A printing method of a microneedle sheet and a microneedle sheet

Abstract

The application discloses a printing method of a microneedle sheet and the microneedle sheet. In the step of printing the microneedle base, the microneedle base is split into at least two microneedle base bodies, and the microneedle base bodies are printed in different time periods and then embedded to form a planar microneedle base. The application can express the internal stress generated in the microneedle base in different time periods and different parts due to the light curing process of the photosensitive resin, and distribute the large internal stress generated in the whole microneedle base to different microneedle base bodies constituting the microneedle base. The internal stress generated by the microneedle base monomer on each microneedle base body is small and is not enough to cause deformation of the microneedle base monomer. Therefore, by combining the control of the printing time period and the control of the printing shape, the problem of the microneedle base being warped and curled is avoided, and the yield and quality of the 3D-printed microneedle sheet are improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical devices, and in particular to a printing method of a microneedle sheet and a microneedle sheet. BACKGROUND

[0002] As a new transdermal drug delivery technology, the microneedle sheet can perform painless, non-invasive, convenient and efficient drug delivery, and is widely concerned and plays an important role in the fields of medicine, medical aesthetics and other related fields. The microneedle sheet is essentially a patch, and an array of microneedles with a size of microns is formed on the patch. The length of the microneedle is greater than the thickness of the stratum corneum of human skin. Compared with other transdermal drug delivery methods, the microneedle sheet can deliver larger molecules without interfering with the nerve endings of the skin, thereby minimizing or completely avoiding pain experienced by the patient. When the microneedle on the microneedle sheet is inserted into the human skin, the microneedle can deliver the load carried in the microneedle directly into the epidermis by piercing the stratum corneum, and the load is absorbed by the capillary and lymphatic vessels and enters the human circulatory system. Since the microneedle sheet does not leave harmful substances in the human skin and does not produce sharp needle waste, it has a unique drug delivery advantage.

[0003] At present, the preparation methods of the microneedle sheet mainly include microtemplate method, droplet blowing method, electric stretching method, thermal stretching method, magnetic rheological stretching photolithography method and 3D printing method. Among them, the 3D printing technology as a new additive manufacturing technology has the technical advantages of fast production speed, high efficiency, low cost and high precision. The 3D printing technology can be divided into fused deposition type printing, inkjet printing, light curing printing and selective laser sintering printing. The commonly used material for light curing printing is light curing resin, which can be cured under the irradiation of ultraviolet light. Therefore, the model can be printed layer by layer under the control of a computer, and the entire model can be printed. Compared with other printing methods, light curing printing has the advantages of high printing precision, fast printing speed and low printing cost. In addition, light curing printing can quickly adjust the geometric shape of the prepared microneedle sheet model, including size, shape, aspect ratio and spacing. Therefore, the microneedle prepared by light curing printing has high sharpness, which is more conducive to penetrating into the human skin for drug delivery.

[0004] The Chinese patent document with publication number CN110693855A discloses a preparation method of a 3D-printed microneedle patch and its application. A double-nozzle fused deposition modeling (FDM) 3D printer is used, one nozzle for printing the base of the microneedle patch and the other nozzle for printing the columnar array of the microneedle patch. The columnar array contains insulin drugs that can intelligently respond to adjust blood glucose. After obtaining the base and columnar array, a glass slide is used to contact the top end of the columnar array and stretched to a predetermined distance to produce microneedle tips. Cross-linking and molding are performed, and after natural drying, a microneedle array patch with certain mechanical properties and containing responsive drugs is formed. The microneedle patch can pierce the skin and intelligently release the loaded drugs according to the blood glucose concentration in the body, intelligently adjusting the blood glucose level. Through 3D printing of microneedles, painless, skin-piercing, and intelligent response-type blood glucose regulation are achieved, which is expected to guide the diagnosis and treatment of diabetes.

[0005] The Chinese patent document with publication number CN113927896A discloses a PDMS microneedle secondary mother plate transfer process based on 3D printing technology and provides its preparation method and application. The invention uses the PDMS transfer process to accurately replicate the resin microneedle positive mold printed by the light-curing printer, greatly simplifying the preparation process of the microneedle template, and has the advantages of size controllability, scalability, high precision, and economic efficiency. The resin microneedle tip template made by 3D printing technology is used as the mother mold for PDMS material transfer, greatly reducing the equipment cost problem in the microneedle preparation process, and has the advantages of economic efficiency, simple operation, flexible mode, personalization, and high precision. The prepared PDMS microneedle negative mold uses PDMS material for mold transfer. In addition to its low cost and simple operation, on the one hand, PDMS material has excellent replication performance, which can maximize the replication ratio of the microneedle array and minimize distortion.

