WO2019087654A1 - Microneedle sheet and production method therefor - Google Patents

Abstract

The purpose of the present invention is to provide: a microneedle wherein an oil component is dispersedly held in a backing; and a production method therefor. This microneedle sheet (10) is provided with a sheetlike main body (20) and a plurality of microneedles (21) on one surface of the sheetlike main body (20). The plurality of microneedles (21) are arranged in a regular pattern such as a lattice, a honeycomb, or a houndstooth pattern on the sheetlike main body (20). The sheetlike main body (20) and the microneedle sheet (21) are integrally formed using the same material. The sheetlike main body (20) and the microneedles (21) contain, as constituent materials, a biosoluble backing (30) and an oil component (31) that is dispersedly held in the backing (30).

Description

Micro needle sheet and method of manufacturing the same

The present invention relates to a microneedle sheet for introducing a target substance into the horny layer of skin using a plurality of microneedles, and a method of manufacturing the same.

In recent years, microneedles have been increasingly used, for example, in the field of medicine and in the field of beauty and health. For example, a microneedle sheet composed of a plurality of microneedles is used to administer a drug from the body surface of the human body such as skin or mucous membrane. For example, in JP-A-2010-94414 (Patent Document 1), a microneedle is formed using a raw material solution in which an in-vivo soluble material such as dextran, chondroitin sulfate, hyaluronic acid and a drug are dissolved in water. There is disclosed a microneedle sheet in which a drug is held in a substrate having in-vivo solubility.

JP, 2010-94414, A

In the conventional microneedle sheet as described above and the method for producing the same, when the oily component is contained, the oily component is difficult to dissolve in water which is the solvent of the raw material liquid, and therefore the base material formed using this raw material liquid There was a possibility that unevenness occurred in the oil component in the medium, and the quality was not stable for each of a plurality of microneedles or for each lot. In addition, when the raw material liquid in which the oil component is emulsified is dried to form the microneedle, the emulsion balance may change in the drying process, and the oil component in the microneedle may not be uniform.

The present invention has been made to solve the problems as described above, and it is an object of the present invention to provide a microneedle having an oil component dispersed and held in a substrate and a method for producing the same.

In order to achieve the above object, according to a first aspect of the present invention, there is provided a sheet-like main body and a plurality of microneedles formed in the sheet-like main body, the microneedle comprising a base having in-vivo solubility, It is a microneedle sheet containing an oil component dispersed and held in a material.

With such a configuration, the oily component is uniformly held in the in-vivo soluble base material, so that microneedles of stable quality can be obtained.

In a second invention according to the first invention, the oily component is vanillyl butyl, oil-soluble vitamin C derivative, retinol and its derivative, astaxanthin, squalane, plant-derived component, ceramide, tocopherol, or two or more of them. It is a microneedle sheet which is a mixture.

With such a configuration, since these components used for cosmetic purposes are uniformly held in the in-vivo soluble base material, the microneedles dissolve in vivo to make these components uniform in the living body. Can be introduced.

A third invention is a microneedle sheet containing 0.5 to 1.0% by weight of vanillyl butyl as an oil component in the constitution of the first or second invention.

With this configuration, the amount of vanillyl butyl supplied to the living body can be limited, and the necessary and sufficient efficacy of vanillyl butyl can be obtained.

A fourth invention is the microneedle sheet according to any one of the first to third inventions, wherein the microneedle contains 0.1 to 0.2% by weight of an emulsifier.

According to this structure, the emulsifier promotes dispersion of the oil component, so that the oil component can be more uniformly held in the microneedle.

A fifth invention is the microneedle sheet according to any of the first to fourth inventions, wherein the sheet-like main body is the same material as the microneedles.

According to this structure, since the oily component is contained in the sheet-like main body, when the microneedle sheet is attached to the skin, the oily component to be used for cosmetic purposes from the surface of the skin by the sheet-like main body Can deliver.

