Microneedle patch and method for manufacturing the microneedle patch

Abstract

The microneedle patch of the present invention comprises an adhesive sheet that is in close contact with the skin, a needle support placed on the adhesive sheet, and a needle body placed on the needle support and having a pointed end, wherein at least one of the needle support and the needle body contains a swellable polymer material that expands when it comes into contact with bodily fluids.

Description

[Technical Field]

[0001] The present invention relates to a microneedle patch and a method for manufacturing a microneedle patch. [Background technology]

[0002] Recent progress in the development of numerous drugs and physiologically active substances for the treatment of diseases has been remarkable. However, when delivering drugs and physiologically active substances into the body, problems of passing through biological barriers (e.g., skin, oral mucosa, and blood-brain barrier) and drug delivery efficiency still remain to be solved.

[0003] Drugs and biologically active substances are commonly administered orally in tablet or capsule form, but many drugs cannot be effectively delivered by these methods alone because they are digested or absorbed in the gastrointestinal tract or eliminated by hepatic mechanisms. Furthermore, some drugs cannot effectively diffuse across the intestinal mucosa. Patient compliance can also be an issue (e.g., for patients who must take drugs at specific time intervals or who are unable to take drugs).

[0004] Another common technique for delivering drugs and physiologically active substances is the use of a conventional needle, which, while more effective than oral administration, has the drawbacks of causing pain at the injection site, local skin damage, bleeding, and infection at the injection site.

[0005] To solve the above problems, various microneedle patches with microneedles have been developed. Microneedle patches developed so far have mainly been used for in vivo drug delivery, blood sampling, and detection of analytes in the body.

[0006] Unlike conventional needles, microneedles are characterized by the fact that they cause no pain or trauma when penetrating the skin. Microneedles must be sharp enough to penetrate the skin, and must also have sufficient physical hardness to penetrate the 10-20 μm stratum corneum, the strongest barrier in the skin. Furthermore, the appropriate length must also be considered to reach the capillaries and increase the efficiency of drug delivery.

[0007] Conventional microneedles are limited to materials such as silicon, polymers, metals, and glass due to limitations in manufacturing methods, and are complicated due to the use of molding (encapsulation) techniques. They also have drawbacks such as drug denaturation, insufficient hardness, and drug loss due to the long manufacturing time. Therefore, there is a constantly growing need for microneedles that have a small enough diameter to penetrate the skin painlessly and a sufficient length to penetrate deep into the skin, yet are hard enough without any particular limitations on the material and minimize drug loss. Summary of the Invention [Problem to be solved by the invention]

[0008] The present invention was created to solve the above-mentioned problems, and its purpose is to provide a microneedle patch having microneedles formed from a swellable polymer material that expands when it comes into contact with body fluids, and a method for manufacturing the same.

[0009] Another object of the present invention is to provide a microneedle patch that has sharpness and sufficient hardness to allow effective drug delivery, and also has enhanced adhesive strength, and a method for manufacturing the same. [Means for solving the problem]

[0010] The above-mentioned objects of the present invention are achieved by a microneedle patch comprising an adhesive sheet that is in close contact with the skin, a needle support that is placed on the adhesive sheet, and a needle body that is placed on the needle support and has a pointed end, wherein at least one of the needle support and the needle body contains a swellable polymer material that expands when it comes into contact with bodily fluids.

[0011] Here, at least one of the needle support and the needle body may contain a drug, and at least one of the needle support and the needle body may supply the drug while expanding when it comes into contact with bodily fluids.

[0012] At least one of the needle support and the needle body may be formed by solidifying a viscous composition in which a swellable polymer material and a drug are dissolved.

[0013] Furthermore, the needle body may comprise a swellable polymer material and be shaped to have a base diameter D corresponding to the diameter of the bottom surface that contacts the needle support, a needle height H corresponding to the perpendicular distance from the bottom surface to the top end, and a needle diameter N corresponding to the diameter of the tip, and the needle body may expand while maintaining its shape so that at least one of the base diameter, the needle height, and the needle diameter increases when it comes into contact with body fluid.

[0014] On the other hand, upon contact with body fluid, the base diameter and the needle diameter may increase by 1.1 times or more but less than 2 times.

[0015] Furthermore, the needle body comprises a swellable polymer material and is shaped to have a base diameter D corresponding to the diameter of the bottom surface that contacts the needle support, a needle height H corresponding to the perpendicular distance from the bottom surface to the top end, and a needle diameter N corresponding to the diameter of the tip, and when the needle body comes into contact with body fluid, any one of the base diameter, needle height, and needle diameter may increase and the other may decrease.

[0016] Furthermore, the adhesive sheet and the needle support may form a single adhesive surface, the needle support may be inserted into the inside of the adhesive sheet from the adhesive surface, and the needle body may be formed extending outward from the adhesive surface.

[0017] Furthermore, the needle supports may be fitted inside the adhesive sheet and arranged in the form of a plurality of recesses spaced apart from one another, and the needle bodies may be arranged on each of the plurality of needle supports.

[0018] Furthermore, the needle support may be fitted inside the adhesive sheet and arranged in layers extending parallel to one another, and the needle bodies may be arranged in multiple numbers spaced apart from one another on the needle support.

[0019] On the other hand, the above-mentioned objects of the present invention are achieved by a method for manufacturing a microneedle patch, which includes the steps of forming a needle support on a base resin, forming an adhesive sheet on the base sheet so as to cover the needle support, forming a cover resin on top of the adhesive sheet and inverting the needle support and the adhesive sheet so that the base resin is positioned on top, removing the base resin, and forming a needle body on the needle support, wherein at least one of the needle support and the needle body contains a swellable polymer material that expands when it comes into contact with body fluids.

[0020] At least one of the needle support and the needle body may be formed by solidifying a viscous composition in which a swellable polymer material and a drug are dissolved.

