JP7283082B2 - drug administration measures - Google Patents

Description

TECHNICAL FIELD The present invention relates to drug administration devices such as microneedles used for drug administration.

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

Japanese Patent Application Laid-Open No. 2006-341089

The drug-containing microneedle 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 medicine is applied to the protrusion, the medicine collects in a round shape at the tip of the protrusion and hardens, thereby deteriorating the puncture performance of the protrusion. Also, the amount of drug that can be applied can be severely limited. Therefore, a method has been proposed in which microneedles made of a water-soluble material have a two-layer structure in the height direction of the projection and a drug is added to the tip of the projection. In this case, when manufacturing microneedles, it is necessary to sequentially fill the intaglio with an aqueous solution containing a drug-containing tip-side forming material and an aqueous solution containing a non-tip-side forming material, which tends to complicate 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 comprising a plurality of protrusions on one surface of a substrate, wherein the protrusions are provided with grooves, a groove containing material is arranged in the grooves, and , the material forming the protrusions contains a water-soluble material and a drug , and the material containing the grooves contains a water-soluble material and a drug , and the solubility in water of the material forming the protrusions is higher than the solubility in water of the material containing the grooves The drug administration device is characterized by being large .

Moreover, it is preferable that the protrusion-forming material contains a water-soluble polymer.

It is also preferred that the channel-accommodating material contains a water-soluble polymer.

Further, it is preferable that the grooves of each protrusion are aligned in one direction.

Further, the water solubility of the protrusion forming material and the water solubility of the groove accommodating material may be different.

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

Further, the solubility in water of the projection forming material may be lower than the solubility in water of the groove accommodating material.

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

1A and 1B are a perspective view and a partial perspective view of a drug administration device according to an embodiment of the present invention; FIG. 4 is an enlarged microscopic photograph of a protrusion of the drug administration device of Example. 4 is an enlarged microscopic photograph of a protrusion of the drug administration device of Example.

A drug administration device according to an embodiment will be described with reference to FIG. FIG. 1(a) is a perspective view of a drug administration device according to an embodiment, and FIG. 1(b) is a partial perspective view showing projections, grooves, and groove-accommodating materials of the drug administration device according to an embodiment. be. As shown in FIGS. 1(a) and 1(b), a drug administration device 10 includes a plate-like substrate 1, a protrusion 2 protruding from the substrate 1, a groove 3 formed in the protrusion 2, a groove containing material 4 received in the groove 3; The substrate 1 has a first surface 1a on which the protrusions 2 are formed and a second surface 1b opposite to the first surface 1a. Supports the base.

In the example shown in FIGS. 1(a) and 1(b), the structure composed of the protrusions 2 and the grooves 3 has a shape obtained by cutting a quadrangular prism obliquely with respect to its extending direction. The protruding portion 2 has a side surface 2a which is a peripheral surface extending vertically from a rectangular bottom surface partitioned within the first surface 1a, and an upper surface 2b 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 from the first surface 1a of the protrusion 2 is the largest at the vertex of the upper surface 2b on the back side of the paper surface.

A groove 3 is formed in the protrusion 2 . The groove 3 extends along a direction perpendicular to the first surface 1a and extends along one of two pairs of opposing sides forming the bottom surface of the protrusion 2 to extend along the first surface 1a. It penetrates the projecting portion 2 in the direction shown in FIG. That is, the groove 3 opens to the upper surface 2b and extends across the upper surface 2b. In the present embodiment, the direction orthogonal to the first surface 1a is an example of the first direction. A direction along one of the sets is an example of a 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. It is open to the More specifically, the grooves 3 are open at two locations among the upper surface 2b and the side surface 2a of the protrusion 2. As shown in FIG. And these openings are connected. Further, the grooves 3 of each protrusion 2 are aligned in one direction.

A groove containing material 4 is accommodated in the groove 3 . In such a configuration, the groove-accommodating 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-accommodating material 4 is exposed 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. 1(a) and 1(b), the bottom of the groove 3 is located inside the protrusion 2 and away from the substrate 1 in the direction perpendicular to the first surface 1a. there is

The length of the protrusion 2 is the length from the first surface 1a of the substrate 1 to the tip of the protrusion 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, the type of drug to be administered, and the like. For example, the length Lt of the protrusion 2 is a length that does not allow the tip of the protrusion 2 to penetrate the stratum corneum, which is the outermost layer of the skin, and reach the nerve layer when the protrusion 2 is stuck into the skin of the human body. , 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 seen from the direction along the first surface 1a and along the direction in which the groove 3 extends, that is, the maximum width Dt of the protrusion 2 seen along the second direction The width Dt of is preferably about 10 μm to 600 μm.

