Microneedle film and method for manufacturing same

Abstract

A microneedle membrane includes a substrate layer, a plurality of microneedles, and a plurality of microstructures. The substrate layer is provided with a first surface and a second surface opposite to the first surface, the first surface is rough relative to the second surface, and the plurality of microneedles are arranged on the substrate layer; wherein the plurality of microneedles are distributed on the first surface of the substrate layer at intervals, the plurality of microstructures are formed on the first surface, and the plurality of microstructures respectively correspond to each microneedle; wherein each microstructure comprises a plurality of grooves, each groove forms a geometrical shape or a line segment on the first surface, and the line segment comprises a straight line and a curve.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of transdermal drug delivery, and in particular to a microneedle film and a manufacturing method thereof. BACKGROUND

[0002] Microneedle patch (MNP) is a new type of transdermal drug delivery system (TDDS). The microneedles on the patch are very short and do not touch the nerves, so there is no pain like subcutaneous injection, and they can carry bioactive ingredients or drugs through the stratum corneum into the human body. MNP technology can be used in various fields such as medical beauty, medicine, preventive medicine, etc. SUMMARY

[0003] The present application provides a microneedle film with good forming rate.

[0004] The present application also provides a manufacturing method of a microneedle film, which helps to improve the forming rate of the microneedle film.

[0005] To achieve one or some or all of the above purposes or other purposes, an embodiment of the present application provides a microneedle film, which comprises a substrate layer, a plurality of microneedles, and a plurality of microstructures. The substrate layer has a first surface and a second surface opposite to the first surface, and the first surface is rougher than the second surface. The plurality of microneedles are arranged on the substrate layer, and the plurality of microneedles are distributed on the first surface of the substrate layer and spaced from each other. The plurality of microstructures are formed on the first surface, and each microstructure corresponds to each microneedle. Each microstructure comprises a plurality of grooves, and each groove forms a geometric shape or a line segment on the first surface, wherein the line segment includes a straight line and a curve.

[0006] In an embodiment of the microneedle film of the present application, the groove has a width of 0.975-120 μm and a depth of 0.975-10 μm, and the distance between adjacent grooves is 0-120 μm.

[0007] In an embodiment of the microneedle film of the present application, the width of the groove is further 0.975-10 μm, and the distance between adjacent grooves is further 0-10 μm.

[0008] In an embodiment of the microneedle film of the present application, the width of the groove is further 9.75-30 μm, and the distance between adjacent grooves is further 9.75-30 μm.

[0009] In an embodiment of the microneedle film of the present application, the width of the groove is further 29.25-70 μm, and the distance between adjacent grooves is further 29.25-70 μm.

[0010] In an embodiment of the microneedle film of the present application, the width of the groove is further 68.25-120 μm, and the distance between adjacent grooves is further 68.25-120 μm.

[0011] In an embodiment of the microneedle film of the present application, at least part of the first surface has a roughness of 0.05-0.1 μm, and the microstructures of adjacent microneedles are connected, overlapped or separated from each other.

[0012] In an embodiment of the microneedle film of the present application, the geometric shape is further circular, and each microstructure further comprises a plurality of circles formed by the grooves on the first surface; wherein the plurality of circles are concentrically distributed with the microneedle as the center.

[0013] In an embodiment of the microneedle film of the present application, the curve is further an arc segment, and each microstructure further comprises a plurality of arc segments formed by the grooves on the first surface; wherein the plurality of arc segments are arranged around the microneedle.

[0014] In an embodiment of the microneedle film of the present application, the geometric shape is further rectangular, and each microstructure further comprises a plurality of similar rectangles formed by the grooves on the first surface; wherein the plurality of similar rectangles are concentrically distributed with the microneedle as the center.

[0015] In an embodiment of the microneedle film of the present application, the geometric shape is further triangular, and each microstructure further comprises a plurality of similar triangles formed by the grooves on the first surface; wherein the plurality of similar triangles are concentrically distributed with the microneedle as the center.

[0016] In an embodiment of the microneedle film of the present application, the microstructure of each microneedle has a first range on the first surface; the grooves in the first range have a width of 0.975-120 μm, and the distance between adjacent grooves is 0-120 μm.

[0017] In an embodiment of the microneedle film of the present application, the microstructure of each microneedle further has a second range on the first surface, and a microstructure of an adjacent microneedle is further distributed in the second range.

[0018] To achieve one or some or all of the above-mentioned objects or other objects, an embodiment of the present application provides a manufacturing method of a microneedle film, comprising the steps of: providing a first mold; the first mold has a bearing seat and a plurality of microneedle structures, the plurality of microneedle structures are arranged on the bearing seat and spaced apart from each other; wherein the surface of the bearing seat is formed with a plurality of micro-groove structures, and each micro-groove structure corresponds to each microneedle structure; each micro-groove structure comprises a plurality of groove structures; the step of dispensing a polymer material into the first mold to form a second mold; and the step of dispensing a microneedle film material into the second mold to form a microneedle film, comprising: forming a plurality of microneedles of the microneedle film corresponding to the plurality of microneedle structures; forming a first surface of the microneedle film corresponding to the surface of the bearing seat, wherein the plurality of microneedles are distributed on the first surface and spaced apart from each other; and forming a plurality of microstructures corresponding to the plurality of micro-groove structures, wherein each microstructure comprises a plurality of groove structures.

[0019] In an embodiment of the rising method, each of the plurality of groove structures further constitutes a geometric shape or a line segment on the surface of the bearing seat, and the plurality of micro-groove structures of adjacent microneedle structures are connected, overlapped or separated from each other.

