Desmoglein reducing agents

Abstract

To provide a new technique for reducing desmoglein.SOLUTION: The desmoglein-reducing agent contains an extract of Citrusjunos as an active ingredient.SELECTED DRAWING: Figure 3

Description

[Technical Field]

[0001] The present invention relates to a desmoglein-reducing agent and a composition for external application to the skin for reducing desmoglein. [Background technology]

[0002] It is known that a decrease in the amount of desmoglein 1 (Dsg1) in the stratum corneum promotes the formation of basket weave, resulting in skin with high barrier function and high stratum corneum flexibility (Patent Document 1) (Figure 1).

[0003] As a prior art, Patent Document 2 reports an agent for reducing desmoglein in stratum corneum cells that contains astaxanthin. Furthermore, Patent Document 3 reports an orally administered agent for inhibiting intercellular adhesion in the skin, which contains licorice extract as an active ingredient. Furthermore, Patent Document 4 reports a desmoglein-reducing agent containing an extract of Thymus vulgaris as an active ingredient. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2017-119665 [Patent Document 2] Japanese Patent Application Laid-Open No. 2016-37501 [Patent Document 3] Japanese Patent Application Publication No. 11-116493 [Patent Document 4] Patent Publication No. 2021-091649 Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide a novel technique for reducing desmogleins. [Means for solving the problem]

[0006] As a result of extensive research efforts, the present inventors have discovered that an extract of yuzu (Citrus junos) has the effect of reducing desmoglein, and have thus completed the present invention.

[0007] The present invention, which solves the above problems, is as follows. [1] A desmoglein reducer containing yuzu (Citrus junos) extract as its active ingredient. In this specification, the concept of "decreasing desmoglein" includes both a decrease in desmoglein and suppression of an increase in desmoglein.

[0008] [2] The desmoglein reducer according to [1], wherein the active ingredient is a Citrus junos extract.

[0009] [3] The desmoglein reducer according to [1] or [2], wherein the target to be reduced is desmoglein 1. Desmoglein 1 is mainly found in the skin. Therefore, the desmoglein-reducing agent of the present invention, which has the effect of reducing desmoglein 1, can more efficiently prevent or improve deterioration of skin conditions.

[0010] [4] The desmoglein-reducing agent according to any one of [1] to [3], which is used for inhibiting intercellular adhesion of human epidermal keratinocytes.

[0011] [5] The desmoglein-reducing agent according to any one of [1] to [4], which is used for improving and / or preventing sensitive skin.

[0012] [6] A desmoglein reducer according to any one of [1] to [5] for improving skin brightness.

[0013] [7] A desmoglein reducer according to any one of [1] to [6] for improving skin clarity.

[0014] [8] A desmoglein reducer according to any one of [1] to [7] for softening the skin.

[0015] [9] A desmoglein-reducing agent according to any one of [1] to [8] for improving and / or preventing stratum corneum desquamation.

[0016]

[10] A composition for external application to the skin for reducing desmoglein, comprising the desmoglein-reducing agent according to any one of [1] to [9].

[0017]

[11] The topical skin composition for reducing desmoglein described in

[10] , which is a body soap or facial cleanser.

[0018]

[12] A topical skin composition for reducing desmoglein described in

[10] or

[11] , which is applied at least once a day for at least two weeks.

[0019]

[13] The composition for external application to the skin for reducing desmoglein according to any one of

[10] to

[12] , wherein the daily application amount of the active ingredient is 0.54 mg or more. [Effects of the Invention]

[0020] According to the present invention, a novel technique for reducing desmogleins can be provided. [Brief explanation of the drawings]

