TW202026030A - Microneedle sheet and method for manufacturing the same including a sheet-like body and a plurality of microneedles on one side of the sheet-like body - Google Patents

Abstract

An object of the present invention is to provide microneedles for allowing oily components to be dispersed and held in a substrate, and a method for manufacturing the same. The microneedle sheet 10 includes a sheet-like body 20 and a plurality of microneedles 21 on one side of the sheet-like body 20. The plurality of the microneedles 21 are regularly arranged on the sheet-like body 20, for example, in a lattice shape, a honeycomb shape, or a zigzag shape. In addition, the sheet-like body 20 and the microneedle sheet 10 are integrally constructed by using the same material. The sheet-like body 20 and the microneedles 21 contain a substrate 30 that is soluble in an organism and oily components 31 that are dispersed and held in the substrate 30 as constituent materials.

Description

Microneedle sheet and manufacturing method thereof

The present invention relates to a microneedle sheet used to introduce a target substance into the stratum corneum of the skin and a method of manufacturing the same.

In recent years, the use of microneedles has increased in medical-related fields and beauty and health-related fields. For example, a microneedle sheet composed of a large number of microneedles has been used to administer drugs from the surface of the human body such as skin and mucous membranes. For example, Japanese Patent Application Laid-Open No. 2010-94414 (Patent Document 1) discloses a microneedle sheet in which a drug is contained in a base material that has biodissolvability. The microneedle sheet is made of dextran, chondroitin sulfate, and hyaluronic acid. It is obtained by forming a microneedle with a raw material solution in which an acid and other biologically soluble materials are dissolved in water. (Prior technical literature) (Patent Document)

Patent Document 1: Japanese Patent Application Publication No. 2010-94414

(Problems to be solved by the invention)

As in the above-mentioned conventional microneedle sheet and its manufacturing method, when the microneedle sheet contains oily components, the oily components are not easily dissolved in the solvent of the raw material liquid, that is, water. Oily ingredients will be uneven, and the quality of most microneedles may be unstable one by one or batch by batch. In addition, when the raw material liquid in which the oily component has been emulsified is dried to form microneedles, the balance of emulsification may change during the drying process and the oily components in the microneedles may be uneven.

In order to solve the above-mentioned problems, the present invention aims to provide a microneedle in which an oily component is dispersed and held in a base material and a method for manufacturing the same. (The way to solve the problem)

In order to achieve the above-mentioned object, the first invention is a microneedle sheet having a sheet-like body and a plurality of microneedles formed in the sheet-like body. The microneedles contain a base material that is soluble in the body and an oily substance dispersed in the base material. ingredient.

If it is constructed in this way, the oily component will be uniformly held in the base material with biodissolvability, so it will become a microneedle with stable quality.

The second invention is the microneedle sheet according to the first invention, wherein the oily components are vanillyl butyl ether, oil-soluble vitamin C derivatives, retinol and its derivatives, reduced astaxanthin, keratin Squalane, plant-derived ingredients, ceramide, tocopherol, or a mixture of two or more of these.

If constructed in this way, the components used for cosmetic purposes will be uniformly maintained in the base material with biological solubility, so the microneedles can be dissolved in the organism to uniformly introduce the components into the organism. in vivo.

The third invention is the microneedle sheet according to the first or second invention, which contains 0.5 to 1.0% by weight of vanillyl butyl ether as an oily component.

With this configuration, the amount of vanillyl butyl ether supplied to the living body can be restricted, so that the necessary and sufficient performance of vanillyl butyl ether can be obtained.

The fourth invention is the microneedle sheet according to any one of the first to third inventions, wherein the microneedles contain 0.1 to 0.2% by weight of emulsifier.

With such a configuration, the emulsifier promotes the dispersion of the oily component, so the oily component can be held in the microneedles more uniformly.

The fifth invention is the microneedle sheet according to any one of the first to fourth inventions, wherein the sheet-shaped body and the microneedles are made of the same material.

