JP2020110344A - Medication administration measures - Google Patents

Abstract

To provide a medication administration device to be manufactured easily.SOLUTION: A medication administration device includes a plurality of projections on one surface of a base plate, each projection includes a groove, a groove storage material is disposed in the groove, a projection shaping material contains a water-soluble material, and the groove storage material contains a water-soluble material. Further, the projection forming material contains a water-soluble polymer. Furthermore, the groove forming material contains a water-soluble polymer. Alternatively, the grooves of the respective projections are aligned in one direction.SELECTED DRAWING: Figure 1

Description

The present invention relates to a drug administration device such as a microneedle used for drug administration.

A microneedle is known as a drug administration device that administers a drug into the body through the skin. The microneedle has a plurality of needle-shaped protrusions on the surface of the base. In the method of administering a drug using a microneedle, the protrusions pierce the skin by pressing the substrate against the skin, and the drug is fed into the body through the holes formed by the protrusions (see, for example, Patent Document 1). ..

JP, 2006-341089, A

The microneedle including the drug is formed, for example, by applying a liquid drug to the surface near the tip of the protrusion and drying the drug. However, in the case of this configuration, when a certain amount or more of the drug is applied to the protrusion, the drug is solidified in a rounded state at the tip of the protrusion and the puncture performance of the protrusion is deteriorated. Also, the amount of drug that can be applied may be severely limited. Therefore, a method has been proposed in which a microneedle formed of a water-soluble material has a two-layer structure in the height direction of the protrusion and a drug is added to the tip of the protrusion. In this case, when manufacturing the microneedles, the intaglio plate needs to be sequentially filled with the aqueous solution containing the tip-side forming material containing the drug and the aqueous solution containing the non-tip-side forming material, which tends to complicate the production.

In view of such circumstances, an object of the present invention is to provide a drug administration device that is easy to manufacture.

In order to solve the above problems, the present invention provides a drug administration device having a plurality of protrusions on one surface of a substrate, wherein the protrusions have a groove, and a groove containing material is arranged in the groove, and The drug administration device is characterized in that the material for forming the protrusion includes a water-soluble material and the groove containing material includes a water-soluble material.

Further, it is preferable that the projection forming material contains a water-soluble polymer.

Further, it is preferable that the groove containing material contains a water-soluble polymer.

Moreover, it is preferable that the grooves of the respective protrusions are aligned in one direction.

Further, the solubility of the protrusion forming material in water may be different from the solubility of the groove containing material in water.

Further, the solubility of the protrusion forming material in water may be higher than the solubility of the groove containing material in water.

The solubility of the protrusion forming material in water may be lower than the solubility of the groove containing material in water.

According to the present invention, it is possible to provide a drug administration device which is easy to manufacture.

It is a perspective view and a partial perspective view of a medicine administration device concerning an embodiment of the present invention. It is an enlarged micrograph of the protrusion part of the chemical|medical agent administration apparatus of an Example. It is an enlarged micrograph of the protrusion part of the chemical|medical agent administration apparatus of an Example.

The drug administration device according to the embodiment will be described with reference to FIG. 1. 1A is a perspective view of a drug administration device according to an embodiment, and FIG. 1B is a partial perspective view showing a protrusion, a groove, and a groove containing material of the drug administration device according to the embodiment. is there. As shown in FIGS. 1A and 1B, the drug administration device 10 includes a plate-shaped substrate 1, a protrusion 2 protruding from the substrate 1, and a groove 3 formed in the protrusion 2. The groove housing material 4 housed in the groove 3 is provided. The substrate 1 has a first surface 1a that is a surface on which the protrusion 2 is formed and a second surface 1b that is a surface opposite to the first surface 1a, and the first surface 1a is the surface of the protrusion 2. It supports the proximal end.

In the example shown in FIGS. 1A and 1B, the structure including the protrusion 2 and the groove 3 has a shape obtained by cutting a quadrangular prism at an angle with respect to the extending direction. The protrusion 2 has a side surface 2a that is a peripheral surface that extends perpendicularly from a rectangular bottom surface defined in the first surface 1a, and an upper surface 2b that is inclined with respect to the bottom surface. All the sides included in the upper surface 2b are inclined with respect to the bottom surface, and the length of the protruding portion 2 from the first surface 1a is the largest at the apex on the back side of the paper surface of the upper surface 2b.

