Heat stress relievers

Abstract

To provide a new heat stress alleviating agent which can be ingested easily, conveniently and safely even by infants and elderly persons susceptible to heat stress such as heatstroke and which rapidly induces perspiration under a heat stress environment to thereby prevent, alleviate, improve a condition and a disease such as the heatstroke due to the heat stress.SOLUTION: There are provided a heat stress alleviating agent containing glycosyl hesperetin as an active ingredient and a basal body temperature maintaining agent containing glycosyl hesperetin as an active ingredient.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a heat stress alleviating agent, and more specifically to a heat stress alleviating agent that functions as a perspiration promoter or a core temperature rise inhibitor under a heat stress environment, and a basal body temperature maintaining agent.

Background Art

[0002] In recent years, due to global warming, the accompanying increase in midsummer days, extremely hot days, and tropical nights, as well as the urban heat island effect, exposure of the human body to heat stress that affects physical health has increased, and the incidence of heat-related illnesses such as heat stroke caused by heat stress has been increasing. Heat stroke has conventionally occurred frequently during exercise or labor in heat stress environments, but due to the influence of global warming, its incidence has recently increased even in daily life. Heat stroke refers to a condition in which, under a heat stress environment, the regulatory functions in the living body are significantly reduced due to insufficient heat dissipation, disruption of the balance of water and salt in the body, and the like. According to its symptoms, it is classified into heat cramp, heat exhaustion, and heat stroke accompanied by thermoregulatory dysfunction, and may lead to death in severe cases.

[0003] In particular, the increase in heat stroke among so-called heat stress-susceptible people, such as infants and young children with underdeveloped perspiration functions, and the elderly whose thermoregulatory functions including perspiration decline with age, has become a social problem. Against this background, valid and effective countermeasures against heat stress are desired.

[0004] In a heat stress environment, a living organism secretes sweat from sweat gland tissue and releases it from the epidermis. When the sweat evaporates, latent heat of vaporization is absorbed, thereby releasing heat from inside the body to regulate body temperature. That is, it is considered that diseases caused by heat stress such as heat stroke can be prevented, alleviated and improved by appropriately promoting perspiration to regulate body temperature.

[0005] As countermeasures against heatstroke, a disease caused by heat stress, in addition to adjustments to the living environment and clothing, frequent hydration and salt intake are recommended, and for example, soft drinks containing a specific sugar content and sodium have been reported (Patent Document 1). Furthermore, as a measure against heatstroke, attention is being paid to thermoregulation by promoting sweating, focusing on the decline in thermoregulatory function due to aging and the decrease in sweat volume due to the immaturity of sweating function in infants and children. As a method of promoting sweating, for example, there are reports of promoting sweating by ingesting a liquid formulation containing non-polymerized catechins and having an osmotic pressure lower than that of body fluids (Patent Document 2). However, such non-polymerized catechins have a strong bitter taste and cannot be easily ingested on a daily basis, and they also contain large amounts of caffeine and other substances that have a stimulating effect, so they are generally considered unsuitable for infants and children. Furthermore, as a sweat-promoting composition that can be consumed in a heat stress environment, it has been proposed to ingest a composition containing milk protein as an active ingredient (Patent Document 3). However, such milk proteins require a large intake of 30g or more per serving, making it difficult to consume them consistently every day. Furthermore, a heatstroke prevention agent characterized by containing an oil composition containing alpha-linolenic acid has been proposed (Patent Document 4), but it has the disadvantage of being difficult to easily incorporate into or process into food and beverages, including sports drinks, due to its low solubility in water. [Prior art documents] [Patent Documents]

[0006] [Patent Document 1] Japanese Patent Publication No. 2015-008712 [Patent Document 2] Japanese Patent Publication No. 2014-019691 [Patent Document 3] Republished Gazette WO2018-123873 [Patent Document 4] Japanese Patent Publication No. 2016-037498 [Overview of the initiative] [Problems that the invention aims to solve]

[0007] This invention has been made in view of the above-mentioned prior art, and the problem it aims to solve is to provide a new heat stress reliever that can be easily, conveniently, and safely ingested by infants and the elderly who are susceptible to the effects of heat stress such as heatstroke, and that quickly promotes sweating in a heat stress environment, thereby preventing, alleviating, or improving symptoms and diseases such as heatstroke caused by heat stress. [Means for solving the problem]

[0008] In order to solve the above problems, the inventors diligently conducted research and, as a result, unexpectedly discovered that oral intake of glycosyl hesperetin alleviates heat stress, and more specifically, that it promotes sweating and suppresses the rise in core body temperature under heat stress conditions, thus completing the heat stress alleviating agent of the present invention.

[0009] As a result of further diligent research efforts, the inventors unexpectedly discovered that oral intake of glycosyl hesperetin helps maintain basal body temperature, and thus completed the basal body temperature maintenance agent of the present invention.

[0010] In other words, the present invention solves the above problems by providing a heat stress mitigating agent containing glycosyl hesperetin as an active ingredient, and a basal body temperature maintenance agent containing glycosyl hesperetin as an active ingredient.

[0011] Regarding hesperidin and its glycosides, there have been reports, for example in Japanese Patent Publication No. 52-105221, of topical antiperspirants characterized by containing them as active ingredients. However, inhibiting sweating is the exact opposite of promoting sweating, which is considered effective in alleviating heat stress. The fact that glycosyl hesperetin has a sweat-promoting effect is an unexpected physiological function of glycosyl hesperetin that could not have been predicted at all before filing this application. [Effects of the Invention]

[0012] The heat stress reliever of the present invention contains glycosyl hesperetin as an active ingredient and can be safely and easily taken orally by humans on a daily and continuous basis without discomfort, and can be provided industrially at low cost. The heat stress reliever of the present invention can effectively promote sweating in a heat stress environment. Furthermore, the heat stress reliever of the present invention can effectively suppress the rise in core body temperature in a heat stress environment. In particular, the heat stress reliever of the present invention has the excellent characteristic of exhibiting the desired effects more significantly when applied to people who are at risk of heatstroke, etc., in so-called heat stress environments such as during summer or when working in the scorching sun.

[0013] The basal body temperature maintenance agent of the present invention contains glycosyl hesperetin as an active ingredient, and can be safely and easily taken orally by humans on a daily and continuous basis without discomfort, and can be provided industrially at low cost. According to the basal body temperature maintenance agent of the present invention, basal body temperature can be effectively maintained. In particular, the basal body temperature maintenance agent of the present invention has the excellent characteristic of exhibiting the intended effects more significantly when applied not only to coldness associated with so-called cold stress environments such as winter or when using air conditioning, but also to people with low body temperature, people with chronic cold sensitivity, and people who are at risk of thermoregulatory disorders such as hot flashes, flushing, and hot fussing due to menopausal symptoms. [Brief explanation of the drawing]

[0014] [Figure 1] This figure shows the time course of the average increase in core body temperature of subjects under heat stress conditions (during exercise at room temperature of 30°C and relative humidity of 50%) after a single dose of glycosyl hesperetin. [Figure 2] This figure shows the changes in basal body temperature of subjects who took glycosyl hesperetin long-term. [Modes for carrying out the invention]

[0015] Hereinafter, embodiments of the present invention will be described. These are merely illustrative of preferred embodiments for carrying out the present invention, and the present invention is not limited to these embodiments in any way.

[0016] The present invention relates to a heat stress alleviating agent comprising glycosyl hesperetin as an active ingredient.

[0017] As used herein, heat stress includes stimuli applied to the body by climatic factors such as summer, midsummer days, extremely hot days, tropical nights and urban heat island effect, environmental factors of high temperature and high humidity such as baths, hot springs, saunas, factories and workplaces, and additionally includes stimuli applied to the body by exertional factors such as those during exercise and labor. Further, as used herein, the expression "under a heat stress environment" means a situation exposed to heat stress caused by said climatic factors, environmental factors and / or exertional factors.

