JP5063543B2 - Method for producing transdermal absorption sheet - Google Patents

Description

  The present invention relates to a method for producing a transdermal absorption sheet in which needle-like convex portions containing a drug are formed on a sheet portion.

  In recent years, high aspect ratio structural sheets such as microneedles and micropillars, on which high-aspect-ratio needle-like convex portions are formed, have been applied in various fields as functional films. For example, if a functional substance is added to a high aspect ratio structure sheet, various functions that take advantage of the characteristics of the high aspect ratio structure are exhibited.

  In particular, in the medical technology field, by using a high aspect ratio structure sheet to which a drug as a functional substance is added, the drug is efficiently transdermally administered to the patient through the patient's skin surface or skin stratum corneum. Absorption systems are drawing attention. This high aspect ratio structural sheet for a transdermal absorption system is generally referred to as a transdermal absorption sheet.

  As a method for producing a transdermal absorption sheet, for example, a cast molding method using a mold having a needle-like concave portion is known. FIG. 5 is a diagram showing a state in which a transdermal absorption sheet is produced by a conventional cast molding method. In this method, in a state where the mold 210 having the needle-like recesses 212 is filled with the polymer solution 220 containing the drug (see FIG. 5A), the polymer solution 220 is dried and solidified (FIG. 5B). (See FIG. 5 (c)). The transdermal absorption sheet 230 in which the microneedles 224 are formed on the sheet portion 226 is manufactured by peeling from the mold 210.

  However, in this method, an expensive drug is added not only to the microneedle 224 that is inserted into the patient's body and directly related to drug administration, but also to the sheet portion 226 that does not contribute much to drug administration. The manufacturing cost of the absorbent sheet 230 is increased. Therefore, the following method has been proposed as a method that enables selective drug addition to the microneedle.

  Patent Documents 1 and 2 disclose a method of manufacturing a transdermal absorption sheet by attaching a liquid material containing a drug to a base material and molding and solidifying the liquid material into a needle shape on the base material. . In this method, since the microneedle is formed as a separate body (separate material) of the base material, the drug can be selectively added to the microneedle by adding the drug only to the liquid material. Thereby, a chemical | medical agent will be added only to the microneedle directly concerned with chemical | medical agent administration, and the addition amount of a chemical | medical agent can be minimized.

  However, in the methods of Patent Documents 1 and 2, since the microneedle and the base material are configured as separate bodies, peeling at the interface between them tends to occur, and the strength of the base of the microneedle may not be sufficient. Therefore, a method is conceivable in which a drug is selectively added to the microneedle after the microneedle and the substrate are integrally formed.

For example, in Patent Documents 3 to 5, after a microneedle composed of a polyester resin, a polycarbonate resin, or the like is formed on a substrate, the drug is applied to the transdermal absorption sheet by coating the drug on the surface of the microneedle. The method of adding is disclosed. According to this method, selective drug addition to the microneedle becomes possible, and the amount of drug added can be minimized.
JP 2003-238347 A JP 2006-346008 A JP-T-2004-504120 JP 2007-190112 A Special table 2008-520433 gazette

  In the methods of Patent Documents 3 to 5, since the drug permeability of polyester resin, polycarbonate resin, or the like, which is a constituent material of the microneedle, is low, the drug is added only to the surface of the microneedle. However, since there is a limit to the amount of drug that can be added to the microneedle surface, it may be difficult to add a necessary and sufficient amount of drug in this method.

  Moreover, in the methods of Patent Documents 3 to 5, there is a large variation in the amount of drug applied to the microneedle surface, and it is difficult to quantitatively add the drug to the transdermal absorption sheet. On the other hand, some drugs cannot achieve the desired efficacy unless the dosage to the patient is strictly adjusted. Therefore, it is desired to develop a method capable of quantitatively adding the drug.

  The present invention has been made in view of such circumstances, and relates to a method for producing a transdermal absorption sheet in which a necessary and sufficient amount of a drug can be selectively and quantitatively added only to a needle-like convex portion.

