Manufacturing method of microneedle patch using thin film

Abstract

The present invention relates to a method for manufacturing a microneedle patch that increases drug delivery efficiency by using a thin film treated with a hydrophobic or hydrophilic surface, a microneedle patch manufactured by said method, and a patch.

Description

Technology Field

[0001] The present invention relates to a method for manufacturing a microneedle patch and a microneedle patch manufactured according to the same, and more specifically, to a method for manufacturing a microneedle patch using a surface-treated thin film and a microneedle patch. Background Technology

[0002] When manufacturing coated microneedle patches, conventional coating methods such as dipping, inkjetting, dispensing, dropping, and spraying are used. The microneedle patch is divided into a microneedle section and a substrate section that fills the space between the microneedle array. Depending on the coating method, the drug location on the microneedle patch may be present only in the microneedle section or on the entire surface of the microneedle section and the substrate section; however, to guarantee the amount injected into the body and to increase drug efficiency during manufacturing, it is desirable to selectively coat only the microneedle section.

[0003] Among coating methods, the dipping method allows for coating only the microneedles by adjusting the height of the drug solution; however, it suffers from low coating efficiency, a high risk of drug contamination due to repeated dipping processes, and difficulties in management. Inkjet and dispensing methods allow for precise drug placement, but they are time-consuming as they only coat the portion where the nozzle touches, and they have many limitations due to high dependence on factors such as the viscosity of the coating material. Spray and droplet methods are convenient for rapid coating, but the drug is coated across the entire patch surface, the coating location cannot be limited, and gravity causes more drug to be coated on the substrate than on the microneedles. These characteristics not only significantly reduce utilization efficiency during drug manufacturing but also present a clinical problem in that the amount of drug to be injected into the body cannot be precisely determined.

[0004] Accordingly, there is a need for methods that are improved over existing ones when manufacturing coated microneedle patches, particularly in terms of enhancing drug utilization efficiency, preventing contamination, and facilitating the manufacturing process. Prior art literature

[65535] Published Patent Application 10-2020-0032461 (Publication Date 2020.03.26) Published Patent Application 10-2017-0122716 (Publication Date 2017.11.06) The problem to be solved

[0005] The present invention aims to solve the aforementioned problem and other related problems.

[0006] One exemplary objective of the present specification is to provide a method for manufacturing a microneedle patch that increases drug delivery efficiency by using a surface-treated thin film.

[0007] The technical problem to be solved by the method for manufacturing a microneedle patch according to the technical concept of the technology disclosed in this specification is not limited to the problem of solving the aforementioned issues, and other unmentioned problems will be clearly understood by a person skilled in the art from the description below. means of solving the problem

[0008] A method for manufacturing a microneedle patch comprising a plurality of microneedles according to an embodiment of the present invention for achieving one objective of the present invention described above comprises: a) a step of positioning a thin film on the microneedles; b) a step of moving the thin film so that only at least a portion of the microneedles are exposed; c) a step of dropping a drug solution onto the thin film on which the microneedles are exposed; d) a step of drying the drug solution dropped onto the thin film on which the microneedles are exposed; and e) a step of removing the thin film.

[0009] b) Step includes applying pressure to penetrate a thin film positioned on a microneedle. Alternatively, the method includes the step of moving a thin film aligned with the microneedle, wherein the thin film has a hole formed at a location where it is smaller than the bottom size of the microneedle and is insertable into the microneedle. The thin film is in a solid form comprising at least one of a metal, a polymer, or a composite material, and the thickness of the thin film is smaller than the height of the microneedle. Alternatively, the thickness of the thin film exceeds the height of the microneedle, and the bottom of the formed hole is smaller than the bottom of the microneedle, and the top of the formed hole is larger than the bottom of the formed hole.

[0010] c) Step includes dropping a single or multiple drug solutions onto a thin film on which microneedles are exposed. Additionally, it includes dropping micro drug solution droplets onto the locations of the microneedles exposed on the thin film so that each micro drug solution droplet comes into contact with only one microneedle.

[0011] The manufacturing method further includes a step of turning the micro-needle inward and drying it after step d).

[0012] The thin film is hydrophobic, and the drug solution contains a water-soluble drug dissolved in water.

[0013] The surface of the microneedle contains insoluble or low-solubility materials.

[0014] The surface of the thin film contains a plurality of nanostructures.

