Microneedle array for cosmetic use

Abstract

To provide novel administration means of a valuable object having a fat dissolving action.SOLUTION: Microneedle formulation contains any one or more types of a lipolytic agent, a fat dissolving agent and a fat metabolism promoter and aims at fat reduction and / or partial slimming and / or skin tightening, and microneedle formulation employs a water-soluble polymer as a base, and is formed of a microneedle array containing one or more types selected from a group consisting of a lipase, a phosphatidylcholine and deoxycholic acid.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a microneedle array for the purpose of subcutaneous fat decomposition and dissolution. More specifically, it relates to the technical field of microneedles containing a fat-dissolving agent or the like as a main component as a valuable component.

Background Art

[0002] Subcutaneous fat accumulation is associated with dysfunction of adipocytes, and the accumulated triglycerides are enzymatically decomposed and further decomposed into fatty acids, glycerol, and / or glycerol esters. For various reasons, triglyceride accumulation occurs in adipocytes, resulting in subcutaneous fat accumulation. As a result, it becomes overweight and causes problems in treatment and aesthetics.

[0003] For obesity presenting an excessive fat layer among this subcutaneous fat accumulation and obesity, a method of directly injecting a composition for removing subcutaneous fat accumulation subcutaneously has been adopted. For this, phosphatidylcholine preparations typified by Lipostabil of Sanofi-Aventis are used (Patent Documents 1, 2). On the other hand, subcutaneous injection of deoxycholic acid is also known. However, it is regarded as a situation problematic from the viewpoint of safety such as pain and skin swelling during the operation, and it can be said that it is a method with a high risk. Also, in the case of injection, the injection needle must be shaken subcutaneously for injection over a certain area. Furthermore, due to unevenness of the injected liquid, the convenience of fat dissolution changes, and unevenness of the skin occurs.

Prior Art Documents

[0005] The object of the present invention is to provide a novel method for administering a valuable substance having a fat-dissolving effect. [Means for solving the problem]

[0006] Microneedles penetrate the stratum corneum, which hinders the absorption of fat-dissolving agents, and are expected to facilitate the diffusion of fat-dissolving agents into the subcutaneous tissue. In particular, they can dissolve subcutaneous fat in obese areas, leading to localized fat reduction, reduction of eye bags, and the creation of a smaller facial contour. Furthermore, they can be expected to have a tightening effect by dissolving subcutaneous fat in sagging areas. Unlike injections, microneedle patches allow for the treatment of a large area with a single application. Until now, there have been no microneedle formulations aimed at fat dissolution, so when microneedling the above-mentioned valuable substances, there was no knowledge whatsoever regarding the concentration of the valuable substances, the frequency of skin application, etc. Therefore, ensuring the combination of valuable substances, the stability of the formulation, and the skin penetration became important challenges. The inventors have solved these problems and succeeded in manufacturing a microneedle formulation containing valuable substances with fat-dissolving properties, thus completing the present invention. The present invention is as follows: [1] A microneedle preparation containing one or more of the following: a fat-decomposing agent, a fat-dissolving agent, or a fat-metabolism-promoting agent, for the purpose of fat reduction and / or localized fat reduction and / or skin tightening. [2] A microneedle preparation for the purpose of fat reduction and / or localized fat reduction and / or skin tightening, containing 0.1% by mass or more of one or more fat-reducing components selected from the group consisting of fat-decomposing agents, fat-dissolving agents and fat-metabolism promoters. [3] A microneedle preparation according to [1] or [2], wherein the lipolytic agent is lipase. [4] The microneedle preparation described in [3], comprising lipase, Mg salt, and Ca salt. [5] The microneedle preparation according to [1] or [2], wherein the fat-dissolving agent is one or more selected from the group consisting of phosphatidylcholine, adenosine triphosphate and its sodium salt, and deoxycholic acid. [6] The microneedle preparation according to [1] or [2], wherein the fat metabolism promoter is one or more selected from the group consisting of amino acids, L-carnitine, inositol, capsaicin, and caffeine. [7] The microneedle preparation according to [6], wherein the amino acid is one or more selected from the group consisting of tyrosine, serine, threonine, phenylalanine, tryptophan, isoleucine, lysine, arginine, betaine, histidine, glutamine, glycine, and cysteine. [8] A microneedle preparation according to any one of [1] to [7], having a needle length of 50 to 350 μm and intended for insertion into the epidermis. [9] A microneedle preparation according to any one of [1] to [7], having a needle length of 351 to 1000 μm and being inserted into the dermis.

