preferred embodiment of the present invention, which may vary according to the intention of viewers or operators, or customs in the field to which the present invention belongs. Therefore, definitions of these terms should be made based on the contents throughout the present specification.

Embodiments of the present invention include a liquid injection type microneedle having a three or more layer structure including a middle portion containing a chemical solution, an upper portion that is located at the upper portion of the middle portion to facilitate penetration into the skin, and a lower portion supporting the middle portion. By manufacturing, the preservation of the chemical solution is strengthened, penetration into the skin is facilitated, and the liquid chemical solution can be administered. At this time, the liquid injection type microneedle according to an embodiment of the present invention is characterized in that it has a structure of three or more layers.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to FIGS. 1 to 7.

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

Referring to FIG. 1, a liquid injection type microneedle 100 according to an embodiment of the present invention includes an upper portion 110, a middle portion 120, and a lower portion 130.

The upper portion 110 is located at the upper end of the middle portion 120 to facilitate penetration into the skin (S). The upper end 110 has a pointed tip shape based on the penetration direction into the skin (S), and is formed in a pyramidal or conical shape such as, for example, a triangle, a square, a pentagonal, a hexagon, etc. It can facilitate penetration. At this time, the upper portion 110 is characterized in that it is made of a material having a stronger strength than the middle portion 120 and the lower portion 130 in order to facilitate perforation of the skin (S).

The upper part 110 according to an embodiment of the present invention allows the liquid injection type microneedle 100 to easily penetrate into the skin S, and protects the middle part 120 including the chemical solution.

Depending on the embodiment, the upper portion 110 may be formed of a water-soluble material that penetrates and melts into the skin S. For example, water-soluble substances include trehalose, oligosaccharide, sucrose, maltose, lactose, cellobiose, hyaluronic acid. acid), alginic acid, pectin, carrageenan, chondroitin sulfate, dextran sulfate, chitosan, polylysine, collagen, gelatin , Carboxymethyl chitin, fibrin, agarose, polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polymethacrylate, hydroxypropylmethylcellulose (HPMC), ethyl Cellulose (EC), hydroxypropyl cellulose (HPC), carboxymethylcellulose (carboxymethylcellulose), cyclodextrin (Cyclodextrin), and may be at least one of gentibiose (gentiobiose).

The middle portion 120 includes a chemical solution that can penetrate into the skin S through the upper portion 110 so as to be melted in a cavity. When the middle portion 120 penetrates into the skin (S) by the upper portion 110, the chemical liquid, which is a meltable water-soluble polymer contained in the cavity, may be absorbed into the skin (S).

The middle portion 120 represents a pyramidal shape or a truncated cone shape such as a triangular, square, pentagonal, hexagonal shape from which the upper portion 110 has been removed, and includes a cavity region that may contain a chemical solution therein. In this case, the cavity region may be preferably located in the upper region above the center of the middle part 120, but depending on the embodiment, the location of the cavity region according to the time when the drug solution is administered, the administration time, and the amount administered. , Size, shape can be applied in various ways. Further, the cavity is the amount of the chemical solution, the evaporation rate and temperature, the shape of the middle portion 120 for the manufacture of the liquid injection type microneedle 100, the viscosity of the chemical solution, the concentration of the chemical solution, the solvent used, the thickness covering the top of the cavity The size and position can be adjusted by

The middle portion 120 may be formed of a water-soluble material in the same manner as the upper portion 110 penetrating into the skin S. However, since the middle part 120 includes a cavity and a liquid chemical liquid contained in the cavity, it is preferable to use a material different from the upper part 110 among water-soluble materials. When the liquid state of the cavity area or the liquid state that can be solidified is injected into the middle part 120, it can be absorbed into the material of the middle part 120, so that a water-soluble material of a material different from that of the upper part 110 It is preferable that the surface of the cavity containing the chemical solution is coated with a waterproof material.

