Brain sedative enhancer

Abstract

The present invention aims to scientifically clarify the effects of milk aroma components on brain function. [Solution] The present invention provides a brain sedative agent whose active ingredient is the aromatic component of milk products. The present invention also provides a brain sedative agent whose brain sedative effect is enhanced by increasing alpha waves in the brainwave spectrum. Furthermore, the present invention provides a method for enhancing the brain sedative effect, which includes the step of applying milk products to the target's sense of smell. Furthermore, the present invention provides a method for enhancing alpha waves in the brainwave spectrum, which includes the step of applying milk products to the target's sense of smell.

Description

Technical Field

[0001] The present invention relates to an agent for improving the sedative effect of the brain, which contains milk-derived aroma components as an active ingredient.

Background Art

[0002] Among the scents of foods, there are not only those that bring a psychological relaxation effect, but also those that have an effect of smoothing or stabilizing brain functions and an activating effect. The following documents are known regarding the effects of food scents on brain functions. Patent Document 1 discloses that aroma components derived from fermented milk using one or more selected from the group consisting of lactic acid bacteria, bifidobacteria, and yeast as raw materials have an effect of activating the cognitive function of the brain, and that the active ingredient is diacetyl (Patent Document 1).

[0003] Patent Document 2 discloses that a jelly food containing a gelling agent having a melting temperature of 25°C or higher and an aroma component improves brain functions and autonomic nerve functions and has a relaxation effect, and the relaxation effect includes enhancement of brain wave alpha waves, decrease in heart rate, decrease in the activity level of the sympathetic nerve, or increase in peripheral skin temperature.

[0004] Patent Document 3 discloses an alpha wave enhancer and a food for enhancing alpha waves, which contain maracuja juice as an active ingredient. Here, since the alpha wave appears predominantly in the occipital region in a quiet and awake state and decreases in a mental activity state such as mental arithmetic, it is used as an index of the stability of brain functions. The dominant frequency of alpha waves in healthy adults is 10.8 Hz on average. When a very slight drowsiness is felt and the brain activity level slightly decreases, the frequency of alpha waves becomes slower, and slow alpha waves around 8 Hz are also mixed in (Non-Patent Document 1). Also, it is known that in the elderly, the dominant frequency of alpha waves gradually changes to 8 - 9 Hz, and the dominant site also becomes widespread (Non-Patent Document 2).

Prior Art Documents

Patent Documents

[0005] [Patent Document 1] Japanese Patent Publication No. 2023-152649 [Patent Document 2] Japanese Patent Publication No. 2003-245048 [Patent Document 3] Patent No. 3318412 [Non-patent literature]

[0006] [Non-Patent Document 1] Teruo Okuma, Hiroo Matsuoka, and Takashi Ueno: Electroencephalogram Interpretation: Step by Step - Introductory Edition, 4th Edition. Igaku-Shoin, Tokyo (2006) [Non-Patent Document 2] Matsuura, Masato: Age-related changes in normal electroencephalograms: adolescence, old age (including normal subtypes). Monograph for those learning clinical electroencephalography from the basics (edited by the Japanese Society of Clinical Neurophysiology Certification Committee), Japanese Society of Clinical Neurophysiology, pp. 63-70, Tokyo (2008). [Overview of the project] [Problems that the invention aims to solve]

[0007] Incidentally, while the aforementioned patent documents disclose the alpha wave-enhancing effects of various foods, the effects of milk and the aroma of milk have not yet been studied. In other words, milk has long been enjoyed by people of all ages as a highly nutritious food (beverage), and various reports have been made regarding its nutritional aspects such as protein and calcium, but the physiological functions of the aroma components (also called fragrance or smell) of milk have not yet been highlighted. The present invention aims to scientifically clarify the effects of milk aroma components on brain function. [Means for solving the problem]

