Barrier function enhancing agent and transepithelial electrical resistance increasing agent

Abstract

The present invention provides a barrier function enhancer and a transepithelial electrical resistance increasing agent, both containing active ingredients that enhance barrier function or increase transepithelial electrical resistance. [Solution] The barrier function enhancing agent and transepithelial electrical resistance increasing agent contains at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, or at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, and glycyrrhizic acid and / or a derivative of glycyrrhizic acid as active ingredients.

Description

【Technical Field】 【0001】 The present invention relates to a barrier function enhancer and an agent for increasing transepithelial electrical resistance. 【Background Art】 【0002】 One of the structures that separates the inside and outside of a living body is epithelial tissue composed of epithelial cells. Epithelial tissue has a barrier function that controls substance permeation, thereby creating an internal environment different from the outside world in the living body. Such a barrier function is mainly formed by cell-cell adhesion, and one such adhesion is a tight junction (hereinafter sometimes referred to as "TJ"). TJ is an intercellular adhesion structure that not only adheres adjacent epithelial cells tightly but also seals the gaps between cells to control the permeation of substances. Proteins such as claudin, occludin, ZO-1, and ZO-2 that constitute TJ are considered to form the skeleton of the TJ strand and control the barrier function of TJ (see Non-Patent Document 1). When the function of TJ is reduced due to a decrease in the expression of these proteins, for example, in the digestive tract, food allergens, pathogenic microorganisms, etc. may invade the body, which is considered to be one of the causes of inflammatory bowel disease and various infectious diseases. In addition, when the function of TJ in the skin is reduced, it is considered to be one of the causes of skin symptoms such as dry skin, rough skin, atopic dermatitis, and various infectious diseases. 【0003】 When histamine in mast cells is released extracellularly, the released histamine causes an inflammatory reaction and exacerbates allergic diseases and inflammatory diseases. In recent years, a mechanism has been known in which histamine suppresses epidermal keratinocyte differentiation and contributes to the impairment of the barrier function in the skin (see Non-Patent Document 2). Therefore, by improving the impairment of the skin barrier function caused by histamine stimulation, the barrier function in epithelial tissue can be strengthened, and in the digestive tract, inflammatory bowel disease, food allergy, various infectious diseases, etc. can be prevented or improved. On the other hand, in the epidermis, skin symptoms such as dry skin, rough skin, atopic dermatitis, and various infectious diseases can be prevented or improved. 【0004】 In epithelial cells, ion permeability between the luminal side and the basement membrane side is restricted by tight junctions (TJs), resulting in trans-epithelial electrical resistance (TER). Therefore, when the barrier function in epithelial cells is impaired, TER also decreases. Thus, it is thought that increasing TER can restore barrier function and prevent or improve diseases caused by impaired barrier function. [Prior art documents] [Non-patent literature] 【0005】 [Non-Patent Document 1] Journal of the Japanese Society of Cosmetic Science, 2007, vol.31, pp.296-301. [Non-Patent Document 2] Gschwandtner M et al., Allergy, January 2013, vol.68(1), pp.37-47 [Overview of the Initiative] [Problems that the invention aims to solve] 【0006】 The present invention aims to provide a barrier function enhancing agent and a transepithelial electrical resistance increasing agent, both of which contain an active ingredient having a barrier function enhancing effect or a transepithelial electrical resistance increasing effect. [Means for solving the problem] 【0007】 To solve the above problems, the barrier function enhancing agent and transepithelial electrical resistance increasing agent of the present invention contains at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment as an active ingredient. Furthermore, the barrier function enhancing agent and transepithelial electrical resistance increasing agent of the present invention contains at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, and glycyrrhizic acid and / or a derivative of glycyrrhizic acid as active ingredients. As a derivative of the above-mentioned glycyrrhizic acid, dipotassium glycyrrhizinate is acceptable. [Effects of the Invention] 【0008】 According to the present invention, it is possible to provide a barrier function enhancer and a transepithelial electrical resistance increasing agent that have excellent barrier function enhancement or transepithelial electrical resistance increasing effects. [Modes for carrying out the invention] 【0009】 Embodiments of the present invention will be described in detail. One embodiment of the barrier function enhancer and transepithelial electrical resistance increasing agent according to this embodiment contains at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment as an active ingredient. 