Sleep-improving agent

Abstract

To provide a new composition having sleep-improving effect.SOLUTION: There are provided a sleep-improving agent for shortening sleep latency, containing a black soybean seed coat extract as an active ingredient, a food and drink, a supplement, a pharmaceutical, a quasi-drug, a feed, a pet food, or the like, containing the sleep-improving agent, and a method for imparting a sleep-improving action, or the like.SELECTED DRAWING: None

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.

[0005] Sleep is also closely related to body temperature, and it is known that prior to sleep, the skin temperature of the hands and feet rises relative to the trunk skin temperature (Non-Patent Document 4). This occurs due to an increase in skin blood flow caused by peripheral vasodilation, which activates heat dissipation from the surface of the hands and feet, and when the core body temperature drops, sleep is induced. It has also been reported that people who are prone to cold hands take longer to release heat from the body, and therefore people with lower peripheral hand skin temperatures have greater difficulty falling asleep (Non-Patent Document 4). [Prior art documents] [Patent documents]

[0006] [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]

[0007] [Non-Patent Document 1] Ministry of Health, Labour and Welfare, Health Bureau, Health Affairs Division, Nutrition Guidance Office. 2019 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) [Non-patent document 4] Japanese Journal of Oncology and Biology, Vol. 78, No. 1, November 2014, pp. 6-9, Special Lecture 1, Human Thermoregulation and Sleep Summary of the Invention [Problem to be solved by the invention]

[0008] An object of the present invention is to provide a novel composition that has a sleep-improving effect. [Means for solving the problem]

[0009] The present inventors have conducted extensive research to solve the above problems and have surprisingly found that ingesting black soybean seed coat extract can shorten sleep quality, particularly sleep onset latency, and improve several aspects of sleep quality, including sleep depth. Furthermore, they have also found that it can increase, maintain, or inhibit a decrease in peripheral skin surface temperature. Thus, the present invention has been completed.

[0010] The present invention provides, for example, the following aspects. [1] A sleep-improving agent containing black soybean seed coat extract as an active ingredient, which shortens the latency time to fall asleep. [2] (a) to (e) below: (a) Sleepiness upon waking, (b) sleep maintenance; (c) Fatigue recovery (d) sleep duration, and (e) Sleep depth The sleep-improving agent according to [1], further comprising at least one effect of improving sleep quality selected from the group consisting of: [3] The sleep-improving agent according to [1] or [2], further comprising the effect of increasing, maintaining, or inhibiting a decrease in peripheral skin surface temperature. [4] The sleep-improving agent according to [3], wherein the peripheral skin surface temperature is the skin surface temperature of the palm of the hand. [5] The sleep-improving agent according to [3] or [4], wherein the effect of increasing, maintaining, or inhibiting a decrease in peripheral skin surface temperature is the effect of increasing, maintaining, or inhibiting a decrease in normal peripheral skin surface temperature. [6] The sleep-improving agent according to any one of [1] to [5], wherein the black soybean hull extract is an acidic extract of black soybean hull. [7] The sleep-improving agent according to any one of [1] to [6], which is in the form of a food or drink, a supplement, or a pharmaceutical composition. [8] A food or drink for improving sleep, comprising the sleep-improving agent according to any one of [1] to [6]. [9] A supplement for improving sleep, comprising the sleep improver according to any one of [1] to [6].

[10] An oral pharmaceutical composition for improving sleep, comprising the sleep-improving agent according to any one of [1] to [6].

[11] A method for imparting a sleep-onset latency shortening effect to a composition, comprising blending a black soybean seed coat extract into the composition.

[12] The composition further comprises the following (a) to (e): (a) Sleepiness upon waking, (b) sleep maintenance; (c) Fatigue recovery (d) sleep duration, and (e) Sleep depth The method according to

[11] , further imparting at least one effect of improving sleep quality selected from the group consisting of:

[13] The method according to

[11] or

[12] , further imparting to the composition an effect of increasing, maintaining, or inhibiting a decrease in peripheral skin surface temperature.

