Dissolved micro-needle formulation

Abstract

To provide a soluble micro-needle formulation comprising niacin and a water-soluble polymer, which is comprehensively superior in terms of formability, pain, solubility, tenseness, and elasticity.SOLUTION: Provided is a soluble micro-needle formulation comprising niacin and a water-soluble polymer.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a dissolving microneedle preparation containing niacin and a water-soluble polymer.

Background Art

[0002] Conventionally, in order to exert components having a cosmetic effect or a pharmacological effect subcutaneously, external preparations containing cosmetic components or medicinal components have been used. Such external preparations are known in liquid, cream, pack, etc. forms, and by applying or sticking these locally, the cosmetic components or medicinal components are transdermally absorbed, and the expected cosmetic effect and pharmacological effect are exerted subcutaneously.

[0003] However, such externally applied preparations in the form of being applied or stuck have drawbacks that during use, before the cosmetic components or medicinal components are transdermally absorbed, they disappear or fall off due to sweating, washing, other external pressures, evaporation, etc. Further, these external preparations have a drawback that due to the skin barrier function, the cosmetic components or medicinal components are not sufficiently transdermally absorbed, and the expected cosmetic effect and pharmacological effect cannot be exerted. In particular, when the cosmetic components or medicinal components are high molecular compounds, they are difficult to be transdermally absorbed, and it is difficult to exert the cosmetic effect and pharmacological effect.

[0004] In addition, skin problems such as dry skin, wrinkles, sagging, firmness, loss of elasticity, and dullness are factors that impair the beauty of the skin, and thus are a source of concern for women who care about beauty. Therefore, for the purpose of improving these skin problems, various skin moisturizers and agents for improving wrinkles, sagging, firmness, elasticity, or dullness have been developed so far. For example, in recent years, methods such as injecting botulinum toxin and injecting collagen have attracted attention as agents for improving wrinkles, sagging, firmness, and elasticity. Injecting botulinum toxin and injecting collagen can utilize injections using needles as methods for causing beauty components and medicinal components to exert their effects subcutaneously, rather than topical agents applied or affixed locally. However, injecting botulinum toxin and injecting collagen cause pain and thus cause discomfort to users. In addition, injections have drawbacks such as causing pain, bleeding, needle marks remaining, and swelling with an increase in the number of uses. Furthermore, injections often need to be performed by experts such as doctors, and it has been difficult for users to use them as appropriate.

[0005] In recent years, transdermal injection of beauty components and medicinal components using fine needle-like protrusions called microneedles has attracted attention. Transdermal injection using microneedles can be achieved by attaching microneedles containing beauty components and medicinal components to the skin, puncturing the microneedles into relatively shallow layers of the skin such as the stratum corneum and dermis, and dissolving the microneedles subcutaneously to allow transdermal absorption of the beauty components and medicinal components. In addition, transdermal injection using microneedles reduces pain compared to normal injections, and furthermore, it does not need to be performed by an expert, so users can use it as appropriate.

[0006] Micro needles are required to have an optimal design according to skin symptoms and diseases, and micro needle preparations used as topical agents are required not to break when piercing the stratum corneum or dermis of the skin. On the other hand, micro needles are also required to have flexibility so as not to cause pain, bleeding, or swelling at the local site where they are pierced into the stratum corneum or dermis of the skin. Therefore, it is necessary for micro needle preparations to have both strength enough to withstand piercing into the stratum corneum or dermis of the skin and flexibility that does not cause a feeling of pain or the like.

[0007] In addition, micro needle preparations used as topical agents are required to have solubility or biodegradability under the skin after piercing the stratum corneum or dermis of the skin.

[0008] However, since it is difficult to mold a micro needle preparation that combines such strength and flexibility and also has solubility, there have been only limited reports on the constituent components of micro needle preparations so far. Examples of micro needle preparations that combine strength, flexibility, and solubility include, for example, micro needles (Patent Document 1) mainly made of a mixture of maltose and dextran, and micro needles (Patent Document 2) mainly made of a mixture of a water-soluble polymer and one or more saccharides selected from the group consisting of glucose, fructose, sucrose, lactose, and trehalose. However, the micro needles described in Patent Document 1 need to be heated to a temperature above the melting point of maltose after mixing maltose and a physiologically active substance and molded into the shape of a needle, and it is difficult to use a physiologically active substance with poor thermal stability. Also, in the invention of Patent Document 2, although the dissolution rate of the micro needles can be promoted, the pain and discomfort when piercing the micro needles are not considered.

Prior Art Documents

Patent Documents

[0009]

Patent Document 1

Patent Document 2

SUMMARY OF THE INVENTION

PROBLEMS TO BE SOLVED BY THE INVENTION

[0010] An object of the present invention is to provide a novel micro-needle preparation that has never existed before. More specifically, in view of the above circumstances, an object of the present invention is to provide a dissolving micro-needle preparation having moldability that combines strength, flexibility, and solubility. Further, in view of the above circumstances, an object of the present invention is to provide a dissolving micro-needle preparation having excellent solubility. Further, in view of the above circumstances, an object of the present invention is to provide a dissolving micro-needle preparation having excellent cosmetic effects for improving skin moisturization, wrinkles, sagging, firmness, elasticity, or dullness.

MEANS FOR SOLVING THE PROBLEMS

[0011] The inventors of the present invention conducted intensive studies to solve the above problems. Surprisingly, by containing niacin and a water-soluble polymer, compared with the case of using only the water-soluble polymer, it has excellent moldability, combines strength, flexibility, and solubility, and a dissolving micro-needle preparation having excellent cosmetic effects can be produced, and it has been found that a dissolving micro-needle preparation with reduced pain during and after puncture can be produced. Further, by containing a polyhydric alcohol in addition to niacin and a water-soluble polymer, it has been found that a dissolving micro-needle preparation having even more excellent moldability, solubility, and cosmetic effects, and further reduced pain during and after puncture can be produced.