  The invention described in claim 1 is an application step of applying a polymer solution containing a biodegradable polymer having a gelling property as a solid component to a mold having a needle-like recess, and an inverted shape of the needle-like recess. In the solidifying step of solidifying the polymer solution so that a polymer sheet having a certain needle-like convex portion is formed, a peeling step of peeling the polymer sheet formed in the solidifying step from the mold, and the peeling step Including a drug penetration step of immersing only the needle-like convex portion of the polymer sheet in a drug solution containing the drug so that the drug penetrates into the needle-like convex portion of the peeled polymer sheet. The present invention relates to a method for producing a transdermal absorption sheet.

  According to the manufacturing method according to claim 1, since only the needle-like convex portion of the polymer sheet is immersed in the drug solution in the drug infiltration step, selective drug addition to the needle-like convex portion of the polymer sheet is possible. Become.

  In addition, since the polymer sheet is formed using a biodegradable polymer having gelling property, the polymer sheet absorbs the drug solution and swells when immersed in the drug solution. As the polymer sheet swells, the drug penetrates not only into the surface of the needle-like convex portion of the polymer sheet but also into the inside. Thus, since a chemical | medical agent can be osmose | permeated inside the acicular convex part of a polymer sheet, a required and sufficient quantity of chemical | medical agents can be added easily.

  Furthermore, the amount of drug added can be quantitatively adjusted by appropriately changing the immersion conditions (drug temperature, immersion time, etc.) in the drug solution.

  In the present specification, the “solid component” of the polymer solution refers to a component that remains on the mold as a solid (polymer sheet) after the polymer solution is solidified. In addition, in this specification, the expression “selectively” adding a drug to the needle-shaped protrusions is not limited to the case where all of the drug is added only to the needle-shaped protrusions of the polymer sheet. It also refers to the case where it is added to the convex shape.

  The invention described in claim 2 relates to a method for producing a transdermal absorption sheet according to claim 1, wherein the biodegradable polymer is gelatin.

  According to the production method of the second aspect, it is possible to quickly form a polymer sheet by using gelatin that is easily gelled as a solid component in the polymer solution. In addition, since gelatin has a property of shrinking when solidified, the polymer sheet can be easily peeled from the mold by the action of shrinkage stress generated inside the polymer sheet.

  The invention described in claim 3 relates to a method for producing a transdermal absorption sheet according to claim 2, wherein the polymer solution contains the gelatin and saccharide as solid components.

  According to the production method of the third aspect, by using gelatin and saccharide as solid components in the polymer solution, a polymer sheet in which the gelatin component and the saccharide component are mixed can be formed. Since the saccharide component is relatively easily eluted in the drug solution, when the polymer sheet is immersed in the drug solution, a large number of micropores are formed in the needle-like convex portions of the polymer sheet, and the drug solution is formed in the numerous micropores Penetration phenomenon occurs. Thereby, the chemical | medical agent osmosis | permeation to the acicular convex part of a polymer sheet can be accelerated.

  Invention of Claim 4 includes the drying process which dries the polymer sheet which the said chemical | medical agent osmose | permeated to the inside of the said acicular convex part, It is any one of Claims 1-3 characterized by the above-mentioned. The present invention relates to a method for producing a transdermal absorption sheet.

  According to the manufacturing method which concerns on Claim 4, the shape of a needle-like convex part can be improved by drying the polymer sheet which the shape of the needle-like convex part deteriorated by the deformation | transformation accompanying swelling.

  The invention described in claim 5 includes a filling step of filling the needle-shaped concave portion with the polymer solution applied to the mold. The present invention relates to a method for producing a transdermal absorption sheet.

  According to the manufacturing method which concerns on Claim 5, the percutaneous absorption sheet which has a needle-shaped convex part of a high aspect ratio can be manufactured by filling the polymer melt in the concave part of the mold.

  The invention described in claim 6 relates to a method for producing a transdermal absorption sheet according to any one of claims 1 to 5, wherein the mold contains a silicone resin.

  According to the manufacturing method concerning Claim 6, it becomes possible to peel a polymer sheet easily from a mold by using the silicone resin excellent in peelability.