[14] The method described in

[13] , wherein the peripheral skin surface temperature is the skin surface temperature of the palm of the hand.

[15] The method described in

[13] or

[14] , wherein the effect of increasing, maintaining, or inhibiting a decrease in the peripheral skin surface temperature is the effect of increasing, maintaining, or inhibiting a decrease in the peripheral skin surface temperature under normal conditions.

[16] The method according to any one of

[11] to

[15] , wherein the black soybean seed coat extract is an acidic extract of black soybean seed coat.

[17] A method for producing a sleep-improving agent for shortening sleep onset latency, comprising using black soybean seed coat extract as an active ingredient.

[18] The sleep-improving agent is selected from the group consisting of the following (a) to (e): (a) Sleepiness upon waking, (b) sleep maintenance; (c) Fatigue recovery (d) sleep duration, and (e) Sleep depth The method described in

[17] , further comprising at least one effect of improving sleep quality selected from the group consisting of:

[19] The method described in

[17] or

[18] , wherein the sleep-improving agent further has the effect of increasing, maintaining, or inhibiting a decrease in peripheral skin surface temperature.

[20] The method described in

[19] , wherein the peripheral skin surface temperature is the skin surface temperature of the palm of the hand.

[21] The method described in

[19] or

[20] , wherein the effect of increasing, maintaining, or inhibiting a decrease in the peripheral skin surface temperature is the effect of increasing, maintaining, or inhibiting a decrease in the peripheral skin surface temperature under normal conditions.

[22] The method according to any one of

[17] to

[21] , wherein the black soybean seed coat extract is an acidic extract of black soybean seed coat. [Effects of the Invention]

[0011] The present invention provides a sleep-improving agent that improves sleep quality, particularly sleep onset latency. The sleep-improving agent also improves several aspects of sleep quality, including sleep depth, and increases or maintains peripheral skin surface temperature or inhibits a decrease in peripheral skin surface temperature. Because the sleep-improving agent contains a 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 foods 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 foods and beverages, feed, and pet food, it is possible to impart sleep-improving effects to the oral compositions. [Brief explanation of the drawings]

[0012] [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. [Figure 7-1]1 shows the change in sleep latency in subjects who ingested black soybean husk extract. [Figure 7-2] 1 shows the change in sleep latency in subjects who ingested black soybean husk extract. [Figure 8-1] 1 shows the change in N3 total time in subjects who ingested black soybean husk extract. [Figure 8-2] 1 shows the change in N3 total time in subjects who ingested black soybean husk extract. [Figure 9-1] 1 shows the change in palm skin surface temperature before cooling load in subjects who ingested black soybean husk extract. [Figure 9-2] 1 shows the change in palm skin surface temperature before cooling load in subjects who ingested black soybean husk extract. [Figure 9-3] 1 shows the change in palm skin surface temperature after cooling load in subjects who ingested black soybean husk extract. [Figure 9-4] 1 shows the change in palm skin surface temperature after cooling load in subjects who ingested black soybean husk extract. [Figure 9-5] This shows the change in palm skin surface temperature from cooling load to 30 minutes after loading in subjects who ingested black soybean husk extract. [Figure 9-6] This shows the change in palm skin surface temperature from cooling load to 30 minutes after loading in subjects who ingested black soybean husk extract. [Figure 10-1] 1 shows the results of evaluation of sleep quality (Factor I) in subjects who ingested black soybean husk extract. [Figure 10-2] 1 shows the results of evaluation of sleep quality (Factor I) in subjects who ingested black soybean husk extract. DETAILED DESCRIPTION OF THE INVENTION

[0013] [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.

[0014] 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.

[0015] 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).

[0016] 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.

[0017] 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.

[0018] 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.

[0019] 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.

[0020] 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.

[0021] 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.

[0022] 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.

