JP2010233674A - Microneedle sheet, its use method and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To immediately remove a sheet alone when sticking a needle into a skin and to leave the needle alone in the skin. <P>SOLUTION: In this microneedle sheet 10 used by sticking biodegradable needles 12 supported to the surface of the sheet 14 into the skin, a proximal section 12B close to the sheet 14, of each needle 12 is formed to be more fragile than the distal section 12A and is configured to have such fragility as to be broken by force pulling the sheet 14 along the skin surface, with the needle 12 being stuck into the skin 16. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a microneedle sheet, a method of using the same, and a manufacturing method thereof, and in particular, a technique of a microneedle sheet that allows a drug to be easily and safely administered to the skin surface layer or the stratum corneum by piercing a skin containing a drug. Regarding improvement.

  In recent years, a microneedle sheet in which a needle, which is a high aspect ratio microneedle, is supported on a sheet surface has been applied as a functional sheet in various fields.

  A typical example of the microneedle sheet is a percutaneous absorption sheet used in the medical technology field. This microneedle sheet can efficiently administer a drug to a patient via the patient's skin surface or skin stratum corneum by using a needle containing the drug as a functional substance.

  For example, Patent Document 1 discloses a microneedle sheet having a double-layered microneedle constituted by a tip portion containing a drug and a root portion having a higher dissolution rate in the living body than the tip portion. . When this microneedle sheet is affixed to the patient's skin, the root portion of the microneedle inserted into the patient body is preferentially dissolved in the patient body, so that only the tip portion of the microneedle may remain in the patient body. it can.

JP 2008-194288 A

  However, the conventional microneedle sheet described in Patent Document 1 has a drawback in that the sheet must remain attached to the skin until the root of the microneedle stabbed in the skin is dissolved in the body. For this reason, for example, when a woman uses the microneedle sheet exposed to the outside, such as a face, a leg, and a hand, many women dislike that the sheet is visible. In particular, there is a problem from the aesthetic sense that the sheet remains when used on the face.

  In this case, in the conventional microneedle sheet, when the sheet is removed by forcibly destroying the root part of the needle by pulling the sheet, the needle protrudes from the skin surface by the force of pulling the sheet, and the needle remains in the skin. There will be fewer parts.

  Further, the conventional microneedle sheet has an adhesive layer on the skin surface side of the sheet and is adhered to the skin. However, since the sheet is easily peeled off when the adhesiveness is deteriorated, there is a problem that the needle comes out together with the peeling of the sheet.

  From such a background, there is a demand for a microneedle sheet that can easily remove only the sheet immediately after the needle of the microneedle sheet is inserted into the skin and leave only the needle in the skin.

  The above-mentioned demand is not limited to the percutaneous absorption sheet containing the drug in the needle, and the same can be said for the placement needle used as a needle treatment tool, for example. This placement needle is used as a simple needle treatment by piercing the body's heel with a needle supported by the sheet, but usually the placement needle is left on for 2 to 3 days. It looks bad.

  The present invention has been made in view of such circumstances. When a needle is inserted into the skin, the microneedle sheet can be removed immediately, and only the needle can be left in the skin. It aims to provide a method.

  Claim 1 of the present invention is a microneedle sheet in which a biodegradable needle supported on the surface of the sheet is stabbed into the skin and used in order to achieve the object, and the root of the needle close to the sheet The microneedle sheet is characterized in that the portion is formed to be more brittle than the tip, and has a degree of brittleness that can be broken by a force of pulling the sheet along the skin surface while the needle is inserted into the skin. To do.

  According to the microneedle sheet of the present invention, after the needle is stabbed into the skin, the base of the needle is destroyed by immediately pulling the sheet along the skin. This allows the sheet to be removed from the needle, leaving only the needle in the skin. In addition, since the needle remaining in the skin is biodegradable, it is not dissolved in the body.

  Thereby, even when the microneedle sheet of the present invention is used for a face, a foot, a hand, etc. exposed to the outside, it can be made clear from the appearance whether the microneedle sheet is used.

  A brittle material can also be used as a method of making the needle root portion brittle. Moreover, you may make it have brittleness by making a shape of a base part, for example, making a cut | notch shape into a base part, or making it thin, and making it easy to break.

  In the present invention, when the brittleness of the root portion is expressed by a bending yield stress, the bending yield stress is preferably 0.5 MPa or more and 10 MPa or less.

  If the bending yield stress at the root portion is less than 0.5 MPa, it is too easy to be destroyed, so that molding itself becomes difficult. In addition, if the bending yield stress at the root exceeds 10 MPa, the needle is broken at a portion other than the root because it is difficult to break (hard to break) by pulling the sheet along the skin surface with the needle stabbed in the skin. Or when the sheet is removed from the needle, the needle easily protrudes from the skin surface.

  Therefore, if the bending yield stress of the root part material is 0.5 MPa or more and 10 MPa or less brittle, the root part is easily and surely broken by the force of pulling the sheet so that only the needle does not protrude from the skin surface. Can leave.

  In this invention, it is preferable that the bending yield stress of the said base part is 1/2 or less of the bending yield stress of the front-end | tip part which is a needle front end side rather than the said base part.

  In this way, by defining the bending yield stress of the root portion with respect to the tip portion to 1/2 or less, only the root portion can be easily and reliably destroyed when the sheet is pulled along the surface of the skin, The tip can be left in the skin without being destroyed. It is more preferable that the bending yield stress of the root portion with respect to the tip portion is 1/3 or less.

  Here, the base portion of the needle refers to a portion within 1/3 of the base end position in the total length of the needle from the base end (sheet surface) to the tip of the needle. Further, the bending yield stress at the root portion is a stress at a location where the bending yield stress is the smallest among the root portions, and the bending yield stress at the tip portion is a stress at the location where the bending yield stress is greatest among the tip portions.

  In the present invention, it is preferable that the tip portion contains gelatin and the root portion contains saccharide or a mixture of saccharide and gelatin.

  This is because the gelatin contained in the tip is biodegradable and water-soluble, and since it shrinks and hardens when the gelatin aqueous solution is dried, it is a material for the tip that requires sufficient hardness to pierce the skin. Is preferred. Saccharides are biodegradable and water-soluble, similar to gelatin, but are suitable as a material for the root part because they are brittle and not as hard as gelatin even when the aqueous saccharide solution is dried. If the saccharide alone as the material for the root part is too brittle, there is a problem that the brittleness can be adjusted by including a mixture of gelatin and saccharide appropriately mixed.

