Sleep aids

Abstract

Provided are: a sleep improving agent containing a black soybean hull extract as an active ingredient; a food or beverage product, a supplement, a pharmaceutical product, a quasi-pharmaceutical product, a feed, a pet food, or the like containing the sleep improving agent; a method for imparting sleep improving effect; and the like.

Description

[Technical Field]

[0001] The present invention relates to a sleep-improving agent, a method for producing the sleep-improving agent, a method for using the sleep-improving agent, etc. [Background technology]

[0002] According to the 2019 National Health and Nutrition Survey, 69.1% of people experience some level of anxiety or worry about their sleep quality. A particularly high percentage cited issues such as "feeling sleepy during the day" and "waking up at night is bothersome." Additionally, it has been reported that the average sleep time of Japanese people is decreasing year by year (Non-Patent Document 1). It has also been reported that lack of sleep correlates with decreased work performance (Non-Patent Document 2), and the economic loss in Japan due to sleep-related problems was estimated at 15 trillion yen as of 2016 (Non-Patent Document 3). Sleep problems are a societal issue that requires immediate action.

[0003] Treatments for poor sleep quality include pharmacotherapy using sleep-improving drugs such as benzodiazepines and antihistamines. Although these conventional drugs have the effect of improving sleep, they are not necessarily a sufficient solution because they have side effects such as psychiatric symptoms and muscle relaxation.

[0004] On the other hand, sleep-improving foods and beverages containing active ingredients derived from food sources are composed of ingredients that are commonly consumed, and therefore have fewer side effects than pharmaceuticals. Food and beverage ingredients that have been reported to have sleep-improving effects include theanine (Patent Document 1), glycine (Patent Document 2), ornithine (Patent Document 3), gamma-aminobutyric acid (GABA; Patent Document 4), arginine (Patent Document 5), glutathione (Patent Document 6), disrupted cells of microorganisms belonging to the genus Bacillus subtilis, such as Bacillus subtilis natto (Patent Document 7), sake yeast (Patent Document 8), zinc and sugars or sugar alcohols (Patent Document 9), casein hydrolysate and minerals (Patent Document 10), sesamin compounds (Patent Document 11), pumpkin seed extract (Patent Document 12), Fraxinus plants or extracts thereof, Siberian larch extract, dihydroquercetin, dihydrokaempferol, and naringenin (Patent Document 13). However, there is a demand for a drug that can provide even better sleep-improving effects. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2001 / 074352 [Patent Document 2] Japanese Patent Application Laid-Open No. 2006-333872 [Patent Document 3] Japanese Patent Application Laid-Open No. 2006-342148 [Patent Document 4] Japanese Patent Application Laid-Open No. 2007-63236 [Patent Document 5] Japanese Patent Application Laid-Open No. 2007-230954 [Patent Document 6] Japanese Patent Application Laid-Open No. 2008-56628 [Patent Document 7] Japanese Patent Application Laid-Open No. 2008-137941 [Patent Document 8] Japanese Patent Application Laid-Open No. 2015-214518 [Patent Document 9] International Publication No. 2015 / 099102 [Patent Document 10] Japanese Patent Application Laid-Open No. 2009-13143 [Patent Document 11] Japanese Patent Application Laid-Open No. 2010-285427 [Patent Document 12] Japanese Patent Application Laid-Open No. 2012-206943 [Patent Document 13] International Publication No. 2013 / 051727 [Non-patent literature]

[0006] [Non-Patent Document 1] Ministry of Health, Labour and Welfare, Health Bureau, Health Affairs Division, Nutrition Guidance Office. FY2019 National Health and Nutrition Survey Report, Ministry of Health, Labour and Welfare [Non-patent document 2] Okajima, I., Komada, Y., Ito, W., & Inoue, Y. (2021). Sleep debt and social jetlag associated with sleepiness, mood, and work performance among workers in Japan. International Journal of Environmental Research and Public Health, 18(6), 2908 [Non-patent document 3] Hafner, M., Stepanek, M., Taylor, J., Troxel, WM, & Van Stolk, C. (2017). Why sleep matters-the economic costs of insufficient sleep: a cross-country comparative analysis. Rand health quarterly, 6(4) Summary of the Invention [Problem to be solved by the invention]

[0007] An object of the present invention is to provide a novel composition that has a sleep-improving effect. [Means for solving the problem]

[0008] The present inventors have conducted extensive research to solve the above problems and have surprisingly found that ingesting black soybean seed coat extract can improve sleep quality, thus completing the present invention.