[0015] A plurality of nanostructures include at least one of nanoislands, nanoposts, or nanoholes arranged regularly or irregularly.

[0016] The thin film is hydrophilic, and the drug solution contains a lipophilic drug dissolved in an organic solvent.

[0017] The surface of the thin film includes a hydrophilic pattern.

[0018] The surface of the microneedle contains a water-soluble substance.

[0019] The surface of the thin film is chemically treated.

[0020] The thin film is modified to be hydrophilic or hydrophobic.

[0021] Hydrophobic modification is carried out by the reflux method, the two-step acid-base catalysis method, or the direct condensation method.

[0022] The modifier for hydrophobic modification of the above thin film is selected from the group consisting of methoxytrimethylsilane, hexamethyldisiloxane, hexamethyldisilane, and trimethoxymethylsilane.

[0023] A microneedle patch according to one embodiment of the present invention is characterized by being manufactured by the manufacturing method defined above.

[0024] A microneedle patch according to another embodiment of the present invention comprises a substrate portion; a microneedle portion having a shape protruding from the substrate portion, wherein the microneedle portion comprises a drug coating portion formed only on the surface of at least a portion of the protruding portion. Here, the drug is water-soluble and the surface of the microneedle comprises a non-soluble or low-solubility substance, or the drug is lipophilic and the surface of the microneedle comprises a water-soluble substance.

[0025] A microneedle patch according to another embodiment of the present invention comprises a substrate portion; and a microneedle portion having a shape protruding from the substrate portion, wherein the microneedle portion comprises a drug coated only on the surface of at least a portion of the protruding shape, and the microneedle portion comprises a drug concentration portion in which the drug is concentrated and coated at a point adjacent to the insertion position of a thin film used for drug coating. Effects of the invention

[0026] According to one embodiment of the present invention, a hydrophobic surface is used to coat only the microneedle portion excluding the substrate portion of a microneedle patch and to quantify its mass. The coated microneedle patch manufactured thereby can guarantee the precise dosage of a drug in the body and increase drug utilization efficiency in manufacturing by minimizing wasted drugs.

[0027] However, the effects according to one embodiment of the technology disclosed in this specification are not limited to those mentioned above, and other unmentioned effects will be clearly understood by a person skilled in the art from the description below. Brief explanation of the drawing

[0028] A brief description of each drawing is provided to help to better understand the drawings cited in this specification. FIG. 1 is a schematic diagram illustrating a method for manufacturing a microneedle patch according to one embodiment of the present invention. FIGS. 2 and FIGS. 3 are drawings showing a thin film according to one embodiment of FIGS. 1. FIG. 4 is a drawing showing the form in which a drug solution according to one embodiment of FIG. 1 is dropped. FIG. 5 is a diagram showing detailed steps of a method for manufacturing a microneedle patch according to one embodiment of the present invention. FIG. 6 is a drawing showing a microneedle patch according to one embodiment of the present invention. Specific details for implementing the invention

[0029] The technology disclosed in this specification is subject to various modifications and may have various embodiments, and specific embodiments are illustrated in the drawings and described in detail. However, this is not intended to limit the technology disclosed in this specification to specific embodiments, and it should be understood that the technology disclosed in this specification includes all modifications, equivalents, and substitutions that fall within the spirit and scope of the technology disclosed in this specification.

[0030] In describing the technology disclosed in this specification, if it is determined that a detailed description of related prior art could unnecessarily obscure the essence of the technology disclosed in this specification, such detailed description is omitted. Additionally, numbers used in the description of this specification (e.g., 1st, 2nd, etc.) are merely identification symbols to distinguish one component from another.

[0031] In this specification, when a component is described as being "connected" or "combined" with another component, it should be understood that the component may be directly connected or combined with the other component, but unless otherwise specifically stated, it may also be connected or combined through another component in between.

[0032] In this specification, components expressed as '~part' may consist of two or more components combined into a single component, or a single component may be divided into two or more components according to more detailed functions. Furthermore, each component described below may additionally perform some or all of the functions performed by other components in addition to the primary function it is responsible for, and it is obvious that some of the primary functions performed by each component may be exclusively performed by other components.

[0033] Expressions such as “first,” “second,” “first,” or “second” used in various embodiments of this specification may modify various components regardless of order and / or importance and do not limit such components. For example, without departing from the scope of the technology disclosed in this specification, the first component may be named the second component, and similarly, the second component may be renamed the first component.

