JP6880942B2 - Transdermal administration device - Google Patents

Description

The present invention relates to a transdermal administration device used for administration of a drug.

As a method of administering a drug such as a vaccine into the body, a method using a microneedle is known. The microneedle is provided with a protrusion having a needle shape pointed toward the tip on the surface of the substrate portion. The administration method using a microneedle is a method in which a hole is formed in the skin by piercing a protrusion into the skin, and the drug is administered by sending the drug into the skin through the hole. Since the length of the protrusion is a length that does not reach the nerve cells of the dermis layer in the skin, the administration method using a microneedle has a hole in the skin as compared with the method of administering a drug subcutaneously using an injection needle. Pain when is formed is suppressed.

In one method of administering a drug using a microneedle, a microneedle having a through hole formed through the substrate and the protrusion in the extending direction of the protrusion is used, and the liquid drug is intradermally discharged through the through hole. (See, for example, Patent Document 1). Such microneedles are used, for example, attached to a syringe barrel like an injection needle. When administering the drug, the pusher provided in the injection tube is pushed, so that the drug filled in the outer cylinder of the injection tube is pressed toward the protrusion, and as a result, the drug is projected through the through hole. It comes out from the tip of the part and enters the skin.

Japanese Unexamined Patent Publication No. 2015-70869

By the way, the skin may have wrinkles and slacks, and may have high elasticity. Therefore, it may be difficult to pierce the skin sufficiently to a depth corresponding to the length of the protrusion, or to maintain a constant posture of the protrusion pierced by the skin while the drug is being administered. .. Therefore, it has been proposed to administer a drug using a transdermal administration device provided with a microneedle and an annular support surrounding the microneedle.

When administering a drug using a transdermal administration device, the admin stretches the skin in the area surrounded by the support by pressing the skin with the support, piercing this area with a protrusion, and then the protrusion. Pressurize the drug toward.

Here, the drug released from the protrusion while the pressurization of the drug is continued spreads into the skin centering on the protrusion. However, since the support presses against the skin, it is difficult for the drug to spread outside the portion of the skin located below the support. As a result, the amount of drug that can be injected intradermally is constrained by the size of the area surrounded by the support.

It is possible to increase the injection amount of the drug by increasing the inner diameter of the support having an annular shape, but the increase in the inner diameter is such that the support pierces the skin at the center of the ring, that is, at the position where the protrusion is pierced. This leads to a decrease in the ability to stretch and an increase in the size of the transdermal administration device.
An object of the present invention is to provide a transdermal administration device capable of increasing the injection amount of a drug into the skin.

The transdermal administration device that solves the above-mentioned problems is a substrate portion having a substrate surface and a protrusion that protrudes from the substrate surface, and has a flow path that opens to the peripheral surface of the protrusion inside the protrusion. The administration unit having the protrusion and the support having a plurality of supports to be abutted against the object to be administered are provided, and the plurality of supports are mutually used when viewed from a direction facing the substrate surface. A gap is provided between the support portions adjacent to the base surface and a gap is provided between the base surface and the support portion to surround the base surface, and the administration portion and the support are separated from each other by the plurality of support portions. The protrusion is configured to be relatively displaceable with respect to the support along the extending direction of the protrusion from a position in the enclosed space to the outside of the space.

According to the above configuration, when the drug is administered, in the region below the support portion in the skin, that is, in the region pressed by the support portion, the drug spreads outward in the radial direction of the region surrounding the protrusion. However, in the region below the gap between the supports, the drug spreads beyond this region to the outside in the radial direction. Therefore, it is possible to increase the injection amount of the drug into the skin as compared with the case where a support having a closed ring and no gap on the ring is used.

In the above configuration, the circle having the smallest inner diameter is the outermost circle among the plurality of virtual circles in which all the support portions are located inside the circle when viewed from the direction facing the substrate surface. Of a plurality of circles that are virtual circles centered on the center of the substrate surface and whose support portions are not located inside the circle, the circle having the largest inner diameter is the innermost circle, and the outermost circle. The ratio of the total area of the area occupied by the end of each support portion in contact with the administration target to the area inside the circle and outside the innermost circle is 0.2 or more and 0.8 or less. There may be.

According to the above configuration, both the size of the support portion that presses the skin and the size of the gap between the support portions are appropriately secured. Therefore, it is possible to achieve both that the function of stretching the skin by the support is satisfactorily exhibited and that the amount of the drug that spreads from below the gap between the supports to the outside is suitably secured.
In the above configuration, the positions of the ends of the support portions in contact with the administration target may coincide with each other in the extending direction of the protrusions.

According to the above configuration, since the skin is easily pressed evenly by each support portion, the function of stretching the skin by the support is satisfactorily exhibited, and the position of the transdermal administration device with respect to the skin is likely to be stable.

In the above configuration, the plurality of support portions may include the support portion in which the position of the end portion of the support portion in contact with the administration target is different from that of the other support portion in the extending direction of the protrusion portion.