[0021] [Figure 1] FIG. 1 is a diagram illustrating the relationship between a stained image and the stratum corneum structure. [Figure 2] 1 is a photograph showing the state of immersion in Example 1. [Figure 3] 1 is a graph showing the desmograin amount ratio of the first layer of tape stripping. [Figure 4] This is a stained image of desmoglein 1 in the first layer of tape stripping. [Figure 5] 1 is a graph showing the desmograin amount ratio of the second layer of tape stripping. [Figure 6] This is a stained image of desmoglein 1 in the second layer of tape stripping. [Figure 7]1 is a graph showing the desmograin amount ratio of the third layer of tape stripping. [Figure 8] This is a stained image of desmoglein 1 in the third layer of tape stripping. [Figure 9] Photographs comparing the condition of the skin before and after use of the topical skin composition of this example. [Figure 10] Photographs comparing the condition of the skin before and after use of the topical skin composition of this example. [Figure 11] Photographs comparing the condition of the skin before and after use of the topical skin composition of this example. [Figure 12] Photographs comparing the condition of the skin before and after use of the topical skin composition of this example. [Figure 13] Photographs comparing the condition of the skin before and after use of the topical skin composition of this example. DETAILED DESCRIPTION OF THE INVENTION

[0022] The following describes embodiments of the present invention to help understand the present invention. Note that the following embodiments are examples of specific embodiments of the present invention, and can be modified as appropriate within the scope of the claims.

[0023] <1> Desmoglein reducer The desmoglein-reducing agent of the present invention contains a yuzu extract as an active ingredient.

[0024] In particular, the desmoglein-reducing agent of the present invention preferably contains yuzu pod extract as an active ingredient. The sac, also known as sand sac, is a long, thin sac found inside the sac of citrus fruits. The sac is usually discarded, but in this invention, a new use has been found for the sac of yuzu.

[0025] The extract can be obtained, for example, by the following method. First, 1 to 30 parts by weight of solvent is added to 1 part by weight of yuzu sap, and the mixture is immersed for several days at room temperature or for several hours at temperatures near the boiling point. After immersion, the mixture is cooled to room temperature, and if desired, any unwanted materials are removed, followed by removal of the solvent by vacuum concentration or other methods. The desired extract can then be obtained by fractionation using column chromatography packed with silica gel or ion exchange resin.

[0026] The extraction solvent is preferably a polar solvent, and suitable examples include one or more selected from water, alcohols such as ethanol, isopropyl alcohol, and butanol, polyhydric alcohols such as 1,3-butylene glycol and polypropylene glycol, ketones such as acetone and methyl ethyl ketone, and ethers such as diethyl ether and tetrahydrofuran. Of these, ethanol is a preferred extraction solvent. In particular, an aqueous ethanol solution can be preferably used. The concentration of the aqueous ethanol solution is preferably 10% by mass or more, more preferably 30% by mass or more, and even more preferably 40% by mass or more. The concentration of the aqueous ethanol solution is preferably 90% by mass or less, more preferably 70% by mass or less, and even more preferably 60% by mass or less.

[0027] The content of yuzu extract in the desmoglein-reducing agent of the present invention is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, even more preferably 0.008% by mass or more, and particularly preferably 0.01% by mass or more, calculated on solid content. The content of the yuzu extract is 0.1% by mass or less, preferably 0.05% by mass or less, and more preferably 0.02% by mass or less.

[0028] The desmoglein-reducing agent of the present invention preferably targets desmoglein 1 for reduction.

[0029] The desmoglein-reducing agent of the present invention is preferably used to inhibit intercellular adhesion of human epidermal keratinocytes. In this specification, the term "intercellular adhesion" refers to abnormalities in stratum corneum adhesion (progression of stratum corneum stratification due to increased cell adhesion) caused by an increase in desmosomal proteins (a group of proteins including desmoglein) (see Patent Nos. 4197194 and 4002635 for details). In addition, in this specification, the concept of "inhibiting intercellular adhesion" includes both prevention and improvement of intercellular adhesion.

[0030] Here, by inhibiting intercellular adhesion of human epidermal keratinocytes, stratification of the stratum corneum is inhibited, and an effect of inhibiting stratum corneum desquamation can be obtained. That is, the desmoglein-reducing agent of the present invention can be used to prevent or improve stratum corneum desquamation. As used herein, "stratum corneum delamination" refers to the peeling off of multiple layers of the stratum corneum from the skin surface. Whether or not the skin is in a state where stratum corneum delamination is possible can be confirmed by collecting a sample of the stratum corneum by tape stripping, staining the collected sample, and observing it.

