Compositions used to exert sedative effects, methods for producing the same, foods and beverages, and bath additives

Abstract

The present invention provides a novel composition that contains a naturally occurring component as an active ingredient and is capable of exerting a sedative effect on the autonomic nervous system and / or central nervous system. [Solution] The composition contains as an active ingredient one or more pyrazines selected from (A) 2-ethyl-5(6)-methylpyrazine, (B) 2-ethyl-3,5(6)-dimethylpyrazine, and (C) 2,3,5-trimethylpyrazine, and is used to exert a sedative effect on the autonomic nervous system and / or central nervous system.

Description

[Technical Field]

[0001] The present invention relates to a composition used to exert a sedative effect, a method for producing the composition, and a food, drink, and bath additive containing the composition. [Background technology]

[0002] The nervous system consists of peripheral nerves, a fine network that spreads out like a net throughout every part of the body, and the central nervous system, where information collected from the peripheral nerves is further concentrated.

[0003] The central nervous system consists of the brain and spinal cord, and is responsible for processing information received from the entire body and issuing commands. On the other hand, the peripheral nerves connect the central nervous system with nerves that are distributed to various organs inside and outside the body, transmitting information.The peripheral nerves include motor nerves and autonomic nerves. The autonomic nervous system, which is made up of the sympathetic and parasympathetic nervous systems, regulates certain processes in the body, such as blood pressure and respiratory rate. When the balance between the sympathetic and parasympathetic nervous systems is disrupted, systemic symptoms such as fatigue, insomnia, and fatigue persist, as well as organic symptoms such as headaches, palpitations, shortness of breath, dizziness, hot flashes, lightheadedness, diarrhea, constipation, and sensitivity to the cold, are known to appear. Mental symptoms such as emotional instability, irritability, anxiety, and depression are also known to appear.

[0004] Components contained in tea, such as theanine, are widely known to have a relaxing effect. For example, Non-Patent Document 1 reports that consuming green tea after working on a computer makes the parasympathetic nervous system dominant, improves attention, and relieves mental fatigue. Patent Document 1 discloses a composition for regulating the autonomic nervous system that contains black tea extract as an active ingredient, and Patent Document 2 discloses an autonomic nervous system regulator that is characterized by containing aroma components derived from black tea leaves, particularly hotrienol and furaneol. Patent Document 3 discloses an agent for enhancing autonomic nervous system symptoms containing a tea leaf extract, which contains 0.13% by weight or more of delphinidin or its glycosides, 23.0% by weight or less of catechins, and 0.6% by mass or more of hydrolyzable tannins relative to the dry weight of the tea leaf extract, and when the tea leaf extract is heated at a temperature of 100°C for 120 minutes, the residual rate of delphinidin or its glycosides in the tea leaf extract is 90% or more.

[0005] Furthermore, in Patent Document 4, the present applicant has proposed an autonomic nervous system regulator and a beverage for regulating the autonomic nervous system, the active ingredient of which is a roasted green tea extract, more specifically, a roasted green tea extract containing, as a solids concentration, catechins, theanine, caffeine, and pyrazines. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] Watanabe et al., Journal of the Japanese Society of Complementary and Alternative Medicine, Vol. 10, No. 1: 9-16 (2013) [Patent documents]

[0007] [Patent Document 1] JP 2017-109997 A (Patent No. 6964974) [Patent Document 2] JP 2019-163248 A (Patent No. 6625775) [Patent Document 3] Japanese Patent Application Publication No. 2018-138026 [Patent Document 4] Japanese Patent Application Laid-Open No. 2024-69950 Summary of the Invention [Problem to be solved by the invention]

[0008] Tea has become a staple in Japanese life as a healthy drink. Among these, hojicha has established a unique position as a tea unique to Japan. Hojicha is a representative Japanese tea with a rich aroma made by roasting green tea, but there have been few research reports on its components, and its functionality has not been fully elucidated.

[0009] The present invention is based on new findings obtained through research into the effects of aromatic components contained in roasted green tea on the nervous system, and aims to provide a composition used to exert a sedative effect, a method for producing the same, and uses of the composition. [Means for solving the problem]

[0010] [1] A first aspect of the present invention is a composition containing a pyrazine as an active ingredient, which is used to exert a sedative effect on the autonomic nervous system and / or the central nervous system.

[0011] [2] A second aspect of the present invention is the composition of the first aspect, wherein the pyrazines are one or more selected from the following (A) to (C): (A) 2-Ethyl-5(6)-methylpyrazine (B) 2-Ethyl-3,5(6)-dimethylpyrazine (C) 2,3,5-trimethylpyrazine

[0012] [3] A third aspect of the present invention is a composition according to the first or second aspect, wherein the sedative effect on the autonomic nervous system is a parasympathetic nervous stimulation effect and / or a sympathetic nervous suppression effect. [4] A fourth aspect of the present invention is the composition of the third aspect, characterized in that the parasympathetic nervous system stimulating effect is an increase in the pupil constriction rate. [5] A fifth aspect of the present invention is the composition according to the third aspect, characterized in that the sympathetic nerve inhibitory effect is to increase peripheral skin temperature.

[0013] [6] A sixth aspect of the present invention is a composition according to any one of the first to fifth aspects, wherein the sedative effect on the central nervous system is an effect of reducing the amount of oxygenated hemoglobin in the prefrontal cortex, as assessed by NIRS (near-infrared spectroscopy).