[0009] The present invention provides, for example, the following aspects. [1] A sleep aid containing black soybean seed coat extract as an active ingredient to improve sleep quality. [2] The quality of sleep is as follows: (a) to (d): (a) drowsiness, (b) sleep onset and sleep maintenance; (c) fatigue recovery, and (d) Sleeping time The sleep-improving agent according to [1], which is at least one selected from the group consisting of: [3] The sleep-improving agent according to [1] or [2], wherein the black soybean husk extract is an acidic extract of black soybean husk. [4] The sleep-improving agent according to any one of [1] to [3], which is in the form of a food or drink, a supplement, or a pharmaceutical composition. [5] A food or drink for improving sleep, comprising the sleep-improving agent according to any one of [1] to [4]. [6] A supplement for improving sleep, comprising the sleep-improving agent according to any one of [1] to [4]. [7] An oral pharmaceutical composition for improving sleep, comprising the sleep-improving agent according to any one of [1] to [4]. [8] A method for imparting a sleep-improving effect to a composition, comprising blending black soybean seed coat extract into the composition. [9] A method for producing a sleep-improving agent, comprising using black soybean seed coat extract as an active ingredient. [Effects of the Invention]

[0010] The present invention provides a sleep-improving agent that improves sleep quality. Because the sleep-improving agent contains food-derived black soybean seed coat extract as an active ingredient, it is highly safe and, as shown in the examples below, highly effective. Thus, the present invention provides a sleep-improving agent that can be safely ingested by humans and animals. Furthermore, by mixing the sleep-improving agent of the present invention or the black soybean seed coat extract as an active ingredient with ingredients such as food and beverages, supplements, pharmaceuticals, quasi-drugs, feed, and pet food, it is possible to produce foods and beverages, supplements, pharmaceuticals, quasi-drugs, feed, and pet food that have sleep-improving effects. Furthermore, by adding the sleep-improving agent of the present invention to oral compositions such as food and beverages, feed, and pet food, it is possible to impart a sleep-improving effect to the oral compositions. [Brief explanation of the drawings]

[0011] [Figure 1] This is a capillaroscopy image of a subject who took black soybean husk extract. [Figure 2-1] This shows the improvement in the number of capillaries in subjects who took black soybean seed coat extract. [Figure 2-2] 1 shows the improvement effect on capillary length in subjects who took black soybean husk extract. [Figure 3] 1 shows the results of evaluation of sleep quality (Factor I) in subjects who ingested black soybean husk extract. [Figure 4] 1 shows the results of evaluation of sleep quality (factor II) in subjects who ingested black soybean husk extract. [Figure 5] 1 shows the results of sleep quality (Factor IV) evaluation in subjects who ingested black soybean husk extract. [Figure 6] 1 shows the results of evaluation of sleep quality (Factor V) in subjects who ingested black soybean husk extract. DETAILED DESCRIPTION OF THE INVENTION

[0012] [1] Sleep aids The sleep-improving agent of the present invention (hereinafter also simply referred to as "the improving agent of the present invention") is a composition for improving sleep, characterized by containing an extract of black soybean seed coat as an active ingredient.

[0013] In this specification, black soybeans refer to the black seeds (grains) (black soybeans) of a short-day annual plant belonging to the genus Glycine max (L.) Merrill of the family Fabaceae. There are various varieties of black soybeans, such as Chuseihikarikuro, Tokachikuro, Iwaikuro, Tamadaikoku, Tanbaguro, Shinanoguro, and Karikui, but the seeds of any variety of black soybean may be used in the present invention.

[0014] The raw material can be black soybean seed coats, which are obtained by separating black soybeans into seed coats and embryos (cotyledons and hypocotyls) by, for example, using a separator etc. The black soybean seed coats may be in a raw or dried state, and may be in the form as separated, or may be crushed, pulverized, or shredded (including crushed, pulverized, coarsely ground, powdered, and shredded forms).

[0015] Commonly used methods can be used to extract black soybean seed coats. Examples include, but are not limited to, immersing raw or dried black soybean seed coats (whole, or in coarse, powdered, shredded, crushed, or pulverized form) in an aqueous solvent; extracting while stirring as needed; and percolation. The temperature conditions used for extraction are not particularly limited, and may be low, room temperature, or heated (including high) conditions. However, heated conditions (including high temperatures) that increase extraction efficiency are preferred. More specifically, when extraction is performed with a hydrous lower alcohol (described below), the temperature is 30°C or higher, preferably in the range of 40°C to 60°C. While not limited, extraction under such temperature conditions for 60 minutes or longer, preferably 90 to 120 minutes, allows for sufficient extraction of the desired black soybean seed coat components (extract). When extraction is performed with an acidic aqueous solution, the temperature is 50°C or higher, preferably in the range of 50 to 80°C, and although not limited, extraction is performed under such temperature conditions for 10 minutes or more, preferably 20 to 120 minutes.

[0016] The water-soluble solvent used for extraction is not particularly limited, and examples thereof include water, lower alcohols, and mixtures thereof. Examples of lower alcohols include lower alcohols having 1 to 4 carbon atoms, such as methanol, ethanol, propanol, isopropyl alcohol, and butanol. A preferred example of a lower alcohol is ethanol. A preferred example of a water-soluble solvent is water or a water-containing lower alcohol (particularly water-containing ethanol), and water is more preferred because it is easy to work with during extraction or purification. When a water-containing lower alcohol is used as a solvent, the amount of lower alcohol contained therein is preferably 80% by volume or less.

