JP2021007449A - Microneedle - Google Patents

Abstract

To provide a microneedle in which a user can obtain a wearing feeling during a retention time in a state of being punctured to skin.SOLUTION: A microneedle 1 includes a substrate 12 having a first surface 12A and a second surface 12B, and multiple protrusions 11 protruding from the first surface 12A of the substrate 12. The shape of a joining surface of the multiple protrusions 11 with the first surface 12A of the substrate 12 is quadrangular, and at least a part of the multiple protrusions 11 is arranged so that one side of the quadrangular joining surface may become substantially parallel with one side of the quadrangular joining surface of the adjacent two protrusions 11. Also, the substrate 12 includes a striped uneven structure 13 between the two protrusions 11 where one side of the joining surface is disposed substantially in parallel. Then, the striped uneven structure 13 is made substantially in parallel to two sides for sandwiching the striped uneven structure 13.SELECTED DRAWING: Figure 1

Description

The present invention relates to microneedles.

Methods of administering the drug to the human body include oral administration, administration to the skin dermis layer or vein by puncturing the skin, administration to the local dermis layer by applying an ointment to the skin surface, and local dermis by application to the skin surface. Methods such as administration to the layer can be mentioned.
Among these, in recent years, the development of microneedles having protrusions, which are a plurality of minute needles, has been promoted as an instrument for administering a drug into the body by a method of sticking or puncturing with an applicator. As the material of the microneedle, a material that is harmless even if it is dissolved or remains in the living body is selected so that there is no adverse effect even if a part of the needle-shaped body is broken by puncture and remains in the body.

International Publication No. 2005/08162 Japanese Unexamined Patent Publication No. 2006-334419

When using a microneedle, a minute needle is punctured into the skin, but the holding time in the state of being punctured into the skin varies depending on the type of microneedle.
An object of the present invention is to provide a microneedle that allows a user to obtain a feeling of wearing during a holding time in a state of being punctured into the skin.

The microneedle according to one aspect of the present invention is a microneedle including a substrate having a first surface and a second surface, and a plurality of protrusions protruding from the first surface of the substrate, and is a plurality of microneedles. The shape of the joint surface of the protrusion with the first surface of the substrate is quadrangular, and at least a part of the plurality of protrusions has a quadrangular shape of two adjacent protrusions on one side of the quadrangular joint surface. The substrate is arranged so as to be substantially parallel to one side of the joint surface, and the substrate has a striped uneven structure between two protrusions having one side of the joint surface arranged substantially parallel to each other. The gist of the structure is that it is substantially parallel to one side of the striped uneven structure.

According to the microneedle according to the present invention, it is possible for the user to obtain a feeling of wearing during the holding time in a state of being punctured into the skin.

It is a perspective view which shows the structure of the microneedle which concerns on 1st Embodiment of this invention. It is a top view and a cross-sectional view of the microneedle of FIG. It is a perspective view which shows the structure of the microneedle which concerns on 2nd Embodiment of this invention. FIG. 3 is a top view and a cross-sectional view of the microneedle of FIG. It is a perspective view which shows the structure of the microneedle which concerns on 3rd Embodiment of this invention. FIG. 5 is a top view and a cross-sectional view of the microneedle of FIG.

An embodiment of the present invention will be described. It should be noted that the present embodiment shows an example of the present invention, and the present invention is not limited to the present embodiment. In addition, various changes or improvements can be added to the present embodiment, and the modified or improved forms may be included in the present invention.

First, the microneedle 1 according to the first embodiment will be described with reference to the perspective view of FIG. 1, the top view of FIG. 2 (a), and the cross-sectional view of FIG. 2 (b).
The microneedle 1 according to the first embodiment includes a substrate 12 having a first surface 12A and a second surface 12B, and a plurality of protrusions 11 protruding from the first surface 12A of the substrate 12. The protrusion 11 acts as a needle for perforating the skin.

The shape of the joint surface of the plurality of protrusions 11 with the first surface 12A of the substrate 12 is quadrangular, and at least a part of the plurality of protrusions 11 has one side of the quadrangular joint surface adjacent to the 2 The protrusions 11 are arranged so as to be substantially parallel to one side of the quadrangular joint surface. That is, the plurality of protrusions 11 are arranged in a so-called grid pattern (matrix shape) so that the opposite sides of the adjacent protrusions 11 are substantially parallel to each other on the first surface 12A of the substrate 12. Have been placed.