[0020] In an embodiment of the rising method, the groove structure has a width of 1-120 μm and a depth of 1-10 μm, and the spacing between adjacent groove structures is 0-120 μm.

[0021] In an embodiment of the rising method, the width of the groove structure is further 1-10 μm, and the spacing between adjacent groove structures is further 0-10 μm.

[0022] In an embodiment of the rising method, the width of the groove structure is further 10-30 μm, and the spacing between adjacent groove structures is further 10-30 μm.

[0023] In an embodiment of the rising method, the width of the groove structure is further 30-70 μm, and the spacing between adjacent groove structures is further 30-70 μm.

[0024] In an embodiment of the rising method, the width of the groove is further 70-120 μm, and the spacing between adjacent grooves is further 70-120 μm.

[0025] In an embodiment of the rising method, the step of forming the second mold further comprises:

[0026] forming a plurality of tapered holes in the second mold corresponding to the plurality of microneedle structures;

[0027] forming a bottom surface in the second mold corresponding to the surface of the bearing seat, wherein the plurality of tapered holes are distributed on the bottom surface and spaced apart from each other; and

[0028] forming a plurality of micro-convex structures corresponding to the plurality of micro-groove structures, wherein each of the micro-convex structures comprises a plurality of convex structures.

[0029] The present application adopts a plurality of micro-structures, so the adhesion between the microneedle film material and the mold is better, which helps to ensure the forming rate of the microneedle film. Therefore, the film forming condition is improved, the microneedle structure is complete, and the production yield is improved.

[0030] In order to make the above and other purposes, features and advantages of the present application more obvious and easy to understand, the following specific examples are described in detail below, and the accompanying drawings are described as follows. BRIEF DESCRIPTION OF DRAWINGS

[0031] Figure 1 It is a side view schematic diagram of the microneedle film of the first embodiment of the present application.

[0032] Figure 2 It is a side view schematic diagram of the microneedle film of the first embodiment of the present application. Figure 1 It is a partial top view schematic diagram of the first embodiment.

[0033] Figure 3 It is a partial top view schematic diagram of the first embodiment of the present application. Figure 2 It is a partial sectional view along AA' schematic diagram.

[0034] Figure 4A It is a partial sectional view schematic diagram of the microneedle film of the second embodiment of the present application.

[0035] Figure 4B It is a partial sectional view schematic diagram of the microneedle film of the third embodiment of the present application.

[0036] Figure 4C It is a partial sectional view schematic diagram of the microneedle film of the fourth embodiment of the present application.

[0037] Figure 4D It is a partial sectional view schematic diagram of the microneedle film of the fifth embodiment of the present application.

[0038] Figure 5A It is a partial top view schematic diagram of the microneedle film of the sixth embodiment of the present application.

[0039] Figure 5B It is a partial top view schematic diagram of the microneedle film of the seventh embodiment of the present application.

[0040] Figure 5C It is a partial top view schematic diagram of the microneedle film of the seventh embodiment of the present application. Figure 5B It is a partial enlarged schematic diagram.

[0041] Figure 5D It is a partial top view schematic diagram of the microneedle film of the eighth embodiment of the present application.

[0042] Figure 5E It is a partial top view schematic diagram of the microneedle film of the ninth embodiment of the present application.

[0043] Figure 5F Figure 1 is a schematic view of a microneedle patch according to an embodiment of the present application. Figure 5E Figure 2 is a schematic view of a microneedle film according to an embodiment of the present application.

[0044] Figure 5G Figure 3 is a schematic view of a microneedle film according to a first embodiment of the present application.

[0045] Figure 5H Figure 4 is a schematic view of a microneedle film according to a second embodiment of the present application.

[0046] Figure 5I Figure 5 is a schematic view of a microneedle film according to a third embodiment of the present application.

[0047] Figure 6A Figure 6 is a schematic view of a microneedle film manufacturing method according to an embodiment of the present application.

[0048] Figure 6B Figure 7 is another schematic view of a microneedle film manufacturing method according to an embodiment of the present application.

[0049] Figure 7A Figure 8 is an implementation schematic view of a microneedle film manufacturing method according to an embodiment of the present application.

[0050] Figure 7B Figure 9 is another implementation schematic view of a microneedle film manufacturing method according to an embodiment of the present application.

[0051] In the drawings:

[0052] 1: microneedle patch

[0053] 10: microneedle film

[0054] 10': microneedle film material

[0055] 100: microneedle

[0056] 150: bottom

[0057] 200: base layer

[0058] 210: first surface

[0059] 220: second surface

[0060] 300: microstructure

[0061] 3000, 3000a-3000d: groove

[0062] 50: first mold

[0063] 510: microneedle structure

[0064] 520: bearing seat

[0065] 530: micro-groove structure

[0066] 5300: trench structure

[0067] 60': polymeric material

[0068] 60: second mold

[0069] 610: tapered hole

[0070] 620: bottom surface

[0071] 630: micro-protrusion

[0072] 6300: protrusion structure

[0073] 70: carrier layer

[0074] S910-S930, S921-S923: steps

[0075] W: width

[0076] D: depth

[0077] I, I': interval

[0078] L: first length

[0079] A: range

[0080] E: edge

[0081] A1: first range

[0082] A2: second range DETAILED DESCRIPTION

[0083] The foregoing and other technical contents, features and effects of the present application will be apparent from the following detailed description of a preferred embodiment, which is illustrated in reference with the accompanying drawings. Directional terms mentioned in the following embodiments are only for reference with the accompanying drawings. Therefore, the directional terms are used for illustration, not for limitation. In addition, the terms "first", "second", etc. mentioned in the specification or patent claim are only used for naming elements or distinguishing different embodiments or ranges, not for limiting the upper or lower limit of the number of elements.