[0017] The water-soluble solvent used for extraction is preferably adjusted to an acidic state in order to enhance the stability of the black soybean seed coat components (extract). Although not particularly limited, the pH range of the water-soluble solvent is preferably about pH 1 to 4, and more preferably pH 1 to 2. To adjust the pH of the water-soluble solvent to fall within this range, a suitable acidic substance such as an organic acid or an inorganic acid can usually be used.

[0018] Specific examples of acidic substances include inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, and boric acid; and organic acids such as methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, 10-camphorsulfonic acid, and fluorosulfonic acid (all sulfonic acids), formic acid, acetic acid, citric acid, and oxalic acid (all carboxylic acids). Acids having a sulfo group are preferred, and specific examples include sulfuric acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, 10-camphorsulfonic acid, and fluorosulfonic acid. Among these, sulfuric acid is preferred. By heating at a low temperature of 50 to 80°C in the presence of an acid having a sulfo group, a polyphenol-containing extract containing a large amount of low-polymerized proanthocyanidins and a low content of cyanidin 3-glucoside can be obtained. The normality of the acid in the water-soluble solvent is not particularly limited as long as it is within the above-mentioned pH range, but is preferably in the range of 0.01 to 0.5N, more preferably 0.03 to 0.5N.

[0019] The resulting black soybean seed coat extract can be used as an improving agent of the present invention as is, but if necessary, further purification processes such as removal of solids by filtration, coprecipitation, or centrifugation, activated carbon treatment, or adsorption treatment may be performed. For example, to increase the concentration of polyphenols in the black soybean seed coat extract, a synthetic adsorbent can be used for purification. Examples of synthetic adsorbents include porous cross-linked polymer resins such as styrene and methacrylic acid esters. Examples of styrene-based resins include Diaion HP20, HP21, Sepabeads SP825, SP70, and SP700, and examples of acrylic resins include Diaion HP2MGL and Amberlite XAD7HP. Purification using a synthetic adsorbent can be performed using conventional methods. For example, the resulting extract can be passed through a synthetic adsorbent packed in a glass tube to adsorb the extract. After washing out impurities and acids with water, the polyphenols adsorbed on the resin can be eluted using an organic solvent or a mixture of an organic solvent and water.

[0020] The black soybean seed coat extract thus prepared can be used as an improving agent of the present invention as is, but may be subjected to concentration and / or drying treatment from the viewpoint of administration or food and beverage manufacturing. Furthermore, if necessary, the extract may be sterilized to reduce the number of bacteria in the extract or to improve the shelf life of the extract, as long as the effects of the present invention are not impaired. Such sterilization can be carried out by known methods, such as UHT sterilization and retort sterilization. The black soybean seed coat extract of the present invention may be an extract, a diluted or concentrated solution of the extract, or a dried product obtained by drying the extract.

[0021] The black soybean seed coat extract prepared as described above preferably contains polyphenols at a content of about 30% w / w or more, more preferably about 40% w / w or more, for example, about 50% w / w to 70% w / w, or for example, about 55% w / w to 65% w / w. More preferably, the black soybean seed coat extract contains, among polyphenols, proanthocyanidins and their constituent monomers, catechin and epicatechin, at a total content of 10% w / w or more, preferably 15% w / w or more, more preferably 20% w / w or more, even more preferably 25% w / w or more, and even more preferably 30% w / w or more. More preferably, the composition contains low-molecular-weight (dimer to nonamer) proanthocyanidins such as procyanidin B2, procyanidin C1, and cinnamtannin A2, or catechin and epicatechin, which are monomers that constitute proanthocyanidins, thereby increasing the absorbability into the body upon ingestion.

[0022] The sleep-improving agent of the present invention has a sleep-improving effect. In this specification, "sleep improvement" means "improvement of sleep quality." Sleep quality refers to psychological sensations that can be felt (or recognized or evaluated) mainly upon waking up, and improvement of sleep quality means, for example, improvement in the sense of good sleep, deep sleep, refreshment, relief, concentration, ability to fall asleep, and recovery from fatigue that are felt upon waking up.

[0023] In this specification, "sleep quality" is evaluated, for example, by the five factors of the OSA Sleep Inventory (MA version). The OSA Sleep Inventory (MA version) is a psychological scale for assessing sleep reflection upon waking, developed and standardized by Shuichiro Shirakawa, chairman of the Japan Sleep Improvement Council. This questionnaire consists of 16 items divided into five factors: Factor 1: sleepiness upon waking, Factor 2: initiation and maintenance of sleep, Factor 3: frequent dreaming, Factor 4: fatigue recovery, and Factor 5: sleep length. Each question item is multiple-choice with four options, and higher scores indicate better sleep. The OSA Sleep Inventory (MA version) has undergone all standardization procedures and is highly reliable and reproducible. The sleep perception obtained using this questionnaire is a statistical scale of daily fluctuations in sleep perception.