[10] A microneedle preparation according to any one of [1] to [9], comprising a microneedle array with a water-soluble polymer as a base and containing one or more selected from the group consisting of lipase, phosphatidylcholine, and deoxycholic acid.

[11] A microneedle preparation according to any one of [1] to [9], comprising a microneedle array based on a water-soluble polymer and containing one or more selected from the group consisting of lipase, phosphatidylcholine, deoxycholic acid, tyrosine, L-carnitine, and caffeine.

[12] A microneedle preparation according to any one of [1] to

[11] , wherein the fat-dissolving agent consists of a combination of phosphatidylcholine and deoxycholic acid.

[13] A microneedle preparation according to any one of [1] to

[12] , further containing an enzyme-fermented plant extract.

[14] A microneedle formulation according to any one of [1] to

[13] , wherein the support film having an adhesive layer on one side is on the side opposite to the side on which the microneedles are densely arranged.

[15] The microneedle preparation according to

[14] , wherein the microneedle preparation comprises a soluble microneedle array, and the adhesive layer contains the same component as the lipolytic agent, lipolytic agent, or lipolytic agent contained in the soluble microneedle array, at the same concentration as or less than the concentration in the microneedle array.

[16] A microneedle preparation for reducing eye bags, as described in any of [1] to

[15] . [Effects of the Invention]

[0007] According to the present invention, subcutaneous fat can be easily and uniformly dissolved. [Brief explanation of the drawing]

[0008] [Figure 1] A cross-sectional view showing an example of a method for manufacturing a microneedle array according to the present invention. [Figure 2A] Photograph of the area under the eyelid before use in Test Example 2 [Figure 2B] Photograph of the area under the eyelid after use in Test Example 2 [Figure 3] Graph showing the change in subcutaneous fat thickness in Test Example 3 [Modes for carrying out the invention]

[0009] Microneedle formulations (microneedle arrays) This formulation consists of a microneedle array in which cone-shaped, pyramidal, or needle-shaped microneedles, each 50 to 1000 μm in height, are arranged in a dense network on a substrate 10 to 200 μm thick. When inserting a microneedle formulation into the epidermis, a needle length of 50 to 350 μm is preferable. When inserting a microneedle formulation into the dermis, a needle length of 351 to 1000 μm is preferable.

[0010] The microneedles contain a valuable substance dissolved or dispersed in a suspension within the base. Alternatively, the valuable substance may be applied to the tip of the needle.

[0011] The micro needle preparation of the present invention contains, as a valuable substance, at least one of a lipolytic agent, a lipolytic agent or a fat metabolism promoter. The valuable substance is a component that acts on fat reduction and is contained in the micro needle preparation at 0.1% by mass or more. The micro needle preparation of the present invention is preferably used for the purpose of fat reduction or / and partial slimming or / and muscle tightening. The content of the valuable substance is preferably 0.1 to 100% by mass, more preferably 0.2 to 80% by mass, for the decomposition, dissolution or promotion of fat metabolism of subcutaneous fat. Further, the amount of the valuable substance per square centimeter is preferably 1 μg to 1000 mg. In addition to the valuable substances having lipolytic, lipolytic and fat metabolism promoting effects in the micro needle array, components that promote fat burning, components that promote the decomposition and excretion of fat from fat cells, muscle tightening components, etc. can be used in combination to enhance the lipolytic and lipolytic effects.

[0012] Examples of the lipolytic agent include lipolytic enzymes such as lipase, and hormones such as glucagon, adrenaline, noradrenaline, ghrelin, growth hormone, testosterone, and cortisol. Also, according to the care site and purpose, protease as a proteolytic enzyme, collagenase as a collagen degrading enzyme, hyaluronidase as a hyaluronic acid degrading enzyme, and enzyme-fermented plant extracts obtained by fermentation extraction from vegetables, fruits and seaweeds can be used in combination effectively. The lipolytic agent is preferably lipase. When using lipase, a stabilizer of lipase may coexist. For example, glycerol, glycine, mercaptoethanol, Triton X-100, Triton N-101, deoxycholic acid, Mg 2+ ions, Ca 2+ ions, BSA, salts, etc. may be mentioned. Mg 2+ ions and Ca 2+ ions may coexist as a salt.