[0012] That is, the present invention is as follows. [1] A dissolving micro-needle preparation containing niacin and a water-soluble polymer. [2] A dissolving micro-needle preparation containing niacinamide and a water-soluble polymer. [3] A dissolving micro-needle preparation containing niacin and hyaluronic acid having an average molecular weight of 10,000 or more or a salt thereof. [4] A dissolving micro-needle preparation containing niacin, a water-soluble polymer, and a polyhydric alcohol. [5] A dissolving micro-needle preparation containing niacin, a water-soluble polymer, and at least one polyhydric alcohol selected from glycerin or 1,3-butylene glycol. [6] A dissolving micro-needle preparation containing niacin and a water-soluble polymer, characterized in that niacin is blended with the water-soluble polymer at a ratio of 100:0.1 to 500. [7] A dissolving micro-needle preparation containing niacin, a water-soluble polymer, and a polyhydric alcohol, characterized in that the polyhydric alcohol is blended with the water-soluble polymer at a ratio of 100:0.1 to 500.

Advantages of the Invention

[0013] According to the dissolving micro-needle preparation of the present invention, it has the strength not to break when puncturing the stratum corneum and dermis of the skin, and the flexibility and solubility to avoid causing pain, thereby reducing the discomfort during and after application. Further, according to the dissolving micro-needle preparation of the present invention, it can exhibit excellent cosmetic effects of moisturizing the skin, improving wrinkles, sagging, firmness, elasticity or dullness.

Brief Description of the Drawings

[0014]

Figure 1

Modes for Carrying Out the Invention

[0015] The dissolving micro-needle preparation of the present invention is characterized by containing niacin and a water-soluble polymer.

[0016] Hereinafter, the composition of the present invention will be described based on its preferred embodiments.

[0017] <Dissolving Micro-Needle Preparation> The dissolving microneedle preparation of the present invention comprises a substrate and a plurality of microneedles disposed on the substrate. The microneedles constituting the dissolving microneedle preparation of the present invention contain niacin and a water-soluble polymer as a base.

[0018] The preparation of the dissolving microneedle of the present invention has a structure in which one or more microneedles are formed on the surface of the substrate.

[0019] The substrate of the dissolving microneedle preparation of the present invention is not particularly limited as long as it is in a sheet form capable of forming, placing, and holding microneedles on its surface. The substrate may be a sheet having the same composition as the microneedles, or a sheet having a composition different from that of the microneedles (for example, a composition in which other components are blended into the composition of the microneedles, or a composition that does not contain the components constituting the microneedles). In the case of a composition different from that of the microneedles, examples of the components used include sheets formed from polymethyl methacrylate, cellulose acetate, ethyl cellulose, polyethylene resin, polypropylene resin, vinyl chloride-based resin, polyamide-based resin, polyester resin, urethane resin, silicone resin, aluminum, and the like. From the viewpoints of production efficiency and simplicity, it is desirable that the substrate of the microneedles is composed of a sheet having the same composition as the microneedles. By making the composition the same as that of the microneedles, the substrate and the microneedles can be integrally molded.

[0020] The thickness of the substrate of the dissolving microneedle preparation of the present invention is not particularly limited as long as it can form, place, and hold microneedles on its surface. However, since it has a thickness sufficient to serve as a support for puncturing the skin with the microneedles, 20 μm or more is preferable, 40 μm or more is more preferable, and 50 μm or more is even more preferable.

[0021] The shape of the substrate of the dissolving microneedle preparation can be appropriately set according to the application site. For example, it includes circular, elliptical, drop-shaped, crescent-shaped, triangular, square, and other polygons. The size of the substrate can also be appropriately set according to the application site. For example, in the case of a circular or elliptical shape, the diameter (major axis) is preferably 1 mm or more and 100 mm or less, more preferably 1 mm or more and 80 mm or less, and even more preferably 1 mm or more and 50 mm or less. In the case of a polygon, the longest side (long side) is preferably 1 mm or more and 100 mm or less, more preferably 1 mm or more and 80 mm or less, and even more preferably 1 mm or more and 50 mm or less. Also, when the size of the substrate of the dissolving microneedle preparation is expressed in terms of area, it is 2 preferably 5 mm 2 or more and 4000 mm 2 or less, more preferably 8 mm 2 or more and 3000 mm 2 or less, and even more preferably 10 mm 2 or more and 2000 mm

[0022] or less. In the dissolving microneedle preparation of the present invention, the larger the number of microneedles, the more the expected cosmetic effect and pharmacological effect can be exerted. Therefore, it is desirable that a plurality of microneedles are formed on the substrate. The number of microneedles is preferably 20 or more, more preferably 50 or more, and even more preferably 100 or more.

[0023] The number of microneedles per unit area on the surface of the substrate of the dissolving microneedle preparation of the present invention may be appropriately set according to the distance between the tip of one microneedle and the tip of the microneedle adjacent thereto, and is not particularly limited. However, in order to have a strength that can withstand piercing the stratum corneum and dermis of the skin, per 1 cm 2 of the surface of the substrate, 30 to 500 are preferred, 40 to 400 are more preferred, and 50 to 300 are even more preferred.

[0024] The distance between the microneedles of the dissolving microneedle preparation of the present invention may be appropriately set and is not particularly limited. However, in order to deliver beauty components and medicinal components to the stratum corneum and dermis to exert a beauty effect, and to provide strength to withstand puncture of the skin's cutin and dermis, the distance between one microneedle and the tip of the microneedle adjacent to it is preferably 50 to 3000 μm, more preferably 70 to 2500 μm, and even more preferably 100 to 2000 μm.