[0034] In this specification, the expressions “optional” and “optional” mean that the event or environment described subsequently may or may not occur, and that the description includes cases where the event or environment occurs and cases where it does not occur.

[0035] In this specification, when a part such as a film, layer, region, or component is described as being "on" or "on" another part, it includes not only cases where it is immediately on top of the other part, but also cases where another film, layer, region, component, etc. is interposed therein.

[0036] In this specification, an object of "nano" refers to an object having at least one dimension in the nm range. Nano-sized objects may have any of a wide range of shapes and may be formed from a wide range of materials, and include, for example, nanowires, nanotubes, nanoflatlets, nanoparticles, and other nanostructures.

[0037] In this specification, an object of “micro” refers to an object having at least one dimension in the μm range. Typically, each dimension of a micro-sized object is in the μm range or exceeds the μm range. Micro-sized objects may have any of a wide range of shapes and may be formed from a wide range of materials, including, for example, microwires, microtubes, microparticles, and other microstructures.

[0038] Unless otherwise defined, all terms used in this specification (including technical and scientific terms) may be used in a meaning that is commonly understood by those skilled in the art to which the present invention pertains. Additionally, terms defined in commonly used dictionaries are not to be interpreted ideally or excessively unless explicitly and specifically defined otherwise.

[0039] Hereinafter, a method for manufacturing a microneedle patch according to a preferred embodiment will be described in detail.

[0040] A method for manufacturing a microneedle patch according to one embodiment of the present invention basically comprises the steps of: positioning a thin film on a microneedle; moving the thin film so that only at least a portion of the microneedle is exposed; dropping a drug solution onto the thin film on which the microneedle is exposed; drying the drug solution dropped onto the thin film on which the microneedle is exposed; and removing the thin film.

[0041] The basic structure of the microneedle patch manufactured by the method of manufacturing the microneedle patch of this embodiment comprises a substrate and a plurality of microneedle patches having a shape protruding from the substrate, and each of the plurality of microneedle patches comprises a drug formed only on the surface of at least a portion of the protruding part. Here, i) the drug may be water-soluble and the surface of the microneedle part may comprise a non-soluble or low-solubility substance, or ii) the drug may be lipophilic and the surface of the microneedle part may comprise a water-soluble substance. In particular, the microneedle part of the microneedle patch manufactured by this embodiment is characterized by including a drug concentration part in which the drug is concentrated and coated at a point adjacent to the insertion position of the thin film used for drug coating.

[0042] The present invention relates to a method for coating drugs and active substances on a microneedle patch for transdermal drug delivery, and provides a method that is improved over existing methods in terms of enhancing drug utilization efficiency, preventing contamination, and ease of manufacturing.

[0043] Microneedle patches utilize multiple microneedle structures ranging in length from approximately 10 to 5000 µm to form numerous micro-perforations on the skin surface, through which drugs can be delivered into the body painlessly. This method utilizes transdermal immune cells and does not pass through the digestive system, making it more efficient and reducing side effects compared to existing drug delivery methods such as oral administration or syringe injection.

[0044] FIG. 1 schematically illustrates a method for manufacturing a microneedle patch according to an embodiment of the present invention, FIG. 2 and FIG. 3 illustrate a thin film according to an embodiment of FIG. 1, and FIG. 4 illustrates a form in which a drug solution according to an embodiment of FIG. 1 is dropped. FIG. 5 illustrates the structure of a microneedle patch manufactured by such a manufacturing method.

[0045] Referring to the drawings, a microneedle patch (1) is prepared in which a plurality of microneedle portions (12) are provided on a substrate portion (11), and a thin film (2) is positioned on the microneedle. Here, the thin film (2) may be surface-treated or modified to be hydrophobic, hydrophilic, oleophilic, lipophilic, etc., so as to have a predetermined surface characteristic. The surface treatment or modification method may be performed by a physical or chemical method.