  Invention of Claim 7 is related with the manufacturing method of the transdermal absorption sheet as described in any one of Claims 1-6 in which the said chemical | medical solution contains at least one of alcohol and water. .

  According to the manufacturing method which concerns on Claim 7, the chemical | medical agent penetration to the acicular convex part of a polymer sheet can be accelerated by using the chemical | medical solution containing alcohol and / or water which is easy to swell a polymer sheet.

  Invention of Claim 8 is related with the manufacturing method of the transdermal absorption sheet as described in any one of Claims 1-7 whose diameters of the said acicular recessed part are 50 micrometers or more and 300 micrometers or less.

  Invention of Claim 9 is related with the manufacturing method of the percutaneous absorption sheet as described in any one of Claims 1-8 whose depth of the said acicular recessed part is 200 micrometers or more and 2000 micrometers or less. .

  The invention described in claim 10 is the transdermal absorption sheet according to any one of claims 1 to 9, wherein the mold includes a plurality of mold units in which the needle-like recesses are formed. It relates to the manufacturing method.

  According to the manufacturing method which concerns on Claim 10, a percutaneous absorption sheet can be efficiently manufactured by using the large-area mold containing a plurality of mold units.

  According to the present invention, after a polymer sheet is formed from a gelling polymer, only the needle-like convex portions of the polymer sheet are immersed in the drug solution, so that a necessary and sufficient amount of the drug is only on the needle-like convex portions. A percutaneous absorption sheet added selectively and quantitatively can be produced.

  Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. First, a method for producing a transdermal absorption sheet according to an embodiment of the present invention will be described, and then a structural example of the transdermal absorption sheet produced by the method will be described.

  FIG. 1 is a diagram showing a method for producing a transdermal absorption sheet according to an embodiment of the present invention.

  First, as shown to Fig.1 (a), the mold 10 which has the needle-shaped recessed part 12 is prepared. The needle-like recess 12 is a region that is recessed as compared to the flat surface 16 of the mold 10, and the shape of the needle-like recess 12 is preferably determined so as to obtain a microneedle having a desired shape. For example, from the viewpoint of forming a high-aspect-ratio microneedle having a sharp tip, it is preferable that the width (diameter) of the needle-like recess 12 is 50 to 300 μm and the curvature radius of the deepest portion 14 is 10 μm or less. Moreover, it is preferable that the depth of the acicular recessed part 12 is 200-2000 micrometers.

  Although the material of the mold 10 is not particularly limited, a resin having a good releasability such as a silicone resin can be used from the viewpoint of preventing damage when the polymer sheet is peeled off.

  Next, as shown in FIG. 1B, a polymer solution 20 is applied to the mold 10. At this time, for the purpose of facilitating casting into the mold 10, a frame may be provided around a region where the needle-like recesses 12 of the mold 10 are arranged, and the polymer solution 20 may be applied to the frame. .

  Examples of the method for applying the polymer solution 20 include bar coating, spin coating, spray coating, and dropping using a dispenser. Especially, since the aspect which dripped the polymer solution 20 using a dispenser can control the dripping amount with high precision irrespective of the viscosity of the polymer solution 20, it is preferable.

  The applied amount (film thickness) of the polymer solution 20 is preferably adjusted as appropriate in consideration of the concentration of the solid component in the polymer solution 20 so that a transdermal absorption sheet having a desired film thickness can be obtained. . For example, the application amount (film thickness) of the polymer solution 20 can be adjusted in the range of 0.1 to 10 mm.

  The polymer solution 20 includes a gelling polymer (gelling polymer) constituting the solid component and a solvent that dissolves the gelling polymer.

  The gelling polymer in the polymer solution 20 is a material (biodegradable material) that is easily decomposed in vivo from the viewpoint of efficiently administering a drug without placing a burden on the patient, and has biocompatibility. It is preferable that it is a material (biocompatible material). Specifically, polymers such as gelatin, agarose, pectin, gellan gum, carrageenan, xanthan gum, alginic acid, starch, and cellulose can be used. Among them, gelatin is preferable from the viewpoint of rapidly forming a polymer sheet because it has a property of being relatively easily gelled. Further, since gelatin has a property of shrinking when dried and solidified, the peelability of the polymer sheet from the mold is improved by the action of shrinkage stress generated inside the polymer sheet.