According to the above configuration, by adjusting the position of the end portion of the support portion, it is possible to adjust the timing of pressing the skin by each support portion and the magnitude of the pressing. Therefore, it is possible to adjust the shape of the marks left on the skin when the drug is administered.
In the above configuration, the support may be configured so that a plurality of support portions form a part of a single symbol when viewed from a direction facing the substrate surface.

According to the above configuration, after administration of the drug, the skin to be administered has a recess formed around the substrate surface and the portion where the support portion is located, a region surrounded by the support portion, and a support portion. A pattern composed of a convex portion formed around a region extending outward from the region where the gap between the portions was located remains. Therefore, it is possible to reduce the discomfort of the recipient due to the trace of administration, and thus the discomfort of the recipient with respect to the administration of the drug.

According to the present invention, the amount of the drug injected into the skin can be increased.

FIG. 5 is a cross-sectional view showing an outline of a cross-sectional structure of the transdermal administration device for one embodiment of the transdermal administration device. The plan view which shows the planar structure of the microneedle and the support about the transdermal administration device of one Embodiment. It is a figure which shows the procedure of administration of the drug using the transdermal administration device of one Embodiment, and is the figure which shows the state which the support is arranged on the skin. It is a figure which shows the procedure of administration of the drug using the transdermal administration device of one Embodiment, and is the figure which shows the state which the skin was stabbed in the protrusion. It is a figure which shows the procedure of administration of the drug using the transdermal administration device of one Embodiment, and is the figure which shows the state which the drug is injected into the skin. It is a figure which shows the procedure of administration of the drug using the transdermal administration device of one Embodiment, and is the figure which shows the state which the drug is injected into the skin. The figure which shows typically the surface of the skin after administration of a drug using the transdermal administration device of one embodiment. Top view showing the planar structure of microneedles and supports for other forms of transdermal administration devices. The figure which shows typically the surface of the skin after administration of a drug using another form of transdermal administration device. It is a figure which shows the procedure of administration of the drug using the transdermal administration device of another form, and is the figure which shows the state which the drug is injected into the skin. It is a figure which shows the procedure of administration of the drug using the transdermal administration device of another form, and is the figure which shows the state which the drug is injected into the skin. The perspective view which shows the perspective structure of the transdermal administration device of a modified example. The figure which shows the arrangement of the support part in the transdermal administration device of Example 1. FIG. The figure which shows the arrangement of the support part in the transdermal administration device of Example 2. FIG. The figure which shows the arrangement of the support part in the transdermal administration device of Example 3. FIG. (A) is a diagram showing a photograph of the surface of the skin after administration using the transdermal administration device of Example 1, and (b) is an arrangement of a convex region and a concave region in FIG. 16 (a). The figure which shows typically. (A) is a diagram showing a photograph of the surface of the skin after administration using the transdermal administration device of Example 2, and (b) is an arrangement of a convex region and a concave region in FIG. 17 (a). The figure which shows typically. (A) is a diagram showing a photograph of the surface of the skin after administration using the transdermal administration device of Example 3, and (b) is an arrangement of a convex region and a concave region in FIG. 18 (a). The figure which shows typically.

An embodiment of the transdermal administration device will be described with reference to FIGS. 1 to 7.
[Structure of transdermal administration device]
The configuration of the transdermal administration device will be described with reference to FIGS. 1 and 2.
As shown in FIG. 1, the transdermal administration device 10 includes a microneedle 20 which is an example of an administration unit, and a support 30 for supporting the skin to be administered.
The microneedle 20 includes a base portion 21 having a base surface 21S and a protrusion 22 protruding from the base surface 21S.

The base surface 21S supports the base end of the protrusion 22. The shape of the base surface 21S is not particularly limited, and the base surface 21S may have a circular shape or a polygonal shape. As shown in FIG. 1, the base portion 21 has a tubular shape extending in the direction opposite to the protrusion 22 with respect to the base surface 21S, and is based on one of the two tubular ends of the base portion 21 as an end surface. It has a body surface 21S and has a structure in which the other of the two cylinder ends is open. The base portion 21 may have a portion where the outer diameter gradually changes or a portion where the outer diameter changes stepwise between the two cylinder ends. The inner surface of the substrate portion 21 constitutes a flow path for supplying a liquid drug to the microneedle 20. Alternatively, the substrate portion 21 may have a flat plate shape and may be connected to a tubular member constituting the flow path.

The shape of the protrusion 22 is not particularly limited as long as it can pierce the skin. The protrusion 22 may have a conical shape or a pyramid shape, or may have a cylindrical shape or a polygonal column shape. Alternatively, the protrusion 22 may have a shape in which the bottom surface of the cone is connected to the upper surface of the pillar, a shape obtained by cutting a prism or a cylinder diagonally with respect to the extending direction, or a shape of the pillar. A solid in which the bottom surface of a cone is connected to the upper surface may be cut diagonally with respect to the extending direction thereof.

