Microneedle Patch and Method for Manufacturing the Same

Abstract

To provide a microneedle patch that minimizes bleeding and inflammation, and a method of manufacturing the same.SOLUTION: A microneedle patch includes: a base 100 including an invasive part and a non-invasive part; and a microneedle 200 located in the invasive part of the base, where at least a portion of the microneedle is loaded with a drug, and no microneedle is located in the non-invasive part.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a microneedle patch and a method for manufacturing the same, and more particularly, to a microneedle patch including an invasive part where microneedles are located and a non-invasive part where microneedles are not located, and a method for manufacturing the same.

Background Art

[0002] Conventional drug injection using a syringe requires an injection by a professional and has problems such as pain. To solve such problems, a microneedle type drug injection system has been developed.

[0003] A microneedle is a system that transmits an active ingredient into the skin by passing through the stratum corneum, which is a skin barrier layer. It is a new system that combines the efficacy of an existing syringe and the convenience of a patch, and has recently achieved many technological advancements.

[0004] The microneedle may penetrate the stratum corneum of the skin, enter the epidermis or dermis of the skin, stay in the skin for several minutes to several hours, and be decomposed by body fluids to absorb the drug into the body.

[0005] Generally, a microneedle is used for the delivery of active substances such as drugs and vaccines in vivo, the detection of in vivo analytes, and biopsy. The delivery of pharmaceutically or chemically active ingredients using microneedles aims to deliver active substances through the skin rather than through the body's circulatory system such as blood vessels or lymphatic vessels. Therefore, the microneedle must have sufficient physical strength to penetrate the skin and preferably cause less pain.

[0006] The microneedle may be configured such that a drug is loaded at a sharp end and the central part is hollow inside. When the microneedle directly penetrates the affected area, it may induce bleeding and inflammation.

Summary of the Invention

Problems to be Solved by the Invention

[0007] One object of the present invention for solving the above problems is to provide a microneedle patch that minimizes bleeding and inflammation and a method for manufacturing the same.

Means for Solving the Problems

[0008] A microneedle patch according to an embodiment of the present invention for achieving the above object includes a base including an invasive part and a non-invasive part, and microneedles located in the invasive part of the base, at least a part of the microneedles being loaded with a drug, and the non-invasive part having no microneedles located therein.

[0009] According to one aspect, a non-invasive part may be located at the center of the base, and an invasive part may be located at an end of the base.

[0010] According to one aspect, the invasive part may be located surrounding the non-invasive part.

[0011] According to one aspect, the microneedles may include a first part and a second part, and the drug may be loaded only in the second part.

[0012] According to one aspect, the microneedles may include a first part and a second part, and a higher concentration of the drug may be loaded in the second part than in the first part.

[0013] According to one aspect, the invasive part may be provided with a plurality of microneedles, and the drug loading state of each of the plurality of microneedles may be determined by the distance from the non-invasive part.

[0014] According to one aspect, the base may include a biodegradable polymer.

[0015] According to one aspect, the base may include one or more of hyaluronic acid, carboxymethyl cellulose, polyvinyl alcohol, chitosan, collagen, and polyvinylpyrrolidone.

[0016] According to one aspect, at least a part of the base and the microneedle may include the same substance.

[0017] According to one aspect, the drug loaded on the microneedle may include a drug having at least one of a hemostatic or analgesic effect.

[0018] According to one aspect, the drug loaded on the microneedle may include at least one of tranexamic acid, fibrin, thrombin, tannic acid, chitin, lidocaine, salicylic acid, ketoprofen, loxoprofen, flurbiprofen, piroxicam, felbinac, diclofenac diethylammonium, indomethacin, and antihistamine.

[0019] According to one aspect, the height of the microneedle may be 100 μm to 5000 μm.

[0020] According to one aspect, the radius of the microneedle may be 50 μm to 500 μm.

[0021] A method for manufacturing a microneedle patch according to one embodiment includes the steps of preparing a mold including an invasive part with grooves formed therein and a non-invasive part without grooves formed therein, and applying a polymer onto the mold to form a microneedle patch including microneedles and a base, wherein the microneedle patch may include an invasive part where the microneedles are located and a non-invasive part where the microneedles are not located.