[0024] The improving agent of the present invention preferably has the following properties (a) to (d): (a) drowsiness, (b) sleep onset and sleep maintenance; (c) fatigue recovery, and (d) Sleeping time The quality of sleep can be improved by at least one selected from the group consisting of:

[0025] [2] Oral composition The improving agent of the present invention is preferably an oral composition having any form that can be orally ingested (or administered). By orally taking (administering, ingesting) the improving agent of the present invention, the quality of sleep can be improved.

[0026] The oral composition may be used in any form, including pharmaceutical compositions, foods, beverages, and supplements, as long as it is suitable for oral ingestion (or administration). In this specification, pharmaceutical compositions include drugs and quasi-drugs. In this specification, foods, beverages, and supplements include functional foods, such as foods for specified health uses (SHS), foods with functional claims, and foods with nutrient function claims, whose efficacy has been approved by a designated organization. Examples of these so-called health foods include those that claim to "improve sleep quality," "improve the feeling of deep sleep," "reduce the number of awakenings during sleep," "improve sleep depth," "improve sleep rhythm," "improve satisfaction upon waking," "improve the feeling of extended sleep time," "support quality nighttime sleep," and "improve sleep onset." The oral composition is preferably a food, beverage, or supplement, and more preferably a food, beverage, or supplement that is a SHS or a food with functional claims that can claim its action or effect. The oral composition may also be feed or pet food for non-human animals (including livestock, poultry, and pets).

[0027] Orally ingested (or administered) forms include, for example, liquid, jelly, and solid forms.

[0028] The improving agent of the present invention may be in the form of, for example, a pharmaceutical composition or a supplement, and specific examples include a liquid (including extract and syrup) or jelly form prepared from the black soybean seed coat extract prepared by the above extraction method; a powder, fine granules, or granules prepared by formulating the extract into powder or granules using conventional methods; a capsule (hard capsule, soft capsule) prepared by filling a capsule with a liquid, powder, or granules; or a tablet form prepared by further compressing the powder or granules.

[0029] The improving agent of the present invention may be the black soybean seed coat extract itself, or it may be prepared into various oral intake (or administration) forms by combining the black soybean seed coat extract with edible carriers or additives that are pharmaceutically acceptable or acceptable in the fields of food, drink, or feed. Additives such as excipients, disintegrants, binders, surfactants, absorption enhancers, adsorbents, fillers, preservatives, stabilizers, emulsifiers, and solubilizers can be selected appropriately depending on the dosage form of the improving agent of the present invention. Carriers and additives that can be used include those known in the art.

[0030] For example, when the improving agent of the present invention is in the form of a liquid preparation, the carrier or additive may be, for example, water, ethanol, sucrose, invert sugar, glucose, maltose, reduced starch syrup, or the like.

[0031] For example, when the improving agent of the present invention is in the form of a solid preparation such as a tablet, the agent may contain, for example, excipients such as lactose, sucrose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, silicic acid, etc.; binders such as water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, polyvinylpyrrolidone, crystalline cellulose, hydroxypropylcellulose, hypromellose, sodium alginate, etc.; dry starch, powdered agar, powdered laminarin, sodium bicarbonate, etc. Disintegrants such as thorium, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, stearic acid monoglyceride, starch, crospovidone, povidone, and low-substituted hydroxypropyl cellulose may also be used; disintegration inhibitors such as stearin, cocoa butter, and hydrogenated oil; absorption promoters such as quaternary ammonium salts and sodium lauryl sulfate; humectants such as glycerin; adsorbents such as starch, lactose, kaolin, bentonite, and colloidal silicic acid; and lubricants such as purified talc, stearates, boric acid powder, and polyethylene glycol. Furthermore, tablets may be coated with conventional coatings, such as sugar-coated tablets, gelatin-encapsulated tablets, enteric-coated tablets, film-coated tablets, or double-layered or multi-layered tablets, as needed. Furthermore, a composition containing the active ingredient may be filled into conventional capsules made from materials such as gelatin, pullulan, starch, gum arabic, and hydroxypropylmethylcellulose (HPMC), to form capsules. When the formulation is in the form of a pill, for example, excipients such as glucose, lactose, starch, cacao butter, hardened vegetable oil, kaolin, talc, etc., binders such as powdered gum arabic, powdered tragacanth, gelatin, ethanol, etc., disintegrants such as laminarin, agar, etc. may be used.

[0032] These dosage forms can all be prepared using conventional methods in the art. For example, tablets can be obtained by adding the above-mentioned active ingredient and other excipients necessary for obtaining tablets, mixing and dispersing them thoroughly, and then compressing them into tablets. For example, powders can be obtained by adding the above-mentioned active ingredient and other excipients necessary for obtaining powders, mixing them using a suitable method, and pulverizing them.