[0018] As used herein, the expression "alleviation of heat stress" means promotion of perspiration and suppression of core body temperature elevation under a heat stress environment, and the expression "heat stress alleviating agent" means an agent having a heat stress alleviating effect.

[0019] Glycosyl hesperetin, which is used as the active ingredient of the heat stress alleviating agent of the present invention, encompasses all general compounds in which a saccharide is bound to hesperetin, and preferred specific examples thereof include hesperidin, 7-O-β-glucosyl hesperetin, α-glycosyl hesperidin and the like.

[0020] Hesperidin, also called vitamin P, has a structure in which rutinose composed of rhamnose and glucose is bound to hesperetin, and is a compound represented by the structural formula shown in the following Chemical Formula 1, and is a component abundantly contained in citrus peels and the like.

[0021] Chemical Formula 1:

Chemical Formula

[0022] Furthermore, 7-O-β-glucosylhesperetin is a compound represented by the following chemical formula 2, having a structure in which the rhamnose group constituting the rutinose in hesperidin has been removed, and is characterized by higher water solubility compared to hesperidin. 7-O-β-glucosylhesperetin can be produced, for example, by reacting a solution containing hesperidin with α-L-rhamnosidase (EC 3.2.1.40), as shown in Japanese Patent Publication No. 10-323196.

[0023] Chemical formula 2: [ka]

[0024] Furthermore, α-glycosyl hesperidin is a compound in which sugars (such as D-glucose, D-fructose, or D-galactose) are α-bonded to hesperidin in equimolar or greater amounts. A typical example of α-glycosyl hesperidin is α-glucosyl hesperidin, represented by chemical formula 3 below, in which one molecule of glucose is α-bonded to the glucose molecule in the rutinose structure of hesperidin (also known as enzyme-treated hesperidin, glycosylated hesperidin, water-soluble hesperidin, or glycosylated vitamin P). For example, a commercially available product containing α-glucosyl hesperidin is the product "Hayashibara Hesperidin S" (Hayashibara Sales Co., Ltd.).

[0025] Chemical formula 3: [ka]

[0026] Glycosyl hesperetin is a safe and versatile substance that has been widely used as an ingredient in various foods and beverages, cosmetics, quasi-drugs, and pharmaceuticals. In particular, α-glycosyl hesperidin has higher water solubility and is easier to handle compared to hesperidin and 7-O-β-glucosyl hesperetin. In the body, like hesperidin and 7-O-β-glucosyl hesperetin, it is hydrolyzed to hesperetin by the action of endogenous enzymes and exhibits the physiological activity inherent to hesperetin.

[0027] In this invention, glycosyl hesperetin can be used regardless of its origin, manufacturing method, purity, etc., as long as it is glycosyl hesperidin. However, a high-purity product with fewer impurities is preferably used, and the high-purity product may be high-purity glycosyl hesperetin obtained through a crystallization process.

[0028] For example, hesperidin can be industrially produced in desired quantities by extracting it from hesperidin-containing plants such as citrus fruits, peels, seeds, and unripe fruits using appropriate solvents such as water or alcohol. Furthermore, α-glycosyl hesperidin can be industrially produced in desired quantities at low cost by reacting a glycosyltransferase with a solution containing hesperidin and an α-glucosyl sugar compound, as disclosed in, for example, Japanese Patent Publication No. 11-346792, to produce α-glycosyl hesperidin, and then collecting it.In addition, 7-O-β-glucosyl hesperetin can be produced by reacting hesperidin with α-L-rhamnosidase to release rhamnose from hesperidin, and then collecting it, in desired quantities, at low cost.

[0029] Furthermore, the same applicant as the present application has improved the manufacturing method to eliminate the off-flavors and discoloration that were previously considered drawbacks of glycosyl hesperetin. As a result, they have established glycosyl hesperetin with reduced off-flavors, discoloration, and odor (hereinafter, "off-flavors, discoloration, and odor" may be collectively referred to as "off-flavors, etc.") and a manufacturing method thereof, which were disclosed in the republished brochure WO2015 / 133483. Glycosyl hesperetin with reduced off-flavors, etc. has the excellent advantage of being able to be safely and easily ingested orally by humans on a daily basis without discomfort, and can be provided industrially at a low cost. Therefore, glycosyl hesperetin with reduced off-flavors, etc. can be advantageously used as a suitable glycosyl hesperetin for carrying out the present invention.

[0030] Furthermore, in this specification, when simply referred to as glycosyl hesperetin, unless otherwise specified, it may mean a glycosyl hesperetin mixture mainly composed of one or more selected from hesperidin, α-glycosyl hesperidin, and 7-O-β-glucosyl hesperetin. In addition, it is preferable that the glycosyl hesperetin used as an active ingredient contains α-glycosyl hesperidin, and it is preferable that α-glycosyl hesperidin contains α-glucosyl hesperidin, as this more significantly exhibits the intended effects of the present invention, namely, the effect of promoting sweating and the effect of suppressing the rise in core body temperature.

[0031] The content of glycosyl hesperetin as referred to in the present description means: taking a glycosyl hesperetin-containing composition as a sample, diluting or dissolving the sample in purified water to 0.1% (w / v), filtering the solution through a 0.45 μm membrane filter, then subjecting it to high performance liquid chromatography (HPLC) analysis under the following conditions, using reagent grade hesperidin (sold by Wako Pure Chemical Industries, Ltd.) as a standard substance, calculating based on the area of peaks appearing in the chromatogram at UV 280 nm and the molecular weight of each component such as hesperidin and α-glycosyl hesperidin (including α-glucosyl hesperidin, etc.), and it refers to the sum of the contents of each component corresponding to glycosyl hesperetin in the composition converted to the mass of anhydrous substance. The method for quantifying the content of each component corresponding to glycosyl hesperetin by said HPLC analysis is as shown in (1) to (4) below.

[0032] <HPLC analysis conditions> HPLC apparatus: "LC-20AD" (manufactured by Shimadzu Corporation) Degasser: "DGU-20A3" (manufactured by Shimadzu Corporation) Column: "CAPCELL PAK C18 UG 120" (manufactured by Shiseido Co., Ltd.) Detection: UV detector "SPD-20A" (manufactured by Shimadzu Corporation) Data processing apparatus: "Chromatopac C-R7A" (manufactured by Shimadzu Corporation) Sample injection volume: 10 μL Eluent: water / acetonitrile / acetic acid (80 / 20 / 0.01, volume ratio) Flow rate: 0.7 mL / min Temperature: 40°C Measurement wavelength: 280 nm

[0033] <Quantification of glycosyl hesperetin> (1) Hesperidin content: analyzed by HPLC, calculated based on the ratio between the peak area of the sample and the peak area of reagent grade hesperidin (sold by Wako Pure Chemical Industries, Ltd.) as a standard substance with a predetermined concentration. (2) α-glucosyl hesperidin content: This is calculated by analyzing the peak area using HPLC, and comparing it to the peak area of ​​a standard reagent hesperidin (sold by Wako Pure Chemical Industries, Ltd.) at a predetermined concentration, and based on the molecular weight ratio of α-glycosyl hesperidin to hesperidin. (3) 7-O-β-glucosylhesperetin content: Analyzed by HPLC, and calculated based on the ratio of the peak area to the peak area of ​​the standard substance reagent hesperidin (sold by Wako Pure Chemical Industries, Ltd.) at a predetermined concentration, and the molecular weight ratio of 7-O-β-glucosylhesperetin to hesperidin. (4) Other glycosyl hesperetin content: This is calculated by analyzing the peak area using HPLC, and then comparing it to the peak area of ​​a standard substance, reagent hesperidin (sold by Wako Pure Chemical Industries, Ltd.), at a predetermined concentration, and the molecular weight ratio of other glycosyl hesperetins to hesperidin.