[0008] To address the above issues, we investigated the effects of milk aroma components on brain function using electroencephalography (EEG), a psychophysiological method. The results showed that the power value of alpha waves was significantly higher when humans smelled milk. Alpha waves are predominantly present in the occipital lobe during rest and wakefulness, and decrease during mental activity such as mental arithmetic; therefore, they are considered an indicator of brain function stability. From this, we discovered a new use for milk products—that the aroma (fragrance components) of milk has an awakening and brain-stabilizing effect, i.e., a brain-sedative effect—and thus completed the present invention. In other words, the present invention has the following configuration. <1> A brain-sedative agent that uses the aromatic components of milk as its active ingredient. <2> The improved calming effect on the brain is due to the enhancement of alpha waves in the brainwave spectrum. <1> A brain sedative enhancer as described above. <3> Milk products are those made by degassing raw milk under reduced pressure to reduce the dissolved oxygen concentration in the liquid to 3 ppm or less, and then sterilizing it at 120-150°C for 2-10 seconds. <1> A brain sedative enhancer as described above. <4> Used as an anti-stress agent <1> A brain sedative enhancer as described above. <5> Used as a fragrance composition <1> A brain sedative enhancer as described above. <6> Pharmaceuticals <1> A brain sedative enhancer as described above. <7> A method for enhancing the calming effect on the brain, which includes a process of applying milk products to the target's sense of smell. <8> A method for enhancing alpha brain waves, which includes a step of applying milk products to the target's sense of smell. <9> A method for reducing stress, which includes a process of applying milk products to the target's sense of smell. [Effects of the Invention]

[0009] According to the present invention, the calming effect of the brain can be improved by using the aroma components of milk as an active ingredient. The brain calming effect improver of the present invention does not necessarily require the intake (administration) of the active ingredient into the body, and the effect is achieved by acting on the sense of smell, so it has high safety. Therefore, it can be added and used in various products such as fragrances, cosmetics, foods, pharmaceuticals, feed additives, detergents for textile products, and textile products without selecting the target person and without restrictions on the usage mode.

Brief Description of the Drawings

[0010] [Figure 1] Shows the brain wave measurement sites based on the international 10 - 20 method. [Figure 2] Shows the electroencephalogram topographic map (n = 17) of the α2 band (10.0 - 13.0 Hz) of the subject when smelling the odor of each sample by natural breathing. [Figure 3] Shows the electroencephalogram topographic map (n = 14) of the α2 band (10.0 - 13.0 Hz) of the subject when smelling the odor of each sample. [Figure 4] Shows the power value (n = 17) of the α2 band (10.0 - 13.0 Hz) when smelling the odor of each sample. [Figure 5] Shows the power value (n = 14) of the α2 band (10.0 - 13.0 Hz) when smelling the odor of each sample. [Figure 6] Shows the results of subjective evaluation (n = 17) by the VAS method. [Figure 7] Shows the results of subjective evaluation (n = 14) by VAS.

Modes for Carrying Out the Invention

[0011] (Brain calming effect improver) The brain calming effect improver of the present invention uses the aroma components of milk as an active ingredient. By making the active ingredient act on the sense of smell of the subject, the calming effect of the brain can be improved. In this specification, making the aroma component act on the sense of smell of the subject and making the subject smell the odor (also referred to as fragrance) are used synonymously. The effect of improving brain sedation can be evaluated by measuring electroencephalography (EEG). Among EEGs, alpha waves, which reflect the level of arousal and the stability of brain function, can be used as an indicator, with alpha2 waves being preferred. Alpha waves appear predominantly in the occipital lobe when at rest and awake, and decrease during mental activity such as mental arithmetic, thus serving as an indicator of the stability of brain function. The dominant frequency of alpha waves in healthy adults is an average of 10.8 Hz, and when a slight drowsiness occurs and the level of brain activity decreases somewhat, the frequency of alpha waves slows down, and slower alpha waves of around 8 Hz also begin to appear (Non-Patent Literature 1). Furthermore, it is known that in old age, the dominant frequency of alpha waves slows down to 8-9 Hz, and the dominant brain region also becomes more widespread (Non-Patent Literature 2). Thus, in this invention, when the aroma components of a sample are applied to the sense of smell, if an effect of enhancing alpha brain waves is observed compared to when no effect is applied or when odorless distilled water is applied to the sense of smell, it can be evaluated as having an effect of improving the sedative effect on the brain.

[0012] (Electroencephalogram alpha wave enhancer / anti-stress agent) The brain sedative enhancer of the present invention can be used as an alpha wave enhancer because it stabilizes the brain by enhancing alpha waves in the brainwave spectrum. Furthermore, the brain sedative enhancing agent of the present invention can also be used as an anti-stress agent. In the present invention, "stress" refers to the functional changes that occur in the mind and body when various external stimuli act as a burden. "Anti-stress" means preventing these functional changes from occurring. "Anti-stress" also includes "stress reduction." "Stress reduction" means preventing or making it less likely for functional changes to occur in the mind and body even when various external stimuli act as a burden.

