Dissolving microneedle preparation

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 type microneedle preparation containing niacin and a water-soluble polymer. [Background technology]

[0002] Conventionally, topical preparations containing cosmetic ingredients or medicinal ingredients have been used to exert cosmetic or pharmacological effects subcutaneously. Such topical preparations are known to be in the form of liquids, creams, packs, etc., and by applying or attaching them to a localized area, the cosmetic ingredients or medicinal ingredients are absorbed transdermally, and the expected cosmetic or pharmacological effects are exerted subcutaneously.

[0003] However, such topical preparations applied or pasted have the drawback that the cosmetic and medicinal ingredients disappear or fall off during use due to sweating, washing, other external pressure, evaporation, etc., before being absorbed percutaneously. In addition, these topical preparations have the drawback that the cosmetic and medicinal ingredients are not sufficiently absorbed percutaneously due to the barrier function of the skin, and the expected cosmetic and pharmacological effects cannot be exerted. In particular, when the cosmetic and medicinal ingredients are polymer compounds, they are difficult to absorb percutaneously, making it difficult to exert the cosmetic and pharmacological effects.

[0004] In addition, skin conditions such as dry skin, wrinkles, sagging, firmness, loss of elasticity, and dullness are factors that impair the beauty of the skin, and are therefore a source of worry for women who care about beauty. Therefore, in order to improve these skin conditions, various skin moisturizers and agents for improving wrinkles, sagging, firmness, elasticity, or dullness have been developed. For example, in recent years, methods of injecting botulinum toxin and injecting collagen have attracted attention as agents for improving wrinkles, sagging, firmness, and elasticity. Injection of botulinum toxin and injection of collagen can be performed by injection using a needle as a method for exerting beauty ingredients or medicinal ingredients subcutaneously, rather than using topical agents that are applied or pasted locally. However, injection of botulinum toxin and injection of collagen cause pain, which causes discomfort to users. In addition, injections have the disadvantages of causing pain, bleeding, and leaving needle wounds and swelling as the number of times they are used increases. Furthermore, injections often need to be administered by a professional such as a doctor, making it difficult for users to administer them appropriately.

[0005] In recent years, transdermal injection of cosmetic ingredients and medicinal ingredients using fine needle-like protrusions called microneedles has been attracting attention. In transdermal injection using microneedles, a microneedle containing cosmetic ingredients and medicinal ingredients is attached to the skin, and the microneedle is punctured into a relatively shallow layer of the skin such as the stratum corneum or dermis, and the cosmetic ingredients and medicinal ingredients are absorbed transdermally by dissolving the microneedle subcutaneously. In addition, transdermal injection using microneedles causes less pain than normal injections, and does not need to be performed by a specialist, so that the user can use it as appropriate.

[0006] Microneedles are required to be optimally designed according to skin symptoms and diseases, and microneedle preparations used as topical agents are required not to break when puncturing the keratin or dermis of the skin. On the other hand, microneedles are also required to have flexibility so as not to cause pain, bleeding, or swelling at the site where the keratin or dermis of the skin is punctured. Therefore, microneedle preparations must be strong enough to withstand puncturing the keratin or dermis of the skin, and flexible enough not to cause pain.

[0007] Furthermore, microneedle preparations used as external preparations are required to be soluble or biodegradable under the skin after puncturing the stratum corneum or dermis of the skin.

[0008] However, since it is difficult to mold a microneedle preparation that has both strength and flexibility and also has solubility, only limited components of the microneedle preparation have been reported so far. Examples of microneedle preparations that have both strength, flexibility, and solubility include a microneedle made mainly of a mixture of maltose and dextran (Patent Document 1) and a microneedle made mainly of a mixture of a water-soluble polymer and one or more sugars selected from the group consisting of glucose, fructose, sucrose, lactose, and trehalose (Patent Document 2). However, the microneedle described in Patent Document 1 requires that maltose and a physiologically active substance are mixed, and then heated to a temperature equal to or higher than the melting point of maltose to be molded into the shape of the needle, making it difficult to use a physiologically active substance with poor thermal stability. In addition, although the invention of Patent Document 2 aims to accelerate the dissolution rate of the microneedle, no consideration is given to the pain or discomfort felt when the microneedle is inserted. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] JP 2005-152180 A [Patent Document 2] JP 2013-189432 A Summary of the Invention [Problem to be solved by the invention]

[0010] The present invention aims to provide a new microneedle preparation that has never been seen before. More specifically, in view of the above circumstances, the present invention aims to provide a dissolving microneedle preparation that has moldability that combines strength, flexibility, and solubility. In view of the above circumstances, the present invention also aims to provide a dissolving microneedle preparation that has excellent solubility. In view of the above circumstances, the present invention also aims to provide a dissolving microneedle preparation that has excellent cosmetic effects for moisturizing the skin and improving wrinkles, sagging, firmness, elasticity, or dullness. [Means for solving the problem]

[0011] The present inventors have conducted intensive research to solve the above problems, and have surprisingly found that, compared with the case where only a water-soluble polymer is used, by containing niacin and a water-soluble polymer, a dissolving microneedle preparation having excellent moldability, strength, flexibility, and solubility, and excellent cosmetic effect can be produced, and a dissolving microneedle preparation having reduced pain during and after puncturing can be produced.Furthermore, by containing polyhydric alcohol in addition to niacin and a water-soluble polymer, a dissolving microneedle preparation having even more excellent moldability, solubility, and cosmetic effect, and further reduced pain during and after puncturing can be produced.