[0034] As described above, the glycosyl hesperetin contained as the active ingredient in the heat stress mitigating agent of the present invention means a composition mainly comprising one or more compounds selected from (1) hesperidin, α-glycosyl hesperidin (such as α-glucosyl hesperidin), and 7-O-β-glucosyl hesperetin, which are compounds having a hesperetin skeleton, i.e., a glycosyl hesperetin mixture, and may also contain (2) flavonoids such as naringin, diosmin, neoponsirin, and glucosyl naringin, which are thought to be derived from the raw materials for its manufacture or to be produced as a by-product in the manufacturing process, and (3) trace components such as salts. The glycosyl hesperetin may contain hesperetin to the extent that the intended effects of the present invention are not hindered. Furthermore, the glycosyl hesperetin used in the present invention may also appropriately incorporate hesperetin whose dispersibility in solvents such as water has been enhanced by known physical or chemical methods, to the extent that the intended effects of the present invention are not hindered.

[0035] The glycosyl hesperetin, or glycosyl hesperetin mixture, contained as the active ingredient in the heat stress mitigating agent of the present invention, preferably has a total glycosyl hesperetin content per dry solid that is typically 50% by mass or more and less than 100% by mass, preferably 60% by mass or more and less than 100% by mass, more preferably 70% by mass or more and less than 100% by mass, even more preferably 80% by mass or more and less than 100% by mass, and even more preferably 85% by mass or more and less than 100% by mass. The upper limit of the glycosyl hesperetin content per dry solid that is contained as the active ingredient in the heat stress mitigating agent of the present invention is usually 99% by mass, which can be provided industrially in relatively large quantities, inexpensively and easily, but may be as low as 98% by mass for even lower costs, and even lower as low as 97% by mass or less for even lower costs. However, if the glycosyl hesperetin content per dry solid of the glycosyl hesperetin is low, it will inevitably be used in larger quantities compared to those with a high content. As a result, the operation becomes complicated and handling becomes difficult. Therefore, it is desirable that the lower limit of the glycosyl hesperetin content be 50% by mass or more, preferably 60% by mass or more, more preferably 70% by mass or more, even more preferably 80% by mass or more, and even more preferably 85% by mass or more.

[0036] A more preferred embodiment of the glycosyl hesperetin contained as the active ingredient in the heat stress mitigating agent of the present invention is α-glycosyl hesperidin containing α-glucosyl hesperidin. In this case, the preferred content of α-glucosyl hesperidin in the glycosyl hesperetin is usually 60% by mass or more and less than 100% by mass, preferably 70% by mass or more and less than 100% by mass, and more preferably 75% by mass or more and less than 100% by mass, based on dry solids. Furthermore, the upper limit of the α-glucosyl hesperidin content in the glycosyl hesperetin contained as the active ingredient in the heat stress mitigating agent of the present invention is basically less than 100% by mass as described above, but from the viewpoint of providing the heat stress mitigating agent of the present invention at a lower cost, it may also be a low content of 99% by mass or less, more preferably 95% by mass or less, and even more preferably 90% by mass or less, which can usually be provided industrially in relatively large quantities, inexpensively and easily. Furthermore, the lower limit of the α-glucosyl hesperidin content is usually 60% by mass or more, preferably 70% by mass or more, and more preferably 75% by mass or more, for the same reasons as the glycosyl hesperetin content in the glycosyl hesperetin mixture described above.

[0037] The present invention relates to a basal body temperature maintenance agent containing glycosyl hesperetin as an active ingredient.

[0038] The average human basal body temperature is approximately 36.5°C, which is considered the temperature at which enzymes in the body are most active, immune function is most vigorous, and health is maintained. However, in recent years, basal body temperature has been decreasing due to various factors, such as the effects of diet (skipping breakfast, extreme dieting, deficiencies in minerals, vitamins, and protein, smoking), disruption of lifestyle rhythms (nocturnal lifestyle, lack of sleep, inactivity during the day), environmental factors (winter, air conditioning, etc.), and aging. It is known that the body temperature of people with a decreased basal body temperature is 0.5 to 1.5°C lower than the average basal body temperature. Such a decrease in basal body temperature can lead to discomfort such as chills and fatigue, delayed wound healing, weakened immunity, decreased metabolism, decreased enzyme activity, low blood pressure, poor circulation such as cold hands and feet, stiff shoulders, lower back pain, and joint pain, impaired organ function such as constipation and diarrhea, and neurological disorders such as depression and other physical dysfunctions. In extreme cases, a decrease in basal body temperature can even be fatal. Therefore, it is important to properly regulate basal body temperature to approach the average basal body temperature of 36.5°C in order to maintain good health.

[0039] In this specification, basal body temperature refers to body temperature measured in a resting state upon waking, and usually refers to body temperature measured sublingually. Furthermore, in this specification, maintaining basal body temperature means bringing the basal body temperature close to the average basal body temperature of 36.5°C and maintaining it therein. In this specification, a person with a tendency towards low basal body temperature and a person with a tendency towards high basal body temperature refer to a person whose average sublingual basal body temperature is less than 36.2°C and 36.2°C or higher, respectively. More precisely, it refers to a person whose average sublingual basal body temperature is less than 36.1°C and 36.3°C or higher, respectively. Even more precisely, it refers to a person whose average sublingual basal body temperature is less than 36.0°C and 36.4°C or higher, respectively.

[0040] Glycosyl hesperetin, used as the active ingredient in the heat stress mitigating agent of the present invention as described above, can also be used as the active ingredient in a basal body temperature maintenance agent.

[0041] The heat stress reliever and basal body temperature maintenance agent of the present invention contains various glycosyl hesperetins as active ingredients. As will be described in detail later, when a person takes a heat stress reliever and basal body temperature maintenance agent containing glycosyl hesperetin as an active ingredient orally on a daily basis, the effects of promoting sweating and suppressing the rise in core body temperature are exerted, as well as effectively maintaining basal body temperature. Furthermore, heat stress relievers and basal body temperature maintenance agents containing glycosyl hesperetin as an active ingredient can not only prevent, alleviate, and improve symptoms and diseases caused by heat stress, such as heatstroke, but can also be expected to improve, alleviate, and prevent skin disorders and skin conditions such as edema and dry skin, as well as have a detoxifying effect. In addition to preventing, alleviating, and improving sleep disorders and symptoms associated with sleep disorders such as insomnia, including difficulty falling asleep, difficulty maintaining sleep, and difficulty sleeping soundly, it can also help with menopausal symptoms in women and men, as well as vasomotor symptoms such as hot flashes, flushing, abnormal sweating, palpitations, dizziness, emotional instability, tinnitus, irritability, anxiety, depression, insomnia, headache, lethargy, memory loss, and fatigue. It can be advantageously used as a so-called functional food for alleviating, preventing or improving neuropsychiatric symptoms such as fatigue, musculoskeletal symptoms such as stiff shoulders, lower back pain and joint pain, digestive symptoms such as nausea and loss of appetite, skin and mucous membrane symptoms such as dry skin and itching, and urogenital symptoms such as urinary disorders, frequent urination, sexual dysfunction and vulvar discomfort. It can also be used to prevent, alleviate or improve various diseases such as lifestyle-related diseases like abnormal blood sugar, abnormal blood pressure, abnormal dyslipidemia, abnormal uric acid levels and obesity, metabolic syndrome, heart disease, liver disease, kidney disease, brain disease, neurological disease, allergic diseases, infectious diseases, and malignant tumors. Furthermore, it can be advantageously used as a health food, beauty food, nutritional functional food, health functional food, functional food, food for specified health uses, quasi-drug, and pharmaceutical. Furthermore, heat stress relievers and basal body temperature maintenance agents containing glycosyl hesperetin as an active ingredient may also be incorporated into other functional foods, health foods, beauty foods, nutritional functional foods, health functional foods, functional foods, foods with health claims, foods for specified health uses, quasi-drugs, pharmaceuticals, or food and beverages as appropriate.