[0025] The shape of the microneedles of the dissolving microneedle preparation of the present invention is not particularly limited as long as the shape is needle-like. However, in order to achieve both strength to withstand puncture of the skin's cutin and dermis and flexibility that does not cause pain, and to make the microneedles easily dissolve subcutaneously, for example, conical, frustum-shaped, rod-shaped, columnar, or coiled shapes can be mentioned. The microneedle may have the same diameter at the tip and the bottom surface in contact with the surface of the substrate, or the diameter may taper from the bottom surface to the tip. The tip diameter of the microneedle is preferably 3 to 200 μm, more preferably 4 to 150 μm, and even more preferably 5 to 100 μm in order to achieve both strength to withstand puncture of the skin's cutin and dermis and flexibility that does not cause pain. The diameter of the bottom surface of the microneedle in contact with the surface of the substrate of the dissolving microneedle preparation of the present invention is preferably 50 to 500 μm, more preferably 70 to 450 μm, and even more preferably 100 μm to 400 μm in order to deliver beauty components and medicinal components to the stratum corneum and dermis to exert a beauty effect and to provide strength to withstand puncture of the skin's cutin and dermis.

[0026] The height (length) of the microneedles of the dissolving microneedle preparation of the present invention may be appropriately set and is not particularly limited. However, in order to deliver beauty components and medicinal components to the stratum corneum and dermis to exert a beauty effect, and to achieve both strength to withstand puncture of the skin's cutin and dermis and flexibility that does not cause pain, the height from the grounding surface of the substrate to the tip is preferably 40 to 2000 μm, more preferably 50 to 1500 μm, and even more preferably 100 to 1000 μm.

[0027] The manufacturing method of the dissolving microneedle preparation of the present invention is not particularly limited and can be manufactured by a known method. For example, as the manufacturing method of the dissolving microneedle preparation of the present invention, for example, an aqueous solution in which the components constituting the microneedle are dissolved is cast on a mold in which the shape of the microneedle preparation is drilled so that the microneedle part and the substrate part can be formed, and after evaporating and drying the moisture at room temperature or by heating, there is a method of peeling the formed microneedle array from the mold. By this method, a microneedle array in which the microneedle and the substrate have the same composition is manufactured. Further, as a manufacturing method different from the above, an aqueous solution in which the components constituting the microneedle are dissolved is cast on a mold in which the shape of the microneedle is drilled, evaporated and dried at room temperature or by heating, and then a substrate is laminated thereon, and after bonding or adhering the bottom surface part of the microneedle formed above and the substrate, there is a method of peeling the microneedle from the mold together with the substrate. By this method, a microneedle array in which the microneedle and the substrate have different compositions can be manufactured.

[0028] The dissolving microneedle preparation of the present invention is used by being attached to the skin so that the microneedle punctures the stratum corneum and / or dermis of the skin. Specifically, the dissolving microneedle preparation of the present invention is attached to the skin so that the microneedle punctures the stratum corneum and / or dermis of the skin and left as it is. By doing so, the beauty components and medicinal components in the microneedle are dissolved and eluted by body temperature and moisture such as subcutaneous, and the beauty effect and pharmacological effect by the beauty components and medicinal components are exhibited.

[0029] As described above, since the dissolving microneedle preparation of the present invention can deliver beauty components and medicinal components to the subcutaneous stratum corneum and / or dermis, it can exhibit a higher beauty effect and medicinal effect than external preparations applied or attached locally, and is useful as a cosmetic.

[0030] <Niacin> Niacin is a general term for nicotinic acid and derivatives of nicotinic acid, also known as vitamin B3, and is an essential component for the metabolism of carbohydrates, lipids, and proteins. The niacin or its derivatives in the present invention are not particularly limited, and either nicotinic acid or derivatives of nicotinic acid may be used. However, in terms of excellent moldability and solubility, and excellent improvement in skin firmness and elasticity, it is preferable to use derivatives of nicotinic acid, and it is particularly preferable to use niacinamide (nicotinic acid amide). The niacin of the present invention may be used alone or in combination of two or more. In addition, the niacin used in the present invention can be, for example, extracted from natural products or synthesized by known methods.

[0031] Niacinamide is a type of derivative of nicotinic acid and is an amide compound of nicotinic acid, also known as nicotinic acid amide, nicotinamide, and pyridine-3-carboxylic acid. Niacinamide is known to have effects such as acne vulgaris and whitening effect.

[0032] In the composition before drying in the process of forming the micro-needles of the dissolving type micro-needle preparation of the present invention, that is, in the composition before forming the micro-needles, the upper limit value of the blending amount of niacin is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and excellent improvement in skin firmness and elasticity, it is preferably 0.0001% by weight or more, more preferably 0.0005% by weight or more, further preferably 0.001% by weight or more, and most preferably 0.005% by weight or more based on the total amount of the base of the micro-needles. Also, in the composition before forming the micro-needles of the dissolving type micro-needle preparation of the present invention, the lower limit value of the blending amount of the water-soluble polymer is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and excellent improvement in skin firmness and elasticity, it is preferably 20% by weight or less, more preferably 10% by weight or less, still more preferably 5% by weight or less, and most preferably 1% by weight or less based on the total amount of the base of the micro-needles.