[0084] The present application provides a microneedle film, which can be made into a microneedle patch for transdermal drug delivery. Figure 1 A side view of a microneedle film according to an embodiment of the present application is shown in FIG. 1. As shown in FIG. 1, the microneedle film 100 includes a carrier layer 70, a plurality of microneedles 600, and a plurality of micro-protrusions 630. Figure 1As shown, the microneedle film 10 includes a plurality of microneedles 100 and a base layer 200, with the plurality of microneedles 100 disposed on the base layer 200. The microneedles 100 have a base 150 connected to the base layer 200. The microneedles 100 can be tapered, such as a cone, triangular pyramid, or quadrangular pyramid, with the base 150 being relatively wide and gradually tapering upward. The vertical distance from the base 150 to the top tip of the microneedle 100 corresponds to the height of the microneedle 100. The height of the microneedle 100 can be, for example, 150 μm to 1000 μm.

[0085] The base layer 200 has a first surface 210 and a second surface 220 opposite to the first surface 210. The roughness of the first surface 210 and the second surface 220 are preferably different. For example, one of the surfaces may be rough and the other may be smooth, or one of the surfaces may be rougher than the other. Figure 1 In some embodiments, the first surface 210 is rougher than the second surface 220, and the plurality of microneedles 100 are further spaced apart and distributed on the first surface 210 of the base layer 200. In this case, the second surface 220 may correspond to the bottom surface of the microneedle film 10. The spacing between adjacent microneedles 100 may be, for example, 0.5 to 5 mm, including, but not limited to, 0.5 mm, 1.0 mm, 1.5 mm, 2.0 mm, 2.5 mm, 3.0 mm, 3.5 mm, 4.0 mm, 4.5 mm, and 5 mm. The microneedles 100 are preferably evenly distributed on the first surface 210. In some embodiments of the present invention, the plurality of microneedles 100 may be arranged in rows or columns and evenly distributed on the first surface 210, but not limited to this. For example, a random distribution of the plurality of microneedles 100 on the first surface 210 may also achieve a uniform distribution effect. The bottom surface of the microneedle film 10 may further be used to set a carrier layer (described later) and form a microneedle patch. The material of the carrier layer is generally different from that of the microneedle film 10. The material of the carrier layer can be, for example, a natural or synthetic material such as non-woven fabric, cotton, polyester film, or film, which can provide support and make the microneedle film 10 or its microneedle patch more suitable for handling and application to the body surface.

[0086] Figure 2 for Figure 1 A partial top view of an embodiment of the present invention. Figure 2 The shape of the microneedle 100 shown is a quadrangular pyramid, but is not limited thereto. The microneedle film 10 further has a plurality of microstructures 300 formed on the first surface 210. The first surface 210 may have a roughness as described above due to the plurality of microstructures 300. In some embodiments of the present invention, the first surface 210 may have a roughness (Ra) of, for example, 0.05 to 0.1 μm. Figure 2As shown, the microstructure 300 can be formed into a geometric shape such as a circle on the first surface 210, but is not limited thereto. The microstructure 300 can also be formed into other geometric shapes such as a rectangle, a triangle, or other polygons. Figure 3 for Figure 2 A partial cross-sectional view along AA' is shown in FIG. Figures 2-3 As shown, the microstructure 300 may be formed on a portion of the first surface 210 adjacent to or close to the bottom 150 of each microneedle 100 , and further, a plurality of microstructures 300 may be distributed on the first surface 210 between adjacent microneedles 100 .

[0087] The microstructure 300 may further include grooves 3000. In the XY plane where the first surface 210 is located, the grooves 3000 are indicated by dotted lines, but in reality they can be continuous and uninterrupted. In addition, the number of grooves 3000 in each microstructure 300 is not limited to the number shown in the figure. The grooves 3000 of the microstructure 300 may have various shapes. For example, the grooves 3000 may have different shapes depending on the mold used in the manufacture of the microneedle film 10 (described later). Figure 3 As shown, the cross section of the groove 3000 of the microstructure 300 is in the shape of an inverted triangle, but the present invention is not limited thereto. Figures 4A-4D The shapes of the grooves 3000 of the microstructures 300 are shown as examples. Figure 4A In the embodiment of the present invention, the groove 3000a (3000) is a sawtooth groove with an inverted triangular cross section. Figure 4B In the embodiment of the present invention, the grooves 3000b (3000) are also serrated and distributed continuously. Figure 4C In the embodiment, the groove 3000c (3000) has an arc-shaped cross section and a smooth bottom. Figure 4D In the embodiment, the groove 3000d (3000) has a rectangular cross-section and a flat bottom. In addition, the microstructure 300 on the same microneedle film 100 is not limited to one type. For example, the same microneedle film 100 can have multiple groove 3000 shapes.