[0014] [7] A seventh aspect of the present invention is a composition used to exert a sedative effect on the central nervous system, which contains 2,3,5-trimethylpyrazine as an active ingredient.

[0015] [8] An eighth aspect of the present invention is the composition according to any one of the first to seventh aspects, characterized in that the composition is for nasal administration. [9] A ninth aspect of the present invention is the composition according to any one of the first to eighth aspects, wherein the composition contains 10 ppb to 1000 ppb of pyrazines.

[0016]

[10] A tenth aspect of the present invention is a food or drink to which the composition according to any one of the first to ninth aspects is added.

[11] An eleventh aspect of the present invention is a bath additive containing the composition of any one of the first to ninth aspects.

[0017]

[12] A twelfth aspect of the invention is a method for producing a composition used to exert a sedative effect on the autonomic nervous system and / or the central nervous system, characterized in that an extract is obtained by extracting roasted tea leaves, and the extract is separated and purified to obtain a composition containing pyrazines. [Effects of the Invention]

[0018] The pyrazines, which are the active ingredients of the composition proposed by the present invention, are components that can be obtained from natural products such as roasted green tea. When ingested intranasally, the composition proposed by the present invention can exert a sedative effect on the autonomic nervous system and / or the central nervous system. For example, the sedative effect on the autonomic nervous system can increase the pupil constriction rate by stimulating the parasympathetic nervous system, or can increase peripheral skin temperature by suppressing the sympathetic nervous system. In particular, a composition containing 2,3,5-trimethylpyrazine as an active ingredient exerts a sedative effect on the central nervous system when taken intranasally, and can reduce the amount of oxygenated hemoglobin in the prefrontal cortex as assessed by NIRS (near-infrared spectroscopy), for example, by reducing cerebral blood flow. The composition proposed by the present invention is safe because it is made from ingredients derived from natural products, and has the effects described above, so it can be used as a food or drink, or even as a bath additive. [Brief explanation of the drawings]

[0019] [Figure 1] FIG. 1 shows the results of measuring the pupil constriction rate after smelling the control and each pyrazine fragrance. [Figure 2] FIG. 1 shows the results of measuring peripheral skin temperature (fingertip temperature) after smelling the control and each pyrazine fragrance. [Figure 3] This is a graph comparing the change in pupil constriction rate (ΔCR) after smelling the scent of each pyrazine. [Figure 4] This is a graph comparing the change (Δ°C) in peripheral skin temperature (fingertip temperature) after smelling the scent of each pyrazine. [Figure 5] FIG. 1 shows the results of a subjective questionnaire after smelling the scent of the control and each pyrazine. [Figure 6] FIG. 1 shows the results of the Multifaceted Mood Scale (MMS) after smelling the control and each pyrazine fragrance. [Figure 7] FIG. 1 shows the results of measuring the amount of oxygenated hemoglobin in the prefrontal cortex after smelling the control and each pyrazine fragrance. [Figure 8] This is a diagram showing the layout of the sections (16 channels) of the prefrontal cortex of a subject wearing light-receiving sensors when measuring cerebral blood flow. DETAILED DESCRIPTION OF THE INVENTION

[0020] The present invention will now be described based on exemplary embodiments, although the present invention is not limited to the following embodiments.

[0021] <Sedative Composition of the Present Invention> A composition according to one embodiment of the present invention (also referred to as the "sedative composition of the present invention") contains pyrazines as active ingredients, has a sedative effect on the autonomic nervous system and / or the central nervous system, and is a composition used to exert said sedative effect.

[0022] Here, "sedative effect on the autonomic nervous system and / or central nervous system" means a sedative effect on the autonomic nervous system, a sedative effect on the central nervous system, or both of these sedative effects.

[0023] (pyrazines) Pyrazine is a heterocyclic compound with the molecular formula C4H4N2. The "pyrazines" that are the active ingredients of the sedative composition of the present invention include pyrazine and its derivatives. Among them, from the viewpoint of sedative action on the autonomic nervous system and / or the central nervous system, one or more pyrazines selected from the following (A) to (C) are particularly preferred. (A) 2-Ethyl-5(6)-methylpyrazine (B) 2-Ethyl-3,5(6)-dimethylpyrazine (C) 2,3,5-trimethylpyrazine

[0024] Pyrazines are known to be widely present in heated processed foods, including processed foods such as coffee, roasted green tea, and dried bonito, as well as chocolate, grilled meat, and natto, and are known to be components that contribute to the pleasant aroma of foods. For example, in the case of roasted green tea, analysis of the components contained in roasted green tea using the AEDA (Aroma Extract Dilution Analysis) method revealed that pyrazines, especially the above-mentioned (A) to (C), are components with high FD factors (Flavor Dilution Factors), that is, are the most important components in the composition of the aroma of roasted green tea. Pyrazines, at least the pyrazines (A) to (C) above, can be purchased individually or can be obtained by separating or purifying from an extract of roasted tea leaves, i.e., hojicha (roasted tea). Thus, pyrazines are naturally occurring components.