【0010】 The tea used to obtain the green tea extract as the active ingredient in the barrier function enhancer and transepithelial electrical resistance increasing agent according to this embodiment is manufactured using the leaves and stems of the tea plant (scientific name: Thea sinensis), a plant of the Camellia family, as the raw material. Tea is broadly classified into three types based on the manufacturing method: "fermented tea," "semi-fermented tea," and "unfermented tea." In this embodiment, unfermented tea, such as green tea or matcha, is used as the raw material for extraction. 【0011】 In this embodiment, "green tea" refers to tea produced through a process of rolling the tea leaves. In this embodiment, "matcha" refers to tencha (tea leaves grown under cover and dried without being rolled in a tencha furnace, etc.) that has been ground into a powder using a stone mill, etc. The method for producing matcha differs from the method for producing green tea in that it does not involve a process of rolling the tea leaves. It should be noted that "tea leaves" may include any part of the plant, such as new shoots, mature leaves, or stems, and are not limited to the harvested part or the proportion of each part. 【0012】 The method of producing green tea is not particularly limited and can be carried out by conventional methods, but for example, it can be produced by steaming, rolling, and drying the tea leaves. Examples of green tea include sencha, deep-steamed sencha, gyokuro, kabusecha, tamaryokucha, kamanobicha, bancha, kukicha, mecha, and hojicha, but among these, sencha is preferred. In addition, tea is sometimes branded with the name of the place of origin, and examples of green tea include Uji tea, Sayama tea, Shizuoka tea, Ise tea, and Chiran tea (all registered trademarks). 【0013】 The method for producing matcha is not particularly limited and can be carried out by conventional methods, but for example, it can be produced by steaming, cooling, and drying tea leaves (tencha) and then grinding them into a powder using a stone mill. The method for producing matcha differs from the method for producing green tea in that it does not involve the process of kneading the tea leaves. Examples of matcha in this embodiment include Kyoto matcha. 【0014】 The coix seed extract used to obtain the coix seed extract as the active ingredient in the barrier function enhancing agent and transepithelial electrical resistance increasing agent according to this embodiment is the seed of Coix lachrymal-jobi L., an annual plant belonging to the genus Coix in the grass family. Coix seed has traditionally been used for purposes such as diuresis, clearing dampness, clearing heat, draining pus, relieving paralysis, strengthening the spleen, and relieving pain. 【0015】 The substances contained in the extract from the above-mentioned raw materials that have barrier function-enhancing and transepithelial electrical resistance-increasing effects can be detailed to obtain an extract that has barrier function-enhancing and transepithelial electrical resistance-increasing effects. The extract may include any of the following: the extract obtained from the raw materials by the extraction process, a diluted or concentrated extract, a dried product obtained by drying the extract, or a crude or refined product thereof. 【0016】 The above extract can be obtained by subjecting the extraction raw material directly to extraction with an extraction solvent, or by drying the extraction raw material and then subjecting it to extraction with an extraction solvent as it is or after pulverizing it using a crusher. The drying of the extraction raw material may be carried out under the sun or using a commonly used dryer. Also, a pretreatment such as degreasing may be performed using a nonpolar solvent such as hexane and then used as an extraction raw material. By performing a pretreatment such as degreasing, the extraction treatment of plants with a polar solvent can be efficiently carried out. 