A groove 3 is formed in the protrusion 2. The groove 3 extends along a direction orthogonal to the first surface 1 a, and extends in a direction along one of two facing sides forming the bottom surface of the protrusion 2 along the first surface 1 a. It penetrates through the protrusion 2 in the closed direction. That is, the groove 3 opens in the upper surface 2b and extends so as to cross the upper surface 2b. In the present embodiment, the direction orthogonal to the first surface 1a is an example of the first direction, and among the directions along the first surface 1a, two pairs of facing sides forming the bottom surface of the protrusion 2 are formed. The direction along one set is an example of the second direction.

In other words, the groove 3 defines a space that is recessed toward the substrate 1 along the first direction, and this space extends continuously along the second direction so that the groove 3 forms one of the side surfaces 2a. There is an opening in the section. More specifically, the groove 3 is opened at the upper surface 2b of the protrusion 2 and at two positions on the side surface 2a. And these openings are connected. In addition, the grooves 3 of each protrusion 2 are aligned in one direction.

A groove containing material 4 is contained in the groove 3. In such a configuration, the groove containing material 4 is exposed on the surface of the drug administration device 10 when viewed from the direction facing the first surface 1a, and the groove containing material 4 is exposed even when viewed from the direction parallel to the first surface 1a. It is exposed on the surface of the drug administration device 10.

As shown in FIGS. 1A and 1B, the bottom of the groove 3 is located inside the protrusion 2 and at a position away from the substrate 1 in the direction orthogonal to the first surface 1a. There is.

The length of the protruding portion 2 is the length from the first surface 1a of the substrate 1 to the tip of the protruding portion 2 in the direction orthogonal to the first surface 1a. The length of the protrusion 2 may be determined according to the purpose of perforation by the protrusion 2 and the type of drug to be administered. For example, the length Lt of the protrusion 2 is set such that the tip of the protrusion 2 penetrates the stratum corneum, which is the outermost layer of the skin, when the protrusion 2 is pierced into the skin of the human body, and does not reach the nerve layer. When set to, the length Lt of the protrusion 2 is preferably in the range of 100 μm or more and 2 mm or less. In addition, the maximum width Dt of the protrusion 2 viewed from the direction along the first surface 1a and the direction in which the groove 3 extends, that is, the maximum width of the protrusion 2 viewed along the second direction. The width Dt is preferably about 10 μm to 600 μm.

The size of the groove 3 may be determined according to the dose of the target drug within a range that does not excessively reduce the mechanical strength of the protrusion 2. It is preferable that the groove containing material 4 contains a drug. For example, the width Dm of the groove 3 viewed along the second direction is preferably 1/5 to 1/2 of the width Dt of the protrusion 2. If the width Dm is smaller than ⅕ of the width Dt, sufficient mechanical strength can be obtained for the protrusions 2, but it becomes difficult to fill the groove housing material 4 in the grooves 3, and the grooves 3 can be filled. The amount of groove containing material 4 is reduced. On the other hand, if the width Dm is larger than 1/2 of the width Dt, the groove 3 can be filled with a large amount of the groove containing material 4, but it becomes difficult to secure the mechanical strength of the protrusion 2. When the width Dm changes, it is preferable that the minimum value of the width Dm is ⅕ or more of the width Dt and the maximum value of the width Dm is ½ or less of the width Dt.

Further, the length Lm from the first surface 1a to the bottom of the groove 3 in the direction orthogonal to the first surface 1a is preferably 1/3 or more of the length Lt of the protrusion 2. When the length Lm is ⅓ or more of the length Lt, the groove containing material 4 contained in the groove 3 is smoothly supplied into the body. Further, the length Lm is preferably 4/5 or less of the length Lt. When the length Lm is 4/5 or less of the length Lt, the groove containing material 4 filled in the groove 3 is likely to be retained in the groove 3.

The protrusion 2 has a pointed tip, and the tip, which is the apex of the tip, is not located on the straight line A extending in the direction in which the protrusion 2 extends through the center of the bottom surface of the protrusion 2. When viewed from the direction facing the first surface 1 a, the tip of the protrusion 2 is located at the edge of the protrusion 2. As shown in FIG. 1A, the number of protrusions 2 is not particularly limited as long as it is two or more (a plurality).