[0023] The sleep-improving agent of the present invention has a sleep-improving effect. As used herein, "sleep improvement" refers to "improvement of sleep quality." While the definition of "sleep quality" has not been scientifically established, sleep quality refers to psychological sensations that can be felt (or recognized or evaluated) not only during sleep but also upon waking. Therefore, improving sleep quality refers to, for example, improvements in the sense of comfortable sleep, deep sleep, refreshment, liberation, concentration, ability to fall asleep, and feeling of recovery from fatigue felt upon waking. Furthermore, in relation to falling asleep, shortening the sleep onset latency is also included in improving sleep quality. As used herein, "sleep onset latency" refers to the time required to fall asleep from a waking state (the time required from turning off the lights to sleep until sleep begins). Sleep quality can be evaluated using sleep onset latency as an index, and shortening sleep onset latency means improving sleep quality, i.e., the ease of falling asleep. Furthermore, increasing the time spent in non-REM sleep is also included in improving sleep quality. Non-REM sleep can be divided into three stages: N1, N2, and N3, depending on the depth of sleep. N1 and N2 are light sleep, and N3 is deep sleep. Sleep quality can be evaluated using the time spent in N3 sleep as an index, and an increase in N3 sleep time indicates an improvement in sleep quality, i.e., an increase in the feeling of deep sleep. Furthermore, increasing or maintaining peripheral skin surface temperature, or suppressing a decrease in peripheral skin surface temperature, and increasing the number or length of capillaries promote heat dissipation, which acts dominantly against the decrease in core body temperature during sleep and promotes sleep onset, thereby improving sleep quality.

[0024] Although there is no single, well-defined method for assessing "sleep quality," it can be assessed by both subjective and objective assessments. Subjective assessments include the Pittsburgh Sleep Quality Index (PSQI) and the OSA Sleep Inventory (MA version), which include not only qualitative assessments but also quantitative assessments such as sleep duration. Objective assessments include polysomnograms (PSG) using electroencephalography (EEG) and activity monitors, as well as temperature measurements. While objective assessments can assess the association between short sleep durations and poor health, they have limitations, such as the lack of correlation between long sleep durations and health outcomes. Therefore, it is preferable to assess sleep quality using both subjective and objective assessments.

[0025] In this specification, "sleep quality" is subjectively evaluated, for example, using five factors from the OSA Sleep Questionnaire (MA version). The OSA Sleep Questionnaire (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 Questionnaire (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.

[0026] In this specification, "sleep quality" can be further evaluated objectively by measuring electroencephalograms (EEG) and body temperature during sleep onset and sleep. Electroencephalograms can be measured using electroencephalography, magnetic resonance imaging, near-infrared spectroscopy, invasive techniques, magnetoencephalography, and the like. Examples of electroencephalography include the InSomnograf (manufactured by S'UIMIN Co., Ltd.) and the EEG headset AE-120A (manufactured by Nihon Kohden Corporation). Body temperature can be measured using, for example, a contact thermometer, which measures by directly contacting the temperature-sensing part with the subject, or a non-contact thermometer, which measures without contacting the temperature-sensing part. Examples of non-contact thermometers include radiation thermometers and thermographs. Examples of thermographs include the InfReC R450 (manufactured by Nippon Avionics) and the infrared thermocamera SK-8500 (manufactured by Sato Keiryoki Seisakusho Co., Ltd.). Body temperature is particularly measured by measuring the skin temperature of peripheral areas, such as the surface skin temperature of the hands and feet.

[0027] Electroencephalograms (EEG) can determine whether a living organism is active or asleep. EEG is classified into five stages: wakefulness, REM sleep, and non-REM sleep (N1, N2, and N3). Wakefulness indicates an active state. Sleep is further classified into REM sleep and non-REM sleep, which is further divided into three stages (N1, N2, and N3) according to the depth of sleep. REM sleep is the lightest sleep, while non-REM sleep stages N1 and N2 are light sleep, and N3 is deep sleep. When falling asleep, a person transitions from the wakefulness stage, which is an active state, to the sleep stage N1. Furthermore, prior to falling asleep, peripheral skin temperature rises and core body temperature drops. Therefore, sleep latency can be measured by measuring EEG or body temperature.