【0017】 Examples of the solvent used for extraction include water, a hydrophilic organic solvent, or a mixture thereof, etc., and it is preferably used at room temperature or a temperature below the boiling point of the solvent. Components having an action of enhancing the barrier function and an action of increasing the transepithelial electrical resistance contained in the extraction raw material can be easily extracted by an extraction treatment using a polar solvent as the extraction solvent. 【0018】 Examples of the water that can be used as the extraction solvent include, for example, pure water, tap water, well water, mineral water, mineralized water, hot spring water, spring water, fresh water, etc., and also those obtained by subjecting these to various treatments. Treatments applied to water include, for example, purification, heating, sterilization, filtration, ion exchange, adjustment of osmotic pressure, buffering, etc. Therefore, the water that can be used as the extraction solvent in the present invention also includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer solution, phosphate buffered saline, etc. 【0019】 Examples of the hydrophilic organic solvent that can be used as the extraction solvent include lower aliphatic alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, isopropyl alcohol, etc.; lower aliphatic ketones such as acetone, methyl ethyl ketone, etc.; polyhydric alcohols having 2 to 5 carbon atoms such as 1,3-butylene glycol, propylene glycol, glycerin, etc. 【0020】 When using a mixed solution of two or more polar solvents as an extraction solvent, the mixing ratio can be adjusted as appropriate. For example, when using a mixed solution of water and a lower aliphatic alcohol, it is preferable to mix 1 to 90 parts by volume of the lower aliphatic alcohol with 10 parts by volume of water. When using a mixed solution of water and a lower aliphatic ketone, it is preferable to mix 1 to 40 parts by volume of the lower aliphatic ketone with 10 parts by volume of water. When using a mixed solution of water and a polyhydric alcohol, it is preferable to mix 1 to 90 parts by volume of the polyhydric alcohol with 10 parts by volume of water. 【0021】 For the extraction process, there is no need to adopt a special extraction method as long as the soluble components contained in the extraction raw material can be eluted into the extraction solvent, and extraction can be carried out at room temperature or under reflux heating. For example, the extraction raw material is put into a treatment tank filled with the extraction solvent, and after standing for 30 minutes to 4 hours with stirring as necessary to elute the soluble components, the extract can be obtained by filtration to remove the solid matter. When the extraction solvent is distilled off from the obtained extract, a paste-like concentrate is obtained, and a dried product is obtained by further drying this concentrate. The extraction conditions may be about 1 to 4 hours at 50 to 95 °C when water is used as the extraction solvent. Also, when a mixed solvent of water and ethanol is used as the extraction solvent, it may be about 30 minutes to 4 hours at 40 to 80 °C. 【0022】 The extract obtained as described above may be subjected to treatments such as dilution, concentration, drying, and purification according to conventional methods in order to obtain a diluted solution or concentrated solution of the extract, a dried product of the extract, or a crude purified product or purified product thereof. 【0023】 Note that the obtained extract can be used as it is as an active ingredient of a barrier function enhancer and a trans-epithelial electrical resistance increasing agent, but a concentrated solution or a dried product is preferred. In obtaining the dried product, carriers such as dextrin and cyclodextrin may be added to improve hygroscopicity. 【0024】 Furthermore, since the above extract has a distinctive odor and taste, it is possible to purify it for purposes such as decolorization and deodorization, provided that it does not reduce its physiological activity. However, since it is not used in large quantities when added to cosmetics, etc., there is no practical problem even if it is left unpurified. Purification can be carried out by methods such as activated carbon treatment, adsorption resin treatment, or ion exchange resin treatment. 【0025】 The rice ferment product, which serves as the active ingredient in the barrier function enhancer and transepithelial electrical resistance increasing agent according to this embodiment, is a rice ferment product made by fermenting rice with Saccharomyces verona. Unless otherwise stated, the rice ferment product includes any of the following: a fermented liquid obtained by fermenting rice with Saccharomyces verona, a diluted or concentrated fermented liquid, a dried product obtained by drying the fermented liquid, or a crude or refined product thereof. 