[0013] (Active ingredients) The milk products from which the aroma components that are the active ingredients of this invention are derived refer to the types of milk specified in the Ministerial Ordinance on Milk and Dairy Products, such as "milk," "component-adjusted milk," "low-fat milk," "non-fat milk," "processed milk," "milk beverage," "fermented milk," "lactic acid bacteria beverage," and "sterilized lactic acid bacteria beverage."

[0014] In the present invention, the sterilization conditions for milk products may be any conditions that satisfy the provisions for sterilization of milk products under the Food Sanitation Act, but sterilization by ultra-high temperature short-time sterilization (UHT) is preferred because it yields milk products with excellent shelf life. Milk products to which the present invention is applied can also be obtained using low-temperature pasteurization (LTLT), high-temperature long-time sterilization (HTLT), or high-temperature short-time sterilization (HTST). The sterilization method may be either indirect or direct. For indirect sterilization, plate heat exchange systems, tubular heat exchange systems, scraping heat exchange systems, etc., can be used. For direct sterilization, steam injection systems and steam infusion systems, etc., can be used. The method of sterilization in the present invention is not particularly limited, but indirect sterilization is preferred. For heating temperature and time for sterilization, for example, 120°C to 150°C for 2 to 10 seconds is preferred, and 130°C to 135°C for 2 to 5 seconds is more preferred.

[0015] In the method for producing milk products according to the present invention, a step to reduce the dissolved oxygen in the milk products before pasteurization may be performed. Methods for reducing dissolved oxygen include degassing and nitrogen replacement, but vacuum degassing is preferred due to concerns about deterioration of flavor. To reduce the dissolved oxygen concentration in milk products by vacuum degassing, for example, membrane degassing or vacuum degassing can be used, but all known methods for degassing dissolved oxygen under reduced pressure can be applied to the present invention. Membrane degassing is a method in which milk products are passed through one side of a hydrophobic membrane that allows only gas to pass through, such as a hollow fiber membrane, and the gas in the liquid is separated and reduced by reducing the pressure on the other side of the membrane. Vacuum degassing is a method in which milk products are immersed in a vacuum to separate and reduce the gas in the liquid, and deaulators are typical vacuum degassing devices. The dissolved oxygen concentration in the liquid by vacuum degassing is preferably 5 ppm or less, and more preferably 3 ppm or less. Furthermore, the above heat sterilization is preferably performed after degassing under reduced pressure. A more preferred embodiment is a method in which raw milk is degassed under reduced pressure to reduce the dissolved oxygen concentration in the liquid to 3 ppm or less, and then heat sterilized at 120 to 150°C for 2 to 10 seconds. Furthermore, the milk products of this invention are filled into containers and distributed after heat sterilization.

[0016] The containers for filling milk products according to the present invention include aseptic filling and packaging containers that allow for long-term storage, and containers that allow for refrigerated storage (non-aseptic packaging containers, chilled distribution product packaging containers), etc., to accommodate various distribution methods. Furthermore, the filling containers may be containers that transmit sunlight or fluorescent light. That is, transparent containers made of glass or synthetic resin, containers made of semi-transparent glass or synthetic resin, containers made of polyethylene-coated paper, paper containers, etc. Furthermore, the form and shape of the containers are not particularly limited, such as bottles or boxes. In addition, containers with a transparent or semi-transparent light-transmitting window in part of them are also included.

[0017] The temperature of the milk products used to allow the aroma components of the present invention to act on the sense of smell is any temperature at which the aroma components volatilize, for example, preferably 20°C or lower, and more preferably 3°C to 6°C.

[0018] (Target audience) The subjects to whom the brain sedative-enhancing agent of the present invention is applied are not particularly limited and include humans and other mammals. Since the active ingredient is a milk-derived aroma component and its safety is ensured, it can be applied to humans of all ages, from children to adults. Furthermore, it may be applied to healthy subjects, subjects who expect improved brain sedation, or subjects experiencing stress. Methods for influencing the sense of smell include placing milk or other dairy products near the target's nose, using a diffuser to release aromatic components into the air, or influencing the target's sense of smell through the fragrance composition described later. If the fragrance composition is a food or beverage, the target's sense of smell can also be influenced by consuming it. The brain sedative enhancer of the present invention can also be used as an anti-stress agent, making it suitable for individuals who wish to improve or prevent ailments caused by stress (including both medical and non-medical symptoms).