The protrusion 22 is formed with a through hole 22a that penetrates the protrusion 22 in the extending direction of the protrusion 22. Of both ends of the through hole 22a in the extending direction, one end opens to the peripheral surface of the protrusion 22, and the other end penetrates the base surface 21S. It communicates with the space in the flow path of the drug located on the side opposite to the side where the protrusion 22 is located with respect to the substrate surface 21S. The inner surface of the through hole 22a constitutes a flow path for the drug connected from this flow path.

The number of protrusions 22 included in the microneedle 20 may be one or a plurality. When the microneedle 20 includes one protrusion 22, the protrusion 22 is preferably located at the center of the substrate surface 21S. When the microneedle 20 includes a plurality of protrusions 22, the plurality of protrusions 22 are arranged on the substrate surface 21S, for example, in a grid pattern, a circular shape, or a concentric circle shape.

The length H of the protrusion 22 is the length from the base surface 21S to the tip of the protrusion 22 in the direction in which the protrusion 22 extends, that is, in the direction orthogonal to the base surface 21S. The length H of the protrusion 22 is preferably a length that penetrates the stratum corneum, which is the outermost layer of the skin, and does not reach the subcutaneous layer, and specifically, is preferably 200 μm or more and 2000 μm or less.

The width D of the protrusion 22 is the maximum length of the protrusion 22 in the direction parallel to the substrate surface 21S. For example, when the protrusion 22 has a conical shape, the diameter of the circle indicated by the bottom surface of the protrusion 22 partitioned within the base surface 21S is the width D of the protrusion 22, and the protrusion 22 has a quadrangular pyramid shape. When, the length of the diagonal line of the square indicated by the bottom surface of the protrusion 22 is the width D of the protrusion 22. The width D of the protrusion 22 is preferably 150 μm or more and 1000 μm or less.

The support 30 includes a plurality of support portions 31. Each support portion 31 extends in the same direction as the protrusion portion 22 extends, and the plurality of support portions 31 surround the microneedle 20 with a gap between the support portion 31 and the base surface 21S.

In the extending direction of the protrusion 22, the positions of the end portions of the support portion 31 on the distal end side are the same in the plurality of support portions 31. In other words, the tip surface, which is the surface that each support portion 31 has on the end portion on the tip end side of the protrusion 22, is located in one surface parallel to the base surface 21S. The configuration of the end portion of the support portion 31 on the side opposite to the tip surface is not particularly limited, and for example, a plurality of support portions 31 may be connected to one member at the end portion on the side opposite to the tip surface. Good.

The transdermal administration device 10 includes a drive unit 40 which is a mechanism for displacing the microneedle 20 with respect to the support portion 31 of the support 30 in the direction from the base end to the tip end of the protrusion 22. The drive unit 40 relatively displaces the protrusion 22 from a position in the space surrounded by the plurality of support parts 31 toward the outside of the space along the extending direction of the protrusion 22. For example, the microneedle 20 may be configured to be able to reciprocate with respect to the support 30 in a direction perpendicular to the substrate surface 21S. The drive unit 40 may realize such a displacement by a mechanical structure such as a spring included in the drive unit 40, or may realize such a displacement by an electric configuration driven by applying a voltage.

As shown in FIG. 2, when viewed from the direction facing the base surface 21S, the plurality of support portions 31 surround the base surface 21S with a gap between the support portions 31 and the base surface 21S, that is, the plurality of supports. The portion 31 surrounds the protrusion 22 with a gap between it and the protrusion 22. There is also a gap between the supporting portions 31 that are adjacent to each other. In other words, when viewed from the direction facing the base surface 21S, the plurality of support portions 31 are located on a virtual ring surrounding the base surface 21S and the protrusions 22. When the microneedle 20 includes a plurality of protrusions 22, the ring is a ring that surrounds all the protrusions 22. FIG. 2 shows an example in which the three support portions 31 are arranged on a ring surrounding the base surface 21S and the protrusions 22. Each of these support portions 31 has a band shape extending along the annulus when viewed from the direction facing the substrate surface 21S.

The separation distance Ls for each support portion 31 is the shortest distance between the support portion 31 and the base surface 21S when viewed from the direction facing the base surface 21S. The separation distance Ls may be different for each support portion 31, or may be the same in the plurality of support portions 31. The separation distance Ls is preferably 0.3 cm or more and 2.0 cm or less. The shortest distance between the support portion 31 and the protrusion 22 when viewed from the direction facing the substrate surface 21S is preferably 0.4 cm or more and 2.5 cm or less.

The adjacent distance Ln for each of the support portions 31 adjacent to each other is the shortest distance between the support portions 31 adjacent to each other along the ring surrounding the base surface 21S and the protrusion 22. The adjacent distance Ln may be different for each of the two supporting portions 31 adjacent to each other, or may be the same. That is, the size of the gap between the support portions 31 adjacent to each other does not have to be constant, and the support portions 31 may be arranged at equal intervals along the ring. The adjacent distance Ln is preferably 0.3 cm or more and 2.0 cm or less.