[0088] Furthermore, the mold for manufacturing the microneedle film 10 has a plurality of microneedle structures and a plurality of microgroove structures (described later), wherein the microneedle structure is used to form the microneedles 100, and the microgroove structure is reflected on the first surface 210 of the base layer 200 to form the microstructure 300. The microgroove structure of the mold can be formed by, for example, cutting. The microgroove structure includes a plurality of groove structures, and the groove structure can be different due to the different tools used for cutting. Figure 3 and Figures 4A-4D The different cross-sectional shapes shown in the figure also provide the grooves 3000 of the microstructure 300 with various distribution patterns (described later). The microgroove structure on the mold helps to increase the adhesion of the microneedle film 10 material to the mold, thereby improving the film formation of the microneedle film 10 and increasing the film formation yield.

[0089] The width of the groove structure of the mold can be, for example, 1-120 μm, the depth can be, for example, 1-10 μm, including 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm, and 10 μm, and the spacing between adjacent groove structures can be, for example, 0-120 μm. Thus, as shown in FIGS. 3A and 3B, when the groove structure of the mold is reflected on the microneedle film 10, the grooves 3000 of the microstructure 300 have a width W of approximately 1-120 μm, a depth D of approximately 1-10 μm, including 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm, and 10 μm, and a spacing I between adjacent grooves 3000 of approximately 0-120 μm, where the width W is the width of the groove 3000 perpendicular to its direction of extension on the first surface 210. In embodiments of the present application, based on the properties of the material of the microneedle film 10 and the shrinkage of the volume when molded, the width W of the groove 3000 can be 1-120 μm or less, for example, reduced by 1-2.5% and further having a width W of 0.975-120 μm, where 0.975 μm is the result of a reduction of 2.5% of the intended width W of 1 μm. Based on the same reasoning, the depth D can be 1-10 μm or less, for example, reduced by 1-2.5% and further 0.975-10 μm, and the spacing I can also be reduced by 1-2.5% and further 0.975-120 μm. That is, the width W, the depth D, and the spacing I of the groove 3000 are substantially the same as the width, the depth, and the spacing of the groove structure on the mold, but can be slightly smaller based on the properties of the material of the microneedle film 10 and the shrinkage of the material when molded. The shrinkage is, for example, 1-2.5%. Figure 3 Figures 4A-4D

[0090] ​​The width and pitch of the trench structures can be coordinated with each other to allow the mold to achieve the optimal gripping force on the microneedle film 10 material. Thus, the width W of the trench 3000 is also coordinated with the pitch I. In some embodiments of the present application, when the width of the trench structure is 1-10 μm and the width W of the trench 3000 is 1-10 μm, the pitch between adjacent trench structures is preferably 1-10 μm and the pitch I between adjacent trenches 3000 is preferably 0-10 μm. For example, when the width W is, for example, 5 μm, the pitch I can be, for example, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 μm, or a combination thereof, but is not limited thereto. It should be noted that, based on the shrinkage relationship, the width W can further be 0.975-10 μm and the pitch I can further be 0.975-10 μm. When the width of the trench structure is 10-30 μm and the width W of the trench 3000, based on the shrinkage relationship, is 9.75-30 μm, the pitch between adjacent trench structures is preferably 10-30 μm and the pitch I between adjacent trenches 3000 is preferably 9.75-30 μm. For example, when the width W is, for example, 20 μm, the pitch I can be, for example, 9.75, 10, 15, 20, 25, 29.7, 30 μm, or a combination thereof, but is not limited thereto. When the width of the trench structure is 30-70 μm and the width W of the trench 3000, based on the shrinkage relationship, is 29.25-70 μm, the pitch between adjacent trench structures is preferably 30-70 μm and the pitch I between adjacent trenches 3000 is preferably 29.25-70 μm. For example, when the width W is, for example, 50 μm, the pitch I can be, for example, 29.25, 30, 35, 40, 45, 50, 55, 60, 65, 69.3, 70 μm, or a combination thereof, but is not limited thereto. Also, when the width of the trench structure is 70-120 μm and the width W of the trench 3000, based on the shrinkage relationship, is 68.25-120 μm, the pitch between adjacent trench structures is preferably 70-120 μm and the pitch I between adjacent trenches 3000 is preferably 68.25-120 μm. For example, when the width W is, for example, 100 μm, the pitch I can be, for example, 68.25, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 118.8, 120 μm, or a combination thereof, but is not limited thereto. In any of the microstructures 300, the pitch I between adjacent trenches 3000 can be uniform or can be non-uniform within a certain range as described above.

[0091] As described above, the microstructure 300 can be formed on the portion of the first surface 210 adjacent to or near the base 150 of each microneedle 100. Furthermore, in certain embodiments of the present invention, the multiple microstructures 300 on the first surface 210 can correspond to a plurality of microneedles 100. In other words, each microneedle 100 can be equipped with a microstructure 300. The microgrooves used to form the microstructures 300 on the mold can be formed using a cutting tool, such as a milling cutter. The microgrooves can be distributed to match the microneedle structures on the mold. For example, a milling cutter can be used to form microgrooves around each microneedle structure, with the microgrooves positioned adjacent to or near the microneedle structure. Forming microgrooves near the microneedle structures helps ensure the mold's grip on the material near the microneedles 100 and helps ensure proper microneedle 100 formation. In certain embodiments of the present invention, the microgrooves can achieve a microneedle 100 forming rate of over 97.5% for the microneedle film 10.