[0046] According to one embodiment, the outer surface of the thin film (2) may be chemically treated to have hydrophobicity. The thin film (2) is chemically treated by coating it with a hydrophobic coating layer. This hydrophobic coating layer may include fluorocarbon, hydrocarbon, polyethylene, or polydimethylsiloxane. A silane coupling agent may be used as the hydrophobic coating layer. For example, silane coupling agents include Trichloro(octadecyl)silane, Trimethoxy(octadecyl)silane, Dichlorodimethylsilane, etc., which are mainly composed of hydrocarbons, and include CH3-, CH2- groups, etc. at the terminals and side chains. In addition, for example, a silane coating agent of fluorocarbon is Trichloro(1 H ,1 H ,2 H ,2 H -perfluorooctyl)silane, 1 H ,1 H ,2 H ,2 H -Perfluorodecanethiol, 1 H ,1 H ,2 H ,2 HExamples include perfluorooctyltriethoxysilane, which also contains CF3-, CF2- groups in the side chains and terminals, and various groups such as -0H, -NH2, -SH, vinyl group, -Cl, -OCH3, and -0CH2CH3 can be used in the substrate reaction region, but CF3- and CF2- groups are included in the side chains and terminals. Additionally, for example, Poly(dimethylsiloxane) type coating agents include bis(3-aminopropyl) terminated poly(dimethylsiloxane) [Poly(dimethylsiloxane), bis(3-aminopropyl) terminated]; hydroxyl-terminated polydimethylsiloxane [Poly(dimethylsiloxane), hydroxy terminated], and the main component is Poly(dimethylsiloxane), and various groups such as -NH2, -SH, vinyl group, -Cl, -OCH3, and -0CH2CH3 can also be used in the substrate reaction region.

[0047] According to one embodiment, in addition to a coating agent containing silane, any material capable of achieving hydrophobicity through a vapor phase and liquid phase coating process can be used for the coating layer. For example, compounds such as -CnHm compounds (where n and m are integers) such as CH2, CH3, C2H8, etc., which have good release properties, -CnFm compounds (where n and m are integers) such as C2F4, C2F6, CF2, CF3, etc., or -Si-O-CH3 or SinHm compounds (where n and m are integers) can be used as hydrophobic coating agents.

[0048] According to one embodiment, the surface of the thin film (2) includes a plurality of nanostructures. The nanostructures may include nanoislands, nanoposts, or nanoholes arranged regularly or irregularly.

[0049] According to one embodiment, the nanostructure may include a plurality of nanofibers, nanopillars, or nanoholes having a polygonal columnar shape or a polygonal pyramidal shape with a cross-section of any polygon, such as a circle or a triangle, square, pentagon, or hexagon. The plurality of nanofibers, nanopillars, or nanoholes may be formed evenly over the entire exposed surface of the thin film (2) and may be arranged in a plurality of rows and a plurality of columns. The cross-section of the nanofibers, nanopillars, or nanoholes may be circular or n-gonal—where n is a natural number greater than or equal to 3.

[0050] According to one embodiment, each nanoisland, nanopillar, or nanohole is primarily at the nanometer level, but in this specification, the concept is used to include several micrometers. For example, each nanoisland, nanopillar, or nanohole may have a diameter (D) of about 12 nm to about 30 µm, and the center-to-center distance (L) between two adjacent nanoislands, nanopillars, or nanoholes may be about 30 nm to about 300 µm. Additionally, each nanopillar may have a height (H) of about 50 nm to about 50 µm, but is not limited thereto.

[0051] According to one embodiment, the nanostructure can be manufactured by a nanoimprint lithography process, but is not limited thereto, and can also be manufactured by a method using pseudo-replication molding or by optical photoexposure or laser lithography processes. For example, it can be manufactured by fabricating a mold of a desired pattern having a nanoscale structure using an electron beam (E-Beam), and then transferring the pattern onto a substrate using the fabricated mold as a mask.

[0052] According to one embodiment, the nanostructure may include a hydrophobic material or be coated by a hydrophobic coating layer to lower the surface energy. If the nanostructure includes a hydrophobic material, coating by a separate hydrophobic coating layer may not be required. For example, the hydrophobic material may be selected from the group consisting of polydimethylsiloxane (PDMS), polytetrafluoroethylene (PTFE), fluorocarbon compounds, hydrocarbons, and mixtures thereof. As a hydrophobic material, a material comprising one or more CF3- or CF2- groups, etc., at the ends and side chains of a molecular chain including both high and low molecular weight materials may be used. For example, the fluorocarbon compound may be tetrafluoromethane (CF4), tetrafluoroethylene (C2F4), hexafluoroethane (C2F6), hexafluoropropylene (C3F6), fluorobutylene (C4F6), cyclic octafluorobutane (C-C4F8), or decafluorobutane (C4F 12 It may be selected from the group consisting of ), octafluoropropane (C3F8) and mixtures thereof.