[0042] Furthermore, when glycosyl hesperetin is used for the aforementioned purposes, when used in combination with one or more other plant or animal-derived substances, extracts, or compounds having sweat-promoting effects, core body temperature rise-inhibiting effects, and basal body temperature maintenance effects, the sweat-promoting effects, core body temperature rise-inhibiting effects, and basal body temperature maintenance effects of glycosyl hesperetin are exerted more effectively, and the prevention, alleviation, and improvement of heat stress, improvement, alleviation, and prevention of skin disorders and skin quality, prevention, alleviation, and improvement of sleep disorders and symptoms associated with sleep disorders, prevention, alleviation, and improvement of menopausal disorders and symptoms associated with menopausal disorders, and prevention, alleviation, and improvement of various diseases are exerted even more effectively.

[0043] Other animal and plant-derived substances, their extracts, or compounds that have effects of promoting sweating, suppressing the rise in core body temperature, and maintaining basal body temperature include animal substances and their extracts such as bovine gallstones, pearl jasmine, oyster shell, viper, earthworm skin, bear antler, antelope horn, and deer antler; artichoke, eyebright, Japanese ash, green oak, goosefoot, madder, red reed, autumn olive, agrimony, agni fruit, akebia, acai fruit, chives, asafoetida, ashwagandha, Japanese cypress, catechu tree, ahi amarillo, ahi limon, rapeseed, sawtooth oak, and amachazu. Ru, anise, American witch hazel, aristine, arnica, angelica, epimedium, Japanese knotweed, Italian parsley, ginkgo, winterflower, strawberry, thread lily, seaweed, catnip, fig, dill, ipe bark, Japanese maple, rock lily, Indian lily, fennel, witch hazel, wintergreen, turmeric, red almond, udo, plum, evergreen oak, ulpicia, Epimedium brevicornum, rosehip, echinacea, perilla, shallot, Eleutherococcus senticosus, broom, elm campure, elder, elba mate, oak Barley, allspice, astragalus, astragalus palm, phellodendron bark, coptis japonica, milk thistle, large-leaved vine, large-leaved lily, plantain, large-leaved buckwheat, barley, sea beans, ginseng, lily of the valley, onion, tiger lily, oregano, orange, kava, ground jasmine, leucocephala, sansho pepper, pumpkin seeds, catuaba bark, valerian, lily of the valley, turnip, kabosu, chamomile, mustard, trifoliate orange, guarana, caramel, cardamom, curry plant, wild ginger, licorice, bellflower, dock, tree pepper, caraway Wild garlic, apricot kernel, kumquat, calendula, betel leaf, Clerodendrum trichotomum, camphor tree bark, gardenia, cumin, Sophora flavescens root, clary sage, Lilium medeoloides, walnut, grapefruit, watercress, clove, black mustard, Schizonepeta tenuifolia, caper, Cassia seed, Geranium thunbergii, lingonberry, pepper, Monochoria vaginalis, coriander, Sargassum fuciformis, pomegranate, sweet potato, Ziziphus jujuba, saffron, sarsaparilla, hawthorn, Japanese pepper, Shikuwasa, Angelica pubescens, Shishito pepper, Perilla, winged bean, Lithospermum erythrorhizon, Cinnamomum cassia bark, branches, and root bark, Spiraea japonica,Peony, jasmine, peony, Ophiopogon japonicus, ginger, Cimicifuga, Rheum officinale, Aster scaber, white mustard, Chlorophytum chinense, Aster tataricus, Agarwood, Sudachi citrus, Stevia, Spanish licorice, sage, savory, nettle, plantain, St. John's wort, valerian, wild mustard, dandelion, elderberry, butterbur, horseradish, cinnamon bark, branches, and root bark, celery, angelica tree, gentian, buckwheat, sorrel, rhubarb, radish, beech, thyme, Takasa Lilium maculatum, Polygonum cuspidatum, Cardamine hirsuta, Davila rugosa, Onion, Lilium maculatum, Tarragon, Chicory, Chervil, Chives, Chadebugue, Clove, Senna chinnebari, Centella asiatica, Tree onion, Polygonum multiflorum, Daisy, Dill, Devil's claw, Farfugium japonicum, Lilium longiflorum, Devil's claw root, Tencha, Chili pepper, Angelica root, Star anise fruit, Peach kernel, Houttuynia cordata, Passionflower, Thornless, Panax japonicus, Eucommia ulmoides leaf, Tomato, Tormentilla, Rumex rotundifolia, Feverfew, Jujube, Wormwood, Chives, Elderberry, Garlic, Trombethus chinensis, No Palmetto, Aster tataricus, Wild onion, Leek, Basil, Mint, Lilium auratum, Bush clover, Star lily, Ginger, Taro, Parsley, Patchouli, Passionflower, Passion fruit, Job's tears, Vanilla, Habanero, Pfaffia root, Paprika, Nutsedge, Tribulus terrestris, Jack honey, Jalapeño, Bell pepper, Prunus campanulata, Hyssop, Cypress, Long pepper, False long pepper, Sunflower, Dwarf jasmine, Allium schoenoprasum, Lilium pumilum, Crepis japonica, Areca nut, Bhut Jolokia, Plum vine, Fenugreek seeds, Fennel, Butterbur, Hyacinth bean, Black star Yu, pomelo, loofah, safflower, safflower ragwort, henna, rue, angelica tree, peony, hops, ephedra, marjoram, silver vine, matillus, pine, edelwood, mate tea, Madonna lily, milk thistle seeds, horse chestnut seeds, mandarin orange, Bupleurum falcatum root, Mitsuba, Mitsuba deutzia, myoga ginger, Akebia quinata, purple coneflower, mozuku seaweed, willow, daylily, Japanese bellflower, yam, mountain lily, mountain shallot, yuzu, water cider, aster, lychee seeds, lime, shallot, lavender, lamb's ear, Regal lily, leek,Plants such as Ryukyu bamboo, Ryukyu raspberry, unripe apples, linden flowers, rooibos, arugula, rhubarb, borage, lettuce, lemon, lemongrass, lemon thyme, lemon verbena, lemon balm, lemon myrtle, forsythia, rosehip, rose pink buds, rosemary, rose red, roselle, laurel, rocoto, rosea, logwood, scallions, wasabi, burnet, lotus, persimmon leaves, licorice leaves, black soybean seed coats, black rice seeds, ginger lily leaves, narrow-leaved lily, Western willow, and other plants or their extracts; as well as seaweed, seaweed, and other similar materials. Extracts from various seaweeds; extracts from raw coffee beans, sweet potato shochu lees, bracket fungus mycelium and Agaricus mycelium; and polyphenols such as resveratrol, quercetin, chlorogenic acid, anthocyanins, curcumin, kaempferol, catechins, and flavonoids; carotenoids such as astaxanthin, β-cryptoxanthin, lycopene, fucoxanthin, lutein, crocetin, retinol, retinal, retinoic acid, and β-carotene; pilocarpines such as pilocarpine hydrochloride; ephedrine, aspirin, sodium salicylate, insulin, and Lenalin, acetylcholine, salicin, salicylic acid, choline salicylate, diflunisal, ethenzamide, mefenamic acid, diclofenac, sulindac, indomethacin, felbinac, etodolac, tolmetin, naptomen, ibuprofen, flurbiprofen, ketoprofen, naproxen, fenoprofen, oxabrozin, loxoprofen, zaltoprofen, ketrolac, piroxicam, ampiroxicam, meloxicam, lornoxicam, tenoxicam, celecoxib, valdecoxib, parecoxib sodium, thiaramide hydrochloride, Tinolysine hydrochloride, Epirizole, Emorphazone, Mepirizole, Acetaminophen, Phenylbutazone, Oxyphenylbutazone, Ketophenylbutazone, Feprazone, Sulfinpyrazone, Antipyrine, Sulpyrine, Isopropylantipyrine, Glycine, Theanine, GABA, Sake yeast, Diphenhydramine hydrochloride, Zolpidem tartrate, Triazolam, Zopiclone, Eszopiclone, Etizolam, Brotizolam, Rilmazafone hydrochloride, Lormetazepam, Flunitrazepam, Estazolam, Nitrazepam, Quazepam, Flurazepam hydrochloride,Haloxazolam, ramelteon, suvorexant, mirtazapine, amitriptyline, mianserin, trazodone, risperidone, olanzapine, quetiapine, levomepromazine, chlorpromazine, alliin, allicin, capsaicin, dihydrocapsaicin, shogaol, gingerol, zingerone, zingiberene, piperine, sanshool, sanshoamide, geranol, allyl isothiocyanate, phenethyl isothiocyanate, sinigrin, sinalbin, sulforaphane glucosinolate, equol, isoflavone, L-tyrosine, L-phenylalanine, L-tryptophan, 1,3,5-trihydroxybenzene, 3,4-dihydroxyphenylacetic acid, L-3,4-dihydroxyphenylalanine, 4-(2-aminoethyl)benzene-1,2-diol, noradrena Examples include phosphorus, adrenaline, 5-hydroxytryptamine, caffeic acid, ifenprodyl, alpha-lipoic acid, 4-hydroxychalcone, ergothioneine, resveratrol, carnosine, carnitine, salsolinol hydrobromide, sinapic acid, ferulic acid, cinnamic acid, tocopheryl nicotinate, alpha-tocopherol, beta-tocopherol, gamma-tocopherol, delta-tocopherol, alpha-tocotrienol, beta-tocotrienol, gamma-tocotrienol, delta-tocotrienol, nicotinamide, proanthocyanidin, hydrolyzable tannin, catechol, chlorogenic acid, isochlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, caffeoylquinic acid and other chlorogenic acids, leucocyanidin, prunin, procyanidol oligomer, glucosylrutin, glucosylnaringin, etc.