[0025] Here, in the present invention, "hojicha" refers to tea leaves obtained by roasting crude tea or finished tea (hereinafter also referred to as roasted tea leaves). The "roasting" in the above "roasted tea leaves" refers to roasting the tea leaves. The "roasted tea leaf extract" is a composition obtained by extracting roasted tea leaves with water, warm water or hot water, or even steam. Examples of the "separation or purification" method include a method using liquid-liquid partition, a method using an adsorbent and adsorption / desorption with water, a water-soluble solvent, or a mixed solvent thereof, etc. For example, a method of further purifying pyrazines by subjecting them to various types of chromatography can be mentioned.

[0026] (Analgesic effect) Generally, "sedative effect" means the effect of calming overactive nervous system activity, and the analgesic effect of the sedative composition of the present invention is a sedative effect on the autonomic nervous system and / or central nervous system.

[0027] The sedative composition of the present invention can exert a sedative effect on the autonomic nervous system and / or the central nervous system, for example, by nasal administration. Here, in the present invention, "nasal inoculation" includes not only the case where the composition is directly inoculated into the body via the nasal cavity, but also the case where volatiles of the composition are inoculated into the body via the nasal cavity. The sedative effect on the autonomic nervous system includes an effect of stimulating the parasympathetic nervous system and / or an effect of suppressing the sympathetic nervous system. More specifically, the action of activating the parasympathetic nervous system is manifested as a symptom such as an increased rate of pupil constriction, for example. The effect of suppressing the sympathetic nervous system is manifested as a symptom such as an increase in peripheral skin temperature. On the other hand, its sedative effect on the central nervous system can reduce cerebral blood flow, which is manifested as a decrease in the amount of oxygenated hemoglobin in the prefrontal cortex, as assessed by near-infrared spectroscopy (NIRS).

[0028] Among the pyrazines, for example, among the pyrazines (A) to (C) above, (C) 2,3,5-trimethylpyrazine has a particularly excellent sedative effect on the central nervous system. Therefore, when administered intranasally, a composition containing 2,3,5-trimethylpyrazine as an active ingredient exerts a sedative effect on the central nervous system and reduces cerebral blood flow, thereby reducing the amount of oxygenated hemoglobin in the prefrontal cortex as assessed by NIRS, for example.

[0029] (Required intake and content) The concentration of pyrazines in the sedative composition of the present invention varies depending on the method of use, but is preferably 10 ppb (mass) to 1000 ppb (mass) in mass terms, and more preferably 20 ppb (mass) or more or 400 ppb (mass) or less. It is believed that if the concentration of pyrazines is 10 ppb (mass) or more, a physiological effect is produced even if the scent cannot be sensed, and the effects of the sedative composition of the present invention can be exerted. The above concentration of pyrazines is the total content of pyrazines in the sedative composition of the present invention.

[0030] (Method of producing the sedative composition of the present invention) As an example of the method for producing the sedative composition of the present invention, a method for producing the sedative composition of the present invention from roasted tea leaves, i.e., from roasted tea leaves, will be described.

[0031] An example of a method for producing the sedative composition of the present invention is a method in which roasted tea leaves are extracted to obtain an extract, and the extract is separated or purified to increase the concentration of pyrazines, thereby obtaining a composition containing pyrazines.

[0032] The roasted tea leaves may be tea leaves obtained by roasting crude tea or finished tea. In this case, the variety of the crude tea or the finished tea, the tea cultivation method, and the harvest time are not limited. For example, first-season tea, second-season tea, third-season tea, fourth-season tea, autumn / winter tea, etc. can be used. It is also possible to combine two or more types of tea leaves that differ in tea variety, tea cultivation method, harvest time, etc. From the viewpoint of effectively obtaining the autonomic nervous system regulating effect of the sedative composition of the present invention, it is particularly preferable to use first-season tea. The term "crude tea" refers to tea leaves obtained by steaming fresh leaves, roasting them, etc. to kill the green color, and then rolling and drying them, while the term "finished tea" refers to tea leaves obtained by further finishing the crude tea.

[0033] Roasting refers to a process of roasting tea leaves, and specifically, methods known to those skilled in the art can be used, such as heating by direct contact with a heating body such as a frying pan, hot air roasting, sand roasting, far-infrared roasting, open-pot roasting, rotating drum roasting, and medium roasting. When roasting, it is preferable to roast at 150°C to 300°C in order to increase the content of pyrazines.

[0034] Roasted tea leaves can be extracted by extracting them with water, warm water, hot water, or even steam. Water, warm water, and hot water are not clearly distinguishable, but for example, water at 80°C or higher is considered hot water, water at 40°C or higher but less than 80°C is considered warm water, and water at less than 40°C is considered water. The extraction temperature, for example, under atmospheric pressure is preferably 20° C. to 100° C., more preferably 50° C. to 100° C., even more preferably 70° C. to 99° C., and most preferably 90° C. to 99° C. By performing the extraction within the above temperature range, an extract can be obtained efficiently. The extraction is preferably carried out at a pH of 2.0 to 8.0, more preferably at a pH of 3.0 or higher or 7.5 or lower.