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

[0013] The dissolving microneedle preparation of the present invention has a strength that does not break when puncturing the stratum corneum or dermis of the skin, and flexibility and solubility that do not cause pain, thereby reducing the discomfort felt when and during application. In addition, the dissolving microneedle preparation of the present invention can exert an excellent cosmetic effect of moisturizing the skin and improving wrinkles, sagging, firmness, elasticity, or dullness. [Brief description of the drawings]

[0014] [Figure 1] 1 is a graph showing evaluations of solubility and firmness / elasticity of Examples 3 to 9. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

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

[0016] The composition of the present invention will be described below based on preferred embodiments thereof.

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

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

[0019] The substrate of the dissolving microneedle formulation of the present invention is not particularly limited as long as it is in the form of a sheet on which microneedles can be formed, placed, and held. The substrate may be a sheet of the same composition as the microneedle, or a sheet of a different composition from the microneedle (for example, a composition of the microneedle containing other components, or a composition not containing the components constituting the microneedle). In the case of a composition different from the microneedle, the components used include, for example, sheets formed from polymethyl methacrylate, cellulose acetate, ethyl cellulose, polyethylene resin, polypropylene resin, vinyl chloride resin, polyamide resin, polyester resin, urethane resin, silicone resin, aluminum, etc. From the viewpoint of efficiency and simplicity of production, it is desirable that the substrate of the microneedle is composed of a sheet of the same composition as the microneedle. By making the substrate have the same composition as the microneedle, the substrate and the microneedle 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 is possible to form, place and hold microneedles on its surface, but in order to have a thickness sufficient to function as a support for inserting the microneedles into the skin, the thickness is preferably 20 μm or more, more preferably 40 μm or more, and even more preferably 50 μm or more.

[0021] The shape of the substrate of the dissolving microneedle preparation can be appropriately set according to the application site, and examples thereof include a circle, an ellipse, a teardrop shape, a crescent shape, a triangle, a rectangle, 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 circle or an ellipse, the diameter (long 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 addition, 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. In addition, when the size of the substrate of the dissolving microneedle preparation is expressed in terms of area, it is 5 mm 2 More than 4000mm 2 Less than 8mm is preferable 2 More than 3000mm 2 Less than 10mm is preferable. 2 More than 2000mm 2 The following is even more preferred:

[0022] The number of microneedles in the dissolving microneedle preparation of the present invention is preferably more than one, since the more the microneedles, the more the expected cosmetic and pharmacological effects can be exerted. 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 adjacent microneedle, and is not particularly limited. However, in order to provide the substrate with strength sufficient to withstand puncturing into the stratum corneum and dermis of the skin, the number of microneedles per unit area on the surface of the substrate is preferably set to 1 cm. 2 The number of fibers per unit is preferably 30 to 500, more preferably 40 to 400, and even more preferably 50 to 300.

[0024] The distance between the microneedles in the dissolving microneedle formulation of the present invention may be set appropriately and is not particularly limited, but in order to deliver cosmetic ingredients and medicinal ingredients to the stratum corneum or dermis to exert a cosmetic effect, and in order to provide strength sufficient to withstand puncturing the stratum corneum or dermis of the skin, the distance between one microneedle and the tip of an adjacent microneedle 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 microneedle of the dissolving microneedle preparation of the present invention is not particularly limited as long as it is needle-shaped, but in order to achieve both strength that can withstand puncturing into the keratin and dermis of the skin and flexibility that does not cause pain, and to make the microneedle easily dissolve subcutaneously, examples include cone-shaped, truncated cone-shaped, rod-shaped, columnar, and cone-shaped. The tip and the bottom surface that contacts the surface of the substrate may have the same diameter, 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 that can withstand puncturing into the keratin and dermis of the skin 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 cosmetic ingredients and medicinal ingredients to the stratum corneum and dermis to exert a cosmetic effect, and in order to have the strength to withstand puncturing into the stratum corneum and dermis of the skin.