[0031] The desmoglein-reducing agent of the present invention is preferably used for improving and / or preventing sensitive skin.

[0032] Here, "sensitive skin" in this specification refers to a skin type with reduced resistance to external stimuli (dryness, ultraviolet rays, application of chemical compounds) (reduced skin irritation threshold). More specifically, "sensitive skin" in this specification refers to the skin types listed in (1) and / or (2). (1) "Skin that reacts to substances such as topical medicines, cosmetics, plants, ultraviolet rays, and metals, and is prone to skin problems. Also, skin that is hypersensitive to allergens (pollen, fragrances, etc.) and irritants (alcohol, etc.)" (2) "Skin that is temporarily more susceptible to skin problems due to lack of sleep, overwork, menstruation, seasonal changes, mental stress, etc."

[0033] In addition, in this specification, "for the improvement and / or prevention of sensitive skin" refers to the improvement of skin quality with reduced resistance to external stimuli (reduced skin irritation threshold) and / or the prevention of reduced resistance to external stimuli in skin quality (reduced skin irritation threshold).

[0034] Furthermore, areas of the skin with low brightness have a high concentration of desmoglein 1. Here, the decrease in skin brightness is thought to be due to stratification of the stratum corneum. In view of the above findings, the active ingredient of the present invention can reduce desmoglein, thereby improving skin brightness. That is, the active ingredient of the present invention can also be used as a skin lightening agent. In this specification, "improving skin brightness" refers to reducing the difference in brightness between skin in a normal state and skin whose brightness has decreased due to the excessive presence of desmoglein.

[0035] Furthermore, the active ingredient of the present invention can provide a skin condition with a more transparent appearance, that is, the active ingredient of the present invention can also be used as an agent for improving skin transparency.

[0036] Furthermore, areas with high skin hardness have a high concentration of desmoglein 1. Here, the cause of skin hardness is thought to be the stratification of the stratum corneum. Based on the above findings, reducing desmoglein makes the skin softer. In other words, the active ingredient of the present invention can reduce desmoglein, thereby providing a skin softening effect, and can also be used as a skin softener.

[0037] Here, softening the skin allows other medicinal ingredients to penetrate more efficiently, so by reducing desmoglein with the active ingredient of the present invention, it is possible to obtain the effect of allowing medicinal ingredients such as whitening agents to penetrate the skin more efficiently. That is, the active ingredient of the present invention can also be used as an aid for the penetration of medicinal ingredients into the skin.

[0038] In particular, the active ingredient of the present invention is preferably used as a whitening ingredient penetration aid for use in combination with a whitening agent.

[0039] <2> Skin external composition for reducing desmoglein The present invention also relates to a composition for external application to the skin for reducing desmoglein, which contains the above-mentioned desmoglein-reducing agent.

[0040] Suitable examples of external skin compositions include body soaps, facial cleansers, cosmetics, pharmaceuticals, and oral compositions.

[0041] The solid content of the yuzu extract in the composition for external use on skin is 0.001% by mass or more, preferably 0.005% by mass or more, and more preferably 0.008% by mass or more. The solid content of the yuzu extract in the composition for external use on skin is 0.1% by mass or less, preferably 0.05% by mass or less, and more preferably 0.01% by mass or less.

[0042] Furthermore, the desmoglein-reducing external skin composition of the present invention is preferably applied at least once a day, more preferably at least twice a day, and even more preferably at least three times a day. Furthermore, the external skin composition for reducing desmoglein according to the present invention is preferably applied for one week or more, more preferably two weeks or more, and even more preferably three weeks or more.

[0043] Furthermore, the daily application amount of the yuzu gall extract in the desmoglein-reducing external skin composition of the present invention is preferably 0.54 mg or more, more preferably 0.7 mg or more, and even more preferably 1.0 mg or more. Furthermore, the daily application amount of the yuzu gall extract in the desmoglein-reducing external skin composition of the present invention is preferably 100 mg or less, more preferably 10 mg or less, and even more preferably 5.0 mg or less.