  In the present invention, the root portion may contain bubbles.

  This is one of the methods for adjusting the brittleness of the root portion, and the brittleness can be adjusted by adjusting the amount of bubbles to be included. For example, even when the root material is formed of gelatin, the degree of brittleness can be increased by including bubbles in the gelatin.

  In this invention, it is preferable that the base support part which supports this root part is formed in the said sheet | seat side of the said base part.

  This is because when there is a repulsive force due to the elasticity of the skin when the needle is stabbed into the skin, it is difficult for the entire length of the needle to stab into the skin and it is destroyed at the proximal end position of the needle (opposite the needle tip). Then, the needle tends to jump out of the skin surface.

  However, in the present invention, since the root support part is formed on the sheet side of the root part, when the sheet is pulled along the surface of the skin, the distal end side is slightly broken from the proximal end position of the needle. On the other hand, the root support part is removed together with the sheet. This makes it difficult for the needle to jump out of the skin surface after removing the sheet. In this case, it is preferable that the root portion is formed in a layer thickness of 5 to 30% of the total length of the needle at a position of 100 to 200 μm from the base end position of the total length of the needle.

  That is, when the needle has a three-layer structure of the tip portion, the root portion, and the root support portion, it is preferable that the root support portion is formed at a position near the distal end side by 100 to 200 μm from the base end position. .

  This is because when the needle is pierced into the skin, the needle tends to jump from the skin surface by 100 to 200 μm due to the elasticity of the skin. If it is formed to a layer thickness of ˜30%, it is possible to reliably prevent the needle from jumping out from the skin surface after removing the sheet.

  In the present invention, it is preferable that the tip portion has a substantially conical shape or a substantially pyramid shape, and the base portion has a substantially cylindrical shape or a substantially prismatic shape.

  It is preferable that the tip has a conical shape or a pyramid shape with a sharp tip so that the tip can be easily pierced by the skin. However, when the entire needle is formed in a cone or a pyramid shape, the diameter of the root portion becomes thick and is difficult to be destroyed. . In the present invention, since the root portion is formed in a columnar shape or a prismatic shape, the root portion can be easily broken while securing the performance of being easily pierced by the skin at the tip portion.

  In the present invention, it is preferable that a slipping layer is formed on the skin surface side of the sheet. Since the sliding layer is formed on the skin surface side of the sheet, the friction between the skin and the sheet can be reduced when the sheet is pulled along the surface of the skin. Although not particularly noted, the microneedle sheet of the present invention does not require an adhesive layer to be adhered to the skin as in the prior art.

  In this invention, it is preferable that the said sheet | seat is formed with the pick part pinched with a finger | toe when pulling this sheet | seat.

  The microneedle sheet has a small product size and is difficult to pull the sheet. However, the microneedle sheet can be easily and accurately pulled because a pinch portion is formed on the sheet with a finger. Thereby, since the root part can be destroyed with high accuracy, it is possible to prevent the entire needle from coming out of the skin when pulled. In this case, it is more preferable that a ring for inserting a finger is formed in the knob portion.

  In this invention, it is preferable that the said front part contains the chemical | medical agent.

  This is a case where the microneedle sheet is used as a percutaneous absorption sheet. By containing a drug at the tip, the drug can be administered into the body from the tip of the needle remaining in the skin, and the sheet can be removed. As a result, the use of the microneedle sheet is not apparent.

  It should be noted that even when a microneedle sheet is used as a placement needle, for example, when the tip portion does not contain a medicine, it is not apparent from the appearance that the placement needle is used.

  According to a thirteenth aspect of the present invention, there is provided a method of using the microneedle sheet according to any one of the first to twelfth aspects of the invention, wherein the puncturing step of piercing the needle into the skin, and the sheet with a finger. A breaking step of grasping and pulling along the surface of the skin to break a brittle root portion of the needle, and a sheet removing step of removing the sheet from the skin surface and leaving only the needle in the skin. A method for using the microneedle sheet is provided.

  The thirteenth aspect specifies the method of using the microneedle sheet of the present invention.

  According to a fourteenth aspect of the present invention, there is provided a microneedle sheet manufacturing method in which a biodegradable needle supported on the surface of a sheet is stabbed into the skin and used to achieve the above object. A first application step of applying a tip portion dissolving solution including a tip portion material forming the tip portion of the needle, and a first filling of the applied tip portion dissolving solution into the needle-like recess of the mold. Filling step, a first removing step of removing the remaining solution of the tip portion dissolving liquid remaining on the surface of the mold, and the mold surface after the remaining solution of the tip portion dissolving solution is removed, A second application step of applying a root part solution containing a root part material that forms the root part of the needle; and filling the space part in the needle-shaped recess with the applied root part solution. Roots continuously on the mold surface A second filling step for forming a plate-like surface of the part solution, a drying step for drying and solidifying the tip part solution and the root part solution, and the tip part and the root part. A method for producing a microneedle sheet, comprising: a peeling step of peeling a needle molded product constituted from a mold; and a sheet sticking step of sticking the sheet to the plate-like surface of the needle molded product. provide.

  Claim 14 specifies the method for producing the microneedle sheet of the present invention, and the microneedle sheet of the present invention can be produced by this production method.

  The manufacturing method of this invention WHEREIN: It is preferable to provide the process of shape | molding the base support part which supports the said base part in the said sheet | seat side of the said base part.

  Further, in the manufacturing method of the present invention, the sheet is composed of an adhesive layer portion to be attached to the needle molded product, and a non-adhesive layer portion if the adhesive layer is not provided, and the adhesive layer portion is the needle. It is preferable to perform the peeling step and the sheet sticking step at a time by sticking to a molded product and peeling.

  According to the present invention, when the needle is inserted into the skin, it is possible to immediately remove only the sheet and leave only the needle in the skin. Therefore, for example, even when a woman uses a microneedle sheet exposed to the outside, such as a face, a leg, and a hand, the appearance can be obscure. Moreover, the conventional problem that the needle comes off together with the peeling of the sheet can be solved.