[0022] According to one aspect, a non-invasive part may be located at the center of the manufactured microneedle patch, and an invasive part may be located at the edge of the microneedle patch.

[0023] According to one aspect, the non-invasive part of the manufactured microneedle patch may be located surrounded by the invasive part.

[0024] According to one aspect, the step of forming the microneedle patch may include a step of applying a polymer containing a drug to the groove of the mold to form a second part of the microneedle, and a step of applying a polymer on the mold to form a first part of the microneedle and a base.

[0025] A method for manufacturing a microneedle patch according to another embodiment may include a step of preparing a mold having grooves formed therein, a step of applying a polymer on the mold to form a base having an invasive part including microneedles, and a step of removing a part of the microneedles to form a non-invasive part.

[0026] According to one aspect, the non-invasive part may be located at the center of the manufactured microneedle patch, and the invasive part may be located at the end of the microneedle patch.

[0027] According to one aspect, the step of forming a base having an invasive part including the microneedles may include a step of applying a polymer containing a drug to the groove of the mold to form a second part of the microneedle, and a step of applying a polymer on the mold to form a first part of the microneedle and a base.

Advantages of the Invention

[0028] The disclosed technology may have the following effects. However, it should not be understood that the scope of the rights of the disclosed technology is limited thereby, in the sense that a specific embodiment must include all of the following effects or only the following effects.

[0029] The microneedle patch according to one embodiment of the present invention described above includes an invasive part where the microneedles are located and a non-invasive part where the microneedles are not located, and can prevent additional bleeding at the affected area and minimize the inflammatory response.

[0030] In addition, the microneedle patch can be manufactured in a simple and economical way.

Brief Description of the Drawings

[0031]

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Embodiments for Carrying Out the Invention

[0032] The present invention may be subject to various modifications and may have various embodiments. However, specific embodiments are illustrated in the drawings and will be described in detail.

[0033] However, this is not intended to limit the present invention to specific embodiments, and it must be understood to include all modifications, equivalents, and alternatives included in the spirit and technical scope of the present invention.

[0034] Terms such as first, second, etc. may be used to describe various components, but the components shall not be limited by such terms. The terms are used only for the purpose of distinguishing one component from another. For example, without departing from the scope of the present invention, the first component may be named the second component, and similarly the second component may be named the first component. The term "and / or" includes any combination of a plurality of related listed items or any one of the plurality of related listed items.

[0035] When a component is referred to as being "connected to" or "coupled to" another component, it should be understood that it can be directly connected or coupled to the other component, but there may be other components in between. On the other hand, when a component is referred to as being "directly connected to" or "directly coupled to" another component, it should be understood that there are no other components in between.

[0036] The terms used in this application are merely used to describe specific embodiments and are not intended to limit the present invention. Singular expressions include plural expressions unless clearly stated otherwise in the context. In this application, terms such as "including" or "having" are intended to specify the presence of features, numbers, steps, operations, components, parts, or combinations thereof described in the specification, and should not be construed as precluding the presence or addition of one or more other features, numbers, steps, operations, components, parts, or combinations thereof.

[0037] Unless otherwise defined, all terms used herein, including technical and scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Terms defined in commonly used dictionaries are to be interpreted as having a meaning that coincides with the meaning in the context of the relevant art and are not to be interpreted in an idealized or overly formal sense unless clearly defined in this application.

[0038] Hereinafter, with reference to the accompanying drawings, preferred embodiments of the present invention will be described in more detail. In describing the present invention, for the sake of easy overall understanding, the same reference numerals are used for the same components in the drawings, and duplicate descriptions of the same components are omitted.

[0039] FIG. 1 is a diagram showing a microneedle patch according to this embodiment. Referring to FIG. 1, the microneedle patch according to this embodiment includes a base 100 and microneedles 200 located on the base 100. According to one aspect, at least a part of the microneedles 200 may be loaded with a drug.