The maximum diameter Wm of the support 30 is the maximum length of the support 30 in the direction along the substrate surface 21S. That is, the maximum diameter Wm is the distance between the ends of the most distant support portions 31 among the plurality of support portions 31. The maximum diameter Wm is preferably 0.8 cm or more and 5.0 cm or less. Furthermore, the maximum diameter Wm is preferably 1.0 cm or more and 2.5 cm or less.

A plurality of virtual circles surrounding all the support portions 31 when viewed from the direction facing the substrate surface 21S, that is, the most of the plurality of virtual circles in which all the support portions 31 are located inside the circle. The circle with a small inner diameter is the outermost circle Co, which is a virtual circle centered on the center of the base surface 21S, and among a plurality of virtual circles in which none of the support portions 31 is located inside the circle. The circle with the largest inner diameter is the innermost circle Ci. The center of the base surface 21S is the center of gravity of the figure indicated by the outer shape of the base surface 21S. The outermost circle Co is in contact with at least one support portion 31, and the innermost circle Ci is also in contact with at least one support portion 31.

In the region inside the outermost circle Co and outside the innermost circle Ci, the ratio of the region occupied by the end portion in contact with the administration target for all the support portions 31 is the occupancy ratio Or, which is the occupancy ratio. Or is preferably 0.2 or more and 0.8 or less. In other words, the occupancy ratio Or is the ratio of the total area of the tip surfaces of each support portion 31 to the area obtained by subtracting the area of the innermost circle Ci from the area of the outermost circle Co.

[Manufacturing method of microneedles]
The material and manufacturing method of the transdermal administration device 10 will be described.
The material for forming the protrusion 22 is not particularly limited, and the protrusion 22 may be made of a metal material such as silicon, stainless steel, titanium, a cobalt-chromium alloy, or a magnesium alloy. Further, the protrusion 22 may be formed of a resin material such as a general-purpose plastic, a medical plastic, and a cosmetic plastic. Examples of the resin material include polyethylene, polypropylene, polystyrene, polyamide, polycarbonate, cyclic polyolefin, polylactic acid, polyglycolic acid, polycaprolactone, acrylic, urethane resin, aromatic polyetherketone, epoxy resin, and these resins. Examples include copolymer materials. The material of the base portion 21 is not particularly limited, and the base portion 21 may be formed from, for example, the material exemplified as the material of the protrusion 22 described above.

The microneedle 20 may be an integrally molded product in which the base portion 21 and the protrusion 22 are integrally formed, or the microneedle 20 is formed by joining the base portion 21 and the protrusion 22 after they are formed separately. It may be formed by a combination of a metal material and a resin material. When the base portion 21 and the protrusion 22 are formed separately, or when the microneedle 20 is formed by a combination of a metal material and a resin material, each of the separate parts constituting the microneedle 20 is required. A sealant, an adhesive, a gasket, an O-ring, or the like for bringing the portions in close contact with each other may be used in combination.

As a method for forming the microneedle 20, for example, a method of forming the through hole 22a after forming the outer shape of the base portion 21 and the protrusion 22 by machining is used. Alternatively, when the microneedle 20 is formed from a resin material, the microneedle 20 may be formed by using injection molding using a plurality of movable molds. Alternatively, the microneedles 20 may be formed by a combination of injection molding and machining. For example, after the outer shape of the base portion 21 and the protrusion 22 is formed by injection molding, the through hole 22a is formed by machining. Examples of the machining method used for forming the through hole 22a include laser machining.

The material for forming the support portion 31 constituting the support 30 is not particularly limited, and the support portion 31 is formed of, for example, a metal material or a resin material. Examples of the metal material include aluminum, stainless steel, and brass. On the other hand, as the resin material, polyethylene, polypropylene, polystyrene, polyamide, polycarbonate, cyclic polyolefin, polylactic acid, polyglycolic acid, polycaprolactone, acrylic, urethane resin, aromatic polyetherketone, epoxy resin, and these resins Copolymerized materials and the like are exemplified. The support portion 31 may be formed by machining, injection molding, or the like, depending on the material thereof.

[Action]
With reference to FIGS. 3 to 7, the method of using the transdermal administration device 10 of the present embodiment and its operation will be described.
Immediately before the transdermal administration device 10 is used for drug administration, the tip of the protrusion 22 is set to be located closer to the proximal end of the support 30 than the tip surface of the support 31 in the support 30. There is. That is, the protrusion 22 is located in the space surrounded by the plurality of support 31s. Further, the transdermal administration device 10 is filled with a liquid drug M.