[0035] The extraction process is not particularly limited as long as it can dissolve the soluble components contained in the roasted tea leaves used as the extraction material into the extraction solvent, and can be carried out according to various conventional methods, such as batch or continuous (drip) methods. For example, in the case of a batch process, the extraction material is immersed in an extraction solvent in an amount (by mass) 10 to 50 times, preferably 15 to 30 times, and more preferably 15 to 25 times the amount of the extraction material, and the soluble components are extracted by stirring or leaving the mixture at room temperature, under heating, or under reflux, followed by filtration to remove the extraction residue, thereby obtaining an extract. To increase the content of aroma compounds, especially pyrazines, the solvent may be removed from the extract to obtain a concentrate. In this case, the distillate obtained using a spinning cone column or the like may be returned to the extract to further increase the concentration of aroma compounds. Alternatively, aroma components, especially pyrazines, may be extracted and recovered. Steam distillation is an example of such a method. This method involves blowing steam into roasted green tea leaves or an extract, cooling and liquefying the components that volatilize with the steam, and recovering them as a distillate. Examples of such methods include atmospheric steam distillation, pressurized steam distillation, and reduced-pressure steam distillation.

[0036] The extract of roasted tea leaves obtained as described above is preferably separated and purified so as to increase the concentration of pyrazines. Examples of methods for separation or purification include a method using liquid-liquid distribution, and a method using an adsorbent and adsorption / desorption with water, a water-soluble solvent, or a mixed solvent thereof.

[0037] For example, the product can be further purified by various types of chromatography to increase the concentration of pyrazines. In this case, for example, devices such as open column chromatography, flash chromatography such as medium pressure liquid chromatography (MPLC) or high performance liquid chromatography (HPLC), and centrifugal liquid-liquid partition chromatography that does not use a carrier can be used as the chromatography. The carriers used for separation may be those used in various types of chromatography such as reverse-phase column chromatography, normal-phase column chromatography, gel permeation chromatography (GPC), and ion exchange chromatography, as well as a combination of various types of chromatography treatments such as synthetic adsorbents. The order in which the eluate is treated with various types of chromatography is not particularly limited.

[0038] Furthermore, the extract of roasted tea leaves obtained as described above can also be rectified under normal pressure or reduced pressure, if necessary.

[0039] The extract, separated liquid or purified liquid of roasted tea leaves obtained as described above may be used as the sedative composition of the present invention as is, or the extract, separated liquid or purified liquid may be added to water, other liquid or other composition to prepare the sedative composition of the present invention. The prepared sedative composition of the present invention can be stored for a longer period by lowering the oxygen concentration in the air by nitrogen substitution or the like and then storing it in a freezer.

[0040] (safety) The active ingredients of the sedative composition of the present invention can be derived from natural ingredients that have been orally ingested by humans for many years, and therefore, it can be said that their safety is guaranteed from the viewpoint of dietary experience.

[0041] <Use of the sedative composition of the present invention> The sedative composition of the present invention is preferably used for nasal administration, and although the pyrazines can be used as they are, they can also be provided in various forms as compositions that can be administered nasally. The sedative composition of the present invention is preferably in a liquid form for nasal administration, for example, so that the volatile components can be easily inhaled through the nasal cavity.

[0042] The sedative composition of the present invention may be provided as, for example, a food or drink, a bath additive, an air freshener, a liquid detergent, a solid detergent, a cosmetic, a protective hygiene material, an oral composition, or the like, as long as the active ingredient can be administered intranasally and has a sedative effect on the autonomic nervous system and / or the central nervous system.

[0043] The sedative composition of the present invention is preferably in a form that allows the volatile components to be easily inhaled through the nasal cavity. For example, it is preferable to include a component that promotes evaporation, such as alcohol, or to make it possible to heat the container. It is also contemplated that the compositions may be sprayable, such as aerosols, containing the active ingredient in solution or dispersion, or nebulizable compositions containing a dispersion of the active ingredient in an aqueous, organic, or aqueous / organic medium.

[0044] (food and drink) The sedative composition of the present invention can be provided as a food or drink having a sedative effect on the autonomic nervous system and / or the central nervous system.

[0045] For example, purified pyrazines or roasted green tea extract or a purified product thereof may be added to known foods and beverages, or foods and beverages prepared to increase the concentration of pyrazines, such as roasted green tea. In this case, the "purified pyrazines" are preferably one or more pyrazines selected from the above-mentioned (A) to (C).

[0046] When the sedative composition of the present invention is provided as a food or drink, it can be provided as a food for specified health uses, a food with nutrient function claims, a food with functional claims, a so-called health food (functional food, health supplement), a soft drink, etc., but is not limited to these. In this case, it is also possible to make the food or drink labeled as having the pharmacological action of pyrazines.

[0047] Examples of preferred forms of food and drink include candy, jelly, tablet candy, beverages, soup, noodles, rice crackers, Japanese sweets, frozen desserts, baked goods, etc. Preferred are packaged beverages such as tea beverages (including roasted green tea beverages), grain tea beverages (including barley tea beverages), coffee beverages, carbonated beverages, sports drinks, and near water.

[0048] When the sedative composition of the present invention is provided as a food or beverage, the concentration of pyrazines is preferably 10 ppb (mass) to 1000 ppb (mass) in terms of mass, and more preferably 20 ppb (mass) or more or 400 ppb (mass) or less. It is believed that if the concentration of pyrazines is 10 ppb (mass) or more, a physiological effect is produced even if the scent cannot be sensed, and the effects of the sedative composition of the present invention can be exerted.

[0049] (Sedative drink of the present invention) A sedative beverage according to one embodiment of the present invention (referred to as the "sedative beverage of the present invention") is a beverage containing pyrazines as active ingredients.