[0040] The base 100 may include a polymer substance. As an example, the base 100 may include hyaluronic acid, but is not limited thereto. The base 100 may include a biodegradable polymer, specifically, one or more of hyaluronic acid, carboxymethyl cellulose, polyvinyl alcohol, chitosan, collagen, and polyvinyl pyrrolidone.

[0041] The microneedle 200 may include a first portion 210 and a second portion 220. The second portion 220 may be located farther away from the base 100 than the first portion 210. According to one aspect, the second portion 220 of the microneedle 200 may contain a drug inside, and as an example, it may contain a hemostatic agent. For example, the second portion 220 may contain a drug having at least one of the effects of hemostasis or analgesia. In one embodiment, the second portion 220 may contain tranexamic acid, but is not limited thereto. Specifically, the second portion 220 may contain drugs having a hemostatic or analgesic effect such as tranexamic acid, fibrin, thrombin, tannic acid, chitin, lidocaine, salicylic acid, ketoprofen, loxoprofen, flurbiprofen, piroxicam, felbinac, diclofenac diethylammonium, indomethacin, antihistamine, etc. According to one aspect, the drug may be loaded only on the second portion of the microneedle.

[0042] According to one aspect, at least a part of the base 100 and the microneedle 200 may contain the same substance. Although not limiting, more specifically, the base 100 and the first portion 210 of the microneedle 200 may be connected to each other and may be made of the same substance. As an example, the base 100 and the first portion 210 of the microneedle 200 may contain hyaluronic acid. Depending on the embodiment, a higher concentration of the drug may be loaded on the second portion of the microneedle than on the first portion. For example, the base 100 and the first portion 210 of the microneedle 200 may contain a low concentration of tranexamic acid. The second portion 220 of the microneedle 200 may contain hyaluronic acid containing a higher concentration of tranexamic acid than the first portion 210. Or the base 100 and the first portion 210 of the microneedle 200 may not contain tranexamic acid.

[0043] As shown in FIG. 1, the microneedle patch according to this embodiment includes an invasive portion A where the microneedles 200 are located and a non-invasive portion B where the microneedles are not located. In the microneedle patch according to this embodiment, the non-invasive portion B may be positioned at a site where bleeding occurs or where the trauma is severe, and drugs may be delivered through the invasive portion A. Therefore, where bleeding has occurred or where the microneedles 200 do not invade a severely traumatized portion, additional bleeding at the wound site can be prevented and the inflammatory response can be minimized.

[0044] As shown in FIG. 1, the non-invasive portion B may be surrounded and positioned by the invasive portion A. That is, the non-invasive portion B may be located at the center of the patch and the invasive portion A may be located at the edge. Therefore, when attaching the patch, the non-invasive portion B may be positioned at the affected area and the invasive portion A may be located around the affected area, so that drugs can be delivered to the affected area by the microneedles around the affected area. However, the shapes of the invasive portion A and the non-invasive portion B may be diverse and are not limited to the shapes shown in FIG. 1. As shown in FIG. 1, the patch may be circular, but is not limited thereto, and the shape of the patch may be diverse.

[0045] On one hand, according to one aspect, the invasive part is provided with a plurality of microneedles, and the loading state of the drug in each of the plurality of microneedles may be determined by the distance from the non-invasive part. For example, among the plurality of microneedles arranged in the invasive part, the microneedles close to the non-invasive part (i.e., the affected part) contain drugs, while the microneedles far from the non-invasive part may not contain drugs. That is, when looking at the patch along the horizontal axis, it may be composed in the order of (center) non-invasive part - invasive part containing drug - (end) invasive part not containing drug. Or, according to the distance from the wound, that is, the distance from the non-invasive part of the patch, the concentration of the drug contained in the microneedles of the invasive part may be adjusted. For example, the closer the microneedle is to the non-invasive part, the higher the concentration of the drug loaded may be configured. Therefore, while performing hemostasis or drug delivery to the affected part more efficiently, the problem of the strength of the entire microneedle patch can be improved.

