Composition containing γ-aminobutyric acid

Abstract

The present invention provides a composition that contains γ-aminobutyric acid (GABA) as an active ingredient and is used for ameliorating or preventing confusion and / or bewilderment in a subject. The composition according to the present invention is preferably capable of ameliorating or preventing confusion and / or bewilderment evaluated by Profile of Mood States 2nd Edition (POMS2).

Description

γ-aminobutyric acid-containing composition

[0001] The present invention relates to gamma-aminobutyric acid (GABA)-containing compositions, and in particular to GABA-containing compositions for ameliorating or preventing confusion and / or bewilderment in a subject.

[0002] In recent years, γ-aminobutyric acid (GABA, 4-aminobutyric acid) has attracted attention as an amino acid that is widely distributed in nature and does not impair the flavor of foods when added to them. GABA is an inhibitory neurotransmitter found in large quantities in the mammalian central nervous system. It is known to suppress the excessive secretion of excitatory neurotransmitters, calm nerve excitement, and exert relaxation and anti-stress effects. It is also known to have a wide range of physiological activities, including hypotensive and cholesterol-lowering effects, and suppression of immune system decline. Because GABA is found in vegetables, grains, and the human body, it is easy to add to foods, and GABA-containing chocolate and numerous supplements are commercially available.

[0003] The present inventors have found that GABA can improve or prevent confusion and / or bewilderment in a subject.

[0004] Therefore, according to a main aspect of the present invention, the following inventions are provided: (Item 1) A composition for improving or preventing a state of confusion and / or bewilderment in a subject, comprising γ-aminobutyric acid (GABA) as an active ingredient. (Item 2) The composition according to any one of the above items, wherein the state of confusion and / or bewilderment is assessed by POMS2 (Profile of Mood States 2nd Edition). (Item 3) The composition according to any one of the above items, which suppresses and / or prevents an increase in the assessment score of the state of confusion and / or bewilderment. (Item 4) The composition according to any one of the above items, for improving or preventing a state of confusion and / or bewilderment caused by cognitive load. (Item 5) A composition for improving or preventing a state of confusion and / or bewilderment caused by cognitive load in a subject, comprising γ-aminobutyric acid (GABA) as an active ingredient, and wherein the state of confusion and / or bewilderment is assessed by POMS2 (Profile of Mood States 2nd Edition). (Item 6) The composition according to any one of the above items, wherein the cognitive load is caused by e-sports. (Item 7) The composition according to any one of the above items, wherein the GABA content is about 10 mg to about 1000 mg. (Item 8) The composition according to any one of the above items, wherein the GABA content is at least 200 mg. (Item 9) The composition according to any one of the above items, wherein the composition is taken orally. (Item 10) The composition according to any one of the above items, wherein the composition is a beverage, food, supplement, food additive, quasi-drug, or pharmaceutical. (Item 11) The composition according to any one of the above items, wherein the composition is in the form of a liquid, powder, tablet, or capsule. (Item 12) The composition according to any one of the above items, wherein the composition is for improving scores in games and / or e-sports. (Item 13) The composition according to any one of the above items, wherein the composition is a food product, the packaging of the food product being labeled as containing GABA as an active ingredient and for improving or preventing confusion and / or bewilderment. (Item 14) A composition according to any one of the preceding items for improving or preventing a state of mental sluggishness and / or decreased attention.(Item 15) A method for improving confusion and / or bewilderment in a subject, comprising administering to the subject a composition containing gamma-aminobutyric acid (GABA) as an active ingredient.

[0005] It is contemplated that one or more of the above features may be provided in combinations other than those explicitly stated, and further embodiments and advantages of the present disclosure will be recognized by those skilled in the art upon reading and understanding the following detailed description, if necessary.

[0006] Note that features and significant actions and effects of the present disclosure other than those described above will become clear to those skilled in the art by referring to the following description of the preferred embodiments of the present invention and the drawings.

[0007] According to the present invention, the ingestion of a GABA-containing composition can improve or prevent confusion and / or bewilderment in a subject, thereby enabling the subject to make calm and rational decisions similar to those under normal circumstances and promoting decision-making based on appropriate information, making the composition highly useful in daily life.

[0008] Furthermore, the compositions of the present invention can reduce confusion and / or embarrassment, thereby improving productivity and work efficiency in the subject, improving task quality, and reducing stress and psychological burden.

[0009] FIG. 1 is a graph showing the effect of sample intake on POMS2 test results when performing a game (multitasking) task, comparing a GABA-intake group with a placebo-intake group. FIG. 2 is a graph showing game (multitasking) scores when performing a game (single-tasking) task, comparing a GABA-intake group with a placebo-intake group. FIG. 3 is a graph showing the effect of sample intake on POMS2 test results when performing a game (single-tasking) task, comparing a GABA-intake group with a placebo-intake group. FIG. 4A is a graph showing game (single-tasking) scores when performing a game (single-tasking) task, comparing a GABA-intake group with a placebo-intake group. Average values ​​for Total Score and Acc Total Score (total accuracy (%)) are shown. FIG. 4B is a graph showing game (single-tasking) scores when performing a game (single-tasking) task, comparing a GABA-intake group with a placebo-intake group. 5 shows the average values ​​of rt Total Score (total reaction speed (%)) and kill Total Score (number of kills). Fig. 5 is a graph showing the effect of sample intake on the POMS2 CB score in the performance of a game (multitasking) task when theanine, ornithine hydrochloride, or saffron extract is taken.