The chemical solution contained in the cavity in the middle portion 120 may be formed of a biocompatible material and an additive. For example, the biocompatible material is carboxymethylcellulose (CMC), hyaluronic acid (HA), alginic acid, pectin, carrageenan, chondroitin sulfate (Chondroitin Sulfate). , Dextran Sulfate, Chitosan, polylysine, carboxymethyl chitin, fibrin, agarose, pullulan, polyanhydride 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, chlorosulfonate polyolefin (chlorosulphonate) polyolefins), polyethylene oxide, polyvinylpyrrolidone (PVP), hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC), hydroxypropylcellulose (HPC), carboxymethyl cellulose, At least one of Cyclodextrin, Maltose, Lactose, Trehalose, Cellobiose, Isomaltose Turanose and Lactulose A copolymer and a cell of monomers containing or forming such a polymer It may contain at least any one of ulose.

In addition, additives include trehalose, oligosaccharide, sucrose, maltose, lactose, cellobiose, hyaluronic acid, Alginic acid, Pectin, Carrageenan, Chondroitin Sulfate, Dextran Sulfate, Chitosan, Polylysine, Collagen, Gelatin, Carboxymethyl Carboxymethyl chitin, fibrin, agarose, polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polymethacrylate, hydroxypropylmethylcellulose (HPMC), ethylcellulose (EC ), hydroxypropyl cellulose (HPC), carboxymethyl cellulose, cyclodextrin, gentibiose, cetrimide (alkyltrimethylammonium bromide (Cetrimide)), hexadecyltrimethylammonium bromide (CTAB )), Gentian Violet, benzethonium chloride, docusate sodium salt, a SPAN-type surfactant, polysorbate (Tween) , Sodium dodecyl sulfate (SDS), benzalkonium chloride, and glyceryl oleate.

In addition, the chemical solution contained in the cavity in the middle portion 120 may be formed by mixing a biocompatible material and an active ingredient. The active ingredient includes, but is not limited to, protein/peptide drugs, hormones, hormone analogs, enzymes, enzyme inhibitors, signaling proteins or portions thereof, antibodies or portions thereof, single chain antibodies, binding proteins or binding domains thereof, and antigens. , Adhesion proteins, structural proteins, regulatory proteins, toxin proteins, cytokines, transcriptional regulatory factors, blood coagulation factors, and at least one of vaccines. More specifically, the protein/peptide drugs include 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 , ACTH (adrenocorticotropic hormone), TNF (tumor necrosis factor), atobisban, buserelin, cetrorelix, deslorelin, desmopressin , Dynorphin A (1-13), elcatonin, eleidosin, eptifibatide, GHRHII (growth hormone releasing hormone-II), gonadorelin ), goserelin, hisstrelin, leuprorelin, lypressin, octreotide, oxytocin, pitressin, secretin ), sincalide, terlipressin, thymopentin, thymosine, triptorelin, bivalirudin, carbetocin, Cyclosporine, exedine, lanreotide, LHRH (luteinizing hormone releasing hormone), naparerin ( nafarelin), parathyroid hormone, pramlintide, T-20 (enfuvirtide), thymalfasin, and ziconotide.

In addition, the solvent of the chemical solution contained in the cavity in the middle portion 120 may dissolve the biocompatible material. These solvents include DI water, methanol, ethanol, chloroform, dibutyl phthalate, dimethyl phthalate, ethyl lactate, and glycerin. (Glycerin), isopropyl alcohol (Isopropyl alcohol), lactic acid (Lactic acid), may include at least one of inorganic and organic solvents including propylene glycol (Propylene glycol).

The liquid injection type microneedle 100 according to an embodiment of the present invention forms a cavity in a specific area inside the middle part 120, and includes a liquid chemical inside the cavity and injects it into the skin S. , It is characterized in that a quantitative amount of the drug is administered, whereby the present invention strengthens the preservation of the drug, facilitates penetration into the skin, and makes it possible to administer a liquid drug.

The lower part 130 supports the middle part 120. The lower end 130 has a prismatic or cylindrical shape such as a triangular, square, pentagonal, hexagonal, etc., and supports the upper end 110 and the middle part 120.