The size of the grooves 3 may be determined according to the desired dosage of the drug within a range that does not excessively reduce the mechanical strength of the protrusions 2 . It is preferable that the groove-accommodating material 4 contains a drug. For example, the width Dm of the groove 3 as viewed in 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 1/5 of the width Dt, although sufficient mechanical strength can be obtained for the protrusions 2, it becomes difficult to fill the grooves 3 with the groove-accommodating material 4, and the grooves 3 can be filled. The amount of channel containing material 4 is reduced. On the other hand, if the width Dm is larger than half the width Dt, the groove 3 can be filled with a large amount of the groove-accommodating material 4, but it becomes difficult to ensure the mechanical strength of the protrusion 2. FIG. When the width Dm changes, it is preferable that the minimum value of the width Dm is 1/5 or more of the width Dt, and the maximum value of the width Dm is 1/2 or less of the width Dt.

Also, the length Lm from the first surface 1a to the bottom of the groove 3 in the direction perpendicular to the first surface 1a is preferably 1/3 or more of the length Lt of the protrusion 2. As shown in FIG. When the length Lm is 1/3 or more of the length Lt, the groove-accommodating material 4 accommodated in the groove 3 can be smoothly supplied into the body. Furthermore, 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-accommodating material 4 filled in the grooves 3 is easily retained in the grooves 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 that passes through the center of the bottom surface of the protrusion 2 and extends in the direction in which the protrusion 2 extends. , the tip of the protrusion 2 is positioned at the edge of the protrusion 2 when viewed from the direction facing the first surface 1a. As shown in FIG. 1A, the number of protrusions 2 is not particularly limited as long as it is two or more (plurality).

The medicine injection device 10 has a plurality of protrusions 2 . Each of the plurality of projections 2 may be arranged regularly or irregularly on the surface of the substrate 1 . For example, the plurality of protrusions 2 are arranged in a grid pattern or concentrically.

When the drug administration device 10 is used, the substrate 1 is pressed against the skin with the projections 2 facing the skin, thereby causing the projections 2 to perforate the skin. As a result, the material for forming the protrusions 2 and the material for accommodating the grooves 4 dissolve in the moisture 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 made of a biocompatible water-soluble material. Examples of biocompatible water-soluble materials include carboxymethylcellulose (CMC), methylcellulose (MC), hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), ethylcellulose, hydroxyethylcellulose, polyvinyl alcohol (PVA), polyacrylic acid. polyacrylamide (PAM), polyethylene oxide (PEO), pullulan, alginate, starch, pectin, chitosan, chitosan succinamide, oligochitosan, chondroitin sulfate and other water-soluble polymers. However, the water-soluble polymer in the water-soluble material is not limited to specific materials. Polysaccharides such as dextran, dextrin, trehalose, and maltose can be used as biocompatible water-soluble materials. However, polysaccharides in water-soluble materials are not limited to specific materials.

In addition, in the drug administration device 10, it is preferable that the substrate 1 and the protrusion 2 are integrally manufactured from the same material.

In drug delivery device 10, channel containing material 4 is preferably formed from a biocompatible, water-soluble material. Examples of biocompatible water-soluble materials include carboxymethylcellulose (CMC), methylcellulose (MC), hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), ethylcellulose, hydroxyethylcellulose, polyvinyl alcohol (PVA), polyacrylic acid. polyacrylamide (PAM), polyethylene oxide (PEO), pullulan, alginate, starch, pectin, chitosan, chitosan succinamide, oligochitosan, chondroitin sulfate and other water-soluble polymers. However, the water-soluble polymer in the water-soluble material is not limited to specific materials. Polysaccharides such as dextran, dextrin, trehalose, and maltose can be used as biocompatible water-soluble materials. However, polysaccharides in water-soluble materials are not limited to specific materials.

In addition, the groove containing material 4 can contain a drug. Various proteins, pharmacologically active substances, cosmetic compositions and the like can be used as drugs. The type of delivery product to be delivered into the skin is selected according to the purpose. Examples of pharmacologically active substances include vaccines for influenza and the like, pain relievers for cancer patients, biologics, gene therapy agents, injections, oral agents, skin application preparations, and the like. In transdermal administration using the drug administration device 10, a delivery product is administered through 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 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 vaccines to children because it does not involve pain during administration. In addition, transdermal administration using the drug administration device 10 is suitable for administration of oral drugs to children who have difficulty swallowing oral drugs, because it is not necessary to drink the delivered product during administration.