The shape of the protrusion 11 can be, for example, a quadrangular pyramid shape, a quadrangular prism shape, or a combination of a quadrangular pyramid shape and a quadrangular prism shape, but is not limited to these shapes. Further, the side wall of the protrusion 11 may be formed with a constriction or a step, or may be formed with a groove. Further, the tip of the quadrangular pyramid-shaped protrusion 11 may have a flat surface.

The substrate 12 includes a striped concave-convex structure 13 between two protrusions 11 having one side of the joint surface arranged substantially parallel to each other. The striped concavo-convex structure 13 is substantially parallel to two sides sandwiching the striped concavo-convex structure 13. The striped uneven structure 13 is formed by arranging the concave portions extending linearly and the convex portions in parallel.
The height H of the protrusion 11 is the length from the first surface 12A to the tip of the protrusion 11 in the thickness direction of the substrate 12, that is, in the direction orthogonal to the first surface 12A of the substrate 12. The height H of the protrusion 11 is preferably 50 μm or more and 2 mm or less.

The width D of the protrusion 11 is the maximum value of the length of the protrusion 11 in the direction along the first surface 12A of the substrate 12, that is, in the direction parallel to the first surface 12A. For example, when the protrusion 11 has a regular quadrangular pyramid shape or a regular quadrangular prism shape, the length of the diagonal line of the square on the first surface 12A of the substrate 12 partitioned by the bottom of the protrusion 11 is the length of the protrusion 11. The width is D. Further, for example, when the protrusion 11 has a conical shape or a cylindrical shape, the diameter of the circle partitioned by the bottom of the protrusion 11 is the width D of the protrusion 11. The width D of the protrusion 11 is preferably 1 μm or more and 1 mm or less. The aspect ratio A (A = H / D), which is the ratio of the length H to the width D of the protrusion 11, is preferably 1 or more and 10 or less.

Next, the microneedle 1 according to the second embodiment will be described with reference to the perspective view of FIG. 3, the top view of FIG. 4 (a), and the cross-sectional view of FIG. 4 (b).
The configuration of the microneedle 1 according to the second embodiment is substantially the same as that of the microneedle 1 according to the first embodiment, but in the case of the microneedle 1 according to the first embodiment, the first surface 12A of the substrate 12 The concave-convex structure 13 is formed by providing the concave portion with respect to the first surface 12A of the substrate 12, whereas in the case of the microneedle 1 according to the second embodiment, the convex portion is provided with respect to the first surface 12A of the substrate 12. The uneven structure 13 is formed by the above.
As described above, the microneedle of the present invention may have a concave-convex structure by forming a concave portion with respect to the first surface of the substrate, or may have a concave-convex structure by forming a convex portion. Further, the concave-convex structure may be formed by forming both the convex portion and the concave portion.

Next, the microneedle 1 according to the third embodiment will be described with reference to the perspective view of FIG. 5, the top view of FIG. 6A, and the cross-sectional view of FIG. 6B.
The configuration of the microneedle 1 according to the third embodiment is almost the same as that of the microneedle 1 according to the first embodiment, but is different in the following points. That is, in the case of the microneedle 1 according to the first embodiment, the concave-convex structure 13 is formed only on the portion between the adjacent protrusions 11 (hereinafter referred to as “inter-projection portion”) on the first surface 12A of the substrate 12. However, in the case of the microneedle 1 according to the third embodiment, the concave-convex structure is formed not only on the inter-projection portion but also on the portion of the first surface 12A of the substrate 12 other than the inter-projection portion. 13 is formed.

That is, in the case of the microneedle 1 according to the third embodiment, as shown in FIG. 6A, the concave-convex structure 13 formed only in the inter-projection portion and the plurality of inter-projection portions. It has both a concavo-convex structure 13 that is continuously formed.
As described above, in the microneedle of the present invention, it is sufficient that the uneven structure is formed at least in the inter-projection portion, but the concavo-convex structure may be formed in addition to the inter-projection portion. Further, the uneven structure may be formed on the outer portion of the first surface 12A of the substrate 12 in the protrusion forming region defined by the protrusions located on the outermost side.