[0028] The improving agent of the present invention has the effect of shortening the sleep onset latency time. For example, when the improving agent of the present invention is administered in a daily dose of 10 mg or more, for example, about 10 to 500 mg, preferably about 25 to 400 mg, and more preferably about 50 to 300 mg, converted into the amount of black soybean seed coat extract per adult (body weight 50 kg) for one week or more, the sleep onset latency time is shortened, for example, by 1 minute or more, preferably by 2 minutes or more, more preferably by 5 minutes or more, and even more preferably by 6 minutes or more, 7 minutes or more, 10 minutes or more, 15 minutes or more, or 20 minutes or more, compared to when the improving agent of the present invention is not administered.

[0029] Furthermore, the improving agent of the present invention has the following (a) to (e): (a) Sleepiness upon waking, (b) sleep maintenance; (c) Fatigue recovery (d) sleep duration, and (e) Sleep depth The quality of sleep can be improved by at least one selected from the group consisting of:

[0030] Specifically, the "depth of sleep" can be determined by measuring the time spent in deep sleep, for example, the time spent in N3, which is deep sleep. Sleep cycles are usually repeated three to five times per night during sleep stages. Therefore, the "depth of sleep" is determined based on the total time spent in deep sleep (for example, N3 hours) per night. That is, the longer the time spent in deep sleep, the deeper the sleep (the longer the time spent in deep sleep). Therefore, the improving agent of the present invention has the effect of extending the time spent in deep sleep, for example, the total time spent in N3. For example, when the improving agent of the present invention is administered at a daily dose of 10 mg or more, for example, about 10 mg to 500 mg, preferably about 25 to 400 mg, and more preferably about 50 to 300 mg, converted into the amount of black soybean seed coat extract per adult (body weight 50 kg) for one week or more, the total N3 time is extended, for example, by 1 minute or more, preferably by 5 minutes or more, more preferably by 10 minutes or more, more preferably by 15 minutes or more, 20 minutes or more, 30 minutes or more, 40 minutes or more, or 50 minutes or more, compared to when the improving agent of the present invention is not administered.

[0031] Furthermore, the improving agent of the present invention has the effect of increasing or maintaining peripheral skin surface temperature or suppressing a decrease in peripheral skin surface temperature. The improving agent of the present invention exerts the above-mentioned effect when the living body is in an active state, including normal times, as well as upon waking up, going to bed, or sleeping. Furthermore, the improving agent of the present invention exerts the above-mentioned effect even under cooling conditions, particularly when the peripheral skin surface is cooled. When the improving agent of the present invention is administered for one week or more at a daily dose of 10 mg or more, e.g., about 10 mg to 500 mg, preferably about 25 to 400 mg, more preferably about 50 to 300 mg, and even more preferably about 50 to 100 mg, calculated as the amount of black soybean seed coat extract per adult (body weight 50 kg), the agent increases or maintains the peripheral skin surface temperature by, for example, 0.3°C or more, preferably 0.5°C or more, more preferably 1.0°C or more, and even more preferably 1.2°C or more, 1.5°C or more, 1.8°C or more, 2.0°C or more, or 2.5°C or more, compared to when the improving agent of the present invention is not administered, or inhibits a decrease in peripheral skin surface temperature. As used herein, "normal" refers to a state in which the living body is active and at rest (all waking activities performed in a sitting or recumbent position with an energy expenditure of 1.5 METs or less) or low-intensity (less than 3 METs) physical activity in daily life. In addition, as used herein, "upon waking up" refers to the time from waking up to getting out of bed. Examples of peripheral skin surfaces include the skin surfaces of the hands and feet, and more specifically, the skin surfaces of the backs of the hands, backs of the feet, and palms. METs (metabolic equivalents) are an index of energy expenditure during physical activity, calculated by dividing the energy expenditure during physical activity by the energy expenditure in a sitting-at-rest state, with the sitting-at-rest state being expressed as 1 MET.