[0021] Furthermore, the step of forming the needle body may include providing a pair of structures on the needle support, each of which forms a base needle, moving the pair of structures toward each other so that a pair of base needles formed on each structure come into contact with each other, and moving the pair of structures away from each other so that the pair of base needles adhere to and are pulled by each other, deforming their shapes, and the deformed base needles form the needle body.

[0022] On the other hand, the needle support may include a plurality of supports formed at a distance from one another on the base resin, the adhesive sheet may cover each of the plurality of supports, and the needle body may be formed on each of the plurality of supports.

[0023] The needle body may be formed in a plurality of parts spaced apart from one another on the needle support. [Effects of the Invention]

[0024] The microneedle patch and its manufacturing method of the present invention having the above-mentioned configuration have the advantage that the surface area and volume expand when contacted with body fluids, allowing for effective drug delivery. [Brief explanation of the drawings]

[0025] [Figure 1] 1A to 1C are diagrams showing a schematic diagram of a procedure for producing a microneedle patch sheet according to one embodiment of the present invention. [Figure 2] Plan view of a sheet made according to Figure 1. [Figure 3] FIG. 2 is a diagram showing a schematic diagram of a procedure for producing a microneedle patch according to one embodiment of the present invention using the sheet shown in FIG. 1. [Figure 4] Side view of a microneedle patch fabricated according to the procedure in Figure 3. [Figure 5] 10A to 10C are diagrams showing a schematic diagram of a procedure for producing a microneedle patch sheet according to another embodiment of the present invention. [Figure 6] Plan view of a sheet made according to Figure 5. [Figure 7] FIG. 6 is a diagram showing a schematic procedure for producing a microneedle patch according to another embodiment of the present invention using the sheet shown in FIG. 5. [Figure 8] Side view of a microneedle patch fabricated according to the procedure in Figure 7. [Figure 9] 1 is a diagram showing a schematic diagram of changes in the needle body in a microneedle patch according to one embodiment of the present invention. [Figure 10] Photographs showing an experiment on changes in the needle body in a microneedle patch according to one embodiment of the present invention. [Figure 11] Photographs showing an experiment on changes in the needle body in a microneedle patch according to one embodiment of the present invention. [Figure 12] Photographs showing an experiment on changes in the needle body in a microneedle patch according to one embodiment of the present invention. [Figure 13] Photographs showing an experiment on changes in the needle body in a microneedle patch according to one embodiment of the present invention. [Figure 14] 10A and 10B are diagrams showing schematic changes in the needle body in a microneedle patch according to another embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0026] Hereinafter, a microneedle patch and a method for manufacturing the same according to an embodiment of the present invention will be described in detail with reference to the accompanying drawings.

[0027] Figure 1 is a diagram showing a schematic diagram of the procedure for producing a sheet 190 of a microneedle patch according to one embodiment of the present invention, and Figure 3 is a diagram showing a schematic diagram of the procedure for producing a microneedle patch according to one embodiment of the present invention using the sheet 190 shown in Figure 1.

[0028] A microneedle patch according to one embodiment of the present invention can be formed using the procedures shown in Figures 1 and 3. That is, Figures 1 and 3 are diagrams showing the procedures for manufacturing a microneedle patch of the present invention, and it should be understood that the shape shown in Figure 3(c), which corresponds to the final step, shows microneedle patches 170, 170a.

[0029] First, as shown in Fig. 1(a), a needle support 110 may be formed by spotting onto a first base resin 100. The first base resin 100 corresponds to a sheet temporarily prepared for forming the needle support 110. That is, the first base resin 100 is omitted from the sheet 190 for the finally completed patch.

[0030] The first base resin 100 may be provided in the shape of a flat plate, for example, a synthetic resin, transparent PET film.

[0031] The needle supports 110 may be formed by spotting a large number of needle supports on the first base resin 100. For example, the needle supports 110 may be composed of a plurality of needle supports, including a first support 1101, a second support 1102, and a third support 1103, which are spaced apart from one another. The supports 1101, 1102, and 1103 may be arranged in the same shape as one another or may be arranged in order.

[0032] In this case, the needle supports 110 may be formed by spotting the first viscous composition onto the upper surface of the first base resin 100 at predetermined intervals and solidifying the spots. This allows the supports 1101, 1102, and 1103 to be identical overall, but to be formed into slightly different shapes depending on the influence of adhesive strength, external wind, etc. Details of the first viscous composition that forms the needle supports 110 will be described later.

[0033] Furthermore, the needle supports 110 may be formed into a variety of shapes using a variety of methods on the first base resin 100. Each of the supports 1101, 1102, and 1103 may form a roughly circular, elliptical, or curved surface due to surface tension, and may be formed into a hemispherical shape (hereinafter referred to as "hemispherical") on the first base resin 100.

[0034] In this case, the arrangement, intervals and number of the supports 1101, 1102 and 1103 may be varied as necessary. For example, the supports 1101, 1102 and 1103 may be regularly arranged to form a lattice.

[0035] 1(b), an adhesive sheet 120 may be formed on the first base resin 100 and the needle support 110. That is, the adhesive sheet 120 may be formed on the first base resin 100 so as to cover the needle support 110. As a result, the needle support 110 is disposed between the adhesive sheet 120 and the first base resin 100.

[0036] The adhesive sheet 120 is formed above the needle support 110 so as to completely cover the needle support 110 .

[0037] Next, in the state shown in Fig. 1(b), a first cover resin 130 is attached to the top of the adhesive sheet 120. After this, the needle support 110 and the adhesive sheet 120 are inverted and arranged as shown in Fig. 1(c) so that the first base resin 100 is arranged on top. In other words, the shape shown in Fig. 1(b) is inverted and arranged so that the first cover resin 130 is located at the bottom and the first base resin 100 is located on top.