[0044] The dosage of the heat stress reliever and basal body temperature maintenance agent of the present invention can be appropriately adjusted depending on the frequency of intake and the physical condition of the person taking the agent. When glycosyl hesperetin, the active ingredient, is considered entirely as hesperidin and converted by mass (hereinafter simply referred to as "hesperidin equivalent" in this specification), the dosage is usually 1 to 5 times a day, preferably 2 to 3 times a day, with each dose ranging from 10 to 3,000 mg in hesperidin equivalent, preferably 20 to 2,000 mg, more preferably 30 to 1,000 mg, and even more preferably 50 to 500 mg. Furthermore, while the heat stress reliever and basal body temperature maintenance agent of the present invention can produce the desired effects even with a single or several doses, it is preferable to take it for at least 2 weeks, more preferably 4 weeks, and even more preferably 8 weeks. Furthermore, if the intake falls below the lower limit, the intended effects may be significantly reduced or not exerted at all. Conversely, if the intake exceeds the upper limit, the effects commensurate with the dosage will not be exerted, which is undesirable from an economic standpoint.

[0045] The heat stress reliever and basal body temperature maintenance agent of the present invention can be used in various solid, granular, powder, suspension, paste, jelly, and liquid forms, such as lozenges, cod liver oil drops, complex vitamins, mouth fresheners, mouth fragrance tablets, oral and enteral nutritional supplements, and oral medications. It can also be incorporated into various compositions in the aforementioned forms. Furthermore, in the methods of using the aforementioned forms and incorporating them into various compositions in the aforementioned forms, one or more known methods such as mixing, kneading, blending, adding, dissolving, immersion, penetration, spraying, coating, misting, and injection can be appropriately used in the process until the compositions are completed. The amount of glycosyl hesperetin included as the active ingredient in the heat stress reliever and basal body temperature maintenance agent of the present invention is at the discretion of the user as long as the desired effects are achieved.

[0046] The present invention will be explained in more detail by the following experiment.

[0047] <Experiment 1: Effects of glycosyl hesperetin intake on subjects' sweat volume and core body temperature under heat stress conditions> In this study, subjects were given either a test sample containing glycosyl hesperetin or a placebo sample, and changes in sweat volume and core body temperature were measured under heat stress conditions (during exercise at room temperature of 30°C and humidity of 50%).

[0048] <Experiment 1-1: Preparation of Glycosyl Hesperetin> Glycosyl hesperetin was prepared according to the method described in Example 1 of the brochure with international publication number WO2015 / 133483. Specifically, 4 parts by mass of a 1N aqueous sodium hydroxide solution was heated to 80°C, 1 part by mass of hesperidin and 7 parts by mass of dextrin (DE20) were added, and the mixture was dissolved with stirring for 30 minutes to a pH of 9.0. To this, 30 units of cyclodextrin glucanotransferase derived from Diobacillus stearothermophilus Tc-91 strain (accession number FERM BP-11273 at the Patent Organism Depository Center (IPOD), National Institute of Technology and Evaluation, located at 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan) were added per dextrin gram, and the mixture was reacted for 18 hours while maintaining a pH of 6.9 and a temperature of 50°C. Next, the remaining enzyme in the resulting enzyme reaction solution was inactivated by heating. Then, 100 units of glucoamylase (trade name "Glucozyme", manufactured by Nagase ChemteX Corporation) were added per gram of solid content of the enzyme reaction solution, and the reaction was carried out for 5 hours while maintaining pH 5.0 and 55°C to produce α-glucosyl hesperidin. The resulting enzyme reaction solution was heated to inactivate the remaining enzyme, filtered, and the filtrate was passed through a column packed with a porous synthetic adsorbent, trade name "Diaion HP-10" (sold by Mitsubishi Chemical Corporation) using SV2. Next, the column was washed with purified water, and then the ethanol aqueous solution concentration was gradually increased while passing the filtrate through the column. The α-glucosyl hesperidin-containing fraction was collected, concentrated under reduced pressure, and powdered to obtain a pale yellow glycosyl hesperetin powder. The glycosyl hesperetin powder obtained in this example contained 80.0% by mass of α-glucosyl hesperidin, 12.3% by mass of hesperidin, and 7.7% by mass of other components. In terms of glycosyl hesperetin composition, it was equivalent to commercially available glycosyl hesperetin (product name "Hayashibara Hesperidin S" (Hayashibara Sales Co., Ltd.)).

[0049] <Experiment 1-2: Preparation of test samples> As shown in Table 1, 250 mg of glycosyl hesperetin powder obtained in Experiment 1-1 was completely dissolved in 200 mL of commercially available Near Water (mandarin orange flavor) to prepare the test sample. Only commercially available Near Water was used as the placebo sample.

[0050] [Table 1]

[0051] <Glycosyl hesperetin intake study> Four healthy adult males (ages 26-51) were included as subjects. They were given 200 mL of either the test sample or a placebo sample without being informed. After resting for 20 minutes, they exercised in a room set to 30°C and 50% humidity. The exercise load consisted of 30 minutes of step-ups on a 15 cm high step platform, performed 20 times per minute. All subjects wore commercially available clothing made of the same material throughout the study. The study was a crossover, single-dose, double-blind trial. Subjects who received the test sample first received the placebo sample, and subjects who received the placebo sample first received the test sample. A one-day interval was left between trials to eliminate the influence of the previously administered sample.

[0052] <Evaluation items and evaluation methods> The evaluation items were the amount of sweat and the change in core body temperature under heat stress conditions (during exercise at room temperature of 30°C and relative humidity of 50%), and both were measured. Sweat amount was calculated by subtracting the weight of clothing worn before exercise from the weight of clothing worn after exercise, and the average sweat amount for four subjects was calculated. Core body temperature was evaluated every minute from the start of exercise until the end of exercise (30 minutes later). Core body temperature during exercise was measured using a temperature probe for ear thermometers with a thermistor temperature sensor, and a data-collecting handheld thermometer (Gram Co., Ltd., LT-8A). The average increase in core body temperature was calculated by using the core body temperature immediately before exercise as the baseline value, determining the temperature change every minute from the start of exercise, and calculating the average for four subjects. Table 2 shows the average amount of sweat for subjects under heat stress conditions. Figure 1 and Table 3 show the average change in core body temperature under heat stress conditions.