As shown in FIG. 3, when the drug is administered, the support 30 is first pressed against the skin Sk to which the drug is administered. As a result, the tip surface of the support portion 31 comes into contact with the skin Sk, and the support portion 31 presses the skin Sk. When the support 30 is pressed against the skin Sk, the skin Sk in the region inside the portion pressed by the support 30 is stretched and supported at a predetermined position, and the skin Sk is stretched.

As shown in FIG. 4, the microneedle 20 is subsequently lowered. That is, the protrusion 22 is moved with respect to the support 30 in the direction from the base end to the tip of the protrusion 22. As a result, the protrusion 22 is pierced from the tip into the skin Sk in the region inside the portion pressed by the support 30. In the state of being stuck in the skin Sk, the protrusion 22 may be located in the space surrounded by the plurality of support portions 31, or may protrude out of this space.

As shown in FIG. 5, the drug M packed in the transdermal administration device 10 is subsequently pressurized. As a result, the drug M passes through the through hole 22a of the protrusion 22 and exits into the skin from the vicinity of the tip of the protrusion 22.

While the pressurization of the drug M is continued, the drug M is continuously released from the protrusion 22 and spreads into the skin. In the region where the drug M has spread, the liquid drug M accumulates in the skin, causing the skin Sk to swell and swell. At this time, in the region pressed from the support portion 31 in the skin Sk, that is, the pressing region Ps which is a region located below the support portion 31, the tissue is clogged by being pressed by the support portion 31. Therefore, the drug M is difficult to spread. Further, in the pressing region Ps, the swelling of the skin Sk is regulated by the pressing from the support portion 31. Therefore, in the region surrounding the protrusion 22 where the pressing region Ps is located at the tip of the protrusion 22 in the radial direction, the drug M spreads around the region inside the pressing region Ps in the radial direction. Further, the swelling of the skin Sk is suppressed even in the region pressed by the substrate surface 21S.

On the other hand, as shown in FIG. 6, in the region surrounding the protrusion 22, the region where the pressing region Ps does not exist at the tip in the radial direction, that is, the region below the gap between the support portions 31 is located. The drug M spreads outward in the radial direction according to the amount of the drug M released.
When the administration of the drug M is completed, the protrusion 22 is pulled out from the skin, and the pressure on the skin by the support 30 is released.
FIG. 7 is a diagram schematically showing the surface of the skin after the transdermal administration device 10 is removed after administration of the drug.

As shown in FIG. 7, when viewed from the direction facing the surface of the skin Sk, a convex region R1 that is raised by injecting the drug and a concave region R2 that is recessed by leaving a trace of pressure are observed. Will be done. The regions other than the convex region R1 and the concave region R2 are regions in which the flatness equivalent to that before administration of the drug is maintained.

In the region where the base surface 21S was pressed and the region where the tip surface of the support portion 31 was pressed, that is, the region which was the pressing region Ps, the swelling of the skin due to the injection of the drug was suppressed, and further. , The skin is dented by pressing, and the region centered on these regions becomes the concave region R2. That is, the concave region R2 is positioned so that the other concave regions R2 are lined up on the ring surrounding one concave region R2 located at the center.

In the region where the pressing region Ps is located ahead of the protrusion 22 in the radial direction, the region inside the concave region R2 formed in the portion of the pressing region Ps, that is, inside the ring. A convex region R1 is formed around the region. On the other hand, in the region where the region below the gap between the support portions 31 is located at the tip in the radial direction with the protrusion 22 as the center, in addition to the region inside the ring, from the gap of the surrounding concave region R2. The convex region R1 extends to the outside in the radial direction of the ring.

As described above, a pattern composed of the convex region R1 and the concave region R2 is formed on the skin after the administration of the drug. These patterns gradually disappear as the drug is absorbed and diffused into the body.

As described above, according to the transdermal administration device 10 of the present embodiment, when the drug is administered, the spread of the drug outward in the radial direction of the region surrounding the protrusion 22 is restricted in the region below the support portion 31. However, in the region below the gap between the support portions 31, the drug spreads beyond this region to the outside in the radial direction. Therefore, as compared with the case where a support having a closed ring and no gap on the ring is used, it is possible to increase the injection amount of the drug into the skin without expanding the ring of the support.

Therefore, even a drug that requires a large amount of administration, for example, a drug that requires administration of 200 μL or more, can be administered without a step such as concentration for reducing the dose. Therefore, the transdermal administration device 10 of the present embodiment is particularly suitable for administration of 200 μL or more of a drug, and smooth administration of such a drug is possible.

[Other forms of support]
In the above description, the embodiment in which the number of the support portions 31 is 3 is illustrated, but the number of the support portions 31 included in the support body 30 may be two or four or more. Further, in the above description, the embodiment in which the plurality of support portions 31 are located on the virtual ring surrounding the base surface 21S has been illustrated, but the virtual ring in which the plurality of support portions 31 are located is a rectangle or a virtual ring. It may be a ring made of other polygons, a ring made of an ellipse, or a ring having a shape composed of a combination of straight lines and curves not included in such a figure. Further, the shape of the support portion 31 as viewed from the direction facing the substrate surface 21S, that is, the shape of the tip surface of the support portion 31, does not have to be strip-shaped.