Sectional drawing which shows the one aspect | mode of the microneedle sheet | seat of this invention Sectional drawing which shows another aspect of the microneedle sheet | seat of this invention Illustration of how to use microneedle seat Step diagram of how to use microneedle sheet Explanatory drawing explaining the sheet | seat of a microneedle sheet | seat Illustration of auxiliary jig for microneedle seat Step diagram of microneedle sheet manufacturing method Explanatory drawing explaining a pressure filling device Explanatory drawing explaining the excess lysate removal apparatus by a centrifugal method Explanatory drawing of test results of examples

  Hereinafter, preferred embodiments of a microneedle sheet of the present invention, a method of using the same, and a method of manufacturing the same will be described in detail with reference to the accompanying drawings.

  In addition, although the microneedle sheet | seat of this invention is applicable to various fields as a sheet | seat which has functionality, in this Embodiment, it demonstrates by the example as a transdermal absorption sheet currently used in the medical technical field.

  FIG. 1 is a cross-sectional view showing an example of a structure example of a microneedle sheet.

  As shown in FIG. 1, in the microneedle sheet 10, microneedles 12 are vertically supported on the surface of a sheet (for example, a resin sheet) 14. The number of needles 12 should just be one or more, and usually a plurality of needles 12 are arranged on the sheet 14 surface in the shape of a lattice.

  The needle 12 is composed of a tip portion 12A containing a drug and a root portion 12B not containing the drug, and the root portion 12B close to the skin surface of the needle stabbed in the skin is a force that pulls the sheet 14 along the skin surface. Has brittleness that can be broken.

  Here, as shown in FIG. 1, the root portion 12 </ b> B of the needle 12 is a portion within 1/3 of the base end position of the total needle length (H) from the base end (sheet surface) to the tip of the needle 12. Say. When the needle 12 is formed in a two-layer structure of the tip portion 12A and the root portion 12B, the needle portion other than the root portion 12B becomes the tip portion 12A.

  When the brittleness of the material of the root portion 12B is expressed by a bending yield stress, the bending yield stress is preferably in the range of 0.5 MPa to 10 MPa, more preferably in the range of 2 MPa to 6 MPa. When the tip 12A and the root 12B of the needle 12 are viewed in a relative relationship of bending yield stress, the bending yield stress of the root 12B is ½ or less of the bending yield stress at the tip 12A, More preferably, it is 1/3 or less.

  This is because the tip portion 12A needs to be hard enough not to be broken (not broken) when the needle 12 is inserted into the skin, and the root portion 12B is broken when the sheet 14 is pulled along the surface of the skin. It is because the brittleness for (break) is required. Therefore, when the bending yield stress of the root portion 12B is regulated to ½ or less of the tip portion 12A, the needle 12 can be surely inserted into the skin and the sheet 14 is pulled along the surface of the skin. In addition, only the root portion 12B can be easily and reliably destroyed. As a result, only the distal end portion 12A remains in the skin without being destroyed.

  Here, the bending yield stress of the root portion 12B is the stress at the location where the bending yield stress is the smallest in the root portion 12B, and the bending yield stress of the tip portion 12A is the location where the bending yield stress is greatest in the tip portion 12A. Stress. As a method for making the root portion 12B of the needle 12 brittle, a brittle material can be used. Moreover, you may make it have brittleness by making a shape of the base part 12B, for example, making a cut | notch shape into a base part, or making it thin and making it easy to break.

  Then, when the bending yield stress of the tip portion 12A and the root portion 12B is defined by the selection of the material, the bending yield stress is measured by the following method.

  That is, the force when bending and yielding the tip portion material forming the tip portion 12A or the root portion material forming the root portion 12B is measured by the following procedure.

  (1) Preparation of dissolved solution: The material at the tip or root is dissolved in hot water at 50 ° C. to prepare a 20% (solid content) solution.

  (2) Production of measurement sheet: A measurement sheet having a width of 10 mm and a thickness of 1 mm is produced by injecting the solution into a mold and then drying.

  (3) Bending test: A measurement sheet is installed between a pair of spaced mounting tables, and a stress is measured when the measurement sheet yields when a load is applied to the measurement sheet from above the measurement sheet.

  The tip material constituting the tip 12A of the needle 12 is preferably a material (biodegradable material) that is easily decomposed in vivo and a material having biocompatibility (biocompatible material). Specifically, polymers having gelling properties (gelling polymers) such as gelatin, agarose, pectin, gellan gum, carrageenan, xanthan gum, alginic acid, starch and cellulose, and polymers such as acrylic and polystyrene can be used. . Among these tip materials, it is preferable that the bending yield stress is 15 to 25 MPa (average 20 MPa) and water-soluble gelatin is used. The bending yield stress of the tip material other than gelatin was not described. However, as described above, the needle 12 needs to have a hardness that does not break when the needle 12 is inserted into the skin, and the lower limit of the bending yield stress of gelatin. It is preferable to use a tip material that satisfies a certain 15 MPa or more.

  The base material constituting the base 12B of the needle 12 is preferably a material (biodegradable material) that is easily decomposed in a living body and a material having biocompatibility (biocompatible material). Further, the root part material needs to have brittleness as described above, and a material containing saccharides can be preferably used. Specific types of saccharides that can be used include monosaccharides such as glucose, fructose, and galactose, disaccharides such as lactose, maltose, sucrose, and trehalose, and polysaccharides such as dextrin, starch, and pullulan. Among the root materials, dextrin is a material having a relatively small bending yield stress, and the bending yield stress is in the range of 0.5 to 1 MPa (average 0.75 MPa). As a material having a relatively large bending yield stress among the root portion materials, pullulan is used, and the bending yield stress is in the range of 7 to 10 MPa (average 8.5 MPa).

  Therefore, the root material can be composed of only saccharides if the type of saccharide is appropriately selected. However, the bending yield stress is 0. It is preferable to adjust so that it may become the range of 5 MPa or more and 10 MPa or less. For example, the bending yield stress of a mixture in which gelatin and dextrin are mixed at a ratio of 1: 1 is 10 to 15 MPa (average 12.5 MPa), and the bending yield stress of a mixture in which the mixture is mixed at a ratio of 1: 2 is 6 to 10 MPa. (Average 8 MPa). Moreover, the bending yield stress of the mixture in which gelatin and dextrin are mixed at a ratio of 1: 3 is in the range of 4 to 6 MPa (average 5 MPa). Thus, by mixing the tip portion material with the root portion material, the bending yield stress of the root portion 12B can be appropriately adjusted, and also contributes to improving the adhesion between the tip portion 12A and the root portion 12B. . In addition, when the bending yield stress of the root portion material is less than 0.5 MPa, the material is easily broken and the molding itself becomes difficult.