[0032] Therefore, as used herein, sleep improvement includes shortening of sleep onset latency, as described above, and preferably further includes improvement of at least one quality of sleep selected from the group consisting of (a) sleepiness upon awakening, (b) sleep maintenance, (c) fatigue recovery, (d) sleep duration, and (e) sleep depth, particularly an increase in the total time of N3 non-REM sleep, and / or an increase or maintenance of peripheral skin surface temperature or inhibition of a decrease in peripheral skin surface temperature.

[0033] [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.

[0034] 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).

[0035] Orally ingested (or administered) forms include, for example, liquid, jelly, and solid forms.

[0036] 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.

[0037] 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.

[0038] 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.

[0039] 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.

[0040] 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.

[0041] 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.

[0042] 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.

[0043] 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.

[0044] The content of the black soybean seed coat extract in the improving agent of the present invention can be appropriately determined depending on the type of dosage form and the type of application (e.g., pharmaceutical composition, food and drink, 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 changed 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, converted into the amount of black soybean seed coat extract (dry amount) contained in the improving agent of the present invention, is 10 mg or more, for example, approximately 10 to 500 mg, preferably approximately 25 to 400 mg, and more preferably approximately 50 to 300 mg. It is usually administered orally once a day or in two to 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 taken with a meal, or within 30 minutes before or after a meal, although this is not a limitation.

[0045] [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.

[0046] 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.

[0047] 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, without limitation, 10 mg or more, e.g., approximately 10 to 500 mg, preferably approximately 25 to 400 mg, and more preferably approximately 50 to 300 mg, calculated as the amount of black soybean seed coat extract (dry amount) contained in the sleep-improving agent of the present invention. It is usually administered orally once a day or in two or three divided doses.

[0048] 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.

[0049] 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.

[0050] 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]

[0051] The present invention will be explained in more detail below by showing experimental examples, but the present invention is not limited to these examples.

[0052] 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.

[0053] [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%).

[0054] [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.

[0055] (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.

[0056] (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 absorbance of the control group as B, and the absorbance of 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 flavanol content was calculated as catechin equivalents.

[0057] (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)

[0058] (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. The elution conditions were as follows: A standard solution of cyanidin 3-glucoside was also 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)

[0059] 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.

[0060] [Table 1]

[0061] [Test Method 1] The study was a double-blind, parallel-group comparative study. 69 subjects (ages 20-65, mean age 41) were assigned to three groups: a placebo group (Group 1) and a test food group (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) listed in Table 2 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.

[0062] The test diets used were black soybean seed coat extract-containing diets (Test Diets 1 and 2) and a control diet (Placebo 1). The formulations of each test diet are shown below. (Test Diet 1: low dose of 100 mg / day) Tablets containing 100 mg of black soybean seed coat extract 2 per 3 tablets (polyphenol content 58%) (Test Diet 2: high dose of 300 mg / day) Tablets containing 300 mg of black soybean seed coat extract 2 per 3 tablets (polyphenol content 58%) (Placebo 1) Tablets not containing black soybean seed coat extract (replaced with dextrin) Note that Placebo was prepared so that there was no significant difference in calories, etc. from Test Diets 1 and 2. Table 2 shows the nutritional component tables of each test diet.

[0063]

Table 2

[0064] <Measurement of capillaries> The measurement of capillaries was carried out before the intake of the test diet (any one day within 2 weeks before the start of intake) and 12 weeks after the intake. Using a capillary scope (Atto Corporation), the capillaries on the nail bed of the left ring finger were photographed. The number and length of the capillaries were calculated using software (Capillary Analysis System, a system for quantifying the photographed capillary images).

[0065] <Evaluation of sleep quality using the OSA sleep questionnaire> 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 for five weekdays. Using the average scores for each of the five weekdays, 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) were assessed upon awakening the following morning. The OSA Sleep Questionnaire (MA version) consists of the following 16 items, each rated on a four-point scale. Each of the following 16 items is 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.

[0066] [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.

[0067] <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).

