JP2017070425A - Mold, and method for producing sheet - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a mold which can remove the air and can prevent liquid leakage, and a method for producing a sheet.SOLUTION: A mold 10 comprises a first face 12 and a second face 14 facing each other, and a plurality of recesses 16 each penetrating a first opening 16A of the first face 12 and a second opening 16B of the second face 14 and tapered toward from the first face 12 to the second face 14. The mold also comprises an annular projection 20 that is positioned around the second opening 16B and closes the second opening 16B when the second face 14 is fixed to a plate.SELECTED DRAWING: Figure 2

Description

  The present invention relates to a mold and a sheet manufacturing method.

  In recent years, a micro-needle array (Micro-Needle Array) has been known as a new dosage form that can administer drugs such as insulin, vaccine (Vaccines), and hGH (human growth hormone) into the skin without pain. ing. The microneedle array is an array of biodegradable microneedles (also referred to as microneedles or microneedles) containing a drug. By attaching the microneedles to the skin, the microneedles pierce the skin, the microneedles are absorbed in the skin, and the drug contained in the microneedles can be administered into the skin. The microneedle array is also called a transdermal absorption sheet.

  In general, in a method of manufacturing a microneedle array, a mold having a plurality of inverted holes is produced from an original plate having a plurality of protrusions. A microneedle array can be manufactured by filling a plurality of holes in a mold with a raw material containing a drug, drying and solidifying the raw material, and peeling the molded product from the mold.

  However, in the above manufacturing method, since air exists in the holes of the mold, it takes time to fill the holes with the raw material, and there is a problem that it is not easily filled. In order to solve this problem, it has been proposed to provide a through hole in the mold.

  Patent Document 1 discloses that air in a mold recess is vented by a through-hole that is provided in the mold recess and closes by the elasticity of the base material when no load is applied.

  Patent Document 2 discloses that a waterproof and moisture-permeable material is provided on the surface of a through-hole provided in a mold to remove air from the recess and prevent leakage of the chemical solution.

Japanese Patent No. 5558772 International Publication No. WO2014 / 077243

  However, in the technique of Patent Document 1, no consideration is given to preventing the chemical solution (polymer solution) from leaking out of the concave portion of the mold. Moreover, in the technique of patent document 2, the process of providing a waterproof moisture-permeable material and a waterproof moisture-permeable material is needed in production of a mold, and the work burden and cost of production increase.

  The present invention has been made in view of such circumstances, and provides a mold that can be manufactured relatively easily, can remove air from a recess, and can prevent liquid leakage, and a sheet manufacturing method. The purpose is to do.

  According to one aspect of the present invention, the mold passes through the first surface and the second surface facing each other, the first opening on the first surface and the second opening on the second surface, and from the first surface to the second surface. The mold has a plurality of concave portions that are tapered toward the end, and has an annular protrusion that is positioned around the second opening and closes the second opening when the second surface is fixed to the plate.

  Preferably, the length of the second opening is 10 to 60 μm, the height of the protruding portion from the second surface is 10 to 80 μm, and the length of the third opening of the protruding portion is 1 to 40 μm.

  Preferably, the protruding portion is tapered in a sectional view.

  Preferably, the mold is made of an elastic material.

  Preferably, the mold is made of a silicone resin.

  According to another aspect of the present invention, in the sheet manufacturing method, the second surface of the mold is fixed to a suction plate made of a porous material, and the second opening is closed by a protrusion, and the suction plate is sucked. However, the method includes a step of supplying a liquid to the concave portion of the mold, a step of drying the liquid to form a sheet, and a step of peeling the sheet from the mold.

  Preferably, the liquid is composed of a water-soluble material.

  Preferably, the sheet is a microneedle array.

  According to the mold of the present invention, it can be produced relatively easily, air can be removed from the recess, and liquid leakage can be prevented. According to the sheet manufacturing method of the present invention, air can be removed from the recesses and liquid leakage can be prevented.

It is a perspective view of a mold. It is a partial cross section figure of a mold. It is a partial expanded sectional view of a mold. It is a perspective view of a type | mold. It is process drawing which shows a part of manufacturing process of a mold. It is process drawing which shows a part of manufacturing process of a mold. It is the elements on larger scale of the protruding pattern at the time of mold formation, and a separation sheet. It is process drawing which shows the procedure which manufactures the type | mold which has a protruding pattern. It is process drawing which manufactures a microneedle array. It is the elements on larger scale of a mold preparation process.

