JP2015043829A - Percutaneous absorption medicine sheet - Google Patents

Abstract

PROBLEM TO BE SOLVED: To allow sufficient and rapid infiltration of a medicine into a body through skin by only sticking a percutaneous absorption medicine sheet onto the skin.SOLUTION: A percutaneous absorption medicine sheet 10 includes: a microneedle-equipped base material 11 having a lot of microneedles 20; an adhesive cover film 15 provided on a face on the microneedle 20 side of the microneedle-equipped base material 11; and a medicine 17 interposed between the microneedle-equipped base material 11 and the cover film 15. The microneedles 20 of the microneedle-equipped base material 11 have an average diameter of a base part thereof of 100-1,000 μm, and have an average height of 100-1,000 μm. A hardness of the microneedle-equipped base material 11 is larger than a hardness of the cover film 15.

Description

  The present invention relates to a transdermally absorbable drug sheet mixed with a drug, and more particularly to a transdermally absorbable drug sheet capable of administering a drug into the body from the skin.

  In order to administer a drug from the skin into the body, a transdermal drug sheet mixed with the drug has been used.

  By sticking such a transdermal drug sheet on the skin, the drug in the transdermal drug sheet gradually penetrates into the body through the skin.

  The conventional percutaneously absorbable drug sheet allows the drug to penetrate from the skin into the body simply by sticking on the skin as described above, and its usage is simple.

  However, it takes time for the drug in the transdermal drug sheet to penetrate into the body through the skin, and the drug may not sufficiently penetrate into the body.

JP-A-10-218793

  The present invention has been made in consideration of the above points, and by simply attaching a transdermal drug sheet to the skin, the drug can penetrate into the body sufficiently and quickly through the skin. An object is to provide a skin-absorbing drug sheet.

  The present invention relates to a percutaneously absorbable drug sheet, a substrate with microneedles including a large number of microneedles provided on one surface, and a cover having adhesiveness provided on the surface on the microneedle side of the substrate with microneedles A film and a drug interposed between the substrate with microneedles and the cover film, and the microneedles of the substrate with microneedles have an average diameter of the base of 100 to 1000 μm, and an average height of 100 to 1000 μm, the average diameter of the tip is 2 to 50 μm, the substrate with microneedles is formed by micro-molding, and the hardness of the substrate with microneedles is greater than the hardness of the cover film It is a transdermal drug sheet.

  The present invention is a transdermal drug sheet characterized in that a release film is provided on the outside of a cover film so as to be peeled off.

  The present invention is the transdermal drug sheet, wherein the substrate with microneedles is molded by precision injection molding using an intermediate mold, melt extrusion fine transfer molding, or nanoimprint molding.

  The present invention is the transdermal drug sheet, wherein the intermediate mold is formed by thermal transfer molding or electroforming with respect to the master mold.

  In the present invention, a first uneven surface comprising a large number of protrusions and a large number of valleys is formed on the surface of the cover film on the substrate side with microneedles, and the valleys of the first uneven surface are positions corresponding to the microneedles. The protrusion of the 1st uneven surface is formed in the position corresponding to between microneedles, It is a transdermal drug sheet characterized by the above-mentioned.

  In the present invention, a second uneven surface comprising a large number of protrusions and a large number of valleys is formed on the surface of the cover film opposite to the substrate with microneedles, and the valleys of the second uneven surface correspond to the microneedles. The transdermal drug sheet is characterized in that the protrusion on the second irregular surface is formed at a position corresponding to between the microneedles.

  In the present invention, the substrate with microneedles is preferably made of a plastic resin. Examples of the plastic resin material include biodegradable polymers such as polylactic acid, polyglycolide, polylactic acid-co-polyglycolide, pullulan, capronolactone, polyurethane, and polyanhydride. Examples of the non-degradable polymer include polycarbonate, polymethacrylic acid, ethylene vinyl acetate, polytetrafluoroethylene, polyoxymethylene, cycloolefin polymer (COP), and cycloolefin copolymer (COC). Of these, biodegradable polymers are particularly preferred.