[0092] like Figure 2 As shown, a plurality of microstructures 300 are formed on the first surface 210 of the base layer 200, and the plurality of microstructures 300 correspond to the plurality of microneedles 100 respectively. Figure 2 In the embodiment, the microstructure 300 of each microneedle 100 includes a plurality of grooves 3000, and each groove 3000 forms a geometric shape, such as a circle, on the first surface 210. The circles formed by the plurality of grooves 3000 can be distributed in a concentric circle pattern with the position of the microneedle 100 as the center. Figure 2 In the embodiment, the range from the innermost groove 3000 to the outermost groove 3000 is equivalent to the range A of the microstructure 300 of each microneedle 100 on the first surface 210, and the range A has an edge E. Figure 2 As shown, the microstructures 300 of adjacent microneedles 100 may be connected to each other, that is, the edges E of adjacent microstructures 300 may be connected, but the present invention is not limited thereto. Figure 2 As shown, the bases 150 of adjacent microneedles 100 may be spaced apart by a first length L. In some embodiments of the present invention, the distance between the edge E of the area A of the microstructure 300 of any microneedle 100 and the base 150 of the adjacent microneedle 100 may be less than half of the first length L, and the edge E may enter the area A of the microstructure 300 of the adjacent microneedle 100.

[0093] Figures 5A-5B Other types of microstructures 300 are shown. Figure 5A As shown, the microstructures 300 of adjacent microneedles 100 are separated from each other. Figure 5B As shown, the microstructures 300 of adjacent microneedles 100 partially overlap each other. The aforementioned range A may further include a first range A1 and a second range A2. Figure 5BIn the embodiment shown, the microstructures 300 in the first range Al preferably do not have overlapping conditions, and the width W and the pitch I of the grooves 3000 are as previously described, wherein when the width W is 0.975-10 μm, the pitch I is preferably 0.975-10 μm, when the width W is 9.75-30 μm, the pitch I is preferably 9.75-30 μm, when the width W is 29.25-70 μm, the pitch I is preferably 29.25-70 μm, and when the width W is 68.25-120 μm, the pitch I is preferably 68.25-120 μm. Figure 5B The second range A2 of the embodiment shown is in a crescent shape, and the second range A2 can further have microstructures 300 corresponding to other microneedles 100, that is, in the second range A2, the portions between the plurality of microstructures 300 are partially overlapped, including intersection, coincidence, or alternatively reserved. Figure 5C The embodiment shown is a magnified view of the second range A2. As shown, Figure 5C When the microstructures 300 are overlapped, the pitch I of the grooves 3000 at the overlapping portion can be smaller, and the pitch I' occurs. For example, if the grooves 3000 of the microstructures 300 of each microneedle 100 have a width W of 10 μm and a pitch I of 10 μm, at the overlapping portion with the microstructures 300 of the adjacent microneedle 100, it can be observed that the pitch I' of the grooves 3000 is less than 10 μm, but not limited thereto. That is, the overlapping portion can have a situation where the grooves 3000 are distributed more densely.

[0094] It should be noted that the second range A2 can also only have the grooves 3000 of one microstructure 300. For example, as shown in Figures 5B-5C , for example, any microstructure 300 is substantially circular as shown in Figure 5B , and includes a plurality of grooves 3000, but most of the microstructures 300 lack the crescent-shaped area as shown in Figure 5C on the screen, for example, on the right.

[0095] Figures 5D-5E is a partial top view schematic diagram of a microneedle film of another embodiment of the present application. Figure 5D The embodiment of Figure 2 is different from in that the plurality of grooves 3000 forms a plurality of similar rectangles on the first surface 210. Figure 5E The embodiment of Figure 2 is different from in that the plurality of grooves 3000 forms a plurality of similar triangles on the first surface 210, and the microstructures 300 of the adjacent microneedles 100 partially overlap each other. In the embodiment of Figure 5E , the second range A2 of any microstructure 300 is in a smaller triangle. The second range A2 has microstructures 300 from adjacent microneedles 100. Figure 5F is a magnified view of the second range A2 in Figure 5E . As shown, Figure 5FAs shown, some grooves 3000 from different microstructures 300 intersect, some overlap, some do not interfere with each other, or one of them is retained. In the case where the grooves 3000 overlap, multiple grooves 3000 can be partially overlapped and merged to produce a width W greater than the average. In some embodiments of the present invention, Figure 5E The second area A2 shown may also only retain the groove 3000 of one of the microstructures 300, that is, most of the microstructures 300 are missing on the screen, for example, the right side. Figure 5F The small triangular area shown.

[0096] Figure 5G FIG. 1 is a partial top view of a microneedle membrane according to another embodiment of the present invention. Figure 5G In the embodiment of FIG. 5 , each groove 3000 of the microstructure 300 is also substantially circular. Figure 5G Examples and Figure 2 The difference is that the multiple grooves 3000 are not distributed in a concentric circle pattern, but are arranged in sequence around the microneedle 100 and adjacent grooves 3000 partially overlap each other. Based on the results produced by the cutting tool processing on the mold, in some embodiments of the present invention, it can also be reflected on the microneedle film 10 that only a portion of the groove 3000 of each microstructure 300 is retained. In other words, even if the cutting tool is processed on the mold in a continuous circular manner along the periphery of the microneedle structure to form a groove structure, and the circular processing trajectories partially overlap each other, the formed microgroove structure and its microstructure 300 can be as Figure 5H As shown, any trench structure and its trench 3000 , for example, the right portion thereof, is no longer visible due to the processing of the trench structure behind it.