[0019] According to another aspect of the present invention, a method for promoting a calming effect on the brain, a method for enhancing alpha waves in the brain, and an anti-stress method are provided, which include a step of applying the aroma components of milk products to the target sense of smell.

[0020] (Fragrance composition / Pharmaceutical product) The brain sedative enhancer of the present invention can take any form as long as the effects of the present invention are achieved. That is, it may be in the form of food or beverage, or other dosage forms, and can be used as a "flavoring composition". Dosage forms include solid or powdered preparations such as powders, fine granules, granules, tablets, capsules, and pills, as well as liquid preparations such as suspensions, emulsions, syrups, and extracts. In this specification, "fragrance composition" refers to a composition added to fragrances, cosmetics, foods, pharmaceuticals, etc., for the purpose of imparting fragrance. The fragrance composition of the present invention is used by adding it to fragrances, cosmetics, pharmaceuticals, foods, feed additives, detergents for textiles, textile products, etc., in the form of extracts obtained by extracting volatile fragrance components from milk products at or above room temperature using methods such as steam distillation, vacuum distillation, or solvent extraction, or concentrates obtained by concentrating fermented milk or extracts using methods such as evaporation or membrane concentration. The fragrance composition of the present invention may be in the form of a fragrance composition containing other components, by including other components in addition to the milk-derived components, as long as the effects of the present invention are not impaired. The other components can be appropriately selected depending on the form of the fragrance composition of the present invention, etc., but examples include various synthetic fragrances, natural fragrances, natural essential oils, plant extracts, fixatives, solvents, suspending agents, solubilizers, antioxidants, colorants, sweeteners, etc. The present invention will be described in more detail below with reference to examples, but these are merely illustrative and the present invention is not limited in any way by them. [Examples]

[0021] [Example 1] The following tests were conducted to investigate the effect of sedating the brain when the scent of milk products is applied to the sense of smell. 1. Sample preparation Raw milk was pressurized and sprayed into a deaeration tank adjusted to a vacuum of -0.098 to -0.100 MPa to form fine particles, and then degassed under reduced pressure at a temperature of 20°C or below until the dissolved oxygen concentration was 3 ppm or less. A HACH dissolved oxygen meter was used to measure the dissolved oxygen. The mixture after degassing was preheated to 80°C in a plate heat exchanger and then homogenized in a homogenizer. The homogenization pressure was 15 MPa. After homogenization, the milk was heat-sterilized in a plate sterilizer at 130°C for 2 seconds and then cooled to 10°C or below in a plate heat exchanger to obtain the milk sample. The average values ​​of Fat and SNF of the raw milk used were Fat 3.95 and SNF 8.90. Milk 5 to 7 days after production was used as the sample for the test. Distilled water (odorless) was used as a control.

[0022] 2. Subjects Seventeen women aged 18-22 (average age 19.5 ± 1.3 years) were included as subjects. Exclusion criteria include BMI (kg / m²). 2 Participants were those with a blood alcohol content of 35.0 or higher or 17.0 or lower, those who have been diagnosed with a mental disorder (including developmental disorders, brain dysfunction, and sleep disorders), those with ear, nose, and throat disorders, those with serious liver, kidney, heart, respiratory, endocrine, or metabolic diseases, pregnant women, smokers, those who regularly use drugs that may affect brain function, mental function, or sleep, those who regularly use supplements or health foods that may affect brain function, mental function, or sleep, those with food allergies to milk or dairy products, those participating as subjects in other studies, and others deemed unsuitable by the principal investigator. This research was conducted with the approval of the Research Ethics Committee of Jumonji Gakuen Women's University (Approval Number JEC2023011).

[0023] 3.Measurement method 3-1. Electroencephalography (EEG) (1)Measurement method A portable multi-purpose bioamplifier (Polymate AP1132; manufactured by TEAC Corporation) was used for electroencephalogram (EEG) measurements. EEG cap electrodes (Waveguard CA-116; manufactured by eemagine Medical Imaging Solutions GmbH) were attached to the subject's head, and electroencephalograms were measured at 19 locations on the scalp (F) according to the international 10-20 method (Figure 1). p1 ,F p2 F7, F3, F Z F4, F8, T7, C3, C Z ,C4,T8,T4,P3,P Z A special measurement gel was injected into the P4, T5, O1, and O2 points. The reference electrodes were the connected bilateral earlobes (A1 and A2). With one of the samples presented under the subject's nose, the electroencephalogram (EEG) was recorded for 3 minutes while the subject was sitting with their eyes closed and smelling the sample through natural breathing.