[0068] [Test Method 2] The study was a double-blind, parallel-group comparative study. 64 subjects (30-66 years old, mean age 46 years) were assigned to two groups: a placebo group and a test food group (low dose 100 mg / day group) (placebo group: 32 (16 men, 16 women), test food group: 32 (16 men, 16 women)). Subjects were instructed to take one tablet of each test food (test food 3 or placebo 2) listed in Table 3 after dinner for 12 weeks. Electroencephalograms (EEGs), peripheral body temperature, and sleep quality were measured. Test days were the week before the start of test food intake (week 0) and at weeks 4, 8, and 12 after the start of test food intake. An EEG monitor was worn at bedtime the night before the test day to measure EEG during sleep, and the following morning, sleep quality was assessed by completing the OSA Sleep Questionnaire (MA version) upon awakening. In addition, peripheral body temperature was measured before ingestion of the test food (week 0) and 12 weeks after the start of test food ingestion. The implementation period of Test Method 2 was from August 29, 2023 to September 25, 2023 for the start period (before ingestion of the test food (week 0)), and from November 21, 2023 to December 23, 2023 for the 12-week examination period.

[0069] The test foods used were a food containing black soybean husk extract (test food 3) and a control food (placebo 2). The composition of each test food is shown below. (Test Food 3: Low Dose 100mg / day) Tablets containing 100mg of black soybean husk extract 2 (58% polyphenol content) per tablet (Placebo 2) Tablets containing no black soybean husk extract (replaced with dextrin) Placebo 2 was prepared so that there would be no significant difference in terms of calorie content etc. from test food 3. Table 3 shows the nutritional information for each test food.

[0070] [Table 3]

[0071] The subjects were healthy individuals. Specifically, 64 subjects were selected based on the following inclusion criteria, exclusion criteria, and dropout / discontinuation criteria. Selection criteria: Applicants must meet all of the following criteria. (i) Healthy individuals (ii) People who are dissatisfied with the feeling of fatigue upon waking and the quality of their sleep (short sleep time, difficulty falling asleep, difficulty sleeping soundly, dreaming, inability to recover from fatigue, etc.) in their daily lives. (iii) Subjects who are deemed by the investigator to be suitable for participation in the study based on the results of the Beck Depression Inventory-Second Edition (BDI-II) questionnaire in the pre-intake test. (iv) Japanese men and women aged between 30 and 65 at the time of obtaining consent (v) Among those who meet (i) to (iv) and do not meet the following exclusion criteria, those who have low sleepiness upon waking in the OSA sleep questionnaire in the pre-intake test. Exclusion criteria: Those who meet any of the following criteria. (i) Subjects currently undergoing treatment for or with a history of malignant tumor, heart failure, or myocardial infarction (ii) Persons with pacemakers or implantable cardioverter defibrillators (iii) Persons currently undergoing treatment for the following chronic diseases: Cardiac arrhythmia, liver damage, kidney damage, cerebrovascular disease, rheumatism, diabetes, dyslipidemia, hypertension, and other chronic diseases (iv) People who regularly consume foods for specified health uses or foods with functional claims (v) People who regularly take medicines (including herbal medicines) or supplements (vi) People with allergies (medicines or test food-related foods), especially those with allergies to soybeans, pollen, or milk (vii) Pregnant, breastfeeding, or intending to become pregnant during the study period (viii) Persons who have participated in other clinical trials within the 28 days prior to obtaining consent, or who plan to participate during the trial period (ix) Any other person who the investigator deems inappropriate for this study (x) Anyone who has an infant under the age of one in the household (xi) A person who sleeps with an infant (a child between the age of one and the age of entering elementary school) (xii) A person who lives with and needs to care for a person requiring care. (xiii) A person who sleeps with multiple people in the same bed (xiv) Persons who have irregular sleep hours and habits due to night shifts, etc. (xv) Subjects who urinate twice or more at night (xvi) People with irregular lifestyles (irregular meal times, insufficient sleep, etc.) (xvii) Persons who regularly consume more than moderate alcohol (an average of approximately 20g of pure alcohol per day (500mL of beer, 180mL of sake, 90mL of shochu, 60mL of whiskey / brandy, 180mL of wine, 500mL of chuhai)). (xviii) Persons receiving treatment for insomnia or sleep disorders (xix) Subjects who consume foods or beverages containing ingredients that are thought to affect sleep quality (GABA, crocetin, L-theanine, lactic acid bacteria, etc.) Dropout / Discontinuation Criteria: Study participants who met any of the following criteria were considered to have dropped out or discontinued the study. (i) If the trial is suspended due to the participant's circumstances (ii) If it is discovered that the instructions of the investigator or the trial administrator have not been followed. (iii) Significant deviation from the compliance requirements set out in the Protocol (iv) Any other reason that the investigator deems it appropriate to drop out the subject. (v) A serious adverse event occurs and the investigator determines that the participant should be discontinued from the study. (vi) When the investigator determines that the participant is unable to continue the trial due to objective symptoms. (vii) Any other reason in which the investigator determines that it is difficult to continue the trial.