[0053] [Table 2]

[0054] As shown in Table 2, the average amount of sweat produced by subjects in this study was 55.2 ± 32.7 g in the placebo group, compared to 59.4 ± 34.2 g in the test sample group, which was clearly higher. In other words, it was confirmed that the intake of glycosyl hesperetin significantly increased the amount of sweat produced by subjects under heat stress conditions.

[0055] [Table 3]

[0056] Furthermore, as shown in Table 3, in the placebo group, the average increase in core body temperature increased with time: 0.10±0.03℃ at 5 minutes after the start of exercise, 0.25±0.06℃ at 10 minutes, 0.41±0.10℃ at 20 minutes, and 0.47±0.12℃ at 30 minutes. On the other hand, in the test sample group, the average increase was 0.07±0.07℃ at 5 minutes after the start of exercise, 0.18±0.09℃ at 10 minutes, 0.33±0.10℃ at 20 minutes, and 0.38±0.12℃ at 30 minutes. Also, as shown in Figure 1, the average change in core body temperature in the test sample group (indicated by "■" in Figure 1) was clearly more gradual compared to the placebo group (indicated by "○" in Figure 1). Therefore, it was shown that ingestion of the test sample containing glycosyl hesperetin significantly suppressed the rise in core body temperature under heat stress conditions.

[0057] As shown in Tables 2 and 3 and Figure 1, it was confirmed that ingesting glycosyl hesperetin under heat stress conditions increased sweating and suppressed the rise in core body temperature. Therefore, glycosyl hesperetin is found to be useful as an active ingredient in heat stress relief agents.

[0058] <Experiment 2: Effects of long-term intake of glycosyl hesperetin on basal body temperature> Subjects were given a test sample in tablet form (740 mg / tablet) with the composition shown in Table 4 below for an extended period, and changes in basal body temperature were measured.

[0059] [Table 4]

[0060] <Long-term intake study of glycosyl hesperetin> Eighteen healthy adult males (aged 23 to 63) were included as subjects. The subjects were given one tablet of the test sample (a glucosyl hesperetin-containing tablet with the composition shown in Table 4 above) once a day at any time of their choosing for eight consecutive weeks.

[0061] <Evaluation items and evaluation methods> Each subject measured and recorded their basal body temperature every morning upon waking while at rest, using a basal body thermometer (Terumo Corporation, model C531). The measurement involved placing the tip of the thermometer under the tongue and holding it there for 5 minutes with the mouth lightly closed. Basal body temperature measurements were conducted for a total of 16 weeks, starting 4 weeks before the test sample intake as a pre-experiment observation, continuing through the 8-week test sample intake period, and ending 4 weeks after the end of test sample intake. The mean and standard deviation of basal body temperature for each week were calculated.

[0062] Based on the average basal body temperature for the week prior to sample intake, subjects were divided into a high basal body temperature group (9 subjects with a tendency towards high basal body temperature, where the average basal body temperature for the week prior to sample intake was 36.2°C or higher) and a low basal body temperature group (9 subjects with a tendency towards low basal body temperature, where the average basal body temperature for the week prior to sample intake was less than 36.2°C). The results of the stratified analysis are shown in Table 5 and Figure 2.

[0063] <Statistical analysis> Measurement values ​​were expressed as mean ± standard deviation (SD). Statistical analysis was performed using Microsoft Excel 2013 (Microsoft Japan Co., Ltd.), comparing the results with the mean values ​​for the week prior to the test. Paired t-tests were used for statistical analysis. A significance level (p-value) of less than 0.05 (risk level less than 5%) was considered statistically significant.

[0064] [Table 5]

[0065] As shown in Table 5 and Figure 2, for subjects who ingested the test sample containing glycosyl hesperetin, the mean basal body temperature each week from 4 weeks before test sample intake through 8 weeks of intake to 4 weeks after intake showed no significant difference in the high basal body temperature group compared to the mean value in the week before test sample intake. In contrast, in the low basal body temperature group, the basal body temperature was significantly higher in 1 to 5 weeks after the start of test sample intake, 7 to 8 weeks after the start of test sample intake, and 1 to 4 weeks after the end of intake, compared to the mean value in the week before test sample intake (significance level (p value) less than 0.05, however, the significance level (p value) was less than 0.01 in the 3rd week after the start of intake). Specifically, the study showed that ingestion of the test sample containing glycosyl hesperetin resulted in the basal body temperature of the high-temperature group (subjects with a tendency towards high basal body temperature, whose average basal body temperature for the week prior to test sample intake was 36.2°C or higher) remaining at around the average basal body temperature of 36.5°C, while in the low-temperature group (subjects with a tendency towards low basal body temperature, whose average basal body temperature for the week prior to test sample intake was less than 36.2°C) rising and approaching the appropriate temperature range of around the average basal body temperature of 36.5°C.

[0066] As clearly shown in Figure 2, ingestion of the test sample containing glycosyl hesperetin resulted in the high basal body temperature group (indicated by "●" in Figure 2) maintaining their basal body temperature at around the average basal body temperature of 36.5°C, while in the low basal body temperature group (indicated by "■" in Figure 2), their basal body temperature was raised to approach the appropriate temperature range of around 36.5°C, thus maintaining their basal body temperature. This result indicates that glycosyl hesperetin is useful as an active ingredient in basal body temperature maintenance agents.

[0067] The present invention will be described in detail below based on examples, but the present invention is not limited to these examples. [Examples]

[0068] <Powdered heat stress reliever> A commercially available α-glucosyl hesperidin-containing powder (product name "Hayashibara Hesperidin S", sold by Hayashibara Co., Ltd.) was used as a heat stress reliever. This product exhibits a sweat-promoting effect or a core body temperature rise-suppressing effect, and can be added to various beverages such as water, tea, black tea, and coffee, as well as other foods and beverages, for daily oral intake. It is a heat stress reliever with excellent storage stability and thermal stability. [Examples]

[0069] A heat stress reliever in tablet form of 250 mg was obtained by uniformly mixing 1 part by mass of glycosyl hesperetin-containing powder (α-glucosyl hesperidin 82% by mass, hesperidin 1% by mass, 7-O-β-glucosyl hesperetin 8% by mass, other components 9% by mass) (Hayashibara Pharmaceutical Co., Ltd. product), 19 parts by mass of α,α-trehalose dihydrate crystal-containing powder (product name "Treha", Hayashibara Sales Co., Ltd.), 0.1 parts by mass of citric acid, and 0.1 parts by mass of sodium chloride. The mixture was compressed according to a conventional method, and a heat stress reliever in tablet form of 250 mg per tablet was obtained. This product has excellent effects in promoting sweating or suppressing the rise in core body temperature. When administered daily to patients who have developed heatstroke or to people at risk of developing heatstroke, at a rate of approximately 25 to 1000 mg of the above glycosyl hesperidin per adult, it can alleviate or improve symptoms and effectively delay or prevent the onset of heatstroke. [Examples]

[0070] A heat stress reliever in the form of a soft drink was uniformly dissolved in 5000 parts by mass of water, 200 parts by mass of sugar, 100 parts by mass of α,α-trehalose dihydrate crystal-containing powder (product name "Treha", sold by Hayashibara Co., Ltd.), 6 parts by mass of citric acid, 6 parts by mass of sodium chloride, 0.2 parts by mass of potassium chloride, 0.05 parts by mass of calcium lactate, 0.01 parts by mass of magnesium chloride, 5 parts by mass of α-glucosyl hesperidin crystal powder (purity 99% by mass or higher, manufactured by Hayashibara Co., Ltd.), and 0.1 parts by mass of ascorbic acid 2-glucoside anhydrous crystal-containing powder (product name "Ascofresh", sold by Hayashibara Co., Ltd.). This product exhibits a sweat-promoting effect or a core body temperature rise-suppressing effect, and is a heat stress reliever with good flavor and taste. [Examples]