[0046] FIG. 2 is a diagram showing a configuration using the microneedle patch according to this embodiment for hemostasis. In FIG. 2A, the liver where bleeding has occurred is schematically shown, and as shown in FIGS. 2B and 2C, the microneedle patch according to this embodiment may be attached. As described above, the microneedle patch according to this embodiment may include an invasive part and a non-invasive part where the microneedles are located. As shown in FIGS. 2B and 2C, the non-invasive part of the microneedle patch may be located at the affected part where bleeding occurs. In this case, since the microneedles of the microneedle patch do not invade the affected part, additional bleeding can be prevented and the occurrence of inflammation can be prevented.

[0047] D in FIG. 2 is an image in which a microneedle patch with microneedles located in the entire area is applied to the affected area, and E in FIG. 2 is an image in which a microneedle patch including an invasive part and a non-invasive part is applied to the affected area. Referring to D in FIG. 2, in the case of a microneedle patch with microneedles located in the entire area, where the microneedles are also located in the affected area where bleeding has occurred, it may stimulate the affected area and induce additional bleeding. However, referring to E in FIG. 2, a microneedle patch with microneedles located only in a partial area can prevent additional bleeding where the microneedles do not penetrate the affected area. The drug can be transmitted to the affected area through the invasive part where the microneedles are located to stop bleeding or treat the wound.

[0048] FIG. 3 is a diagram showing a cross-section A of a microneedle patch and an actual image B according to an embodiment. The microneedle patch shown in FIG. 3 has TXA (Tranexamic acid) loaded in the second part. The base and needles shown in FIG. 3 may contain a biodegradable polymer. Through FIG. 3B, it can be confirmed that TXA is loaded on the microneedles of the microneedle patch.

[0049] FIG. 4 is a diagram showing a method for manufacturing a microneedle patch according to an embodiment. Referring to FIG. 4, after preparing a PDMS mold, a hyaluronic acid solution containing a high concentration of TXA (Tranexamic acid) may be applied. Through this, the tip portion of the microneedle loaded with the drug (the second portion 220 of the microneedle 200 shown in FIG. 1) is formed. Next, a hyaluronic acid solution containing a low concentration of TXA is used to form the second portion 220 and the base 100 of the microneedle 200 shown in FIG. 1. After drying at room temperature, the microneedle patch is separated from the mold. Although not shown in FIG. 4, in order to form a non-invasive portion corresponding to the affected area, a step of removing the microneedle may be further included. At this time, the removal of the microneedle may be performed by a physical method. When manufacturing by such a method, the microneedle may be appropriately removed and used according to the shape of the affected area.

[0050] Alternatively, a microneedle patch according to this embodiment may be manufactured using a mold in which an invasive portion and a non-invasive portion are divided. FIG. 5 is a diagram showing a method for manufacturing a microneedle patch according to another embodiment. Referring to FIG. 5, a master mold is fabricated using a UV curable polymer. At this time, the master mold includes an invasive portion where the microneedle is located and a non-invasive portion where the microneedle is not located. Next, a mold is formed using the master mold, and a microneedle patch loaded with the drug may be manufactured through a process of applying a hyaluronic acid containing the drug to the mold and then separating it. As shown in FIG. 5, in the case of the manufacturing method according to this embodiment, when manufacturing a microneedle patch using a mold in which an invasive portion and a non-invasive portion are divided, a step of removing the microneedle as in the manufacturing method of FIG. 4 may not be included.

[0051] In one embodiment, the concentration of the drug loaded in the second portion 220 of the microneedle 200 in FIG. 1 may be 10 mg / mL to 30 mg / mL. This is a concentration range in which the drug can be uniformly distributed without precipitation. FIG. 6 is a diagram showing precipitation depending on the content of TXA (Tranexamic acid) loaded in ionized water. Referring to FIG. 6, when the concentration of TXA is 10 mg / mL to 30 mg / mL, a uniform solid layer is formed, but when the concentration exceeds 40 mg / mL, precipitation occurs and it was confirmed that the distribution of TXA in the patch becomes non-uniform.