[0050] The "pyrazines" that are the active ingredients of the sedative beverage of the present invention are the same as the "pyrazines" that are the active ingredients of the sedative composition of the present invention described above.

[0051] The sedative beverage of the present invention preferably contains pyrazines in a proportion of 10 ppb to 1000 ppb by mass, and more preferably 20 ppb or more or 400 ppb or less. Furthermore, the sedative beverage of the present invention preferably contains pyrazines in a ratio of 0.001 to 0.2 parts by mass per 100 parts by mass of catechins, more preferably 0.005 parts by mass or more or 0.1 parts by mass or less, and even more preferably 0.01 parts by mass or more or 0.08 parts by mass or less. For example, a preferred example of the sedative beverage of the present invention contains catechins in an amount of 1 to 1000 ppm, preferably 10 ppm or more and 800 ppm or less, and preferably 50 ppm or more and 500 ppm or less; theanine in an amount of 0.1 to 100 ppm, preferably 1 ppm or more and 50 ppm or less, and preferably 3 ppm or more and 30 ppm or less; caffeine in an amount of 1 to 1000 ppm, preferably 30 ppm or more and 500 ppm or less, and preferably 50 ppm or more and 300 ppm or less; and pyrazines in an amount of 10 to 400 ppb, preferably 15 ppb or more and 300 ppb or less, and preferably 20 ppb or more and 250 ppb or less.

[0052] The soluble solids content (Brix) of the sedative beverage of the present invention is preferably 0.10 to 0.50% by mass, more preferably 0.15% by mass or more or 0.45% by mass or less, and particularly preferably 0.20% by mass or more or 0.40% by mass or less.

[0053] The sedative beverage of the present invention can be produced, for example, by extracting roasted tea leaves to obtain an extract, and then diluting, concentrating or adjusting the components of the extract as necessary.

[0054] In this case, the ingredients may be adjusted as needed by blending pyrazines, known beverage ingredients such as pure water, dairy ingredients such as milk, skim milk powder, whole milk powder, concentrated milk, and fresh cream, mineral ingredients, as well as additives such as antioxidants such as ascorbic acid and sodium ascorbate, flavorings, pH adjusters such as sodium bicarbonate, emulsifiers, preservatives, sweeteners, colorings, thickening stabilizers, seasonings, and strengtheners, either alone or in combination.

[0055] The extract prepared as described above can be sterilized and packaged in a conventional manner to produce a packaged beverage. Examples of filling containers include plastic containers such as so-called PET bottles, as well as bottles, cans, and paper containers such as Tetra Pak (registered trademark).

[0056] Sterilization and filling methods include, for example, conventional methods that are carried out under the sterilization conditions stipulated in the Food Sanitation Act. For beverages in plastic containers (e.g., PET bottled beverages), examples include hot pack filling, in which the extract is sterilized at high temperature and filled at a temperature of about 80 to 90°C, aseptic filling, in which the sterilized extract is cooled and filled into a sterilized container in an aseptic environment, and other filling methods. More specifically, for beverages in plastic containers, UHT sterilization (holding the extract at 120 to 150°C for 1 to several tens of seconds) may be carried out. For canned beverages, after filling into the container, heat sterilization, for example, retort sterilization, or sterilization under appropriate pressure (1.2 kg / cm) may be carried out. 2 etc.), and sterilize by heating at 121°C for 7 minutes.

[0057] (bath additives) The sedative composition of the present invention can be provided as a bath additive (also referred to as "the bath additive of the present invention") that has a sedative effect on the autonomic nervous system and / or the central nervous system. For example, the bath additive of the present invention can be prepared by using purified pyrazines or roasted green tea extract (liquid) or its purified product (liquid) in place of the fragrance components or herbal ingredients of conventionally known bath additives, or by adding them to the fragrance components or herbal ingredients of conventionally known bath additives. In this case, the "purified pyrazines" are preferably one or more pyrazines selected from the above-mentioned (A) to (C).

[0058] Examples of known bath additive components include fennel, Scutellaria root, Phellodendron bark, chamomile, magnolia bark, fermented rice extract, Judaea herb, Calamus, Cnidium rhizome, Tangerine peel, Angelica acutiloba, spruce, chili pepper, carrot, yuzu, mugwort, Saghurt, mint leaf, ginger, licorice, cinnamon bark, papain, pancreatin, protease, liquid lanolin, jojoba oil, glycerin, casein, stearyl alcohol, olive oil, soybean oil, liquid paraffin, white petrolatum, propylene glycol, skim milk powder, squalane, honey, polyethylene glycol, rice germ oil, and the like. The herbal medicine is not particularly limited and any known herbal medicine can be used, but examples thereof include tannins, flavonoids, green tea, sophora flower, and scutellaria root.

[0059] The concentration of pyrazines in the bath additive of the present invention is preferably 10 ppb to 1000 ppb when dissolved in hot water, in which case it is preferable to incorporate the pyrazines into the bath additive at a ratio of 0.001 to 1% by mass, particularly 0.003% by mass or more or 0.7% by mass or less.