[0033] In the composition after drying in the process of forming the microneedles of the dissolving microneedle preparation of the present invention, that is, in the composition after molding of the microneedles, the upper limit value of the blending amount of niacin is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, etc., it is preferably 0.01% by weight or more, more preferably 0.1% by weight or more, still more preferably 0.5% by weight or more, and most preferably 1% by weight or more based on the total amount of the base of the microneedles. Further, in the composition after molding of the microneedles of the dissolving microneedle preparation of the present invention, the lower limit value of the blending amount of the water-soluble polymer is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, etc., it is preferably 95% by weight or less, more preferably 75% by weight or less, still more preferably 55% by weight or less, and most preferably 40% by weight or less based on the total amount of the base of the microneedles.

[0034] <Water-soluble polymer> A water-soluble polymer is a molecule having a structure in which 5 or more low-molecular compounds such as monosaccharides are bonded and having the property of dissolving in water. The low-molecular compounds constituting the water-soluble polymer may be of one type or two or more types. The water-soluble polymer used in the present invention is not particularly limited as long as it is a component used in microneedle preparations or cosmetics. For example, cellulose derivatives such as hyaluronic acid, starch, and cellulose gum, xanthan gum, carrageenan, pectin, and dextrin can be mentioned. Examples of cellulose derivatives include cellulose gum (carboxymethyl cellulose), methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, methyl hydroxyethyl cellulose, methyl hydroxypropyl cellulose, and carboxymethyl cellulose. Among these, it is preferable to use hyaluronic acid, xanthan gum, carrageenan, and dextrin in terms of excellent moldability and solubility, and improvement of skin firmness and elasticity, etc., and it is more preferable to use hyaluronic acid. The water-soluble polymer of the present invention may be used alone or in combination of two or more.

[0035] <Hyaluronic acid> For the dissolving microneedle preparation of the present invention, it is preferable to use hyaluronic acid as the water-soluble polymer. Hyaluronic acid is a mucopolysaccharide in which glucuronic acid and N-acetyl-D-glucosamine are bound. The hyaluronic acid of the present invention is not particularly limited, and any of hyaluronic acid, acetyl hyaluronic acid, a derivative of hyaluronic acid or acetyl hyaluronic acid, or a salt thereof may be used, or hydrolyzed hyaluronic acid or a salt thereof may be used. Among these, hyaluronic acid, sodium hyaluronate, sodium acetyl hyaluronate, hydrolyzed hyaluronic acid or sodium hydrolyzed hyaluronate are preferably used in terms of excellent moldability and solubility, and excellent improvement in skin firmness and elasticity. More preferably, sodium hyaluronate or sodium acetyl hyaluronate is used, and even more preferably, sodium hyaluronate is used. The hyaluronic acid of the present invention may be used alone or in combination of two or more. The hydrolyzed hyaluronic acid in the present invention means hyaluronic acid having an average molecular weight of 1,000 or more and 10,000 or less.

[0036] The molecular weight of the hyaluronic acid used in the present invention varies depending on the number and type of repeating units and is not particularly limited. Hyaluronic acid having a weight average molecular weight of several hundreds to several millions may be used, or hydrolyzed hyaluronic acid having an average molecular weight of 1,000 or more and 10,000 or less may be used. Among these, those having an average molecular weight of 50,000 or more are preferably used, those having an average molecular weight of 100,000 or more are more preferably used, and those having an average molecular weight of 1,000,000 or more are even more preferably used in terms of excellent moldability and solubility, and excellent improvement in skin firmness and elasticity.

[0037] For the hyaluronic acid used in the present invention, commercially available products can be used, or those extracted from animal tissues or produced by fermentation methods such as microbial culture can also be used. Examples of those extracted from animal tissues include those extracted from chicken combs. Since chicken combs have been used for food for a long time, there are no problems in terms of safety even when added to microneedles, so chicken comb extracts may be used as hyaluronic acid.

[0038] In the composition before drying in the process of forming the microneedles of the dissolving type microneedle preparation of the present invention, that is, in the composition before molding the microneedles, the upper limit value of the blending amount of the water-soluble polymer is not particularly limited. However, in terms of excellent moldability and solubility, and excellent improvement in skin firmness and elasticity, etc., it is preferably 0.001% by weight or more, more preferably 0.005% by weight or more, further preferably 0.01% by weight or more, and most preferably 0.05% by weight or more with respect to the total amount of the base of the microneedles. Also, in the composition before molding the microneedles of the dissolving type microneedle preparation of the present invention, the lower limit value of the blending amount of the water-soluble polymer is not particularly limited. However, in terms of excellent moldability and solubility, and excellent improvement in skin firmness and elasticity, etc., it is preferably 30% by weight or less, more preferably 20% by weight or less, even more preferably 10% by weight or less, and most preferably 5% by weight or less with respect to the total amount of the base of the microneedles.

[0039] In the composition after drying in the process of forming the microneedles of the dissolving type microneedle preparation of the present invention, that is, in the composition after molding of the microneedles, the upper limit value of the blending amount of the water-soluble polymer is not particularly limited, but in terms of excellent moldability and solubility, and excellent improvement in skin firmness and elasticity, etc., 1% by weight or more is preferable with respect to the total amount of the base of the microneedles, more preferably 5% by weight or more, still more preferably 10% by weight or more, and most preferably 30% by weight or more. Further, in the composition after molding of the microneedles of the dissolving type microneedle preparation of the present invention, the lower limit value of the blending amount of the water-soluble polymer is not particularly limited, but in terms of excellent moldability and solubility, and excellent improvement in skin firmness and elasticity, etc., 99% by weight or less is preferable with respect to the total amount of the base of the microneedles, more preferably 95% by weight or less, still more preferably 90% by weight or less, and most preferably 85% by weight or less.