[0097] Figure 5H FIG. 1 is a partial top view of a microneedle membrane according to another embodiment of the present invention. Figure 5H In the embodiment, each groove 3000 of the microstructure 300 constitutes a curved line segment, and a plurality of curved line segments are arranged around the microneedle 100. In some embodiments, the curved line segment may be an arc segment. It should be noted that, Figure 2 and Figures 5A-5H For example only, the blank portion on the first surface 210 does not necessarily mean that the microstructures 300 are not distributed. Furthermore, the microstructures 300 may be distributed throughout the first surface 210. The portion of the first surface 210 where the microstructures 300 are distributed may have a roughness (Ra) of, for example, 0.05 to 0.1 μm. For example, the portion where the microstructures 300 are distributed may have a roughness of 0.05, 0.06, 0.07, 0.08, 0.09, 0.1 μm, or a combination thereof.

[0098] Figure 5IFig. 1 is a schematic diagram of a top view of a microneedle film according to an embodiment of the present application. The microneedle film 10 includes a plurality of microneedles 100 and a first surface 210. The microneedles 100 are distributed on the first surface 210. The microneedle film 10 can be formed by a method described below. Figure 5I Fig. 2 is a schematic diagram of a top view of a microneedle film according to another embodiment of the present application. The microneedle film 10 includes a plurality of microneedles 100 and a first surface 210. The microneedles 100 are distributed on the first surface 210. The microneedle film 10 can be formed by a method described below. Figures 5A-5I Fig. 3 is a schematic diagram of a top view of a microneedle film according to another embodiment of the present application. The microneedle film 10 includes a plurality of microneedles 100 and a first surface 210. The microneedles 100 are distributed on the first surface 210. The microneedle film 10 can be formed by a method described below.

[0099] Fig. 4 is a schematic diagram of a top view of a microneedle film according to another embodiment of the present application. The microneedle film 10 includes a plurality of microneedles 100 and a first surface 210. The microneedles 100 are distributed on the first surface 210. The microneedle film 10 can be formed by a method described below. Figure 6A Fig. 5 is a schematic diagram of a top view of a microneedle film according to another embodiment of the present application. The microneedle film 10 includes a plurality of microneedles 100 and a first surface 210. The microneedles 100 are distributed on the first surface 210. The microneedle film 10 can be formed by a method described below. Figures 7A-7B Fig. 6 is a schematic diagram of a top view of a microneedle film according to another embodiment of the present application. The microneedle film 10 includes a plurality of microneedles 100 and a first surface 210. The microneedles 100 are distributed on the first surface 210. The microneedle film 10 can be formed by a method described below.

[0100] Fig. 7 is a schematic diagram of a top view of a microneedle film according to another embodiment of the present application. The microneedle film 10 includes a plurality of microneedles 100 and a first surface 210. The microneedles 100 are distributed on the first surface 210. The microneedle film 10 can be formed by a method described below. Figure 7A Fig. 8 is a schematic diagram of a top view of a microneedle film according to another embodiment of the present application. The microneedle film 10 includes a plurality of microneedles 100 and a first surface 210. The microneedles 100 are distributed on the first surface 210. The microneedle film 10 can be formed by a method described below. Figure 7AAs shown, multiple microneedle structures 510 are spaced apart from each other and arranged at an appropriate distribution density on a support 520. The spacing between adjacent microneedle structures 510 can be, for example, 0.5 to 5 mm. The microneedle structures 510 can have a shape that is wide at the bottom and narrow at the top, such as a cone, triangular pyramid, or quadrangular pyramid. The height of the microneedle structures 510 can be, for example, 150 to 1000 μm.

[0101] The micro-groove structure 530 on the surface of the support seat 520 can be formed by cutting. Specifically, it can be milling. The micro-groove structure 530 includes a plurality of groove structures 5300, and the groove structure 5300 can be formed by a cutting tool such as a milling cutter. Different milling cutters can form groove structures 5300 of different shapes, such as a triangular cross-section, or an arc shape, or a rectangle. The width of the groove structure 5300 can be, for example, 1 to 120 μm, the depth can be, for example, 1 to 10 μm, and the spacing between adjacent groove structures 5300 can be, for example, 0 to 120 μm. Moreover, through the processing action of the cutting tool, the groove structure 5300 can be further formed into a geometric shape or line segment on the surface of the support seat 520 (see Figure 2 、 5A 5H). In addition, the cutting tool can be used to form micro-grooves 530 around each micro-needle structure 510, but the present invention is not limited thereto. The micro-grooves 530 of adjacent micro-needle structures 510 can be connected to each other, overlapped, or separated from each other.

[0102] like Figure 7A As shown, step S920 includes distributing the polymer material 60' to the support 520 and the plurality of microneedle structures 510 and microgroove structures 530 thereon. The polymer material 60' may be, for example, polyethylene, polypropylene, polylactic acid, polybutylene succinate, polydimethylsiloxane, but is not limited thereto. Figure 6B As shown, step S920 further includes step S921: forming a plurality of tapered holes in the second mold corresponding to the plurality of microneedle structures, step S922: forming a bottom surface in the second mold corresponding to the surface of the support seat, and step S923: forming a plurality of microconvex structures corresponding to the plurality of microgrooves, wherein each microconvex structure includes a plurality of protrusion structures. The second mold 60 may be a master mold. Figure 7A As shown, multiple tapered holes 610 within the second mold 60 are formed from polymeric material 60' through the microneedle structure 510 of the first mold 50. Multiple micro-convex structures 630 are formed from polymeric material 60' through the micro-groove structure 530 of the first mold 50. Each micro-convex structure 630 includes multiple protrusion structures 6300. The width of each protrusion structure 6300 can be, for example, 1 to 120 μm, the height can be, for example, 1 to 10 μm, and the spacing between adjacent protrusion structures 6300 can be, for example, 0 to 120 μm. The polymeric material 60' that contacts the surface of the carrier 520 forms the bottom surface 620 within the second mold 60.