[0052] Referring to FIG. 1, the radius D1 of the microneedle 200 may be 50 μm to 500 μm. Also, the distance H1 between the microneedle 200 may be 100 μm to 5000 μm. Further, the height D2 of the microneedle 200 may be 100 μm to 5000 μm. When the size of the microneedle is less than 100 μm, it is difficult to sufficiently pierce the skin stratum corneum, and when it is 5000 μm or more, it is structurally unstable due to a high aspect ratio, so it tends to break without being able to penetrate the skin. The tip diameter of the microneedle 200 may be 5 μm to 50 μm. The tip diameter of the microneedle 200 means the hemispherical structure observed at the tip of the microneedle. The tip angle of the microneedle 200 means the angle of the tip of the microneedle observed from the side, and means the size of the acute angle measured with reference to the virtual apex when the tip of the microneedle has an ideal conical structure. The tip diameter and tip angle of the microneedle are designed to have an appropriate level of sharpness for penetrating the skin.

[0053] That is, since the size of the microneedle patch according to the present embodiment is fine, the invasion can be minimized.

[0054] Figure 7 shows an image of the micro-needle patch manufactured according to this embodiment and an image applied to an actual affected area. Referring to A in Figure 7, the micro-needle patch contains hyaluronic acid, and TXA (Tranexamic acid) is loaded at one end of the micro-needle. B in Figure 7 is an image of the actually manufactured micro-needle patch, and methylene blue was loaded to confirm the presence of TXA. As shown in B of Figure 7, the part where TXA was loaded was confirmed to be blue. C in Figure 7 is an image of a micro-needle patch in which micro-needles are uniformly formed without distinguishing between invasive and non-invasive parts, and D and E in Figure 7 are images of micro-needle patches in which invasive and non-invasive parts are distinguished. As shown in F of Figure 7, after removing a part of the liver tissue of a male rat, a micro-needle patch with invasive and non-invasive parts distinguished according to this embodiment was attached. G in Figure 7 is an interface image of the liver tissue to which such a micro-needle patch was attached. As shown in G of Figure 7, it was confirmed that the micro-needles were not located in the affected area (Non-invasive region), but only in the area surrounding the affected area.

[0055] Since such a micro-needle patch in which the micro-needles are located only in a part of the area requires less force for attachment, the patch can be attached to the affected area with a minimum pressure.

[0056] Figure 8 shows a diagram showing the forces A and B applied to one micro-needle of the micro-needle patch and the forces C and D required when attaching the patch. Referring to A and B in Figure 8, it was confirmed that the forces applied to one micro-needle in each of the micro-needle patches without a non-invasive area (No non-invasive area) and the micro-needle patches with a non-invasive area (Small non-invasive area, Large non-invasive area) are similar.

[0057] On the other hand, referring to C and D in FIG. 8, it was confirmed that the micro-needle patch (P-MN patch) in which the invasive part and the non-invasive part are divided can be attached with less force than the micro-needle patch (MN patch) in which the micro-needles are uniformly located without dividing the invasive part and the non-invasive part. That is, the micro-needle patch according to the present embodiment can reduce the pressure for attachment, and can reduce the influence of the pressure on the bleeding wound.

[0058] FIG. 9 shows the results of a hemostasis experiment on the liver of rats with respect to various substances. As shown in FIG. 9A, liver trauma was induced in the experimental rats. Next, the bleeding volume and the hemostasis time were measured for the micro-needle patch (P-MN) in which the invasive part and the non-invasive part are divided, the micro-needle patch (MN) in which the micro-needles are uniformly located without dividing the invasive part and the non-invasive part, the patch without needles (Patch), the spray (Spray), and the intravenous injection (IV), and these are shown in FIG. 9B. Referring to FIG. 9B, it was confirmed that the micro-needle patch (P-MN) in which the invasive part and the non-invasive part are divided reduces the bleeding time the most. On the other hand, in the micro-needle patch (MN) in which the micro-needles are uniformly located without dividing the invasive part and the non-invasive part, the bleeding volume increased. Through this, it was confirmed that when the micro-needles of the micro-needle patch are located at the affected part, additional bleeding can be induced.