  The present invention is not particularly limited as long as the cover film is a polymer material film. For example, biodegradable polymers such as polylactic acid, polyglycolide, polylactic acid-co-polyglycolide, pullulan, capronolactone, polyurethane, and polyanhydride. Can be mentioned. Polycarbonate, polymethacrylic acid, ethylene vinyl acetate, polytetrafluoroethylene, polyoxymethylene, cycloolefin polymer (COP), cycloolefin copolymer (COC), and other water-soluble polymers, hyaluron, which are non-degradable polymers A film in which sodium oxide, sodium alginate, or the like is formed in a sheet shape is preferable. In particular, a biodegradable polymer or a water-soluble polymer is particularly preferable because the film portion is highly likely to come into contact with the body.

  As described above, according to the present invention, the drug penetrates into the body sufficiently and quickly through the skin just by attaching the transdermal drug sheet to the skin. Thus, the drug can be easily administered into the body.

FIG. 1 is a diagram showing a first embodiment of a transdermal drug sheet according to the present invention. FIG. 2 is a diagram showing the action of the transdermal drug sheet. Fig.3 (a) is a figure which shows the base material with a microneedle, Comprising: FIG.3 (b)-(d) is a figure which shows the shape of the microneedle provided in the base material with a microneedle. Fig.4 (a) is a figure which shows the base material with a microneedle, FIG.4 (b) is a figure which shows the shape of the microneedle provided in the base material with a microneedle. FIG. 5 is a view showing a second embodiment of the transdermal drug sheet according to the present invention. FIG. 6 is a view showing the action of the transdermal drug sheet. FIG. 7 is a diagram showing the action of the transdermal drug sheet. FIG. 8 is a view showing the action of the transdermal drug sheet. FIG. 9 is a diagram showing a third embodiment of a transdermal drug sheet. FIG. 10 is a diagram showing a substrate with microneedles. FIG. 11 is a layout view showing microneedles of a substrate with microneedles. FIG. 12 shows the structure of the skin. FIG. 13 is a diagram showing a procedure for producing a substrate with microneedles. FIG. 14 is a view showing a specific example of a transdermal drug sheet.

First Embodiment Hereinafter, a first embodiment of a transdermally absorbable drug sheet according to the present invention will be described with reference to the drawings.

  1 to 4 and FIGS. 12 to 13 are views showing a first embodiment of a transdermal drug sheet according to the present invention.

  First, the structure of the transdermally absorbable drug sheet will be described with reference to FIGS.

  As shown in FIG. 1 to FIG. 4, the transdermally absorbable drug sheet 10 has a drug 17 mixed inside, and the drug 17 mixed inside by being attached to the surface of the skin 1 enters the body through the skin 1. To penetrate.

  Such a transdermal drug sheet 10 includes a substrate 12, a substrate 11 with microneedles including a plurality of microneedles 20 provided on one surface of the substrate 12, and a substrate 11 with microneedles. The cover film 15 provided on the surface on the microneedle 20 side and having adhesiveness, and the medicine 17 interposed between the substrate 11 with microneedle and the cover film 15 are provided.

  In this case, the substrate 12 of the substrate 11 with microneedles and the numerous microneedles 20 are made of plastic resin and are integrally formed.

  Further, the microneedles 20 of the substrate 11 with microneedles are formed on the substrate 12 at equal intervals by a fine molding process, and each microneedle 20 has a very fine shape. For example, the microneedle 20 has an average diameter of the base portion of 100 to 1000 μm, an average height of 100 to 1000 μm, and an average diameter of the tip of 2 to 50 μm.

On the other hand, the cover film 15 is a film of a polymer material, and the hardness of the cover film 15 is smaller than the hardness of the substrate 11 with microneedles. For example, the hardness of the cover film 15 is Rockwell hardness of R100 or less. The hardness of the needle-equipped substrate 11 is greater than R100 in terms of Rockwell hardness. (Measurement method of hardness conforms to JIS K7202-2)
A release film 19 is provided on the outside of the cover film 15 having adhesiveness so as to be peelable from the cover film 15.

  Next, each component will be described below with reference to FIGS.

  As described above, the microneedles 20 of the substrate 11 with microneedles have a fine shape, and the outer shape thereof has a conical shape having a vertex 20a (FIGS. 3A and 3B). Alternatively, the microneedle 20 may have a square cone shape having an apex 20a (FIG. 3C). The microneedle 20 may have a triangular cone shape having a vertex 20a (FIG. 3D). In addition, it may have a polygonal shape.