【0026】 The rice used as the fermentation raw material for rice fermentation products is obtained from the grass plant Oryza sativa. Rice is cultivated throughout Japan and is readily available from these regions. There are no particular restrictions on the fermentation raw material, and it can be selected as appropriate depending on the purpose, but examples include unhulled rice, brown rice, polished rice, or mixtures thereof, with polished rice being preferred among these. 【0027】 Rice fermentation products are obtained by fermenting rice with Saccharomyces verona. The fermentation process can be carried out, for example, by dispersing rice in water and inoculating it with fermenting microorganisms. 【0028】 Before inoculating with Saccharomyces verona, it is preferable to perform a decomposition treatment of the starch contained in the rice and / or the cell wall of the rice, from the viewpoint of improving fermentation efficiency. 【0029】 Starch decomposition treatments include, for example, enzyme treatment and inoculation with Aspergillus oryzae, with enzyme treatment being particularly preferred. Examples of starch-degrading enzymes include amylases such as α-amylase, β-amylase, glucoamylase, and isoamylase, but from the viewpoint of improving fermentation efficiency, α-amylase and glucoamylase are particularly preferred, and glucoamylase is even more preferred. On the other hand, cell wall decomposition treatments are preferably performed using enzymes such as cellulase and xylanase. 【0030】 The resulting processed liquid may be subjected to desired means such as cooling, heating, pH adjustment, or sterilization to inactivate enzymes and koji mold, or it may be inoculated with microorganisms that carry out fermentation as is. 【0031】 The microorganism that carries out fermentation is Saccharomyces veronae (also known as Lachancea thermotolerans). 【0032】 The fermentation process using the above microorganisms can be carried out, for example, by placing the fermentation raw materials and the above microorganisms in a fermentation tank and treating them at a temperature range of 20 to 40°C, preferably 25 to 35°C, for 12 to 72 hours, preferably 18 to 48 hours. Furthermore, if the pH of the reaction solution is adjusted to 5.0 to 7.0, preferably 6.0 to 7.0, at the start of the fermentation process, the fermentation process will proceed favorably. This fermentation process is terminated by subjecting the fermentation solution to a desired means such as cooling, heat sterilization, or filtration to inactivate the fermentation bacteria. 【0033】 The fermentation liquid obtained in this way may be used as is as a fermented product, or it may be diluted or concentrated as appropriate before being used as a fermented product. The concentrate may be further dried or subjected to crude purification. 【0034】 Furthermore, other embodiments of the barrier function enhancing agent and transepithelial electrical resistance increasing agent according to this embodiment all contain at least one selected from the group consisting of the above-mentioned green tea extract, the above-mentioned matcha extract, the above-mentioned coix seed extract, and the above-mentioned rice ferment product, and glycyrrhizic acid and / or a glycyrrhizic acid derivative as active ingredients. 【0035】 Although the detailed mechanism by which the combined use of at least one substance selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment with glycyrrhizic acid and / or a glycyrrhizic acid derivative dramatically improves barrier function and increases transepithelial electrical resistance is unknown, as shown in the test examples below, the combined use of at least one substance selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment with glycyrrhizic acid and / or a glycyrrhizic acid derivative exhibits excellent barrier function enhancement and transepithelial electrical resistance increasing effects. 【0036】 Other embodiments of the barrier function enhancing agent and transepithelial electrical resistance increasing agent according to this embodiment may include a formulation containing at least one active ingredient selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, and glycyrrhizic acid and / or a glycyrrhizic acid derivative, wherein the desired barrier function enhancing effect and transepithelial electrical resistance increasing effect are exerted by using this formulation; or the formulation may include a formulation containing at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment (hereinafter sometimes referred to as "Formulation 1") and a formulation containing glycyrrhizic acid and / or a glycyrrhizic acid derivative (hereinafter sometimes referred to as "Formulation 2"), wherein the desired barrier function enhancing effect and transepithelial electrical resistance increasing effect are exerted by using Formulation 1 and Formulation 2 in combination. 