[0013] Examples of fat solvents include phosphatidylcholine, hiba extract, tyrosine, adenosine triphosphate and its sodium salt, thuja occidentalis, persian silk tree, methylpropanediol, mannuronic acid methylsilanol, mugwort, karakusa kemman, deoxycholic acid, chenodeoxycholic acid, etc. Furthermore, xanthine derivatives (such as caffeine, theophylline, theobromine, xanthine, aminophylline, choline theophylline, diprophylline, proxiphylline and oxtrifylline, etc.), extract of cocculus orbiculatus, extract of thistle, extract of stephania tetrandra, extract of zedoary, extract of karakusa kemman, extract of platycodon grandiflorum (platycodon root), extract of euonymus alatus, extract of pepper, extract of sarashina yoma root, extract of tsupokusa, extract of gardenia fruit, extract of fumaria officinalis, extract of strawberry leaves, etc. are also included. The fat solvent is preferably at least one selected from the group consisting of phosphatidylcholine, adenosine triphosphate and its sodium salt, and deoxycholic acid. Among them, the fat solvent composed of a combination of phosphatidylcholine and deoxycholic acid is more preferable as it also improves the stability of phosphatidylcholine.

[0014] Examples of fat metabolism promoters include amino acids such as tyrosine, serine, threonine, phenylalanine, tryptophan, isoleucine, lysine, arginine, betaine, histidine, glutamine, glycine, cysteine, etc. Examples of components that promote fat burning include L-carnitine, inositol, capsaicin, caffeine, coenzyme Q10, catechin, etc. The fat metabolism promoter is preferably at least one selected from the group consisting of amino acids, L-carnitine, inositol, capsaicin, and caffeine, and it is also preferable to use at least one of the above-mentioned amino acids.

[0015] In the case of non-dissolvable microneedles, the microneedle array of the present invention is manufactured by injection molding, press molding, etc., and the tip of the needle is coated with a valuable substance and dried before use. As a base material, plastics such as PGA (polyglycolic acid), PLGA (polylactic acid-glycolic acid copolymer), PET (polyethylene terephthalate), and polyethylene are convenient for molding.

[0016] In the present invention, a soluble microneedle array is more preferred. Suitable base materials include water-soluble or biodegradable polymers, such as sodium hyaluronate, hyaluronic acid oligomers and their derivatives, sodium chondroitin sulfate, hydroxypropyl cellulose, proteoglycans, gelatin, polyvinylpyrrolidone, hydrolyzed collagen, carboxymethylcellulose, polyvinyl alcohol, dextran, dextrin, etc. While it is simplest to dissolve the valuable substance in the base, it may also be applied to the needle tip.

[0017] While the above-mentioned beneficial substances and base are essential components in this invention, the addition of other beneficial substances for skin is not limited. Examples include pigment inhibitors, moisturizers, metabolic activators, antioxidants, reactive oxygen species scavengers, and radical scavengers.

[0018] Pigmentation inhibitors The present invention may include the addition of pigmentation inhibitors. Specific examples of pigmentation inhibitors include p-aminobenzoic acid derivatives, salicylic acid derivatives, benzenesulfonamide derivatives, imidazole derivatives, naphthalene derivatives, hydroxyanthranilic acid or its salts and their derivatives, anthranilic acid derivatives, coumarin derivatives, allantoin derivatives, nicotinic acid derivatives, ascorbic acid or its salts and their derivatives, tocopherol or its salts and their derivatives, tocotrienol or its salts and their derivatives, kojic acid or its derivatives, oxybenzone, benzophenone, guaiazulene, shikonin, baicalin or its salts and their derivatives, baicalein or its salts and their derivatives Examples include berberine or its salts and derivatives thereof, apigenin or its salts and derivatives thereof, luteolin or its salts and derivatives thereof, kaempferol or its salts and derivatives thereof, quercetin or its salts and derivatives thereof, quercitrin or its salts and derivatives thereof, isoquercitrin or its salts and derivatives thereof, rutin or its salts and derivatives thereof, myricetin or its salts and derivatives thereof, naringenin or its salts and derivatives thereof, hesperidin or its salts and derivatives thereof, glutathione or its salts and derivatives thereof, ellagic acid or its salts and derivatives thereof, etc.