[0103] like Figure 7B As shown, step S930 includes allowing the microneedle film material 10' to further enter the tapered hole 610 and distributing the microneedle film material 10' to the bottom surface 620 of the second mold 60 and the microconvex structure 630 on the bottom surface 620. The microneedle film material 10' can be, for example, maltose, sucrose, trehalose, lactose, dextrin, maltodextrin, β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin, dextran, pullulan, sodium hyaluronate, methyl vinyl ether-maleic anhydride copolymer, sodium carboxymethyl cellulose, methylcellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, gelatin, polyvinyl alcohol, polyvinyl pyrrolidone, polyethylene glycol, polylactic acid, polyglycolic acid, polylactic-glycolic acid copolymer, chitosan, combinations thereof, or other biocompatible materials suitable for transdermal drug delivery. Step S930 can further include drying the microneedle film material 10' to form the microneedle film 10.

[0104] The micro-convex structure 630 increases the contact area between the second mold 60 and the microneedle film material 10', particularly the contact area between the surface where the tapered holes 610 are located and the microneedle film material 10'. Furthermore, during the formation of the microneedle film material 10' into the microneedle membrane 10, the micro-convex structure 630 increases the grip of the bottom surface 620 on the microneedle film material 10', thereby facilitating adhesion of the microneedle film material 10' to the second mold 60 and ensuring that the microneedle film material 10' is not easily separated from the second mold 60 before forming is complete. In certain embodiments of the present invention, the grip of the bottom surface 620 and the micro-convex structure 630 on the microneedle film 10 can be inferred by measuring the ease with which the microneedle film 10 can be peeled off from the bottom surface 620. A greater tear-off force indicates a greater grip of the bottom surface 620 and the micro-convex structure 630 on the microneedle film 10. Compared to conventional male molds without microgrooves and female molds without micro-convex structures, the second mold 60 of the present invention can achieve a tear-off force that is more than doubled. Furthermore, embodiments of the present invention can further enhance the tear-off force by varying the width and spacing of the protrusions 6300, as well as by combining these widths and spacings. For example, when the width of the protrusions 6300 is 30-70 μm and the spacing between adjacent protrusions 6300 is 30-70 μm, the tear-off force can be doubled. When the width of the protrusions 6300 is 1-10 μm and the spacing between adjacent protrusions 6300 is 1-10 μm, the tear-off force can be increased by more than double. However, it is understood that the relationship between the width and spacing of the protrusions 6300 and the tear-off force can vary depending on the microneedle film material 10'. In other words, the width and spacing of the protrusions 6300 can be adjusted to the microneedle film material 10' to achieve the optimal gripping force. The following example illustrates the tear-off force measured for different protrusions 6300 widths and spacings on an area of ​​65*45 mm.

[0105]

[0106] Note: Fix the tearing starting point on the dynamometer and apply force at 90 degrees vertically

[0107] When the microneedle film material 10' is dried to form the microneedle film 10, the microneedle film material 10' within the tapered hole 610 can be formed into the microneedles 100 of the microneedle film 10, the microneedle film material 10' in contact with the bottom surface 620 can be formed into the first surface 210, and the microneedle film material 10' on the microconvex structure 630 can be formed into the microstructure 300 on the first surface 210. Because the groove structure 5300 and the protrusion structure 6300 formed therefrom have a width of, for example, 1 to 120 μm, a depth of, for example, 1 to 10 μm, and a pitch of, for example, 0 to 120 μm, the groove 3000 formed by the protrusion structure 6300 has a width W of approximately 1 to 120 μm, a depth D of approximately 1 to 10 μm, and a pitch I of approximately 0 to 120 μm. Based on the properties of the microneedle film material 10 ′ and its shrinkage during molding, the microneedle film 10 can be slightly reduced, and the grooves 3000 therein can have a shrinkage rate of 1 to 2.5% in terms of width W, depth D, and spacing I compared to the groove structure 5300 of the first mold 50. For example, when the width of the groove structure 5300 of the first mold 50 is 100μm and the depth is 5μm, and the spacing between adjacent groove structures 5300 is 100μm, the width W of the formed groove 3000 can be 97.5~100μm, for example, 97.5μm, 98μm, 98.5μm, 99μm, 99.5μm, 100μm, the depth D of the groove 3000 can be 4.875~5μm, for example, 4.875μm, 4.9μm, 4.95μm, 5μm, and the spacing I between adjacent grooves 3000 can be 97.5~100μm, for example, 97.5μm, 98μm, 98.5μm, 99μm, 99.5μm, 100μm, but is not limited to this.

[0108] like Figure 7B As shown, after the microneedle film 10 is formed, a carrier layer 70 can be further provided on its bottom surface, i.e., the second surface 220, and the mold can be released to form a microneedle patch 1. In summary, the microneedle film 10 and the microneedle patch 1 of the embodiment of the present invention have a high degree of molding completion, so the film forming condition is improved, the microneedles 100 are structurally complete and of normal size, which helps to improve the production yield.

[0109] Although the present invention has been disclosed above with reference to the embodiments, they are not intended to limit the present invention. Those skilled in the art may make modifications and improvements without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention shall be determined by the scope of the appended claims.