【0037】 In another embodiment of the barrier function enhancing agent and transepithelial electrical resistance increasing agent according to this embodiment, the mixing ratio (by mass) of at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment as an active ingredient and glycyrrhizic acid and / or a glycyrrhizic acid derivative may be, for example, about 1:5 to 1:10. If the mixing ratio of at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment and glycyrrhizic acid and / or a glycyrrhizic acid derivative is within the above range, excellent barrier function enhancing and transepithelial electrical resistance increasing effects will be exhibited. Note that the above mixing ratio is a value on a solid content basis. 【0038】 Glycyrrhizic acid derivatives include, for example, glycyrrhizic acid (C 42 H 62 O 16 It can be obtained by reacting with an alkali. Examples of glycyrrhizic acid derivatives include dipotassium glycyrrhizate, trisodium glycyrrhizate, and monoammonium glycyrrhizate, with dipotassium glycyrrhizate being preferably used. 【0039】 Dipotassium glycyrrhizinate is C 42 H 60 K2O 16 It is a compound with a molecular weight of 899.1, represented by [formula]. 【0040】 Dipotassium glycyrrhizinate may be prepared by chemical synthesis or may be a commercially available product. 【0041】 There are no particular restrictions on the chemical synthesis method, and it can be appropriately selected depending on the purpose. For example, one method involves reacting glycyrrhizic acid with potassium hydroxide (KOH), etc. 【0042】 There are no particular restrictions on the method of obtaining glycyrrhizic acid, and it can be appropriately selected depending on the purpose. For example, methods include using commercially available products, or obtaining it from plant extracts containing glycyrrhizic acid by at least one of isolation and purification. 【0043】 The plant extract containing glycyrrhizic acid may be any of the following: an extract obtained using a plant containing glycyrrhizic acid as the raw material; a diluted or concentrated solution of said extract; a dried product obtained by drying said extract; or a crude or purified product thereof. 【0044】 As will be clear from the examples described later, the green tea extract, matcha extract, coix seed extract, and rice ferment obtained as described above, as well as the mixture of at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment with glycyrrhizic acid and / or a glycyrrhizic acid derivative, have barrier function enhancing effects and transepithelial electrical resistance increasing effects, and in particular have the effect of improving barrier function impairment caused by histamine stimulation. Therefore, these effects can be utilized and used as active ingredients in barrier function enhancing agents and transepithelial electrical resistance increasing agents. 【0045】 One embodiment of the barrier function enhancer or transepithelial electrical resistance increasing agent of this embodiment may consist of only at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, or it may be a formulation of at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment. Another embodiment of the barrier function enhancer or transepithelial electrical resistance increasing agent of this embodiment may consist only of a mixture of at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, and glycyrrhizic acid and / or a glycyrrhizic acid derivative, or it may be a formulation of a mixture of at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, and glycyrrhizic acid and / or a glycyrrhizic acid derivative. 【0046】 At least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, and a mixture of at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, and glycyrrhizic acid and / or a glycyrrhizic acid derivative, can be formulated into any dosage form such as powder, granules, tablets, or liquid by conventional methods using pharmaceutically acceptable carriers such as dextrin and cyclodextrin, or any other auxiliary agents. In this case, auxiliary agents such as excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, and odor-masking agents can be used. At least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, and a mixture of at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment with glycyrrhizic acid and / or a glycyrrhizic acid derivative, can be used in combination with other compositions (e.g., skin cosmetics), and can also be used as ointments, topical solutions, patches, etc. 