[0059] FIG. 10 is a diagram showing and quantitatively showing the inflammatory sites when various types of patches are attached to liver wounds. That is, A in FIG. 10 is a patch without needles (Patch), and the inflammatory site when this is attached to a liver wound is shown in B of FIG. 10. C in FIG. 10 is a micro-needle patch (MN patch) in which the micro-needles are uniformly located without dividing the invasive part and the non-invasive part, and the inflammatory site when this is attached to a liver wound is shown in D of FIG. 10. E in FIG. 10 is a micro-needle patch (P-MN patch) in which the invasive part and the non-invasive part are divided, and the inflammatory site when this is attached to a liver wound is shown in F of FIG. 10.

[0060] Also, the inflammatory regions at B, D, and F in Fig. 10 were quantified and shown in G of Fig. 10. Referring to Fig. 10, it was confirmed that in the microneedle patch (MN patch) where the microneedles were uniformly located without distinction between the invasive part and the non-invasive part, the inflammatory region was the widest and the numerical value of the inflammatory region was also shown to be the highest.

[0061] Referring to Fig. 10F, in the case of the microneedle patch (P-MN patch) where the invasive part and the non-invasive part were distinguished, the inflammatory region was shown to be narrow in the part where the microneedles were not located, and as shown in Fig. 10G, it was confirmed that the inflammatory reaction was weaker compared to the microneedle patch (MN patch) where the microneedles were uniformly located. Also, it was confirmed that the numerical value of the inflammatory region of the microneedle patch (P-MN patch) where the invasive part and the non-invasive part were distinguished was shown to be the lowest.

[0062] In the medical field, the anticoagulant heparin is often administered to patients. Therefore, a hemostasis experiment was conducted on the liver injury of heparin-treated rats in the same manner as in Fig. 9 and shown in Fig. 11. A in Fig. 11 is a diagram briefly showing heparin-treated rats, and B in Fig. 11 is a diagram showing the measurement of the blood loss amount and the hemostasis time for the microneedle patch (P-MN) where the invasive part and the non-invasive part were distinguished, the microneedle patch (MN) where the microneedles were uniformly located without distinction between the invasive part and the non-invasive part, the patch without needles (Patch), the spray (Spray), and the intravenous injection (IV). The results in Fig. 11B were shown to be similar to the results in Fig. 9B. That is, it was confirmed that the microneedle patch (P-MN) where the invasive part and the non-invasive part were distinguished reduced the bleeding time the most. However, in the case of Fig. 11B, in a state where heparin was injected and the self-coagulation function was reduced, it was revealed that the blood loss amount increased somewhat due to the attachment of the microneedle patch.

[0063] The micro-needle patch according to this embodiment may appropriately remove and use the micro-needles according to the usage environment. FIG. 12 is a diagram showing an example of the use of the micro-needle patch. Referring to FIG. 12A, a liver having an asymmetric affected part is shown. As shown in FIG. 12B, after positioning the micro-needle patch on the liver, the region where the non-invasive part is located is shown through the shape of the wound. As shown in the following FIGS. 12C and 12D, the micro-needles located in the non-invasive part are removed, and as shown in FIG. 12E, the micro-needle patch may be attached to the asymmetric affected part. That is, the micro-needle patch according to this embodiment may remove and use the micro-needles according to the usage environment. Therefore, it can be applied to affected parts of various shapes.

[0064] FIG. 13 is a diagram showing the maximum adhesive force of the micro-needle patch according to this embodiment. In FIG. 13, the maximum adhesive force (Liver interface) between liver tissues and the maximum adhesive force (MN patch interface) between liver tissue and the micro-needle patch are shown. Referring to FIG. 13, the maximum adhesive force (MN patch interface) between liver tissue and the micro-needle patch is shown to be even higher than the maximum adhesive force (Liver interface) between liver tissues. Therefore, it was confirmed that the micro-needle patch according to this embodiment adheres stably to liver tissue.

[0065] Figure 14 is a diagram showing the drug release profile of the microneedle patch according to this embodiment. The black line in Figure 14 represents the amount of drug dissolved over time when the microneedles were exposed in a mimetic body fluid (phosphate buffered saline) after being attached to the liver, and the red line represents the amount of drug dissolved over time when the microneedles were exposed in the mimetic body fluid (phosphate buffered saline) without being attached to the liver. That is, when the microneedle patch is attached to the tissue, the drug tends to be absorbed into the skin at a certain level even when there is a large amount of body fluid around the tissue. Through Figure 14, it was confirmed that the microneedle patch according to this embodiment stably releases the drug into the liver tissue.