[0044] When an oral composition is prepared, it is preferable to prepare a food composition containing the active ingredient of the present invention. Specifically, it can be in the form of a supplement having the dosage form of a general food, tablet, granule, drink, or the like.

[0045] When provided in the form of a composition for external use on the skin, the composition is not particularly limited, and may contain any optional ingredient that is commonly used, as long as it does not impair the effects of the present invention. For example, optional ingredients such as whitening ingredients, wrinkle-reducing ingredients, anti-inflammatory ingredients, and extracts derived from animals and plants may be included. These optional ingredients may be commercially available and used, or may be synthesized by known methods and used. Each optional ingredient may have two or more effects (for example, a whitening effect and an anti-wrinkle effect). The optional components may be selected appropriately depending on the dosage form.

[0046] Examples of whitening ingredients include 4-n-butylresorcinol, ascorbic acid glucoside, 3-O-ethyl ascorbic acid, tranexamic acid, arbutin, 1-triphenylmethylpiperidine, 1-triphenylmethylpyrrolidine, 2-(triphenylmethyloxy)ethanol, 2-(triphenylmethylamino)ethanol, 2-(triphenylmethyloxy)ethylamine, triphenylmethylamine, triphenylmethanol, triphenylmethane, and aminodiphenylmethane, N-(o-toluoyl)cysteic acid, N-(m-toluoyl)cysteic acid, N-(p-toluoyl)cysteic acid, N-(p-methoxybenzoyl)cysteic acid, N-benzoyl-serine, and N-(p-methyl)-2-methyl-2-methyl-1 ... Examples of such benzoylserine include N-(p-ethylbenzoyl)serine, N-(p-methoxybenzoyl)serine, N-(p-fluorobenzoyl)serine, N-(p-trifluoromethylbenzoyl)serine, N-(2-naphthoyl)serine, N-(4-phenylbenzoyl)serine, N-(p-methylbenzoyl)serine methyl ester, N-(p-methylbenzoyl)serine ethyl ester, N-(2-naphthoyl)serine methyl ester, N-benzoyl-O-methylserine, N-(p-methylbenzoyl)-O-methylserine, N-(p-methylbenzoyl)-O-acetylserine, N-(2-naphthoyl)-O-methylserine, dexpanthenol W, and niacinamide.

[0047] The content of the whitening ingredient is usually 0.0001 to 30% by mass, preferably 0.001 to 10% by mass, and more preferably 0.01 to 5% by mass (dry mass in the case of an extract).

[0048] Examples of wrinkle-reducing ingredients include vitamin A or its derivatives such as retinol, retinal, retinoic acid, tretinoin, isotretinoin, tocopherol retinoate, retinol palmitate, and retinol acetate.Further examples include ursolic acid benzyl ester, ursolic acid phosphate, betulinic acid benzyl ester, benzilic acid phosphate, trifluoroisopropyl oxopropylaminocarbonylpyrrolidinecarbonylmethylpropylaminocarbonylbenzoylamino sodium acetate, and niacinamide.

[0049] The content of the wrinkle-reducing ingredient is usually 0.0001 to 30% by mass, preferably 0.001 to 10% by mass, and more preferably 0.01 to 5% by mass (dry mass in the case of an extract).

[0050] Examples of anti-inflammatory ingredients include kurarinone, glabridin, glycyrrhizinic acid, glycyrrhetinic acid, pantothenyl alcohol, niacinamide, and tranexamic acid, and preferred examples include glycyrrhizinic acid and its salts, alkyl glycyrrhetinates and their salts, and glycyrrhetinic acid and its salts. The content of the anti-inflammatory component is usually 0.01 to 30% by mass, preferably 0.1 to 10% by mass, and more preferably 1 to 5% by mass (dry mass in the case of an extract).