[0033] The improving agent of the present invention may be in the form of a food or drink, in addition to the dosage forms described above. The food or drink may be in any orally ingestible form, such as a solution, suspension, emulsion, jelly (gel), sol, powder, or solid molding, and is not particularly limited. Specific examples include instant foods such as instant noodles, retort pouch foods, canned foods, microwave foods, instant soups, miso soups, and freeze-dried foods; beverages such as soft drinks, fruit juice drinks, vegetable drinks, soy milk drinks, coffee drinks, tea drinks, powdered drinks, concentrated drinks, nutritional drinks, and alcoholic beverages; flour products such as bread, pasta, noodles, cake mix, fried chicken flour, and breadcrumbs; sweets such as candy, caramel, chewing gum, chocolate, cookies, biscuits, cakes, pies, snacks, crackers, Japanese sweets, and dessert sweets; sauces, processed tomato seasonings, and flavors. Examples of suitable foods include seasonings, cooking mixes, sauces, dressings, soups, curry and stew bases, and other condiments; processed oils and fats, such as butter, margarine, and mayonnaise; dairy products such as milk drinks, yogurt, cheese, fermented milk, lactic acid bacteria drinks, ice cream, and cream; processed egg products such as pudding and mayonnaise; processed seafood products such as fish ham and sausage and fish paste products; processed livestock products such as meat ham and sausage; processed agricultural products such as canned agricultural products, jams and marmalades, pickles, boiled beans, and cereals; frozen foods, and nutritional foods. While not limited to these, polyphenols derived from black soybean seed coat extracts are highly stable in acidic environments, and therefore, acidic foods and beverages are preferred to suppress precipitation and color loss. Such foods and beverages can be produced, for example, by mixing the black soybean seed coat extract with the ingredients of the food and beverage during the manufacturing process.

[0034] The improving agent of the present invention may also be in the form of feed or pet food. Examples of the form of feed or pet food include pellets, mash, granules, crumbles, flakes, and expanders. The feed or pet food can be produced, for example, by mixing the black soybean seed coat extract with the raw materials of the feed or pet food and, if necessary, the carrier or additive during the production process.

[0035] Furthermore, the improving agent of the present invention may be an additive added to a composition such as a pharmaceutical composition, a food or drink, a supplement, a feed, or a pet food. The additive may be added to the composition after it has been produced, or may be added to or mixed with the raw materials during the production process of the composition. The composition is preferably an oral composition.

[0036] The content of the black soybean seed coat extract in the improving agent of the present invention can be set as appropriate depending on the type of dosage form and type of application (e.g., pharmaceutical composition, food and beverage, supplement, feed, pet food, additive, etc.), with an upper limit of 100% by mass. The intake amount (administration amount) of the composition of the present invention can be appropriately adjusted depending on the type of subject (human or various animals), gender, age, and condition and severity of symptoms of the subject. For example, the daily intake (administration amount) for an adult (body weight 50 kg) of the present invention, calculated as the amount of black soybean seed coat extract (dry weight) contained in the improving agent, is typically about 10 to 500 mg, e.g., about 25 to 400 mg, and preferably about 50 to 300 mg. It is usually administered orally once a day or in two or three divided doses. The timing of intake (administration) is not particularly limited and may be, for example, during breakfast, lunch, or dinner. It may also be administered with a meal, or within 30 minutes before or after a meal, but is not limited thereto.

[0037] [3] How to use black soybean husk extract The present invention also provides a method for using black soybean seed coat extract (hereinafter also referred to as "the method of use of the present invention"). One embodiment of the method is a method for using black soybean seed coat extract to impart a sleep-improving effect to a composition, comprising blending the black soybean seed coat extract into the composition. Another embodiment is a method for using black soybean seed coat extract to produce a composition for improving sleep. In this specification, blending includes adding and mixing. The method of use includes, for example, adding the black soybean seed coat extract to a produced composition, or adding or mixing the black soybean seed coat extract with the raw materials of the composition during the production process of the composition. The composition may be a pharmaceutical composition, food or drink, supplement, feed, pet food, etc., and is preferably an oral composition.

[0038] Oral compositions include compositions that are orally administered to humans or animals, or compositions that are ingested by humans or animals, specifically oral pharmaceuticals, oral quasi-drugs, foods and beverages, supplements, feed, pet food, etc. The amount of black soybean seed coat extract added to or blended into the oral composition is not particularly limited, as long as it is an amount that can impart a sleep-improving effect to the oral composition.

[0039] A further embodiment of the method of use of the present invention provides a method for improving sleep, comprising administering black soybean seed coat extract to a subject. Examples of subjects include humans and non-human animals (e.g., livestock, poultry, pets, etc.). The dosage of black soybean seed coat extract can be determined appropriately depending on the type, sex, age, and condition and severity of symptoms of the subject. For example, the daily dosage for a human adult (body weight 50 kg) is typically about 10 to 500 mg, e.g., about 25 to 400 mg, and preferably about 50 to 300 mg. It is usually administered orally once a day or in two or three divided doses.