[0060] (Air freshener) The sedative composition of the present invention can be provided as a fragrance (also referred to as the "fragrance of the present invention") that has a sedative effect on the autonomic nervous system and / or the central nervous system. For example, the fragrance of the present invention can be prepared by using purified pyrazines or roasted green tea extract (liquid) or its purified product (liquid) in place of the fragrance components or herbal ingredients of a conventionally known fragrance, or by adding it to the fragrance components or herbal ingredients of a conventionally known fragrance. In this case, the "purified pyrazines" are preferably one or more pyrazines selected from the above-mentioned (A) to (C).

[0061] The aromatic agent of the present invention may take the form of a room fragrance, an aroma candle, an indoor aroma oil, a solid aromatic agent solidified with a gelling agent, or the like. The aromatic agent of the present invention can be used by evaporating into the atmosphere at room temperature or after heating. In particular, room fragrances and indoor aroma oils can be used as room fragrances by applying or spraying them onto scented paper, or by scattering or diffusing the scent using a diffuser.

[0062] The concentration of pyrazines in the fragrance of the present invention is preferably 10 ppb to 1000 ppb when dispersed or diffused from the fragrance, and in this case, it is preferable to blend the pyrazines in the fragrance at a ratio of 0.001 to 1 mass %, particularly 0.003 mass % or more or 0.7 mass % or less, converted into mass.

[0063] <Explanation of terms> In the present invention, when the expression "X to Y" (X and Y are any numbers) is used, unless otherwise specified, it means "X or more and Y or less," as well as "preferably larger than X" or "preferably smaller than Y." Furthermore, when it is expressed as "X or more" (X is any number) or "Y or less" (Y is any number), it also includes the intention that "it is preferable that it is greater than X" or "it is preferable that it is less than Y." [Example]

[0064] The present invention will be described in more detail below with reference to examples, although the present invention is not limited to these examples. In the following examples, "%" indicates "% by mass" unless otherwise specified.

[0065] <Test 1> The main aroma components of roasted green tea extract, (A) 2-ethyl-5(6)-methylpyrazine, (B) 2-ethyl-3,5(6)-dimethylpyrazine, and (C) 2,3,5-trimethylpyrazine, were analyzed by GC-MS.

[0066] (Hojicha extract) The raw tea used was roasted first-grade tea from Shizuoka Prefecture in a roaster at 180°C for 10 minutes. The raw tea was extracted with 50 times the amount of distilled water at 95°C for 2 minutes, and the tea leaves were filtered through a 100-mesh sieve to obtain a roasted tea extract.

[0067] (GC-MS analysis method) Pyrazines in roasted green tea extract were analyzed by solid-phase microextraction (SPME) and GC-MS. The analytical sample was prepared by placing 10 mL of sample solution and 3 g of sodium chloride in a glass vial, adding 5 μL of an internal standard (0.1% cyclohexanol), and then subjecting the mixture to GC-MS. After equilibrating the sample at 60°C for 10 minutes, the headspace gas in the glass vial was extracted at 60°C for 30 minutes using a Supelco SPME fiber (50 / 30 μm Divinylbenzene / Carboxen / Polydimethylsiloxane, Sigma-Aldrich). An Agilent 7890A gas chromatograph was used. The chromatography column used was an Agilent DB-WAX (0.25 mm ID x 60 m x 0.25 μm). The carrier gas was helium (inlet pressure: 82.7 kPa), the inlet temperature was 240°C, and the injection method was splitless injection. The oven temperature was held at 35°C for 3 minutes, then increased to 240°C at a rate of 5°C / min and held at 240°C for 5 minutes. The mass detector used was an Agilent 5975A MSD. The ionization voltage was 70 eV (EI), the ion source temperature was 230°C, and the measurement mode was SIM / scan (SIM mode: m / z: 81.1, 94.1, 108.1, 121.1, 122.1, 135.1, scan mode: m / z: 29–250). The aroma component concentrations were calculated using calibration curves obtained from the respective standards.

[0068] (result) (A) 2-Ethyl-5(6)-methylpyrazine 140 ppb (mass) (B) 2-Ethyl-3,5(6)-dimethylpyrazine 133 ppb (mass) (C) 2,3,5-trimethylpyrazine 105 ppb (mass)

[0069] <Test 2> In this study, as a physiological evaluation, we measured pupil constriction rate (a parasympathetic nervous index) and peripheral skin temperature (a sympathetic nervous index) to investigate autonomic nervous activity. Furthermore, as a psychological evaluation, we conducted a questionnaire survey using a Visual Analogue Scale (VAS) and a survey using the Multifaceted Mood Scale (MMS) to investigate subjective mood. Additionally, to evaluate aspects of the central nervous system, we measured changes in cerebral blood flow (oxygenated hemoglobin) in the prefrontal cortex as an index of brain activity.

[0070] 1. Test sample Test sample 1: (A) 2-ethyl-5(6)-methylpyrazine (purity 99.0%, Combi-Blocks) Test sample 2: (B) 2-ethyl-3,5(6)-dimethylpyrazine (purity ≥ 98.0%, Tokyo Chemical Industry Co., Ltd.) Test sample 3: (C) 2,3,5-trimethylpyrazine (purity ≥ 98.0%, Tokyo Chemical Industry Co., Ltd.) The test samples were diluted to a concentration of 100 ppb with distilled water immediately before the start of the measurement, and placed in a vacuum insulated tumbler and provided at room temperature (approximately 20°C). The control was distilled water.