[0038] In this case, the first cover resin 130 corresponds to the bottom surface, and the first base resin 100 corresponds to the top surface. The first cover resin 130 may be provided in the shape of a flat plate, like the first base resin 100, and may be provided in the shape of a synthetic resin or a transparent PET film, for example. That is, the first cover resin 130 and the first base resin 100 may be provided with the same or different structures, and may be given different names for ease of explanation.

[0039] As shown in (d) of Figure 1, the first base resin 100 is removed, and the needle support 110 and the adhesive sheet 120 are arranged in a predetermined shape on top of the first cover resin 130 to form a microneedle patch sheet 190.

[0040] FIG. 2 is a plan view photograph of a sheet 190 made according to the procedure of FIG.

[0041] 1 and 2, the needle support 110 is disposed in a state of being fitted inside the adhesive sheet 120. For example, it can be said that the needle support 110 is disposed by being fitted into an engraved pattern recessed inside the adhesive sheet 120. In this case, the engraved pattern may be formed, for example, in an approximately hemispherical, curved, or semi-elliptical shape.

[0042] Here, the needle support 110 being hemispherical is merely an example, and the needle support 110 may be formed in a variety of shapes, such as a curved shape, a semi-elliptical shape, etc., in addition to a hemispherical shape.

[0043] Furthermore, the needle support 110 may be fitted into the adhesive sheet 120 to form one surface of the adhesive sheet 120. As described above, since the first base resin 100 is arranged in a flat shape, the needle support 110 and the adhesive sheet 120 adhered thereto can form one flat surface. When the first base resin 100 is removed, the one surface formed by the needle support 110 and the adhesive sheet 120 is exposed. Hereinafter, this one surface will be referred to as an adhesive surface. For example, the adhesive surface may refer to the surface that comes into contact with the skin.

[0044] Furthermore, as described above, the supports 1101, 1102, and 1103 are spaced apart from one another, with the adhesive sheet 120 exposed and disposed between the supports 1101, 1102, and 1103. As a result, when the adhesive surface comes into contact with the skin, adhesive strength can be increased via the adhesive sheet 120 disposed between the supports 1101, 1102, and 1103. In addition, the supports 1101, 1102, and 1103 can be more effectively adhered, thereby increasing the efficiency of medication.

[0045] Figure 3 is a diagram showing a schematic diagram of a procedure for producing microneedle patches 170, 170a according to one embodiment of the present invention using the sheet shown in Figure 1. The following will be described in order.

[0046] 3(a), a second viscous composition for forming a base needle 140 may be spotted on the upper part of the needle support 110. The second viscous composition may be composed of the same material as the first viscous composition for the needle support 110, or a different material from the first viscous composition for the needle support 110. Details of this will be described later.

[0047] The base needles 140 may be formed in a number corresponding to the needle supports 110. For example, the base needles 140 may be formed in a plurality of numbers, each including a first base 1401, a second base 1402, and a third base 1403 formed on each support 1101, 1102, and 1103. In detail, the first base 1401 is formed on the top of the first support 1101, the second base 1402 is formed on the top of the second support 1102, and the third base 1403 is formed on the top of the third support 1103.

[0048] Although not shown, it is also possible for a plurality of base needles 140 to be spotted on the upper surface of one needle support 110. In this case, the base needles 140 may be spotted separately on the upper surface of one needle support 110.

[0049] Meanwhile, the supports 1101, 1102, and 1103 and the bases 1401, 1402, and 1403 are named differently for ease of explanation, but they correspond to the same component. Furthermore, the supports 1101, 1102, and 1103 and the bases 1401, 1402, and 1403 are formed from viscous compositions and may be formed into slightly different shapes, but this is not related to the characteristics of the present invention.

[0050] In other words, base needles 140 may be spotted on the upper surfaces of a plurality of supports 1101, 1102, and 1103 spaced apart from one another, and the base needles 140 may protrude above the adhesive surface formed by the needle supports 110 and the adhesive sheet 120. Hereinafter, the shape shown in Figure 3(a) will be referred to as a structure 150.

[0051] Next, as shown in Fig. 3(b), a pair of structures 150, 150a are arranged facing each other. At this time, each structure 150, 150a is formed in the same manner as in Fig. 3(a) described above, and corresponds to the same components as each other.

[0052] Thus, the first structure 150 comprises a first needle support 110, a first adhesive sheet 120 and a first base needle 140, and the second structure 150a comprises a second needle support 110a, a second adhesive sheet 120a and a second base needle 140a.

[0053] Specifically, the first structure 150 and the second structure 150a are arranged so that the first base needle 140 and the second base needle 140a face each other. That is, the first structure 150 and the second structure 150a are arranged so that the adhesive surface of the first structure 150 and the adhesive surface of the second structure 150a face each other. Then, the first structure 150 and the second structure 150a move relative to each other, and the first base needle 140 and the second base needle 140a come into contact with each other.

[0054] For example, the second structure 150a is placed with its adhesive surface facing upward. Then, the first structure 150 is placed on top of the second structure 150a with its adhesive surface facing downward. Then, the first structure 150 is lowered so that the first base needle 140 and the second base needle 140a come into contact with each other.

[0055] At this time, the first needle support 110 and the second needle support 110a, the first adhesive sheet 120 and the second adhesive sheet 120a are arranged so as not to contact each other. Furthermore, the needle supports 110, 110a and the adhesive sheets 120, 120a are completely solidified and do not deform even when they contact each other.

[0056] In contrast, the first base needle 140 and the second base needle 140a may be in contact with each other and deformed in shape, corresponding to a state in which the viscous composition is not solidified. That is, the structures 150, 150a are disposed in contact with each other when the base needles 140, 140a are not completely solidified.

[0057] 3(c), the structures 150, 150a are moved relative to each other in directions away from each other, whereby the base needles 140, 140a are pulled toward each other and solidified.

[0058] The base needles 140, 140a adhered to each other undergo a pulling and solidification process to form the needle bodies 160, 160a, thereby manufacturing the microneedle patches 170, 170a of the present invention. That is, the microneedle patches 170, 170a include the needle supports 110, 110a, the adhesive sheets 120, 120a, and the needle bodies 160, 160a.

