JP5897293B2 - Microneedle sheet and manufacturing method thereof, and stamper for microneedle sheet - Google Patents

Description

  The present invention relates to a microneedle sheet for injecting a drug into the epidermis of the skin, a method for producing the same, and a stamper for the microneedle sheet.

  The microneedle sheet is obtained by arranging minute needles (microneedles) at a predetermined density on a fixed member. The microneedle is generally formed in a conical shape having a length from the base to the tip of about 1 μm to 600 μm and a diameter of the base of about 0.3 μm to 400 μm. 1): It has a high aspect ratio of (1.5 to 3). The microneedle sheet is used to insert a drug by placing the microneedle into the epidermis portion of the skin by applying it to the skin portion of the human body. The fixing member may be any member that fixes a large number of microneedles, and various types of members such as a sheet-like member and a circular plate-like member are used.

  The length of the microneedle is about several hundred μm as described above, and can be used with almost no colic. Further, when the microneedle sheet is separated from the skin, the microneedle portion is formed of a self-dissolving substance so that the human body is not affected even if the microneedle remains in the skin.

  Among drugs inserted into the human body using such microneedles, expensive drugs are included. For this reason, it has been proposed that the microneedle is formed in a multilayer structure so that the drug is included only in the insertion portion of the microneedle at the tip of the skin and the drug is not included in the portion other than the tip (for example, patents). Reference 1).

  A conventional method for manufacturing a microneedle sheet having such a multi-layered microneedle will be described with reference to FIG.

  First, a stamper 90 in which a plurality of conical recesses 91 are formed is prepared. The stamper 90 is formed by pressing a flat original plate on which protrusions corresponding to the individual microneedles are formed against the stamper base material. In the stamper base material, a plurality of conical recesses corresponding to the plurality of protrusions of the original plate are formed, and these become the stamper 90. Each protrusion of the original plate is formed by a method such as micromachining, vacuum processing, or photolithography. The protrusion has a conical shape or a pyramid shape having a cross-sectional shape such as a circle, a corner, or an ellipse.

  A first needle material 92 containing a drug is filled in each recess 91 of the stamper 90. The first needle raw material 92 is filled in a fixed amount by using, for example, a dispenser at the tip portion in each recess 91 and then dried.

  Next, the second needle raw material 93 not containing a drug is filled in each of the recesses 91 filled with the first needle raw material 92. The second needle raw material 93 is filled on the first needle raw material 92 using, for example, a squeegee 94 and then dried.

  Then, a fixed base is affixed on the stamper 90, and the needle raw materials filled in the respective recesses 91 are fixed to the fixed base. By separating the fixed base from the stamper 90, a microneedle sheet having a two-layer structure including a first layer containing a drug made of the first needle raw material 92 and a second layer made of the second needle raw material 93 is obtained. Complete.

JP 2010-94414 A

  However, the conventional method for manufacturing a microneedle sheet having a microneedle having a multilayer structure has the following problems.

  When each of the recesses 91 filled with the first needle raw material 92 is filled with the second needle raw material 93 containing no drug using the squeegee 94, bubbles 95 are formed in the concave portion 91 as shown in FIG. It may be involved. Thus, in the microneedle sheet formed in the state in which the bubbles 95 are entrained, the first layer containing the drug cannot be reliably fixed to the second layer, and functions as a microneedle. There is a problem that it cannot be done.

  Generally, in the conventional microneedle, the height of the first layer containing the chemical solution is formed to be about 300 μm. In recent years, there is a demand for reducing the filling amount of the first layer to a necessary limit from the viewpoint of efficiently using a drug in a microneedle sheet.

  However, in the case where the filling amount of the first needle raw material 91 into the concave portion 91 is reduced, there may be a problem that the bubbles 95 are more easily involved when the second needle raw material 93 is filled. .

  Accordingly, an object of the present invention is to provide a microneedle sheet, a method for manufacturing the same, and a stamper for the microneedle sheet, which can suppress the entrainment of bubbles in the microneedle having a multilayer structure. is there.