With such a configuration, the sheet-like body contains oily ingredients, so when the microneedle sheet is applied to the skin, the sheet-like body can make oily ingredients used for cosmetic purposes reach the skin from the surface of the skin.

The sixth invention is a method for manufacturing microneedles. The method for manufacturing a microneedle sheet with a sheet-like body and a large number of microneedles formed on the sheet-like body includes the following steps: adding biologically soluble materials and oily components to In the solvent, a raw material liquid in which oily components have been emulsified is obtained; the raw material liquid is filled into a mold with a large number of recesses corresponding to the shape of the microneedles; and the raw material liquid filled in the mold is dried.

With such a configuration, the sheet-shaped body and microneedles are formed using a raw material liquid emulsified from a biologically soluble material and an oily component, so that the oily component can be dispersed and maintained in a sheet formed of a substrate with biological solubility In the body and the microneedle.

The seventh invention is a method for manufacturing a microneedle sheet. The method for manufacturing a microneedle sheet having a sheet-like body and a large number of microneedles formed on the sheet-like body includes the following steps: combining the soluble material in the body with the oily component Add it to the solvent to obtain the raw material liquid with emulsified oily ingredients; drop the raw material liquid on the sheet body; make the raw material liquid dripped on the sheet body contact the lifting member; lift the lifting member to drop it on the sheet The raw material liquid of the shaped body is formed into a needle shape; and the needle-shaped raw material liquid is dried.

With such a configuration, a raw material liquid obtained by emulsifying an in vivo soluble material and an oily component is used to form the microneedles, so that the oily component can be dispersed and held in the microneedles formed by the base material having in vivo solubility.

The eighth invention is the manufacturing method of the microneedle sheet according to the sixth or seventh invention, wherein the step of obtaining the raw material liquid is to add an emulsifier to the solvent.

With such a configuration, the emulsifier contained in the raw material liquid promotes the emulsification of the oily component in the raw material liquid, so that a microneedle sheet in which the oily component is more uniformly dispersed can be obtained. (Effect of Invention)

According to the present invention, a microneedle sheet containing oily ingredients with better quality can be obtained.

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

1( a ), the microneedle sheet 10 according to the first embodiment of the present invention includes a sheet-like body 20 and a plurality of microneedles 21 on one side of the sheet-like body 20. The plurality of microneedles 21 can be regularly arranged on the sheet-shaped body 20 in a grid, honeycomb, or zigzag shape, or can also be arranged irregularly. In addition, the sheet-shaped body 20 and the microneedle 21 may be formed integrally using the same material.

The sheet-shaped body 20 is used to hold a plurality of microneedles 21. The top view shape of the sheet-like body 20 can be any shape that fits the attachment part. For example, when used under the eyes, it can be made into a curved jade shape that curves along the line under the eyes and used in the mouth. At this time, it can be made into a circular ring shape with a hollow center part so as to surround the periphery of the mouth. Other shapes include rectangular shapes, polygonal shapes, or circular shapes. In addition, the thickness of the sheet-like body 20 can be set to, for example, 20 μm or more and 500 μm or less, preferably 30 μm or more and 100 μm or less, so that the overall mechanical strength of the sheet can be ensured and it can be flexibly deformed according to the shape of the skin.

The microneedle 21 is used for insertion into a living body, for those who introduce a drug into the living body. The shape of the microneedle 21 is, for example, a cone shape, a truncated cone shape, or a stratified volcanic shape. In addition, the stratified volcanic shape represents a shape in which the side surface of a cone or truncated cone is curved inward. The height of the microneedle 21 (the height at which the microneedle 21 protrudes from the sheet-like body 20) can be set to, for example, 10 μm or more and 500 μm or less, preferably 50 μm or more and 200 μm or less, so that it can be inserted into a living body. The density of the microneedles 21 may be, for example: 100 / cm ² or more 500 / cm ² or less.

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

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

The substrate 30 with biological solubility, for example: hyaluronic acid, chondroitin sulfate, pullulan, dextran, trixian gum, tamarind gum, glycogen, chitin, chitosan , Agarose, pectin, carboxyvinyl polymer and their derivatives. In addition, these materials may be used alone, or two or more of them may be mixed.