[0071] <Hard candy-type heat stress reliever> 10 parts by mass of α,α-trehalose dihydrate crystal-containing powder (product name "Treha", sold by Hayashibara Co., Ltd.) and 20 parts by mass of water were concentrated under reduced pressure at 155°C until the moisture content was approximately 2% or less. Then, the mixture was cooled to 120°C. 0.5 parts by mass of citric acid, 0.5 parts by mass of α-glucosyl hesperidin-containing powder (product name "Hayashibara Hesperidin S", sold by Hayashibara Co., Ltd.), 0.01 parts by mass of sodium chloride, and appropriate amounts of lemon flavoring were mixed in. Finally, the mixture was molded and packaged according to conventional methods to obtain a hard candy-type heat stress reliever. This product is useful as a heat stress reliever that exhibits a sweat-promoting effect or a core body temperature rise-suppressing effect, and has good flavor and taste. [Examples]

[0072] Three parts by mass of gum base were heated and melted until softened. Six parts by mass of α,α-trehalose (product name "Treha", sold by Hayashibara Co., Ltd.) and one part by mass of glycosyl hesperetin-containing powder (α-glucosyl hesperidin 82% by mass, hesperidin 1% by mass, 7-O-β-glucosyl hesperetin 8% by mass, other components 9% by mass) (Hayashibara Co., Ltd. product) were added. Further, 0.1 parts by mass of citric acid and appropriate amounts of coloring and flavoring agents were mixed together. The mixture was then kneaded, molded, and packaged using a conventional method to obtain chewing gum containing α-glucosyl hesperidin. This product exhibits a sweat-promoting effect or a core body temperature rise-suppressing effect and is useful as a heat stress reliever with good flavor and texture. [Examples]

[0073] A compound was prepared consisting of 30 parts by mass of maltose (product name "Maltose PH", sold by Hayashibara Co., Ltd.), 3 parts by mass of monosodium glutamate, 2 parts by mass of glycine, 2 parts by mass of sodium chloride, 2 parts by mass of citric acid, 0.3 parts by mass of magnesium carbonate, 1 part by mass of calcium lactate, 5 parts by mass of α-glucosyl hesperidin crystalline powder (purity 99% by mass or higher, Hayashibara Co., Ltd.), 0.02 parts by mass of thiamine, and 0.02 parts by mass of riboflavin. This compound was divided into 30g portions in laminated aluminum bags and heat-sealed to prepare a heat stress relief agent in the form of an enteral or oral nutritional supplement. This product exhibits a sweat-promoting effect or a core body temperature rise-suppressing effect, and can be dissolved in approximately 250 to 500 mL of sterile water per bag and administered enterally or orally as a heat stress relief agent, making it advantageous as a liquid for improving and preventing heatstroke. [Examples]

[0074] <Heat stress relief agent in capsule form> A heat stress reliever in capsule form was obtained by uniformly mixing 10 parts by mass of calcium acetate monohydrate, 50 parts by mass of magnesium L-lactate trihydrate, 57 parts by mass of maltose, 20 parts by mass of α-glucosyl hesperidin-containing powder (product name "Hayashibara Hesperidin S", sold by Hayashibara Co., Ltd.), 12 parts by mass of γ-cyclodextrin inclusion compound containing 20% ​​vitamin E, and 1 part by mass of ginger extract powder. The mixture was then processed into granules using a granulation machine, and the resulting granules were sealed in gelatin capsules according to a conventional method, with each capsule containing 150 mg of the contents. This product exhibits a sweat-promoting effect or a core body temperature rise-suppressing effect, and can be advantageously used as a capsule for improving and preventing heatstroke. [Examples]

[0075] <Powdered heat stress reliever> A powder containing glycosyl hesperetin (α-glucosyl hesperidin 82% by mass, hesperidin 1% by mass, 7-O-β-glucosyl hesperetin 8% by mass, other components 9% by mass) (Hayashibara Co., Ltd. product) was mixed with 10 parts by mass of sucrose, 3 parts by mass of maltitol, and 15 parts by mass of water-soluble dietary fiber (product name "Fiberixa", Hayashibara Co., Ltd.). The mixture was then placed in stick-shaped light-shielding and moisture-proof packaging containers in 5g portions to obtain a heat stress relief agent in powder form. This product exhibits a sweat-promoting effect or a core body temperature rise-suppressing effect. One to two packets can be added to various beverages such as water, tea, black tea, coffee, or other foods and drinks and taken orally on a daily basis. Because this product has excellent sweat-promoting effects, it has effects on improving swelling, dry skin, promoting metabolism, and detoxification, and is also useful as a beauty health food. [Examples]

[0076] Ten parts by mass of L-ascorbic acid, nineteen parts by mass of α-glucosyl hesperidin crystalline powder (purity 99% or higher, Hayashibara Co., Ltd.), seventy parts by mass of maltose (product name "Sanmalto", Hayashibara Co., Ltd.), and one part by mass of sucrose stearate were uniformly mixed and then compressed into tablets by a conventional method to obtain a heat stress reliever in tablet form. This product is useful as a heat stress reliever that exhibits a sweat-promoting effect or a core body temperature rise-suppressing effect, and has a good flavor and texture. Because this product has excellent sweat-promoting effects, it also has effects that improve swelling, dry skin, promote metabolism, and have a detoxification effect, making it useful as a beauty health food as well. [Examples]

[0077] <Gummy candy-type heat stress reliever> 150 parts by mass of commercially available α-maltosyltrehalose-containing syrup (product name "Hellodex", sold by Hayashibara Co., Ltd.) was heated under reduced pressure to concentrate it to a moisture content of 15% by mass. 13 parts by mass of gelatin dissolved in 18 parts by mass of water according to a conventional method was then mixed uniformly with 2 parts by mass of α-glucosylhesperidin-containing powder (product name "Hayashibara Hesperidin S", sold by Hayashibara Co., Ltd.), 2 parts by mass of citric acid, 0.1 parts by mass of anhydrous crystalline ascorbic acid 2-glucoside powder (product name "Ascofresh", sold by Hayashibara Co., Ltd.), 0.1 parts by mass of sodium chloride, and appropriate amounts of coloring and flavoring agents. The mixture was then molded and packaged to obtain a gummy candy-type heat stress reliever containing α-glucosylhesperidin. This product exhibits a sweat-promoting effect or a core body temperature rise-suppressing effect, and is useful as a heat stress reliever with good flavor and texture. Because this product has excellent sweat-inducing properties, it has effects such as improving swelling, dry skin, promoting metabolism, and detoxification, making it useful as a beauty and health food. [Examples]

[0078] <Supplement-type heat stress reliever> A heat stress reliever in supplement form was obtained by uniformly mixing 1 part by mass of glycosyl hesperetin-containing powder (α-glucosyl hesperidin 82% by mass, hesperidin 1% by mass, 7-O-β-glucosyl hesperetin 8% by mass, other components 9% by mass) (Hayashibara Co., Ltd. product), 50 parts by mass of water-soluble dietary fiber (product name "Fiberixa", Hayashibara Co., Ltd.), 10 parts by mass of α,α-trehalose dihydrate crystal-containing powder (product name "Treha", Hayashibara Co., Ltd.), 1 part by mass of glycine, 0.1 parts by mass of theanine, 0.1 parts by mass of GABA, and 0.1 parts by mass of carnitine. The mixture was then filled into stick-shaped paper containers coated on the inside with aluminum foil at 3g each. This product is useful as a heat stress reliever in supplement form, exhibiting a sweat-promoting effect or a core body temperature rise-suppressing effect, and having a good flavor and taste. Because this product is excellent at suppressing the rise in core body temperature, it has a sleep-inducing effect, sleep-inducing effect, and sleep-improving effect, making it useful as a health food. [Examples]