[0024] (2) Analysis method For the analysis of background electroencephalogram (EEG) activity, we used the Mapping Play Analysis program (manufactured by Norpro Light Systems Co., Ltd.). Each epoch was defined as 2 seconds, and 10 artifact-free epochs were selected. Power values ​​in the α2 (10.0~13.0Hz) band were then obtained using FFT analysis.

[0025] 3-2. Subjective evaluation (VAS method) Immediately after the electroencephalogram (EEG) measurement, a subjective evaluation of the sample's odor was performed using a visual analog scale (VAS). The evaluation criteria included odor intensity (not detectable at all - maximum intensity) and odor preference (not at all desirable - maximum preference). A 100mm line segment was drawn for each category, and participants evaluated the odor by marking an "X" on the line segment.

[0026] 3-3.Statistical analysis Data from all 17 participants were included in the statistical analysis. Additionally, for the "odor intensity" item on the VAS, participants who scored higher for milk (ML) than for distilled water (DW, odorless control) were considered to have appropriately perceived the odor of the sample. Statistical analysis was also performed on these 14 participants. IBM SPSS 26.0 was used for the statistical analysis. Paired t-tests were used for data following a normal distribution, and Wilcoxon signed-rank tests were used for data not following a normal distribution.

[0027] 4. Test Results 4-1. Electroencephalogram background activity (1) Evaluation results (i) In the case of all subjects (n=17) Figure 2 shows an electroencephalogram (EEG) topographic map in the α2 band. Figure 4 shows the power values ​​for each region. In multiple regions, mainly the occipital lobe where alpha waves are dominant, the α2 power values, which indicate a state of both alertness and rest, were significantly higher in the case of the smell of milk.

[0028] (ii) Case where only subjects who could perceive the odor of the sample (n=14) Figure 3 shows the electroencephalogram (EEG) topographic map in the α2 band. Figure 5 shows the power values ​​for each region. The trends were similar to those observed in all subjects (n=17).

[0029] (2) Consideration In this example, the power value of alpha2 waves in the 10.0-13.0 Hz range was significantly higher when smelling milk (ML) compared to distilled water (DW, odorless control). From the above, it has been shown that the smell of milk has an effect of stabilizing brain function.

[0030] 4-2. Subjective evaluation using VAS (1) Evaluation results (i) In the case of all subjects (n=17) The results of the subjective evaluation using the VAS method are shown in Figure 6. Significant differences were observed in "odor intensity" among the samples, with milk (ML) being rated as having a significantly stronger odor than distilled water (DW, odorless control). No significant differences were found in "odor preference."

[0031] (ii) Case where only subjects who could perceive the odor of the sample (n=14) The results of the subjective evaluation using the VAS method are shown in Figure 7. The trends were similar to those observed for all subjects (n=17) mentioned above.

[0032] (2) Consideration Significant differences were observed between samples in the "odor intensity" category, confirming that most subjects were able to distinguish the scents of the samples. Furthermore, as mentioned above, when only the 14 subjects who were judged to be able to perceive the odor based on their "odor intensity" score were considered valid, the results did not differ significantly from those of all subjects in any parameter. Therefore, the results obtained in this example can be said to be observations made regardless of whether or not the subjects were able to perceive the odor.

Claims

1. A brain-sedative agent that uses the aromatic components of milk as its active ingredient.

2. The brain sedative agent according to claim 1, wherein the improvement in the brain sedative effect is due to the enhancement of alpha waves in the brainwaves.

3. The brain sedative agent according to claim 1, wherein the milk is milk obtained by degassing raw milk under reduced pressure to reduce the dissolved oxygen concentration in the liquid to 3 ppm or less, and then heat-sterilizing it at 120 to 150°C for 2 to 10 seconds.

4. A brain sedative agent according to claim 1, used as an anti-stress agent.

5. The brain sedative effect enhancing agent according to claim 1, used as a fragrance composition.

6. A pharmaceutical agent that enhances the sedative effect on the brain, as described in claim 1.

7. A method for enhancing the calming effect on the brain, which includes a process of applying milk products to the target's sense of smell.

8. A method for enhancing alpha brain waves, which includes a step of applying milk products to the target's sense of smell.

9. A method for reducing stress, which includes a process of applying milk products to the target's sense of smell.

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