  Hereinafter, preferred embodiments of the present invention will be described with reference to the accompanying drawings. The present invention is illustrated by the following preferred embodiments. Changes can be made by many techniques without departing from the scope of the present invention, and other embodiments than the present embodiment can be utilized. Accordingly, all modifications within the scope of the present invention are included in the claims.

  Here, in the drawing, portions indicated by the same symbols are similar elements having similar functions. In addition, in the present specification, when a numerical range is expressed using “˜”, upper and lower numerical values indicated by “˜” are also included in the numerical range.

  The mold of this embodiment will be described with reference to FIGS. 1 to 3 by taking a mold for forming a microneedle array as an example. 1 is a perspective view of a mold for forming a microneedle array, FIG. 2 is a partial cross-sectional view of the mold for forming a microneedle array, and FIG. 3 is a microneedle array formed in a circled portion of FIG. FIG.

  As shown in FIG. 1, a mold 10 for molding a microneedle array (hereinafter, mold 10) has a three-dimensional shape having a first surface 12 and a second surface 14 that face each other. In this embodiment, the mold 10 has a sheet shape having the first surface 12 and the second surface 14 having a large area with respect to the thickness, but is not limited to this shape. As long as the 1st surface 12 and the 2nd surface 14 space apart and the recessed part 16 mentioned later can be formed, the shape is not limited.

  The mold 10 has a plurality of recesses 16 that pass through the first opening 16 </ b> A of the first surface 12 and the second opening 16 </ b> B of the second surface 14 and are tapered from the first surface 12 toward the second surface 14. ing. The recess 16 is a through hole that penetrates the first opening 16 </ b> A of the first surface 12 and the second opening 16 </ b> B of the second surface 14.

  The concave pattern 18 is configured by regularly arranging the plurality of concave portions 16. In the present embodiment, nine concave patterns 18 are formed in the mold 10, and each concave pattern 18 is composed of 25 concave portions 16 arranged 5 × 5. The number and arrangement of the concave patterns 18 and the number and arrangement of the concave parts constituting the concave pattern 18 are appropriately determined according to the shape of the microneedle array to be manufactured.

  As shown in FIGS. 2 and 3, the recess 16 has a tapered shape from the first surface 12 toward the second surface 14 in a cross-sectional view. Therefore, the area of the second opening 16B is smaller than the area of the first opening 16A.

The mold 10 of the present embodiment has an annular protrusion 20 on the second surface 14 that is positioned around the second opening 16B and is tapered in a sectional view. As shown in FIGS. 2 and 3, the protruding portion 20 has a tapered shape at the tip end side as it is away from the second surface 14 in a cross-sectional view. Moreover, the protrusion part 20 has the cyclic | annular shape by planar view surrounding the circumference | surroundings of the 2nd opening 16B. A third opening 20 </ b> A is formed at the tip of the annular protrusion 20. The inner wall 16C of the recess 16 extends from the first opening 16A over the second opening 16B to the inner wall 20B of the protrusion 20 and extends to the third opening 20A. The area of the third opening 20A is smaller than the area of the second opening 16B. In the present embodiment, the protruding portion 20 has a tapered shape in a cross-sectional view. However, the present invention is not limited to this, and when the second surface 14 is fixed to a plate, the protruding portion 20 has the second opening 16B. If it can be closed, the shape of the protrusion part 20 will not be limited.

  The height H from the second surface 14 of the protrusion 20 is, for example, preferably 10 to 80 μm, more preferably 20 to 70 μm, and still more preferably 30 to 60 μm. The length L1 of the first opening 16A is preferably 200 to 1000 μm, more preferably 250 to 800 μm, and even more preferably 300 to 600 μm. The length L2 of the second opening 16B is preferably 10 to 60 μm, more preferably 15 to 50 μm, and still more preferably 20 to 40 μm. The length L3 of the third opening 20A is preferably 1 to 40 μm, more preferably 3 to 30 μm, and even more preferably 5 to 20 μm.

  The length L1 of the first opening 16A is defined by two intersections between a virtual straight line connecting the first surfaces 12 and the inner wall 16C of the recess 16, and is the length of the two intersections. The length L2 of the second opening 16B is defined by two intersections between a virtual straight line connecting the second surfaces 14 and the inner wall 16C of the recess 16, and is the length of the two intersections. The length L3 of the third opening 20A is defined as the distance between the tips of the protrusions 20.