  The shape of the needle 12 is, for example, a column shape such as a cylinder or a prism, a cone shape such as a cone or a pyramid, a shape combining a column shape and a cone shape (referred to as a “conical column shape”), and the like. A similar shape may be used. However, as shown in FIG. 1, it is more preferable that the needle 12 has a conical column shape having a conical tip portion 12A and a columnar root portion 12B.

  The needle 12 is preferably a high aspect ratio structure with a sharp pointed tip from the viewpoint of reducing pain given to the patient. For example, the width (diameter) of the needle 12 is preferably 50 to 200 μm, and the radius of curvature of the tip of the needle 12 is preferably 10 μm or less. The height of the needle 12 is preferably 100 to 2000 μm. The aspect ratio of the needle 12 is preferably 2 or more and 10 or less. Here, the aspect ratio A of the needle 12 is defined by A = H / D using the length H and the width (diameter) D of the needle 12, as shown in FIG. The length of the needle 12 means the projection length H from the surface of the sheet 14.

  Further, as the sheet 14, for example, a resin sheet such as polyethylene terephthalate resin (PET) or polyethylene naphthalate resin (PEN) can be suitably used.

  FIG. 2 shows another embodiment of the microneedle sheet 10 in which the needle 12 is formed in a three-layer structure by providing a root support portion 12C on the sheet 14 side of the root portion 12B. In this case, the bending yield stress of the root support portion 12C is preferably equal to that of the tip portion 12A.

  Thus, by providing the needle 12 with the root support portion 12C, the root portion 12B is moved closer to the distal end portion 12A side by a predetermined distance. It is preferably formed so as to approach from the base end position of the entire length of the needle to a position of 100 to 200 μm and to have a layer thickness of 5 to 30% of the total length of the needle from this position. Moreover, when it sees by the layer thickness ratio with the front-end | tip part 12A, the base part 12B, and the base support part 12C in the needle full length, 40 to 70% is made into the front-end | tip part 12A, and 5-30% is made into the 1st base part 12B. The remainder is preferably the root support portion 12C.

  Next, a method of using the microneedle sheet 10 of the present invention will be described using the microneedle sheet 10 of FIG. 1 configured as described above.

  As shown in FIG. 3, after the needle 12 of the microneedle sheet 10 is stabbed into the skin 16, immediately while pressing the sheet 14 with the left hand finger 18 from above, the knob 14 </ b> A at the end of the sheet 14 is moved to the right hand. Are picked by the two fingers 20 and 20 and pulled in the direction of the arrow along the surface of the skin 16. Thereby, the brittle root portion 12 </ b> B of the needle 12 is broken (broken), and the sheet 14 is removed from the needle 12. In this case, the root portion on the sheet side of the destroyed root portion is removed together with the sheet 14. Thereby, only the needle 12, in particular, the distal end portion 12 </ b> A containing the drug can be left in the skin 16. Further, since the needle 12 remaining in the skin 16 is biodegradable, it is not dissolved in the living body.

  4 will be further described with reference to the schematic diagram of FIG. 4. As shown in FIG. 4A, the needle 12 of the microneedle sheet 10 is pressed against the skin as shown in FIG. The needle 14 is inserted into the skin 16 by pressing the sheet 14 from above. Next, as shown in FIG. 4C, the sheet 14 is pulled along the surface of the skin 16 while being pressed. As a result, as shown in FIG. 4D, only the needle 12 remains in the skin 16 and the sheet 14 is removed.

  In the above method of use, when the needle 12 is stabbed into the skin 16, there is a repulsive force due to the elasticity of the skin 16. Therefore, it is difficult to pierce the entire length of the needle 12 into the skin 16, and generally the needle 12 protrudes from the surface of the skin 16 by about 100 to 200 μm. Therefore, depending on the position where the root portion 12B is broken, the needle 12 remaining in the skin 16 may be projected from the skin surface. In this case, if the microneedle sheet 10 shown in FIG. 2 is used, the root portion 12B is formed at a layer thickness of 5 to 30% at a position 100 to 200 μm from the base end position of the entire length of the needle. It is possible to effectively prevent the needle 12 remaining in the skin 16 from jumping out from the surface of the skin 16.

  Thereby, even when the microneedle sheet 10 of the present invention is used for a face, a foot, a hand, etc. exposed to the outside, it may not be apparent from the appearance whether the microneedle sheet 10 is used. it can.

  In addition, since the microneedle sheet 10 itself is small in use of the microneedle sheet 10, there is a drawback that the sheet 14 is difficult to pull. However, by improving as shown in FIGS. 5 and 6, the sheet 14 can be easily pulled. can do.

  FIG. 5 (A) is an enlarged area for picking up the sheet 14 with a finger, and has an area that can be easily picked up with two fingers on the opposite side of the needle arrangement region 22 (dashed line portion) where the needles 12 are arranged and supported. A knob 14A is provided.

  FIG. 5B shows the knob 14A in a ring shape. For example, by inserting an index finger into the ring, the sheet 14 can be easily pulled.

  FIG. 6 also shows an auxiliary jig 24 that reliably breaks (folds) the root portion 12B of the needle 12 when the sheet 14 is pulled along the surface of the skin 16.

  As shown in FIG. 6A, the auxiliary jig 24 is formed in a thin plate shape made of metal or plastic that is thinner than the layer thickness of the root portion 12 </ b> B of the needle 12. A hole 26 into which the needle 12 is inserted is formed in the front end surface of the auxiliary jig 24 formed in a thin plate shape, and a pressing portion 28 for pressing the auxiliary jig 24 is formed in the rear end surface. The size of the hole 26 formed in the auxiliary jig 24 is preferably larger than the diameter of the root portion 12B of the needle 12. In addition, the microneedle sheet 10 using the auxiliary jig 24 of FIG. 6A is a case where a total of nine needles 12 are arranged in a lattice pattern on the surface of the sheet 14 in three vertical and horizontal directions. Nine holes 26 corresponding to the needles 12 are also formed on the distal end surface.

  The auxiliary jig 24 is used by inserting the needles 12 into the skin 16 as shown in FIG. 6B with the nine needles 12 of the microneedle sheet 10 inserted into the holes 26 of the auxiliary jig 24, respectively. Then, the sheet 14 is pulled in the direction of the arrow along the skin surface by the two fingers 20, 20 of the right hand while the pressing portion 28 of the auxiliary jig 24 is pressed by the finger 18 of the left hand. Thereby, since the cutting force by the auxiliary jig 24 is applied to the root portion 12B of the needle 12, the root portion 12B can be reliably destroyed. Therefore, it is preferable to sell as a set product in which the microneedle sheet 10 and the auxiliary jig 24 are set.