  In order to achieve the above object, the present invention is configured as follows.

  According to the first aspect of the present invention, in a microneedle sheet including a fixing member and a plurality of cone-shaped needles fixed to the surface of the fixing member, the needle is disposed on the tip side of the cone. A first layer and a second layer that forms a part of the cone and is continuous with the first layer, and in the needle, the angle formed by the opposing side surfaces of the cone is larger in the second layer than in the first layer A microneedle sheet is provided.

  According to the second aspect of the present invention, in the needle, the microneedle according to the first aspect, wherein a step portion for changing an angle formed between the side surface of the first layer and the side surface of the second layer is formed on the side surface of the cone. Provide a sheet.

  According to the third aspect of the present invention, the interface between the first layer and the second layer is in contact with the side surface of the cone, or the position where the interface between the first layer and the second layer is in contact with the side surface of the cone. The microneedle sheet according to the second aspect, in which a step portion is formed at a position on the first layer side, is provided.

  According to the 4th aspect of this invention, a step part is formed only in a part of cone side surface, and the formation position of a step part is arrange | positioned in the same direction along the surface of a fixing member with each needle, 2nd A microneedle sheet according to the aspect or the third aspect is provided.

  According to the fifth aspect of the present invention, there is provided a stamper having a plurality of conical recesses that taper from the front surface to the back surface of a sheet-like base material, which is a method for manufacturing a microneedle sheet. Relative movement of the squeegee and the stamper in the in-plane direction of the stamping process, the first layer forming process of filling the first needle raw material into the respective recesses of the stamper to form the cone-shaped first layer, and the squeegee and stamper Then, the second needle raw material is filled in each of the recesses in which the first layer is formed, and the second layer having a side surface with an angle larger than the angle formed by the opposing side surfaces of the cone in the first layer is formed. And a second layer forming step. The method for producing a microneedle sheet is provided.

  According to the sixth aspect of the present invention, in the preparation step, the inner surface of each recess forms a first part disposed on the tip side of the cone, a part of the cone, and the first part. A stamper having an inner surface of the second portion having a larger angle than the angle formed by the opposing inner surfaces of the cones in the first portion, and in the first layer forming step, The microneedle sheet according to the fifth aspect, in which the first needle raw material is filled in the recess so as to reach or exceed the boundary between the first portion and the second portion on the inner surface of each recess. A manufacturing method is provided.

  According to a seventh aspect of the present invention, in the sixth aspect, the preparation step prepares a stamper in which the boundary between the first portion and the second portion on the inner surface of each recess is formed as a stepped portion. A method for producing a microneedle sheet is provided.

  According to the eighth aspect of the present invention, in the preparation step, a step is formed only on a part of the inner surface of the cone-shaped recess, and the formation position of the step in each recess is along the surface of the stamper. The microneedle according to the seventh aspect, wherein stampers arranged in the same direction are prepared, and the squeegee is moved relative to the stamper in a direction opposite to the direction of the formation position of the step portion in the second layer forming step. A method for manufacturing a sheet is provided.

  According to the ninth aspect of the present invention, there is provided a stamper for a microneedle sheet having a plurality of conical concave portions extending in a tapered manner from the front surface to the back surface of a sheet-shaped base material, The inner surface includes a first portion disposed on the tip side of the cone, and a second portion that forms a part of the cone and continues to the first portion. A stamper for a microneedle sheet is provided in which an inner surface of a second portion has a larger angle than an angle formed by the side surface.

  According to the tenth aspect of the present invention, there is provided the stamper for a microneedle sheet according to the ninth aspect, wherein the boundary between the first portion and the second portion on the inner surface of each recess is formed as a stepped portion. provide.

  According to the eleventh aspect of the present invention, the step is formed only on a part of the inner side surface of the conical recess, and the formation position of the step in each recess is arranged in the same direction along the surface of the base material. A stamper for a microneedle sheet according to the ninth aspect or the tenth aspect is provided.