As the oily ingredient 31, for example, vanillyl butyl ether, oil-soluble vitamin C derivatives, retinol and its derivatives, astaxanthin, squalane, plant-derived ingredients, ceramide, Tocopherol, or a mixture of two or more of these. Among these oily components 31, it is preferable to use vanillyl butyl ether or a mixture containing two or more types of vanillyl butyl ether. When the microneedle sheet 10 using vanillyl butyl ether as the oily component 31 is attached to the site of use, the user will feel a warm stimulus due to the vanillyl butyl ether, so it can be confirmed that the microneedle sheet 10 contains The ingredients have been supplied to the body, and a certain sense of use can be obtained. In addition, the content of vanillyl butyl ether in the microneedle sheet 10 is preferably 0.5 to 1.0% by weight. If the content of vanillyl butyl ether is 0.5% by weight or more, the performance of vanillyl butyl ether can be fully obtained. On the other hand, if the content of vanillyl butyl ether is 1.0% by weight or less, the effectiveness of vanillyl butyl ether will not be too strong.

The emulsifier 32 can be used to promote the emulsification of the oily component 31 in the raw material liquid 50. As the material, for example, nonionic surfactants such as dilaurin glutamic acid sodium lysine can be used. Moreover, 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 will not have spots, the oily component 31 can be dispersed and maintained, and a bubble-free microneedle sheet 10 can be formed.

Then, the manufacturing method of the microneedle sheet 10 shown in FIG. 1(a) is disclosed.

The preparation steps of the raw material liquid 50 are shown. The sodium hyaluronate of the base material 30, the vanillyl butyl ether of the oily component 31, and the sodium dilauroglutamate lysine of the emulsifier 32 are added to the solvent. Then, the solution is mixed using a homomixer to obtain a raw material liquid 50 in which the oily component 31 has been emulsified.

Then, referring to FIG. 2(a), a mold 80 having a plurality of recesses 81 corresponding to the shape of the microneedle 21 is prepared. Then, referring to FIG. 2( b ), the raw material liquid 50 is filled in the mold 80. Then, the raw material liquid 50 is dried until solidified. Then, referring to FIG. 2(c), the dried microneedle sheet 10 is taken out from the mold 80 to manufacture the microneedle sheet 10 shown in FIG. 1(a).

From the above, the microneedle sheet 10 manufactured as described above uses the base material 30 of a biologically soluble material and the raw material liquid 50 in which the oily component 31 is emulsified to form the sheet-like body 20 and the microneedle 21, so it becomes an oily component 31. The microneedle sheet 10 is dispersed and held in the sheet-shaped body 20 and the microneedles 21 formed by using a substrate 30 having in vivo solubility.

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

1(b), in the microneedle sheet 10 according to the second embodiment of the present invention, the microneedles 21 are composed of a base material 30 that is soluble in the body and an oily component 31 dispersed and held in the base material 30 This point is the same as the first embodiment. On the other hand, the sheet-like body 20 is not made of the same material as the microneedle 21, which is different.

As long as the sheet-like body 20 is not the same material as the microneedles 21, the same material as the base material 30 used in the sheet-like body 20 of the first embodiment may be used, or other materials with flexibility may be used. Materials, such as: paper, resin film, and non-woven fabric.

For other materials, the same materials as in the first embodiment of the present invention can be used.

Then, the manufacturing method of the microneedle sheet 10 shown in FIG. 1(b) is disclosed.