[0059] The procedure for forming the needle bodies 160, 160a will be described in more detail below.

[0060] As described above, the first base needle 140 and the second base needle 140a are arranged in an adhesive state to each other, and the first needle support 110 and the first adhesive sheet 120 are moved relatively in a direction away from the second needle support 110a and the second adhesive sheet 120a.

[0061] As a result, the adhered base needles 140, 140a move away from each other, and the ends of the needles 140, 140a are stretched by the adhesive force, reducing their radii. Eventually, the needles 140, 140a are separated into a pair, forming needle bodies 160, 160a each with a cutting edge.

[0062] For example, as shown in FIG. 3, the adhesive end of a generally hemispherical base needle 140, 140a is pulled and deformed into a generally conical needle body 160, 160a.

[0063] That is, the needle bodies 160, 160a can be formed by pulling the base needles 140, 140a adhered to each other by a desired length at a predetermined speed. For example, the base needles 140, 140a adhered to each other are 1) primarily pulled at a first speed by a length corresponding to a first length (primary pulling), 2) stopped pulling and waited for a predetermined time (standby), 3) secondarily pulled at a second speed by a second length (secondary pulling), and 4) separated from each other (cutting). In the separating or cutting step, the base needles 140, 140a may be cut by quickly moving them in a completely solidified state, or may be cut using a cutting tool such as a laser.

[0064] For example, the base needles 140, 140a that are adhered to each other are pulled by an amount corresponding to 10 to 5000 μm at a speed of 0.8 to 600,000 μm / s without blowing air, and then the pulling is stopped and a wait is held for 1 to 100 seconds. Then, while blowing air at a speed of 1 to 100 m / s at the viscous composition, the base needles 140, 140a are secondarily pulled by an amount corresponding to 10 to 5000 μm at a speed of 0.8 to 600,000 μm / s, and then the viscous composition is solidified and cut while blowing air at a speed of 5 to 100 m / s.

[0065] In this case, the first speed, first length, waiting time, second speed, second length, and whether or not to blow air may be set differently as needed, and this can be determined depending on the desired result. In particular, the longer the waiting time after the first pulling is stopped, the larger the diameter of the middle portion and the greater the strength may become. The above method is described in detail in Korean Patent Registration No. 10-1254240 by the applicant.

[0066] In short, the microneedle patches 170, 170a are formed as follows: 1) the needle support 110 is formed on top of the first base resin 100; 2) the adhesive sheet 120 is formed on top of the first base resin 100 to cover the needle support 110; 3) the first cover resin 130 is formed on the top surface of the adhesive sheet 120 and placed upside down; 4) the first base resin 100 is removed to expose the adhesive surface; 5) a pair of structures 150 are provided, each having the base needles 140 formed on the adhesive surface corresponding to the position of the needle support 110; 6) the pair of structures 150, 150a are moved relatively toward each other so that the base needles 140, 140a are adhered to each other; and 7) the structures 150, 150a are moved relatively toward each other again, and the adhered base needles 140, 140a are pulled together to form the needle bodies 160, 160a.

[0067] On the other hand, in the embodiment of Figure 3 described above, both the upper and lower structures 150, 150a are shown to have the base needles 140, 140a formed by spotting, but the present invention is not limited to this in any way.

[0068] For example, although not shown, the second base needle 140a may be spotted only on the second structure 150a located at the bottom. That is, the first needle support 110 of the first structure 150 at the top may not have a base needle spotted thereon. In this case, when the first structure 150 and the second structure 150a move relatively toward each other, the surface of the first needle support 110 of the first structure 150 may move to contact the second base needle 140a of the second structure 150a. After the surface of the first needle support 110 of the first structure 150 contacts the second base needle 140a of the second structure 150a, the first structure 150 and the second structure 150a move relatively away from each other to pull the second base needle 140a. This method is substantially the same as in the above-described embodiment, and therefore will not be described again.

[0069] FIG. 4 is a side view of a microneedle patch prepared according to the procedure of FIG.

[0070] As shown in Fig. 4, a needle body 160 is formed. Meanwhile, the needle body 160 in Fig. 4 is formed from a viscous composition containing chitosan as a swellable polymer material, which will be described later. Details of such a swellable polymer material will be described later.

[0071] Meanwhile, the shapes of the microneedle patches 170 and 170a described above are merely exemplary, and the microneedles of the present invention can be manufactured in a wide variety of shapes. Microneedles having needle structures of other shapes will be described below. However, the microneedle patches 270 and 270a described below can be manufactured using the same procedures as the microneedle patches 170 and 170a described above. Therefore, the same procedures will be referred to in the above description and detailed descriptions will be omitted, and corresponding components will be given the same names and distinguished by using reference numerals.

[0072] Figure 5 is a diagram showing a schematic diagram of the procedure for forming a sheet 290 of a microneedle patch according to another embodiment of the present invention, and Figure 7 is a diagram showing a schematic diagram of the procedure for producing microneedle patches 270, 270a according to another embodiment of the present invention using the sheet 290 shown in Figure 5.

[0073] Microneedle patches 270, 270a according to other embodiments of the present invention may be formed using the procedures shown in Figures 5 and 7. That is, Figures 5 and 7 are diagrams showing the procedures for manufacturing microneedle patches 270, 270a according to the present invention, and it should be understood that the shape shown in Figure 7(c), which corresponds to the final step, shows the microneedle patches 270, 270a.

[0074] 5(a), a third needle support 210 may be formed on the second base resin 200. The third needle support 210 may extend along the top of the second base resin 200. In this case, the third needle support 210 may be formed by coating the first viscous composition on the top of the second base resin 200.

[0075] 5(b), an adhesive sheet 220 may be formed on the second base resin 200 and the third needle support 210. That is, the adhesive sheet 220 may be formed on the second base resin 200 so as to cover the third needle support 210. As a result, the third needle support 210 is disposed between the adhesive sheet 220 and the second base resin 200.