  In the present embodiment, the gelling polymer is used as a solid component because the drug can penetrate into the inside as well as the surface of the microneedle, and the reason is considered as follows.

  The microneedle obtained by solidifying the polymer solution 20 has a three-dimensional network structure formed by chemical or physical polymer crosslinking, and when immersed in a drug solution, the microneedle is formed inside the network structure. Absorbs drug solution and swells. During the swelling of the microneedle, the drug penetrates not only into the surface of the microneedle but also into the inside.

  On the other hand, when a polymer having no gelling property is used as a solid component, the above-mentioned effect cannot be obtained, and the microneedle itself is dissolved in the drug solution by immersion in the drug solution, so that a desired needle shape is obtained. Difficult to maintain. In addition, since the microneedles do not swell when immersed in the drug solution, drug penetration into the microneedles does not occur.

  Next, as shown in FIG.1 (c), the polymer solution 20 provided to the mold 10 is dried and solidified. Examples of the method for drying and solidifying the polymer solution 20 include a method for forcibly volatilizing the solvent of the polymer solution 20 by heating, air blowing, reduced pressure, etc., in addition to the method of naturally drying the polymer solution 20.

  Next, by peeling from the mold 10, a polymer sheet 22 having microneedles 24 as shown in FIG. 1D is obtained.

  As an aspect of peeling of the polymer sheet 22, for example, a method in which a sheet having an adhesive layer on one side is attached to the back surface of the polymer sheet 22 and the whole sheet is peeled off, or a method in which a suction cup is adsorbed on the back surface of the polymer sheet 22 Etc.

  Next, as shown in FIG. 1 (e), only the microneedles 24 of the polymer sheet 22 are immersed in the drug solution 28, thereby allowing the drug to penetrate into the drug penetration region 24 a inside the microneedle 24.

  As a dipping mode of the microneedles 24, for example, a method of hanging the polymer sheet 22 so that only the microneedles 24 are dipped in the drug solution 28, or a polymer sheet 22 in which a portion other than the microneedles 24 is covered with a mask is used as the drug. The method of immersing in the liquid 28 is mentioned. In the former method, only the tip of the microneedle 24 may be immersed in the drug solution 28, or the entire microneedle 24 may be immersed in the drug solution 28.

  The range (drug addition amount) of the drug permeation region 24 a inside the microneedle 24 can be adjusted by the immersion time in the drug solution 28, the temperature of the drug solution 28, and the drug concentration in the drug solution 28.

  The drug solution 28 is a solution in which a drug is dispersed or dissolved in a solvent. 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, cosmetics, etc.

  The solvent in the drug solution 28 is preferably a solvent that easily swells the polymer sheet 22 from the viewpoint of rapidly penetrating the drug into the microneedles 24. For example, water, alcohol, or a mixture thereof is used. it can.

  The drug solution 28 may contain various additives in addition to the drug and the solvent. For example, an adjuvant may be added to the drug solution 28 together with the drug from the viewpoint of more efficiently absorbing the drug in the patient.

  Thereafter, as shown in FIG. 1 (f), the polymer sheet 22 is pulled up from the drug solution 28 and dried to obtain the transdermal absorption sheet 30 in which the drug is added to the drug permeation region 24 a of the microneedle 24. In this way, by drying the polymer sheet 22 after adding the drug, the microneedles 24 deformed by swelling can be returned to the high aspect ratio shape before swelling.

  Next, the structure of the transdermal absorption sheet 30 manufactured by the manufacturing method demonstrated above is demonstrated.

  FIG. 2 is a cross-sectional view showing a structural example of a transdermal absorption sheet produced by the method according to the present embodiment.

  As shown in the figure, the percutaneous absorption sheet 30 has a configuration in which a microneedle 24 is formed on a sheet portion 26, and a drug is added to a drug permeation region 24 a inside the microneedle 24. In the percutaneous absorption sheet 30 having such a configuration, the microneedle 24 inserted into the patient body dissolves when the skin is affixed to the patient's skin, and the drug added to the drug penetration region 24a is released into the patient body. .