[0006] The Chinese patent document with publication number CN110435139A discloses a method for making 3D-printed hollow microneedles and its application, belonging to the field of biological materials. The micro-stereolithography technology in 3D printing technology is used, and a photosensitive material with good biocompatibility is used as the printing material. A Form2 light-curing printer is used to print hollow microneedle arrays with different tip structures and parameters. Through parameter simulation calculation and optimization, hollow microneedle arrays with high mechanical properties and high drug release rates are selected for experiments. The optimized 3D-printed hollow microneedle array can be observed under a microscope to observe the internal aperture, and can successfully pierce the mouse skin. The invention encapsulates the 3D-printed hollow microneedle and a piezoelectric micropump into a minimally invasive insulin infusion system for intelligent in vivo blood glucose regulation. The 3D-printed hollow microneedle array can achieve controllable insulin release under the action of the piezoelectric micropump, successfully regulating blood glucose in the body.

[0007] The above patent documents all disclose technical solutions for preparing microneedle sheets by using a photocuring printing method in the 3D printing technology, and all adopt a scheme of printing the entire microneedle substrate and microneedles at one time, but there are the following problems in the process of photocuring printing the microneedle sheet: as shown in Figure 1 and Figure 2 When the entire microneedle substrate 200 of the microneedle sheet is printed at one time, internal stress is generated due to photocuring of the resin caused by ultraviolet irradiation, and the expression direction of the internal energy generated is upward, and the expression of the internal energy generated by the internal stress is stronger when the microneedle substrate 200 is closer to the edge portion, so that the intensity distribution of the internal energy generated by the internal stress on the entire microneedle substrate 200 is uneven, the internal energy at the edge of the microneedle substrate 200 is greater than that at the center of the microneedle substrate 200, the internal energy is expressed upward, and finally the edge of the microneedle substrate 200 is warped and curled; the microneedle sheet with the problem of warping and curling cannot be closely attached to the human skin, so that the microneedles cannot effectively penetrate into the human skin to deliver drugs, resulting in waste of the loaded drugs, and also seriously affecting the drug delivery effect of the microneedle sheet. SUMMARY

[0008] The technical problem to be solved by the present application is to provide a printing method of a microneedle sheet, which can keep the microneedle substrate in a flat state after printing.

[0009] To solve the above technical problems, the technical scheme adopted by the present application is: a printing method of a microneedle sheet, comprising the steps of printing microneedles and printing a microneedle substrate, in the step of printing the microneedle substrate, the microneedle substrate is divided into at least two microneedle substrate bodies which are printed in different time periods and then embedded to form a planar microneedle substrate.

[0010] Further, the microneedle substrate body comprises a plurality of microneedle substrate monomers arranged in a plane; and the microneedle substrate monomers on different microneedle substrate bodies are arranged in turn and staggered.

[0011] Further, the microneedle substrate has a two-layer or multi-layer structure, and the shapes of the microneedle substrate monomers on each layer of the microneedle substrate are the same or different.

[0012] Further, the shape of the microneedle substrate monomer is a circular ring, an elliptical ring, a rectangular ring, a triangle, a rectangle or a regular polygon; when the shape of the microneedle substrate monomer is a circular ring, an elliptical ring or a rectangular ring, the microneedle substrate monomers are arranged in turn and spaced apart in the plane according to the size; when the shape of the microneedle substrate monomer is a triangle, a rectangle or a regular polygon, the microneedle substrate monomers are arranged in an array and spaced apart in the plane.

[0013] Further, the shape of the microneedle substrate monomer is a circular ring.

[0014] Further, the printing method adopts 3D photosensitive resin printing, and the printing material is photosensitive resin.

[0015] Further, the printing method adopts 3D photosensitive resin printing, and the printing material is photosensitive resin.