[0019] Moisturizer The present invention may contain added humectants. Specific examples of humectants include quince seed, agar or its derivatives, casein, glucose, galactose, mannose, xylose, fructose, maltose, isomaltose, cellobiose, genthiobiose, trehalose, pyralose, 1,3-butylene glycol, glycerin, propylene glycol, polyethylene glycol, dipropylene glycol, 1,2-pentanediol, 1,5-pentanediol, 1,2-hexanediol, 1,6-hexanediol, mannitol and sorbitol, 1,2-propanediol, 1,3-propanediol, polypropylene glycol, and 1,2-butanediol. , 1,3-butanediol, 1,4-butanediol, pentylene glycol, hexylene glycol, 1,3-pentanediol, 1,4-pentanediol, erythritol, pentaerythritol, dipentaerythritol, xylitol, maltitol, inositol, panthenol or its derivatives, dextrin, gelatin, pectin, starch, carrageenan, carboxymethyl chitin or chitosan, chitosan salt, sulfated chitin or chitosan, phosphorylated chitin or chitosan, alginic acid or its salt, hyaluronic acid or its salt, chondroitin sulfate or its salt, β-1,3-glucan, β-1,4-glucan, β-1,Examples include 6-glucan, glucosamine, heparin, ethylcellulose, methylcellulose, carboxymethylcellulose, carboxyethylcellulose, sodium carboxyethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, nitrocellulose, crystalline cellulose, hydroxypropyl methylcellulose, polyvinyl alcohol, polyvinyl methyl ether, polyvinylpyrrolidone, polyacrylates, carboxyvinyl polymers, water-soluble polymers such as dermatan sulfate and keratan sulfate, pyrrolidone carboxylic acid or its salts, polyglutamic acid or its salts, pyrrolidone carboxylic acid contained in natural moisturizing factors, urea, urocanic acid, betaine, sodium lactate, aspartic acid, glutamic acid, isoleucine, histidine, phenylalanine, threonine, serine, valine, proline, glycine, alanine, lysine, arginine, ceramides such as ceramide 1, ceramide 2, ceramide 3, ceramide 4, ceramide 5, ceramide 6II, and ceramide 9.

[0020] Metabolic activators Metabolic activators may be added to the present invention. Specific examples of metabolic activators include: Vitamin A group: retinol or its salts and derivatives thereof, retinal or its salts and derivatives thereof, dehydroretinal or its salts and derivatives thereof, retinoic acid or its salts and derivatives thereof, carotene or its salts and derivatives thereof, lycopene or its salts and derivatives thereof, Vitamin B group: Thiamine or its salts and derivatives thereof, riboflavin or its salts and derivatives thereof, pyridoxine or its salts and derivatives thereof, pyridoxal or its salts and derivatives thereof, cyanocobalamin or its salts and derivatives thereof, folic acid or its salts and derivatives thereof, nicotinic acid or its salts and derivatives thereof, pantothenic acid or its salts and derivatives thereof, biotin or its salts and derivatives thereof, choline or its salts and derivatives thereof, inositol or its salts and derivatives thereof, Vitamin C group: Ascorbic acid or its salts and their derivatives, Vitamin D group: Ergocalciferol or its salts and derivatives thereof, cholecalciferol and its salts and derivatives thereof, Vitamin E group, etc.: Tocopherol or its salts and derivatives thereof, tocotrienol or its salts and derivatives thereof, ubiquinone or its salts and derivatives thereof, linoleic acid or its salts and derivatives thereof, linolenic acid or its salts and derivatives thereof, arachidonic acid or its salts and derivatives thereof, etc., carnitine or its salts and derivatives thereof, ferulic acid or its salts and derivatives thereof, γ-oryzanol or its salts and derivatives thereof, Vitamin P group: Rutin or its salts and derivatives thereof, hesperidin or its salts and derivatives thereof, amino acids and others: Valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid, hydroxylysine, arginine, ornithine, histidine or derivatives thereof, etc., as well as their sulfates, phosphates, nitrates, citrates, or amino acid derivatives such as pyrrolidone carboxylic acid, etc., α-hydroxy acids such as glycolic acid, citric acid, malic acid, tartaric acid, lactic acid, succinic acid, etc., 2-hydroxycarboxylic acids, polyhydroxycarboxylic acids or hydroxypolycarboxylic acids, lactobionic acid, photosensitizer 301, hinokitiol, pantothenic acid or derivatives thereof, allantoin, trimethylglycine, proteoglycans, etc.