[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, but in order to exert a cosmetic effect by delivering cosmetic ingredients and medicinal ingredients to the stratum corneum and dermis, and to achieve both strength sufficient to withstand puncturing the stratum corneum and dermis of the skin and flexibility that does not cause pain, the height from the contact 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 method for producing the soluble microneedle preparation of the present invention is not particularly limited, and can be produced by a known method. For example, as a method for producing the soluble microneedle preparation of the present invention, for example, a method is to cast an aqueous solution in which the components constituting the microneedle are dissolved into a mold in which the shape of the microneedle preparation is perforated so that a microneedle portion and a substrate portion can be formed, and then the formed microneedle array is peeled off from the mold after evaporating water at room temperature or by heating and drying. In this method, a microneedle array in which the microneedle and the substrate have the same composition is produced. In addition, as a production method different from the above, a method is to cast an aqueous solution in which the components constituting the microneedle are dissolved into a mold in which the shape of the microneedle is perforated, and then evaporating water at room temperature or by heating and drying, and then stacking a substrate on it, and bonding or adhering the bottom surface portion of the microneedle formed above to the substrate, and then peeling the microneedle together with the substrate from the mold. In this method, a microneedle array in which the microneedle and the substrate have different compositions can be produced.

[0028] The dissolving microneedle preparation of the present invention is used by adhering it to the skin so that the microneedles puncture 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 microneedles puncture the stratum corneum and / or dermis of the skin and left alone. In this way, the cosmetic ingredient or medicinal ingredient in the microneedle is dissolved and eluted by body temperature and moisture such as subcutaneous, and the cosmetic effect or pharmacological effect of the cosmetic ingredient or medicinal ingredient is exerted.

[0029] In this way, the dissolving microneedle preparation of the present invention can deliver cosmetic ingredients and medicinal ingredients to the subcutaneous stratum corneum and / or dermis, and can therefore exert greater cosmetic and medicinal effects than topical preparations that are applied or stuck locally, making it useful as a cosmetic agent.

[0030] <Niacin> Niacin is a general term for nicotinic acid and niacin, which is a derivative of nicotinic acid, and is also called vitamin B3. It is an essential component for the metabolism of carbohydrates, lipids, and proteins. The niacin or its derivative of the present invention is not particularly limited, and either nicotinic acid or a derivative of nicotinic acid may be used, but it is preferable to use a derivative of nicotinic acid, and it is particularly preferable to use niacinamide (nicotinic acid amide), because of its excellent moldability and solubility, and its excellent effect on improving skin firmness and elasticity. The niacin of the present invention may be used alone or in combination of two or more kinds. In addition, the niacin used in the present invention may be, for example, one extracted from a natural product, or one synthesized by a known method.

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

[0032] The composition before drying in the process of forming the microneedles of the dissolving microneedle preparation of the present invention, i.e., the composition before forming the microneedles, is the amount of niacin blended. under Although there is no particular limit, in terms of excellent moldability, reduction in pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, the content is preferably 0.0001% by weight or more, more preferably 0.0005% by weight or more, even more 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 microneedle. Niacin The amount of above There is no particular limit, but in terms of excellent moldability, reduced pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, the amount is preferably 20% 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, based on the total amount of the microneedle base.

[0033] The composition after drying in the process of forming the microneedles of the dissolving microneedle preparation of the present invention, i.e., the composition after forming the microneedles, is the amount of niacin under Although there is no particular limit, in terms of excellent moldability, reduction in pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, the content is preferably 0.01% by weight or more, more preferably 0.1% by weight or more, even 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 microneedle. Niacin The amount of above There is no particular limit, but in terms of excellent moldability, reduced pain during and after puncturing, excellent solubility, and improved skin firmness and elasticity, the content is preferably 95% by weight or less, more preferably 75% by weight or less, even more preferably 55% by weight or less, and most preferably 40% by weight or less, based on the total amount of the microneedle base.

[0034] <Water-soluble polymer> A water-soluble polymer is a molecule that has a structure in which five or more low molecular weight compounds such as monosaccharides are bonded and has the property of being soluble in water. The low molecular weight compounds that constitute the water-soluble polymer may be 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 and cosmetics, and examples thereof include hyaluronic acid, starch, cellulose derivatives such as cellulose gum, xanthan gum, carrageenan, pectin, and dextrin. Examples of cellulose derivatives include cellulose gum (carboxymethylcellulose), methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, methylhydroxyethylcellulose, methylhydroxypropylcellulose, and carboxymethylcellulose. Among these, hyaluronic acid, xanthan gum, carrageenan, and dextrin are preferably used, and hyaluronic acid is more preferably used, in terms of excellent moldability and solubility, and excellent improvement of skin firmness and elasticity. The water-soluble polymer of the present invention may be used alone or in combination of two or more types.