[0016] Step one, draw black and white pictures as the printing model of microneedles and microneedle substrates according to the shape of microneedles and microneedle substrates, and draw the patterns corresponding to microneedles and microneedle substrate monomers on different microneedle substrate matrices on different pictures, and the microneedle substrate matrices on different pictures can be interlaced and embedded to form the shape of the required microneedle substrate;

[0017] Step two, import the drawn black and white pictures into the 3D printer, print microneedles, and print different microneedle substrate matrices in turn in different time periods, and the printing basis of the microneedle substrate monomers on the latter microneedle substrate matrix is the gap between the adjacent microneedle substrate monomers on the former microneedle substrate matrix.

[0018] Step three, the printing finished product is demolded.

[0019] Further, in step one, when the shape of the microneedle substrate monomer is a circular ring, the circular ring width of the microneedle substrate monomer on the former microneedle substrate matrix is greater than the circular ring width of the microneedle substrate monomer on the latter microneedle substrate matrix, and the circular ring width of the microneedle substrate monomer on each microneedle substrate matrix is not greater than 1 mm.

[0020] Further, in step two, the printing time of each microneedle substrate matrix in each layer of microneedle substrate is 0.5-1.2 s.

[0021] The application further discloses a microneedle sheet prepared by the printing method of the microneedle sheet.

[0022] The application has the following beneficial effects: the application improves the printing technology of the microneedle sheet, divides the microneedle substrate into at least two parts in the process of printing the microneedle substrate, controls the printing time to print different microneedle substrate matrices in different time periods, realizes the printing of the microneedle substrate in different parts, and finally keeps the shape of the printed microneedle substrate unchanged; compared with the scheme of printing the whole microneedle substrate at one time in the prior art, the application can express the internal stress generated in the microneedle substrate in different time periods and different parts due to the light curing process of photosensitive resin, divide the large internal stress generated in the whole microneedle substrate to different microneedle substrate matrices, and the internal stress generated in each microneedle substrate matrix is small and uniformly distributed, which is not enough to cause the deformation of the microneedle substrate monomer, thereby avoiding the problem of the microneedle substrate being warped by controlling the combination of the printing time period and the printing shape, and improving the yield and quality of the 3D printed microneedle sheet. BRIEF DESCRIPTION OF DRAWINGS

[0023] Figure 1 A schematic diagram of the warping of a rectangular microneedle base of a microneedle sheet in the prior art, wherein the arrow direction is the deformation direction, internal stress direction and internal energy expression direction of the microneedle base, and the length of the arrow represents the size of the force;

[0024] Figure 2 A schematic diagram of the warping of a circular microneedle base of a microneedle sheet in the prior art, wherein the arrow direction is the deformation direction, internal stress direction and internal energy expression direction of the microneedle base, and the length of the arrow represents the size of the force;

[0025] Figure 3 A top view schematic diagram of a microneedle base substrate when a circular ring-shaped microneedle base monomer is used in the present application, wherein the arrow direction is the deformation direction, internal stress direction and internal energy expression direction of the microneedle base, and the length of the arrow represents the size of the force;

[0026] Figure 4 A side view schematic diagram of a microneedle base substrate when a circular ring-shaped microneedle base monomer is used in the present application, wherein the arrow direction is the deformation direction, internal stress direction and internal energy expression direction of the microneedle base, and the length of the arrow represents the size of the force;

[0027] Figure 5 A combination schematic diagram of a microneedle base when a circular ring-shaped microneedle base monomer is used in the present application;

[0028] Figure 6 A combination schematic diagram of a microneedle base when an elliptical ring-shaped microneedle base monomer is used in the present application;

[0029] Figure 7 A combination schematic diagram of a microneedle base when a rectangular ring-shaped microneedle base monomer is used in the present application;

[0030] Figure 8 A combination schematic diagram of a microneedle base when a regular hexagonal microneedle base monomer is used in the present application;

[0031] Figure 9 A combination schematic diagram of a microneedle sheet when a circular ring-shaped microneedle base is used in the present application.

[0032] In the figure, the marks are: 100-microneedle, 200-microneedle base, 210-microneedle base substrate, 220-microneedle base monomer. DETAILED DESCRIPTION

[0033] In order to facilitate the understanding of the present application, the present application will be further described below in conjunction with the drawings and examples.

[0034] In the description of the present application, it should be noted that the terms "front", "back", "left", "right", "up", "down", "inner", and the like indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, and are only for the convenience of description, and do not indicate or imply that the devices or components referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as a limitation on the present application.