  The drug permeation region 24a may be formed only at the tip of the microneedle 24, or may be formed throughout the microneedle 24 as illustrated in FIG.

  The film thickness t of the sheet portion 26 is preferably 200 μm or less, more preferably 100 μm or less, from the viewpoint of forming a flexible transdermal absorption sheet 30 that can be flexibly deformed according to the shape of the patient's skin. .

  The shape of the microneedle 24 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”), or these. It may be a shape according to. FIG. 2 illustrates a cone-shaped microneedle 24 having a cone-shaped tip and a columnar root.

  The microneedle 24 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 microneedle 24 is preferably 50 to 300 μm, and the curvature radius of the tip of the microneedle 24 is preferably 10 μm or less. The height of the microneedle 24 is preferably 200 to 2000 μm. Further, the aspect ratio of the microneedle 24 is preferably 1 or more, and more preferably 2 or more. Here, the height of the microneedle 24 means the projection length H from the surface of the sheet portion 26, and the aspect ratio A of the microneedle 24 is the height (projection length) H and width (diameter) of the microneedle 24. ) D is defined by A = H / D.

  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.

  For example, in the above-described embodiment, an example in which the percutaneous absorption sheet 30 is produced by solidifying the polymer solution 20 containing gelatin as a solid component has been described. However, gelatin and saccharides are used as the solid component of the polymer solution 20. May be.

  When the polymer solution 20 contains gelatin and saccharide as solid components, the polymer sheet 22 obtained by solidifying the polymer solution 20 has a structure in which a gelatin component and a saccharide component are mixed. When the microneedle 24 is immersed in the drug solution 28, the saccharide component in the microneedle 24 is eluted into the drug solution, so that a large number of micropores are formed in the microneedle 24 and the drug solution is contained in the numerous micropores. A diffusion phenomenon in which 28 penetrates occurs. Thus, the polymer solution 20 can use gelatin and saccharides as solid components to accelerate the drug penetration into the microneedles 24.

  As the saccharide in the polymer solution 20, monosaccharides such as glucose, fructose and galactose, disaccharides such as maltose, sucrose and trehalose, and polysaccharides such as pullulan can be used. Among them, saccharides having high solubility in a solvent are preferable in that the drying and solidifying time of the polymer solution 20 can be shortened by reducing the amount of the solvent in the polymer solution 20.

  When a polysaccharide is used as the saccharide in the polymer solution 20, a polysaccharide having an average molecular weight of 1,000 to 1,000,000 having a high solubility in the drug solution 28 is used from the viewpoint of reliably accelerating drug penetration into the microneedle 24. It is preferable to do.

  The content ratio (weight basis) of gelatin and saccharide in the polymer solution 20 is preferably 15: 1 to 3: 1 from the viewpoint of achieving both sheet formability and accelerated drug penetration. 4: 1 is more preferable, and 8: 1 to 5: 1 is still more preferable.

  Moreover, although the above-mentioned embodiment demonstrated the example which manufactures a percutaneous absorption sheet using the single mold 10, you may manufacture a percutaneous absorption sheet using the large area mold containing a some mold unit. . FIG. 3 is a diagram showing a large area mold including a plurality of mold units.

  The large-area mold 100 shown in FIG. 3 has a configuration in which a plurality of mold units 110 having needle-like recesses 112 are fixed on a substrate 116 via an adhesive layer 114. If a percutaneous absorption sheet is manufactured using the large-area mold 100, the production efficiency is greatly improved.

  Further, in the above-described embodiment, the example in which the polymer solution 20 is dried and solidified after the polymer solution 20 is applied to the mold 10 has been described. However, the polymer solution 20 is dissolved before the polymer solution 20 is dried and solidified. You may accelerate | stimulate filling to the needle-shaped recessed part 12 of the liquid 20. FIG. As a method of accelerating the filling of the polymer solution 20 into the needle-shaped recess 12, a method of pressurizing the polymer solution 20 after casting the polymer solution 20 into the mold 10, or a method of pressing the polymer solution 20 under reduced pressure in the mold 10. The method of returning to atmospheric pressure after casting is mentioned.