A cosmetic composition is a composition that is used as a cosmetic or beauty product. Cosmetic compositions include, for example, moisturizing agents, colorants, fragrances, and physiologically active substances exhibiting cosmetic effects such as improving effects on wrinkles, acne, stretch marks, and the like, and improving effects on hair loss. If a fragrant material is used as the substance to be delivered, the groove-accommodating material 4 can be scented, so that the drug delivery device 10 suitable for cosmetics can be obtained.

It should be noted that the drug administration device 10 may contain a drug in the protrusion forming material. Moreover, when the protrusion forming material contains a drug, the groove-accommodating material 4 may not contain the drug. However, it is preferable that the groove-accommodating material 4 contains a drug in that the predetermined drug is administered intradermally.

[Manufacturing method of drug administration device]
A method for manufacturing a drug administration device according to an embodiment will be described.

First, a body consisting of a substrate 1 and projections 2 with grooves 3 is formed. The 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 techniques such as injection molding, etching, or the like, depending on the material forming the main body. In addition, it is also possible to produce an original plate of the main body by such a method, and then to produce an intaglio by reversing the unevenness of the original plate by a plating method or a molding method using resin, and then use the produced intaglio to reproduce the main body. can. A main body is formed by filling an intaglio with a solution of a protrusion-forming material for forming the protrusions 2 and the substrate 1, drying it, and then peeling it off from the intaglio.

In the main body of the present embodiment, since the grooves 3 are continuously open 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 through hole or a non-through hole that opens only to a hole is formed, the groove 3 can be easily formed, and the range of processing techniques that can form the groove 3 is widened. In particular, if the grooves 3 formed in each of the plurality of protrusions 2 are arranged in the same opening direction as in the drug administration device 10 according to the embodiment, the plurality of protrusions lined up in a line on the original plate can be formed by dicing. The groove 3 can be continuously formed in the portion 2 without changing the direction of the blade. Moreover, in such a configuration, there is no need 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 enhanced.

Subsequently, the grooves 3 formed in the protrusions 2 of the body are filled with a groove-accommodating material 4 . The channel-accommodating material 4 is filled in the form of a solution or dispersion. As a method for filling the groove-accommodating material 4, for example, a method is used in which the tip of the protrusion 2 is immersed in the liquid surface of the stored drug, and the groove-accommodating material 4 creeps up into the groove 3 by capillary action. Alternatively, the grooves 3 may be filled with the groove-accommodating material 4 by dripping the groove-accommodating material 4 toward the grooves 3 .

Here, in the main body of the present embodiment, the grooves 3 are opened continuously in the direction orthogonal to the first surface 1a and the direction along the first surface 1a. Therefore, compared to a configuration in which a housing portion such as a through hole or a non-through hole that opens only in a direction perpendicular to the first surface 1a is formed in the protrusion 2, the protrusion 2 can be opened from a direction other than the direction perpendicular to the first surface 1a. The groove-accommodating material 4 can enter the groove 3, and the air pushed out from the groove 3 by the groove-accommodating material 4 entering the groove 3 is released from a direction different from the direction in which the groove-accommodating material 4 enters. . Therefore, the groove-accommodating material 4 easily enters the groove 3 .

Further, in the configuration of the present embodiment, it is easy to secure a wide entrance of the groove-accommodating material 4 to the groove 3 . Since the projecting portion 2 is very small, in a configuration in which the accommodating portion is opened only in the direction orthogonal to the first surface 1a, the effect of the surface tension of the groove accommodating material 4 is increased, and the groove accommodating material 4 is not in contact with the groove. Hard to get into 3. In contrast, in the present embodiment, the entrance of the groove-accommodating material 4 to the groove 3 is widened, so that the contact area between the main body and the groove-accommodating material 4 at the entrance of the groove 3 is enlarged. The wettability of the main body with respect to the containing material 4 is improved, and the groove containing material 4 can easily enter the groove 3. - 特許庁

In the drug administration device 10 according to the embodiment, compared to a drug administration device that has a two-layer structure in the height direction of the protrusion and is formed of a water-soluble material, the substrate 1 and the protrusion 2 having the groove 3 The groove accommodating material 4 can be filled after the main body is formed, which facilitates manufacturing. Moreover, both the protrusion forming material and the groove accommodating material 4 are made of a water-soluble material. can be prevented.