[0040] In the composition before drying in the process of forming the microneedles of the dissolving type microneedle preparation of the present invention, that is, in the composition before molding of the microneedles, the upper limit value of the blending ratio of niacin to the water-soluble polymer is not particularly limited, but in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and excellent improvement in skin firmness and elasticity, etc., 0.001% by weight or more is preferable with respect to 100% by weight of the water-soluble polymer, more preferably 0.01% by weight or more, still more preferably 0.1% by weight, and most preferably 0.5% by weight or more. Further, in the composition before molding of the microneedles of the dissolving type microneedle preparation of the present invention, the lower limit value of the blending ratio of niacin to the water-soluble polymer is not particularly limited, but in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and excellent improvement in skin firmness and elasticity, etc., 300% by weight or less is preferable with respect to 100% by weight of the water-soluble polymer, more preferably 200% by weight or less, still more preferably 100% by weight or less, and most preferably 75% by weight or less.

[0041] In the composition after drying in the process of forming the microneedles of the dissolving microneedle preparation of the present invention, that is, in the composition after molding of the microneedles, the upper limit value of the blending ratio of niacin to the water-soluble polymer is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, etc., it is preferably 0.001% by weight or more, more preferably 0.01% by weight or more, further preferably 0.1% by weight, and most preferably 0.5% by weight or more with respect to 100% by weight of the water-soluble polymer. Also, in the composition after molding of the microneedles of the dissolving microneedle preparation of the present invention, the lower limit value of the blending ratio of niacin to the water-soluble polymer is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, etc., it is preferably 300% by weight or less, more preferably 200% by weight or less, further preferably 100% by weight or less, and most preferably 75% by weight or less with respect to 100% by weight of the water-soluble polymer.

[0042] <Polyhydric alcohol> The dissolving microneedle preparation of the present invention preferably contains a polyhydric alcohol. The polyhydric alcohol used in the present invention has two or more hydroxy groups in one molecule and refers to those other than water-soluble polymers. It is not particularly limited as long as it is a component used in microneedle preparations or cosmetics. For example, polyglycerols such as glycerin, diglycerin, triglycerin, and tetraglycerin; ethylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, propylene glycol, dipropylene glycol, polyethylene glycol, 1,3-propanediol; sugar alcohols such as erythritol, maltitol, mannitol, sorbitol, and xylitol; polyglycerol derivatives; and saccharides such as sucrose and trehalose. Among these, glycerin, diglycerin, 1,3-butylene glycol, 1,3-propanediol, maltitol, mannitol, and sorbitol are preferably used in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity. Glycerin, diglycerin, 1,3-butylene glycol, and 1,3-propanediol are more preferably used, and glycerin and 1,3-butylene glycol are even more preferably used. The polyhydric alcohol of the present invention may be used alone or in combination of two or more kinds.

[0043] In the composition before drying in the process of forming the micro needles of the dissolving type micro needle preparation of the present invention, that is, in the composition before molding of the micro needles, the upper limit value of the blending amount of the polyhydric alcohol in the total amount of the base is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, etc., it is preferably 0.0001% by weight or more, more preferably 0.0005% by weight or more, further preferably 0.001% by weight or more, and most preferably 0.005% by weight or more with respect to the total amount of the base of the micro needles. Also, in the composition before molding of the micro needles of the dissolving type micro needle preparation of the present invention, the lower limit value of the blending amount of the polyhydric alcohol in the total amount of the base is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, etc., it is preferably 50% by weight or less, more preferably 10% by weight or less, even more preferably 5% by weight or less, and most preferably 1% by weight or less with respect to the total amount of the base of the micro needles.

[0044] In the composition after drying in the process of forming the micro needles of the dissolving type micro needle preparation of the present invention, that is, in the composition after molding of the micro needles, the upper limit value of the blending amount of the polyhydric alcohol in the total amount of the base is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, etc., it is preferably 0.001% by weight or more, more preferably 0.01% by weight or more, further preferably 0.1% by weight or more, and most preferably 0.5% by weight or more with respect to the total amount of the base of the micro needles. Also, in the composition after molding of the micro needles of the dissolving type micro needle preparation of the present invention, the lower limit value of the blending amount of the polyhydric alcohol in the total amount of the base is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, etc., it is preferably 60% by weight or less, more preferably 50% by weight or less, even more preferably 40% by weight or less, and most preferably 25% by weight or less with respect to the total amount of the base of the micro needles.

[0045] In the composition before drying in the process of forming the microneedles of the dissolving microneedle preparation of the present invention, that is, in the composition before molding the microneedles, the upper limit value of the compounding ratio of the polyhydric alcohol to the water-soluble polymer is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, etc., it is preferably 0.001% by weight or more, more preferably 0.01% by weight or more, further preferably 0.1% by weight, and most preferably 0.5% by weight or more with respect to 100% by weight of the water-soluble polymer. Also, in the composition before molding the microneedles of the dissolving microneedle preparation of the present invention, the lower limit value of the compounding ratio of the polyhydric alcohol to the water-soluble polymer is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, etc., it is preferably 300% by weight or less, more preferably 200% by weight or less, further preferably 100% by weight or less, and most preferably 75% by weight or less with respect to 100% by weight of the water-soluble polymer.

[0046] After drying in the process of forming the microneedles of the dissolving microneedle preparation of the present invention, that is, in the composition after molding, the upper limit value of the compounding ratio of the polyhydric alcohol to the water-soluble polymer is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, etc., it is preferably 0.001% by weight or more, more preferably 0.01% by weight or more, further preferably 0.1% by weight, and most preferably 0.5% by weight or more with respect to 100% by weight of the water-soluble polymer. Also, in the composition after molding the microneedles of the dissolving microneedle preparation of the present invention, the lower limit value of the compounding ratio of the polyhydric alcohol to the water-soluble polymer is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, etc., it is preferably 300% by weight or less, more preferably 200% by weight or less, further preferably 100% by weight or less, and most preferably 75% by weight or less with respect to 100% by weight of the water-soluble polymer.