[0035] <Hyaluronic acid> The dissolving microneedle preparation of the present invention preferably uses 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, derivatives of hyaluronic acid or acetyl hyaluronic acid, or salts thereof may be used, or hydrolyzed hyaluronic acid or its salts may be used. Among these, it is preferable to use hyaluronic acid, sodium hyaluronate, sodium acetyl hyaluronate, hydrolyzed hyaluronic acid, or hydrolyzed sodium hyaluronate, in terms of excellent moldability and solubility, and excellent improvement of skin firmness and elasticity, and it is more preferable to use sodium hyaluronate or sodium acetyl hyaluronate, and it is even more preferable to use sodium hyaluronate. The hyaluronic acid of the present invention may be used alone or in combination of two or more types. In addition, the hydrolyzed hyaluronic acid in the present invention means hyaluronic acid having an average molecular weight of 1,000 to 10,000.

[0036] The molecular weight of the hyaluronic acid used in the present invention varies depending on the number of repeating units and the type, and is not particularly limited, and may use hyaluronic acid with a weight-average molecular weight of several hundred to several million, or may use hydrolyzed hyaluronic acid with an average molecular weight of 1000 to 10,000.Among these, it is preferable to use one with an average molecular weight of 50,000 or more, more preferably one with an average molecular weight of 100,000 or more, and even more preferably one with an average molecular weight of 1,000,000 or more, in terms of excellent moldability and solubility, and excellent improvement of skin firmness and elasticity.

[0037] The hyaluronic acid used in the present invention can be commercially available, can be extracted from animal tissue, or can be produced by fermentation method using microorganism culture.As the hyaluronic acid extracted from animal tissue, for example, can be extracted from cockscomb.Since cockscomb has been used for food for a long time, there is no problem in terms of safety even if it is added to microneedle, so cockscomb extract can be used as hyaluronic acid.

[0038] The composition before drying in the process of forming the microneedles of the dissolving type microneedle preparation of the present invention, i.e., the composition before forming the microneedles, is the amount of water-soluble polymer blended. under The limit is not particularly limited, but in terms of excellent moldability and solubility, and excellent improvement of skin firmness and elasticity, the amount of water-soluble polymer in the total amount of the base of the microneedle is preferably 0.001% by weight or more, more preferably 0.005% by weight or more, even more preferably 0.01% by weight or more, and most preferably 0.05% by weight or more. above The limit is not particularly limited, but in terms of excellent moldability and solubility, as well as improvement of skin firmness and elasticity, the content 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, based on the total amount of the microneedle base.

[0039] The composition after drying in the process of forming the microneedles of the dissolving type microneedle preparation of the present invention, i.e., the composition after forming the microneedles, is the amount of water-soluble polymer blended. under The limit is not particularly limited, but in terms of excellent moldability and solubility, and excellent improvement of skin firmness and elasticity, the amount of water-soluble polymer in the total amount of the base of the microneedle is preferably 1% by weight or more, more preferably 5% by weight or more, even more preferably 10% by weight or more, and most preferably 30% by weight or more. above The limit is not particularly limited, but in terms of excellent moldability and solubility, as well as improving skin firmness and elasticity, the content is preferably 99% by weight or less, more preferably 95% by weight or less, even more preferably 90% by weight or less, and most preferably 85% by weight or less, based on the total amount of the microneedle base.

[0040] The composition before drying in the process of forming the microneedles of the dissolving microneedle preparation of the present invention, i.e., the composition before forming the microneedles, is the blending ratio of niacin to the water-soluble polymer. under The limit is not particularly limited, but in terms of excellent moldability, reduction in pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, the content is preferably 0.001% by weight or more, more preferably 0.01% by weight or more, even more preferably 0.1% by weight or more, and most preferably 0.5% by weight or more, relative to 100% by weight of the water-soluble polymer. above The limit is not particularly limited, but in terms of excellent moldability, reduced pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, the limit is preferably 300% by weight or less, more preferably 200% by weight or less, even more preferably 100% by weight or less, and most preferably 75% by weight or less, relative to 100% by weight of the water-soluble polymer.

[0041] The composition after drying in the process of forming the microneedles of the dissolving microneedle preparation of the present invention, i.e., the composition after forming the microneedles, is the blending ratio of niacin to the water-soluble polymer. under The limit is not particularly limited, but in terms of excellent moldability, reduction in pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, the content is preferably 0.001% by weight or more, more preferably 0.01% by weight or more, even more preferably 0.1% by weight or more, and most preferably 0.5% by weight or more, relative to 100% by weight of the water-soluble polymer. above The limit is not particularly limited, but in terms of excellent moldability, reduced pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, the limit is preferably 300% by weight or less, more preferably 200% by weight or less, even more preferably 100% by weight or less, and most preferably 75% by weight or less, relative 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 hydroxyl groups in one molecule, and is not a water-soluble polymer. There is no particular limitation as long as it is a component used in microneedle preparations and cosmetics, but examples thereof include 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, polyglycerin derivatives, and sugars such as sucrose and trehalose. Among these, it is preferable to use glycerin, diglycerin, 1,3-butylene glycol, 1,3-propanediol, maltitol, mannitol, and sorbitol, and it is more preferable to use glycerin, diglycerin, 1,3-butylene glycol, and 1,3-propanediol, and it is even more preferable to use glycerin and 1,3-butylene glycol, because they are excellent in moldability, reduction of pain during and after puncturing, excellent solubility, and improvement of skin firmness and elasticity, etc. The polyhydric alcohols of the present invention may be used alone or in combination of two or more kinds.