The lower part 130 has a diameter and height of a predetermined size, and this may represent a depth degree of penetration of the liquid injection type microneedle 100 into the skin S. For example, depending on the diameter and height of the lower part 130, the depth at which the upper part 110 and the middle part 120 including the chemical solution penetrate into the skin S can be measured. The height of the lower part 130 may be adjusted according to the degree of depth at which the drug is to be penetrated based on the state, the time at which the drug is administered, the administration time, and the amount to be administered. In addition, the lower part 130 can be adjusted in diameter according to the weight and size of the upper part 110 and the middle part 120 and the degree to which the chemical can be supported, and the time that the lower part 130 melts inside the skin (S). .

The lower portion 130 is formed of a melting material connecting the base portion 10 and the liquid injection type microneedle 100, and separates the liquid injection type microneedle 100 from the base portion 10. For example, the lower part 130 may be formed of a water-soluble soluble material and may be rapidly dissolved, and thus the microneedles 100 formed on the base part 10 may be quickly separated.

In this case, the lower part 130 may be formed of a water-soluble material in the same manner as the upper part 110 and the middle part 120 penetrating into the skin S. However, the lower part 130 may be formed of a material that melts faster than the upper part 110 and the middle part 120 among water-soluble materials. The upper part 110 is for easier skin perforation, the middle part 120 is for more efficient dosing including a liquid chemical, and the lower part 130 is a microneedle formed on the base part 10 Since it is for the rapid separation of 100 and the depth of the liquid injection type microneedle 100 into the skin (S), the microneedle 100 according to an embodiment of the present invention has three layers formed of different materials. It is characterized in that it includes an upper portion 110, a middle portion 120 and a lower portion 130 of the above structure.

The lower part 130 according to an embodiment of the present invention serves to support the upper part 110 and the middle part 120 in the liquid injection type microneedle 100, and may represent a depth of penetration into the skin. As shown in Figure 1, the lower portion 130 is characterized in that it occupies a size and volume smaller than the upper portion 110 and the middle portion 120 in a prismatic or cylindrical shape, whereby the lower portion 130 is a liquid injection type The area, volume, and weight of the microneedle 100 are minimized, and due to the shape of the appropriate size, height, and diameter according to the depth of the liquid injection type microneedle 100 penetrating into the skin (S) It has a supportive effect so that it can be administered.

As shown in FIG. 1, the liquid injection type microneedle 100 may be formed on the base portion 10. The base portion 10 is not provided with a chemical solution, and after the liquid injection type microneedle 100 of the upper portion 110, the middle portion 120, and the lower portion 130 penetrates into the skin S, it can be separated. For example, the base portion 10 is provided in the form of a kind of patch, and can be in close contact with the skin (S).

Unlike the liquid injection type microneedle 100 that penetrates into the skin S, the base portion 10 may be formed of a water-insoluble material that does not dissolve. Accordingly, the base portion 10 does not interfere with the penetrating force of the liquid injection type microneedle 100, and thus, the supply of a fixed amount of the chemical contained in the middle portion 120 can be guided.

For example, the base portion 10 is polyethylene (PE), polypropylene (PP), polytetrafluoroethylene (PTFE), polymethyl methacrylate (PMMA), ethylene vinyl acetate (EVA), polycaprolactone (PCL). ), polyurethane (PU), polyethylene terephthalate (PET), polyethylene glycol (PEG), polyvinyl alcohol (PVA), polylactide (PLA), polylactide-glycolide copolymer (PLGA) and polyglycol It may be formed of at least any one from the group consisting of Ride (PGA).

As shown in Figure 1, the liquid injection type microneedle 100 according to an embodiment of the present invention is located at the upper end of the middle portion 120 and the middle portion 120 containing a chemical solution inside the skin (S) By forming the upper portion 110 that facilitates penetration into the furnace and the lower portion 130 supporting the middle portion 120 in a tree-shaped three or more layer structure, the storage of the chemical solution is strengthened, and It facilitates penetration, and a liquid medicinal solution can be quantitatively administered.

In addition, since the liquid injection microneedle 100 according to an embodiment of the present invention has a tree-shaped structure of three or more layers, the penetration rate of the structure (60%) is minimized by minimizing penetration resistance due to skin elasticity when the skin is attached. Above) and useful ingredients can be absorbed into the skin. In addition, the liquid injection microneedle 100 having a tree shape maximizes the mechanical strength of the structure by applying a three or more layer structure, so that skin penetration is easy.