  Alternatively, as shown in FIGS. 4A and 4B, the microneedles 20 of the substrate 11 with microneedles have a rectangular cone shape having apexes 20a and four side surfaces 21, and are recessed inwardly on each side surface 21. The groove portion 22 may be provided. In this case, the groove 22 functions as a guide path for the medicine 17 that travels through the microneedle 20.

  The substrate 11 with microneedles having such a configuration is manufactured by a procedure as shown in FIG. First, a master mold 11C is produced by precision cutting, and thermal transfer molding is performed using the master mold 11C, or an intermediate mold 11B is fabricated by electroforming.

  The substrate 11 with microneedles can be obtained by performing precision injection molding, melt extrusion fine transfer molding, or nanoimprint molding using the intermediate molding die 11B.

  Further, the surface of the cover film 15 on the side with the microneedle 11 is a first uneven surface 15A, and the surface of the cover film 15 on the side opposite to the microneedle 11 is a flat surface 15S. .

  In this case, the first uneven surface 15A of the cover film 15 has a large number of protrusions 15b and a large number of valleys 15a, and the valley portions 15a of the first uneven surface 15A are formed on the microneedles 20 of the substrate 11 with microneedles. It is formed in the corresponding position.

  A portion of the cover film 15 corresponding to the valley portion 15b is a thin film 15e, and can be easily pierced by the microneedle 20 as described later.

  For the cover film 15, as in the case of the substrate with microneedles 11, a master mold is manufactured by precision cutting, and thermal transfer molding is performed using this master mold, or an intermediate mold is fabricated by electroforming. The intermediate mold can be used for precision injection molding, melt extrusion fine transfer molding, or nanoimprint molding.

  In addition, without using an intermediate mold, a mold is directly manufactured by precision cutting, and the cover film 15 is molded by performing precision injection molding, melt extrusion fine transfer molding, or nanoimprint molding using the mold. Also good.

  When the cover film 15 is made of a silicon-based soft molded product, the cover film 15 is preferably molded by a liquid resin injection molding method (LIM molding method).

  Next, a method for encapsulating the drug 17 between the base 11 with microneedles and the cover film 15 will be described.

  First, the substrate 11 with microneedles and the cover film 15 formed as described above are prepared. Next, the chemical | medical agent 17 is apply | coated to the surface at the side of the microneedle 20 of the base material 11 with microneedle, and the cover film 15 is laminated | stacked on the surface at the side of the microneedle 20 of the base material 11 with microneedle. Next, the outer periphery of the substrate 11 with microneedles and the cover film 15 is bonded or welded, and the drug 17 is sealed between the substrate 11 with microneedles and the cover film 15. Next, the release film 19 is laminated on the cover film 15, and thus the percutaneous absorption drug sheet 10 is obtained.

  In addition, before laminating | stacking the base material 11 with a microneedle and the cover film 15, it is a chemical | medical agent beforehand to the surface at the side of the microneedle 20 of the base material 11 with a microneedle, and the surface at the side of the base material 11 with a microneedle of the cover film 15. 17 may be applied.

  Next, the effect | action of this embodiment which consists of such a structure is demonstrated.

  First, the release sheet 19 of the transdermal drug sheet 10 is peeled from the cover film 15 side to expose the cover film 15 outward (see FIG. 1).

  Next, the percutaneously absorbable drug sheet 10 is attached to the skin 1 from the cover film 15 side, and the percutaneously absorbable drug sheet 10 is pressed against the skin 1 from the substrate 11 side with a microneedle. There is no problem even if the pressing to the skin at this time is performed manually, but a dedicated jig whose pressing energy is, for example, about 0.1 J to 5 J may be used.

  The skin 1 generally comprises an epidermis layer 1a and a dermis layer 1b as shown in FIGS. Then, by pressing against the skin 1 from the side of the transdermal drug sheet 10 and the substrate 11 with microneedles, the microneedles 20 of the substrate 11 with microneedles break through the thin film 15e of the cover film, and further the epidermis of the skin 1 It penetrates the layer 1b and reaches the dermis layer 1b.