[0043] The composition before drying in the process of forming the microneedles of the dissolving microneedle preparation of the present invention, i.e., the composition before forming the microneedles, is the amount of polyhydric alcohol in the total amount of the base. underThe limit is not particularly limited, but in terms of excellent moldability, reduction in pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, the amount of polyhydric alcohol in the total amount of the base of the microneedle is preferably 0.0001% by weight or more, more preferably 0.0005% by weight or more, even more preferably 0.001% by weight or more, and most preferably 0.005% by weight or more. In addition, in the composition of the microneedles of the dissolving microneedle preparation of the present invention before molding, the amount of polyhydric alcohol in the total amount of the base is preferably 0.0001% by weight or more, more preferably 0.0005% by weight or more, and most preferably 0.005% by weight or more. above The limit is not particularly limited, but in terms of excellent moldability, reduced pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, the limit 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, based on the total amount of the microneedle base.

[0044] The composition after drying in the process of forming the microneedles of the dissolving microneedle preparation of the present invention, i.e., the composition after forming the microneedles, is the amount of polyhydric alcohol in the total amount of the base. under The limit is not particularly limited, but in terms of excellent moldability, reduction in pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, the amount of polyhydric alcohol in the total amount of the base of the microneedle is preferably 0.001% by weight or more, more preferably 0.01% by weight or more, even more preferably 0.1% by weight or more, and most preferably 0.5% by weight or more. In addition, in the composition after molding of the microneedles of the dissolving microneedle preparation of the present invention, the amount of polyhydric alcohol in the total amount of the base is preferably 0.001% by weight or more, more preferably 0.01% by weight or more, even more preferably 0.1% by weight or more, and most preferably 0.5% by weight or more. above The limit is not particularly limited, but in terms of excellent moldability, reduced pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, the limit 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, based on the total amount of the microneedle base.

[0045] In the composition before drying in the process of forming the microneedles of the dissolving microneedle preparation of the present invention, i.e., in the composition before forming the microneedles, the blending ratio of the polyhydric alcohol to the water-soluble polymer is under The limit is not particularly limited, but in terms of excellent moldability, reduction in pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, the content is preferably 0.001% by weight or more, more preferably 0.01% by weight or more, even more preferably 0.1% by weight or more, and most preferably 0.5% by weight or more, relative to 100% by weight of the water-soluble polymer. above The limit is not particularly limited, but in terms of excellent moldability, reduced pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, the limit is preferably 300% by weight or less, more preferably 200% by weight or less, even more preferably 100% by weight or less, and most preferably 75% by weight or less, relative 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, i.e., in the composition after molding, the blending ratio of polyhydric alcohol to water-soluble polymer is under The limit is not particularly limited, but in terms of excellent moldability, reduction in pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, the content is preferably 0.001% by weight or more, more preferably 0.01% by weight or more, even more preferably 0.1% by weight or more, and most preferably 0.5% by weight or more, relative to 100% by weight of the water-soluble polymer. above The limit is not particularly limited, but from the viewpoints of excellent moldability, reduction in pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, the amount is preferably 300% by weight or less, more preferably 200% by weight or less, even more preferably 100% by weight or less, and most preferably 75% by weight or less, relative to 100% by weight of the water-soluble polymer.

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

[0048] The dissolving microneedle preparation of the present invention can be added with other components other than the components of the present invention as necessary. As other components other than the components of the present invention, for example, other active ingredients, preservatives, pH adjusters, oils and fats, fragrances, colorants, antioxidants, antibacterial and antifungal agents, alcohols, surfactants such as nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants, inorganic salts, lubricants, solvents, purified water, and other components usually used in skin external preparations can be used. The dissolving microneedle preparation of the present invention is preferably added with purified water in terms of excellent moldability and solubility.

[0049] The composition before drying in the process of forming the microneedles of the dissolving microneedle preparation of the present invention, i.e., the composition before forming the microneedles, is the blending ratio of the total amount of niacin and the water-soluble polymer in the total amount of the base. under The limit is not particularly limited, but in terms of excellent moldability, reduction in pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, when the total amount of the base is taken as 100% by weight, the blending ratio of the total amount of niacin and water-soluble polymer in the total amount of the base is preferably 0.0001% by weight or more, more preferably 0.001% by weight or more, even more preferably 0.01% by weight or more, and most preferably 0.05% by weight or more. In addition, in the composition of the microneedles of the dissolving microneedle preparation of the present invention before molding, above The limit is not particularly limited, but in terms of excellent moldability, reduced pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, the limit is preferably 95% by weight or less, more preferably 50% by weight or less, even more preferably 10% by weight or less, and most preferably 5% by weight or less, assuming the total amount of the base to be 100% by weight.