In addition, the upper end portion 110 of a pyramidal or conical shape forming the liquid injection type microneedle 100 according to an embodiment of the present invention, the middle portion 120 of a pyramidal shape or a truncated cone shape, and the lower end portion 130 of a prismatic or cylindrical shape ) Is characterized by being manufactured by 3D printing technology. Since the present invention uses the 3D printing method, the attachment time is very short compared to the conventional method, the precision is high, the price is low, and at the same time, the number density of the liquid injection type microneedle 100 in the micro patch is increased, and the aspect ratio is improved. I can make it.

2A and 2B are cross-sectional views of a liquid injection type microneedle including a cavity and a chemical solution according to an embodiment of the present invention.

Referring to FIG. 2A, a liquid injection type microneedle 100 according to an embodiment of the present invention includes a middle portion 120 including a cavity 121. The cavity 121 is formed in the shape of a groove in the middle portion 120, and may be formed in a shape and size to contain a chemical solution.

Referring to FIG. 2B, the liquid injection type microneedle 100 according to an embodiment of the present invention may include a cavity 121 containing a chemical solution 122. At this time, it can be seen that the cavity 121 containing the chemical solution 122 is completely located inside the middle portion 120, and when the chemical solution 122 is injected into the cavity 121 area in FIG. 2A, the upper part of the cavity By blocking the chemical solution 122 is sealed. Thereafter, the upper portion 110 is formed on the middle portion 120 to manufacture the liquid injection type microneedle 100 according to an embodiment of the present invention.

As shown in FIG. 2B, the cavity surface 123 in contact with the chemical solution 122 may be coated with a waterproof material. The chemical solution 122 according to an embodiment of the present invention may be in a liquid state or a liquid state capable of solidification. Since the liquid chemical 122 may be absorbed by the middle portion 120, the cavity surface 123 is coated with a waterproof material to block this.

For example, the cavity surface 123 may be coated with a waterproofing agent including a mineral-based material or a lipid-based material. Here, the waterproofing agent is beeswax, oleic acid, soy fatty acid, castor oil, phosphatidylcholine, vitamin E (d-α-tocopherol/Vitamin E), corn oil ( Corn oil) mono-ditridiglycerides (Corn oil mono-ditridiglycerides), cottonseed oil, olive oil, peanut oil, peppermint oil, safflower seed oil ( Safflower oil), Sesame oil, Soybean oil, Hydrogenated vegetable oils, Hydrogenated soybean oil, Caprylic/capric triglycerides derived from coconut oil or palm see oil) and phosphatidylcholine (Phosphatidylcholine), or may be formed of a mixture thereof.

Depending on the embodiment, the cavity surface 123 may be coated with different waterproofing agents depending on the type and state of the chemical solution 122 injected into the cavity, and the size, height, and shape of the cavity 121 are It may be formed in the middle portion 120 in different shapes depending on the type, the state of the drug solution 122, the time when the drug solution 122 is administered, the administration time, and the amount to be administered.

3 is a cross-sectional view of a liquid injection type microneedle having a three or more layer structure according to an embodiment of the present invention.

The liquid injection type microneedle 100 according to an embodiment of the present invention is a microstructure composed of three or more layers, and the upper portion 110 and the middle portion 120 having a pyramidal or conical shape, and a lower portion having a prismatic or cylindrical shape ( 130).

3, the bottom diameter 302 of the middle portion is larger than the bottom diameter 303 of the upper end or the bottom diameter 301 of the lower end, and the bottom diameter 303 of the upper end is greater than the bottom diameter 301 of the lower end. It is characterized by a large one. The size may be determined in the order of the bottom diameter 302 of the middle portion, the bottom diameter 303 of the upper end, and the bottom diameter 301 of the lower end.

In addition, the height 312 of the middle portion may be higher than the height 313 of the upper portion, and the combined height of the height 312 of the middle portion and the height 313 of the upper portion may be higher or lower than the height 311 of the lower portion. That is, in the liquid injection type microneedle 100 according to an embodiment of the present invention, the height 312 of the middle part is the highest, and the height 313 of the upper part and the height 311 of the lower part are the same, or one of the present invention. The liquid injection type microneedle 100 according to the embodiment may be different depending on the applied embodiment. However, the height 311 of the lower end, the height 312 of the middle part, and the height 313 of the upper end of the liquid injection type microneedle 100 according to an embodiment of the present invention are not limited to those shown in FIG. 3, It may have various heights according to the applied embodiment.