[0072] <Electroencephalogram measurement> For the measurement of electroencephalogram, the subject wore an electroencephalograph [Insomnograf, manufactured by S'UIMIN Co., Ltd.] at bedtime. The electroencephalogram measurement was carried out for three days on consecutive weekdays in the week before the start of the test diet (week 0) and the 12th week from the start of the test diet intake. The average value of the data for two days, the second and third days, was adopted as the electroencephalogram for that week. The obtained electroencephalograms were classified into five stages: wakefulness, which is an active state; REM sleep, which is a sleep state; and N1, N2, and N3, which are non-REM sleep states.

[0073] <Measurement of peripheral body temperature> Before the test diet intake (any one day of week 0) and 12 weeks after the start of the test diet intake, the skin surface temperature of the palm of the subject was measured with a thermograph (InfReC R450, manufactured by Nippon Avionics Co., Ltd.). The measurement was carried out after the subject had rested quietly for 30 minutes or more in a room maintained at a constant temperature and humidity, and was performed at normal times (before the cooling load) and immediately after the cooling load. The cooling load was carried out by immersing the hand in water at 15°C for one minute. Furthermore, from the thermograph image, the value [AUC (Area Under the Curve)] (unit: °C·h) indicating the temperature decrease in terms of area from immediately after the cooling load to 30 minutes after the cooling load on the palm surface was determined. The larger the AUC value, the faster the recovery of body temperature after the cooling load.

[0074] <Evaluation of sleep quality using the OSA sleep questionnaire> The evaluation of sleep quality using the OSA sleep questionnaire MA version was carried out in the same manner as in Test Method 1.

[0075] 〔Results and discussion〕 <Effect of shortening sleep latency> As is clear from the electroencephalogram measurement results, the sleep latency was shortened in the test food intake group compared to the placebo intake group (Figs. 7-1 and 7-2). In the placebo intake group, the sleep latency increased by 76.5 seconds from an average of 706.0 seconds before intake to an average of 782.4 seconds 12 weeks after intake, while in the test food intake group, it was shortened by 96.2 seconds from an average of 893.3 seconds before intake to an average of 797.1 seconds 12 weeks after intake. A significant difference between the groups was observed in the change rate of sleep latency (p < 0.05) (Fig. 7-2).

[0076] <Improvement of sleep depth> A stratified analysis was conducted on subjects with poor sleep quality, whose pre-intake morning sleepiness scores were below the median (14.15 points) (15 in the placebo group, 14 in the test food group). As evidenced by EEG measurements, a significant difference was observed between the test food group and the placebo group in the total time of N3, the deepest sleep stage (p<0.05) (Figures 8-1 and 8-2). The placebo group's total N3 time increased by 31.0 seconds from an average of 2092.0 seconds before intake to an average of 2123.0 seconds after 12 weeks of intake, while the test food group's total time increased by 881.8 seconds from an average of 2171.8 seconds before intake to an average of 3053.6 seconds after 12 weeks of intake. Furthermore, the N3 total time during the pre-intake test was an average of 2289.7 seconds for the placebo group and 2978.8 seconds for the test food group for all subjects, but when limited to those whose morning sleepiness score was below the median (14.15 points), the placebo group had an average of 2092.0 seconds, and the test food group had an average of 2171.8 seconds, both of which were shorter. This suggests that the effect of the test food on improving sleep quality was more acutely reflected in the N3 total time for those with poor sleep quality.