[0071] 2. Subjects The subjects were selected based on the following criteria: they did not dislike the aroma of green tea, they did not smoke, they did not have poor circulation, and they were not undergoing any medication. The test was conducted on 9 men and 11 women (42.0±5.2 years old) (mean±standard deviation). The subjects were instructed to try to get as much sleep as possible of the same length and quality as usual the night before the test, to avoid stimulants in their meals before the test, to limit their intake of caffeinated beverages, and to avoid wearing cosmetics on the day of the test.

[0072] 3. Test environment The test room was set at a room temperature of 25°C and a humidity of 50%. Measurement of cerebral blood flow using near-infrared spectroscopy (NIRS) was performed in a test room isolated from the measurement of pupil and peripheral skin temperature, and the room was kept quiet with the windows and doors closed.

[0073] 4. Ethical Considerations This study was conducted in accordance with the ethical standards outlined in the Declaration of Helsinki. The purpose, content, and anticipated risks of the study were explained to the subjects, and their informed consent was obtained through a consent form. This study was conducted under the review and approval of the ethical review committee of Chiyoda Paramedical Care Clinic (CPCC), the contract clinical trial organization. The ethical review approval number is ITE24C1. The study content is registered with the University Hospital Medical Information Network, and the UMIN registration number is UMIN000053673.

[0074] 5. Test Method The subjects entered the testing room 30 minutes before the start of the test to allow them to acclimate to the testing environment. Physiological evaluation consisted of measuring pupillary constriction rate, peripheral skin temperature, and cerebral blood flow in that order. The pupil constriction rate was measured by first inhaling the scent of the control (distilled water) for two minutes after dark adaptation for two minutes, and then inhaling the scent of the test sample for two minutes after dark adaptation for two minutes, and then measuring the pupil constriction rate for two minutes. Peripheral skin temperature and cerebral blood flow were measured using the same procedure as for pupillary constriction, except that the subjects were not dark adapted and sat quietly during the measurements. The scent was presented by placing the test sample in a tumbler approximately 3 cm below the subject's nose, and the lid of the cup was opened immediately before the subject began to smell the scent. The subject was instructed to breathe normally while smelling the scent. In these series of measurements, only one sample was evaluated per day, and three samples were tested by the same subject over three days.

[0075] [Pupil constriction rate measurement] Pupil constriction rate was measured using an electronic pupillometer, Iriscorder Dual C10641 (Hamamatsu Photonics). After dark adaptation for 2 minutes with goggles attached to both eyes and light shielding, light was irradiated for 0.1 seconds, and the pupil constriction rate was calculated from the change in pupil diameter. The effect on autonomic nervous activity, particularly parasympathetic nervous activity, was evaluated by comparing the change in pupil constriction rate due to light stimulation. In this test, pupil diameter was measured after smelling the control or test sample scent. The initial pupil diameter before light stimulation was defined as D1, and the pupil diameter after light stimulation was defined as D2. The change in pupil diameter between D1 and D2 was used to calculate the rate of pupil constriction as the miosis rate (CR) = (D1 - D2) / D1. Furthermore, the miosis rate after smelling the control scent was designated CR1, and the miosis rate after smelling the test sample scent was designated CR2, and the change in miosis rate (ΔCR) between the control and test samples was compared.

[0076] [Measurement of peripheral skin temperature] Peripheral skin temperature was measured by measuring the skin temperature of the index finger (FT) using a temperature logger LT-8A (Gram Co.). By comparing changes in skin temperature at peripheral sites, the effects on autonomic nervous activity, particularly sympathetic nervous activity, were evaluated. In this test, the skin temperature of the center of the ventral side of the fingertip after smelling the control scent was defined as FT1, and the skin temperature of the same area after smelling the test sample scent was defined as FT2, and the change in skin temperature (ΔFT) after smelling the control and test sample scents was compared.

[0077] [Evaluation of mood state by subjective questionnaire] For psychological evaluation, after smelling the control or test sample scent, participants were asked to use a visual analogue scale (VAS) to assess their mood in nine categories: "mood," "comfort," "tension," "anxiety," "anger," "fatigue," "vigor," "drowsiness," and "concentration." Each category was rated on a linear scale from 0 to 100 mm, ranging from "very bad" to "very good" or "very weak" to "very strong." The Multifaceted Mood Scale (MMS) was also evaluated. The MMS consists of a 40-item questionnaire divided into eight subscales: "Depression / Anxiety," "Hostility," "Fatigue," "Active Pleasure," "Inactive Pleasure," "Affiliation," "Concentration," and "Surprise." The scale is rated on a four-point scale (1-4 points) ranging from "Not at all" to "Clearly felt." In this study, the scores for each subscale were totaled after the evaluation, and the subjective mood and emotions after smelling the control and test samples were compared.

[0078] [Measurement of cerebral blood flow] Cerebral blood flow was measured by near-infrared spectroscopy (NIRS) using the OEG-16 optical imaging brain function measurement device (Spectratech) to measure relative oxygenated hemoglobin (Oxy-Hb). In this test, a 16-channel (Figure 8) light-receiving sensor was attached to the prefrontal cortex of the subject, and oxygenated hemoglobin was continuously measured for two minutes while the subject smelled the control and test sample scents. The measured data was averaged for each channel, and the change in oxygenated hemoglobin (ΔOxy-Hb) between the control and test sample was compared.