[0053] According to one embodiment, the outer surface of the thin film (2) can be treated to have hydrophilicity. The hydrophilic treatment is performed by treating the surface of the thin film (2) with plasma, UV (Ultra-Violet) treatment, hydrogen peroxide treatment, or by coating it with amine groups through chemical treatment so that the surface of the thin film (2) has hydrophilic properties. However, it is not limited thereto, and it is obvious that the method of hydrophilic treatment may vary depending on the type of thin film (2). Meanwhile, the thin film (2) in the embodiment of the present invention may be made of Si, glass, SiN, SiO2, Si or glass film coated with metal, etc.

[0054] According to one embodiment, the outer surface of the thin film (2) may be physically treated to have hydrophilicity. For example, a hydrophilic pattern may be separately formed on the surface of the thin film (2). The hydrophilic pattern may be of any shape, for example, a stripe shape or a circular shape. The length of the hydrophilic pattern may be about 1 μm or less, and specifically, the width of the stripe-shaped hydrophilic pattern may be about 1 μm or less, and the diameter of the circular-shaped hydrophilic pattern may be about 1 μm or less.

[0055] In addition, one or more patterns provided in the hydrophilic pattern may be arranged in a regular or irregular structure on the thin film (2).

[0056] According to one embodiment, the hydrophilic pattern can be manufactured through any process obvious to a person skilled in the art, and may include, but is not limited to, photolithography, electron beam lithography, nano-imprint lithography, UV, EUV or soft X-ray lithography, 2D or 3D lithography, stereolithography, soft lithography, focused electron or ion beam, scanning tunneling microscope, scanning probe lithography, atomic force microscope, sol-gel nanofabrication, two or more photon lithography, dip pen lithography, near field lithography, laser-assisted imprint, temperature substrate patterning, laser-based patterning, and laser direct writing processes.

[0057] According to one embodiment, the thin film (2) can be modified to be hydrophilic or hydrophobic. The surface of the thin film (2) can be made to exhibit hydrophilicity and hydrophobicity, and if the thin film (2) is hydrophilic, a reflux method, a two-step acid-base catalysis method, or a direct condensation method can be selected and used to exhibit hydrophobic properties.

[0058] In addition, as an agent for hydrophobic modification of the thin film (2), it may be selected from the group consisting of methoxytrimethylsilane (MTMS), hexamethyldisiloxane (HMDSO), hexamethyldisilane (HMDS), and trimethoxymethylsilane (TMMS). Preferably, methoxytrimethylsilane is used. This is because the smaller the number of carbon atoms, the better the sol-gel reaction occurs, resulting in a higher yield after the reaction. If an agent with more than 6 carbon atoms is used, it is difficult to form a sol-gel reaction.

[0059] Meanwhile, regarding the moving step for combining the microneedle patch (1) and the thin film (2), the thin film (2) may include a plurality of holes to allow it to be inserted into the microneedle (12) as shown in FIGS. 2 and 3. The holes are smaller than the size of the bottom of the microneedle, and when the thin film (2) and the microneedle patch (1) are aligned and combined with each other, at least a portion of the microneedle portion (12) is exposed to the outside, that is, to the top of the thin film (2). The thin film (2) is in a solid form comprising at least one of a metal, a polymer, or a composite material. The thickness of such a thin film (2) is smaller than the height (h) of the microneedle (12). Alternatively, as shown in FIG. 3, the thickness of the thin film (2) can be configured to exceed the height (h) of the micro-needle (12), and the bottom of the processed hole is configured to be smaller than the bottom of the micro-needle (12) and the top of the processed hole is configured to have a larger dimension than the bottom of the processed hole.

[0060] According to one embodiment, the basic structure of the microneedle patch can be manufactured through any process obvious to a person skilled in the art, and, for example, can be made of various materials such as water-soluble, insoluble, low-solubility, biodegradable, curable resins, metals, and silicones through molding, drying, curing, machining, laser processing, photolithography, etc. Depending on the characteristics, required amount, use, and ease of manufacturing of the main material and drug, the active ingredient may be composed by being partially mixed into the main material or coated on the surface. The present invention can provide a method for coating an active substance on a microneedle patch that is generally applicable regardless of the manufacturing method and main material, wherein the drug is not coated on the base portion of the microneedle and the coating is performed only on the tip portion of the microneedle, which is the clinically most desirable configuration for increasing drug use efficiency when manufacturing a coated microneedle patch.