  FIG. 4 is a view showing a pressure filling device that promotes filling of the polymer solution into the needle-like concave portion.

  A pressure filling device 50 shown in FIG. 4 includes a pressure vessel 52 provided with an inlet 58 and a discharge port 60, a pedestal 54 provided inside the pressure vessel 52, and a compressor 56 that feeds pressurized fluid into the pressure vessel 52. including. Below, operation | movement of the pressurization filling apparatus 50 is demonstrated.

  In a state where the mold 10 into which the polymer solution 20 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 dissolution of the pressurized fluid in the polymer solution 20, a gas having a low dissolution rate in the polymer solution 20 should be selected. Is preferred.

  From the viewpoint of preventing an increase in viscosity due to volatilization of the polymer solution 20, a liquid of the same type as the solvent of the polymer solution 20 is stored in the pressure vessel 52 in advance, and the inside of the pressure vessel 52 is saturated with the vapor of the liquid. It is preferable to be in a state.

  As described above, by facilitating the filling of the polymer solution 20 into the needle-shaped recess 12, it becomes possible to quickly fill the entire area of the needle-shaped recess 12 including the deepest portion 14 with the polymer solution 20. . This makes it possible to reliably form the microneedle 24 having a sharp tip.

  By the method according to the above-described embodiment, a percutaneous absorption sheet was prepared as described below, and the selectivity of adding a drug to the needle-like convex portion was evaluated. In this example, in order to evaluate the selectivity of drug addition by a simple method, an evaluation experiment was conducted with a dye as a drug.

<Mold production>
First, a 100 μm tip portion of a cylindrical metal wire having a diameter of 200 μm was cut into a conical shape having a tip curvature radius of 5 μm. Then, a hole is made in the center of a smooth 40 mm × 40 mm copper plate, and 10 × 10 wires are arranged at a pitch of 500 μm so that the tip of the metal wire subjected to tip processing protrudes by 600 μm from the hole. An original plate was prepared by fixing. Using this original plate, a transfer product of silicone rubber (manufactured by Shin-Etsu Chemical Co., Ltd., RTV rubber for Shin-Etsu silicone mold making) was produced, and a mold having a thickness of 5 mm and a size of 45 mm × 45 mm was obtained. 10 × 10 conical columnar recesses were formed in the center of the mold.

<Preparation of polymer solution>
Gelatin (Nitta Gelatin Co., Ltd., Nitta Gelatin 732) was dissolved in warm water at 40 ° C. to prepare an aqueous solution having a gelatin concentration of 20% by weight, and this was kept warm at 40 ° C.

<Polymer solution casting>
An opening of 30 mm × 30 mm was provided in the central portion of a silicone sheet having a size of 40 mm × 40 mm and a thickness of 3 mm (manufactured by Shin-Etsu Finetech Co., Ltd., Shinetsu Silicon Sheet BA grade). The silicone sheet was laminated and adhered to the mold in a state where the conical columnar hole pattern portion of the mold was positioned so as to be exposed from the opening of the silicone sheet. Then, 1 ml of polymer solution was dripped at the mold (silicone sheet opening) to which the silicone sheet was adhered using a dispenser.

<Pressure filling of polymer solution>
In order to prevent volatilization of water which is a solvent of the polymer solution, hot water was stored up to a height of 40 mm at the bottom of the pressure vessel. After heating the inside of a pressure vessel to 40 degreeC with the heating jacket, compressed air was inject | poured in the pressure vessel from the compressor. Thereby, the pressure in the pressure vessel was held at 0.5 MPa for 5 minutes.

<Solidification process>
The mold was taken out from the pressure vessel, put into an oven, and dried at 50 ° C. for 1 hour. The polymer solution was solidified by the drying treatment, and a polymer sheet having a conical columnar needle was obtained.