  The angle θ of the inner wall 16C is preferably 5 to 30 °, more preferably 8 to 25 °, and still more preferably 10 to 20 °. Here, the angle θ means an angle formed between the inner wall 16 </ b> C and a perpendicular to the first surface 12.

  In the present embodiment, the recess 16 has a cone shape in a sectional view, and the angle θ is constant in the recess 16. However, it is not limited to this, The shape of the recessed part 16 can be made into the multistage cone shape, for example. The multi-stage cone shape means a shape in which the inner wall 16C of the recess 16 has a plurality of angles θ.

  It is preferable that the mold 10 and the protruding portion 20 are configured as an integral structure. Here, the integral structure means a structure made from one material. The mold 10 is preferably made of an elastic material. Examples of the elastic material include a silicone resin, a thermoplastic elastomer resin, and EVA (Ethylene-Vinyl Acetate copolymer). Especially, it is preferable that the mold 10 is comprised with a silicone resin. By producing the mold 10 with a silicone resin, the mold 10 and the protrusion 20 can have air permeability and elasticity.

  Next, a method for producing a mold for forming a microneedle array will be described. FIG. 4 is a perspective view of a mold, and FIGS. 5 and 6 are process diagrams showing a part of a mold manufacturing process.

  As shown in FIG. 4, a mold 40 is prepared. The mold 40 includes a protruding pattern 42 on one surface. The protruding pattern 42 refers to a state in which a tapered portion with a tapered tip protruding in a direction away from one surface of the mold 40 is disposed on one surface of the mold 40. The number of protrusions, the positions of the protrusions, etc. are not limited. In the present embodiment, the mold 40 has nine protruding patterns 42. Each protruding pattern 42 is composed of 25 5 × 5 protruding portions.

  As shown in FIG. 5A, a mold 40 having a protruding pattern 42 is disposed on a table 50. On the table 50, a spacer 52 is disposed outside the mold 40 as a gap adjusting mechanism. By adjusting the height of the spacer 52, the distance between the mold 40 and the substrate 64 can be adjusted in the subsequent step of pressing the silicone resin film 60 with the substrate 64, and the thickness of the mold 10 to be manufactured is adjusted. .

  The spacer 52 is provided outside the central portion of each side of the rectangular mold 40 in plan view. It is not limited to this as long as the thickness of the mold can be made constant when the substrate 64 is brought into contact. The spacer 52 may be provided around the periphery of the mold 40 or may be provided outside the corner portion of the mold 40.

  As a material of the spacer 52, a metal such as SUS (Stainless Used Steel) or aluminum, or glass can be used. Since the thickness of the silicone resin film 60 can be adjusted to the height of the spacer 52 by contacting the substrate 64, the spacer 52 is preferably made of a highly rigid material.

  Next, as shown in FIGS. 5B and 5C, a silicone resin solution 58 is applied on the mold 40 to form a silicone resin film 60.

  The method for applying the silicone resin solution 58 is not particularly limited, and examples thereof include application using a spin coater. In addition, when a plurality of regions having the protruding patterns 42 are provided, the slit nozzle 62 can be applied to each region having the protruding patterns 42 with the width of the protruding patterns 42. By applying the silicone resin solution 58 to each region having the protruding pattern 42, the silicone resin solution 58 can be applied only to the position where the mold is manufactured, so that unnecessary application of the silicone resin solution can be prevented. it can.

  Next, the silicone resin film 60 formed on the mold 40 is decompressed to degas the silicone resin film 60. The defoaming of the silicone resin film 60 is performed by placing the silicone resin film 60 together with the base 50, the mold 40, the spacer 52, etc. in a decompression device (not shown) and reducing the pressure in the decompression device. Depressurization means an atmospheric pressure or lower, and it is preferable that the absolute pressure is 20 to 100 Pa. Note that defoaming can be performed by pressurization instead of depressurization.

  The defoaming of the silicone resin film 60 can be confirmed visually or by image recognition using a CCD (Charge-Coupled Device) camera. Since the air contained in the silicone resin film can be removed by defoaming the silicone resin film 60, the shape during molding can be stabilized.