[0061] According to one embodiment, as illustrated in FIG. 6, the microneedle patch (1) comprises a microneedle portion (12) and a substrate portion (11) on which the microneedle portion (12) is supported, and the microneedle portion (12) includes a microneedle tip at the top. The microneedle portion (12) must have strength to be inserted by piercing the skin, and it is preferable to have a sharp tip to facilitate skin piercing. For example, the three-dimensional shape of the microneedle tip may be formed in the shape of a cone, a triangular pyramid, a square pyramid, a hexagonal pyramid, or other polygonal pyramids. Additionally, the tip may have a horn shape as described above, but the lower part may be formed in a column shape.

[0062] According to one embodiment, the height (h) and spacing (w) of the micro-needle portion (12) are determined by the amount of drug to be injected, and although there is no need to specifically limit them, the height (h) may be in the range of 12 to 3000 μm and the spacing (w) may be in the range of 12 to 1500 μm.

[0063] The height of the micro-needle section (11) is related to the amount of drug that can be injected with a single tip. If the height of the tip is too low, the amount of drug becomes too small, and too many tips are required to administer the required amount. Also, if the height of the tip is too high, a problem may arise where the tip is not inserted only into the area to be administered, but is positioned across multiple layers. Additionally, if the spacing of the micro-needle section (11) is too narrow, the tip does not penetrate the skin easily, and if the spacing of the tip is too wide, a disadvantage occurs in that the surface area of ​​the micro-needle structure must be excessively large to form the desired number of tips.

[0064] Referring to Fig. 5, the drying step may further include a step of flipping the microneedle patch over to dry it. After drying has progressed sufficiently—for example, to the point where the solution does not drip—the microneedle patch is flipped over to dry. In the case of a polar solution on a hydrophobic surface (or a non-polar solution on a hydrophilic surface), the contact angle is large, so when flipped, the solution is more likely to accumulate on the side where the solution is present and move toward the microneedle rather than remaining on the film.

[0065] Meanwhile, the contact angle (θ in (f) of FIG. 1) w Since a large surface area is equivalent to aggregation occurring during the drying process, there is some effect even when not turning it over, so this process is not strictly necessary. However, if the surface is turned over, the gravitational effect is added to the surface effect, which can minimize the point where aggregation begins. Therefore, the turning step can be optionally included as needed.

[0066] A method for manufacturing a microneedle patch according to one embodiment of the present invention also includes the steps of: positioning a hydrophilic thin film (2) on a microneedle; pressing and penetrating the thin film (2) positioned on the microneedle or alternatively inserting it into a hole; dropping a drug solution (3) onto the thin film (2); drying the drug solution (3) on the thin film (2) through which the microneedle has penetrated; and removing the thin film (2).

[0067] The step of dropping the drug solution includes dropping a single or multiple drug solutions onto a thin film (2) where the micro-needles are exposed. Additionally, as shown in FIG. 3, micro drug solution droplets may be dropped onto the location of the micro-needles exposed on the thin film (2) so that each micro drug solution droplet comes into contact with only one micro-needle.

[0068] The present invention can maximize the efficiency of drug delivery by using a hydrophobic thin film (2) to deliver a water-soluble drug dissolved in water to a microneedle patch of a non-soluble / low-solubility substance, and by using a hydrophilic thin film (2) to deliver a lipid-soluble drug dissolved in an organic solvent to a microneedle patch of a water-soluble substance. In particular, the hydrophobic the surface of the thin film (2), that is, the larger the contact angle, the smaller the amount of drug remaining on the thin film, thereby securing a very important characteristic that guarantees precise dosage in the body in terms of drug delivery.

[0069] Among the coating elements, the thin film (2) has a higher hydrophobicity, the greater the drug delivery efficiency of the present invention. The drug delivery efficiency varies depending on the characteristics of the coated drug. Here, high drug delivery efficiency refers to the ratio of the total drug on the film that moves toward the microneedle patch and dries during manufacturing; the larger the contact angle of the thin film containing the initial drug solution, the better the utilization efficiency. When using a hydrophilic solution, the higher the hydrophobicity of the film, the higher the contact angle of the solution droplet on the surface and the higher the drug utilization efficiency; when using a lipophilic solution, the higher the hydrophilicity of the film, the higher the contact angle of the solution droplet and the higher the drug utilization efficiency. In other words, the stronger the characteristic opposite to that of the solution intended for manufacturing, the higher the drug utilization efficiency.