[0040] In the method of use of the present invention, the above-mentioned improving agent of the present invention containing black soybean seed coat extract as an active ingredient can also be used in place of the black soybean seed coat extract.

[0041] Furthermore, as another embodiment of the method of use of the present invention, there is provided a method for producing the sleep-improving agent of the present invention, which comprises using black soybean seed coat extract as an active ingredient. The method includes, for example, mixing the black soybean seed coat extract with carriers and / or additives appropriate for the desired dosage form or shape. The desired dosage form or shape can then be formed according to conventional methods. The carriers and additives are as described above.

[0042] The types of black soybeans used as the raw material for the black soybean seed coat extract used in the method of use of the present invention, the method for obtaining black soybean seed coats, and the method for preparing the black soybean seed coat extract, particularly the black soybean seed coat acidic extract which is a preferred embodiment of the extract, are as explained in [1] above, and can be incorporated herein by reference. [Example]

[0043] The present invention will be explained in more detail below by showing experimental examples, but the present invention is not limited to these examples.

[0044] Example 1: Improvement of sleep quality with black soybean husk extract First, we will explain the preparation methods of the black soybean husk extract and the test food, and then the test method and results regarding sleep improvement.

[0045] [Black soybean seed coat extract] The black soybean seed coat extract (acidic hot water extract) was prepared by the following method. (1) 1 kg of raw black soybean seed husks is immersed in 30 L of dilute sulfuric acid (0.3% w / v) as an extraction solvent, and the mixture is stirred and extracted for 20 minutes while being heated to 55-60°C. (2) After extraction, the black soybean seed coat and the liquid are separated into solid and liquid, and the liquid is recovered. (3) The recovered liquid is centrifuged to remove suspended solids that cannot be removed by solid-liquid separation. (4) The obtained extract is loaded into a column containing a synthetic adsorption resin (Sepabeads SP700: manufactured by Mitsubishi Chemical) and allowed to adsorb onto the resin. (5) To wash away any sulfuric acid remaining in the column, water is passed through the column to wash the resin. (6) A 59% by volume aqueous alcohol solution is passed through the column to elute the polyphenols adsorbed on the resin. (7) The recovered eluate (alcohol solution) is evaporated and concentrated by heating under reduced pressure. (8) Dextrin is added as an excipient to the obtained concentrate. (9) Sterilize by heating. (10) The concentrated liquid after heat sterilization was spray-dried to obtain a black soybean seed coat extract (85 g, polyphenol content: Extract 1: 61.10%, Extract 2: 58.08%).

[0046] [Component composition of black soybean seed coat extract] The component composition of the black soybean seed coat extract (acidic hot water extract) obtained above was analyzed by the following method.

[0047] (1) Total Polyphenol Analysis Black soybean seed coat extract was adjusted to a concentration of 7.5 mg / 100 ml with 70% ethanol to prepare a sample solution. 1 ml of the sample solution was added to 5 ml of Folin-Ciocalteu solution and allowed to react. 4 ml of 0.7 M sodium carbonate solution was added, stirred, and allowed to stand at 30°C for 60 minutes. The absorbance at 765 nm was measured using a spectrophotometer. A calibration curve for catechin (Sigma, "(+)-catechin hydrate" C1251-5G) was also prepared, and the total polyphenol content was calculated as catechin equivalents. (2) Total Flavanol (Total Flavan-3-ol) Analysis Black soybean seed coat extract was adjusted to a concentration of 12.5 mg / 100 ml with 50% ethanol to prepare a sample solution. 3 ml of 4% vanillin solution was added to 1 ml of the sample solution, followed by stirring. 1.5 ml of concentrated hydrochloric acid was added and stirred. After allowing to stand at 30°C for 20 minutes, the absorbance at 500 nm was measured using a spectrophotometer. 100% methanol was added to the control instead of the 4% vanillin solution. The spectrophotometer measurement was performed using the absorbance of the test group as A, the control group as B, and the blank group as C, with the absorbance of the sample equal to A, B, and C. A calibration curve for catechin (Sigma, "(+)-catechin hydrate" C1251-5G) was also prepared, and the total amount of flavan-3-ol was calculated as catechin equivalents. (3) Analysis of Catechin, Epicatechin, Procyanidin B2, Procyanidin C1, and Cinnamtannin A2 Black soybean hull extract was adjusted to a concentration of 0.1 mg / ml with 50% ethanol to prepare a sample solution, which was then subjected to HPLC analysis under the following analytical conditions. The analytical conditions were a 0.1% formic acid solution as mobile phase A and acetonitrile as mobile phase B, with elution using the following concentration gradient and conditions. Standard solutions of catechin, epicatechin, procyanidin B2, procyanidin C1, and cinnamtannin A2 were also simultaneously subjected to HPLC analysis, and calibration curves were created for quantification. Gradient: 0-45 min / B: 5-15%, 45-50 min / B: 15-80%, 50-53 min / B: 80%, 53-70 min / B: 5%, Flow rate: 0.7 mL / min, Injection volume: 10 μL, Column oven temperature: 40°C, Fluorescence: Excitation wavelength 276 nm, Emission wavelength: 316 nm, Cadenza CL-C18 column (φ250 mm × 4.6 mm, 3 μm, Imtakt), Guard column (Cadenza CL-C18, φ5 mm × 2 mm, 3 μm, Imtakt) (4) Cyanidin 3-glucoside Analysis The sample solution was prepared by adjusting the concentration of black soybean seed coat extract to 0.1 mg / ml with 1% hydrochloric acid-methanol (1:37, v / v). This was then subjected to HPLC analysis under the following analytical conditions. The mobile phase A was a formic acid:water (3:97, v / v) solution, and the mobile phase B was a formic acid:acetonitrile:water (3:30:67, v / v) solution. Elution was performed using the following concentration gradient and conditions. A standard solution of cyanidin 3-glucoside was also simultaneously subjected to HPLC analysis, and a calibration curve was prepared for quantification. Gradient: 0–50 min / B: 25–50%, 50–55 min / B: 50–100%, 55–60 min / B: 100%, 60–70 min / B: 25%, Flow rate: 0.6 mL / min, Injection volume: 10 μL, Column oven temperature: 40°C, UV: Measurement wavelength: 520 nm, Cadenza CL-C18 column (φ250 mm × 4.6 mm, 3 μm, Imtakt), Guard column (Cadenza CL-C18, φ5 mm × 2 mm, 3 μm, Imtakt)