  Next, the manufacturing method which manufactures the microneedle sheet | seat 10 of FIG. 2 is demonstrated.

  First, as shown in FIG. 7A, on the surface 32A of the mold 32 having the needle-like concave portion 30, a first solution 34 in which the drug and the tip material are dispersed or dissolved in a solvent such as water or alcohol. Apply (dissolution solution application step). The needle-like concave portion 30 is a region that is recessed as compared with the surface 32A of the mold 32, and the shape of the needle-like concave portion 30 is formed in the inverted shape of the needle shape described in FIG.

  The material of the mold 32 is not particularly limited, but it is preferable to use a resin having good releasability such as silicon rubber from the viewpoint of preventing damage when the molded needle molded product is peeled off.

  Examples of the method for applying the first solution 34 include a coating method such as bar coating, spin coating, and spray coating, and a dropping method using an ink jet recording apparatus. In particular, a method of dropping a necessary amount by a dropping method of an ink jet recording apparatus is preferable.

  The application amount of the first lysing solution 34 is appropriately adjusted in consideration of the concentration of the tip material in the first lysing solution 34 so that the tip 12A is formed in a desired region of the needle 12. Moreover, it is preferable that the density | concentration of the front-end | tip part material in the 1st solution 34 is the range of 10-50 mass% from a viewpoint of volatilizing a solvent for a short time, without impairing a moldability.

  In the present specification, the term “drug” is a general term for substances having an effect of exerting any advantageous action on the human body. For example, insulin, nitroglycerin, vaccines, antibiotics, asthma drugs, analgesics, It refers to medical narcotics, local anesthetics, antianaphylaxis drugs, skin disease drugs, sleep-inducing drugs, vitamins, smoking cessation aids, beauty drugs (eg hyaluronic acid), and the like.

  Moreover, the 1st solution 34 may contain various additives other than a chemical | medical agent and tip part material. For example, adjuvant may be added together with the drug from the viewpoint of more efficiently absorbing the drug in the patient.

  Next, as shown in FIG. 7B, the first solution 34 on the mold surface 32A is filled into the needle-shaped recess 30 (solution filling step). As a method of filling the first dissolving liquid 34 into the needle-shaped recess 30, a pressurizing method is usually used.

  FIG. 8 is a view showing a pressure filling apparatus. The pressure filling device 50 shown in the figure includes a pressure vessel 52 having an inlet 58 and a discharge port 60, a pedestal 54 provided inside the pressure vessel 52, and a compressor 56 that sends pressurized fluid into the pressure vessel 52. including. By operating the pressure filling device 50 according to the following procedure, the first dissolution liquid 34 can be filled into the needle-shaped recess 30. That is, in a state where the mold 32 into which the first solution 34 has been cast is placed on the pedestal 54, the pressurized fluid is fed into the pressure-resistant container 52 through the inlet 58 by the compressor 56. As the pressurized fluid, gas or liquid can be used. Examples of the gas that can be used as the pressurized fluid include air. From the viewpoint of preventing the pressurized fluid from being dissolved in the first dissolved solution 34, the gas having a low dissolution rate in the first dissolved solution 34. Is preferably selected. From the viewpoint of preventing an increase in viscosity due to volatilization of the first solution 34, a liquid of the same type as the solvent of the first solution 34 is stored in the pressure vessel 52 in advance, and the inside of the pressure vessel 52 is filled with the liquid. It is preferable to be saturated with steam.

  By operating the pressure filling device 50 according to the above procedure, the first dissolving liquid 34 is quickly filled into the needle-like recess 30.

  In addition to the pressurization method, the decompression method can be adopted as the filling method of the first dissolving liquid 34. The decompression method will be described when the root portion 12B of the needle 12 is formed.

  Next, the first dissolved solution 34A remaining on the mold surface 32A is removed by a centrifugal method (excess dissolved solution removing step). That is, as shown in the excess solution removing device 33 in FIG. 9, the mold 32 is fixed on the rotary table 36 and the rotary table 36 is rotated by the rotary device 39, so that it remains on the mold surface 32A by centrifugal force. The first dissolving liquid 34A is scattered. As a result, as shown in FIG. 7C, the first solution 34 remaining on the mold surface 32A is removed. The method of removing the first solution 34 remaining on the mold surface 32A is not limited to the centrifugal method. For example, a method of blowing wind from the side of the mold surface 32A or using a spatula or the like. There is a method of scraping, but the centrifugal method is particularly preferable. Further, the solution removed from the mold surface 32A can be reused.

  Next, the mold 32 is placed in a drying device (not shown), and the first solution 34 filled in the needle-shaped recess 30 is dried (solution solution drying step). In this case, the pressure vessel 52 can be used as a drying vessel with a structure in which hot air is blown into the pressure filling device 50 described above. As a result, as shown in FIG. 7D, the solvent of the first solution 34 is removed and contracted and solidified, so that a space 38 for filling the next root portion material is formed in the needle-like recess 30. It is formed. However, the drying step is not necessary if the space 38 is formed by the excess solution removal step.

  Next, as shown in FIG. 7 (e), a root portion material for forming the root portion 12 </ b> B of the needle 12 is formed on the mold surface 32 </ b> A on which the first solution 34 is solidified in the needle-shaped recess 30. The 2nd solution 40 disperse | distributed or melt | dissolved in solvents, such as water and alcohol, is provided (solution-solution provision process). Examples of the application method include a coating method such as bar coating, spin coating, and spray coating, and a dropping method using an ink jet recording apparatus. A dropping method using an ink jet recording apparatus is particularly preferable. The application amount of the second solution 40 is such that the root portion 12 </ b> B is formed in a desired region of the needle 12. Specifically, as described above, it is preferable to form a layer thickness of 5 to 30% with respect to the full length of the needle at a position of 100 to 200 μm from the base end position of the full length of the needle. In order to form in this way, the concentration is appropriately adjusted in consideration of the concentration of the root portion material in the second solution 40.

  Next, as in the case of the first solution 34, the solution filling step → the excess solution removing step → the solution drying step is repeated for the second solution 40. As a result, as shown in FIG. 7F, the solidified layer of the second dissolved liquid 40 is laminated on the layer in which the first dissolved liquid 34 is solidified, and the root support portion 12C to be filled next is formed. A space portion 38 for forming is formed.