[0021] Antioxidants Antioxidants may be added to the present invention. Specific examples of antioxidants include ascorbic acid or its salts and derivatives thereof, tocopherol or its salts and derivatives thereof, tocotrienol or its salts and derivatives thereof, butylhydroxytoluene (BHT), butylhydroxyanisole (BHA), coenzyme Qn (n=7~10), pyrroloquinoline quinone, propyl gallate, sesamol, carotenoids, and the like.

[0022] Reactive oxygen species scavenger / Radical scavenger The present invention may include the addition of reactive oxygen species scavengers and radical scavengers. Specific examples of reactive oxygen species scavengers and radical scavengers include superoxide dismutase, catalase, glutathione peroxidase, bilirubin, quercetin, quercitrin, catechin, catechin derivatives, rutin or its derivatives, gallic acid or its salts and their derivatives, curcumin or its salts and their derivatives, transferrin, ceruloplasmin, coenzyme Qn (n=7~10), uric acid, bilirubin, metallothionein, and the like.

[0023] In addition to the above-mentioned components, the present invention may also include components commonly used in topical skin preparations such as cosmetics and pharmaceuticals. It consists of one or more components, such as aqueous components, oily components, plant extracts, animal extracts, powders, surfactants, oils, alcohols, pH adjusters, preservatives, thickeners, pigments, and fragrances, which are part of the base and may also function as valuable substances due to their effects on the skin (for example, skin tightening effect).

[0024] The method for manufacturing the microneedle array of the present invention is not particularly limited and can be manufactured by any conventionally known method. For example, a method can be used in which a raw material aqueous solution is poured into a mold in which the shape of microneedles is perforated, in which a valuable substance is dissolved or suspended in an aqueous solution or suspension consisting of the above-mentioned water-soluble polymer base, and other components are added as needed, and then dried and peeled off. After peeling, it may be cut into the shape of a patch and backed with an adhesive support before use. The above describes a method for manufacturing a dissolvable microneedle array. The microneedle array of the present invention is effective not only in dissolvable form but also in coated form. The method for manufacturing a coated form microneedle array involves preparing a microneedle array in advance by injection molding, press molding, etc., and then coating the needle tips with a mixture of valuable material and base material and drying it.

[0025] The size of a patch consisting of a microneedle array (microneedle patch) is between 0.5 and 300 square centimeters. If the size is less than 0.5 square centimeters, the effect is limited and it is difficult to achieve efficacy. If it exceeds 300 square centimeters, adhesion problems are likely to occur when covering the body surface. To cover a large body surface, multiple microneedle patches of 300 square centimeters or less can be used. The appropriate needle length is 50 to 1000 μm. Microneedles between 50 and 350 μm act on the epidermis. Microneedles longer than that also act on the dermis.

[0026] For a microneedle patch to be stably applied to and retained on the skin, it is not essential, but preferable, for the patch to have an adhesive support on its back. Here, "back" refers to the side opposite to the side where the microneedles are arranged. The adhesive support is a support film having an adhesive layer on one side.

[0027] In the present invention, an adhesive sheet made of a commercially available adhesive can be used as the adhesive layer. Rubber-based adhesives, silicone-based adhesives, etc., can be used, but acrylic adhesives are preferred considering adhesion to the skin and adhesion to the support film. Specifically, copolymers of alkyl acrylates, and copolymers of alkyl acrylates mainly with acrylic acid, acrylamide, vinyl acetate, etc. Plasticizers such as isopropyl myristate or isopropyl palmitate may be added to these adhesives to improve skin adhesion. The thickness of the adhesive layer is preferably 10 μm to 300 μm. Specifically, HiPAS® adhesive (acrylic ester, manufactured by Cosmedi Pharmaceutical Co., Ltd.) and MASCOS10 (trade name) adhesive (acrylic ester, manufactured by Cosmedi Pharmaceutical Co., Ltd.) can be suitably used.

[0028] In this invention, the valuable substance, the fat-dissolving agent, is often a low-molecular-weight compound. In such cases, even if it is contained in the microneedles, the fat-dissolving agent may diffuse into the adhesive layer during long-term storage, resulting in a decrease in the fat-dissolving agent content in the microneedles. The same phenomenon applies to the fat-degrading agent and fat metabolism promoter used. To prevent this, it is effective from the standpoint of storage stability to include the same substance in the adhesive as the valuable substance impregnated into the microneedles to prevent diffusion into the adhesive. The concentration of the fat-dissolving agent, fat-degrading agent, or fat metabolism promoter in the adhesive should preferably be the same as or less than the concentration in the microneedle array.