  Next, as illustrated in FIG. 6A, the separation sheet 66 is brought into close contact with one surface of the substrate 64. The surface to which the separation sheet 66 is closely attached becomes the surface that presses the silicone resin film 60.

  As a material of the substrate 64, metal, porous ceramic, or the like can be used. By using these materials as the substrate 64, the height of the formed mold 10 can be made constant.

  Further, as a material of the separation sheet 66, a fluoro rubber sheet, a Teflon (registered trademark) sheet, a silicone resin sheet subjected to a release treatment, or the like can be used. The peeling treatment can be performed by applying a fluorine-based release agent. The thickness of the separation sheet 66 is preferably 0.1 mm to 0.5 mm.

  The adhesion and separation between the substrate 64 and the separation sheet 66 can be performed by an air suction mechanism and an air ejection mechanism (not shown). The substrate 64 and the separation sheet 66 are peeled from each other by sucking from the opposite surface of the separation sheet 66 of the substrate 64 by the air suction mechanism, and the air is supplied by the air ejection mechanism. Can do. A vacuum pump can be used as the air suction mechanism, and a blower can be used as the air ejection mechanism. Switching between the air suction mechanism and the air ejection mechanism can be performed using, for example, a switching valve. When the substrate and the separation sheet are adhered and peeled using the air suction mechanism and the air peeling mechanism, the substrate 64 is preferably made of a porous ceramic. By using the substrate 64 as a porous material, the separation sheet 66 can be adhered and peeled by sucking and supplying air from the opposite side of the surface of the substrate 64 to which the separation sheet 66 is adhered.

  Next, as shown in FIG. 6B, the substrate 64 is brought into contact with the silicone resin film 60. 6C, the silicone resin film 60 is also pressed by pressing against the spacer 52, and the thickness of the silicone resin film 60, that is, the thickness of the mold 10 to be formed is adjusted. The

  Next, the mold 10 is formed by heating and curing the silicone resin film 60 in a state where the substrate 64 is in contact with the spacer 52 and the silicone resin film 60. As a method for heating the silicone resin film 60, an aluminum heater, an infrared heater, a ceramic heater, an IH (Induction Heating) heater, or the like can be used.

  FIG. 7 is a partially enlarged view of the protruding pattern 42 and the separation sheet 66 at the time of mold formation. As shown in FIG. 7, when the silicone resin film 60 is cured, the height of the spacer 52 is adjusted and the substrate 64 is pressed so that the protrusions of the protrusion pattern 42 of the mold 40 penetrate the silicone resin film 60. Thus, the tip of the protrusion of the protrusion pattern 42 reaches the separation sheet 66.

  Since the projecting pattern 42 penetrates the silicone resin film 60, the recess 10 is formed in the mold 10 through the first opening 16A of the first surface 12 and the second opening 16B of the second surface 14 (FIG. 1 to FIG. 3).

  Furthermore, since the tip of the protruding portion of the protruding pattern 42 reaches the separation sheet 66, the silicone resin film 60 on the second surface 14 around the second opening 16 </ b> B protrudes toward the separation sheet 66. Since the separation sheet 66 is made of an elastic material, the separation sheet 66 is deformed according to the shape of the protruding silicone resin film 60. As a result, an annular protrusion 20 is formed which is located around the second opening 16B and is tapered in a sectional view.

  The protruding portion 20 is hardly formed with a thermoplastic resin, and is formed with a silicone resin. In the case of the thermoplastic resin, it is considered that the thermoplastic resin does not enter around the tip of the protrusion even when the protrusion of the protrusion pattern 42 reaches the separation sheet 66 at the time of molding.

  The tip of the protrusion of the protrusion pattern 42 and the position of the separation sheet 66 can be adjusted by the height of the spacer 52. As described above, the thickness of the separation sheet 66 is in the range of 0.1 mm to 0.5 mm, and the sheet thickness setting is narrower by about 0.03 mm to 0.1 mm than the height of the protruding pattern, The tip of the protruding portion of the protruding pattern 42 can be set to a position where it is stuck in the separation sheet 66. If the thickness of the separation sheet 66 is smaller than the above range, when the substrate 64 is pressed, the tip of the protruding pattern 42 comes into contact with the substrate 64, and the tip of the protruding pattern 42 of the mold 40 is damaged or damaged. There is a case. Even if the mold 10 is manufactured using the mold 40 whose tip of the protruding pattern 42 is damaged, the pattern sheet which is an inversion mold of 40 is not used, and therefore the damaged mold 40 is used for the subsequent manufacture of the mold 10. Therefore, it is important to prevent the tip of the protrusion pattern 42 of the mold 40 from being deformed.