[0076] Thereafter, in the state shown in Fig. 5(b), the second cover resin 230 is placed on top of the adhesive sheet 220, and then the second base resin 200 is turned over so that it is placed on top, as shown in Fig. 5(c). That is, the third needle support 210 and the adhesive sheet 220 are placed upside down.

[0077] Next, as shown in FIG. 5(d), the upper second base resin 200 is removed, and the third needle support 210 and the adhesive sheet 220 are arranged in a predetermined shape.

[0078] FIG. 6 is a plan view of a sheet 290 made according to FIG.

[0079] 5 and 6, the third needle support 210 is inserted into the adhesive sheet 220 and arranged in a single layer, i.e., in a layer extending in parallel. In other words, the third needle support 210 is disposed in a state in which it is entirely inserted inside the adhesive sheet 220. For example, the third needle support 210 may be disposed in a flat plate shape recessed into the adhesive sheet 220. In this case, the adhesive sheet 220 may be exposed along the periphery of the third needle support 210.

[0080] In addition, the third needle support 210 is fitted into the adhesive sheet 220 to form one surface of the adhesive sheet 220. As described above, since the second base resin 200 is arranged in a flat shape, the third needle support 210 and the adhesive sheet 220 adhered thereto can form one flat surface. Hereinafter, such one surface will be referred to as the adhesive surface. For example, the adhesive surface refers to the surface that comes into contact with the affected area.

[0081] Figure 7 is a diagram showing a schematic diagram of a procedure for producing microneedle patches 270, 270a according to one embodiment of the present invention using the sheet 290 shown in Figure 5. The following will be described in order.

[0082] 7(a), a second viscous composition for forming a base needle 240 may be spotted on the top of the third needle support 210. The second viscous composition may be composed of the same material as the first viscous composition for the third needle support 210, or a different material from the first viscous composition for the third needle support 210. This will be described in detail later.

[0083] The base needle 240 may be formed in plural on the third needle support 210. For example, the base needle 240 may include a first base 2401, a second base 2402, and a third base 2403 formed separately from each other. Each of the bases 2401, 2402, and 2403 may be formed in a slightly different shape, but this is not related to the characteristics of the present invention.

[0084] Unlike the needle support 110 described above, the third needle support 210 is formed in the shape of a flat sheet, which allows multiple base needles 240 to be formed on one third needle support 210. This shape has the advantages of being easier to manufacture and being able to more effectively support the needle bodies 260, 260a, which will be described later.

[0085] In other words, a plurality of base needles 240 may be spotted apart from one another on the upper surface of the third needle support 210, and the base needles 240 may protrude above the adhesive surface formed by the third needle support 210 and the adhesive sheet 220. Hereinafter, the shape shown in Figure 7(a) will be referred to as a structure 250.

[0086] Next, as shown in Fig. 7(b), a pair of structures 250, 250a are arranged facing each other. At this time, each structure 250, 250a is formed in the same manner as in Fig. 7(a) described above, and corresponds to the same components as each other.

[0087] Therefore, the third structure 250 comprises a third needle support 210, a third adhesive sheet 220 and a third base needle 240, and the fourth structure 250a comprises a fourth needle support 210a, a fourth adhesive sheet 220a and a fourth base needle 240a.

[0088] Specifically, the third structure 250 and the fourth structure 250a are arranged so that the third base needle 240 and the fourth base needle 240a face each other. That is, the adhesive surface of the third structure 250 and the adhesive surface of the fourth structure 250a face each other. Then, the third structure 250 and the fourth structure 250a move relative to each other, and the third base needle 240 and the fourth base needle 240a come into contact with each other.

[0089] For example, the fourth structure 250a is placed with its adhesive surface facing upward. Then, the third structure 250 is placed on top of the fourth structure 250a with its adhesive surface facing downward. Then, the third structure 250 is lowered so that the third base needle 240 and the fourth base needle 240a come into contact with each other.

[0090] At this time, the third needle support 210 and the second needle support 210a, the first adhesive sheet 220 and the second adhesive sheet 220a are arranged so as not to contact each other. Furthermore, the needle supports 210, 210a and the adhesive sheets 220, 220a are completely solidified and do not deform even when they contact each other.

[0091] In contrast, the third base needle 240 and the fourth base needle 240a may be in contact with each other and deformed in shape, corresponding to a state in which the viscous composition is not solidified. That is, the structures 250, 250a are disposed in contact with each other when the base needles 240, 240a are not completely solidified.

[0092] 7(c), the structures 250, 250a are moved relative to each other in directions away from each other, whereby the base needles 240, 240a are pulled toward each other and solidified.

[0093] The base needles 240, 240a adhered to each other undergo a pulling and solidification process to form the needle bodies 260, 260a, thereby manufacturing the microneedle patches 270, 270a of the present invention. That is, the microneedle patches 270, 270a include the needle supports 210, 210a, the adhesive sheets 220, 220a, and the needle bodies 260, 260a.

[0094] The procedure for forming the needle bodies 260, 260a has been described above in the section on the previous embodiment, and therefore a repeated description will be omitted.

[0095] In this way, the microneedle patches 270, 270a can be formed with needle supports 210, 210a having a different shape from the microneedle patches 170, 170a described above. Furthermore, the microneedle patches 270, 270a can be formed with needle bodies 260, 260a having the same shape as the microneedle patches 170, 170a described above. The needle bodies 160, 160a, 260, 260a will be described in detail below.

[0096] FIG. 8 is a side view photograph of a microneedle patch fabricated according to the procedure of FIG.

[0097] As shown in Fig. 8, a needle body 260 is formed. Meanwhile, in Fig. 8(a), the needle body 260 is formed from a viscous composition containing chitosan as a swellable polymer material, which will be described later, and in Fig. 8(b), the needle body 260 is formed from a viscous composition containing polyvinyl alcohol (PVA) as a swellable polymer material, which will be described later. Details of such swellable polymer materials will be described later.