  According to the present invention, in a needle comprising a first layer disposed on the tip side of a cone and a second layer that forms part of the cone and continues to the first layer, the side surfaces of the cone facing each other The second layer is configured to have a larger angle than the first layer. Therefore, when filling the needle raw material which forms a 2nd layer using a squeegee into the recessed part in which the 1st layer was formed using a squeegee, the entrainment of the bubble in a recessed part can be suppressed.

Sectional drawing of the stamper used with the manufacturing method of the microneedle sheet | seat concerning embodiment of this invention Schematic diagram of the concave portion of the stamper of the present embodiment The flowchart which shows the procedure of the manufacturing method of this Embodiment Explanatory drawing of the 1st needle raw material filling process in the manufacturing method of this Embodiment Explanatory drawing of the 1st needle raw material drying process in the manufacturing method of this Embodiment Explanatory drawing of the 2nd needle raw material filling process in the manufacturing method of this Embodiment Explanatory drawing of the 2nd needle raw material filling process in the manufacturing method of this Embodiment Explanatory drawing of the 2nd needle raw material drying process in the manufacturing method of this Embodiment Explanatory drawing of the adhesive material arrangement | positioning process in the manufacturing method of this Embodiment Explanatory drawing of the microneedle sheet peeling process in the manufacturing method of this Embodiment Schematic diagram of the concave portion of the stamper of the present embodiment Sectional view of the microneedle of the present embodiment Schematic diagram of a concave portion of a stamper according to a modification of the present embodiment Schematic diagram of a concave portion of a stamper according to a modification of the present embodiment Schematic diagram of a stamper according to a modification of the present embodiment Explanatory drawing of the manufacturing method of the conventional microneedle sheet Explanatory drawing of the manufacturing method of the conventional microneedle sheet

  Embodiments according to the present invention will be described below in detail with reference to the drawings.

  A schematic diagram of a stamper 1 used in the method of manufacturing a microneedle sheet according to an embodiment of the present invention is shown in FIG.

  As shown in FIG. 1, the stamper 1 is a sheet-like base material 2 having a conical recess 3 formed therein. The material of the base material 2 is not particularly limited. However, since the microneedle sheet is a pharmaceutical, a material that is not easily contaminated (contaminated) or a material that does not affect the human body is preferable. For example, SUS316L and Hastelloy are suitably used for metals, and PTFE, polypropylene, polyethylene, and the like are suitably used for plastics.

  Each recess 3 extends in a tapered manner from the surface (one surface (upper surface in FIG. 1)) of the base material 2 toward the back surface (the other surface (lower surface in FIG. 1)). The recess 3 is formed as a generally conical or pyramidal space having a cross-sectional shape such as a circle, corner, or ellipse.

  Here, the shape of the recess 3 of the stamper 1 will be described with reference to the schematic diagram of FIG.

  As shown in FIG. 2, the inner side surface of the generally cone-shaped recess 3 forms a first portion 3 a disposed on the tip end side (the lower side in the drawing) of the cone shape, and a part of the cone shape; It is comprised by the 2nd part 3b (illustration upper side) following the 1st part 3a. The angle θ2 formed by the inner surface facing the second portion 3b of the recess 3 is set larger than the angle θ1 formed by the facing inner surface of the first portion 3a. That is, in the generally conical recess 3, the inclined surface of the second portion 3 b is inclined more gently than the inclined surface (inner surface) of the first portion 3 a.

  Further, as shown in FIG. 2, the inclined surfaces of the first portion 3a and the second portion 3b are formed as linear inclined surfaces in a cross-sectional view, and the boundary between the first portion 3a and the second portion 3b. Is a step 3c that changes the angle of the inclined surface from θ1 to θ2.