[0079] [Statistical analysis] Data are expressed as mean ± standard error (SE). Comparisons between control and test samples were performed using a paired t-test (two-tailed). Statistical analysis was performed using the analysis software SPSS Statistics 25 (IBM, USA). A p<0.05 was considered statistically significant, and a p<0.10 was considered to indicate a significant trend.

[0080] 6.Results (Pupillary constriction rate and peripheral skin temperature measurements) Measurement of pupil constriction rate showed that exposure to the scents of the three pyrazines significantly increased pupil constriction rate compared to the control group, with an average increase of 0.03 to 0.06 (Figure 1). These results confirmed that all three pyrazines have the effect of stimulating the parasympathetic nervous system and increasing pupil constriction rate. Furthermore, measurements of fingertip skin temperature showed that inhaling the scent of the three types of pyrazines significantly increased fingertip skin temperature compared to the control group, with an average increase of 0.53 to 0.56°C (Figure 2). These results confirmed that all three types of pyrazines suppress sympathetic nervous activity, dilate peripheral blood vessels, and increase fingertip skin temperature. Furthermore, a one-way analysis of variance was performed on the change in miosis rate (ΔCR) for each pyrazine, and multiple comparisons using the Bonferroni method revealed a significant trend between (A) 2-ethyl-5(6)-methylpyrazine and (C) 2,3,5-trimethylpyrazine (Figure 3). Similarly, a one-way analysis of variance was performed on the change in fingertip skin temperature (ΔFT) between the control and each pyrazine, and no significant differences were observed in the change (Figure 4). These results demonstrate that pyrazines, the main aroma components of roasted green tea, have a sedative effect that suppresses sympathetic nervous activity and enhances parasympathetic nervous activity.

[0081] (Evaluation of mood state by subjective questionnaire) The results of the subjective questionnaire showed that (A) 2-ethyl-5(6)-methylpyrazine significantly reduced scores for "tension" and "anxiety" compared to the control group, and showed a tendency for scores for "anger" and "vigor" to decrease. Furthermore, (C) 2,3,5-trimethylpyrazine significantly reduced scores for "fatigue," increased scores for "drowsiness," and tended to increase scores for "mood" (Figure 5). Furthermore, the results of the multifaceted emotional state scale showed that (A) the scent of 2-ethyl-5(6)-methylpyrazine showed a tendency for decreases in the scores for "depression / anxiety" and "concentration" compared to the control group, (B) the scent of 2-ethyl-3,5(6)-dimethylpyrazine significantly reduced the score for "fatigue" and tended to decrease the score for "depression / anxiety," and (C) the scent of 2,3,5-trimethylpyrazine reduced the score for "concentration" (Figure 6). These results demonstrate that pyrazines, the main aroma components of roasted green tea, also have a psychologically calming effect.

[0082] (Cerebral blood flow measurement results) The results of cerebral blood flow measurements showed that (C) exposure to the scent of 2,3,5-trimethylpyrazine reduced the amount of oxygenated hemoglobin in the prefrontal cortex compared to the control group in all channels except for channel 11. Furthermore, (B) exposure to 2-ethyl-3,5(6)-dimethylpyrazine tended to reduce the amount of oxygenated hemoglobin in the upper frontal region (channels 2, 4, 5, 7, 11, and 14) (Figure 7). These results demonstrate that (B) 2-ethyl-3,5(6)-dimethylpyrazine and (C) 2,3,5-trimethylpyrazine, the main aroma components of roasted green tea, have a sedative effect on the central nervous system, reducing cerebral blood flow.

Claims

1. A composition containing pyrazines as an active ingredient, which is used to exert a sedative effect on the autonomic nervous system and / or the central nervous system.

2. The composition according to claim 1, wherein the pyrazines are one or more selected from the following (A) to (C): (A) 2-ethyl-5(6)-methylpyrazine (B) 2-ethyl-3,5(6)-dimethylpyrazine (C) 2,3,5-trimethylpyrazine

3. The composition according to claim 1, wherein the sedative effect on the autonomic nervous system is a parasympathetic nervous system stimulating effect and / or a sympathetic nervous system inhibiting effect.

4. The composition according to claim 3, characterized in that the parasympathetic nervous system stimulating effect is to increase the pupil constriction rate.

5. The composition according to claim 3, wherein the sympathetic nerve inhibitory effect is to increase peripheral skin temperature.

6. The composition according to claim 1, wherein the sedative effect on the central nervous system is an effect of reducing the amount of oxygenated hemoglobin in the prefrontal cortex as assessed by NIRS (near-infrared spectroscopy).

7. A composition used to exert a sedative effect on the central nervous system, which contains 2,3,5-trimethylpyrazine as an active ingredient.

8. The composition according to any one of claims 1 to 7, characterized in that it is for nasal administration.

9. The composition according to claim 8, comprising 10 ppb to 1000 ppb of pyrazines.

10. A food or drink to which the composition according to any one of claims 1 to 7 has been added.

11. A bath additive comprising the composition according to any one of claims 1 to 7.

12. A method for producing a composition used to exert a sedative effect on the autonomic nervous system and / or central nervous system, characterized in that an extract is obtained by extracting roasted tea leaves, and the extract is separated and purified to obtain a composition containing pyrazines.

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