[0051] Examples of extracts derived from plants and animals include akebia extract, asparagus extract, avocado extract, hydrangea extract, almond extract, arnica extract, aronia extract, apricot extract, ginkgo extract, fennel extract, udo extract, Siberian ginseng extract, emmeiso extract, phellodendron bark extract, Panax ginseng extract, white nettle extract, kakyō extract, pueraria root extract, chamomile extract, carrot extract, artemisia capillaris extract, licorice extract, kiwi extract, cucumber extract, and guava extract. , gardenia extract, kumazasa extract, walnut extract, black rice extract, chlorella extract, mulberry extract, kaempfer extract, alpinia zerumbet extract, gentian extract, rice extract, fermented rice extract, fermented rice bran extract, rice germ oil, salvia extract, soapwort extract, bamboo extract, zanthoxylum extract, Japanese pepper extract, shiitake mushroom extract, rehmannia root extract, lithospermum root extract, perilla extract, linden extract, meadowsweet extract, ginger extract, calamus root extract, horsetail extract, stevia extract, fermented stevia, yarrow Watermelon extract, peppermint extract, sage extract, mallow extract, cnidium extract, Swertia bristle extract, Morus alba extract, rhubarb extract, soybean extract, Chinese laurel extract, dandelion extract, clove extract, chili pepper extract, angelica extract, calendula extract, peach kernel extract, Houttuynia cordata extract, tomato extract, natto extract, carrot extract, garlic extract, hibiscus extract, burdock extract, lotus extract, parsley extract, birch extract, witch hazel extract, holly extract, cypress extract Preferred examples of extracts include loquat extract, coltsfoot extract, butterbur extract, poria extract, loofah extract, peppermint extract, linden extract, pine extract, skunk cabbage extract, melissa extract, mozuku extract, peach extract, cornflower extract, lily extract, coix seed extract, mugwort extract, lavender extract, apple extract, rooibos tea extract, lychee extract, lettuce extract, forsythia extract, astragalus extract, rosemary extract, Roman chamomile extract, and burnet extract.

[0052] The content (dry mass) of the animal and plant-derived extract is usually 0.01 to 30 mass %, preferably 0.1 to 10 mass %, more preferably 0.3 to 3 mass %.

[0053] Other optional ingredients include, for example, water, polyoxyethylene lauryl ether sulfate, α-olefin sulfonate, sodium benzoate, phenoxyethanol, citric acid, sodium citrate, fragrance, polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, maltitol, propylene glycol, dipropylene glycol, diglycerin, isoprene glycol, 1,2-pentanediol, 2,4-hexylene glycol, 1,2-hexanediol, 1,2-octanediol, etc. polyols, fatty acid soaps (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, anionic surfactants such as alkyl sulfate triethanolamine ether, cationic surfactants such as stearyl trimethylammonium chloride, benzalkonium chloride, laurylamine oxide, imidazoline-based amphoteric surfactants (2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt, etc.), betaine-based surfactants (alkyl betaine, amido betaine, sulfobetaine, etc.), acyl methyl taurine, etc. amphoteric surfactants, sorbitan fatty acid esters (sorbitan monostearate, sorbitan sesquioleate, etc.), glycerin fatty acids (glycerin monostearate, etc.), propylene glycol fatty acid esters (propylene glycol monostearate, etc.), hydrogenated castor oil derivatives, glycerin alkyl ether, POE sorbitan fatty acid esters (POE sorbitan monooleate, polyoxyethylene sorbitan monostearate, etc.), POE sorbit fatty acid esters (POE-sorbit monolaurate, etc.), POE glycerin fatty acid esters esters (POE-glycerin monoisostearate, etc.), POE fatty acid esters (polyethylene glycol monooleate, POE distearate, etc.), POE alkyl ethers (POE 2-octyldodecyl ether, etc.), POE alkyl phenyl ethers (POE nonylphenyl ether, etc.), Pluronic (registered trademark) types, POE·POP alkyl ethers (POE·POP 2-decyltetradecyl ether, etc.), Tetronics, POE castor oil·hydrogenated castor oil derivatives (POE castor oil, POE hydrogenated castor oil, etc.), sucrose fatty acid esters,Nonionic surfactants such as alkyl glucosides, moisturizing ingredients such as sodium pyrrolidone carboxylate, lactic acid, and sodium lactate, powders such as mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, anhydrous silicic acid (silica), aluminum oxide, and barium sulfate (which may be surface-treated), inorganic pigments such as cobalt oxide, ultramarine, Prussian blue, and zinc oxide (which may be surface-treated), composite pigments such as iron oxide and titanium dioxide sintered body (which may be surface-treated), pearling agents such as titanium mica, fish phosphorus foil, and bismuth oxychloride (which may be surface-treated), and laked Red No. 202, Red No. 228, Red No. 226, Yellow No. 4, Blue No. 404, Yellow No. 5, Red No. 505, Red No. 230, Red No. 223, Orange No. 201, and Red Examples of suitable organic pigments include organic dyes such as No. 213, Yellow No. 204, Yellow No. 203, Blue No. 1, Green No. 201, Purple No. 201, and Red No. 204; organic powders such as polyethylene powder, polymethyl methacrylate, nylon powder, and organopolysiloxane elastomers; lower alcohols such as ethanol and isopropanol; vitamin B compounds such as vitamin A or a derivative thereof, vitamin B6 hydrochloride, vitamin B6 tripalmitate, vitamin B6 dioctanoate, vitamin B2 or a derivative thereof, vitamin B12, and vitamin B15 or a derivative thereof; vitamin E compounds such as α-tocopherol, β-tocopherol, γ-tocopherol, and vitamin E acetate; vitamin D compounds, vitamin H, pantothenic acid, pantethine, and pyrroloquinoline quinone. The external skin composition of the present invention can be produced by treating the above-mentioned ingredients according to a conventional method.