[0050] The composition after drying in the process of forming the microneedles of the dissolving microneedle preparation of the present invention, i.e., the composition after forming the microneedles, is the blending ratio of the total amount of niacin and the water-soluble polymer in the total amount of the base. under The limit is not particularly limited, but in terms of excellent moldability, reduction in pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, when the total amount of the base is taken as 100% by weight, it is preferably 1% by weight or more, more preferably 5% by weight or more, even more preferably 10% by weight or more, and most preferably 30% by weight or more. In addition, in the composition after molding of the microneedles of the dissolving microneedle preparation of the present invention, the blending ratio of the total amount of niacin and the water-soluble polymer in the total amount of the base is preferably 1% by weight or more, more preferably 10% by weight or more, and most preferably 30% by weight or more. above The limit is not particularly limited, but in terms of excellent moldability, reduced pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, the limit is preferably 99% by weight or less, more preferably 97% by weight or less, even more preferably 95% by weight or less, and most preferably 90% by weight or less, assuming the total amount of the base to be 100% by weight.

[0051] The composition before drying in the process of forming the microneedles of the dissolving microneedle preparation of the present invention, i.e., the composition before forming the microneedles, is the blending ratio of the total amount of niacin, water-soluble polymer and polyhydric alcohol in the total amount of the base. under The limit is not particularly limited, but in terms of excellent moldability, reduction in pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, when the total amount of the base is taken as 100% by weight, the blending ratio of the total amount of niacin, water-soluble polymer and polyhydric alcohol in the total amount of the base is preferably 0.0001% by weight or more, more preferably 0.001% by weight or more, even more preferably 0.01% by weight or more, and most preferably 0.07% by weight or more. aboveThe limit is not particularly limited, but in terms of excellent moldability, reduced pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, the limit is preferably 99.9% by weight or less, more preferably 50% by weight or less, even more preferably 10% by weight or less, and most preferably 5% by weight or less, assuming the total amount of the base to be 100% by weight.

[0052] The composition after drying in the process of forming the microneedles of the dissolving microneedle preparation of the present invention, i.e., the composition after forming the microneedles, is the blending ratio of the total amount of niacin, water-soluble polymer and polyhydric alcohol in the total amount of the base. under The limit is not particularly limited, but in terms of excellent moldability, reduction in pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, when the total amount of the base is taken as 100% by weight, the content of niacin in the total amount of the base is preferably 1% by weight or more, more preferably 5% by weight or more, even more preferably 10% by weight or more, and most preferably 40% by weight or more. 、 water soluble polymer and polyhydric alcohol The total amount of the mixture ratio above There is no particular limit to the content, but in terms of excellent moldability, reduced pain during and after puncturing, excellent solubility, and improved skin firmness and elasticity, the content is preferably 99.9% by weight or less, more preferably 99% by weight or less, even more preferably 95% by weight or less, and most preferably 92.5% by weight or less, assuming that the total amount of the base is 100% by weight.

[0053] When the dissolving microneedle preparation of the present invention contains purified water, the blending ratio of purified water to the total amount of niacin and water-soluble polymer in the composition before drying in the process of forming the microneedles, i.e., the composition before forming the microneedles, is not particularly limited, but in terms of excellent formability, reduced pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, when the total amount of niacin and water-soluble polymer is taken as 1, the blending ratio is preferably 1:0.1 to 100,000, more preferably 1:1 to 10,000, even more preferably 1:10 to 10,000, and most preferably 1:50 to 1,000.

[0054] When the dissolving microneedle preparation of the present invention contains purified water, the blending ratio of purified water to the total amount of niacin and water-soluble polymer in the composition after drying in the process of forming the microneedles, i.e., the composition after forming the microneedles, is not particularly limited, but in terms of excellent moldability, reduced pain during and after puncturing, excellent solubility, and improvement in skin firmness and elasticity, when the total amount of niacin and water-soluble polymer is taken as 1, the blending ratio is preferably 1:0.0001-30, more preferably 1:0.001-20, even more preferably 1:0.01-10, and most preferably 1:0.05-5.