[0048] The black soybean husk extraction test was conducted twice using different raw material lots of black soybean husks, and the analytical results of the component composition of the extracts obtained in each test (extract 1 and extract 2) are shown in Table 1.

[0049] [Table 1]

[0050] [Test food] The test foods used were black soybean husk extract-containing foods (test foods 1 and 2) and a control food (placebo). The composition of each test food is shown below. (Test food 1: low dose 100 mg / day) Three tablets containing 100 mg of black soybean husk extract (58% polyphenol content) (Test food 2: High dose 300 mg / day) Three tablets containing 300 mg of black soybean husk extract (58% polyphenol content) (Placebo) Tablets containing no black soybean husk extract (replaced with dextrin) The placebos were prepared so that there was no significant difference in calorie content from the test meals. Table 2 shows the nutritional information for each test meal.

[0051] [Table 2]

[0052] [Test method] The study was a double-blind, parallel-group comparative study. 69 subjects (ages 20-65, mean age 41) were assigned to three groups: placebo (Group 1) and test food (Group 2: low-dose 100 mg / day group and high-dose 300 mg / day group) (21 in the placebo group, 25 in the low-dose group, and 23 in the high-dose group). Subjects consumed three tablets of each test food (low-dose or high-dose test food, or placebo) for 12 weeks, and capillary blood vessel measurements and sleep quality assessments were performed. Test days were weekdays. Sleep quality was assessed by administering the OSA Sleep Questionnaire (MA version) upon awakening, and capillary blood vessel measurements were performed around 9:00 AM.

[0053] <Capillary Measurement> Capillary measurements were taken before ingestion of the test diet (on any one day within the two weeks leading up to the start of ingestion) and 12 weeks after ingestion. Photographs of the capillaries in the nail bed of the ring finger of the left hand were taken using a capillary scope (Atto Corporation). The number and length of capillaries were calculated using software (Capillary Analysis System, a system that quantifies and converts photographed capillary images).

[0054] <Sleep quality evaluation> Sleep quality was assessed before (the week before initiation of ingestion) and after 12 weeks of ingestion. The OSA Sleep Questionnaire (MA version) was administered upon awakening on five weekdays. The average scores for each of the five weekdays were used to assess five sleep quality factors (Factor I: morning sleepiness, Factor II: sleep onset and sleep maintenance, Factor III: dreaminess, Factor IV: fatigue recovery, and Factor V: sleep duration) before and after 12 weeks of ingestion. The OSA Sleep Questionnaire (MA version) consists of the following 16 items, each rated on a four-point scale. The following 16 items are related to one of the five factors (Factor I: items 2, 4, 8, 14; Factor II: items 3, 7, 10, 13, 16; Factor III: item 9, 12; Factor IV: items 1, 5, 11; Factor V: items 6, 15). 1. I still feel tired 2. They have good concentration 3. I slept soundly 4. It gives you a sense of freedom 5. Feeling tired 6. Good appetite 7. I often dozed off before falling asleep. 8. They have a clear mind 9. I had a lot of nightmares. 10. I fell asleep easily. 11. Feeling uncomfortable 12. I had frequent dreams 13. I woke up frequently during sleep. 14. You can answer surveys quickly and easily 15. I slept a lot. 16. I had a light sleep.