  In forming the root portion 12B, the root portion 12B needs to be molded as a portion having the greatest brittleness in the entire needle 12. Therefore, in order to obtain the necessary brittleness, the second solution 40 is filled with a pressure method. Instead of this, there is a method in which the pressure is reduced. Although not particularly illustrated, the decompression method is a method of returning the atmospheric pressure after applying the second solution 40 on the mold surface 32A under reduced pressure. In the depressurization method, a volatile solvent is used as the type of the solvent used in the second solution 40 to boil and foam under reduced pressure, and bubbles are mixed in the molded root portion 12B. Therefore, by skillfully utilizing this decompression method, bubbles are contained in the root portion 12B and become porous, so that brittleness increases. It is preferable to test in advance in a preliminary test or the like to determine how much the degree of decompression is to be brittle.

  Next, the third solution 42 for forming the root support portion 12C is used to perform the solution application step → the solution filling step → the solution drying step. Thereby, as shown in FIG.7 (g), the root support part 12C is formed in the sheet | seat 14 side of the root part 12B. As can be seen from FIG. 7 (g), the base support portion 12C has a T-shape in which the third solution 42 filled in the needle-like recess 30 forms a thin plate-like portion 42A continuous with the mold surface 32A. Formed as a layer. Therefore, the solution removal step may not be performed, or the centrifugation may be performed to such an extent that the third solution 42 remains in the form of a thin film on the mold surface 32A. Thereby, the needle molded product 44 having a three-layer structure including the tip portion 12A, the root portion 12B, and the root support portion 12C is formed.

  Finally, as shown in FIG. 7 (h), an adhesive sheet is attached to the plate-like portion 42A of the needle molded product 44, and the whole sheet 14 is peeled off (peeling step). Thereby, the microneedle sheet | seat 10 shown in FIG.7 (i) is obtained.

  In this case, as described in the above method of use, the microneedle sheet 10 of the present invention is manufactured for the purpose of removing the sheet 14 immediately after the needle 12 is stabbed into the skin 16 and leaving only the needle 12 in the body. It is a thing. Therefore, as shown in FIG. 7J, it is preferable that the adhesive layer of the sheet 14 exists only in the needle arrangement region 22 in which the needles 12 are arranged.

  The method for peeling the needle molded product 44 is not limited to the above-described pressure-sensitive adhesive sheet, and includes a method in which a suction cup is adsorbed on the back surface of the needle molded product 44 and peeled. In this case, it is necessary to later affix the sheet 14 to the needle molded product 44 peeled from the mold 32 with a suction cup, and it is preferable to affix a sheet having a sliding layer on the affixing side of the sheet 14. Thereby, when the sheet 14 is pulled along the surface of the skin 16, the sliding layer slides with respect to the skin surface, so that the sheet 14 can be easily pulled.

  In addition, in the manufacturing method of the above-mentioned microneedle sheet | seat, it demonstrated in the case of the needle 12 of the 3 layer structure shown in FIG. However, in the case of the two-layer structure of FIG. 1, the root portion 12B may be formed after the tip portion 12A is formed, and the basic manufacturing method is the same.

  As mentioned above, although one Embodiment of this invention was described in detail, this invention is not limited to this, Of course, various improvement and deformation | transformation may be performed in the range which does not deviate from the summary of this invention.

  In this example, a microneedle sheet was produced as shown below by the manufacturing method of the above-described embodiment.

[Test sample 1]
<Mold production>
First, using a wire-like metal having a diameter of 250 μm, a 300 μm tip portion was ground into a conical shape having a tip curvature radius of 5 μm. Then, after making a hole in the center of a smooth 40 mm × 40 mm square copper plate, the tip of the first wire-like metal whose tip was cut as described above was fixed by protruding 1000 μm from the hole. Similarly, the wire-like metals were arranged in a grid pattern with a pitch of 500 μm with the first wire-like metal as a reference. In other words, 10 × 10 wires perpendicular to the surface of the copper plate were arranged and fixed in the form of a lattice to form an original plate. Using this original plate, a transfer product (inverted version of the original plate) is made of silicon rubber (an RTV rubber for Shin-Etsu silicone mold), and the peripheral portion of the transfer product is cut off to obtain a 45 mm × 45 mm square and a thickness of 5 mm. A mold 32 was created. That is, the mold 32 is formed with needle-like recesses 30 having a 10 × 10 lattice arrangement as holes recessed from the mold surface 32A.

<Preparation of 1st-3rd solution>
Gelatin (Nitta Gelatin 732) was dissolved in water to give a 20% by mass aqueous solution. And after stirring at 40 degreeC, it heat-retained at the same temperature for 3 hours, What added ascorbic acid 1% as a chemical | medical agent in this liquid was used as the 1st solution 34 for shape | molding the front-end | tip part 12A. . In addition, the thing which does not add ascorbic acid was used as the 3rd solution 42. The second solution 40 was a mixture of gelatin and dextrin at a mass mixing ratio of 1: 3.

<Application and Filling Step of First Solution>
On the surface 32A of the mold 32 made of silicon rubber, 1.5 mL of the first solution 34 was dropped using an ink jet recording apparatus. And the mold 32 is put in the pressure filling apparatus 50 which heated the inside to 40 degreeC with the jacket, and the pressure in the pressure-resistant container 52 is 0.5 MPa (0.4-1.0 MPa) with the compressed air from a compressor. ) For 3 minutes (2-4 minutes). The parenthesized values are a preferable pressure range and holding time.

  As a result, the first dissolving liquid 34 was filled in the needle-shaped recess 30 of the mold 32. Thereafter, the first solution 34A remaining on the mold surface 32A without entering the needle-shaped recess 30 is removed from the mold 32 by the excess solution removal device 33 at 3000 rpm (2000 to 4000 rpm) for 10 seconds (6 to 20). For 2 seconds). In addition, a preferable number of rotations and holding time are shown in parentheses.

<Drying process of the 1st solution>
The pressure filling device 50 after the filling process is replaced with a drying device, and hot air of 60 ° C. (40 to 70 ° C.) is applied to the mold 32 in the pressure vessel 52 to fill the needle-like recess 30. The first dissolved solution 34 was dried for 2 hours (1 to 4 hours). The parenthesized values are preferred hot air temperatures and drying times. Thereby, the 1st solution 34 of needlelike crevice 30 contracts and solidifies, and tip part 12A of needle 12 is fabricated.