Claims

1. A microneedle membrane, characterized in that include: a base layer having a first surface and a second surface opposite to the first surface, wherein the first surface is rougher than the second surface; A plurality of microneedles are disposed on the base layer; wherein the plurality of microneedles are spaced apart and distributed on the first surface of the base layer; as well as A plurality of microstructures are formed on the first surface, and the plurality of microstructures respectively correspond to each of the plurality of microneedles; wherein each of the microstructures includes a plurality of grooves, and each of the plurality of grooves forms a geometric shape or a line segment on the first surface, wherein the line segment includes a straight line and a curve.

2. The microneedle film according to claim 1, wherein The groove has a width of 0.975-120 μm and a depth of 0.975-10 μm, and a spacing between adjacent grooves is 0-120 μm.

3. The microneedle film according to claim 2, wherein The width of the groove is further 0.975-10 μm, and the interval between adjacent grooves is further 0-10 μm.

4. The microneedle film according to claim 2, wherein The width of the groove is further 9.75-30 μm, and the spacing between adjacent grooves is further 9.75-30 μm.

5. The microneedle film according to claim 2, wherein The width of the groove is further 29.25-70 μm, and the interval between adjacent grooves is further 29.25-70 μm.

6. The microneedle film according to claim 2, wherein The width of the groove is further 68.25-120 μm, and the interval between adjacent grooves is further 68.25-120 μm.

7. The microneedle film according to claim 1, wherein At least a portion of the first surface has a roughness of 0.05-0.1 μm, and the microstructures of adjacent microneedles are connected to, overlapped with, or separated from each other.

8. The microneedle film according to claim 1, wherein The geometric shape is further circular, and each of the microstructures further includes a plurality of circles formed by the plurality of grooves on the first surface; wherein the plurality of circles are distributed in concentric circles with the position of the microneedle as the center.

9. The microneedle film according to claim 1, wherein The curve is further an arc segment, and each of the microstructures further includes a plurality of arc segments formed by the plurality of grooves on the first surface; wherein the plurality of arc segments are arranged around the microneedle.

10. The microneedle film according to claim 1, wherein The geometric shape is further a rectangle, and each of the microstructures further includes a plurality of similar rectangles formed by the plurality of grooves on the first surface; wherein the plurality of similar rectangles are concentrically distributed with the position of the microneedle as the center.

11. The microneedle film according to claim 1, wherein The geometric shape is further a triangle, and each of the microstructures further includes a plurality of similar triangles formed by the plurality of grooves on the first surface; wherein the plurality of similar triangles are concentrically distributed with the position of the microneedle as the center.

12. The microneedle film according to claim 1, wherein The microstructure of each of the plurality of microneedles has a first range on the first surface; the plurality of grooves in the first range each have a width of 0.975 to 120 μm, and the spacing between adjacent grooves is 0 to 120 μm.

13. The microneedle film according to claim 12, wherein The microstructure of each of the plurality of microneedles further has a second range on the first surface, and a microstructure of an adjacent microneedle of the microneedle is further distributed within the second range.

14. A method for producing a microneedle film according to any one of claims 1 to 13, characterized in that: include: Providing a first mold; The first mold has a supporting base and a plurality of microneedle structures, wherein the plurality of microneedle structures are spaced apart and arranged on the supporting base; A plurality of micro-groove structures are formed on the surface of the supporting base, and the plurality of micro-groove structures respectively correspond to each of the plurality of micro-needle structures; and each of the micro-groove structures includes a plurality of groove structures; dispensing a polymeric material into the first mold to form a second mold; as well as Dispensing a microneedle film material to the second mold to form a microneedle film, comprising: forming a plurality of microneedles of the microneedle film corresponding to the plurality of microneedle structures; forming a first surface of the microneedle film corresponding to the surface of the supporting base, wherein the plurality of microneedles are spaced apart and distributed on the first surface; and A plurality of microstructures corresponding to the plurality of microgroove structures are formed, wherein each of the microstructures includes a plurality of grooves.

15. The method for producing a microneedle film according to claim 14, wherein: Each of the plurality of groove structures further forms a geometric shape or a line segment on the surface of the supporting base, and the plurality of micro-groove structures of adjacent micro-needle structures are connected to, overlapped with, or separated from each other.

16. The method for producing a microneedle film according to claim 14, wherein: The groove structure has a width of 1 to 120 μm and a depth of 1 to 10 μm, and a spacing between adjacent groove structures is 0 to 120 μm.

17. The method for producing a microneedle film according to claim 16, wherein: The width of the groove structure is further 1-10 μm, and the spacing between adjacent groove structures is further 0-10 μm.

18. The method for producing a microneedle film according to claim 16, wherein: The width of the groove structure is further 10-30 μm, and the spacing between adjacent groove structures is further 10-30 μm.

19. The method for producing a microneedle film according to claim 16, wherein: The width of the groove structure is further 30-70 μm, and the spacing between adjacent groove structures is further 30-70 μm.

20. The method for producing a microneedle film according to claim 16, wherein: The width of the groove is further 70-120 μm, and the interval between adjacent grooves is further 70-120 μm.

21. The method for producing a microneedle film according to claim 14, wherein: The step of forming the second mold further comprises: forming a plurality of tapered holes in the second mold corresponding to the plurality of microneedle structures; forming a bottom surface in the second mold corresponding to the surface of the supporting base, wherein the plurality of tapered holes are spaced apart and distributed on the bottom surface; and A plurality of micro-convex structures corresponding to the plurality of micro-grooves are formed, wherein each of the micro-convex structures includes a plurality of protrusion structures.

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