  As a result, the cover film 15 is deformed, and the drug 17 interposed between the substrate 11 with microneedles and the cover film 15 travels along the outer surface of the microneedles 20 and penetrates into the epidermis layer 1a and the dermis layer 1b. Thereafter, the drug 17 penetrates from the dermis layer 1b into the subcutaneous tissue 2 (see FIG. 12) and is administered into the body.

  In order for the microneedles 20 of the substrate 11 with microneedles to penetrate the cover film 15 and the skin layer 1a and reach the dermis layer 1b, the average height of the microneedles 20 depends on the thickness of the cover film 15 and the skin. The thickness is preferably equal to or greater than the thickness of the layer 1a.

In addition, the microneedles 20 of the substrate 11 with microneedles are arranged on the substrate 12 at regular intervals when viewed from above, and are arranged in a lattice shape or an equilateral triangle shape, and the density of the microneedles 20 is 10 to 200. Per piece / cm ² .

  As described above, according to the present embodiment, the release film 19 is peeled from the transdermally absorbable drug sheet 10, the cover film 15 side of the absorbable drug sheet 10 is attached to the skin 1, and the absorbable drug sheet 10 is attached to the skin 1 side. The drug 17 in the absorbent drug sheet 10 can be easily and reliably infiltrated into the subcutaneous tissue 2 side through the epidermis layer 1a and the dermis layer 1b.

  Furthermore, since the microneedles 20 of the substrate 11 with microneedles are fine and many are provided, the drug 17 can be efficiently administered into the body without pain to the human body.

  Further, since the drug 17 in the transdermally absorbable drug sheet 10 is provided in a sealed state between the substrate 11 with microneedles and the cover film 15, the drug 17 even if it is a liquid drug 17 having low fluidity. Does not leak outward from the transdermal drug sheet 10. If it is about 10-500 cp as a preferable viscosity, possibility that sufficient transfer | transfer will be made also in a body, preventing a leak will become high.

Second Embodiment Next, a second embodiment of the transdermal drug sheet according to the present invention will be described with reference to the drawings.

  5 to 8 are views showing a second embodiment of the transdermal drug sheet according to the present invention.

  The structure of the transdermally absorbable drug sheet will be described with reference to FIGS.

  The transdermal drug sheet 10 includes a substrate 12, a substrate 11 with microneedles that includes a number of microneedles 20 provided on one surface of the substrate 12, and microneedles 20 of the substrate 11 with microneedles. The cover film 15 is provided on the side surface and has adhesiveness, and the drug 17 interposed between the substrate 11 with microneedles and the cover film 15 is provided.

  In this case, the substrate 12 of the substrate 11 with microneedles and the numerous microneedles 20 are made of plastic resin and are integrally formed.

  Further, the microneedles 20 of the substrate 11 with microneedles are formed on the substrate 12 at equal intervals by a fine molding process, and each microneedle 20 has a very fine shape. For example, the microneedle 20 has an average base diameter of 100 to 1000 μm and an average height of 100 to 1000 μm. The average diameter of the tip is 2 to 50 μm.

On the other hand, the cover film 15 is a polymer material film, the hardness of the cover film 15 is R100 or less in terms of Rockwell hardness, and the hardness of the substrate 11 with microneedles is greater than R100 in terms of Rockwell hardness. . (Measurement method of hardness conforms to JIS K7202-2)
A release film 19 is provided on the outside of the cover film 15 having adhesiveness so as to be peelable from the cover film 15.

  Next, each component will be described below.

  As described above, the microneedles 20 of the substrate 11 with microneedles have a fine shape, and the outer shape thereof has a rectangular cone shape having apexes 20 a and four side surfaces 21. Moreover, the groove part 22 dented inwardly in each side surface 21 is formed (refer FIG. 4). In this case, the groove 22 functions as a guide path for the medicine 17 that travels through the microneedle 20.

  In addition, the surface of the cover film 15 on the side of the substrate 11 with microneedles is a first uneven surface 15A, and the surface of the cover film 15 opposite to the substrate 11 with microneedles is a second uneven surface 15B. ing.