<Second Dissolution Solution Application Step to Drying Step>
The root portion 12 </ b> B is formed by the same method as the first dissolving solution application step to the drying step described above. That is, 1 mL of the second solution 40 for forming the root portion 12B is dropped on the mold surface 32A. Then, after filling the space portion 38 formed on the formed tip portion 12A of the needle-like recess 30 with the pressure filling device 50, the mold 32 is rotated by the excess solution removing device 33, and the mold surface 32A is then rotated. The remaining solution of the second dissolving solution 40 remaining in is removed. Then, instead of the pressure filling device 50 as a drying device, hot air of 60 ° C. (40 to 70 ° C.) is applied to the mold 32 in the pressure vessel 52 to fill the space 38 of the needle-shaped recess 30. The second solution 40 was dried for 1 hour (0.5 to 2 hours). As a result, the root portion 12B is formed on the tip portion 12A in the needle-shaped recess 30 and the space portion 38 for forming the next root support portion 12C on the root portion 12B of the needle-shaped recess 30 is formed. Is formed.

<Third dissolving solution application step to drying step>
Further, in the same manner as described above, 3 mL of the third solution 42 for forming the root support portion 12C is dropped on the mold surface 32A and filled into the needle-like recess 30 with the pressure filling device 50, and then the pressure filling device. A drying apparatus substituting 50 was subjected to a drying treatment at 60 ° C. for 30 minutes. In the case of the third solution 42, since it is necessary to form the plate-like portion 42A, which is a part of the root support portion 12C, on the mold surface 32A, the third dissolution solution 42 is enough to form a thin film on the mold surface 32A. The excess liquid of the solution 42 was removed. Thereby, a needle molded product 44 having a three-layer structure is created from the tip portion 12A, the root portion 12B, and the root support portion 12C.

<Needle molded product peeling process>
The sheet 14 having an adhesive layer only on the needle array region 22 is attached to the plate-like portion 42 </ b> A of the needle molded product 44, and the needle molded product 44 is peeled from the mold 32 together with the sheet 14. Thereby, the microneedle sheet | seat 10 is manufactured. The needle 12 of this microneedle sheet 10 has a layer thickness (length) corresponding to the tip portion 12A of approximately 600 μm, a layer thickness corresponding to the root portion 12B of approximately 200 μm, and a portion corresponding to the root support portion 12C. The layer thickness was about 150 μm (not including the plate-like portion 42A). The microneedle sheet 10 thus manufactured was used as a test sample 1.

  Test needle 1 had a total needle length (including plate-like portion 42A) of 1000 μm, and bending yield stress of root portion 12B was 6 MPa. Furthermore, the bending yield stress of the root portion 12B was 1 / 3.3 of the bending yield stress 20MPa of the tip portion 12A.

[Test sample 2]
Test sample 2 was prepared by replacing the second solution 40 in test sample 1 with dextrin and producing a microneedle sheet in the same manner. The bending yield stress of the root portion 12B in the test sample 2 was 0.5 MPa.

[Test sample 3]
The second solution 40 in the test sample 1 was replaced with a mixture of gelatin and dextrin mixed at a mass mixing ratio of 1: 3, and the sample prepared as a microneedle sheet in the same manner was used as the test sample 3. . The bending yield stress of the root portion 12B in the test sample 3 was 4.5 MPa.

[Test sample 4]
The test sample 4 was obtained by replacing the second solution 40 in the test sample 1 with gelatin and producing a microneedle sheet in the same manner except that the test sample 4 was used. That is, the test sample 4 is a case where the entire needle is made of gelatin having a bending yield stress of 20 MPa.

[Test sample 5]
The test sample 5 is a case where the second solution 40 in the test sample 1 is replaced with a pullulan having a bending yield stress of 10 MPa, and a microneedle sheet is manufactured in the same manner.

[Test sample 6]
The test sample 6 is a case where the second solution 40 in the test sample 1 is replaced with a mixed solution having a mixing ratio of gelatin: dextrin = 1: 1, and the microneedle sheet is manufactured in the same manner. The bending yield stress was 12 MPa when gelatin: dextrin was mixed 1: 1.

[Sheet removal test method]
For the test samples 1 to 6 manufactured as described above, a sheet removal test is performed according to the following procedures (1) to (3), and the root portion of the needle is easily and reliably broken by a pulling force along the skin surface. The preferred degree of brittleness was investigated. As evaluation items, “the length of the needle remaining in the skin” and “the state of needle sticking” were evaluated.

  (1) A microneedle sheet is stabbed into the artificial skin by pressing it with a finger from above the sheet.

  (2) Next, with the finger pressed against the skin surface with the finger, the sheet is pulled in the horizontal direction until the base of the needle breaks (breaks), and the sheet is removed.

  (3) Measure the length of the needle protruding from the artificial skin and the length of the needle remaining on the sheet, calculate the “length of the needle remaining in the skin” and visually check the “needle stick” The condition was evaluated.

[Sheet removal test results]
The test results are shown in the table of FIG. In the table of FIG. 10, “the length of the needle remaining in the skin” is shown as an average of 10 × 10 (100 in total).

  As can be seen from the table of FIG. 10, the test sample 1 has an average of “the length of the needle remaining in the skin” of about 800 μm, and most of the total needle length (1000 μm) can be left in the skin. It was. Further, “needle penetration” was good because all 10 × 10 needles (100 needles in total) did not protrude from the skin surface. From this result, when the bending yield stress at the root portion of the needle is 6 MPa, the root portion can be easily and reliably broken by the force of pulling the sheet, and only the needle can be left in the skin so as not to protrude from the skin surface.

  In the test sample 2, the average of the “length of the needle remaining in the skin” was about 820 μm, and most of the entire needle length (1000 μm) could be left in the skin. In addition, as the “needle sticking condition”, all of 10 × 10 (100 in total) did not protrude from the skin surface and were good. From this result, when the bending yield stress at the base of the needle is 0.5 MPa, it is possible to easily and surely break the base with the force of pulling the sheet and leave only the needle in the skin so as not to protrude from the skin surface. it can.

  In the test sample 3, the average of “the length of the needle remaining in the skin” was about 815 μm, and most of the entire needle length (1000 μm) could be left in the skin. In addition, as the “needle sticking condition”, all of 10 × 10 (100 in total) did not protrude from the skin surface and were good. From this result, when the bending yield stress at the base of the needle is 4.5 MPa, it is possible to easily and surely destroy the base with the force of pulling the sheet and leave only the needle in the skin so as not to protrude from the skin surface. it can.