  Further, by providing the separation sheet 66 between the substrate 64 and the silicone resin film 60, the substrate 64 and the silicone resin film 60 can be easily separated. Since the substrate 64 uses the above-mentioned material, it is not flexible, and if the mold 10 is peeled from the mold 40 in a state where the substrate 64 is disposed, the tip of the protruding pattern 42 of the mold 40 is damaged or damaged. There is a risk of doing. By providing the separation sheet 66, the mold 10 and the substrate 64 can be easily peeled off, the deformation of the protruding pattern 42 can be prevented, and the mold 10 can be manufactured.

  Next, as shown in FIG. 6D, the substrate 64 is peeled from the mold 10. The separation sheet 66 remains attached to the mold 10.

  As shown in FIG. 7, in the present embodiment, the tip of the protrusion pattern 42 of the mold 40 reaches only the separation sheet 66. The substrate 64 can be peeled without damaging the shape.

  In addition, since the substrate 64 includes an air ejection mechanism, only the substrate 64 can be easily peeled by supplying air by the air ejection mechanism.

  Next, as illustrated in FIG. 6E, the mold 10 to which the separation sheet 66 is attached is peeled from the mold 40. Since the substrate 64 is peeled off and the tip of the protruding pattern 42 reaches the separation sheet, the tip of the protruding pattern 42 can be protected and peeled off. When the mold 10 is peeled from the mold 40, it is preferable that the mold 10 be peeled off at the slowest possible speed. This is to prevent the protrusion 20 from being damaged.

  Finally, as shown in FIG. 6 (F), the mold 10 having the concave pattern 18 composed of the concave portion 16 that is the inverted type of the protruding pattern 42 of the mold 40 is manufactured by peeling the separation sheet 66. be able to. When the separation sheet 66 is peeled off, it is preferably peeled off at a speed as slow as possible, for example, about 10 to 30 mm / sec. This is to prevent the protrusion 20 from being damaged.

  Next, a method for manufacturing the mold 40 will be described. As one method, a mold 40 having a plurality of protruding patterns 42 on the surface of the metal substrate can be produced by machining a metal substrate such as Ni by mechanical cutting using a cutting tool such as a diamond bite. .

  As another method, after applying a photoresist on a Si substrate, exposure and development are performed. Then, by performing etching by RIE (Reactive Ion Etching) or the like, the mold 40 having the protruding pattern 42 can be manufactured.

  The above method produces a large mold 40, which may increase the work load and cost. Therefore, a method can be employed in which a small original plate is produced, a small mold is produced from the original plate, a small mold is connected to produce a large mold, and a large mold is produced from the large mold. .

  First, as shown in FIG. 8A, an original plate 70 on which a protruding pattern 72 is formed is prepared. The protruding pattern 72 is composed of 25 protruding portions of 5 × 5, for example. The original plate 70 is smaller than the mold 40 to be created.

  The method for producing the original plate 70 on which the protruding pattern 72 is formed is not particularly limited, but can be produced, for example, as follows. A plurality of protruding patterns 72 can be formed on the surface of the original plate 70 by machining a metal substrate such as Ni by mechanical cutting using a cutting tool such as a diamond bite.

  As another method, after applying a photoresist on a Si substrate, exposure and development are performed. Then, by performing etching by RIE (Reactive Ion Etching) or the like, the protruding pattern 72 can be formed on the surface of the original 70.

  Next, as shown in FIGS. 8B and 8C, a plurality of first molds 74 having concave patterns 76 are manufactured using the original plate 70. As a method of manufacturing the first mold 74, the following method can be used by using a resin. In the first method, a silicone resin with a curing agent added to PDMS (polydimethylsiloxane, for example, Sylgard 184 manufactured by Dow Corning) is poured into the original plate 70, heated at 100 ° C. and cured, and then the original plate 70 is cured. A first mold 74 having a concave pattern 76 that is an inverted type of the protruding pattern 72 is prepared.