[0098] Figure 9 is a diagram showing a schematic diagram of changes in the needle body of a microneedle patch according to one embodiment of the present invention. Figures 9(a) and 9(b) show only the needle bodies 160, 160a, 260, and 260a of the microneedle patches 170, 170a, 270, and 270a described above. Details of one needle body 160 will be described below, and this description will be incorporated herein by reference.

[0099] 9, the needle body 160 may be disposed in a generally circular cone shape. That is, the needle body 160 may be disposed in a shape in which the bottom surface is generally circular and the diameter gradually narrows toward the top, forming a pointed tip. Hereinafter, the diameter of the bottom surface of the needle body 160 will be referred to as the base diameter D, and the perpendicular distance from the bottom surface to the top end will be referred to as the needle height H. Hereinafter, the base diameter D should be understood to be the diameter of the cross section of the part that contacts the needle support 110. The needle height H should be understood to be the perpendicular distance at the needle support 110 or the adhesive surface.

[0100] As described above, the needle body 160 corresponds to a component formed by solidifying a viscous composition. Therefore, the bottom surface of the needle body 160 may not be perfectly circular, and the base diameter D is determined as a rough value. The needle height H may be formed to a set value as needed, but may have a certain error during the pulling or cutting step.

[0101] Meanwhile, the needle body 160 corresponds to a shape formed by cutting by pulling. As a result, the upper end is not a point but forms a predetermined tensile fracture surface, and the generatrix is ​​formed in a curved shape. In this case, the bending rate of the generatrix can be determined by the pulling speed, etc. in the above-described needle body 160 formation procedure.

[0102] As described above, the needle body 160 may be formed by being pulled at a first speed and then pulled again at a second speed. In this case, the second speed may be faster than the first speed. As a result, as shown in FIG. 9, the needle body 160 can form a pointed end that gradually becomes thinner as it advances toward the upper end. In this case, the diameter of the portion pulled at the second speed is referred to as the needle diameter N. Specifically, the needle diameter N corresponds to the diameter of the pointed end of the needle body 160 and can be calculated as its average or median value.

[0103] In addition, the upper end of the needle body 160 may not form a complete shape up to a certain portion due to the formation of a fracture surface. Therefore, the needle diameter N can be replaced with the diameter of the upper end of the needle body 160.

[0104] Meanwhile, at least one of the needle body 160 and the needle support 110 may contain a drug to be administered to the human body. That is, when the microneedle patch 170 according to the present invention is attached to the human body, the drug contained in at least one of the needle body 160 and the needle support 110 can be injected and delivered to the human body.

[0105] For this purpose, at least one of the needle body 160 and the needle support 110 may include swellable hydrophilic polymers that expand when in contact with body fluids.

[0106] When the microneedle patch 170 according to the present invention is attached to the human body and the needle body 160 or the needle support 110 comes into contact with bodily fluids and expands, the drug contained inside the needle body 160 or the needle support 110 can be delivered to the inside of the human body. In this case, the needle body 160 or the needle support 110 can maintain its shape or form without being decomposed even after coming into contact with bodily fluids. In other words, even when the needle body 160 or the needle support 110 expands, it can maintain its basic shape or form.

[0107] Specifically, at least one of the needle body 160 and the needle support 110 may contain a swellable polymer material such as polyvinyl alcohol (PVA) or chitosan. PVA and chitosan are merely examples of swellable polymer materials, and the swellable polymer material is not limited thereto.

[0108] As a result, at least one of the first viscous composition for the needle support 110 and the second viscous composition for the needle body 160 may contain a drug and a swellable polymeric material. In this case, the first viscous composition and the second viscous composition may contain the same swellable polymeric material, or may contain different swellable polymeric materials.

[0109] The drug-containing viscous composition forming the needle body 160 or the needle support 110 will now be described.

[0110] First, we will explain the case where distilled water (Di water) is used as the solvent and PVA is used as the polymer material. 1) Distilled water (50-80% by weight of Di water) is added to a mixer and heated to 50-100°C. 2) PVA (5-30% by weight) is added and stirred at 200-800 RPM until completely dissolved. 3) After complete dissolution, a water-soluble polymer, such as hydroxypropyl methylcellulose (HPMC) (2-20% by weight) or carboxymethyl cellulose (CMC) (2-20% by weight), is added, heated to 50-100°C, and stirred at 200-800 RPM. 4) Next, while maintaining the temperature at 50-100°C, a drug (API: Active Pharmaceutical Ingredient), such as donepezil (5-30% by weight), is added and stirred at 200-800 RPM. 5) After complete dissolution, glycerin (0.3 to 10% by weight) is added at a temperature of 30 to 80°C and stirred at a speed of 100 to 600 RPM until completely dissolved.

[0111] The following describes a case where an aqueous acetic acid solution is used as the solvent and chitosan is used as the polymer material. 1) An aqueous acetic acid solution (50-80% by weight) is placed in a mixer and heated to 30-80°C. 2) Chitosan (5-30% by weight) is added and stirred at 200-800 RPM until completely dissolved. 3) After complete dissolution, a water-soluble polymer, such as HPMC (hydroxypropyl methylcellulose) (2-20% by weight) or CMC (carboxy methylcellulose) (2-20% by weight), is added, heated to 30-80°C, and stirred at 200-800 RPM. 4) Next, while maintaining the temperature at 50-100°C, a drug (API: Active Pharmaceutical Ingredient), such as donepezil (5-30% by weight), is added and stirred at 200-800 RPM. 5) After complete dissolution, glycerin (0.3 to 10 wt %) is added at 30 to 80°C and stirred at a speed of 100 to 600 RPM until completely dissolved.

[0112] Donepezil, which corresponds to the aforementioned drug, is merely a drug used to test the microneedle patch 170 according to the present invention, and the present invention is not limited to the drug. For example, the type of drug that can be contained in the needle body 160 or the needle support 110 is not particularly limited.