[0047] The dissolving microneedle preparation of the present invention is useful for improving skin moisturization, wrinkles, sagging, firmness, elasticity or dullness, and can be suitably used for skin external preparations such as cosmetics, quasi-drugs, and external medicines.

[0048] The dissolving microneedle preparation of the present invention can, if necessary, contain components other than the components of the present invention. Examples of components other than the components of the present invention include other active ingredients, preservatives, pH adjusters, oils and fats, fragrances, colorants, antioxidants, antibacterial and antifungal agents, alcohols, nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, and other surfactants, inorganic salts, lubricants, solvents, purified water, and the like. One or more of the components usually used in skin external preparations can be used. In terms of excellent moldability and solubility, it is preferable to add purified water to the dissolving microneedle preparation of the present invention.

[0049] In the composition before drying in the process of forming the microneedles of the dissolving microneedle preparation of the present invention, that is, in the composition before molding the microneedles, the upper limit of the blending ratio of the total amount of niacin and water-soluble polymer in the total amount of the base is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, when the total amount of the base is 100% by weight, 0.0001% by weight or more is preferable, 0.001% by weight or more is more preferable, 0.01% by weight is further preferable, and 0.05% by weight or more is most preferable. Also, in the composition before molding the microneedles of the dissolving microneedle preparation of the present invention, the lower limit of the blending ratio of the total amount of niacin and water-soluble polymer in the total amount of the base is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, when the total amount of the base is 100% by weight, 95% by weight or less is preferable, 50% by weight or less is more preferable, 10% by weight or less is further preferable, and 5% by weight or less is most preferable.

[0050] In the composition after drying in the process of forming the microneedles of the dissolving type microneedle preparation of the present invention, that is, in the composition after molding of the microneedles, the upper limit value of the blending ratio of the total amount of niacin and the water-soluble polymer in the total amount of the base is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, when the total amount of the base is 100% by weight, 1% by weight or more is preferable, 5% by weight or more is more preferable, 10% by weight is further preferable, and 30% by weight or more is most preferable. Further, in the composition after molding of the microneedles of the dissolving type microneedle preparation of the present invention, the lower limit value of the blending ratio of the total amount of niacin and the water-soluble polymer in the total amount of the base is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, when the total amount of the base is 100% by weight, 99% by weight or less is preferable, 97% by weight or less is more preferable, 95% by weight or less is further preferable, and 90% by weight or less is most preferable.

[0051] In the composition before drying in the process of forming the microneedles of the dissolving type microneedle preparation of the present invention, that is, in the composition before molding of the microneedles, the upper limit value of the blending ratio of the total amount of niacin, the water-soluble polymer and the polyhydric alcohol in the total amount of the base is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, when the total amount of the base is 100% by weight, 0.0001% by weight or more is preferable, 0.001% by weight or more is more preferable, 0.01% by weight is further preferable, and 0.07% by weight or more is most preferable. Further, in the composition before molding of the microneedles of the dissolving type microneedle preparation of the present invention, the lower limit value of the blending ratio of the total amount of niacin, the water-soluble polymer and the polyhydric alcohol in the total amount of the base is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, when the total amount of the base is 100% by weight, 99.9% by weight or less is preferable, 50% by weight or less is more preferable, 10% by weight or less is further preferable, and 5% by weight or less is most preferable.

[0052] In the composition after drying in the process of forming the microneedles of the dissolving microneedle preparation of the present invention, that is, in the composition after molding of the microneedles, the upper limit value of the blending ratio of the total amount of niacin, water-soluble polymer and polyhydric alcohol in the total amount of the base is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, when the total amount of the base is 100% by weight, 1% by weight or more is preferable, 5% by weight or more is more preferable, 10% by weight is further preferable, and 40% by weight or more is most preferable. Further, in the composition after molding of the microneedles of the dissolving microneedle preparation of the present invention, the lower limit value of the blending ratio of the total amount of niacin and water-soluble polymer in the total amount of the base is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, when the total amount of the base is 100% by weight, 99.9% by weight or less is preferable, 99% by weight or less is more preferable, 95% by weight or less is further preferable, and 92.5% by weight or less is most preferable.

[0053] When the dissolving microneedle preparation of the present invention contains purified water, in the composition before drying in the process of forming the microneedles, that is, in the composition before molding of the microneedles, the blending ratio of purified water to the total amount of niacin and water-soluble polymer is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, with respect to the total amount of niacin and water-soluble polymer, when the total amount of niacin and water-soluble polymer is set to 1, 1:0.1 to 100000 is preferable, 1:1 to 10000 is more preferable, 1:10 to 10000 is further preferable, and 1:50 to 1000 is most preferable.

[0054] When the dissolving micro-needle preparation of the present invention contains purified water, in the composition after drying in the process of forming the micro-needle, that is, in the composition after molding the micro-needle, the blending ratio of purified water to the total amount of niacin and water-soluble polymer is not particularly limited. However, in terms of excellent moldability, reduction of pain during and after puncture, excellent solubility, and improvement of skin firmness and elasticity, when the total amount of niacin and water-soluble polymer is set to 1, the ratio of purified water to the total amount of niacin and water-soluble polymer is preferably 1:0.0001 to 30, more preferably 1:0.001 to 20, still more preferably 1:0.01 to 10, and most preferably 1:0.05 to 5.