[0035] The printing method of the microneedle sheet disclosed in the present application improves the step of printing the microneedle substrate in the printing process of the microneedle sheet on the basis of the 3D printing technology currently used for the microneedle sheet, for the two steps of printing the microneedle and printing the microneedle substrate. In the prior art, the 3D printing technology is used for one-time forming in the process of printing the microneedle substrate. In order to avoid the defect of the edge of the microneedle substrate being warped due to the excessive expression of the internal stress of the edge of the microneedle substrate after the microneedle substrate is printed, the printing step of printing in different time periods combined with controlling the printing shape is adopted, the microneedle substrate is printed in different time periods, and the microneedle substrate body printed in different parts can finally form the microneedle substrate of the original planned shape.

[0036] The important technical point of placing the microneedle substrate in the present application is the shape of the microneedle substrate monomer 220 on each part of the microneedle substrate body 210 split from the microneedle substrate 200, which specifically includes the following four specific implementation schemes. The number of splits of the microneedle substrate 200 in the following four specific implementation schemes is two, which is only used for illustration and is not a limitation on the number of splits.

[0037] The first implementation scheme, as shown in Figure 5 The shape of the microneedle substrate monomer 220 is set as a circular ring, the microneedle substrate monomers 220 on the two parts of the microneedle substrate body 210 are sequentially diffused and spaced apart from inside to outside in the horizontal plane, the size of the circular ring-shaped microneedle substrate monomer 220 increases from inside to outside, and the microneedle substrate monomers 220 on the two parts of the microneedle substrate body 210 can be embedded and complementary to form a complete circular microneedle substrate 200.

[0038] The second implementation scheme, as shown in Figure 6 The shape of the microneedle substrate monomer 220 is set as an elliptical ring, like a circular ring, the microneedle substrate monomers 220 on the two parts of the microneedle substrate body 210 are sequentially diffused and spaced apart from inside to outside in the horizontal plane, the size of the elliptical ring-shaped microneedle substrate monomer 220 increases from inside to outside, and the microneedle substrate monomers 220 on the two parts of the microneedle substrate body 210 can be embedded and complementary to form a complete elliptical microneedle substrate 200.

[0039] The third implementation scheme, as shown in Figure 7As shown, the shape of the microneedle base monomer 220 is set as a rectangular ring, as the above-mentioned circular ring and elliptical ring, the microneedle base monomers 220 on the two-part microneedle base substrate 210 are sequentially spread and spaced apart from inside to outside in the horizontal plane, the size of the rectangular ring microneedle base monomer 220 increases sequentially from inside to outside, and the microneedle base monomers 220 on the two-part microneedle base substrate 210 can be embedded to form a complete rectangular microneedle base 200.

[0040] The fourth embodiment is as shown in FIG. 4C. Figure 8 As shown, the shape of the microneedle base monomer 220 is set as a regular hexagon, the microneedle base monomers 220 on the two-part microneedle base substrate 210 are arrayed and spaced apart in the horizontal plane, the microneedle base monomers 220 on the two-part microneedle base substrate 210 can be embedded into the gaps of the microneedle base monomers 220 on the other microneedle base substrate 210, and finally the two-part microneedle base substrates 210 combine to form a planar microneedle base 200. In this embodiment, the shape of the microneedle base monomer 220 can also be selected as a triangle, a rectangle, or other regular polygons, as long as it can be embedded into each other to form a complete planar microneedle base 200.