A sixth invention is a method of manufacturing a microneedle sheet having a sheet-like main body and a plurality of microneedles formed in the sheet-like main body, wherein a biosoluble material and an oily component are added to a solvent, A micro-system comprising the steps of obtaining a raw material liquid in which an oily component is emulsified, filling the raw material liquid in a mold having a plurality of recesses corresponding to the shape of the microneedle, and drying the raw material liquid filled in the mold. It is a manufacturing method of a needle.

According to this structure, the sheet-like main body and the microneedle are formed using the raw material liquid in which the in-vivo soluble material and the oily component are emulsified, and thus the sheet-like main body formed of the in-soluble substrate. The oil component can be dispersed and held in the microneedle.

A seventh invention is a method of manufacturing a microneedle sheet having a sheet-like main body and a plurality of microneedles formed in the sheet-like main body, and adding a biodegradable material and an oil component to a solvent, A step of obtaining a raw material liquid in which an oily component is emulsified, a step of dropping the raw material liquid onto the sheet-like body, a step of bringing a pulling-up member into contact with the raw material liquid dropped onto the sheet-like body It is a manufacturing method of the microneedle sheet provided with the process of forming the raw material liquid dropped on the main body in the shape of a needle into a needle shape, and the step of drying the raw material liquid formed in the needle shape.

According to this structure, since the microneedle is formed using the raw material liquid in which the in-vivo soluble material and the oil-based component are emulsified, the oil-based component is formed in the micro-needle formed of the in-vivo soluble base material. Can be distributed and held.

The eighth invention is the method for producing a microneedle sheet according to the sixth or seventh invention, wherein the step of obtaining the raw material liquid further adds an emulsifying agent to a solvent.

According to this structure, the emulsification of the oil component in the raw material solution is promoted by the emulsifier contained in the raw material solution, so that a microneedle sheet in which the oil component is dispersed more uniformly can be obtained.

According to this invention, it is possible to obtain a microneedle sheet containing an oily component with improved quality.

(A) is a cross-sectional view of the microneedle sheet according to the first embodiment of the present invention, and (b) is a cross-sectional view of the microneedle sheet according to the second embodiment of the present invention. (A) to (c) is the schematic which showed the manufacturing process of the microneedle sheet | seat shown by Fig.1 (a). It is the schematic which showed the manufacturing process of the microneedle sheet which the (a) to (c) showed by FIG.1 (b).

Next, embodiments of the invention will be described with reference to the drawings.

Referring to FIG. 1A, the microneedle sheet 10 according to the first embodiment of the present invention includes a sheet-like main body 20 and a plurality of microneedles 21 on one side of the sheet-like main body 20. The plurality of microneedles 21 may be regularly arranged on the sheet-like main body 20 in, for example, a lattice, a honeycomb, or a zigzag, or may be irregularly arranged. Furthermore, the sheet-like main body 20 and the microneedles 21 are integrally configured using the same material.

The sheet-like main body 20 is for holding a plurality of microneedles 21. The plan view shape of the sheet-like main body 20 may be a shape according to the part to be attached, and for example, when used under the eyes, it may be a curved ball shape along a line under the eyes. When used, it may be in the form of a torus in which the central portion is hollow so as to surround the periphery of the mouth. Other shapes include a rectangular shape, a polygonal shape, or a circular shape. Further, the thickness of the sheet-like main body 20 is, for example, 20 μm or more and 500 μm or less, preferably 30 μm or more so that mechanical strength of the entire sheet can be secured and it can be flexibly deformed according to the shape of the skin. It can be 100 μm or less.

The microneedle 21 is inserted into a living body and is for introducing a drug into the living body. The shape of the microneedle 21 may be, for example, a conical shape, a truncated conical shape, or a Conyde shape. The Conyde shape is a shape in which the side of a conical or frusto-conical shape is curved inward. The height of the microneedles 21 (the protruding height of the microneedles 21 from the sheet-like main body 20) can be, for example, 10 μm or more and 500 μm or less, preferably 50 μm or more and 200 μm or less so that they can be inserted into a living body. The density of the microneedles 21 can be, for example, 100 needles / cm 2 or more and 500 needles / cm 2 or less.