[0070] Hydrophobic properties can be imparted chemically and structurally, and the effects of the present invention can be maximized, particularly through superhydrophobic surfaces with a contact angle of 140 degrees or more, such as the lotus effect and rose petal effect. Conversely, if a hydrophilic surface is used, the drug remains on the surface and the drug utilization rate can be significantly reduced.

[0071] The present invention can be broadly divided into two cases depending on the characteristics of the solution in which the drug is dissolved. A hydrophobic thin film is used when the drug is in a hydrophilic solution, and a hydrophilic thin film is used when the drug is in a hydrophobic solution. In other words, by using a thin film with characteristics opposite to those of the drug solution, the efficiency of drug utilization can be increased.

[0072] According to one embodiment, with reference to FIG. 5, as previously described, a step of turning the microneedle in and drying it after the drying step may be further included. After the organic solvent has sufficiently evaporated, for example, when the solution is no longer dripping, the microneedle patch is turned in and dried.

[0073] According to one embodiment, in the step of dropping a drug solution (3) onto a thin film (2), the drug droplet does not spread on the thin film due to the surface energy of the drug droplet and the contact angle (θ) w ) is formed, and the stronger the hydrophobicity of the surface of the thin film (2), the higher the angle formed at the interface.

[0074] In addition, during the drying process of the drug, the drug droplet is dried while maintaining a high contact angle between the drug droplet and the thin film (2) due to the energy equilibrium between the interfaces. As the concentration of the drug increases, the solvent evaporates, and the drug is coated only on the microneedles, specifically on at least a part of the microneedle section, thereby forming a drug coating section (13). In particular, as confirmed in FIG. 6, during the drying process of the drug, the drug is concentrated and coated at an adjacent location between the thin film that dries the latest in the area of ​​the microneedles in contact with the drug and the area of ​​the microneedles. Thus, the microneedle section (12) in the microneedle patch (1) manufactured according to the present embodiment is characterized by including a drug concentration section (13a) in which the drug is concentrated and coated at a point adjacent to the insertion and bonding location of the thin film (2) used for drug coating.

[0075] When drying is finished and the thin film (2) is peeled off, the residual drug on the thin film (2) is removed, and the drug coated only on the micro-needle portion remains. Drug that is not coated on the micro-needle portion remains as a residual film on the thin film (2), but is removed together with the thin film after drying is finished. Assuming that an appropriate amount of drug solution (3) was initially dropped, as the solvent of the drug droplet evaporates, only the pure drug dried on the micro-needle portion (12) remains, and the thin film (2) has a small surface area, that is, the larger the contact angle, the smaller the amount of drug remaining on the thin film.

[0076] According to one embodiment, a drug solution may be periodically dispensed and microneedle patches may be aligned at each location and dried, or a drug solution may be periodically dispensed and individual microneedles may be aligned at each location and dried.

[0077] According to one embodiment, in the manufacture of the microneedle patch, it is obvious that any additional peripheral physical, chemical, electrical, or mechanical assistance (ultrasonic lenses, transducers, EP, etc.) available to a person skilled in the art may be incorporated.

[0078] Examples

[0079] As an embodiment of the present invention, a microneedle patch containing a microneedle patch was manufactured using a polyethylene thin film, which is one of the hydrophobic films, by the coating method described above. The manufacturing of the microneedle patch is performed by imprinting (similar to the molding method but referred to as imprinting because the dimension is smaller), approximately 1-12 w% of nucleic acid (salmon DNA) in DI (deionized water), a fluorescent material (approx. 1-12% FITC (Fluorescein isothiocyanate)), a contact angle of approximately 90-150 degrees (more than 150 degrees is possible), and a drying time of approximately 1-3 hours (however, the time can be several minutes to several days). This embodiment corresponds to a combination of a hydrophilic drug solution and a hydrophobic thin film.

[0080] Then, a sufficient amount of drug solution was poured onto the microneedle patch and dried.

[0081] After removing the thin film (2), it was confirmed that the drug was coated only on the microneedle part (tip).

[0082] In conclusion, through the method according to one embodiment of the present invention, drug delivery efficiency can be increased during manufacturing, and a very important characteristic that guarantees precise infusion in the body in terms of drug delivery can be secured.