  In this case, the first uneven surface 15A of the cover film 15 has a number of protrusions 15b and a number of valleys 15a, and the second uneven surface 15B has a number of protrusions corresponding to the protrusions 15b of the first uneven surface 15A. 15 d and many valley parts 15 c corresponding to the valley parts 15 a of the first uneven surface 15 </ b> A. The valley 15a of the first uneven surface 15A and the valley 15c of the second uneven surface 15b are formed at positions corresponding to the microneedles 20 of the substrate 11 with microneedles.

  Further, portions of the cover film 15 corresponding to the valleys 15 a and 15 c are thin films 15 e that can be easily pierced by the microneedles 20.

  Next, the effect | action of this embodiment which consists of such a structure is demonstrated.

  First, the release sheet 19 of the transdermally absorbable drug sheet 10 is peeled from the cover film 15 side to expose the cover film 15 outward (see FIG. 5).

  Next, the percutaneously absorbable drug sheet 10 is attached to the skin 1 from the cover film 15 side, and the percutaneously absorbable drug sheet 10 is pressed against the skin 1 from the substrate 11 side with microneedles (see FIG. 6). There is no problem even if the pressing to the skin at this time is performed manually, but a dedicated jig whose pressing energy is, for example, about 0.1 J to 5 J may be used.

  Thus, by pressing against the skin 1 from the side of the transdermally absorbable drug sheet 10 and the substrate 11 with microneedles, the microneedles 20 of the substrate 11 with microneedles break through the thin film 15e of the cover film.

  At this time, the cover film 15 is deformed, and the drug 17 provided between the substrate 11 with microneedles and the cover film 15 is pushed out of the cover film 15 through the microneedles 20.

  Further, the cover film 15 is deformed by pressing the percutaneously absorbable drug sheet 10 against the skin 1, the microneedle 20 is pierced into the epidermis layer 1 a, and the drug 15 travels through the microneedle 20 to the epidermis layer 1 a. Reach (see FIG. 7).

  Furthermore, by pressing the transdermal drug sheet 10 against the skin 1, the microneedles 20 penetrate the epidermis layer 1a and reach the dermis layer 1b. Thereby, the medicine 15 passes through the microneedle 20 and penetrates to the dermis layer 1b (see FIG. 8).

  In this way, the cover film 15 is deformed, and the medicine 17 interposed between the substrate 11 with microneedles and the cover film 15 penetrates the outer surface of the microneedles 20 and penetrates into the epidermis layer 1a and the dermis layer 1b. . Thereafter, the drug 17 penetrates from the dermis layer 1b into the subcutaneous tissue 2 (see FIG. 12) and is administered into the body.

  In order for the microneedles 20 of the substrate 11 with microneedles to penetrate the cover film 15 and the skin layer 1a and reach the dermis layer 1b, the average height of the microneedles 20 depends on the thickness of the cover film 15 and the skin. The thickness is preferably equal to or greater than the thickness of the layer 1a.

In addition, the microneedles 20 of the substrate 11 with microneedles are arranged on the substrate 12 at regular intervals when viewed from above, and are arranged in a lattice shape or an equilateral triangle shape, and the density of the microneedles 20 is 10 to 200. Per piece / cm ² .

  As described above, according to the present embodiment, the release film 19 is peeled from the transdermally absorbable drug sheet 10, the cover film 15 side of the absorbable drug sheet 10 is attached to the skin 1, and the absorbable drug sheet 10 is attached to the skin 1 side. The drug 17 in the absorbent drug sheet 10 can be easily and reliably infiltrated into the subcutaneous tissue 2 side through the epidermis layer 1a and the dermis layer 1b.

  Furthermore, since the microneedles 20 of the substrate 11 with microneedles are fine and many are provided, the drug 17 can be efficiently administered into the body without pain to the human body.

Third Embodiment Next, a third embodiment of the percutaneously absorbable drug sheet according to the present invention will be described with reference to the drawings.

  First, FIG. 9 thru | or 11 is a figure which shows 3rd Embodiment of the transdermal drug substance sheet | seat by this invention.

  The structure of the transdermal drug sheet will be described with reference to FIGS.