Since the middle portion 120 of the liquid injection type microneedle according to an embodiment of the present invention has a cavity containing a chemical solution, it can be formed with the widest volume, the largest bottom diameter 302, and the highest height 312. I can. The upper part 110 is a pyramidal or conical shape for penetrating the skin (S), and the lower surface diameter 303 of the upper end is the same as the upper surface (or tip) diameter of the middle part, and a pyramid or truncated cone forming the middle part 120 It can be determined by the cross-sectional area of the tip. In addition, the height 313 of the upper end may be determined according to the shape of the truncated truncated cone or the truncated cone.

The lower end 130 of the liquid injection microneedle according to an embodiment of the present invention serves to support the upper end 110 and the middle part 120 in the liquid injection microneedle 100, and the depth of penetration into the skin Can represent. Accordingly, the lower part 130 has a smaller volume and lower surface diameter 301 than the upper part 110 and the middle part 120. However, the height 311 of the lower end may be determined according to the depth of penetration into the skin.

The lower end 130 is a prismatic or cylindrical shape and includes a lower surface diameter 301 that is smaller than the lower surface diameter 303 of the upper part and the lower surface diameter 302 of the middle part, and the volume is also smaller than the upper part 110 and the middle part 120. It is characterized by that. Since the lower part 130 represents the degree of depth into the skin (S) and supports the upper part 110 and the middle part 120, the liquid injection type microneedle 100 according to an embodiment of the present invention It is characterized by minimizing area, volume and weight. Accordingly, the lower part 130 has the effect of supporting the liquid injection type microneedle 100 penetrating into the skin (S) so that the amount of the drug can be administered due to the shape of the appropriate size, height, and diameter according to the depth. Represents.

4 is a diagram showing an exemplary view comparing the microneedle manufactured by the method according to the present invention and the conventional method, and FIG. 5 is a perspective view of a liquid injection type microneedle patch manufactured according to an embodiment of the present invention. It is shown.

Referring to FIG. 4, the mold method and the tensile method have a low number density of microneedles, whereas a liquid injection type microneedle according to an embodiment of the present invention manufactured using a lamination method, for example, a 3D printing method, is a mold method. It can be seen that the number density is very high compared to the conventional method due to the limitation of the tensile method, and the aspect ratio is also higher in the liquid injection type microneedle manufactured by the method according to an embodiment of the present invention compared to the mold method and the tensile method. Can be seen. Of course, the method according to the present invention can adjust the aspect ratio of the liquid injection type microneedle, and this aspect ratio may be determined by the field in which the liquid injection type microneedle of the present invention is used, for example, for treatment, medical use, etc. .

In the method (3D printing) of the present invention, skin perforation is advantageous and painless compared to the mold method, and the number density of the liquid-injected microneedles is higher than that of the mold method and the tensile method. In addition, it can be seen that the method according to the present invention has a very short attachment time compared to the existing method, and it can be seen that the precision is also high, and the manufacturing cost is low because it uses a lamination method, for example, a 3D printing method, Therefore, it can be seen that the scalability is high. As described above, the method according to the present invention has a very advantageous advantage in terms of technical and boundary compared to the conventional mold method and tensile method.

That is, the liquid-injected microneedles implemented by the lamination technology by the method according to the present invention have a high aspect ratio, so skin perforation is good, pain is very low, and because of the high number density, the attachment time is very short. In addition, the present invention can implement a liquid-injected microneedle with a high precision of about 5 micrometers, and a desired drug can be placed in a desired position, so that scalability is high.

As shown in FIG. 5, the liquid injection type microneedle 100 manufactured as described above may be manufactured as a liquid injection type microneedle patch formed in plural on the base part 10, and is easily used in the medical field. Can be applied. That is, the present invention can secure high competitiveness in the medical market field by manufacturing the liquid injection type microneedle 100 having a three or more layer structure of a lamination method using 3D printing.