In addition, in the drug administration device 10 according to the embodiment, since the protrusion forming material contains a water-soluble polymer, the strength of the protrusion 2 is sufficient compared to the case where a water-soluble low-molecular-weight material is used. can be

In addition, in the drug administration device 10 according to the embodiment, since the groove-accommodating material 4 contains a water-soluble polymer, the groove-accommodating material 4 fills the grooves 3 more than when a water-soluble low-molecular-weight material is used. The strength of the protrusions 2 thus formed can be made sufficient, and deformation of the protrusions 2 when filling the grooves 3 with the groove-accommodating material 4 can be suppressed.

In addition, in the pharmaceutical injection device 10 according to the embodiment, the grooves 3 of the protrusions 2 are aligned in one direction, so that the groove forming process can be simplified.

Further, the medicine administration device 10 according to the embodiment can be configured such that the water solubility of the protrusion forming material and the water solubility of the groove accommodating material 4 are different. This makes it possible to control the dissolution speed of the protrusion-forming material and the groove-accommodating material 4 into the skin.

In addition, the drug administration device 10 according to the embodiment can be configured such that the solubility of the protrusion forming material in water is higher than the solubility of the groove accommodation material 4 in water. As a result, the dissolution speed of the projection-forming material in the skin can be made faster than the dissolution speed of the groove-accommodating material 4, and the dissolution speed of the groove-accommodating material 4 in the skin can be made slower than the dissolution speed of the projection-forming material. can do. If the groove-accommodating material 4 contains a drug, it is effective when it is desired to slow down the permeation speed of the drug into the skin.

In addition, the drug administration device 10 according to the embodiment can be configured such that the water solubility of the protrusion forming material is lower than the water solubility of the groove accommodation material 4 . As a result, the dissolution speed of the groove-accommodating material 4 in the skin can be made faster than the dissolution speed of the protrusion-forming material, and the dissolution speed of the protrusion-forming material in the skin is equal to the dissolution speed of the groove-accommodating material 4 in the skin. can be slower than If the groove-accommodating material 4 contains a drug, it is effective when it is desired to increase the permeation speed of the drug into the skin.

The drug administration device and the manufacturing method thereof described above will be described using specific examples.

(Example)
[Preparation of the original plate of the main body]
Silicon was used as the material for forming the original plate of the main body consisting of the substrate and the projections having grooves, and by dicing, the projections having the shape shown in FIG. A master of the main body in which 25 pieces were arranged in a shape was produced. The length Lt of the protrusion was 1.2 mm, the width Dt of the protrusion was 300 μm, the length Lm from the first surface of the substrate to the bottom of the groove was 400 μm, and the width Dm of the groove was 100 μm. rice field.

[Production 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% heated to 90° C. was removed by hand to form an intaglio made of nickel.

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

[Medicine filling]
Next, hydroxypropyl cellulose (Wako Pure Chemical Industries) was dissolved in ethanol to prepare a solution of the groove-accommodating material. Evans blue was added to this solution to color it blue. Next, using a syringe with a needle, this solution was filled into the groove fixed to the dedicated holder. Next, it was allowed to stand at room temperature for 5 minutes until it dried and solidified, to obtain a medicine administration device in which the grooves were filled with the groove-accommodating material.

FIG. 2 and FIG. 3 show enlarged microscopic photographs of the protruding portion of the drug administration device obtained.

INDUSTRIAL APPLICABILITY The present invention can be suitably used as a drug administration device used for medical or cosmetic purposes.

REFERENCE SIGNS LIST 1 substrate 2 protrusion 3 groove 4 groove containing material 10 medicine administration device

Claims (4)

A drug administration device comprising a plurality of protrusions on one surface of a substrate,
the protrusion comprises a groove, a groove-receiving material disposed in the groove, and
The material for forming the protrusions contains a water-soluble material and a drug , and
the channel containing material comprises a water-soluble material and a drug ;
A medicine administration device , wherein the solubility in water of the material for forming the protrusions is higher than the solubility in water of the material for accommodating the grooves . 2. The medicine administration device according to claim 1, wherein said protrusion-forming material contains a water-soluble polymer. 3. The drug delivery device according to claim 1 or 2, wherein the groove-accommodating material contains a water-soluble polymer. 4. The drug administration device according to any one of claims 1 to 3, wherein the grooves of each of the protrusions are aligned in one direction.

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