First, in the same manner as in the first embodiment of the present invention, prepare the sodium hyaluronate of the base material 30, the vanillyl butyl ether of the oily component 31, and the dilauric glutamine lysine of the emulsifier 32. The raw material liquid 50 in which sodium is contained in the solvent and the oily component 31 is emulsified. Then, referring to FIG. 3( a ), the raw material liquid 50 is dropped on the sheet body 20. At this time, the raw material liquid 50 is dropped at intervals corresponding to the microneedles 21 finally obtained. Then, referring to FIG. 3(b), the droplets of the raw material liquid 50 dropped on the sheet-shaped body 20 are contacted with the cylindrical or angular column-shaped lifting member 60 respectively. Then, referring to FIG. 3(c), the lifting member 60 is lifted to form the droplets of the raw material liquid 50 into needle shapes. Then, the raw material liquid 50 is dried until solidified, so that the microneedle sheet 10 shown in FIG. 1(b) is manufactured.

From the above, the microneedle sheet 10 manufactured as described above uses the base material 30 which is a biologically soluble material and the raw material liquid 50 in which the oily component 31 has been emulsified to form the microneedles 21 on the sheet body 20. Therefore, This becomes the microneedle sheet 10 in which the oily component 31 is dispersed and held in the microneedles 21 formed of the base material 30 having in vivo solubility.

Referring to Table 1, Examples 1 to 6 and Comparative Example 1 to Comparative Example 8 of the microneedle sheet 10 manufactured by the manufacturing method of the first embodiment are disclosed. The microneedle sheet 10 of each embodiment and comparative example uses sodium hyaluronate as the base material 30, and the base material 30 contains 0.5% by weight or 1.0% by weight of vanillyl butyl ether as the oily component 31, 0.05% by weight to 0.37% by weight as an emulsifier 32 bis sodium lauric glutamate lysine.

[Table 1] Vanillyl Butyl Ether (wt%) Dilaurin Glutamate Sodium Lysine (wt%) Spots Whether there are bubbles Example 1 0.5 0.10 no no Example 2 0.5 0.18 no no Example 3 0.5 0.20 no no Example 4 1.0 0.10 no no Example 5 1.0 0.18 no no Example 6 1.0 0.20 no no Comparative example 1 0.5 0.05 Have Have Comparative example 2 0.5 0.08 no Have Comparative example 3 0.5 0.30 no Have Comparative example 4 0.5 0.37 no Have Comparative example 5 1.0 0.05 Have Have Comparative example 6 1.0 0.08 no Have Comparative example 7 1.0 0.30 no Have Comparative example 8 1.0 0.37 no Have

For the microneedle sheet 10 shown in Example 1 to Example 6 and Comparative Example 1 to Comparative Example 8, the results of the appearance evaluation performed to investigate the optimum range of the content of the emulsifier 32 are disclosed. Appearance evaluation is based on whether it is uniform and whether there are bubbles. When the microneedle sheet 10 has spots, it means that the oily component 31 is not dispersed, which is not ideal. In addition, when the microneedle sheet 10 has bubbles, it is undesirable for the viewpoint that the bubbles cause damage to the appearance of the product, and that the microneedles 21 are not formed in the portion where the bubbles exist.

First, the appearance is evaluated for the presence or absence of spots. As a result, for Examples 1 to 6, Comparative Example 2 to Comparative Example 4, and Comparative Example 6 to Comparative Example 8 in which the content of the emulsifier 32 was in the range of 0.08% by weight to 0.37% by weight, a spotless microparticle was obtained. Needle sheet 10. 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, it was confirmed that the microneedle sheet 10 had spots.

Then, the appearance was evaluated for the presence or absence of bubbles. As a result, regarding 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 Examples 1 to 8 in which the content of the emulsifier 32 was 0.05% by weight, 0.08% by weight, 0.30% by weight, and 0.37% by weight, it was confirmed that the microneedle sheet 10 had bubbles.

From the above, in terms of the content of the emulsifier 32, 0.10% by weight to 0.20% by weight is preferable. With the content of the emulsifier 32 within this range, a microneedle sheet 10 without spots and bubbles can be obtained.

In addition, in the first embodiment of the present invention, the sheet-like body 20 and the microneedle 21 are integrally constructed using the same material, but when the microneedle sheet 10 is used, if the oily component 31 can be supplied to the living body, it may be The part of the sheet-shaped body 20 of the mold 80 and the part of the micro-needle 21 are filled with different materials, and the sheet-shaped body 20 and the microneedle 21 are made of different materials.