[0083] Although the embodiments have been described above with reference to limited examples and drawings, those skilled in the art can make various modifications and variations from the description above. For example, suitable results can be achieved even if the described techniques are performed in a different order than described, and / or components such as the described structures and devices are combined or assembled in a form different from described, or replaced or substituted by other components or equivalents.

[0084] Therefore, other implementations, other embodiments, and equivalents to the claims also fall within the scope of the claims set forth below. Explanation of the symbols

[0086] 1 microneedle patch 11 Substrate part 12 Micro-needle part 13 Drug coating section 13a Drug concentration section 2 thin film 3 drug solution

Claims

Claim 1 A method for manufacturing a microneedle patch comprising a plurality of microneedles, comprising: a) a step of positioning a thin film on the microneedles; b) a step of moving the thin film so that only at least a portion of the microneedles are exposed; c) a step of dropping a drug solution onto the thin film where the microneedles are exposed; d) a step of drying the drug solution dropped onto the thin film where the microneedles are exposed; and e) a step of removing the thin film, wherein step b) comprises a step of moving the thin film, which has a hole processed at a position where it is smaller than the bottom size of the microneedles and is insertable into the microneedles, so as to be aligned with the microneedles, wherein the bottom size of the processed hole is smaller than the bottom size of the microneedles and the top size of the processed hole is larger than the bottom size of the processed hole. Claim 2 A method for manufacturing a microneedle patch according to claim 1, wherein step b) comprises applying pressure to penetrate a thin film positioned on a microneedle. Claim 3 delete Claim 4 A method for manufacturing a microneedle patch according to claim 1, wherein in step b), the thin film is in a solid form including at least one of a metal, a polymer, or a composite material, and the thickness of the thin film is smaller than the height of the microneedle. Claim 5 A method for manufacturing a microneedle patch according to claim 1, characterized in that, in step b), the thickness of the thin film exceeds the height of the microneedle. Claim 6 A method for manufacturing a microneedle patch according to claim 1, wherein step c) comprises dropping a single or multiple drug solutions onto a thin film in which microneedles are exposed. Claim 7 A method for manufacturing a microneedle patch according to claim 1, wherein step c) involves dropping micro drug solution droplets onto the locations of microneedles exposed on a thin film, such that the dropped micro drug solution droplets each come into contact with only one microneedle. Claim 8 A method for manufacturing a microneedle patch according to claim 1, further comprising the step of turning the microneedle over and drying it after step d). Claim 9 A method for manufacturing a microneedle patch according to claim 1, wherein the thin film is hydrophobic and the drug solution comprises a water-soluble drug dissolved in water. Claim 10 A method for manufacturing a microneedle patch according to claim 9, wherein the surface of the microneedle comprises a non-dissolvable or low-solubility material. Claim 11 A method for manufacturing a microneedle patch according to claim 9, wherein the surface of the thin film comprises a plurality of nanostructures. Claim 12 A method for manufacturing a microneedle patch according to claim 11, wherein a plurality of nanostructures comprises at least one of nanoislands, nanoposts, or nanoholes arranged regularly or irregularly. Claim 13 A method for manufacturing a microneedle patch according to claim 1, wherein the thin film is hydrophilic and the drug solution comprises a lipid-soluble drug dissolved in an organic solvent. Claim 14 A method for manufacturing a microneedle patch according to claim 13, wherein the surface of the thin film comprises a hydrophilic pattern. Claim 15 A method for manufacturing a microneedle patch according to claim 14, wherein the surface of the microneedle comprises a water-soluble substance. Claim 16 A method for manufacturing a microneedle patch, wherein the surface of the thin film is chemically treated in claim 1. Claim 17 A method for manufacturing a microneedle patch, wherein the thin film is modified to be hydrophilic or hydrophobic in claim 1. Claim 18 A method for manufacturing a microneedle patch according to claim 17, wherein hydrophobic modification is performed by a reflux method, a two-step acid-base catalysis method, or a direct condensation method. Claim 19 A method for manufacturing a microneedle patch according to claim 17, wherein the modifier for hydrophobic modification of the thin film is selected from the group consisting of methoxytrimethylsilane, hexamethyldisiloxane, hexamethyldisilane, and trimethoxymethylsilane. Claim 20 delete Claim 21 delete Claim 22 delete

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