The drug administration device 10 has a plurality of protrusions 2. Each of the plurality of protrusions 2 may be regularly arranged on the surface of the substrate 1 or may be irregularly arranged. For example, the plurality of protrusions 2 are arranged in a lattice shape or a concentric circle shape.

When the drug administration device 10 is used, the substrate 1 is pressed against the skin with the protrusion 2 facing the skin, whereby the protrusion 2 pierces the skin. As a result, the material forming the protrusions 2 and the groove containing material 4 are dissolved in water around the skin, and these materials are liquefied and sent into the body of the administration target.

In the drug administration device 10, the protrusion forming material is preferably formed of a biocompatible water-soluble material. Biocompatible water-soluble materials include carboxymethyl cellulose (CMC), methyl cellulose (MC), hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC), ethyl cellulose, hydroxyethyl cellulose, polyvinyl alcohol (PVA), polyacrylic acid. Examples thereof include water-soluble polymers such as polymers, polyacrylamide (PAM), polyethylene oxide (PEO), pullulan, alginate, starch, pectin, chitosan, chitosan succinamide, oligochitosan, and chondroitin sulfate. However, the water-soluble polymer in the water-soluble material is not limited to a specific material. Further, as the biocompatible water-soluble material, polysaccharides such as dextran, dextrin, trehalose, maltose can be used. However, the polysaccharide in the water-soluble material is not limited to a specific material.

In the drug administration device 10, the substrate 1 is preferably manufactured integrally with the same material as that of the protrusion 2.

In the drug administration device 10, the groove containing material 4 is preferably formed of a biocompatible water-soluble material. Biocompatible water-soluble materials include carboxymethyl cellulose (CMC), methyl cellulose (MC), hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC), ethyl cellulose, hydroxyethyl cellulose, polyvinyl alcohol (PVA), polyacrylic acid. Examples thereof include water-soluble polymers such as polymers, polyacrylamide (PAM), polyethylene oxide (PEO), pullulan, alginate, starch, pectin, chitosan, chitosan succinamide, oligochitosan, and chondroitin sulfate. However, the water-soluble polymer in the water-soluble material is not limited to a specific material. Further, as the biocompatible water-soluble material, polysaccharides such as dextran, dextrin, trehalose, maltose can be used. However, the polysaccharide in the water-soluble material is not limited to a specific material.

Further, the groove containing material 4 can contain a drug. As the drug, various proteins, pharmacologically active substances, cosmetic compositions and the like can be used. The type of delivery material to be delivered into the skin is selected according to the purpose. Examples of the pharmacologically active substance include vaccines against influenza and the like, pain relievers for cancer patients and the like, biologics, gene therapeutics, injections, oral preparations, preparations for skin application and the like. In transdermal administration using the drug administration device 10, a delivery product is administered to pores formed in the skin. Therefore, transdermal administration using the drug administration device 10 can be used for administration of pharmacologically active substances that require subcutaneous injection, in addition to the pharmacologically active substances used for conventional transdermal administration. In particular, transdermal administration using the drug administration device 10 is suitable for administration of injections such as vaccine to children because it does not cause pain during administration. In addition, transdermal administration using the drug administration device 10 is suitable for administration of an oral agent to a child who has difficulty in taking an oral agent because it is not necessary to drink a delivery product at the time of administration.

The cosmetic composition is a composition used as cosmetics or beauty products. Examples of the cosmetic composition include a moisturizer, a coloring agent, a fragrance, or a physiologically active substance having a cosmetic effect such as an effect of improving wrinkles, acne, stretch marks, and hair loss. When a material having an aroma is used as the delivery material, an odor can be imparted to the groove containing material 4, so that the drug administration device 10 suitable for beauty products can be obtained.

The drug administration device 10 may include a drug in the protrusion forming material. Further, when the protrusion forming material contains a drug, the groove containing material 4 may not contain the drug. However, it is preferable that the groove containing material 4 contains a drug in terms of administering a predetermined drug into the skin.

[Method for manufacturing drug administration device]
A method for manufacturing the drug administration device according to the embodiment will be described.

First, a main body including the substrate 1 and the protrusion 2 having the groove 3 is formed. The main body can be manufactured using various known techniques. For example, the main body is formed by mechanical processing such as dicing or drilling, laser processing, molding technology such as injection molding, etching, or the like, depending on the material forming the main body. In addition, an original plate of the main body is manufactured by such a method, and further, an intaglio plate having the unevenness of the original plate inverted by a plating method or a molding method using a resin is manufactured, and the main plate can be duplicated using the manufactured intaglio plate. it can. The main body is formed by filling the intaglio plate with a solution of the protrusion forming material for forming the protrusions 2 and the substrate 1, drying it, and then peeling it from the intaglio plate.