  As a specific example of the shape and size of the recess 3, the height H of the recess 3 is 500 μm, the width W 1 when the first portion 3 a is virtually extended to the opening of the recess 3 is 270 μm, and the first portion 3 a The angle θ1 is 30 degrees. In addition, it is preferable to set the angle θ1 of the first portion 3a in a range of 25 degrees to 35 degrees in consideration of easiness to pierce the skin. Further, the angle θ2 of the second portion 3b is set larger than the angle θ1 of the first portion 3a, and is preferably set in a range of 30 degrees to 160 degrees. The width W2 of the opening portion of the recess 3 (the width of the opening portion of the second portion 3b) is set to a size larger than 270 μm according to the size of the angle θ2 of the second portion 3b. In addition, it is preferable that the width W2 of the opening part of the recessed part 3 is set so that it may not interfere with the opening part of the adjacent recessed part 3. FIG.

  Such a stamper 1 is formed by pressing a flat original plate on which conical projections corresponding to individual microneedles are formed against the stamper base material 2. Alternatively, the stamper 1 may be formed by a method such as injection molding in which a mold is made of a resin melted in an original plate. Although the material of the original plate is not particularly limited, it may be a metal having excellent durability during the production of a stamper or a material with high machinability and low cost. For example, stainless steel, titanium, tungsten, hastelloy, copper, aluminum, nickel, silicon and the like can be used. Further, the protrusion may be formed by a method using photolithography in addition to processing by cutting out from the main body.

  The height of the projection of the original plate is suitably determined depending on the body part to be transdermally administered and the specifications of the drug. For example, the height of the projection is determined in the range of about 1 μm to 500 μm. The protrusion has a substantially conical shape or a pyramid shape having a cross-sectional shape such as a circle, a corner, or an ellipse. In the stamper base material 2, a plurality of conical recesses 3 corresponding to the plurality of protrusions of the original plate are formed, and these become the stamper 1.

  Next, the manufacturing method of the microneedle sheet of this Embodiment is demonstrated concretely. In the description, a flowchart showing the procedure of the microneedle sheet manufacturing method is shown in FIG. 3, and schematic explanatory views of the state of the stamper and the like in each procedure (process) are shown in FIGS. 4A to 4G.

  First, in step S1 of the flowchart of FIG. 3, the stamper 1 having the configuration shown in FIG. 1 is prepared (step S1). Next, as shown in FIG. 4A, the first needle raw material 11 is supplied onto the surface of the stamper 1, and the squeegee 13 is moved along the surface of the stamper 1, so that a predetermined amount is obtained in each recess 3. The first needle raw material 11 is filled (step S2).

  As shown in the schematic diagram of FIG. 5, in each of the recesses 3, the first needle raw material 11 is filled in the first portion 3 a, and a step portion that is a boundary between the first portion 3 a and the second portion 3 b. It fills so that it may reach a part of 2nd part 3b exceeding 3c. In the present embodiment, the case where the first needle raw material 11 is filled using the squeegee 13 is illustrated, but filling may be performed using a dispenser. The first needle material 11 contains a drug, and is configured, for example, by mixing a drug in a base material common to a second needle material described later. Here, the drug is a pure chemical substance having a physiological activity, for example, peptide protein drugs such as insulin, growth hormone, erythropoietin, and interferon, macromolecular drugs such as vaccine antigen, DNA, RNA, vitamins, Examples include hormones and the like, and those containing these as main components may also be used. The first and second needle raw materials are preferably materials that are discharged without remaining in the body.

  Thereafter, as shown in FIG. 4B, the filled first needle raw material 11 is dried (step S3). This drying process is performed by controlling the drying speed while controlling the evaporation speed from the first needle material 11 by arranging the stamper 1 in a predetermined temperature and humidity environment, for example. As a result, the first needle raw material 11 is solidified in a substantially conical shape at the tip portion in each recess 3, and the first layer 11 of the microneedle (the same reference numeral as the first needle raw material 11 is used). ) Is formed.