【0047】 Furthermore, the barrier function enhancing agent or transepithelial electrical resistance increasing agent of this embodiment may be used as an active ingredient by combining it with other natural extracts that have a barrier function enhancing effect or a transepithelial electrical resistance increasing effect, as needed. 【0048】 The barrier function enhancer or transepithelial electrical resistance increasing agent of this embodiment can generally be administered transdermally or orally, but the most suitable method for prevention or treatment should be selected depending on the type of disease. Furthermore, the dosage of the barrier function enhancer or transepithelial electrical resistance increasing agent of this embodiment can be increased or decreased as appropriate depending on the type and severity of the disease, individual differences among patients, the method of administration, the duration of administration, etc. 【0049】 The barrier function enhancing agent or transepithelial electrical resistance increasing agent of this embodiment enhances the barrier function in epithelial tissue through the barrier function enhancing effect or transepithelial electrical resistance increasing effect of a mixture of at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, and glycyrrhizic acid and / or a glycyrrhizic acid derivative, thereby treating inflammatory bowel disease, food allergies, various infections originating from the gastrointestinal tract, etc.; dry skin, rough skin, atopic dermatitis, allergies It can prevent, treat, or improve skin conditions such as sensitive skin, signs of skin aging, psoriasis, acne (including hidradenitis suppurativa), burns, diaper rash, Netherton syndrome, actinic keratosis, cutaneous mycosis, dermatological conditions, ectodermal dysplasia, contact dermatitis, dermatitis, seborrheic dermatitis, ichthyosis vulgaris, oral and respiratory infections, and various other skin conditions and infections; allergic rhinitis, asthma, irritable bowel syndrome, systemic autoimmune diseases (rheumatoid arthritis, lupus erythematosus, etc.), allergies (food allergies, hay fever, etc.), and lifestyle-related diseases (obesity, type 1 or type 2 diabetes, hypertension, hyperlipidemia, non-alcoholic fatty liver disease (NAFLD), arteriosclerosis, etc.). However, the barrier function enhancing agent or transepithelial electrical resistance increasing agent of this embodiment can be used in all applications other than those listed above where it is significant to exert a barrier function enhancing effect or transepithelial electrical resistance increasing effect. 【0050】 Furthermore, the barrier function enhancing agent or transepithelial electrical resistance increasing agent of this embodiment has excellent barrier function enhancing or transepithelial electrical resistance increasing effects, and is therefore suitable for incorporation into, for example, topical skin preparations or oral compositions. In this case, at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, and a mixture of at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, and glycyrrhizic acid and / or a glycyrrhizic acid derivative may be incorporated as is, or a barrier function enhancing agent or transepithelial electrical resistance increasing agent formulated from at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, and a mixture of at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, and glycyrrhizic acid and / or a glycyrrhizic acid derivative may be incorporated. 【0051】 Here, there are no restrictions on the classification of topical skin preparations, and they broadly include skin cosmetics, quasi-drugs, pharmaceuticals, etc. that are used transdermally. Specifically, examples include ointments, creams, lotions, serums, creams, masks, foundations, lip balms, bath additives, hair tonics, hair lotions, soaps, body washes, etc. 【0052】 The amount of at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment in a topical skin preparation, and the amount of a mixture of at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment with glycyrrhizic acid and / or a glycyrrhizic acid derivative can be appropriately adjusted depending on the type of topical skin preparation, but a preferred blending ratio is 0.0001 to 10% by mass, and a particularly preferred blending ratio is 0.001 to 1% by mass. 