In the main body of the present embodiment, since the groove 3 is open continuously in the direction orthogonal to the first surface 1a and the direction along the first surface 1a, the protrusion 2 has a direction orthogonal to the first surface 1a. Compared with a configuration in which a housing portion such as a through hole or a non-through hole that is opened only in the opening is formed, the groove 3 can be formed easily, and the range of processing techniques capable of forming the groove 3 is expanded. In particular, as in the case of the drug administration device 10 according to the embodiment, when the grooves 3 formed in each of the plurality of protrusions 2 are aligned in the opening direction, the plurality of protrusions arranged in a row by the original plate by dicing. The groove 3 can be continuously formed in the portion 2 without changing the direction of the blade. Further, in such a configuration, it is not necessary to change the processing method for forming the outer shape of the protrusion 2 and forming the groove 3. Therefore, the production efficiency of the main body is improved.

Subsequently, the groove housing material 4 is filled in the groove 3 formed in the protrusion 2 of the main body. The groove containing material 4 is filled in the state of a solution or a dispersion liquid. As a method of filling the groove containing material 4, for example, a method of immersing the tip end of the protrusion 2 in the liquid surface of the stored drug and causing the groove containing material 4 to crawl into the groove 3 by a capillary phenomenon is used. Alternatively, the groove containing material 4 may be filled into the groove 3 by dropping the groove containing material 4 toward the groove 3.

Here, in the main body of the present embodiment, the groove 3 is opened in a continuous manner in a direction orthogonal to the first surface 1a and a direction along the first surface 1a. Therefore, as compared with the configuration in which the protrusion 2 is formed with a housing portion such as a through hole or a non-through hole that opens only in the direction orthogonal to the first surface 1a, from a direction other than the direction orthogonal to the first surface 1a. Also, the groove containing material 4 can enter the groove 3, and the air pushed out from the groove 3 due to the groove containing material 4 entering the groove 3 escapes from a direction different from the direction in which the groove containing material 4 enters. .. Therefore, the groove containing material 4 easily enters the groove 3.

Further, in the configuration of this embodiment, it is easy to secure a wide entrance of the groove containing material 4 into the groove 3. Since the protrusions 2 are very small, the influence of the surface tension of the groove containing material 4 becomes large and the groove containing material 4 becomes a groove when the containing portion is opened only in the direction orthogonal to the first surface 1a. It is difficult to enter 3. On the other hand, in this embodiment, the contact area between the main body and the groove accommodating material 4 at the entrance of the groove 3 is enlarged by ensuring a wide entrance of the groove accommodating material 4 into the groove 3, and as a result, the groove is increased. The wettability of the main body with respect to the containing material 4 is improved, and the groove containing material 4 easily enters the groove 3.

In the drug administration device 10 according to the embodiment, compared with the drug administration device having a two-layer structure in the height direction of the protrusion and made of a water-soluble material, the protrusion 2 having the substrate 1 and the groove 3 After forming the main body, the groove containing material 4 can be filled, and the manufacturing is easy. Further, both the protrusion forming material and the groove containing material 4 are formed of a water-soluble material, and the protrusion 2 can be deformed by one puncture of the skin, so that the drug administration device 10 can be used multiple times. Can be prevented.

Further, in the drug administration device 10 according to the embodiment, since the protrusion forming material contains the water-soluble polymer, the protrusion 2 has a sufficient strength as compared with the case where the water-soluble low molecular weight material is used. Can be

Further, in the drug administration device 10 according to the embodiment, since the groove containing material 4 contains the water-soluble polymer, the groove 3 is filled with the groove containing material 4 as compared with the case of using the water-soluble low molecular weight material. The strength of the formed protrusions 2 can be made sufficient, and the deformation of the protrusions 2 when the groove containing material 4 is filled in the grooves 3 can be suppressed.

Further, in the drug administration device 10 according to the embodiment, the grooves 3 of each protrusion 2 are aligned in one direction, so that the groove forming process can be simplified.