FIG. 8 shows an example in which the three support portions 31 have the shape and arrangement so as to form a part of a single pattern when viewed from the direction facing the substrate surface 21S. The three support portions 31 are configured to represent a part of the face, specifically, the eyebrows, eyes, and mouth. Further, the base surface 21S is also configured to represent a part of the face, specifically the nose, and the support portion 31 and the base surface 21S form a part of the pattern. In this case as well, the separation distance Ls, the adjacent distance Ln, the maximum diameter Wm, and the occupancy ratio Or are defined in the same manner as described above with reference to FIG.

FIG. 9 shows the skin after the transdermal administration device 10 has been removed after administration of the drug using the percutaneous administration device 10 having the support 30 having the support portion 31 having the shape and arrangement shown in FIG. It is a figure which shows typically the surface of.

As shown in FIG. 9, a concave region R2 is formed in a region centered on a region on which the base surface 21S and the support portion 31 are pressed. The convex region R1 is formed in a region surrounded by the support portions 31, and is formed so as to extend outward from a region located below the gap between the support portions 31. As a result, the convex region R1 and the concave region R2 form a facial pattern in which the concave region R2 is visible to the eyebrows, eyes, nose, and mouth, and the convex region R1 is visible to the cheeks and forehead.

As described above, if the plurality of support portions 31 and the base surface 21S are arranged at positions forming the recesses of the pattern formed by the unevenness when viewed from the direction facing the base surface 21S, the drug can be used. After administration, a pattern consisting of irregularities remains on the skin of the administration subject as a trace of administration. Therefore, it is possible to reduce the discomfort of the recipient due to the trace of administration, and thus the discomfort of the recipient with respect to the administration of the drug. The design includes figures, patterns, patterns, characters, symbols, numbers and the like.

Further, in the plurality of support portions 31, the position of the tip end side of the protrusion 22 in the support portion 31 in the extending direction of the protrusion 22, that is, the position of the end portion in contact with the administration target is the position of the other support portion 31. The support portion 31 different from the above may be included. In other words, the tip surfaces of all the support portions 31 do not have to be located in one surface parallel to the substrate surface 21S.

The lower the tip surface of the support portion 31, that is, the closer to the tip side in the extending direction of the protrusion 22, the more the force of pressing the skin by the support portion 31, that is, the force that regulates the swelling of the skin Sk. growing.

FIG. 10 shows an example in which the support 30 includes support portions 31 having different positions of the tip surfaces in the extending direction of the protrusions 22. For example, in the initial stage when the administration of the drug is started, the swelling of the skin Sk is still small because the injection amount of the drug is small. Therefore, in the region below the support portion 31a where the tip surface is located closest to the tip side, the agent is pressed by the support portion 31a to limit the spread of the drug to the outside in the radial direction of the region surrounding the protrusion 22. In the region below the support portion 31b whose tip surface is relatively located on the proximal end side, the pressure of the support portion 31b is weak, and the spread of the drug outward in the radial direction is not easily restricted.

As shown in FIG. 11, when the injection amount of the drug increases and the swelling of the skin Sk increases, the drug is pressed outward from the support portion 31b even in the region below the support portion 31b. Spread is limited. As a result, among the regions surrounding the protrusions 22, the region below the gap between the support portions 31 is located in the radial direction, the inner and outer regions of the region below the support portion 31a, and the lower portion of the support portion 31b. In these areas, the spread of the drug, the height of the unevenness formed on the skin after administration of the drug, and the like can be changed.

In this way, by adjusting the position of the end portion of the support portion 31, it is possible to adjust the timing of pressing the skin by each support portion 31 and the magnitude of the pressing. Therefore, it is possible to adjust the shape of the marks left on the skin when the drug is administered.

As described above, according to the present embodiment, the following effects can be obtained.
(1) A plurality of support portions 31 surround the base surface 21S and the protrusions 22 with a gap between the support portions 31 adjacent to each other and between the base surface 21S and the support portion 31. Therefore, when the drug is administered, in the region below the support portion 31 in the skin, the spread of the drug to the outside in the radial direction of the region surrounding the protrusion 22 is restricted, but the gap between the support portions 31 In the lower region, the agent extends beyond this region to the outside in the radial direction. Therefore, it is possible to increase the injection amount of the drug into the skin as compared with the case where a support having a closed ring and no gap on the ring is used.

(2) In the configuration in which the occupancy ratio Or is 0.2 or more and 0.8 or less, both the size of the support portion 31 that presses the skin and the size of the gap between the support portions 31 are appropriately secured. Therefore, it is possible to achieve both that the function of stretching the skin by the support 30 is satisfactorily exhibited and that the amount of the drug that spreads outward from the lower side of the gap between the support portions 31 is suitably secured.