  The transdermal drug sheet 10 includes a substrate 12, a substrate 11 with microneedles that includes a number of microneedles 20 provided on one surface of the substrate 12, and microneedles 20 of the substrate 11 with microneedles. The cover film 15 is provided on the side surface and has adhesiveness, and the drug 17 interposed between the substrate 11 with microneedles and the cover film 15 is provided.

  In this case, the substrate 12 of the substrate 11 with microneedles and the numerous microneedles 20 are made of plastic resin and are integrally formed.

  Further, the microneedles 20 of the substrate 11 with microneedles are formed on the substrate 12 at equal intervals by a fine molding process, and each microneedle 20 has a very fine shape. For example, the microneedle 20 has an average diameter of the base portion of 10 to 1000 μm and an average height of 10 to 1000 μm. The average diameter of the tip is 2 to 50 μm.

  On the other hand, the cover film 15 is a film of a polymer material, and the hardness of the cover film 15 is smaller than the hardness of the substrate 11 with microneedles. For example, the hardness of the cover film 15 is Rockwell hardness of R100 or less. The hardness of the needle-equipped substrate 11 is greater than R100 in terms of Rockwell hardness.

  A release film 19 is provided on the outside of the cover film 15 having adhesiveness so as to be peelable from the cover film 15.

  Next, each component will be described below with reference to FIGS.

  As shown in FIGS. 9 to 11, the substrate 11 with microneedles includes the substrate 12 and a number of microneedles 20 provided on the substrate 12 as described above.

  Each microneedle 20 includes a conical tip portion 23 having an apex 20 a and a cylindrical base end portion 24 located on the base end side of the tip portion 23. On the outer surface of the cylindrical base end portion 24, a groove portion 24a extending in the longitudinal direction and recessed inward is formed. The groove portion 24a is formed from the epidermis layer 1a to the dermis layer 1b along the outer surface of the microneedle 20 by the drug 17. It functions as a guideway for reaching.

  The microneedles 20 are arranged in a plane triangle shape (see FIG. 11). The base 12 between the microneedles 20 is formed with a curved surface 25 that is drawn inward.

  In addition, the surface of the cover film 15 on the side of the substrate 11 with microneedles is a first uneven surface 15A, and the surface of the cover film 15 opposite to the substrate 11 with microneedles is a second uneven surface 15B. ing.

  In this case, the first uneven surface 15A of the cover film 15 has a number of protrusions 15b and a number of valleys 15a, and the second uneven surface 15B has a number of protrusions corresponding to the protrusions 15b of the first uneven surface 15A. 15 d and many valley parts 15 c corresponding to the valley parts 15 a of the first uneven surface 15 </ b> A. Further, the valley portion 15a of the first uneven surface 15A and the valley portion 15c of the second uneven surface 15B are formed at positions corresponding to the microneedles 20 of the substrate 11 with microneedles.

  Further, portions of the cover film 15 corresponding to the valleys 15 a and 15 c are thin films 15 e that can be easily pierced by the microneedles 20.

  As described above, according to the present embodiment, the microneedle 20 of the substrate 11 with microneedles includes the conical tip portion 23 and the cylindrical base end portion 24 connected to the tip portion 23. After the thin film 15e of the cover film 15 is first pierced by the distal end portion 23, the thin film 15e can be smoothly penetrated by the cylindrical base end portion 24.

  Further, since the curved surface 25 is formed on the surface of the base material 12 between the microneedles 20, the curved surface 25 can be extruded to the skin layer 1a and dermis layer 1b side by the cover film 15 without leaving the medicine 17. it can.

  Next, specific examples of the present invention will be described. This example corresponds to the first embodiment shown in FIGS.

1. How to make a substrate with microneedles (Preparation of microneedle plate)
Master plate of 100 microneedles with a base of 0.25mm x 0.25mm, height of 0.5mm, and 10 protrusions arranged vertically and horizontally at 1mm pitch by cutting into metal Got.

  Next, in order to duplicate the microprotrusions of the microneedle of the prepared microneedle master plate, electroforming was performed using nickel to make a replica master (microneedle preparation plate) from the master plate, and the master A plate for producing microneedles having an intaglio plate opposite in shape was obtained.