[0055] When the dissolving type microneedle preparation of the present invention contains purified water, the composition before drying in the process of forming the microneedles, i.e., the composition before forming the microneedles, is the blending ratio of purified water to the total amount of the base. under The limit is not particularly limited, but in terms of excellent moldability and solubility, when the total amount of the base is taken as 100% by weight, the limit is preferably 30% by weight or more, more preferably 50% by weight or more, even more preferably 90% by weight or more, and most preferably 95% by weight or more. In addition, in the composition of the dissolving microneedle preparation of the present invention before molding the microneedles, the blending ratio of purified water in the total amount of the base is aboveThe limit is not particularly limited, but in terms of excellent moldability and solubility, when the total amount of the base is taken as 100% by weight, it is preferably 99.9% by weight or less, more preferably 99.5% by weight or less, and most preferably 99% by weight or less.

[0056] When the dissolving type microneedle preparation of the present invention contains purified water, the composition after drying in the process of forming the microneedles, i.e., the composition after forming the microneedles, is the blending ratio of purified water to the total amount of the base. under The limit is not particularly limited, but in terms of excellent moldability and solubility, when the total amount of the base is taken as 100% by weight, the limit is preferably 0.5% by weight or more, more preferably 1% by weight or more, even more preferably 5% by weight or more, and most preferably 7.5% by weight or more. In addition, in the composition after molding of the microneedles of the dissolving microneedle preparation of the present invention, the blending ratio of purified water in the total amount of the base is above The limit is not particularly limited, but in terms of excellent moldability and solubility, when the total amount of the base is taken as 100% by weight, it is preferably 70% by weight or less, more preferably 60% by weight or less, and most preferably 50% by weight or less.

[0057] The microneedles of the dissolving microneedle formulation of the present invention may be any microneedles containing the component of the present invention, and may be, for example, needle-shaped projections having a coating layer formed thereon containing the component of the present invention, or needle-shaped projections encapsulating the component of the present invention.

[0058] Representative components other than the components of the present invention contained in the dissolving microneedle preparation of the present invention will be further described below.

[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 and plants used in cosmetics, quasi-drugs, external medicines, etc. Representative examples include glycyrrhizinic 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, resorcin and its derivatives, whitening agents such as glutathione, antiseborrheic agents such as sulfur and thianthrol, bactericides such as salicylic acid and Phellodendron bark extract, tocopherol and its derivatives, plant components such as licorice, aloe, and tea leaves, and hormones such as estradiol. When using plant ingredients, the whole plant, leaves (leaf blades, petioles, etc.), fruits (mature, unripe, etc.), seeds, flowers (petals, ovaries, etc.), stems, rhizomes, roots, tubers, etc. may be used as they are, cut, crushed, pulverized, squeezed, extracted, or may be dried or powdered after such treatment.

[0060] The dissolving microneedle preparation of the present invention moisturizes the skin and improves wrinkles, sagging, firmness, elasticity, or dullness, and has a cosmetic effect, and can therefore be suitably used in any of cosmetics, quasi-drugs, medicines, and other pharmaceuticals intended to improve skin quality, rejuvenate the skin, tighten the skin, condition the skin, refine the skin texture, keep the skin healthy, tighten the skin, moisturize the skin, replenish and maintain the skin's moisture and oil content, maintain the skin's flexibility, protect the skin, prevent the skin from drying, soften the skin, firm the skin, give the skin a glossy finish, smooth the skin, and make fine wrinkles caused by dryness less noticeable.

[0061] The dissolving microneedle preparation of the present invention is not limited to those labeled on the product packaging, etc. with the components of the present invention (niacin and water-soluble polymer) as cosmetic active ingredients for moisturizing the skin, improving wrinkles, sagging, firmness, elasticity, or dullness, etc. For example, the active ingredient may not be specified, or a specific material other than the components of the present invention may be labeled as the active ingredient.

[0062] The dissolving microneedle preparation of the present invention exhibits the effect of improving firmness or elasticity as shown in the examples described below, and can therefore be an excellent composition for improving skin firmness, skin elasticity, and cosmetic composition. EXAMPLES

[0063] The dissolving microneedle preparation of the present invention will be described in more detail below with reference to examples. However, the technical scope of the present invention is not limited to such examples. In the following, unless otherwise specified, "%" represents % by weight. The numerical values ​​of the compositions in Tables 1 to 15 indicate %.

[0064] <Test Example 1: Evaluation of moldability> Sodium hyaluronate with an average molecular weight of 1.2 million to 2.2 million was used as the water-soluble polymer. Niacinamide was used as the niacin. Concentrated glycerin was used as the polyhydric alcohol.