(3) In a configuration in which the positions of the ends of the protrusions 22 on the tip end side of the support portions 31 coincide with each other in the extending direction of the protrusions 22, the skin is likely to be pressed evenly by the support portions 31. Therefore, the function of stretching the skin by the support 30 is satisfactorily exhibited, and the position of the transdermal administration device 10 with respect to the skin is likely to be stable.

(4) In a configuration in which a plurality of support portions 31 include a support portion 31 in which the position of the tip end side of the protrusion 22 on the support portion 31 is different from that of the other support portions 31 in the extending direction of the protrusion 22. By adjusting the position of the end portion of the support portion 31, it is possible to adjust the timing of pressing the skin by each support portion 31 and the magnitude of the pressing. Therefore, it is possible to adjust the shape of the marks left on the skin when the drug is administered.

(5) In the configuration in which the plurality of support portions 31 are arranged so as to form a part of a single symbol when viewed from the direction facing the substrate surface 21S, the skin to be administered is subjected to the administration of the drug. Remains a pattern composed of unevenness. Therefore, it is possible to reduce the discomfort of the recipient due to the trace of administration, and thus the discomfort of the recipient with respect to the administration of the drug.

[Modification example]
The above embodiment can be modified and implemented as follows.
The protrusion 22 may have a flow path inside the protrusion 22 that opens on the peripheral surface of the protrusion 22, and this flow path penetrates the protrusion 22 in the extending direction like the through hole 22a. You don't have to. As shown in FIG. 12, for example, the flow path extends in the extending direction of the protrusion 22, and of the ends thereof, the end on the base end side of the protrusion 22 penetrates the substrate surface 21S. A bent flow path composed of a main flow path 25 m in which the end portion on the tip end side of the protrusion 22 is closed, and a sub flow path 25s extending from the main flow path 25 m and opening on the peripheral surface of the protrusion 22. There may be. Further, as shown in FIG. 12, the protrusion 22 may have a plurality of subchannels 25s. According to such a configuration, the drug is released from the protrusion 22 in the direction in which the skin spreads, so that the drug easily spreads in the skin.

Further, the number of the sub-flow paths 25s and the number of gaps between the support portions 31 match, and the gaps between the support portions 31 are located with respect to the main flow path 25 m when viewed from the direction facing the base surface 21S. It is preferable that one auxiliary flow path 25s extends to each. According to such a configuration, the drug is discharged from the opening of the auxiliary flow path 25s toward the region located below the gap between the support portions 31 in the skin, that is, the region where the drug easily spreads. Therefore, the drug can be efficiently diffused into the skin.

In addition, in FIG. 12, the form in which the protrusion 22 has a shape in which the bottom surface of the quadrangular pyramid is connected to the upper surface of the quadrangular prism and is cut diagonally with respect to the extending direction is illustrated.

The transdermal administration device 10 may be provided with a drug and stored in a state of being filled with the drug, or may not be provided with the drug and the drug may be supplied to the transdermal administration device 10 immediately before administration. ..

-The target to which the drug is administered by the microneedle 20 is not limited to humans, but may be other animals. In addition, each of the above-described configuration of the embodiment and the configuration of the modified example can be implemented in an appropriate combination.

[Example]
The above-mentioned microneedles will be described with reference to specific examples.
<Example 1>
A structure in which polycarbonate is used as the material for the microneedles, and a quadrangular pyramid connected to the upper surface of a quadrangular prism having a square bottom is cut diagonally with respect to its extending direction, together with a tubular base portion by injection molding. Therefore, a structure having a through hole serving as a flow path for the drug was formed. As a result, the microneedles of Example 1 were obtained.

Polycarbonate was used as the material of the support portion, and two support portions having a shape corresponding to a part in the circumferential direction of the cylinder were formed by cutting. The transdermal administration device of Example 1 was obtained by arranging the two supports on an annulus surrounding the substrate surface of the microneedle and assembling the support and the microneedle.

FIG. 13 is a diagram showing the arrangement of the support portion in the transdermal administration device of Example 1. In the transdermal administration device of Example 1, the adjacent distance Ln is constant at 6 mm, and the maximum diameter Wm is 16 mm. Further, the substrate surface is circular, its diameter is 3 mm, the separation distance Ls is constant at 4 mm, and the occupancy ratio Or is 0.75. The length H of the protrusion is 750 μm.

<Example 2>
By the same steps as in Example 1, microneedles having the same shape as in Example 1 were obtained. Further, by the same process as in Example 1, three support portions having a shape corresponding to a part in the circumferential direction of the cylinder were formed. The transdermal administration device of Example 2 was obtained by arranging the three supports on an annulus surrounding the substrate surface of the microneedle and assembling the support and the microneedle.

FIG. 14 is a diagram showing the arrangement of the support portion in the transdermal administration device of Example 2. In the transdermal administration device of Example 2, the adjacent distance Ln is constant at 6 mm, and the maximum diameter Wm is 16 mm. Further, the substrate surface is circular, its diameter is 3 mm, the separation distance Ls is constant at 4 mm, and the occupancy ratio Or is 0.63.