  The second method is a method in which an ultraviolet curable resin that is cured by irradiating ultraviolet rays is poured into the original plate 70, and after irradiating ultraviolet rays in a nitrogen atmosphere, the first mold 74 is peeled off from the original plate 70. In the third method, a plastic resin such as polystyrene or PMMA (polymethyl methacrylate) dissolved in an organic solvent is poured into an original plate 70 coated with a release agent, and the organic solvent is volatilized by drying. This is a method of peeling the first mold 74 from the original plate 70 after being cured.

  The material for forming the first mold 74 is a resin, and it is preferable to use an ultraviolet curable resin or a thermoplastic resin. By using an ultraviolet curable resin or a thermoplastic resin, the first mold 74 can be easily manufactured, and the protruding pattern 42 of the mold 40 can be stably formed.

  Next, as shown in FIG. 8D, a plurality of first molds 74 manufactured from the original plate 70 are joined together to increase the area of the surface 78 on which the concave pattern 76 of the first mold 74 is formed. The assembly mold 80 is manufactured.

  The first collective mold 80 can be manufactured by joining a plurality of first molds 74. The first mold 74 can be joined by, for example, an adhesive. Since the first collective mold 80 becomes a mold of the mold 40 having the protruding pattern 42 manufactured in the next step, the first mold 80 is in a state where the flatness of the surface 78 on which the concave pattern 76 is formed is ensured. It is preferable to form the assembly mold 80. If the flatness of the surface 78 on which the concave pattern 76 is formed is not ensured, a step is formed in the electroforming mold, the mold, and the pattern sheet manufactured in the subsequent process, which is not preferable.

  A method of manufacturing the first collective mold 80 while ensuring the flatness of the concave pattern 76 is not particularly limited. For example, the surface 78 on which the concave pattern 76 of the first mold 74 is formed is directed downward. The flatness of the first collective mold 80 can be ensured by placing it at a position in contact with the substrate and then curing with an adhesive. Thus, by ensuring the flatness of the first collective mold 80 using the substrate, it is possible to suppress the occurrence of steps, deformation, etc., between the first collective mold 80 and the adhesive between the first molds 74. The flatness of the first assembly mold 80 can be ensured.

  The first assembly mold 80 may or may not be manufactured. When the first collective mold 80 is not manufactured, a mold having a protruding pattern is manufactured from the first mold 74. However, it is preferable to manufacture the first collective mold 80 because a large-area mold can be manufactured by one electroforming process. Also in the subsequent steps, since a mold can be manufactured using a large-area mold and a pattern sheet can be manufactured from the mold, the productivity of the pattern sheet can be improved, which is preferable.

  FIG. 8E is a diagram illustrating a process of manufacturing the mold 40 having the protruding pattern 42 using the first collective mold 80. In the following, as an example, a method of manufacturing a mold having a protruding pattern by electroforming will be described.

  In the electroforming process, first, a conductive process is performed on the first assembly mold 80. A metal (for example, nickel) is sputtered on the first mold 74 of the first collective mold 80, and the metal is attached to the surface of the first mold 74 of the first collective mold 80 and the concave pattern 76.

  Next, the first assembly mold 80 that has undergone the conductive treatment is held on the cathode. A metal pellet is held in a metal case to serve as an anode. By immersing the cathode holding the first collective mold 80 and the anode holding the metal pellet in the electroforming liquid and energizing the metal, the concave pattern 76 of the first collective mold 80 is embedded and peeled off. A mold 40 having a protruding pattern 42, that is, a so-called electroformed mold is manufactured (FIG. 8F).

  The method for producing the mold 40 having the protruding pattern 42 is not limited to the above-described method.

  Next, a method for manufacturing a microneedle array using the mold 10 manufactured by the above manufacturing method will be described. FIG. 9 is a process diagram for manufacturing the microneedle array 96, and FIG. 10 is a partially enlarged view of the mold preparation process.

  FIG. 9A shows a mold preparation process. The second surface 14 of the mold 10 is fixed to a suction plate 90 which is a porous flat plate. Before the mold 10 is fixed to the suction plate 90, no force is applied to the protrusion 20 as shown in FIG. 10A, so the second opening 16B is open. Next, as shown in FIG. 10B, when the second surface 14 of the mold 10 is fixed to the suction plate 90, a force is applied to the protruding portion 20 from the suction plate 90 to the recess 16. The protrusion 20 is deformed by this force, and the protrusion 20 closes the second opening 16B. The second opening 16B is closed with or without the protrusion 20 overlapping. As the porous flat plate used as the adsorption plate 90, sintered metal, ceramic, resin, or the like can be used.