  Next, as shown in FIG. 4C, the second needle raw material 12 is supplied onto the surface of the stamper 1, and the squeegee 14 is moved along the surface of the stamper 1, thereby forming the first layer 11. The second needle material 12 is filled into the recess 3 (step S4). As described above, the angle θ2 of the second portion 3b of each recess 3 is set to be larger than the angle θ1 of the first portion 3a, and therefore, when the second needle material 12 is filled by the squeegee 14. In addition, it is possible to suppress the entrainment of bubbles in the recess 3. Therefore, as shown in FIG. 4D, the second needle raw material 12 is reliably filled into the remaining space in the recess 3 filled with the first needle raw material 11 first. Note that the second needle material 12 does not substantially contain a drug. Here, “substantially not containing” means that the drug is not included for the purpose of administering the drug into the human body through the skin, and does not exclude the inclusion of a drug other than the drug in the human body.

  Thereafter, as shown in FIG. 4E, the filled second needle raw material 12 is dried (step S5). In each recess 3, the solvent is evaporated from the second needle raw material 12 to solidify, and a second layer 12 (using the same reference numerals as the second needle raw material 12) joined to the first layer 11 is formed. Is done. In particular, by using a compatible material as a common polymer material for the first needle raw material 11 and the second needle raw material 12, the bonding between the first layer 11 and the second layer 12 can be improved, The integrity of the microneedle having a multilayer structure can be enhanced.

  Next, as shown in FIG. 4F, an adhesive material 16 is disposed using a squeegee 15 on the surface of the stamper 1 in a state where the second layer 12 is formed in each recess 3 (step S6).

  Thereafter, as shown in FIG. 4G, a fixing base (fixing member) 17 is attached on the adhesive material 16 (step S7), and the adhesive material 16 is dried. Thereafter, the fixed base 17 and the adhesive material 16 are peeled off from the surface of the stamper 1. Thereby, the microneedle sheet | seat 20 provided with the some microneedle 21 fixed on the fixed base | substrate 17 via the adhesive material 16 can be obtained (FIG. 4G, step S8). Each microneedle 21 is formed as an integral cone-shaped needle having a two-layer structure including a first layer 11 and a second layer 12.

  Here, the structure of the microneedle 21 which the microneedle sheet | seat 20 manufactured in this way has is demonstrated using the schematic diagram of FIG.

  As shown in FIG. 6, the microneedle 21 has a substantially cone-like shape, and forms the first layer 11 disposed on the tip end side (the lower side in the drawing) of the cone shape and a part of the cone. And a second layer 12 (upper side in the figure) continuous to the first layer.

  The microneedle 21 is formed in accordance with the shape of the concave portion 3 of the stamper 1 described above. Specifically, the angle θ1 formed by the facing side surface 11a of the first layer 11 is set to be smaller than the angle θ2 formed by the facing side surface 12a of the second layer 12, and the side surface 11a of the first layer 11 and A step portion 19 is formed at the boundary with the side surface 12 a of the second layer 12. In addition, the position where the interface between the first layer 11 and the second layer 12 is in contact with the side surface of the microneedle 21 is located closer to the second layer 12 than the stepped portion 19.

  Here, a method of calculating the angle θ1 of the first layer 11 in the microneedle 21 of the present embodiment will be described with reference to FIG.

  As shown in FIG. 6, a position H1 of 20 μm and a position H2 of 250 μm from the tip 21a of the microneedle 21 toward the bottom surface 21b are set as reference height positions. At the respective reference height positions H1 and H2, reference side surface positions P1 and P2 in contact with the side surface of the microneedle 21 are obtained. The angle at which the virtual line L connecting the obtained reference side surface positions P1 and P2 intersects is calculated as the angle θ1 of the first layer 11. Further, at the height position of the tip 21a of the microneedle 21, the width between the respective virtual straight lines L becomes the diameter D of the tip 21a. In addition, when the height of the first layer 11 is less than 250 μm, the reference height position H2 is appropriately set.

  For the calculation of the angle θ2 of the second layer 12, two reference height positions are set with reference to the height position of the step portion 19, and the two reference height positions are By obtaining the reference side surface position in contact with each other, it can be calculated in the same manner as the angle θ1 of the first layer 11.