[0054] When the present invention is used as a composition for external use on the skin, it is preferable that the present invention be in a form labeled with uses such as "for reducing desmoglein," "for inhibiting cell adhesion of epidermal keratinocytes," "for improving and / or preventing sensitive skin," "for improving skin brightness," "for improving skin clarity," "for softening the skin," and "for improving and / or preventing stratum corneum peeling."

[0055] The above-mentioned "representation" includes all representations that have the function of informing consumers of the above-mentioned use. In other words, any representation that can recall or infer the above-mentioned use is considered a "representation" regardless of the purpose of the representation, the content of the representation, the object or medium of the representation, etc. Furthermore, the phrase "labeled" means that there is a labeling action that aims to associate the label with a topical skin composition (product) or the like.

[0056] It is preferable that the act of labeling be one that allows consumers to directly recognize the intended use. Specific examples include the act of describing the intended use on the product or its packaging, and the act of describing the intended use in product advertisements, price lists, or transaction documents (including those provided by electromagnetic means).

[0057] <3> beauty method The present invention can also provide a method for reducing desmoglein, which comprises applying a yuzu extract to the skin. The yuzu extract is preferably a yuzu pod extract. The present invention also preferably relates to a method for decreasing desmoglein 1.

[0058] The method of the present invention can be carried out by sellers of the topical skin composition of the present invention, makeup artists, beauty staff, counselors, estheticians, or general users.

[0059] Here, the method of the present invention does not include medical treatment.

[0060] In addition, a preferred embodiment of the method of the present invention is the above-mentioned <1> The contents relating to desmoglein reducers can be cited. [Example]

[0061] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to the following examples as long as it does not depart from the gist of the invention.

[0062] [Example of manufacturing Yuzu sachet extract] The yuzu sac was made from the sac remaining after squeezing the juice out of the yuzu fruit. 100g of yuzu sage was immersed in 1L of 50% ethanol solution and extracted at room temperature for 24 hours. After extraction, the extract was filtered to obtain yuzu sage extract. The solid content was 3%.