[0041] As shown in FIG. 4A, the microneedle base monomers 220 on the microneedle base substrate 210 are in the form of a circular ring. Figure 3 and Figure 4 The principle of the present application can prevent the edge of the microneedle base 200 from curling and warping. The control principle of the present application can be described as a shape-time control method. On the one hand, the shape is controlled to control the deformation of the microneedle base 200, and on the other hand, the time is controlled to control the deformation of the microneedle base 200. Since the microneedle base 200 is split into at least two-part microneedle base substrates 210, and the microneedle base substrate 210 is composed of multiple microneedle base monomers 220, it is equivalent to splitting the microneedle base 200 into many microneedle base monomers 220. The reason why the microneedle base 200 curls and warps due to deformation is that the internal stress of the edge of the microneedle base 200 is large, the internal stress of the microneedle base 200 near the center position is small, and the internal stress distribution of the microneedle base 200 is uneven in the upward direction. After the microneedle base 200 is split into multiple microneedle base monomers 220, it is equivalent to artificially dividing the internal stress of the microneedle base 200 to improve the uniformity of the internal stress distribution, and the internal stress of each microneedle base monomer 220 is significantly weakened, and the internal stress of each microneedle base monomer 220 is not enough to cause deformation in the direction perpendicular to the plane of the microneedle base 200. Moreover, the microneedle base monomers 220 that make up the microneedle base substrate 210 have special shapes, and these special-shaped microneedle base monomers 220 can control the size and direction of the internal stress and internal energy when the formed photosensitive resin is cured. Figure 3 and Figure 4As shown in the circular microneedle base monomer 220, the internal stress generated after printing is small in the direction perpendicular to the plane of the microneedle base 200, and the internal stress in the horizontal direction pointing to the center of the circle is large. The internal stress in the horizontal direction plays a dominant role in deformation control. Due to the special three-dimensional structure of the circular ring, if the circular ring is subjected to internal stress in the direction of the center of the circle and shrinks in the direction of the center of the circle, the adjacent microneedle base monomers 220 on the two-part microneedle base substrate 210 support each other, limiting the horizontal deformation of the adjacent microneedle base monomers 220, so that the circular microneedle base monomer 220 cannot shrink inward, and each circular microneedle base monomer 220 remains circular relative to the shape change, achieving the purpose of controlling deformation, and finally making the microneedle base 200 flat and not curling.

[0042] Specifically, as shown in the drawings, Figure 9 The printing method of the microneedle sheet disclosed by the application is implemented according to the following steps:

[0043] Step 1: According to the shape of the microneedle base 200 to be printed, a three-dimensional model of the microneedle sheet is constructed using modeling software, the size parameters of each part of the microneedle sheet are determined, and then a picture for printing is drawn according to the determined shape and size parameters. As shown in the drawings, Figure 9 For example, as shown in the drawings, the microneedle base 200 is divided into two-part microneedle base substrates 210. An array of microneedles 100 is drawn on one picture, and two-part microneedle base substrates 210 corresponding to the microneedle base monomers 220 are drawn on the other two pictures. The shape of the microneedle base monomer 220 is a circular ring, and the microneedle base monomers 220 on the two-part microneedle base substrates 210 can form the shape of the complete microneedle base 200.

[0044] In this step, the picture uses black and white colors, for example, the picture base is black, and the microneedle base monomers 220 on the picture are drawn in pure white; if the picture base is white, the microneedle base monomers 220 on the picture are drawn in pure black, then the picture; the format of the picture can be BMP format or PNG format. The specific number of pictures is set according to the number of microneedle base 200 splitting, in this embodiment, the microneedle base 200 uses two pictures to draw two-part microneedle base substrates 210, which can shorten the printing time, and the printing time and cost of the two-part microneedle base substrates 210 are the lowest.

[0045] In order to ensure that each part of the micro-needle base substrate 210 printed in different time periods can be completely embedded and matched, and the micro-needle base monomers 220 on each part of the micro-needle base substrate 210 can be perfectly combined to form the micro-needle base 200, the size of the micro-needle base monomers 220 can be optimized, that is, the width of the annular ring of the micro-needle base monomers 220 on the previously printed micro-needle base substrate 210 is greater than the width of the annular ring of the micro-needle base monomers 220 on the subsequently printed micro-needle base substrate 210, so that the micro-needle base monomers 220 on the subsequently printed micro-needle base substrate 210 can be formed in interference fit with the micro-needle base monomers 220 on the previously printed micro-needle base substrate 210, and it is more conducive to the combination of the micro-needle base 200 as a whole; and the width of the annular ring of the micro-needle base monomers 220 on each micro-needle base substrate 210 is set to be within 1 mm, and the size of 1 mm corresponds to 20 pixels on the picture.