The sheet-like main body 20 and the microneedles 21 contain a base material 30 having in-vivo solubility and an oil component 31 dispersed and held in the base material 30 as constituent materials. The sheet-like main body 20 and the microneedles 21 can be formed by drying the raw material liquid 50 containing these constituent materials in a solvent. Moreover, in order to promote the dispersion of the oily component 31 in the base material 30, an emulsifier 32 may be contained. Furthermore, other additives such as a base 30 and a stabilizer of the oil component 31 may be contained. As a stabilizer, glycerol can be used, for example.

As a solvent of the raw material liquid 50, for example, water, an organic solvent, or a mixed solvent thereof can be used.

For example, hyaluronic acid, chondroitin sulfate, pullulan, dextran, xanthan gum, tamarind gum, glycogen, chitin, chitosan, agarose, pectin, carboxyvinyl polymer and derivatives thereof may be used as the base material 30 having in vivo solubility. it can. In addition, these materials may be used alone or in combination of two or more.

As the oil component 31, for example, vanillyl butyl, oil-soluble vitamin C derivative, retinol and derivatives thereof, astaxanthin, squalane, plant-derived component, ceramide, tocopherol, or a mixture of two or more of them can be used. It is preferable to use 2 or more types of mixtures containing vanillyl butyl or vanillyl butyl among these oil components 31. When the microneedle sheet 10 using vanillyl butyl as the oily component 31 is attached to a site using the user, the user feels a sensation of thermal sensation due to the vanillyl butyl, so the component contained in the microneedle sheet 10 is supplied to the living body It can be confirmed that a certain feeling of use can be obtained. The content of vanillyl butyl in the microneedle sheet 10 is preferably 0.5 to 1.0% by weight. When the content of vanillyl butyl is 0.5% by weight or more, the efficacy of vanillyl butyl can be sufficiently obtained. On the other hand, when the content of vanillyl butyl is 1.0% by weight or less, the amount of vanillyl butyl can be made so strong that the effect is not too strong.

The emulsifier 32 can be used to promote the emulsification of the oil component 31 in the raw material liquid 50. As the material, for example, nonionic surfactants such as disodium lauryl dilauryl glutamate can be used. Further, the content of the emulsifier 32 in the microneedle sheet 10 is preferably 0.1% by weight to 0.2% by weight. If the content of the emulsifier 32 is within this range, the microneedle sheet 10 can not be uneven, the oil component 31 can be dispersed and held, and the microneedle sheet 10 without bubbles can be formed.

Next, a method of manufacturing the microneedle sheet 10 shown in FIG. 1A will be described.

The preparation process of the raw material liquid 50 is shown. Sodium hyaluronate as the base material 30, vanillyl butyl as the oily component 31, and disodium lauryl glutamate as the emulsifier 32 are added into the solvent. Next, the solution is mixed using a homomixer to obtain the raw material liquid 50 in which the oil component 31 is emulsified.

Next, referring to FIG. 2A, a mold 80 having a plurality of recesses 81 corresponding to the shape of the microneedles 21 is prepared. Next, referring to FIG. 2 (b), the raw material liquid 50 is filled in the mold 80. Next, it is dried until the raw material liquid 50 solidifies. Next, referring to FIG. 2C, the dried microneedle sheet 10 is taken out of the mold 80 to manufacture the microneedle sheet 10 shown in FIG. 1A.

As mentioned above, the microneedle sheet 10 manufactured as mentioned above uses the raw material liquid 50 which the base material 30 and the oil component 31 which are in-vivo soluble materials emulsify, and is using the sheet-like main body 20 and the microneedle 21. In order to form, it becomes the microneedle sheet 10 in which the oil component 31 is dispersed and held in the sheet-like main body 20 and the microneedles 21 formed by the base material 30 having in-vivo solubility.

Next, a second embodiment of the present invention will be described with reference to the drawings, focusing on differences from the previous embodiment.