<Peeling process>
After removing the silicone sheet laminated and adhered to the mold, an adhesive tape was attached to the back surface of the polymer sheet, and the adhesive tape was peeled off from the mold to obtain a needle-shaped array sheet.

<Immersion process in dye solution>
The needle part of the needle-shaped array sheet was immersed in the dye solution for 20 seconds. As the dye solution, a solution obtained by adding a dye to a liquid obtained by mixing water and alcohol at a ratio of 1: 1 was used.

<Drying process>
Thereafter, the needle-shaped array sheet was pulled up from the dye solution and dried at 50 ° C. for 30 minutes. Thereby, the needle-shaped array sheet | seat in which dye saturated only to the needle part was able to be produced.

  From this, it was found that according to the method according to the above-described embodiment, it is possible to produce a transdermal absorption sheet in which a drug is selectively added to the needle part.

It is a figure which shows the manufacturing method of the transdermal absorption sheet which concerns on one Embodiment of this invention. It is sectional drawing which shows the structural example of the transdermal absorption sheet manufactured by the method which concerns on this embodiment. It is a figure which shows the large area mold containing a some mold unit. It is a figure which shows the pressure filling apparatus which accelerates | stimulates filling to the needle-shaped recessed part of a polymer solution. It is a figure which shows a mode that a percutaneous absorption sheet is manufactured by the conventional cast molding method.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 10 ... Mold, 12 ... Needle-shaped recessed part, 14 ... Deepest part, 16 ... Flat surface, 20 ... Polymer solution, 22 ... Polymer sheet, 24 ... Microneedle, 26 ... Sheet part, 100 ... Large area mold, 110 ... Mold Unit: 112 ... Needle-shaped recess, 114 ... Adhesive layer, 116 ... Substrate, 50 ... Pressure filling device, 52 ... Pressure vessel, 54 ... Base, 56 ... Compressor, 58 ... Inlet, 60 ... Discharge port, 210 ... Mold, 212 ... acicular recess, 220 ... polymer solution, 224 ... microneedle, 226 ... sheet part, 230 ... transdermal absorption sheet

Claims (10)

An application step of applying a polymer solution containing a biodegradable polymer having a gelling property as a solid component to a mold having a needle-like recess,
A solidification step of solidifying the polymer solution so as to form a polymer sheet having a needle-like convex portion that is an inverted shape of the needle-like concave portion;
A peeling step of peeling the polymer sheet formed in the solidification step from the mold;
A drug infiltration step of immersing only the needle-like protrusions of the polymer sheet in a drug solution containing the drug so that the drug penetrates into the needle-like protrusions of the polymer sheet peeled in the peeling step; A method for producing a transdermal absorption sheet, comprising:   The method for producing a transdermal absorption sheet according to claim 1, wherein the biodegradable polymer is gelatin.   The method for producing a transdermal absorption sheet according to claim 2, wherein the polymer solution contains the gelatin and saccharide as solid components.   The method for producing a percutaneous absorption sheet according to any one of claims 1 to 3, further comprising a drying step of drying the polymer sheet in which the drug has penetrated into the needle-like convex portion.   The method for producing a transdermal absorption sheet according to any one of claims 1 to 4, further comprising a filling step of filling the needle-shaped concave portion with the polymer solution applied to the mold.   The said mold contains a silicone resin, The manufacturing method of the transdermal absorption sheet as described in any one of Claims 1-5 characterized by the above-mentioned.   The method for producing a transdermal absorption sheet according to any one of claims 1 to 6, wherein the drug solution contains at least one of alcohol and water.   The diameter of the said acicular recessed part is 50 micrometers or more and 300 micrometers or less, The manufacturing method of the transdermal absorption sheet as described in any one of Claims 1-7 characterized by the above-mentioned.   The depth of the said needle-shaped recessed part is 200 micrometers or more and 2000 micrometers or less, The manufacturing method of the transdermal absorption sheet as described in any one of Claims 1-8 characterized by the above-mentioned.   The method for producing a percutaneous absorption sheet according to any one of claims 1 to 9, wherein the mold includes a plurality of mold units in which the needle-like recesses are formed.

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