[0029] The microneedle formulation, microneedle array, or microneedle patch of the present invention is applied to the skin from which fat is to be removed. The application area is the entire skin and is not particularly limited. The number of patches to be applied is determined according to the area from which fat is to be removed. The application time for one application is approximately 1 second to 24 hours, and for multiple applications, it is effective to apply them at intervals of 0 to 1 day. It is also effective to instantly dissolve the tips of the microneedles in the skin by supplying water from behind the array immediately after application to the skin, thereby promoting the absorption of beneficial substances into the skin. Such application methods are particularly effective in beauty salons and other similar settings.

[0030] This invention makes it possible to slim down specific areas of the body. It is particularly effective when applied to the face. For example, when applied to the area under the eyelids, it can reduce the puffiness (eye bags) under the eyelids. [Examples]

[0031] The present invention will be described in more detail below with reference to the following examples. These examples are merely illustrative examples of the present invention, and the scope of the present invention is not limited to these examples.

[0032] Example 1 Fabrication of a microneedle array Figure 1 is a cross-sectional view showing an example of a method for manufacturing a microneedle array according to the present invention. In the figure, 1 is a mold in which a cone-shaped microneedle pattern is formed by lithography, which involves irradiating a photosensitive resin with light, and then the cone-shaped microneedle pattern is transferred by electroforming to form a recess 11 for forming cone-shaped microneedles. 2 is a microneedle raw material liquid cast into the recess 11 for forming microneedles. The microneedle formation recesses 11 are cone-shaped with a base diameter of 0.6 mm, a tip diameter of 0.02 mm, and a depth of 0.2 mm, and are arranged in a grid pattern at 0.8 mm intervals. An aqueous solution (microneedle raw material solution) was prepared by dissolving 4 parts by mass of hyaluronic acid (manufactured by Kikkoman Biochemifa, trade name "FCH-SU") and 0.1 parts by mass of lipase (manufactured by Wako Pure Chemical Industries, trade name "Lipase AK Amano") in 100 parts by mass of water at room temperature. To this aqueous solution, 0.2 parts by mass of phosphatidylcholine (Wako Pure Chemical Industries) and 0.8 parts by mass of deoxycholic acid (Wako Pure Chemical Industries), dissolved in ethanol and glycerin, were added to form an oval shape (10 x 50 mm, short axis x long axis). The solution was cast onto mold 1, and after the water in the aqueous solution evaporated, it was peeled off mold 1 and punched out in an oval shape (10 x 50 mm, short axis x long axis).

[0033] Fabrication of a microneedle array with protective adhesive tape The microneedle array with protective adhesive tape of the present invention was obtained by setting an elliptical microneedle array (10 x 50 mm, short axis x long axis) in the center of an adhesive tape with a rectangular support with rounded corners (16 x 60 mm).

[0034] Test Example 1: In vitro test A microneedle array without a support, prepared in Example 1, was placed in close contact with the center of the top surface of a 2cm x 2cm x 1cm thick piece of beef tallow. 40mg of water was dropped onto the center of the microneedle array using a dropper to promote its dissolution. The top surface of the beef tallow was observed after being left at room temperature for 20 hours. The center where the water was dropped formed a lens-shaped depression, with the deepest part of the depression being approximately 1mm. This phenomenon is due to the generation of beef tallow decomposition components by the fat-decomposing and dissolving components incorporated in the microneedles, or the generation of beef tallow-soluble components through interaction with the dissolving components. These products diffused inward within the beef tallow, resulting in the formation of a lens-shaped depression.

[0035] Comparative Test Example 1 The same test was conducted as in Test Example 1, except that the microneedle array that was tightly attached consisted solely of hyaluronic acid. After 20 hours at room temperature, there was no change whatsoever on the surface of the beef tallow.

[0036] Example 2: In vivo study A microneedle array, prepared in the same manner as in Example 1 except that it did not contain lipase, was applied to the underside of the right eyelid of an adult male volunteer before going to bed and removed the following morning. The same application was repeated for four days (a total of four times). Nothing was applied to the underside of the left eyelid. Photographs of the underside of the eyelids before and after the experiment are shown in Figures 2A and 2B. It is clear that the puffiness (eye bag) under the right eyelid was reduced compared to the left eyelid.