[0055] When the dissolving micro-needle preparation of the present invention contains purified water, in the composition before drying in the process of forming the micro-needle, that is, in the composition before molding the micro-needle, the upper limit value of the blending ratio of purified water in the total amount of the base is not particularly limited. However, in terms of excellent moldability and solubility, when the total amount of the base is 100% by weight, 30% by weight or more is preferable, 50% by weight or more is more preferable, 90% by weight or more is still more preferable, and 95% by weight or more is most preferable. Further, in the composition before molding the micro-needle of the dissolving micro-needle preparation of the present invention, the lower limit value of the blending ratio of purified water in the total amount of the base is not particularly limited. However, in terms of excellent moldability and solubility, when the total amount of the base is 100% by weight, 99.9% by weight or less is preferable, 99.5% by weight or less is more preferable, and 99% by weight or less is most preferable.

[0056] When the dissolving type micro-needle preparation of the present invention contains purified water, in the composition after drying in the process of forming the micro-needles, that is, in the composition after molding of the micro-needles, the upper limit value of the blending ratio of purified water in the total amount of the base is not particularly limited. However, in terms of excellent moldability and solubility, when the total amount of the base is 100% by weight, 0.5% by weight or more is preferable, 1% by weight or more is more preferable, 5% by weight or more is further preferable, and 7.5% by weight or more is most preferable. Also, in the composition after molding of the micro-needles of the dissolving type micro-needle preparation of the present invention, the lower limit value of the blending ratio of purified water in the total amount of the base is not particularly limited. However, in terms of excellent moldability and solubility, when the total amount of the base is 100% by weight, 70% by weight or less is preferable, 60% by weight or less is more preferable, and 50% by weight or less is most preferable.

[0057] The micro-needles of the dissolving type micro-needle preparation of the present invention may contain the components of the present invention. For example, they may be needle-like protrusions formed with a coding layer containing the components of the present invention, or may be needle-like protrusions encapsulating the components of the present invention.

[0058] Hereinafter, typical examples of other components other than the components of the present invention contained in the dissolving type micro-needle preparation of the present invention will be further described.

[0059] The active ingredient contained in the dissolving microneedle preparation of the present invention is not particularly limited, and can be used according to the purpose, such as drugs, plants, etc. used in cosmetics, quasi-drugs, external medicines, etc. Typical examples include, for example, glycyrrhizic acid and its derivatives and their salts, glycyrrhetinic acid and its derivatives and their salts, mefenamic acid, phenylbutazone, indomethacin, ibuprofen, ketoprofen, allantoin, guaiazulene, panthenol, anti-inflammatory agents such as allantoin, ascorbic acid and its derivatives and their salts, cysteine and its derivatives and its salts, glabridin, glabrene, liquiritin, isoliquiritin, placenta, hydroquinone and its derivatives, resorcinol and its derivatives, skin whitening agents such as glutathione, anti-seborrheic agents such as sulfur and tiandrol, bactericides such as salicylic acid and peony extract, plant components such as tocopherol and its derivatives, licorice, aloe, tea leaves, and hormones such as estradiol. When using plant components, the whole herb, leaves (leaf blade, petiole, etc.), fruits (ripe, unripe, etc.), seeds, flowers (petals, ovaries, etc.), stems, rhizomes, roots, tubers, etc. can be used as they are, cut, crushed, pulverized, squeezed, extracted, or these processed materials can be dried or powdered for use.

[0060] The dissolving microneedle preparation of the present invention improves skin moisturization, wrinkles, sagging, firmness, elasticity or dullness, and has a cosmetic effect. Therefore, it can improve skin quality, rejuvenate the skin, tighten the skin, smooth the skin, refine the skin texture, keep the skin healthy, tighten the skin, moisturize the skin, supplement and maintain skin moisture and oil, maintain skin softness, protect the skin, prevent skin dryness, soften the skin, give firmness to the skin, give gloss to the skin, smooth the skin, and make fine wrinkles caused by dryness less noticeable. It can be suitably used for any of pharmaceuticals such as cosmetics, quasi-drugs, and drugs.

[0061] The dissolving micro-needle preparation of the present invention is not limited to those in which the components of the present invention (niacin and water-soluble polymer) are indicated as active ingredients for beauty such as skin moisturization, improvement of wrinkles, sagging, firmness, elasticity or dullness in product packaging or the like. For example, it may not specify the active ingredient, or may indicate a specific material other than the components of the present invention as the active ingredient.

[0062] The dissolving micro-needle preparation of the present invention can be excellent as a composition for improving skin firmness, a composition for improving skin elasticity, and a beauty composition by exhibiting the effect of improving firmness or elasticity shown in the examples described later.

Examples

[0063] Hereinafter, the dissolving micro-needle preparation of the present invention will be described in more detail with reference to examples. However, the technical scope of the present invention is not limited to such examples. Hereinafter, unless otherwise specified, “%” represents weight %.

[0064] <Test Example 1 Evaluation of Moldability> As the water-soluble polymer, sodium hyaluronate having an average molecular weight of 1.2 million to 2.2 million was used. As niacin, niacinamide was used. As the polyhydric alcohol, concentrated glycerin was used.

[0065] Sodium hyaluronate having an average molecular weight of 1.2 to 2.2 million was swollen and dissolved in purified water so that the composition before drying became the composition shown in Table 1 to prepare a solution. For Comparative Examples 2 to 4, niacinamide and / or concentrated glycerin were further added to prepare a solution. The solution was poured into a mold and naturally dried at 25 ° C for 24 hours. After natural drying, the composition after drying was confirmed. Then, an adhesive tape was attached and an attempt was made to peel the molded product from the mold, and the possibility of peeling was evaluated according to the following evaluation criteria.

[0066] · Evaluation Criteria for Moldability Completely peelable: ○ Partially non-peelable: △ Non-peelable: ×

[0067] The results are shown in Table 1. Also, the compositions before and after drying are shown in Tables 2 to 5.