  The angle θ1 of the first layer 11 is preferably set in the range of 25 degrees to 35 degrees in consideration of the ease of sticking into the skin, and the angle θ2 of the second layer 12 is the angle of the first layer 11 It is preferably set to be larger than θ1 and set in a range of 30 to 160 degrees. In order to penetrate the skin, the diameter of the tip 21a of the microneedle 21 is preferably 20 μm or less, more preferably about 10 μm. Furthermore, it is preferable that the tip of the microneedle 21 is sharpened. The height of the first layer 11 is preferably set in the range of 50 to 400 μm depending on the amount of insertion into the skin, the amount of drug, and the like.

  In the microneedle 21 shown in FIG. 6, the layer interface 18 between the first layer 11 and the second layer 12 in the microneedle 21 is substantially flat. In this way, when the layer interface 18 is a flat surface, it becomes easy to manage the filling amount of the first needle raw material 11 in each recess 3 with the volume based on the shape of the first layer 11 after filling. . On the other hand, instead of making the layer interface flat as described above, it may be curved. When the layer interface is curved, the contact area between the first layer 11 and the second layer 12 can be increased, and the bond strength can be increased. In addition, the form of such a layer interface can be controlled to a desired shape by the drying time (for example, temperature and humidity environment conditions) of the first needle material 11.

  According to the manufacturing method of the microneedle sheet of the present embodiment, in the stamper 1 that forms the microneedle 21 having the multilayer structure, the angle θ2 of the second portion 3b of each concave portion 3 having a generally conical shape is The first portion 3a is set to be larger than the angle θ1. Therefore, when the second needle raw material 12 is filled into the respective recesses 3 in which the first layer 11 is formed using the squeegee 14, the inclined surface of the second portion 3b that is gentler than the first portion 3a is provided. Utilizing this, it is possible to suppress air bubbles from being caught in the recess 3. Therefore, the second needle raw material 12 is reliably filled using the squeegee 14 in the remaining space in the recess 3 filled with the first needle raw material 11 first. Therefore, in the manufactured microneedle sheet, the occurrence of defects of the microneedle 21 can be suppressed, and the quality can be improved.

  Moreover, in each recessed part 3, while the 1st needle raw material 11 is filled in the 1st part 3a, it passes over the step part 3c which is a boundary of the 1st part 3a and the 2nd part 3b, and the 2nd part It is filled to reach part of 3b. Therefore, the second needle raw material 12 can be filled into the recess 3 without contacting the inclined surface of the first portion 3a, and entrainment of bubbles can be effectively suppressed.

  Instead of the case where the first needle material 11 is filled so as to reach a part of the second portion 3b beyond the step portion 3c which is the boundary between the first portion 3a and the second portion 3b. The first needle material 11 may be filled so as to substantially coincide with the formation position of the stepped portion 3c. If the second needle raw material 12 is not in contact with the inclined surface of the first portion 3a when the second needle raw material 12 is filled, entrainment of bubbles can be suppressed.

  Furthermore, in the recess 3 of the stamper 1, the inclined surface of the first portion 3a on the front end side is formed linearly in a sectional view. In such a shape, the volume center of the space surrounded by the first portion 3 a is positioned closer to the distal end side 21 a of the microneedle 21 than in a shape in which the inclined surface is curved in a direction protruding inward. be able to. Therefore, the height of the first layer 3a containing the drug can be shortened, and the drug can be effectively administered to the skin.

Various other shapes can be adopted as the shape of the recess 3 formed in the stamper 1. For example, as shown in the schematic diagram of FIG. 7A, the second portion is more than the angle θ1 of the first portion 53a on the distal end side while curving the entire side surface of the generally conical recess 53 inward of the recess 53. The angle θ2 of 53b may be set large. In such a shape, there is no stepped portion, and the side surface of the recess 53 can be made smooth.