Referring to FIG. 1 (b), the microneedle sheet 10 according to the second embodiment of the present invention has a base 30 with microneedles 21 having in-vivo solubility and an oil component 31 dispersed and held in the base 30. Are similar to the first embodiment in that they are configured by On the other hand, the difference is that the sheet-like main body 20 and the microneedles 21 are made of different materials.

The sheet-like main body 20 may be the same material as the base material 30 used for the sheet-like main body 20 of the first embodiment, as long as the material is different from the microneedles 21, and another material having flexibility. May be used. As a material, paper, a resin film, and a nonwoven fabric are mentioned, for example.

Other materials may be the same as in the first embodiment of the present invention.

Next, the manufacturing method of the microneedle sheet | seat 10 shown by FIG.1 (b) is shown.

First, in the same manner as in the first embodiment of the present invention, sodium hyaluronate as the base material 30, vanillyl butyl as the oil component 31, and dilauroyl glutamate sodium lysine as the emulsifier 32 are contained in the solvent, and the oil component 31 is emulsified. The raw material liquid 50 is prepared. Next, referring to FIG. 3A, the raw material liquid 50 is dropped onto the sheet-like main body 20. At that time, the raw material liquid 50 is dropped at intervals corresponding to the microneedles 21 finally obtained. Next, referring to FIG. 3B, a cylindrical or prismatic pull-up member 60 is brought into contact with the droplets of the raw material liquid 50 dropped onto the sheet-like main body 20. Next, referring to FIG. 3C, the lifting member 60 is pulled up to form droplets of the raw material liquid 50 in a needle shape. Next, the microneedle sheet 10 shown in FIG. 1B is manufactured by drying until the raw material liquid 50 is solidified.

From the above, the microneedle sheet 10 manufactured as described above is formed on the sheet-like main body 20 by using the raw material liquid 50 in which the base material 30 and the oil component 31 which are in-vivo soluble materials are emulsified. In order to form the microneedle sheet 10, the oil component 31 is dispersed and held in the microneedles 21 formed by the base material 30 having in-vivo solubility.

Referring to Table 1, Examples 1 to 6 and Comparative Examples 1 to 8 of the microneedle sheet 10 manufactured by the manufacturing method according to the first embodiment are shown. The microneedle sheet 10 of each example and comparative example uses sodium hyaluronate as the substrate 30, and 0.5 wt% or 1.0 wt% of vanillyl butyl as the oil component 31 in the substrate 30 as the emulsifier 32. It contains 0.05% by weight to 0.37% by weight of lysine sodium dilauroyl glutamate.

About the microneedle sheet 10 shown in Example 1 to Example 6 and Comparative Example 1 to Comparative Example 8, the result of the appearance evaluation performed to investigate the optimum range as the content of the emulsifier 32 is shown. The appearance evaluation was performed on the presence or absence of unevenness and the presence or absence of air bubbles. Unevenness in the microneedle sheet 10 is not preferable because it indicates that the oil component 31 is not dispersed. Moreover, when there are air bubbles in the microneedle sheet 10, it is not preferable in that the air bubbles impair the appearance of the product and that the microneedles 21 are not formed in the air bubbles.

First, the appearance was evaluated for the presence or absence of unevenness. As a result, for Examples 1 to 6 and Comparative Examples 2 to 4 and Comparative Examples 6 to 8 in which the content of the emulsifier 32 is in the range of 0.08% by weight to 0.37% by weight, An even microneedle sheet 10 was obtained. On the other hand, in Comparative Example 1 and Comparative Example 5 in which the content of the emulsifier 32 was 0.05% by weight, unevenness was observed in the microneedle sheet 10.

Next, appearance evaluation was performed about the presence or absence of air bubbles. As a result, in Examples 1 to 6 in which the content of the emulsifier 32 was in the range of 0.10% by weight to 0.20% by weight, microneedles without bubbles were obtained. On the other hand, in Comparative Example 1 to Comparative Example 8 in which the content of the emulsifier 32 is 0.05% by weight, 0.08% by weight, 0.30% by weight, and 0.37% by weight, the microneedle sheet 10 contains bubbles. The existence was confirmed.