[0068]

Table 1

[0069]

Table 2

[0070]

Table 3

[0071]

Table 4

[0072]

Table 5

[0073] As is clear from the results shown in Table 1, when sodium hyaluronate was contained (Comparative Example 1), and when niacinamide and sodium hyaluronate were contained (Example 1), it was possible to completely peel off from the mold, and a dissolving type micro needle preparation could be molded. On the other hand, when sodium hyaluronate and concentrated glycerin were contained (Comparative Example 2), it could not be peeled off from the mold, and a dissolving type micro needle preparation could not be molded. Further, although it could not be peeled off when sodium hyaluronate and concentrated glycerin were contained (Comparative Example 2), when niacinamide was further contained in sodium hyaluronate and concentrated glycerin (Example 2), it could be completely peeled off from the mold, and a dissolving type micro needle preparation could be molded. That is, it can be seen that when niacinamide and sodium alluronate are contained, the moldability is excellent. Also, it can be seen that when niacinamide is contained in hyaluronic acid and concentrated glycerin, the moldability is improved and a dissolving type micro needle preparation can be molded. Therefore, a dissolving type micro needle preparation can be obtained by containing niacinamide, a water-soluble polymer, and a polyhydric alcohol.

[0074] <Test Example 2 Evaluation of Solubility and Stickiness / Elasticity> As the water-soluble polymer, sodium hyaluronate having an average molecular weight of 1.2 million to 2.2 million was used. As the water-soluble polymer, sodium acetylated hyaluronate having an average molecular weight of 100,000 was used. As niacin, niacinamide was used. As the polyhydric alcohol, concentrated glycerin was used. As the polyhydric alcohol, 1,3-butylene glycol was used.

[0075] The hyaluronic acid described in Table 6 was swollen and dissolved in purified water so that the composition before drying became the composition of Table 6, and a solution was prepared. For Comparative Example 2 and Examples 3 and onwards, niacinamide and / or the polyhydric alcohol described in Table 6 were further added to prepare a solution. The solution was poured into a mold and naturally dried at 25°C for 24 hours. After natural drying, the composition after drying was confirmed. Thereafter, an adhesive tape was attached, the molded product was peeled off from the mold, and a dissolving-type microneedle preparation was obtained. The obtained dissolving-type microneedle preparation was applied under the eyes of three men and three women for 1 hour, and the solubility and stickiness / elasticity during and after puncture were scored according to the following evaluation criteria and evaluated.

[0076] ·Evaluation criteria for solubility The dissolution time of the microneedle is less than 15 minutes: 3 The dissolution time of the microneedle is 15 minutes or more and less than 30 minutes: 2 The dissolution time of the microneedle is 30 minutes or more and less than 60 minutes: 1 The dissolution time of the microneedle is 60 minutes or more: 0

[0077] ·Evaluation criteria for stickiness / elasticity The stickiness / elasticity 1 hour after application is significantly better than before application: 3 The stickiness / elasticity 1 hour after application is better than before application: 2 The stickiness / elasticity 1 hour after application is slightly better than before application: 1 The stickiness / elasticity 1 hour after application is unchanged compared to before application: 0

[0078] The average score given by each of the three men and three women was calculated, and the test products were evaluated as ◎, ○, △, × according to the following criteria. ·Evaluation criteria for test products The average score is 2.5 or more: ◎ The average score is 1.5 or more and less than 2.5: ○ The average score is 0.5 or more and less than 1.5: △ The average score is less than 0.5: ×

[0079] The results are shown in Figure 1 and Table 6. Also, the compositions before and after drying are shown in Tables 2 and 7 to 14.

[0080]

Table 6

[0081]

Table 7

[0082]

Table 8

[0083]

Table 9

[0084]

Table 10

[0085]

Table 11

[0086]

Table 12

[0087]

Table 13

[0088]

Table 14

[0089] As is clear from the results shown in Fig. 1 and Table 6, when niacinamide was not contained (Comparative Example 1), both solubility and stickiness / elasticity were poor, and it was not an overall excellent preparation. However, when niacinamide and sodium hyaluronate or sodium acetylated hyaluronate were contained (Examples 3 to 9), it was excellent in solubility or stickiness / elasticity, and it was found that it was an overall excellent dissolving type microneedle preparation. Further, when concentrated glycerin or 1,3-butylene glycol was contained in addition to niacinamide, sodium hyaluronate or sodium acetylated hyaluronate, it was further excellent in solubility or stickiness / elasticity, and it was found that it was an overall extremely excellent dissolving type microneedle preparation. Moreover, Examples 5, 7 to 9 were excellent in pain reduction compared to the comparative examples.

[0090] Hereinafter, formulation examples of various aspects of the dissolving type microneedle preparation of the invention will be given. However, the technical scope of the present invention is not limited to such formulation examples. Hereinafter, unless otherwise specified, “%” represents weight %.

[0091] <Formulation Examples 1 and 2>

[0092]

Table 15

[0093] A solution was prepared by dissolving a water-soluble polymer, niacin, and a polyhydric alcohol in purified water so that the composition before drying became the composition described in Table 15. When the solution was poured into a mold and naturally dried at 25°C for 24 hours, a microneedle preparation having good moldability could be obtained. The obtained microneedle preparation was excellent in pain reduction, and also excellent in solubility and stickiness / elasticity.

Industrial Applicability

[0094] Since the composition of the present invention can be used as so-called cosmetics, quasi-drugs, and pharmaceuticals, it is industrially useful.

Claims

1. A soluble microneedle formulation containing niacin and a water-soluble polymer.

2. The soluble microneedle according to claim 1, further containing a polyhydric alcohol.

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