[0113] Alternatively, the needle support 110 or the base needle may be formed according to the procedure described above using the viscous composition formed as described above, and then deformed to form the needle body 160. At least one of the needle support 110 or the needle body 160 formed in this manner has the property of expanding or swelling when combined with body fluids.

[0114] For example, the needle support 110 and the needle body 160 may be formed using the same viscous composition or different viscous compositions, where the same viscous composition may be defined as a composition containing the same swellable polymer material and further containing a drug.

[0115] In addition, different viscous compositions may be defined as compositions in which only one of the compositions for the needle support 110 and the needle body 160 contains a swellable polymer material, or compositions in which the swellable polymer materials contained in the compositions are different, or compositions in which a drug is contained or not.

[0116] For example, the needle support 110 may include PVA and the needle body 160 may include chitosan, or vice versa. Additionally, at least one of the needle support 110 and the needle body 160 may contain a drug.

[0117] The following describes in detail the case where the needle body 160 contains a swellable polymer material. Figure 9(a) above shows the original state of the needle body 160, and Figure 9(b) shows the state of the needle body 160 after coming into contact with body fluid and expanding.

[0118] The needle body 160 can change its base diameter D, needle height H, and needle diameter N when combined with body fluid. In particular, at least one of the base diameter D, needle height H, and needle diameter N can increase in the range of 1 to 200%. As a result, the surface area and volume of the needle body 160 can be increased.

[0119] For example, the needle body 160 may be formed with a base diameter D of approximately 807 μm, a needle height H of approximately 413 μm, and a needle diameter N of approximately 90 μm. When combined with bodily fluid, the needle body 160 changes to a base diameter D' of approximately 1048 μm, a needle height H' of approximately 426 μm, and a needle diameter N of approximately 158 μm. As a result, the base diameter D increases by approximately 30%, and the needle diameter N increases by approximately 76%. It can be seen that the needle height H remains almost unchanged, but the bulk and surface area of ​​the needle body 160 increase as a result.

[0120] 10 to 13 are photographs showing an experiment on the change in the needle body of a microneedle patch according to one embodiment of the present invention.

[0121] 10 and 11 show the needle body 160 containing chitosan, a swellable polymer material. Fig. 10 shows the original state of the needle body 160, and Fig. 11 shows the state after contact with a body fluid replicating solution (PBS: Phosphate Buffer Saline).

[0122] 10 and 11, for the needle body shown on the left, the base diameter was changed from 809.15 μm to 1029.4 μm, the needle height H was changed from 404.91 μm to 407.84 μm, and the needle diameter N was changed from 96.13 μm to 171.90 μm. Also, for the needle body shown on the right, the base diameter was changed from 806.33 μm to 1068.94 μm, the needle height H was changed from 423.85 μm to 445.7 μm, and the needle diameter N was changed from 84.53 μm to 145.65 μm.

[0123] 12 and 13 show the needle body 160 containing PVA, a swellable polymer material. Fig. 12 shows the original state of the needle body 160, and Fig. 13 shows the state after contact with a body fluid replicating solution (PBS: Phosphate Buffer Saline).

[0124] 12 and 13, for the needle body shown on the left, the base diameter was changed from 873.61 μm to 1002.10 μm, the needle height H was changed from 614.74 μm to 614.67 μm, and the needle diameter N was changed from 123.8 μm to 155.85 μm. Also, for the needle body shown on the right, the base diameter was changed from 888.55 μm to 1044.70 μm, the needle height H was changed from 611.85 μm to 607.46 μm, and the needle diameter N was changed from 123.84 μm to 167.5 μm.

[0125] These experimental results confirm that the surface area and volume of the needle body increase when it comes into contact with body fluid. At this time, the needle height H remains relatively constant, but the base diameter D and needle diameter N increase, confirming that the needle body expands laterally. In other words, when it comes into contact with body fluid, the base diameter D and needle diameter N increase by more than 1.1 times but less than 2 times, and the needle height H changes relatively little.

[0126] Furthermore, as described above, at least one of the needle support 110 and the needle body 160 may contain a drug. That is, in the microneedle patch 170 of the present invention, 1) the needle body 160 may contain a drug, 2) the needle support 110 may contain a drug, or 3) both the needle body 160 and the needle support 110 may contain a drug.

[0127] Table 1 below shows experimental values ​​obtained by measuring the actual drug content when a drug is contained in the needle support or needle body.

[0128] [Table 1]

[0129] In the cases of A and B, 4 mg of drug was included only in the viscous composition for forming the needle-shaped support, and the amount of drug was measured again after the needle-shaped support was actually formed. The experiment was conducted assuming that A contained chitosan, and B contained PVA. As a result, in the case of A, 3.88 mg of drug was measured, which is 97.0% of the theoretical value, and in the case of B, 3.97 mg of drug was measured, which is 99.2% of the theoretical value. This shows that the drug is effectively contained even when the drug is only contained in the needle-shaped support.

[0130] In the cases of C and D, 4 mg of drug was included only in the viscous composition for forming the needle body, and the amount of drug was measured again after the needle body was actually formed. The experiment was conducted assuming that C contained chitosan, and D contained PVA. As a result, in the case of C, 3.95 mg of drug was measured, which is 98.7% of the theoretical value, and in the case of D, 3.96 mg of drug was measured, which is 99.0% of the theoretical value. In other words, it can be seen that the drug is effectively contained even when the drug is only contained in the needle body.

[0131] In the cases of E and F, 4.75 mg of drug was included in the viscous composition for forming the needle support and needle body, and the amount of drug was measured again after the needle support and needle body were actually formed. The experiment was conducted assuming that E contained chitosan, and F contained PVA. As a result, in the case of E, 4.68 mg of drug was measured, which is 98.5% of the theoretical value, and in the case of F, 4.68 mg of drug was measured, which is 98.6% of the theoretical value. In other words, it can be seen that the drug was effectively contained even when both the needle support and the needle body contained the drug.