<Example 3>
By the same steps as in Example 1, microneedles having the same shape as in Example 1 were obtained. Further, by the same process as in Example 1, four support portions having a shape corresponding to a part in the circumferential direction of the cylinder were formed. The transdermal administration device of Example 3 was obtained by arranging the four supports on an annulus surrounding the substrate surface of the microneedle and assembling the support and the microneedle.

FIG. 15 is a diagram showing the arrangement of the support portion in the transdermal administration device of Example 3. In the transdermal administration device of Example 3, the adjacent distance Ln is constant at 6 mm, and the maximum diameter Wm is 16 mm. Further, the substrate surface is circular, its diameter is 3 mm, the separation distance Ls is constant at 4 mm, and the occupancy ratio Or is 0.5.

<Administration test>
The drug administration test was performed using the transdermal administration devices of Examples 1 to 3. Each transdermal administration device was filled with pure water as a drug, a support was pressed against the skin removed from a 12-week-old Wistar rat, and a protrusion was pierced. Then, the drug was pressurized toward the protrusion, and 600 μL of the drug was injected. After administration of the drug, the transdermal administration device was removed from the skin and the surface of the skin was observed. FIG. 16A is a photograph of the surface of the skin after administration using the transdermal administration device of Example 1, and FIG. 16B is a convex region and a concave region in FIG. 16A. It is a figure which shows typically the arrangement with. FIG. 17 (a) is a photograph of the surface of the skin after administration using the transdermal administration device of Example 2, and FIG. 17 (b) shows a convex region and a concave region in FIG. 17 (a). It is a figure which shows typically the arrangement with. FIG. 18A is a photograph of the surface of the skin after administration using the transdermal administration device of Example 3, and FIG. 18B is a convex region and a concave region in FIG. 18A. It is a figure which shows typically the arrangement with.

As shown in FIGS. 16 to 18, in each of the embodiments, the convex region extends outward beyond the region below the gap between the support portions. Therefore, it is suggested that it is possible to increase the injection amount of the drug into the skin as compared with the case where the closed ring support is used.

10 ... Transdermal administration device, 20 ... Microneedle, 21 ... Base part, 21S ... Base surface, 22 ... Projection part, 30 ... Support, 31 ... Support part, 40 ... Drive part, Co ... Outer circle, Ci ... Inner circle, Sk ... skin, Ps ... pressing region, Ln ... adjacent distance, Ls ... separation distance, Wt ... maximum diameter, R1 ... convex region, R2 ... concave region.

Claims (7)

A substrate portion having a substrate surface, a administration portion having a protrusion protruding from the substrate surface and having a flow path that opens to the peripheral surface of the protrusion inside the protrusion, and an administration portion having the protrusion.
A support having a plurality of supports having an apical surface abutting on the subject of administration, and
The administration unit is provided with a drive unit that is a mechanism that displaces the administration unit from a position in the space surrounded by the plurality of support portions toward the outside of the space and pierces the protrusion into the administration target.
When viewed from the direction facing the base surface, the plurality of support portions have a gap between the support portions adjacent to each other and a gap between the base surface and the support portion. Surrounding,
In the administration portion, the tip of the protrusion is located from the first position where the tip of the protrusion is located closer to the base end side of the support than the tip surface of the support, and the tip of the protrusion is located from the first position. Also, a transdermal administration device configured to be displaceable at a second position near the tip surface of the support portion. The second position is a position in a space surrounded by the plurality of the support portions.
The transdermal administration device according to claim 1. The second position is a position outside the space surrounded by the plurality of the support portions.
The transdermal administration device according to claim 1. Seen from the direction facing the substrate surface
Of the plurality of virtual circles in which all the supports are located inside the circle, the circle having the smallest inner diameter is the outermost circle.
A virtual circle centered on the center of the substrate surface, and the circle having the largest inner diameter is the innermost circle among a plurality of circles in which none of the support portions are located inside the circle.
The ratio of the total area of the area occupied by the end of each support portion in contact with the administration target to the area of the region inside the outermost circle and outside the innermost circle is 0.2 or more. 8. The transdermal administration device according to any one of claims 1 to 3, which is 8 or less. The transdermal administration device according to any one of claims 1 to 4 , wherein the positions of the ends of the support portions in contact with the administration target in the extending direction of the protrusions coincide with each other. Any of claims 1 to 4, wherein the plurality of support portions include the support portion in which the position of the end portion of the support portion in contact with the administration target is different from that of the other support portion in the extending direction of the protrusion portion. The transdermal administration device according to item 1. Claims 1 to 6 in which the supports are arranged so that a plurality of support portions each form a part of a symbol and form a single symbol as a whole when viewed from a direction facing the substrate surface. The transdermal administration device according to any one of the following items.

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