Also, in the first embodiment of the present invention, if the microneedle sheet 10 is taken out from the mold 80 in the manufacturing step of the microneedle sheet 10 but the microneedle sheet 10 is not used immediately, the microneedle sheet 10 may not be removed from The mold 80 is taken out and the mold 80 is used as a protective sheet for protecting the microneedle sheet 10.

In the second embodiment of the present invention, the raw material liquid 50 is formed into a needle shape by the pulling member 60, but if the microneedle 21 formed by drying the raw material liquid 50 is inserted into a living body, it can also be used The lifting member 60 forms the raw material liquid 50 into other shapes such as a truncated cone shape or a stratified volcanic shape.

In addition, in the second embodiment of the present invention, a cylindrical or angular column-shaped lifting member 60 is used to form the droplets of the raw material liquid 50 into needles, but a flat-plate lifting member 60 may be used to simultaneously transfer most liquid The drop is formed into a needle shape.

In addition, in each of the above embodiments of the present invention, in order to obtain the emulsified raw material liquid 50, a homomixer is used to promote the emulsification of the raw material liquid 50, but when the raw material liquid 50 is easily emulsified, the homomixer may not be used.

10: Microneedle sheet 20: sheet body 21: Microneedle 30: Substrate 31: Oily ingredients 32: emulsifier 50: Raw material liquid 60: Lifting member 80: Mode 81: recess

In FIG. 1, (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. In FIG. 2, (a) to (c) are schematic diagrams showing the manufacturing steps of the microneedle sheet shown in FIG. 1(a). In Fig. 3, (a) to (c) are schematic diagrams showing the manufacturing steps of the microneedle sheet shown in Fig. 1(b).

10: Microneedle sheet

20: sheet body

21: Microneedle

30: Substrate

31: Oily ingredients

Claims (8)

A microneedle sheet is provided with a sheet-like body and a plurality of microneedles formed on the sheet-like body. The microneedles contain a substrate with biodissolvability and oily components dispersed and retained in the substrate. For example, the microneedle sheet of item 1 in the scope of patent application, wherein the oily ingredients are vanillyl butyl ether, oil-soluble vitamin C derivatives, retinol and its derivatives, reduced astaxanthin (astaxanthin), dogfish Alkanes, plant-derived ingredients, ceramide, tocopherol, or a mixture of two or more of these. For example, the microneedle sheet of item 1 or 2 of the scope of patent application contains 0.5 to 1.0% by weight of vanillyl butyl ether as the oily component. For example, the microneedle sheet of item 1 or 2 of the scope of patent application, wherein the microneedle contains 0.1 to 0.2% by weight of emulsifier. For example, the microneedle sheet of item 1 or 2 in the scope of patent application, wherein the sheet-shaped body and the microneedle are made of the same material. A method for manufacturing microneedles is a method for manufacturing a microneedle sheet having a sheet-like body and a large number of microneedles formed on the sheet-like body. The method includes the following steps: adding biologically soluble materials and oily components to a solvent, Obtain a raw material liquid in which oily ingredients have been emulsified; fill the raw material liquid in a mold having many recesses corresponding to the shape of the microneedles; and dry the raw material liquid filled in the mold. A method for manufacturing a microneedle sheet is a method for manufacturing a microneedle sheet having a sheet-like body and a plurality of microneedles formed on the sheet-like body, and includes the following steps: Adding the soluble material and oily components in the body to the solvent to obtain the raw material liquid with emulsified oily components; dripping the raw material liquid on the sheet body; contacting and pulling the raw material liquid dripped on the sheet body Member; the lifting member is lifted to form the raw material liquid dropped on the sheet-shaped body into a needle shape; and the raw material liquid formed into a needle shape is dried. For example, the method for manufacturing a microneedle sheet according to item 6 or 7 of the scope of patent application, wherein the step of obtaining the raw material liquid is to add an emulsifier to the solvent.

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