【0053】 An oral composition refers to a substance that poses little risk to human health and is ingested orally or via the gastrointestinal tract in normal social life, and is not limited to the administrative classifications of food, pharmaceuticals, quasi-drugs, etc. Therefore, the "oral composition" in this embodiment broadly includes general foods, animal feed, health foods, functional foods (foods for specified health uses, foods with nutritional function claims, foods with functional claims), quasi-drugs, pharmaceuticals, etc., that are ingested orally. The oral composition in this embodiment is preferably an oral composition that can display on the oral composition or its packaging the desirable effects of at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, and a mixture of at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, and glycyrrhizic acid and / or a glycyrrhizic acid derivative. It is particularly preferable that it be a functional food (foods for specified health uses, foods with nutritional function claims, foods with functional claims), a quasi-drug, or a pharmaceutical. 【0054】 The amount of at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment in the oral composition, and the amount of a mixture of at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, and glycyrrhizic acid and / or a glycyrrhizic acid derivative, can be appropriately changed considering the intended use, symptoms, gender, etc. However, considering the general intake of the oral composition to which it is added, it is preferable that the daily extract intake for adults be approximately 1 to 1000 mg. When the oral composition to which it is added is in the form of granules, tablets, or capsules, the amount of at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, and the amount of a mixture of at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment, and glycyrrhizic acid and / or a glycyrrhizic acid derivative added is usually 0.0001 to 10% by mass relative to the oral composition to which it is added, and preferably 0.001 to 1% by mass. 【0055】 Furthermore, the barrier function enhancer or transepithelial electrical resistance increasing agent of this embodiment has excellent barrier function enhancer or transepithelial electrical resistance increasing effects, particularly the effect of improving barrier function impairment caused by histamine stimulation, and can therefore be suitably used as a reagent for research on the mechanisms of action of these agents. 【0056】 While the barrier function enhancing agent or transepithelial electrical resistance increasing agent of this embodiment is suitably applied to humans, it can also be applied to animals other than humans, as long as the respective effects are achieved. [Examples] 【0057】 The present invention will be described in more detail below with reference to test examples, but the present invention is not limited in any way to the test examples described below. In the test examples described below, dipotassium glycyrrhizinate (manufactured by Maruzen Pharmaceutical Co., Ltd.) was used as the test sample for the glycyrrhizic acid derivative. 【0058】 [Manufacturing Example 1] Production of green tea extract 10g of Uji tea (registered trademark) was mixed with 150mL of 80% ethanol, and extracted using a reflux extractor at 80-90°C for 2 hours. The mixture was then filtered while hot. The residue was subjected to the same extraction process. The resulting extracts were combined and concentrated under reduced pressure, and then dried in a vacuum dryer to obtain green tea extract (2g). 【0059】 [Manufacturing Example 2] Production of Coix Seed Extract 100 g of coarsely crushed Job's tears seeds were added to 1500 mL of a 50% by volume 1,3-butylene glycol solution, and the mixture was heated and extracted, then filtered. The resulting extract was dried to obtain Job's tears extract (6 g). 【0060】 [Manufacturing Example 3] Production of fermented rice 0.1 kg of polished rice flour was mixed with 1 kg of water and dispersed. The mixture was sterilized at 110°C for 5 minutes, then glucoamylase was added and the mixture was reacted at 60°C for 1 hour. Subsequently, Saccharomyces verona (manufactured by Akita Konno Shoten Co., Ltd.) was inoculated into the resulting enzyme-treated solution and fermented at 30°C for 24 hours. The resulting fermented liquid was sterilized at 110°C for 5 minutes. The resulting culture solution was filtered through diatomaceous earth, and the filtrate was concentrated to dryness to obtain a fermented product of rice with Saccharomyces verona (approximately 64 g). 