From the above, the result that the content of the emulsifier 32 is preferably 0.10% by weight to 0.20% by weight was obtained. By setting the content of the emulsifier 32 within this range, it is possible to obtain the microneedle sheet 10 without unevenness and bubbles.

In the first embodiment of the present invention, the sheet-like main body 20 and the microneedles 21 are integrally formed using the same material, but when the microneedle sheet 10 is used, the oily component 31 is supplied into the living body If possible, different material is filled in a portion corresponding to the sheet-like main body 20 of the mold 80 and a portion corresponding to the micro-needle 21, and the sheet-like main body 20 and the micro needle 21 are made of different materials It is also good.

In the first embodiment of the present invention, the microneedle sheet 10 is removed from the mold 80 in the manufacturing process of the microneedle sheet 10, but when the microneedle sheet 10 is not immediately used, the microneedle sheet 10 is used. The mold 80 may be used as a protective sheet for protecting the microneedle sheet 10 without taking it out of the mold 80.

Furthermore, in the second embodiment of the present invention, although the raw material liquid 50 is formed into a needle shape by the pulling-up member 60, the microneedle 21 formed by drying the raw material liquid 50 is inserted in the living body If it is, the raw material liquid 50 may be formed into a frusto-conical shape or another shape such as a Conyde shape by the lifting member 60.

Furthermore, in the second embodiment of the present invention, the droplet of the raw material liquid 50 is formed in a needle shape using the cylindrical or prismatic pulling-up member 60, but using the flat plate-like pulling-up member 60 A plurality of droplets may be simultaneously formed in a needle shape.

Furthermore, in the above embodiments of the present invention, the emulsification of the raw material liquid 50 is promoted using a homomixer in order to obtain the emulsified raw material liquid 50, but in the case where the raw material liquid 50 is easily emulsified , It is not necessary to use a homomixer.

DESCRIPTION OF SYMBOLS 10 microneedle sheet 20 sheet-like main body 21 microneedle 30 base material 31 oil-based component 32 emulsifier 50 raw material liquid 60 pulling-up member 80 type 81 recessed part

Claims (8)

Sheet-like body,
And a plurality of microneedles formed on the sheet-like body,
The microneedle is a microneedle sheet containing a substrate having in-vivo solubility and an oily component dispersed and held in the substrate. The microparticle according to claim 1, wherein the oily component is vanillyl butyl, an oil-soluble vitamin C derivative, retinol and a derivative thereof, astaxanthin, squalane, a plant-derived component, ceramide, tocopherol, or a mixture of two or more thereof. Needle seat. The microneedle sheet according to claim 1 or 2, wherein 0.5 to 1.0% by weight of vanillyl butyl is contained as the oily component. The microneedle sheet according to any one of claims 1 to 3, wherein the microneedle contains an emulsifier at 0.1 to 0.2% by weight. The microneedle sheet according to any one of claims 1 to 4, wherein the sheet-like main body is the same material as the microneedles. A method of manufacturing a microneedle sheet, comprising: a sheet-like main body; and a plurality of microneedles formed on the sheet-like main body,
Adding a bio-soluble material and an oily component to a solvent to obtain a raw material liquid in which the oily component is emulsified;
Filling the raw material liquid in a mold having a plurality of recesses corresponding to the shape of the microneedles;
And d) drying the raw material liquid filled in the mold. A method of manufacturing a microneedle sheet, comprising: a sheet-like main body; and a plurality of microneedles formed on the sheet-like main body,
Adding a bio-soluble material and an oily component to a solvent to obtain a raw material liquid in which the oily component is emulsified;
Dropping the raw material solution onto the sheet-like body;
Bringing a pull-up member into contact with the raw material liquid dropped onto the sheet-like main body;
Forming the needle-shaped raw material liquid dropped into the sheet-like main body by pulling up the pulling-up member;
And d) drying the raw material liquid formed into a needle shape. The method for producing a microneedle sheet according to claim 6 or 7, wherein the step of obtaining the raw material liquid further adds an emulsifier into a solvent.

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