[0077] <Effect of increasing, maintaining, or inhibiting a decrease in peripheral body temperature> In the placebo group, palm skin surface temperature decreased immediately after the cooling load, whereas in the test food group, palm skin surface temperature barely decreased (Figures 9-1 to 9-6). Furthermore, significant differences in surface temperature were observed between the groups both before and after the cooling load (p<0.01). Therefore, it was found that ingestion of black soybean seed coat extract resulted in resistance to and recovery from the cooling load. Thus, ingestion of black soybean seed coat extract increased, maintained, or inhibited the decline in peripheral body temperature during normal (before the cooling load) and after the cooling load. This may promote heat dissipation during sleep, lowering core body temperature and promoting sleep onset, improving sleep quality. In addition, in the placebo group, palm skin surface temperature decreased before and after ingestion. This is likely due to the decrease in temperature and body temperature between the start of the study (week 0) and the end of the study (week 12) during the early to late autumn period.

[0078] <Improvement of sleep quality> The results of sleep quality evaluation using the OSA Sleep Questionnaire MA version showed that the intake of black soybean husk extract improved all sleep quality items except for factor III (dreaming), as in test method 1. In particular, factor I (morning sleepiness) showed an improvement over time in the black soybean husk extract intake group, and there was a significant difference between the groups (<0.05 after 8 weeks of intake, <0.01 after 12 weeks of intake) (Figures 10-1 and 10-2).

[0079] 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.

[0080] 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. 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.

[0081] Formulation example 3: Individually wrapped stick jelly Individually packaged stick jellies 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. 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]

[0082] 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 shortening sleep onset latency, comprising as an active ingredient a black soybean seed coat extract extracted in the presence of an acid having a sulfo group.

2. The following (a) to (e): (a) morning sleepiness, (b) sleep maintenance; (c) Fatigue recovery (d) sleep duration, and (e) Depth of sleep The sleep-improving agent according to claim 1, further comprising at least one effect of improving sleep quality selected from the group consisting of:

3. The sleep-improving agent according to claim 1, further comprising the effect of increasing, maintaining, or inhibiting a decrease in peripheral skin surface temperature.

4. The sleep-improving agent according to claim 3, wherein the peripheral skin surface temperature is the skin surface temperature of the palm of the hand.

5. The sleep-improving agent according to claim 3, wherein the effect of increasing, maintaining or inhibiting a decrease in peripheral skin surface temperature is the effect of increasing, maintaining or inhibiting a decrease in peripheral skin surface temperature under normal conditions.

6. The sleep-improving agent according to any one of claims 1 to 5, which is in the form of a food or drink, a supplement, or a pharmaceutical composition.

7. A method for imparting to a composition an effect of shortening the latency to fall asleep, comprising blending a black soybean seed coat extract extracted in the presence of an acid having a sulfo group into the composition.

8. The composition is then mixed with the following (a) to (e): (a) morning sleepiness, (b) sleep maintenance; (c) Fatigue recovery (d) sleep duration, and (e) Depth of sleep The method according to claim 7, further providing at least one effect of improving sleep quality selected from the group consisting of:

9. The method according to claim 7, further comprising imparting to the composition an effect of increasing, maintaining, or inhibiting a decrease in peripheral skin surface temperature.

10. A method for producing a sleep-improving agent for shortening sleep onset latency, comprising using as an active ingredient a black soybean seed coat extract extracted in the presence of an acid having a sulfo group.

11. The sleep-improving agent comprises any one of the following (a) to (e): (a) morning sleepiness, (b) sleep maintenance; (c) Fatigue recovery (d) sleep duration, and (e) Depth of sleep 11. The method of claim 10, further comprising at least one sleep quality improving effect selected from the group consisting of:

12. The method according to claim 7, wherein the sleep-improving agent further has the effect of increasing, maintaining, or inhibiting a decrease in peripheral skin surface temperature.

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