(Replication of resin microneedle)
As a microneedle molding material, a 2 mm thick sheet of ZEONOR (manufactured by ZEON Corporation, model number Zeonor 1060R), which is a cycloolefin polymer, is a cyclic olefin resin. Incidentally, the glass transition temperature of the used cycloolefin polymer 1060R: 100 ° C., MFR: 280 ° C., 21.18 N, 60 g / min.

  The zeonore sheet, which is the cycloolefin polymer, is heated to 120 ° C. that is equal to or higher than the glass transition temperature (100 ° C.), and the zeonore sheet is heated at 120 ° C. that is equal to or higher than the glass transition temperature, The microneedle preparation plate was cooled while being pressed and pressed, and after the temperature was sufficiently lowered to near room temperature, hot pressing (thermal imprinting) was performed to peel in the cone length direction. Thereby, the base material 11 with a microneedle which has the resin-made microneedles 20 and the base material 12 which have the same shape as the master shape mentioned above was obtained.

2. How to make drug As model drug 17, polyvinylpyrrolidone (manufactured by Nippon Shokubai Co., Ltd .: PVP K-90 0.06 g) and caffeine (manufactured by Wako Pure Chemical Industries, Ltd.) 0.02 g dissolved in 1 g of purified water were used. .

3. How to make the whole A few ml of the model drug 17A is dropped on the substrate 11 with microneedles, covered with a gelatin film (cover film) 15 having a thickness of about 5 μm, and the gelatin film 15 on the outer periphery of the microneedle 20 is covered with an adhesive 10A. A transdermal drug sheet 10 as shown in FIG. 14 was prepared.

4). Experiment / Evaluation Confirm that the microneedle 20 is pierced into the PDMS by breaking the gelatin film (cover film) 15 by pressing the percutaneously absorbable drug sheet 10 as the above sample on PDMS (polydimethylsiloxane) created as model skin. At the same time, it was confirmed that the drug 17 permeates into the PDMS through the portion perforated by the microneedle 20.

DESCRIPTION OF SYMBOLS 1 Skin 1a Skin layer 1b Dermal layer 10 Percutaneous absorption chemical | medical agent sheet | seat 11 Base material 12 with a microneedle Base material 15 Cover film 15A 1st uneven surface 15B 2nd uneven surface 15S Flat surface 17 Drug 19 Release film 20 Microneedle

Claims (8)

In transdermal drug sheets,
A substrate with a microneedle comprising a number of microneedles provided on one surface;
A cover film having adhesiveness provided on the microneedle side surface of the substrate with microneedles,
A drug interposed between the substrate with microneedles and the cover film,
The microneedle of the substrate with microneedles has an average diameter of the base of 100 to 1000 μm, an average height of 100 to 1000 μm, and the substrate with microneedles is molded by a fine molding process,
A percutaneously absorbable drug sheet characterized in that the hardness of the substrate with microneedles is greater than the hardness of the cover film.   2. The transdermal drug sheet according to claim 1, wherein a release film is provided on the outside of the cover film so as to be peelable.   The transdermal drug sheet according to claim 1, wherein the base with microneedles is molded by precision injection molding using an intermediate mold, melt extrusion fine transfer molding, or nanoimprint molding.   The transdermal drug sheet according to claim 3, wherein the intermediate mold is formed by thermal transfer molding or electroforming with respect to the master mold.   A first concavo-convex surface composed of a large number of protrusions and a large number of troughs is formed on the surface of the cover film on the substrate side with microneedles, and the troughs of the first concavo-convex surface are formed at positions corresponding to the microneedles, The transdermal drug sheet according to claim 1, wherein the protrusions on the first uneven surface are formed at positions corresponding to the microneedles.   A second concavo-convex surface comprising a large number of protrusions and a large number of valleys is formed on the surface of the cover film opposite to the substrate with microneedles, and the valleys of the second concavo-convex surface are formed at positions corresponding to the microneedles. 6. The transdermal drug sheet according to claim 5, wherein the protrusions on the second irregular surface are formed at positions corresponding to the microneedles.   The transdermal drug sheet according to any one of claims 1 to 6, wherein the substrate with microneedles is made of a plastic resin.   The percutaneously absorbable drug sheet according to any one of claims 1 to 7, wherein the cover film is a polymer material film.

Images