Further, the drug administration device 10 according to the embodiment may have a configuration in which the solubility of the protrusion forming material in water and the solubility of the groove containing material 4 in water are different. As a result, the dissolution speed of the protrusion forming material and the groove containing material 4 into the skin can be controlled.

Further, the drug administration device 10 according to the embodiment may be configured such that the solubility of the protrusion forming material in water is higher than the solubility of the groove containing material 4 in water. Thereby, the dissolution speed of the protrusion forming material in the skin can be made faster than the dissolution speed of the groove containing material 4, and the dissolution speed of the groove containing material 4 in the skin can be made slower than the dissolution speed of the protrusion forming material. can do. When the groove containing material 4 contains a drug, it is effective when it is desired to slow down the penetration speed of the drug into the skin.

Further, the drug administration device 10 according to the embodiment can be configured such that the solubility of the protrusion forming material in water is smaller than the solubility of the groove containing material 4 in water. Thereby, the dissolution speed of the groove containing material 4 into the skin can be made faster than the dissolution speed of the protrusion forming material, and the dissolution speed of the protrusion forming material into the skin can be increased. Can be slower than. When the groove containing material 4 contains a drug, it is effective when it is desired to speed up the penetration of the drug into the skin.

The above-mentioned drug administration device and manufacturing method thereof will be described with reference to specific examples.

(Example)
[Preparation of the original plate]
Silicon is used as a material for forming an original plate of a main body composed of a substrate and protrusions having grooves, and the protrusions having the shape shown in FIG. An original plate of 25 main bodies arranged in a circle was prepared. The length Lt of the protrusion is 1.2 mm, the width Dt of the protrusion is 300 μm, the length Lm from the first surface of the substrate to the bottom of the groove is 400 μm, and the width Dm of the groove is 100 μm. It was

[Fabrication of intaglio]
Next, a nickel film having a thickness of 500 μm is formed on the original plate formed of the silicon substrate by a plating method, and the silicon substrate is wet-etched with an aqueous potassium hydroxide solution having a weight percent concentration of 30% and heated to 90° C. And removed to make an intaglio plate made of nickel.

[Production of the main body]
Next, chitosan succinamide was dissolved in water to prepare a main body forming aqueous solution (protrusion forming material). Rhodamine B was added to this aqueous solution and colored red. Next, the intaglio plate was filled with a main body-forming aqueous solution that forms a main body composed of the substrate and the protrusions having the grooves. Next, the intaglio plate was heated at 90° C. for 10 minutes using a heat source to dry and solidify the projection forming material. Here, a hot plate was used as a heat source. Next, the solidified projection forming material was peeled from the intaglio plate to obtain a main body.

[Drug filling]
Next, hydroxypropyl cellulose (Wako Pure Chemical Industries, Ltd.) was dissolved in ethanol to prepare a solution of the groove containing material. Evans blue was added to this solution and it was colored blue. Next, this solution was filled in a groove fixed to a dedicated holder using a syringe with a needle. Next, the mixture was allowed to stand at room temperature for 5 minutes until it was dried and solidified to obtain a drug administration device in which the groove containing material was filled.

2 and 3 show enlarged micrographs of the protrusions of the obtained drug administration device.

INDUSTRIAL APPLICABILITY The present invention can be suitably used as a drug administration device used for medical treatment, cosmetic use and the like.

DESCRIPTION OF SYMBOLS 1 Substrate 2 Projection part 3 Groove 4 Groove accommodation material 10 Drug administration device

Claims (7)

A drug administration device comprising a plurality of protrusions on one surface of a substrate,
The protrusion includes a groove, and the groove containing material is disposed in the groove, and
The material forming the protrusions includes a water-soluble material, and
The drug administration device, wherein the groove containing material includes a water-soluble material. The drug administration device according to claim 1, wherein the protrusion forming material contains a water-soluble polymer. The drug administration device according to claim 1, wherein the groove containing material contains a water-soluble polymer. The drug administration device according to claim 1, wherein the grooves of each of the protrusions are aligned in one direction. 5. The drug administration device according to claim 1, wherein the solubility of the protrusion forming material in water and the solubility of the groove containing material in water are different from each other. The drug administration device according to claim 5, wherein the solubility of the protrusion forming material in water is higher than the solubility of the groove containing material in water. The drug administration device according to claim 5, wherein the solubility of the protrusion forming material in water is smaller than the solubility of the groove containing material in water.