[0079] <Yogurt-type heat stress reliever> 30 parts by mass of α-glucosyl hesperidin crystalline powder (purity 99% by mass or higher, Hayashibara Co., Ltd. product), 700 parts by mass of skim milk powder, and 4,000 parts by mass of purified water were mixed to prepare a raw material for fermented milk (yogurt mix). This was heat-sterilized at 95°C for 10 minutes and then cooled to 45°C. Next, 100g of the mixed starter was inoculated, and the mixture was fermented in a tank at 47°C for 5 hours, after which it was cooled to below 8°C to obtain a yogurt-type heat stress reliever. This product is useful as a heat stress reliever that exhibits a sweat-promoting effect or a core body temperature rise-suppressing effect, and has good flavor and taste. When administered daily at a rate of 100-500g per adult, it can alleviate or improve symptoms, and effectively delay or prevent the onset of heatstroke in patients who have developed heatstroke or in people at risk of developing heatstroke. Because this product is excellent at suppressing the rise in core body temperature, it has a sleep-inducing effect, sleep-inducing effect, and sleep-improving effect, making it useful as a health food. [Examples]

[0080] <Powdered form of basal body temperature maintenance agent> 10 parts by mass of α-glucosyl hesperidin-containing powder (product name "Hayashibara Hesperidin S", Hayashibara Sales Co., Ltd.), 9 parts by mass of α,α-trehalose dihydrate crystal-containing powder (product name "Treha", Hayashibara Sales Co., Ltd.), 1 part by mass of lactosucrose (product name "Nyuka Oligo", Hayashibara Sales Co., Ltd.), 30 parts by mass of dextrin, 0.1 parts by mass of ascorbic acid 2-glucoside anhydrous crystal-containing powder (product name "Ascofresh", Hayashibara Sales Co., Ltd.), and 0.1 parts by mass of coenzyme Q10 were stirred and mixed, and 5 g portions were placed in stick-shaped light-shielding and moisture-proof packaging containers to obtain a powder-type basal body temperature maintenance agent. This product exerts a basal body temperature maintenance effect, and can be taken orally on a daily basis by adding 1 to 2 packets per day to various beverages such as water, tea, black tea, coffee, or other foods and drinks. [Examples]

[0081] <Basal body temperature maintenance agent in the form of mixed sweeteners> A basal body temperature maintenance agent in the form of a mixed sweetener was obtained by heating 100 parts by mass of isomerized liquid sugar, 1 part by mass of α,α-trehalose dihydrated crystal-containing powder (product name "Treha", sold by Hayashibara Co., Ltd.), 1 part by mass of lactosucrose (product name "Nyuka Oligo", sold by Hayashibara Co., Ltd.), and 1 part by mass of glycosyl hesperetin-containing powder (α-glucosyl hesperidin 82% by mass, hesperidin 1% by mass, 7-O-β-glucosyl hesperetin 8% by mass, other components 9% by mass) (Hayashibara Co., Ltd. product) at 80°C for 30 minutes. This product has good flavor and taste, and is useful as a liquid mixed sweetener with excellent basal body temperature maintenance effect that is easy to heat and prepare in various foods and beverages. [Examples]

[0082] A basal body temperature maintenance agent in the form of a health supplement beverage was prepared by mixing and dissolving 40 parts by mass of isomerized sugar, 2 parts by mass of maltitol, 10 parts by mass of black vinegar, 5 parts by mass of apple cider vinegar, 2 parts by mass of citric acid, 2 parts by mass of malic acid, 2 parts by mass of concentrated apple juice, and 2 parts by mass of α-glucosyl hesperidin crystalline powder (purity 99% by mass or higher, manufactured by Hayashibara Co., Ltd.). This product has good flavor and taste and is useful as a basal body temperature maintenance agent. [Examples]

[0083] <Powdered form of basal body temperature maintenance agent> 10 parts by mass of α-glucosyl hesperidin-containing powder (product name "Hayashibara Hesperidin S", Hayashibara Sales Co., Ltd.), 3 parts by mass of α,α-trehalose dihydrate crystal-containing powder (product name "Treha", Hayashibara Sales Co., Ltd.), 1 part by mass of maltitol, 15 parts by mass of water-soluble dietary fiber (product name "Fiberixa", Hayashibara Sales Co., Ltd.), 0.1 parts by mass of royal jelly (product name "Hayashibara Royal Jelly", Hayashibara Sales Co., Ltd.), 0.1 parts by mass of soy isoflavones, and 0.1 parts by mass of placenta extract were stirred and mixed, and 5g portions were placed in stick-shaped light-shielding and moisture-proof packaging containers to obtain a powder form of basal body temperature maintenance agent. This product has excellent basal body temperature maintenance effects, and therefore has effects that improve cold sensitivity and menopausal symptoms, and is also useful as a beauty health food. [Examples]

[0084] A basal body temperature maintenance agent in tablet form was obtained by uniformly mixing 29 parts by mass of glycosyl hesperetin-containing powder (α-glucosyl hesperidin 82% by mass, hesperidin 1% by mass, 7-O-β-glucosyl hesperetin 8% by mass, other components 9% by mass) (Hayashibara Pharmaceutical Co., Ltd. product), 70 parts by mass of maltose (product name "Sanmalto", Hayashibara Sales Co., Ltd.), and 1 part by mass of sucrose stearate ester, 0.1 part by mass of garlic extract, 0.1 part by mass of maca extract, 0.1 part by mass of oyster extract, 0.1 part by mass of zinc, 0.05 part by mass of arginine, and 0.05 part by mass of citrulline. This mixture was then compressed into tablets by a conventional method. Because this product has excellent basal body temperature maintenance effects, it has effects that improve cold sensitivity and menopausal symptoms, and is also useful as a beauty health food. [Industrial applicability]

[0085] As described above, the present invention relates to a heat stress reliever containing glycosyl hesperetin as an active ingredient, based on the unique finding that glycosyl hesperetin exhibits a remarkable sweat-promoting effect and a core body temperature rise-suppressing effect in humans. Furthermore, the present invention relates to a basal body temperature maintenance agent containing glycosyl hesperetin as an active ingredient, based on the unique finding that glycosyl hesperetin exhibits a remarkable basal body temperature maintenance effect in humans. The heat stress reliever or basal body temperature maintenance agent of the present invention is effective in maintaining and restoring health when used regularly by healthy people or sick people. In particular, the heat stress reliever of the present invention can be used as a sweat-promoting agent or a core body temperature rise-suppressing agent, and when applied to people who are at risk of heatstroke, etc., in so-called heat stress environments such as summer or during labor, it has the excellent characteristic of exhibiting the desired effects more significantly compared to other subjects. Furthermore, the basal body temperature maintenance agent of the present invention has the excellent characteristic of exhibiting more pronounced effects when applied not only during so-called cold stress such as winter or when using air conditioning, but also to people who are at risk of chronic cold sensitivity or thermoregulatory disorders due to menopausal symptoms. [Explanation of symbols]

[0086] In Figure 1, ○: Placebo sample group ■: Test sample intake group

[0087] In Figure 2, ●: Basal body temperature high group ■: Basal body temperature low group *: A statistically significant difference is indicated when the significance level (p-value) is less than 0.05 (p-value less than 5%). **: A statistically significant difference is observed when the p-value (significance level) is less than 0.01 (risk level less than 1%).

Claims

1. A human core body temperature rise inhibitor in a heat stress environment, comprising glycosyl hesperetin as an active ingredient, The aforementioned glycosyl hesperetin is a core body temperature rise inhibitor containing α-glucosyl hesperidin.

2. The core body temperature rise inhibitor according to claim 1, wherein the glycosyl hesperetin further comprises hesperidin and / or 7-O-β-glucosyl hesperetin.

3. The core body temperature rise inhibitor according to claim 1 or 2, characterized in that it is used to administer to humans orally in a dose of 50 to 500 mg in hesperidin equivalent per dose.

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