[0065] A solution was prepared by swelling and dissolving sodium hyaluronate having an average molecular weight of 1.2 to 2.2 million in purified water so that the composition before drying would be the composition in Table 1. 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. Thereafter, 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] ·Moldability evaluation criteria Completely removable: Yes Partially impossible to peel off: △ Impossible to peel: ×

[0067] The results are shown in Table 1. 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 mold a dissolving type microneedle preparation. On the other hand, when sodium hyaluronate and concentrated glycerin were contained (Comparative Example 2), it was not possible to peel off from the mold and mold a dissolving type microneedle preparation. Also, although it was not possible to peel off when sodium hyaluronate and concentrated glycerin were contained (Comparative Example 2), it was possible to completely peel off from the mold and mold a dissolving type microneedle preparation when sodium hyaluronate and concentrated glycerin were further contained with niacinamide (Example 2). That is, it is understood that when niacinamide and sodium hyaluronate were contained, it was excellent in moldability. Also, it is understood that when niacinamide was contained in hyaluronic acid and concentrated glycerin, moldability was improved and it became possible to mold a dissolving type microneedle preparation. Therefore, by containing niacinamide, a water-soluble polymer and a polyhydric alcohol, a dissolving type microneedle preparation can be obtained.

[0074] <Test Example 2: Evaluation of solubility and firmness / elasticity> Sodium hyaluronate with an average molecular weight of 1.2 million to 2.2 million was used as the water-soluble polymer. As the water-soluble polymer, acetylated sodium hyaluronate with an average molecular weight of 100,000 was used. Niacinamide was used as the niacin. Concentrated glycerin was used as the polyhydric alcohol. As the polyhydric alcohol, 1,3-butylene glycol was used.

[0075] A solution was prepared by swelling and dissolving hyaluronic acid shown in Table 6 in purified water so that the composition before drying was the composition shown in Table 6. For Comparative Example 2 and Examples 3 to 4, niacinamide and / or polyhydric alcohol shown 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, adhesive tape was applied, and the molded product was peeled off from the mold to obtain a dissolving type microneedle preparation. The obtained dissolving type microneedle preparation was applied under the eyes of three men and women for 1 hour, and the solubility and firmness / elasticity at the time of puncturing and after puncturing were evaluated by assigning points according to the following evaluation criteria.

[0076] Solubility evaluation criteria Microneedle dissolution time less than 15 minutes: 3 Microneedle dissolution time: 15 minutes or more but less than 30 minutes: 2 Microneedle dissolution time: 30 minutes or more but less than 60 minutes: 1 Microneedle dissolution time is 60 minutes or more: 0

[0077] · Evaluation criteria for elasticity and firmness The firmness and elasticity of the patch one hour after application were significantly improved compared to before application: 3 The firmness and elasticity of the patch one hour after application was improved compared to before application: 2 The firmness and elasticity of the patch one hour after application was slightly improved compared to before application: 1 The firmness and elasticity after 1 hour of application was unchanged compared to before application: 0

[0078] The scores given by the three men and three women were averaged and the test products were rated using the following criteria: ◎, ○, △, ×. Evaluation criteria for test items Average score of 2.5 or above: ◎ Average score is between 1.5 and 2.5: ○ Average score is 0.5 or more but less than 1.5: △ Average score less than 0.5: ×

[0079] The results are shown in Figure 1 and Table 6. 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 Figure 1 and Table 6, when niacinamide is not contained (Comparative Example 1), both solubility and firmness / elasticity are poor, and it is not a preparation that is excellent overall, but when niacinamide and sodium hyaluronate or acetylated sodium hyaluronate are contained (Examples 3 to 9), it is excellent in solubility or firmness / elasticity, and it is an excellent dissolving type microneedle preparation overall. Furthermore, when concentrated glycerin or 1,3-butylene glycol is contained in addition to niacinamide, sodium hyaluronate or acetylated sodium hyaluronate, it is further excellent in solubility or firmness / elasticity, and it is an extremely excellent dissolving type microneedle preparation overall. Moreover, Examples 5, 7 to 9 are excellent in reducing pain compared to Comparative Examples.

[0090] Below, various formulation examples of the dissolving microneedle preparation of the present invention are given. However, the technical scope of the present invention is not limited to such formulation examples. Hereinafter, "%" means % by weight unless otherwise specified.

[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 would be as shown in Table 15. The solution was poured into a mold and allowed to dry naturally at 25°C for 24 hours, resulting in a microneedle preparation with good moldability. The resulting microneedle preparation is excellent in reducing pain, and also has excellent solubility, firmness, and elasticity. [Industrial Applicability]

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

Claims

1. Niacin, and A dissolving microneedle preparation containing one or more polymers selected from hyaluronic acid, sodium hyaluronate, sodium acetylated hyaluronate, hydrolyzed hyaluronic acid, and hydrolyzed sodium hyaluronate, A dissolving microneedle preparation in which, in the composition after molding, when the total amount of the base is taken as 100% by weight, the content of purified water is 7.5% by weight or more and 70% by weight or less, the blended amount of niacin is 0.1% by weight or more and 40% by weight or less, and the blended amount of the polymer is 30% by weight or more and 90% by weight or less.

2. The dissolving microneedle according to claim 1, further comprising a polyhydric alcohol.

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