In the microneedle 1 according to the first, second, and third embodiments shown in FIGS. 1 to 6, the concave-convex structure 13 having a rectangular cross-sectional shape is formed, but the cross section of the concave-convex structure 13 is formed. The shape is not limited to this, and the uneven structure 13 having a curved cross-sectional shape may be used.
Further, in the microneedle 1 according to the first and third embodiments shown in FIGS. 1, 2, 5 and 6, a recess is formed in the flat first surface 12A, which is shown in FIGS. 3 and 4. In the microneedle 1 according to the second embodiment, a convex portion is formed on the flat first surface 12A, but the concave-convex structure 13 is not limited to this, and the concave-convex structure 13 is flat. It does not have to have a surface.

The uneven structure 13 formed on the surface of the first surface 12A of the substrate 12 preferably has a height difference of 0.1 μm or more and 10.0 μm or less. The height difference of the concave-convex structure 13 is obtained by the difference between the maximum height and the minimum height of the adjacent concave and convex portions constituting the concave-convex structure 13. When there are a plurality of combinations of concave portions or convex portions, the average value is the height difference. The effect of the present invention can be further enhanced by setting the height difference of the uneven structure 13 within the above range.

Further, in the concave-convex structure 13 formed on the surface of the first surface 12A of the substrate 12, it is preferable that there is at least one combination of the concave portion and the convex portion in the portion between the adjacent protrusions 11. Further, in the concave-convex structure 13 formed on the surface of the first surface 12A of the substrate 12, it is preferable that there are at least two or more combinations of concave and convex portions in the portion between the adjacent protrusions 11. Furthermore, it is preferable that there are at least three or more.

As described above, since the microneedle 1 according to the first, second, and third embodiments has a striped uneven structure 13 in the portion between the protrusions, when the protrusion 11 is punctured into the skin, the skin Moisture on the surface of the surface moves to the recesses of the uneven structure 13. Thereby, the user can obtain a feeling of wearing during the holding time in the state of being punctured into the skin. The microneedles 1 according to the first, second, and third embodiments can be used, for example, in medical applications, MEMS (Micro Electro Mechanical Systems) devices, optical members, drug discovery, cosmetics, cosmetic applications, and the like.

The microneedles 1 and the manufacturing method thereof according to the first, second, and third embodiments will be described in more detail below.
[Detailed configuration of microneedle 1]
The microneedles 1 according to the first, second, and third embodiments are preferably formed from a biocompatible material. As the material constituting the microneedle 1, for example, silicon, metals such as stainless steel, titanium and manganese, and thermoplastic resins such as medical silicone, polylactic acid, polyglycolic acid, polycarbonate and cyclic olefin copolymer are used. be able to.

Further, the microneedle 1 may be made of a material in which at least a part of the protrusion 11 is dissolved by water, that is, a water-soluble material. As the water-soluble material, a water-soluble polymer or a polysaccharide can be used. Examples of the water-soluble polymer include carboxymethyl cellulose (CMC), methyl cellulose (MC), hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC), polyvinyl alcohol (PVA), polyacrylic acid-based polymer, polyacrylamide (PAM), and the like. Examples include polyethylene oxide (PEO), purulan, alginate, pectin, chitosan, chitosan succinamide, oligochitosan. Examples of polysaccharides include trehalose and maltose.

Further, the microneedle 1 according to the first, second, and third embodiments can hold the drug on the surface of the protrusion 11. Further, the microneedle 1 according to the first, second, and third embodiments can hold a drug inside the protrusion 11 when a material dissolved by water is used as a material for forming the protrusion 11. it can.

As the drug, various proteins, pharmacologically active substances, cosmetic compositions and the like can be used. The type of delivery delivered into the skin is selected according to the purpose. Examples of the pharmacologically active substance include vaccines for influenza and the like, painkillers for cancer patients, biologics, gene therapy agents, injections, oral preparations, skin-applied preparations and the like.

In the transdermal administration using the microneedle 1 according to the first, second, and third embodiments, the drug is supplied to the puncture hole formed in the skin. Therefore, in the transdermal administration using the microneedle 1 according to the first, second, and third embodiments, in addition to the pharmacologically active substance used for the conventional transdermal administration, administration of a pharmacologically active substance that requires subcutaneous injection. Can also be used. In particular, the microneedle 1 according to the first, second, and third embodiments is suitable for administration of a drug for children because it does not cause pain during administration. Further, in the transdermal administration using the microneedle 1 according to the first, second, and third embodiments, it is not necessary to take the delivery product at the time of administration, so that it is difficult for children and the elderly to take the oral preparation. Suitable for administration of oral preparations to people.