[0066] Such a microneedle patch according to this embodiment has excellent hemostatic performance for various bleeding sites.

[0067] Figure 15 is a diagram measuring the hemostatic performance of the microneedle patch according to this embodiment on a wound of a rat's skin. It was confirmed that the microneedle patch (P-MN) according to this embodiment has excellent hemostatic performance compared to the control group (contrast).

[0068] Figure 16 is a diagram measuring the hemostatic performance of the microneedle patch according to this embodiment on a wound of a rat's heart. It was confirmed that the microneedle patch (P-MN) according to this embodiment has excellent hemostatic performance compared to the control group (contrast).

[0069] Figure 17 is a diagram measuring the hemostatic performance of the microneedle patch according to this embodiment on a wound of a rat's kidney. It was confirmed that the microneedle patch (P-MN) according to this embodiment has excellent hemostatic performance compared to the control group (contrast).

[0070] FIG. 18 is a diagram comparing the inflammatory responses of a microneedle patch (P-MN patch) with an invasive part and a non-invasive part separated, a microneedle patch (MN patch) with microneedles uniformly located without separation of the invasive part and the non-invasive part, and a patch without needles (Patch). FIG. 18A is an image of the microneedle patch (P-MN patch) with an invasive part and a non-invasive part separated, the microneedle patch (MN patch) with microneedles uniformly located without separation of the invasive part and the non-invasive part, and the patch without needles (Patch) stained with hematoxylin and eosin. FIG. 18B is a diagram quantifying neutrophils per unit area for the microneedle patch (P-MN patch) with an invasive part and a non-invasive part separated, the microneedle patch (MN patch) with microneedles uniformly located without separation of the invasive part and the non-invasive part, and the patch without needles (Patch). Next, FIG. 18C is a diagram quantifying plasma cells per unit area for the microneedle patch (P-MN patch) with an invasive part and a non-invasive part separated, the microneedle patch (MN patch) with microneedles uniformly located without separation of the invasive part and the non-invasive part, and the patch without needles (Patch). Referring to FIG. 18, it was confirmed that the number of neutrophils per unit area of the microneedle patch (P-MN patch) with an invasive part and a non-invasive part separated was shown to be the lowest, indicating that the inflammatory response occurred the weakest.

[0071] Figure 19 is a diagram comparing the inflammatory response of a microneedle patch with a distinction between invasive and noninvasive areas (P-MN patch), a microneedle patch with no distinction between invasive and noninvasive areas and evenly positioned microneedles (MN patch), and a patch without needles. Figure 19A shows images of CD3 immunohistochemical staining of a microneedle patch with a distinction between invasive and noninvasive areas (P-MN patch), a microneedle patch with no distinction between invasive and noninvasive areas and evenly positioned microneedles (MN patch), and a patch without needles, and Figure 19B is a diagram quantifying the number of T lymphocytes per unit area for a microneedle patch with a distinction between invasive and noninvasive areas (P-MN patch), a microneedle patch with no distinction between invasive and noninvasive areas and evenly positioned microneedles (MN patch), and a patch without needles.

[0072] Referring to Figure 19, it was confirmed that the number of T lymphocytes per unit area in the microneedle patch (P-MN patch), which has a division between invasive and non-invasive areas, was the lowest, and that the inflammatory reaction was the weakest.

[0073] As described above, the microneedle patch according to the present embodiment includes an invasive portion where the microneedles are located and a non-invasive portion where the microneedles are not located. Therefore, the microneedles can deliver drugs without directly penetrating the affected area, and additional bleeding and inflammatory reactions can be minimized. Such a microneedle patch may be manufactured using a mold including the invasive portion and the non-invasive portion, or may be manufactured by a method of physically removing the microneedles, and the manufacturing method is simple and applicable to affected areas of various shapes.