[0063] [Example 1] The reagents used for stratum corneum desmoglein staining are listed below. Xylene (Fujifilm Wako Pure Chemical Industries) · 4% paraformaldehyde · Phosphate buffer solution (Fujifilm Wako Pure Chemical Industries) Dulbecco's Phosphate Buffered Saline Powder (Ca, Mg-free) (Fujifilm Wako Pure Chemical Industries, Ltd.) Block Ace Powder (KAC) Triton X-100 (Nacalai Tesque) ·Anti Desmoglein 1, Mouse Mono(Dsg-1-P23)(funakoshi) ·Goat anti Mouse IgG(H+L)Cross Adsorbed Secondary Antibody,Alexa Fluor488(Invitrogen) Fluoromount G (Cosmo Bio)

[0064] The desmoglein 1-reducing effect of yuzu gall extract was verified using the following procedure. 1 mL of the yuzu sachet extract produced by the method in [Production Example of Yuzu Sachet Extract] was mixed with 199 mL of purified water to prepare a 0.5% yuzu sachet extract. As a control sample, 0% yuzu jar extract was prepared by mixing 1 mL of 50% aqueous ethanol solution with 199 mL of purified water. Petri dishes containing 50 mL each of 0.5% yuzu extract and a control sample were placed in an incubator and maintained at 41°C. Two 21 mm filter papers (No. 5B) were immersed in the samples that had reached 41°C, and the samples were again maintained at 41°C.

[0065] Next, a 0.5% yuzu arborescens extract site and a control sample site were set up on the outside of the subject's forearm. Filter paper soaked in 0.5% yuzu arborescens extract was placed in the 0.5% yuzu arborescens extract site, and filter paper soaked in the control sample was placed in the control sample site (see Figure 2). The filter paper was replaced after 5 minutes, and the conditions were maintained for a total of 10 minutes (see Figure 2).

[0066] After 10 minutes, the filter paper was removed, and any remaining water droplets on the skin were removed with Kimwipes.Then, the first, second, and third layers of the stratum corneum on the outer side of the forearm were sampled using the tape stripping method with Cellotape (registered trademark).

[0067] Next, the cellophane-covered tape was cut into pieces of approximately 4 x 4 mm and attached to a glass slide. The slide was placed in a slide staining rack and immersed in xylene for 10 minutes twice. The slide was then dried until no water droplets remained.

[0068] The dried slides were returned to the rack and washed with PBS, then fixed in 4% PFA for 15 minutes, and then washed again with PBS.

[0069] Next, 0.5% TritonX / PBS was placed in the container containing the slide and left to stand at room temperature for 5 minutes for permeabilization. After washing with PBS, the slide was then immersed in 20% Block Ace and left to stand at room temperature for 1 hour for blocking.

[0070] Next, the slides were gently wiped with Kimwipes and cotton swabs to remove any moisture, without touching the samples, and then framed with liquid blocker. Primary antibody (Anti-Desmoglein 1, Mouse-Mono (Dsg-1-P23) stock solution) was added dropwise and left to stand at room temperature for 2 hours. The slides were then washed three times for 5 minutes with PBS.

[0071] Next, secondary antibody (Goat anti-Mouse IgG (H+L) Cross-Adsorbed Secondary Antibody, Alexa Fluor 488) was diluted 1:200 in PBS and incubated at room temperature for 1 hour. All subsequent steps were protected from light. The sections were then washed three times for 5 minutes with PBS and twice with distilled water.

[0072] Finally, the sections were mounted with Fluoromount-G, sealed with nail polish, and stored in the dark at 4°C. Observations were made using a fluorescence microscope from the following day onwards.

[0073] The desmoglein amount ratio in the first layer of tape stripping is shown in Figure 3. As shown in Figure 3, the amount of desmoglein 1 in the 0.5% yuzu garnish extract was 65.3% of that in the 0% yuzu garnish extract.

[0074] Figure 4 shows a stained image of desmoglein 1 in the first layer of tape stripping. Figure 4 shows that desmoglein 1 was reduced by 0.5% Yuzu gall extract.