A cosmetic composition is a composition used as a cosmetic or a beauty product. Examples of the cosmetic composition include moisturizers, colorants, fragrances, physiologically active substances and the like. Examples of the physiologically active substance include a physiologically active substance that exhibits a cosmetic effect such as an improving effect on wrinkles, acne, stretch marks, and the like and an improving effect on hair loss.

[Manufacturing method of microneedle 1]
The substrate 12, the protrusion 11, and the concave-convex structure 13 of the microneedle 1 according to the first, second, and third embodiments can be manufactured by using various known techniques. For example, depending on the material constituting the microneedle 1, it can be formed by machining such as dicing or drilling, molding technology such as laser processing or injection molding, etching or the like. Further, an original plate of the microneedle 1 is produced by such a method, and an intaglio plate in which the unevenness of the original plate is inverted is produced by a plating method or a molding method using a resin, and the microneedle 1 is formed using the produced intaglio plate. Can be duplicated.

Examples and comparative examples of the present invention are shown below.
Grinding was performed to form linear grooves on the surface of the alumina substrate. Further, the same grinding process was performed in the direction orthogonal to the linear groove to prepare a structure having protrusions on the substrate. Further, a concavo-convex structure was formed between the protrusions of the structure by grinding to prepare a microneedle prototype.
Next, an intaglio was prepared from the microneedle original plate. Specifically, a nickel film was formed on the surface of the microneedle original plate by the plating method. Next, an intaglio was prepared by peeling the nickel film from the microneedle original plate.

From the obtained intaglio, microneedles made of polyglycolic acid were produced. A through hole was formed in the protrusion of the obtained polyglycolic acid microneedle by laser processing to prepare a microneedle having the through hole. In the obtained polyglycolic acid microneedle of the example, protrusions having a height of H200 μm and a width of D50 μm are arranged in a grid pattern in 4 columns × 4 rows. Further, five recesses are formed in the portion between the protrusions between the adjacent protrusions, forming an uneven structure. The height difference of the uneven structure was 3 μm.

At the same time, as a comparative example, a microneedle that does not form an uneven structure was produced. The microneedles of the comparative example were produced by the same production method as the microneedle of the example except for the step of forming the uneven structure. In the obtained polyglycolic acid microneedle of the comparative example, protrusions having a height of H200 μm and a width of D50 μm are arranged in a grid pattern in 4 columns × 4 rows. Further, the portion between the protrusions between the adjacent protrusions is a flat surface.

The microneedles of Examples and Comparative Examples were punctured into artificial skin. At this time, a small amount of water droplets were placed on the artificial skin, and a microneedle was punctured toward the water droplets on the artificial skin. Then, the artificial skin was observed with the microneedle punctured. As a result of observation, in the microneedles of the comparative example, it was confirmed that water droplets leaked to the outer peripheral portion of the microneedles. On the other hand, in the microneedles of the examples, it was not confirmed that water droplets leaked to the outer peripheral portion of the microneedles.

1 ... Microneedle 11 ... Protrusion 12 ... Substrate 12A ... First surface 12B ... Second surface 13 ... Concavo-convex structure

Claims (3)

A microneedle comprising a substrate having a first surface and a second surface, and a plurality of protrusions protruding from the first surface of the substrate.
The shape of the joint surface of the plurality of protrusions with the first surface of the substrate is quadrangular.
At least a part of the plurality of protrusions is arranged so that one side of the quadrangular joint surface is substantially parallel to one side of the quadrangular joint surface of the two adjacent protrusions.
The substrate has a striped concavo-convex structure between two protrusions whose one side is arranged substantially parallel to each other, and the striped concavo-convex structure sandwiches the striped concavo-convex structure. A microneedle that is almost parallel to one side. The microneedle according to claim 1, wherein the height difference of the uneven structure is 0.1 μm or more and 10.0 μm or less. The microneedle according to claim 1 or 2, wherein the height of the protrusion from the first surface of the substrate is within the range of 50 μm or more and 2 mm or less.

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