【0061】 [Test Example 1] Skin barrier function enhancement test (measurement of electrical resistance value TER) Human normal neonatal epidermal keratinocytes (NHEKs) were cultured in human normal neonatal epidermal keratinocyte medium (KGM) and then harvested by trypsin treatment. The harvested cells were 2.2 × 10⁶ 5 After diluting with KGM to a concentration of cells / mL, 0.5 mL of the sample was seeded in the upper layer of each well of a 12-well transwell (Corning, 12 mm diameter, 0.4 μm pore), and 1.5 mL of KGM was added to the lower layer of each well. The cells were cultured for 3 days. After the culture period, 0.5 mL of the test sample (sample concentrations are shown in Table 1), dissolved in KGM containing 1000 μmol / L histamine and 1.5 mmol / L CaCl2, was added to the upper layer of each well. Then, 1.5 mL of KGM containing 1000 μmol / L histamine and 1.5 mmol / L CaCl2 was added to the lower layer of each well, and the cells were cultured for 3 days to induce tight junction formation. Electrical resistance (TER) was measured at 24, 48, and 72 hours after the addition of the test sample using the Millicell-ERS resistance measurement system (Millipore). The barrier formation acceleration rate (%) of the test sample was calculated using the following formula, with the control's barrier formation acceleration rate (%) set to 100%. The results are shown in Table 1. 【0062】 Barrier formation promotion rate (%) = A / B × 100 In the formula, A represents "TER when the test sample is added," and B represents "TER when the test sample is not added." 【0063】 [Table 1] 【0064】 As shown in Table 1, green tea extract, coix seed extract, and rice ferment were confirmed to be excellent in improving skin barrier dysfunction caused by histamine stimulation. Furthermore, it was confirmed that the combined use of green tea extract or coix seed extract with dipotassium glycyrrhizate can additively or synergistically improve the effect of improving skin barrier dysfunction caused by histamine stimulation. 【0065】 [Test Example 2] Skin barrier function enhancement test (measurement of electrical resistance value TER) Except for the use of freeze-dried samples of "Waism <Uji Tea>" (product name, manufactured by Maruzen Pharmaceutical Co., Ltd., 80% ethanol extract of Uji Tea®) as a green tea extract, freeze-dried samples of "Waism <Kyoto Matcha>" (product name, manufactured by Maruzen Pharmaceutical Co., Ltd., 80% ethanol extract of Uji Matcha®) as a matcha extract, freeze-dried samples of "Waism <Yokuinin>" (product name, manufactured by Maruzen Pharmaceutical Co., Ltd., 50% 1,3-butylene glycol extract of coix seed) as a coix seed extract, freeze-dried samples of "Rice Ferment Liquid PD" (product name, manufactured by Maruzen Pharmaceutical Co., Ltd.) as a rice ferment product, and dipotassium glycyrrhizinate (manufactured by Maruzen Pharmaceutical Co., Ltd.) as a glycyrrhizic acid derivative, the electrical resistance (TER) was measured and the barrier formation promotion rate (%) was calculated in the same manner as in Test Example 1. The results are shown in Table 2. 【0066】 [Table 2] 【0067】 As shown in Table 2, green tea extract, matcha extract, coix seed extract, and rice ferment were confirmed to be excellent in improving skin barrier dysfunction caused by histamine stimulation. Furthermore, it was confirmed that the combined use of green tea extract, matcha extract, coix seed extract, or rice ferment with dipotassium glycyrrhizinate can additively or synergistically improve the effect of improving skin barrier dysfunction caused by histamine stimulation. [Industrial applicability] 【0068】 The barrier function enhancer and transepithelial electrical resistance increasing agent according to this embodiment can greatly contribute to enhancing the barrier function in epithelial tissue (prevention, treatment, or improvement of inflammatory bowel disease, food allergies, and various infectious diseases originating from the gastrointestinal tract; prevention, treatment, or improvement of skin conditions such as dry skin, rough skin, atopic dermatitis, and various infectious diseases).

Claims

[Claim 1] A barrier function enhancer characterized by containing at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment as an active ingredient. [Claim 2] The barrier function enhancing agent according to claim 1, further comprising glycyrrhizic acid and / or a derivative of glycyrrhizic acid as the active ingredient. [Claim 3] The barrier function enhancing agent according to claim 2, characterized in that the derivative of glycyrrhizic acid is dipotassium glycyrrhizate. [Claim 4] A barrier function enhancer according to claim 1 or 2, characterized by having the effect of improving skin barrier dysfunction caused by histamine stimulation. [Claim 5] A transepithelial electrical resistance increasing agent characterized by containing at least one selected from the group consisting of green tea extract, matcha extract, coix seed extract, and rice ferment as an active ingredient. [Claim 6] The transepithelial electrical resistance increasing agent according to claim 5, further comprising glycyrrhizic acid and / or a derivative of glycyrrhizic acid as the active ingredient. [Claim 7] The transepithelial electrical resistance increasing agent according to claim 6, characterized in that the derivative of glycyrrhizic acid is dipotassium glycyrrhizinate.

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