  In the present embodiment, the projecting portion 20 has a tapered shape in a sectional view. Therefore, the protrusion 20 can be easily deformed.

  FIG. 9B shows a step of supplying the polymer solution 92 to the concave portions 16 of the concave pattern 18 of the mold 10 while sucking the suction plate 90.

  As a material of the polymer solution 92 forming the microneedle array 96, a water-soluble material is preferably used. It is preferable to use a biocompatible resin as the resin polymer material of the polymer solution used for manufacturing the microneedle array. Such resins include sugars such as glucose, maltose, pullulan, sodium chondroitin sulfate, sodium hyaluronate, hydroxyethyl starch, proteins such as gelatin, and biodegradable polymers such as polylactic acid and lactic acid / glycolic acid copolymers. It is preferable to use it. Among these materials, gelatin-based materials have adhesiveness to many base materials and have strong gel strength as a material to be gelled, so that they can be in close contact with the base material, and the microneedle array 96 is peeled off from the mold 10 In doing so, since the microneedle array 96 can be peeled off using a base material (not shown), it can be suitably used. Although the concentration varies depending on the material, it is preferable that the concentration is such that 10 to 50% by mass of the resin polymer is contained in the polymer solution 92 containing no drug. Further, the solvent used for dissolution may be volatile even if it is other than warm water, and methyl ethyl ketone (MEK), alcohol, or the like can be used. And in the polymer solution 92, it is possible to dissolve together the medicine to be supplied into the body according to the application. The polymer concentration of the polymer solution containing the drug (when the drug itself is a polymer, the concentration of the polymer excluding the drug) is preferably 0 to 30% by mass. Here, the water-soluble material means a material that is soluble in water.

  As a method for preparing the polymer solution 92, when a water-soluble polymer (gelatin or the like) is used, the water-soluble powder may be dissolved in water, and the drug may be added after dissolution, or the liquid in which the drug is dissolved Alternatively, a water-soluble polymer powder may be put in and dissolved. If it is difficult to dissolve in water, it may be dissolved by heating. The temperature can be appropriately selected depending on the type of the polymer material, but it is preferable to heat at a temperature of about 60 ° C. or lower. The viscosity of the polymer resin solution is preferably 100 Pa · s or less, more preferably 10 Pa · s or less, in the case of a solution containing a drug. In the case of a solution that does not contain a drug, it is preferably 2000 Pa · s or less, more preferably 1000 Pa · s or less. By appropriately adjusting the viscosity of the polymer solution 92, it becomes easy to inject the solution into the needle-shaped recess of the mold. For example, the viscosity of the polymer solution 92 can be measured with a capillary tube viscometer, a falling ball viscometer, a rotary viscometer, or a vibration viscometer.

  The chemical | medical agent contained in the polymer solution 92 will not be limited if it has a function as a chemical | medical agent. In particular, it is preferable to select from peptides, proteins, nucleic acids, polysaccharides, vaccines, pharmaceutical compounds belonging to water-soluble low molecular weight compounds, or cosmetic ingredients.

  As a method for injecting such a polymer solution 92 into the recess 16 of the mold 10, for example, coating using a spin coater can be mentioned.

  The second opening 16B of the concave portion 16 of the mold 10 is closed at first glance due to deformation of the protruding portion 20, and thus is in a watertight state. Therefore, even if the suction plate 90 is sucked, the polymer solution 92 does not leak out.

  On the other hand, the second opening 16B is not in an airtight state because the protruding portion 20 is closed by deformation. Therefore, air can be removed from the recess 16 by sucking the suction plate 90. Prevention of leakage of the polymer solution 92 and removal of air from the recess 16 can be achieved.

  FIG. 9C shows a process in which the polymer solution 92 is dried to form a polymer sheet 94. For example, the polymer solution 92 supplied to the mold 10 can be dried by blowing air. The polymer sheet 94 means a state after the polymer solution 92 is subjected to a desired drying process. The moisture content of the polymer sheet 94 is appropriately set. In addition, since it will become difficult to peel when the water content of a polymer becomes too low by drying, it is preferable to leave the water content in the state of maintaining elasticity.