[0132] On the other hand, FIG. 14 is a diagram schematically showing changes in the needle body in a microneedle patch according to another embodiment of the present invention.

[0133] Referring to Figure 14, according to the applicant's experiments, when the needle body comes into contact with body fluid, it can be deformed so that any one of the base diameter D, the needle height H, and the needle diameter N increases and the other decreases.

[0134] For example, the shape of FIG. 14(a) can be deformed to that of FIG. 14(b) when it comes into contact with body fluid. It can be seen that the needle body shown in FIG. 14(b) has a relatively increased base diameter D'' compared to the shape of FIG. 14(a), but the needle height H'' is reduced. In this case, the needle diameter N'' may be approximately the same or even larger.

[0135] Furthermore, the shape of Figure 14(a) can be deformed to the shape of Figure 14(c) when it comes into contact with body fluids. It can be seen that the needle body shown in Figure 14(c) has a relatively reduced base diameter D''' compared to the shape of Figure 14(a), but the needle height H''' is increased. In this case, the needle diameter N''' may be approximately the same or even larger.

[0136] In the needle bodies shown in (b) and (c) of Figure 14, when they come into contact with body fluids, any one of the base diameter D, the needle height H, and the needle diameter N increases and expands, allowing the drug contained in the needle body to be injected into the human body.

[0137] In other words, at least one of the needle support and the needle body of the present invention may contain a swellable polymer material or a drug. In this case, the needle support and the needle body should be understood as a single "microneedle." The microneedle refers to a component that is at least partially inserted into the skin to inject a drug.

[0138] For example, if the needle support and the needle body are formed from the same viscous composition, each formed using the manufacturing procedures described above, the needle support and the needle body can form an integral microneedle.

[0139] Although the present invention has been described above with reference to preferred embodiments, those skilled in the art will be able to implement the present invention with various modifications and variations without departing from the spirit and scope of the present invention as set forth in the claims below. Therefore, as long as the modified embodiments essentially include the elements of the claims of the present invention, they should all be considered to be included in the technical scope of the present invention.

Claims

1. An adhesive sheet that adheres to the skin, a needle support placed on the adhesive sheet; a needle body disposed on the needle support and having a pointed end; Equipped with A microneedle patch, characterized in that at least one of the needle support and the needle body contains a swellable polymer material that expands when it comes into contact with body fluids.

2. At least one of the needle support and the needle body contains a drug; The microneedle patch according to claim 1 , wherein at least one of the needle support and the needle body supplies the drug while expanding when contacted with body fluid.

3. The microneedle patch of claim 1, wherein at least one of the needle support and the needle body is formed by solidifying a viscous composition in which a swellable polymer material and a drug are dissolved.

4. the needle body includes a swellable polymer material and is shaped to have a base diameter (D) corresponding to the diameter of the bottom surface that contacts the needle support, a needle height (H) corresponding to the perpendicular distance from the bottom surface to the top end, and a needle diameter (N) corresponding to the diameter of the pointed end, The microneedle patch of claim 1 , wherein the needle body increases at least one of the base diameter, the needle height, and the needle diameter when in contact with bodily fluid.

5. The microneedle patch of claim 4, wherein the base diameter and the needle diameter increase by 1.1 times or more and less than 2 times when contacted with body fluid.

6. the needle body includes a swellable polymer material and is shaped to have a base diameter (D) corresponding to the diameter of the bottom surface that contacts the needle support, a needle height (H) corresponding to the perpendicular distance from the bottom surface to the top end, and a needle diameter (N) corresponding to the diameter of the pointed end, The microneedle patch of claim 1 , wherein when the needle body comes into contact with bodily fluid, one of the base diameter, the needle height, and the needle diameter increases and the other decreases.

7. the adhesive sheet and the needle support form one adhesive surface; The microneedle patch of claim 1, wherein the needle support is positioned by being inserted into the inside of the adhesive sheet from the adhesive surface, and the needle body is formed by extending outward from the adhesive surface.

8. The needle supports are fitted inside the adhesive sheet and arranged in a plurality of recesses spaced apart from one another; The microneedle patch according to claim 7 , wherein the needle bodies are respectively disposed on the plurality of needle supports.

9. The needle supports are fitted inside the adhesive sheet and arranged in layers extending parallel to each other, The microneedle patch according to claim 7, wherein the needle bodies are arranged in a plurality at intervals on the needle support.

10. forming a needle support on a base resin; forming an adhesive sheet on the base sheet so as to cover the needle support; forming a cover resin on the adhesive sheet, and then turning the needle support and the adhesive sheet upside down so that the base resin is disposed on top; removing the base resin; forming a needle body on the needle support; Including, A method for manufacturing a microneedle patch, characterized in that at least one of the needle support and the needle body contains a swellable polymer material that expands when it comes into contact with body fluids.

11. The method for manufacturing a microneedle patch described in claim 10, characterized in that at least one of the needle support and the needle body is formed by solidifying a viscous composition in which a swellable polymer material and a drug are dissolved.

12. The step of forming the needle body includes: a pair of structures each having a base needle formed on the needle support; Relatively moving the pair of structures toward each other so that the pair of base needles formed on each of the pair of structures come into contact with each other; The pair of base needles are attached to each other and pulled, and the pair of structures are moved relatively away from each other so that the shape is deformed; The method for manufacturing a microneedle patch according to claim 10, wherein the deformed base needle forms the needle body.

13. the needle support comprises a plurality of supports formed on the base resin at intervals; the adhesive sheet covers each of the plurality of supports, The method for manufacturing a microneedle patch according to claim 10, wherein the needle bodies are formed on the plurality of supports, respectively.

14. The needle body is The method for manufacturing a microneedle patch according to claim 10, wherein a plurality of needles are formed on the needle support and spaced apart from each other.

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