  Further, as shown in the schematic diagram of FIG. 7B, a stepped portion 63c may be provided only on a part of the side surface of the concave portion 63 constituted by the first portion 63a and the second portion 63b. In this case, as shown in FIG. 7C, it is preferable to arrange the stepped portions 63 c in the same direction along the surface of the base material 2. Entrainment of bubbles can be suppressed by moving the squeegee in the direction opposite to the formation direction of the stepped portion 63c and filling the needle material.

  In the above description, a case of a two-layer structure has been described as an example of a microneedle having a multilayer structure, but the present invention can also be applied to a structure of three or more layers.

  It is to be noted that, by appropriately combining arbitrary embodiments of the various embodiments described above, the effects possessed by them can be produced.

  INDUSTRIAL APPLICABILITY The present invention can be widely used for a microneedle sheet for inserting a drug into the epidermis, a manufacturing method thereof, and a stamper for the microneedle sheet.

DESCRIPTION OF SYMBOLS 1 Stamper 2 Base material 3 Recess 3a 1st part 3b 2nd part 3c Step part 11 1st needle raw material, 1st layer 12 2nd needle raw material, 2nd layer 13-15 Squeegee 16 Adhesive material 17 Fixed base 20 Micro Needle seat 21 Microneedle 21a Tip 21b Bottom

Claims (5)

In a microneedle sheet comprising a fixing member and a plurality of cone-shaped needles fixed to the surface of the fixing member,
The needle includes a first layer disposed on the tip side of the cone, and a second layer that forms a part of the cone and continues to the first layer,
In the needle, the stepped portion to change the face angle of the side surfaces is rather large, the second layer than the first layer, the side surface and the angle of the side surface of the second layer of the first layer of cones of the cone side one A microneedle sheet that is formed only on the portion, and the stepped portion is formed in the same direction along the surface of the fixing member at each needle. The step portion is located at a position where the interface between the first layer and the second layer is in contact with the cone side surface, or at a position closer to the first layer than a position where the interface between the first layer and the second layer is in contact with the cone side surface. The microneedle sheet according to claim 1 , wherein the microneedle sheet is formed. A method of manufacturing a microneedle sheet,
A preparation step of preparing a stamper having a plurality of conical concave portions extending tapered from the front surface of the sheet-shaped base material toward the back surface;
A first layer forming step of filling the first needle raw material into each of the recesses of the stamper to form a cone-shaped first layer;
The squeegee and the stamper are moved relative to each other in the in-plane direction of the stamper, the second needle material is filled in the respective recesses in which the first layer is formed, and the angle formed between the opposing side surfaces of the cone in the first layer look including a second layer forming step of forming a second layer having a side surface of an angle greater than,
In the preparation step, the inner surface of each recess includes a first portion disposed on the tip side of the cone, and a second portion that forms part of the cone and continues to the first portion, The inner surface of the second portion has a larger angle than the angle formed by the opposing inner surfaces of the cones in one portion, and the step between the first portion and the second portion on the inner surface of each recess As the stepper is formed only on a part of the inner side surface of the conical recess, and the stamper in which the position of the step in each recess is arranged in the same direction along the surface of the stamper,
A method of manufacturing a microneedle sheet, wherein, in the second layer forming step, the squeegee is moved relative to the stamper in a direction opposite to the direction in which the stepped portion is formed . The first needle raw material is filled in the concave portion so as to reach or exceed the boundary between the first portion and the second portion on the inner surface of each concave portion in the first layer forming step. 4. A method for producing a microneedle sheet according to 3 . A stamper for a microneedle sheet having a plurality of conical concave portions extending tapered from the front surface to the back surface of a sheet-shaped base material,
The inner surface of each recess includes a first portion disposed on the tip side of the cone, and a second portion that forms part of the cone and continues to the first portion,
Than the angle of the inner surface facing the cone in the first portion, the inner surface of the second portion have a large angle, the boundary between the first portion and the second portion in the inner surface of each concave stepped portion The step is formed only on a part of the inner surface of the conical recess, and the formation position of the step in each recess is arranged in the same direction along the surface of the base material. Stamper for microneedle seat.

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