[0046] In step two, the drawn black and white picture is imported into the 3D printer, and the printing material is selected to be photosensitive resin. If the light source system of the 3D printer adopts DLP PRO6500S light machine, the corresponding size of the printed drawn black and white picture is set to be 1920 pixels in length x 1080 pixels in width, and the base color of the picture is set to be black. If the light source system of the 3D printer adopts DLP Lightcrafter4500 light machine, the corresponding size of the printed drawn black and white picture is set to be 1140 pixels in length x 912 pixels in width, and the base color of the picture is set to be black. The drawn black and white picture is imported into the 3D printer, and the printing parameters and printing time are set. The specific printing steps of the micro-needle 100 are the existing technology which is not improved in the present application, and will not be described here. The printing time of each picture corresponding to the micro-needle base substrate 210 is set to be 0.5-1.2S, and 0.5S is the best printing time. Different micro-needle base substrates 210 are printed in different time periods, and the printing basis of the micro-needle base monomers 220 on the subsequent micro-needle base substrate 210 is the gap between the adjacent micro-needle base monomers 220 on the previous micro-needle base substrate 210. After the printing in different time periods is completed, the complete micro-needle base 200 is obtained.

[0047] In step three, the printing finished product is demolded. The micro-needle base 200 of the final product micro-needle sheet remains flat, and the edge of the micro-needle base 200 does not appear to be warped. When the micro-needle sheet is used for drug delivery, the micro-needle base 200 can be tightly attached to the surface of the human skin, and the micro-needle 100 can completely penetrate into the human skin to deliver the loaded drug.

[0048] The present application also discloses a micro-needle sheet prepared by the printing method of the micro-needle sheet.

Claims

1. A method for printing microneedles, comprising the steps of printing microneedles (100) and printing a microneedle substrate (200), characterized in that: In the step of printing microneedle substrate (200), the microneedle substrate (200) is split into at least two parts of microneedle substrate matrix (210), which are printed in stages and then interlocked to form a planar microneedle substrate (200). The microneedle substrate (210) includes a plurality of microneedle substrate monomers (220) arranged in a planar manner; the microneedle substrate monomers (220) on different microneedle substrates (210) are arranged alternately in sequence; The shape of the microneedle substrate monomer (220) is a circular ring, an elliptical ring, a rectangular ring, a triangle, a rectangle, or a regular polygon; when the shape of the microneedle substrate monomer (220) is a circular ring, an elliptical ring, or a rectangular ring, the microneedle substrate monomers (220) are arranged in a series of intervals from the inside to the outside on the plane according to their size; when the shape of the microneedle substrate monomer (220) is a triangle, a rectangle, or a regular polygon, the microneedle substrate monomers (220) are arranged in an array of intervals on the plane. The printing method uses 3D photosensitive resin printing, and the printing material is photosensitive resin.

2. The method for printing microneedles as described in claim 1, characterized in that: The microneedle substrate (200) has a two-layer or multi-layer structure, and the microneedle substrate monomers (220) on each layer of the microneedle substrate (200) may have the same or different shapes.

3. The method for printing microneedles as described in claim 1, characterized in that: The microneedle substrate monomer (220) is annular in shape.

4. A method for printing microneedles as described in any one of claims 1 to 3, characterized in that: Includes the following steps: Step 1: Draw black and white images of the microneedles (100) and microneedle substrates (200) as printing models based on the shapes of the microneedles (100) and microneedle substrates (200). Draw the patterns corresponding to the microneedles (100) and the patterns corresponding to the microneedle substrate units (220) on different microneedle substrate substrates (210) on different images. The microneedle substrate substrates (210) on different images can interlock and interlock to form the shape of the required microneedle substrate (200). Step 2: Import the drawn black and white image into the 3D printer, print microneedles (100) and print different microneedle substrates (210) in sequence at different time periods. The printing basis of the microneedle substrate unit (220) on the next microneedle substrate (210) is the gap between the adjacent microneedle substrate units (220) on the previous microneedle substrate (210). Step 3: Print the finished product and unmold it.

5. The method for printing microneedles as described in claim 4, characterized in that: In step one, when the microneedle substrate monomer (220) is annular, the annular width of the microneedle substrate monomer (220) on the previous microneedle substrate substrate (210) is greater than the annular width of the microneedle substrate monomer (220) on the subsequent microneedle substrate substrate (210); the annular width of the microneedle substrate monomer (220) on each microneedle substrate substrate (210) is not greater than 1 mm.

6. A microneedle sheet, characterized in that: The microneedle sheet is prepared by the microneedle sheet printing method described in claim 5.

Images