[0037] Example 2 Preparation of test microneedle arrays and protective adhesive tapes A microneedle array was prepared in the same manner as in Example 1. The main composition of the array was 72 parts by mass of hyaluronic acid, 5 parts by mass of phosphatidylcholine, 15 parts by mass of sodium deoxycholate, and 5 parts by mass of hydrolyzed collagen, per 100 parts by mass of the microneedle array. The prepared microneedle array was punched out into an elliptical shape and subjected to testing in the same manner as in Example 1. In the adhesive tape with support, a rubber-based adhesive was used, and to prevent the transfer of phosphatidylcholine and sodium deoxycholate from the array to the adhesive, the adhesive also contained phosphatidylcholine and sodium deoxycholate. Specifically, the adhesive (100 parts by mass) contained 1 part by mass each of phosphatidylcholine and sodium deoxycholate in a basic composition consisting of styrene-isoprene resin, tackifying resin, and oil. The microneedle array with protective adhesive tape obtained in the same manner as in Example 1 had the same shape as in Example 1.

[0038] Test Example 3 Three adult female volunteers had the microneedle array with protective adhesive tape from Example 2 applied to their cheeks before going to bed and removed the following morning. A similar application was repeated three times a week for two weeks to evaluate the effectiveness of the microneedle array. Subcutaneous fat thickness at the microneedle array application sites was measured before and after the test using a subcutaneous fat thickness meter SR-803 (Tanita Corporation). The results are shown in Table 1 and Figure 3. The principle of measuring subcutaneous fat thickness is as follows: Fat conducts very little electricity, while muscle and intradermal water are conductive. This method evaluates subcutaneous fat thickness by measuring the electrical conductivity of the cheek area. In Table 1 and Figure 3, the subcutaneous fat thickness before use is set to 100, and the values ​​after use are shown. It is clear that the application of this microneedle array reduced the subcutaneous fat in the cheeks.

[0039] [Table 1]

[0040] As demonstrated by the efficacy tests above, this microneedle array shows a quantitative effect in reducing subcutaneous fat. To date, no other microneedle or transdermal patch possesses such efficacy. [Explanation of symbols]

[0041] 1. Mold 2. Microneedle raw material solution 11 Recess for forming microneedles

Claims

1. A microneedle formulation for use in fat reduction and / or localized fat reduction and / or skin tightening, containing 0.1% by mass or more of one or more fat-reducing components selected from the group consisting of fat-decomposing agents, fat-dissolving agents and fat-metabolism promoters, The component that acts to reduce fat is the fat-dissolving agent, The aforementioned fat-dissolving agent consists of a combination of phosphatidylcholine and deoxycholic acid. The aforementioned microneedle formulation consists of a soluble microneedle array, A support film having an adhesive layer on one side is placed on the side opposite to the side where the microneedles are densely arranged. The adhesive layer contains the same components as the lipolytic agent, lipolytic agent, or lipolytic agent contained in the soluble microneedle array, at the same concentration as or less than the concentration in the microneedle array, in the microneedle formulation.

2. The component that acts to reduce fat includes the fat-decomposing agent, The microneedle formulation according to claim 1, wherein the lipolytic agent is lipase.

3. The microneedle formulation according to claim 2, comprising an Mg salt and a Ca salt.

4. The component that acts to reduce fat includes the fat metabolism promoter, The microneedle formulation according to any one of claims 1 to 3, wherein the fat metabolism promoter is one or more selected from the group consisting of amino acids, L-carnitine, inositol, capsaicin, and caffeine.

5. The microneedle formulation according to claim 4, wherein the amino acid is one or more selected from the group consisting of tyrosine, serine, threonine, phenylalanine, tryptophan, isoleucine, lysine, arginine, betaine, histidine, glutamine, glycine, and cysteine.

6. A microneedle formulation according to any one of claims 1 to 5, wherein the needle has a length of 50 to 350 μm and is inserted into the epidermis.

7. A microneedle formulation according to any one of claims 1 to 5, wherein the needle has a length of 351 to 1000 μm and is inserted into the dermis.

8. The aforementioned dissolvable microneedle array is based on a water-soluble polymer, according to any one of claims 1 to 7.

9. A microneedle preparation according to any one of claims 1 to 8, further comprising an enzyme-fermented plant extract.

10. A microneedle formulation for reducing under-eye bags, according to any one of claims 1 to 9.

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