[0075] The desmoglein amount ratio in the second layer of tape stripping is shown in Figure 5. As shown in Figure 5, the amount of desmoglein 1 in the 0.5% yuzu garnish extract was 53.3% of that in the 0% yuzu garnish extract.

[0076] Figure 6 shows a stained image of desmoglein 1 in the first layer of tape stripping. Figure 6 shows that desmoglein 1 was reduced by 0.5% Yuzu gall extract.

[0077] The desmoglein amount ratio in the third layer of tape stripping is shown in Figure 7. As shown in Figure 7, the amount of desmoglein 1 in the 0.5% yuzu garnish extract was 70.8% of that in the 0% yuzu garnish extract.

[0078] Furthermore, Figure 8 shows a stained image of desmoglein 1 in the third layer of tape stripping. Figure 8 shows that desmoglein 1 was reduced by 0.5% Yuzu gall extract.

[0079] The results of Figures 3 to 8 show that desmoglein 1 was reduced by 0.5% yuzu sage extract through the first to third layers of tape stripping.

[0080] [Prescription example] The topical skin composition of the present invention was prepared according to the following formulation. Specifically, ingredients A, B, and C were each heated to 70°C, stirred, and solubilized. B was added to A, and then C was gradually added and stirred. The mixture was then stirred and cooled to obtain a cleansing agent. The yuzu arborescens extract was prepared as described above in [Production Example of Yuzu Arborescens Extract].

[0081] (stomach) ·Water 73.09 parts by weight Polyoxyethylene lauryl ether sulfate 10 parts by weight α-olefin sulfonate 10 parts by weight Coconut oil fatty acid monoethanolamide 5 parts by weight

[0082] (B) Sodium benzoate 0.5 parts by weight Phenoxyethanol 0.5 parts by weight Citric acid 0.01 parts by weight Sodium citrate 0.1 parts by weight

[0083] (c) Yuzu sage extract 0.3 parts by weight ·Fragrance 0.5 part by weight

[0084] [Example 2] The monitors were asked to use the topical skin composition manufactured according to the formulation example once a day for two weeks, and the skin conditions before and after use were compared. Comparative photographs are shown in Figures 9 to 13.

[0085] 9 and 10 show that the skin brightness and transparency improved. In particular, in Figures 11 to 13, before use, the left side of the photograph was whitish and the skin was dry. On the other hand, after two weeks of use, the whitish area was no longer visible. In other words, by using the topical skin composition prepared according to the formulation example, the sensitive skin was improved and the skin was softened. In addition, the stratum corneum delamination was improved. [Industrial Applicability]

[0086] According to the present invention, a desmoglein-reducing agent and a desmoglein-reducing composition for external application to the skin can be provided.

Claims

1. A desmoglein reducer containing yuzu (Citrus junos) extract as its active ingredient.

2. 2. The desmoglein reducing agent according to claim 1, wherein the active ingredient is a Citrus junos pod extract.

3. The desmoglein-reducing agent according to claim 1 or 2, wherein the target to be reduced is desmoglein 1.

4. The desmoglein-reducing agent according to claim 1 or 2, for inhibiting intercellular adhesion of human epidermal keratinocytes.

5. The desmoglein-reducing agent according to claim 1 or 2 for improving and / or preventing sensitive skin.

6. The desmoglein reducing agent according to claim 1 or 2 for improving skin brightness.

7. The desmoglein-reducing agent according to claim 1 or 2 for improving skin clarity.

8. The desmoglein reducing agent according to claim 1 or 2 for softening the skin.

9. The desmoglein-reducing agent according to claim 1 or 2, for improving and / or preventing stratum corneum desquamation.

10. A composition for external application to the skin for reducing desmoglein, comprising the desmoglein-reducing agent according to claim 1 or 2.

11. The external skin composition for reducing desmoglein according to claim 10, which is a body soap or facial cleanser.

12. 11. The external skin composition for reducing desmoglein according to claim 10, which is applied at least once a day for at least two weeks.

13. 11. The composition of claim 10, wherein the daily dosage of the active ingredient is 0.54 mg or more.

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