6 is a flowchart illustrating an operation of a method for manufacturing a liquid injection type microneedle according to an exemplary embodiment of the present invention, and FIG. 7 is a liquid injection type microneedle manufacturing method according to an exemplary embodiment of the present invention. It shows the steps in which the needle is manufactured.

The liquid injection type microneedle 100 according to an embodiment of the present invention illustrated in FIG. 7 manufactured by the manufacturing method of FIG. 6 is manufactured through a 3D printing method.

6, in step 610, a lower end is formed. In the method for manufacturing a liquid injection type microneedle according to an embodiment of the present invention, the lower end 130 having a prismatic shape or a cylindrical shape may be formed on the base portion 10.

The lower part 130 has a diameter and height of a predetermined size, and this may represent a depth degree of penetration of the liquid injection type microneedle 100 into the skin S. For example, depending on the diameter and height of the lower part 130, the depth at which the upper part 110 and the middle part 120 including the chemical solution penetrate into the skin S can be measured. The height of the lower part 130 may be adjusted according to the degree of depth at which the drug is to be penetrated based on the state, the time at which the drug is administered, the administration time, and the amount to be administered. In addition, the lower part 130 can be adjusted in diameter according to the weight and size of the upper part 110 and the middle part 120 and the degree to which the chemical can be supported, and the time that the lower part 130 melts inside the skin (S). .

In step 620, on the lower end, an initial stop having a cavity 121 shape is formed. As shown in Figure 7 (a), the liquid injection type microneedle manufacturing method according to an embodiment of the present invention forms an initial stop in the shape of a cavity 121 on the lower end 130, and the upper end of the cavity 124 Is an open form. In this case, the cavity region may be preferably located in the upper region above the center of the middle part 120, but depending on the embodiment, the location of the cavity region according to the time when the drug solution is administered, the administration time, and the amount administered. , Size, shape can be applied in various ways. In addition, the initial interruption portion may have a shape of a truncated cone or a truncated cone including the shape of the cavity 121.

According to an embodiment, in step 620, the liquid injection type microneedle manufacturing method according to an embodiment of the present invention manufactures an initial stop in the shape of the cavity 121 by 3D printing, and the manufactured initial stop is at the lower end 130 A method of stacking on the upper end or a method of manufacturing an initial stop having a shape of a truncated cone or a truncated cone having the shape of the cavity 121 on the lower end 130 may be represented as shown in FIG. 7(a).

In step 630, a chemical solution 122 that penetrates and melts into the cavity 121 is injected. Referring to FIG. 7B, the method of manufacturing a liquid injection microneedle according to an embodiment of the present invention may inject a chemical solution 122 into the cavity 121. However, when the liquid state or the liquid state that can be solidified is injected into the cavity 121, it may be absorbed by the material of the middle part 120, so the cavity surface is coated with a waterproof material. .

In step 640, the intermediate portion 120 is formed by blocking the upper end 124 of the cavity into which the chemical solution 122 is injected. Referring to Figure 7 (c), the liquid injection microneedle manufacturing method according to an embodiment of the present invention, when the chemical solution 122 is injected into the cavity 121, the open cavity top 124 is blocked. The cavity 121 containing the chemical solution 122 is sealed in the middle part 120. In this case, the liquid injection type microneedle manufacturing method according to an embodiment of the present invention may block the upper cavity 124 with the material of the middle portion 120 through a 3D printing method.

Thereafter, in step 650, on the middle portion 120, the upper end portion 110 is formed. Referring to Figure 7 (d), the liquid injection type microneedle manufacturing method according to an embodiment of the present invention is located at the upper end of the middle portion 120 to facilitate penetration into the skin (S) the upper end 110 Can be formed. The upper end 110 has a pointed tip shape based on the penetration direction penetrating into the skin S, and is formed in, for example, a pyramidal or conical shape to facilitate penetration into the skin S.