  FIGS. 9D and 9E are views showing a state in which the polymer sheet 94 is peeled from the mold 10 to form a microneedle array 96, and FIG. 9F shows a state in which the microneedle array 96 is cut, It is a figure explaining the process used as individual microneedle array 96A, 96B, 96C.

  The microneedle array 96 peeled from the mold 10 is set in a cutting device (not shown), and the position for cutting the microneedle array 96 is determined. Basically, the cutting position is determined so that each of the regions 98A, 98B, and 98C having the protruding pattern 98 is provided. As shown in FIG. 9F, the microneedle array 96 is cut into a plurality of individual microneedle arrays 96A, 96B, and 96C.

  In the present embodiment, the case where the polymer sheet 94 is formed by filling the polymer dissolution liquid 92 into the concave pattern 18 of the mold 10 and drying is described, but the present invention is not limited to this.

  For example, the polymer solution containing the drug is filled in the concave pattern 18 of the mold 10 and dried, and then the polymer solution not containing the drug is filled in the concave pattern 18 of the mold 10 and dried, whereby the polymer sheet 94 is obtained. Can be formed.

  In addition, the mold 10 may be used only once for the first time and may be preferably disposable. When the microneedle array 96 is used as a medicine, it is preferably disposable in consideration of the safety of the manufactured microneedle array 96 to the living body. Moreover, since it becomes unnecessary to wash | clean the mold 10 by making it disposable, the cost by washing | cleaning can be reduced. In particular, when the microneedle array 96 is used as a medicine, a high cleaning performance is required, so that the cleaning cost increases.

  The protruding shape of the microneedle array 96 to be manufactured is not particularly limited as long as the tip is tapered, but for example, a conical shape or a pyramid shape such as a triangular pyramid or a quadrangular pyramid is used. Can do. Further, it can be formed by a tapered needle part and a frustum part connected to the needle part.

  The height of the protruding portion of the protruding pattern 98 is in the range of 100 μm to 2000 μm, and preferably 200 μm to 1500 μm.

  Since the microneedle array 96 having the protruding pattern 98 to be manufactured is a duplicate of the mold 40 having the protruding pattern 42, the shape of the protruding pattern 42 of the mold 40 or the shape of the protruding pattern 72 of the original 70. By making a desired shape, the protruding pattern 98 of the microneedle array 96 to be manufactured can be a desired shape.

  Although the manufacturing method of the microneedle array has been described as a manufacturing method of the sheet, it is not particularly limited, and it is not particularly limited as long as it is a liquid capable of producing the sheet of the mold 10 instead of the polymer solution.

DESCRIPTION OF SYMBOLS 10 ... Mold, 12 ... 1st surface, 14 ... 2nd surface, 16 ... Recessed part, 16A ... 1st opening, 16B ... 2nd opening, 16C ... Inner wall, 18 ... Recessed pattern, 20 ... Protruding part, 20A ... 3rd Opening, 20B ... inner wall, 40 ... mold, 90 ... adsorption plate, 92 ... polymer solution, 94 ... polymer sheet, 96 ... microneedle array, 98 ... projection pattern

Claims (8)

A plurality of first and second surfaces facing each other, a first opening on the first surface, and a second opening on the second surface, and tapering from the first surface toward the second surface. A mold having a recess,
A mold having an annular protrusion that is positioned around the second opening and closes the second opening when the second surface is fixed to a plate.   The length of the second opening is 10 to 60 μm, the height of the protrusion from the second surface is 10 to 80 μm, and the length of the third opening of the protrusion is 1 to 40 μm. Item 2. The mold according to Item 1.   The mold according to claim 1, wherein the protruding portion is tapered in a sectional view.   The mold according to claim 1, wherein the mold is made of an elastic material.   The mold according to any one of claims 1 to 4, wherein the mold is made of a silicone resin. A mold preparing step of fixing the second surface of the mold according to any one of claims 1 to 5 to an adsorption plate of a porous body, and closing the second opening by the protruding portion;
Supplying liquid to the recess of the mold while sucking the suction plate;
Drying the liquid to form a sheet;
Peeling the sheet from the mold;
The manufacturing method of the sheet | seat which has.   The sheet manufacturing method according to claim 6, wherein the liquid is made of a water-soluble material.   The sheet manufacturing method according to claim 6 or 7, wherein the sheet is a microneedle array.

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