[0055] [Results / Discussion] <Capillary improvement effect> Improvements in capillary function were confirmed in the test diet group compared with the placebo group. Figure 1 shows capillary images of the low-dose group taken before and after 12 weeks of intake. Figures 2-1 and 2-2 show graphs of changes in capillary length and number. Improvements in capillary length (with significant differences between groups) were observed in both the low-dose and high-dose groups (Figure 2-2). In particular, the high-dose 300 mg group showed significant improvements in capillary length and number after 12 weeks compared with the placebo group (p<0.05) (Figures 2-1 and 2-2). These results demonstrate that black soybean seed coat extract intake improves the number and length of capillaries. Improvements in capillary function increase peripheral blood circulation, which promotes heat dissipation during sleep, lowering core body temperature and promoting sleep onset, leading to improved sleep quality.

[0056] <Improvement of sleep quality> Analysis was performed on 65 subjects who could be evaluated before and 12 weeks after taking the test diet (four subjects were unable to be evaluated due to forgetting to fill out the MA version of the OSA Sleep Questionnaire). The results are shown in Figures 3 to 6. Although there were no significant differences between groups, improvements were observed in all sleep quality items except for factor III (dreaming) as a result of taking black soybean husk extract. Intra-group comparisons showed that the group that took black soybean husk extract showed improvements over time in factor I (sleepiness upon waking), factor IV (fatigue recovery), and factor V (sleep time).

[0057] An example of a formulation for black soybean husk extract is shown below. Prescription example 1: Soft capsule Soft capsules were prepared using the following raw materials according to a standard method: The black soybean husk extract used was the black soybean husk extract prepared according to the method in Experimental Example 1. Vegetable oil: 158.6mg Gelatin: 135.2mg Black soybean husk extract: 100mg Glycerin: 30.2mg Lecithin: 30mg Beeswax: 26mg Vitamin E: 20mg.

[0058] Prescription Example 2: Tablets Tablets were prepared according to a standard method using the following raw materials: The black soybean husk extract prepared according to the method of Example 1 was used as the black soybean husk extract. Dextrin: 179.69mg Black soybean husk extract: 100mg Reduced starch syrup: 28.56mg Crystalline cellulose: 26.51 mg Calcium stearate: 5.25mg Fine silicon dioxide: 5.25 mg Hydroxypropylcellulose: 4.77mg.

[0059] Formulation example 3: Individually wrapped stick jelly Individually packaged stick jellies were prepared according to a standard method using the following ingredients: The black soybean husk extract used was the black soybean husk extract prepared according to the method of Example 1. Rare sugar syrup: 1000mg Black soybean husk extract: 100mg Gelling agent (thickening polysaccharide): 100mg Sweeteners (xylitol, sucralose, thaumatin, acesulfame potassium): 70mg Fragrance: 20mg Water: 8710mg [Industrial Applicability]

[0060] The sleep-improving agent of the present invention containing the black soybean hull extract as an active ingredient is useful because it can be used in a wide range of applications, such as medicines, quasi-drugs, foods and drinks, supplements, feed, and pet food.

Claims

1. A sleep-improving agent for improving the quality of sleep, comprising as an active ingredient a black soybean seed coat extract extracted at 50 to 80°C in the presence of an acid having a sulfo group.

2. The quality of sleep is determined based on the following (a) to (d): (a) sleepiness upon waking, (b) sleep onset and sleep maintenance; (c) fatigue recovery, and (d) Sleep time The sleep-improving agent according to claim 1, which is at least one selected from the group consisting of:

3. The sleep-improving agent according to claim 1 or 2, which is in the form of a food or drink, a supplement, or a pharmaceutical composition.

4. A food or drink for improving sleep, comprising the sleep-improving agent according to claim 1 or 2.

5. A supplement for improving sleep, comprising the sleep improver according to claim 1 or 2.

6. An oral pharmaceutical composition for improving sleep, comprising the sleep-improving agent according to claim 1 or 2.

7. A method for imparting a sleep-improving effect to a composition, comprising blending a black soybean seed coat extract extracted at 50 to 80°C in the presence of an acid having a sulfo group into the composition.

8. A method for producing a sleep-improving agent, comprising using as an active ingredient a black soybean seed coat extract extracted at 50 to 80°C in the presence of an acid having a sulfo group.

9. The sleep-improving effect is one of the following (a) to (d): (a) sleepiness upon waking, (b) sleep onset and sleep maintenance; (c) fatigue recovery, and (d) Sleep time The method according to claim 7, wherein the effect is to improve at least one selected from the group consisting of:

10. The sleep-improving agent comprises any one of the following (a) to (d): (a) sleepiness upon waking, (b) sleep onset and sleep maintenance; (c) fatigue recovery, and (d) Sleep time The method according to claim 8, which has the effect of improving at least one selected from the group consisting of:

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