Claims

1. A base including an invasive part and a non-invasive part, including microneedles located in the invasive part of the base, wherein a drug is loaded in the base, wherein at least a part of the microneedles is loaded with a drug, wherein the non-invasive part has no microneedles located therein, wherein the concentration of the drug loaded in the base is different from the concentration of the drug loaded in the microneedles, wherein the invasive part is provided with a plurality of microneedles, wherein the drug loading state of each of the plurality of microneedles is determined by the distance from the non-invasive part, A microneedle patch.

2. The non-invasive part is located at the center of the base, The microneedle patch according to claim 1, wherein the invasive part is located at the end of the base.

3. The microneedle patch according to claim 1, wherein the invasive part is located surrounding the non-invasive part.

4. The microneedle includes a first part and a second part, The microneedle patch according to claim 1, wherein a drug with a higher concentration than that of the first part is loaded in the second part.

5. The microneedle patch according to claim 1, wherein the base includes a biodegradable polymer.

6. The microneedle patch according to claim 1, wherein the base includes one or more of hyaluronic acid, carboxymethyl cellulose, polyvinyl alcohol, chitosan, collagen, and polyvinyl pyrrolidone.

7. The microneedle patch according to claim 1, wherein at least a part of the base and the microneedles includes the same substance.

8. The microneedle patch according to claim 1, wherein the drug loaded in the microneedles includes a drug having at least one effect of hemostasis or analgesia.

9. The microneedle patch according to claim 1, wherein the drug loaded in the microneedles includes at least one of tranexamic acid, fibrin, thrombin, tannic acid, chitin, lidocaine, salicylic acid, ketoprofen, loxoprofen, flurbiprofen, piroxicam, felbinac, diclofenac diethylammonium, indomethacin, and antihistamine.

10. The microneedle patch according to claim 1, wherein the height of the microneedle is 100 μm to 5000 μm.

11. The radius of the micro-needle is 50 μm to 500 μm, and the micro-needle patch according to claim 1.

12. Preparing a mold including an invasive part with grooves and a non-invasive part without grooves; Applying a polymer onto the mold to form a micro-needle patch including micro-needles and a base, The micro-needle patch includes an invasive part where the micro-needles are located and a non-invasive part where the micro-needles are not located, The base is loaded with a drug, At least a part of the micro-needles is loaded with a drug, The concentration of the drug loaded on the base is different from the concentration of the drug loaded on the micro-needles, The invasive part is provided with a plurality of micro-needles, The loading state of the drug in each of the plurality of micro-needles is determined by the distance from the non-invasive part, A method for manufacturing a micro-needle patch.

13. A non-invasive part is located at the center of the manufactured micro-needle patch, An invasive part is located at the edge of the micro-needle patch, and the method for manufacturing a micro-needle patch according to claim 12.

14. The non-invasive part of the manufactured micro-needle patch is surrounded by the invasive part, and the method for manufacturing a micro-needle patch according to claim 12.

15. The step of forming the micro-needle patch Applying a polymer containing a drug into the grooves of the mold to form a second part of the micro-needles; Applying a polymer onto the mold to form a first part of the micro-needles and the base, and the method for manufacturing a micro-needle patch according to claim 12.

16. Preparing a mold with grooves; Applying a polymer onto the mold to form a base having an invasive part including micro-needles; Removing a part of the micro-needles to form a non-invasive part, The base is loaded with a drug, At least a part of the micro-needles is loaded with a drug, The concentration of the drug loaded on the base is different from the concentration of the drug loaded on the micro-needles, The invasive part is provided with a plurality of micro-needles, The loading state of the drug in each of the plurality of micro-needles is determined by the distance from the non-invasive part, Method for manufacturing a microneedle patch.

17. A non-invasive part is located at the center of the manufactured microneedle patch, The method for manufacturing a microneedle patch according to claim 16, wherein an invasive part is located at the end of the microneedle patch.

18. The step of forming a base having an invasive part including the microneedle includes The step of applying a polymer containing a drug to the groove of the mold to form a second part of the microneedle, The method for manufacturing a microneedle patch according to claim 16, which includes the step of applying a polymer onto the mold to form a first part of the microneedle and the base.

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