  In the test sample 4, the average of the “length of the needle remaining in the skin” is extremely short as about 200 μm, and the “needle sticking degree” is 10 × 10 (total of 100) more than half of the sheet is the sheet. Together they slipped out of the skin. From this result, when the base part of the needle is formed of the same material as the tip part, it does not break with the force of pulling the sheet, or even if it breaks, the part other than the root part near the skin surface of the needle is broken. I understand.

  In the test sample 5, the average of the “length of the needle remaining in the skin” was about 600 μm, and more than half of the total length of the needle could be left in the skin. Moreover, there was little jumping out from the skin surface in the “needle sticking condition”. From this result, when the bending yield stress at the base of the needle was 10 MPa, the brittleness of the base was almost satisfactory.

  In the test sample 6, the average of “the length of the needle remaining in the skin” was about 500 μm, and half of the total length of the needle remained in the skin, but the “needle sticking condition” was conspicuously protruding from the skin surface. It was. From this result, it is understood that the brittleness of the root portion is not insufficient when the bending yield stress at the root portion of the needle is 12 MPa.

  As can be seen from the above test results, in Test Samples 1 to 3 and 5 using materials that are sufficiently brittle than Test Samples 4 and 6 as the material of the root portion 12B, the sheet is pulled horizontally along the skin surface. Thus, the root portion 12B can be easily and reliably broken (folded), and only the needle 12 can be left in the skin 16.

  Therefore, in order to easily and reliably break the root portion when the sheet is pulled, it is necessary to make the root portion of the needle more brittle than the tip portion, and furthermore, the bending yield stress of the root portion 12B. As for, it turned out that the range of 10 MPa of test sample 5 to 0.5 MPa of test sample 3 is preferable.

  DESCRIPTION OF SYMBOLS 10 ... Microneedle sheet | seat, 12 ... Needle, 12A ... Tip part, 12B ... Root part, 12C ... Root support part layer, 14 ... Sheet, 14A ... Grab part of sheet, 16 ... Skin, 18, 20 ... Finger of hand , 22 ... Needle arrangement region, 24 ... Auxiliary jig, 26 ... Hole, 28 ... Holding part of auxiliary jig, 30 ... Needle-shaped recess of mold, 32 ... Mold, 33 ... Excess dissolved solution removing device, 34 ... First dissolution Liquid 36, rotating table 39 39 rotating device 40 second dissolving liquid 42 third dissolving liquid 44 needle molded product 50 pressure filling device 52 pressure vessel 54 pedestal 56 ... Compressor, 58 ... Inlet, 60 ... Drain

Claims (16)

A microneedle sheet that is used by inserting a biodegradable needle supported on the surface of the sheet into the skin,
The root part of the needle near the sheet is formed to be more brittle than the tip part, and has a brittleness degree that can be broken by a force that pulls the sheet along the skin surface while the needle is inserted into the skin. A featured microneedle sheet.   The microneedle sheet according to claim 1, wherein when the brittleness of the root portion is expressed by a bending yield stress, the bending yield stress is 0.5 MPa or more and 10 MPa or less.   3. The microneedle sheet according to claim 2, wherein the bending yield stress of the root portion is ½ or less of the bending yield stress of the tip portion that is on the needle tip side with respect to the root portion.   The microneedle sheet according to any one of claims 1 to 3, wherein the tip portion includes gelatin, and the root portion includes a saccharide or a mixture of saccharide and gelatin.   The microneedle sheet according to claim 1, wherein bubbles are contained in the root portion.   The microneedle sheet according to any one of claims 1 to 5, wherein a root support portion that supports the root portion is formed on the sheet side of the root portion.   The microneedle sheet according to claim 6, wherein the root portion is formed in a layer thickness of 5 to 30% of the total length of the needle at a position of 100 to 200 µm from the base end position of the total length of the needle.   The microneedle sheet according to any one of claims 3 to 7, wherein the tip portion has a substantially conical shape or a substantially pyramid shape, and the root portion has a substantially cylindrical shape or a substantially prismatic shape.   The microneedle sheet according to any one of claims 1 to 8, wherein a sliding layer is formed on the skin surface side of the sheet.   The microneedle sheet according to any one of claims 1 to 9, wherein a pinch portion is formed on the sheet to be picked with a finger when the sheet is pulled.   The microneedle sheet according to claim 10, wherein a ring for inserting a finger is formed in the knob.   The microneedle sheet according to any one of claims 1 to 11, wherein a drug is contained in the tip portion. A method of using the microneedle sheet according to any one of claims 1 to 12,
A puncturing step of inserting a needle into the skin;
A breaking step of picking the sheet with a finger and pulling it along the surface of the skin to break the brittle root of the needle;
A method of using a microneedle sheet, comprising: a sheet removing step of removing the sheet from the skin surface and leaving only the needle in the skin. In a method for producing a microneedle sheet, wherein a biodegradable needle supported on the surface of the sheet is stabbed into the skin and used,
A first application step of applying, to the mold surface, a tip solution containing a drug and a tip material forming the tip of the needle;
A first filling step of filling the applied tip portion dissolving solution into the needle-like concave portion of the mold;
A first removal step of removing the remaining liquid of the distal end portion dissolving liquid remaining on the surface of the mold;
A second application step of applying a root part solution containing a root part material that forms the root part of the needle to the mold surface after the residual liquid of the tip part solution has been removed;
A second filling step of filling the applied root portion dissolving solution into the space in the needle-like recess and forming a plate-like portion continuous with the mold surface;
A drying step of drying and solidifying the solution for the tip portion and the solution for the root portion;
A peeling step of peeling a needle molded product constituted by the tip portion and the root portion from the mold;
A method of manufacturing a microneedle sheet, comprising: a sheet attaching step of attaching the sheet to the plate-like surface of the needle molded product.   15. The method of manufacturing a microneedle sheet according to claim 14, further comprising a step of forming a root support portion that supports the root portion on the sheet side of the root portion.   The sheet is composed of an adhesive layer portion to be attached to the needle molded product and a non-adhesive layer portion if the adhesive layer is not provided, and the adhesive layer portion is attached to the needle molded product and peeled off. The method for producing a microneedle sheet according to claim 14, wherein the peeling step and the sheet sticking step are performed at a time.

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