Each of the upper portion 110, the middle portion 120, and the lower portion 130 of the liquid injection type microneedle 100 according to an embodiment of the present invention is formed of different materials. The upper portion 110, the middle portion 120, and the lower portion 130 may be the same water-soluble material, but the upper portion 110 to facilitate penetration, the middle portion 120 containing a chemical solution, and support thereof, and the base portion ( The lower part 130 to facilitate separation from 10) may be formed of a material having different characteristics in the water-soluble material. For example, the upper portion 110 and the lower portion 130 may be a material that melts within a faster time than the middle portion 120 so that a fixed amount of the chemical solution provided in the middle portion 120 can be injected.

As described above, although the embodiments have been described by the limited embodiments and drawings, various modifications and variations are possible from the above description by those of ordinary skill in the art. For example, the described techniques are performed in a different order than the described method, and/or the components of the described system, structure, device, circuit, etc. are combined or combined in a different form from the described method, or other components Alternatively, even if replaced or substituted by equivalents, appropriate results can be achieved.

Therefore, other implementations, other embodiments, and claims and equivalents fall within the scope of the claims to be described later.

100: liquid injection type microneedle
110: upper part
120: middle
121: cavity
122: chemical solution
123: cavity surface
124: cavity top
130: lower part

Claims (16)

In the liquid injection type microneedle having a three or more layer structure,
A middle portion that penetrates into the interior of the skin and includes a chemical solution that is melted in a cavity;
A lower end supporting the middle portion; And
The upper part is located at the top of the middle part to facilitate penetration
Liquid injection type microneedle comprising a. The method of claim 1,
The middle part
A liquid-injection type microneedle comprising a cavity having a constant size inside the cavity and containing the chemical liquid in a liquid state in the cavity. According to claim 2,
The middle part
A liquid injection type microneedle, characterized in that the chemical liquid is sealed by blocking an upper end of the cavity containing the chemical liquid. According to claim 2,
The surface of the cavity in contact with the chemical liquid is coated with a waterproof material that does not react with the chemical liquid. The method of claim 1,
The upper end and the middle portion have a pyramidal or conical shape, and the lower end portion has a prismatic or cylindrical shape. The method of claim 5,
A bottom diameter of the middle portion is larger than a bottom diameter of the upper end or a bottom diameter of the lower end, and the bottom diameter of the upper end is larger than a bottom diameter of the lower end. The method of claim 5,
The lower part
A liquid-injection type microneedle that is located on the lowermost layer of a three-layer or more structure and is coupled to a pyramidal cone of the middle portion or a diameter of a bottom surface of the cone, and has a diameter capable of supporting the middle portion including the upper end and the chemical solution. The method of claim 1,
The lower part
A liquid injection type microneedle, characterized in that it is formed of a melting material connecting the base portion and the liquid injection type microneedle to separate the liquid injection type microneedle from the base portion. The method of claim 1,
The upper part, the middle part, and the lower part are formed of different materials. Forming a lower end;
Forming an initial stop portion having a cavity shape on the lower portion;
Injecting a chemical solution that penetrates into the skin and melts into the cavity;
Forming the middle portion by blocking the upper end of the cavity into which the chemical solution is injected; And
Forming an upper end on the middle portion
A method of manufacturing a liquid injection type microneedle comprising a. The method of claim 10,
Forming the initial interruption part
A method of manufacturing a liquid-injected microneedle, characterized in that coating a waterproof material that does not react with the chemical liquid on the surface of the cavity in contact with the chemical liquid. The method of claim 10,
The step of forming the interruption part
A method of manufacturing a liquid injection type microneedle, characterized in that the chemical liquid is sealed by blocking the upper end of the cavity containing the chemical liquid. The method of claim 10,
Injecting the chemical solution
A method of manufacturing a liquid injection type microneedle, characterized in that injecting the chemical solution formed of a biocompatible material. The method of claim 10,
The method of manufacturing the liquid injection microneedle
A method of manufacturing a liquid-injection-type microneedle, characterized in that the liquid-injection-type microneedles of the lower end, the middle, and the upper end are manufactured using a 3D printing method. The method of claim 10,
The method of manufacturing the liquid injection microneedle
A method of manufacturing a liquid injection type microneedle for manufacturing the liquid injection type microneedle having a three or more layer structure by forming the lower part, the middle part, and the upper end part of different materials. A microneedle patch comprising a liquid-injectable microneedle manufactured by the method of any one of claims 10 to 15.

Images