[0010] The present disclosure will now be described with reference to the best mode. Throughout this specification, singular expressions should be understood to include the plural concept unless otherwise specified. Therefore, singular articles (e.g., "a," "an," "the," etc. in English) should be understood to include the plural concept unless otherwise specified. Furthermore, it should be understood that terms used in this specification are used in the sense commonly used in the art unless otherwise specified. Therefore, unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by those skilled in the art to which this disclosure belongs. In the event of conflict, the present specification (including definitions) will prevail.

[0011] The following provides definitions of terms particularly used in this specification and / or explains basic technical content as appropriate.

[0012] As used herein, "about" means ±10% of the preceding numerical value.

[0013] As used herein, the term "confusion and / or bewilderment" refers to a transient or significant increase in the "Confusion-Bewilderment (CB)" score in the POMS2 (Profile of Mood States 2nd Edition) psychological test, or in other psychological tests known in the art that correspond to the CB score in POMS2, after the occurrence of a given factor, compared to before the occurrence of the factor. Examples of other psychological tests known in the art that correspond to the CB score in POMS2 include "feeling of instability" in the "Subjective Symptom Survey (compiled by the Fatigue Research Group of the Japan Society for Occupational Health (2000))" and "feeling of depression" in the "Short-Term Occupational Stress Questionnaire."

[0014] As used herein, the expression "ameliorate or prevent" confusion and / or bewilderment caused by a certain ingredient means that the degree of confusion and / or bewilderment is significantly reduced when the ingredient is ingested compared to the degree of confusion and / or bewilderment when the ingredient is not ingested.

[0015] As used herein, "transient" after the occurrence of a certain factor means within 3 hours after the occurrence of the certain factor.

[0016] In this specification, "eSports" is an abbreviation for "electronic sports" and, in a broad sense, refers to competitions played using electronic devices. In a narrow sense, "eSports" refers to competitions using computer games or video games when those games are considered to be sports competitions. ESports competitions include not only sports games, but also shooting games, simulation games, fighting games, racing games, puzzle games, card games, and RPGs, but are not limited to these.

[0017] In this specification, "VDT work" refers to work using VDTs (Visual Display Terminals) such as displays and keyboards.

[0018] In this specification, "digital work" refers primarily to work that utilizes computers and the Internet. Specific examples of digital work include communication using communication tools such as email and chat, data processing and database management, website and application development, online marketing, and digital content production.

[0019] (Preferred Embodiments) Preferred embodiments of the present disclosure will be described below. The embodiments provided below are provided for a better understanding of the present disclosure, and the scope of the present disclosure should not be limited to the following description. Therefore, it is clear that those skilled in the art can make appropriate modifications within the scope of the present disclosure in light of the description herein. In addition, the following embodiments of the present disclosure can be used alone or in combination.

[0020] In one aspect of the present invention, there is provided a composition for improving or preventing a confused and / or bewildered state in a subject, comprising gamma-aminobutyric acid (GABA) as an active ingredient. In one embodiment, there is provided a composition for improving or preventing a confused and / or bewildered state in a subject, comprising gamma-aminobutyric acid (GABA) as an active ingredient for improving or preventing a confused and / or bewildered state in a subject.

[0021] Because γ-aminobutyric acid (GABA) is an amino acid widely distributed in nature, such as in vegetables and grains, in one embodiment of the present invention, the origin of GABA is not particularly limited as long as it is suitable for use in foods and beverages. For example, GABA-containing plant extracts or purified products may be used, or GABA may be prepared from a fermented product obtained by adding glutamic acid decarboxylase or a microorganism containing the enzyme, such as lactic acid bacteria, to a raw material containing glutamic acid. GABA-containing products and commercially available GABA may also be used in the composition of the present invention, provided that the effects of the composition are not impaired.

[0022] In one embodiment, when a subject ingests the composition of the present invention, the subject's confusion and / or embarrassment can be improved or prevented. Confusion and / or embarrassment can be assessed using the Profile of Mood States 2nd Edition (POMS2) or other equivalent psychological tests known in the art. Examples of other psychological tests known in the art include, but are not limited to, the Profile of Mood States (POMS), the State-Trait Anxiety Inventory (STAI), the Depression and Anxiety Mood Scale (DAMS), and the Positive Mood Scale (PMS). Among these, an example of an assessment equivalent to the CB component of the POMS2 is the "concentrated mood" component of the PMS. Psychological tests vary in test methodology depending on the target population, such as for adults and adolescents, and in the number of questions, such as the full version and the abbreviated version. The test method and number of questions can be appropriately selected depending on the subject's condition. Therefore, in one embodiment of the present disclosure, there is provided a composition for improving or preventing confusion and / or bewilderment in a subject as assessed by POMS2, which comprises gamma-aminobutyric acid (GABA) as an active ingredient.

[0023] For example, the POMS measures the factors of "Anger-Hostility (AH)," "Confusion (C)," "Depression-Dejection (D)," "Fatigue (F)," "Tension-Anxiety (TA)," "Vigor (V)," and "Total Mood Disturbance (TMD)."

[0024] POMS2 is a questionnaire survey used for subjective evaluation. In POMS2, the factors of "Anger-Hostility (AH)," "Confusion-Bewilderment (CB)," "Depression-Dejection (DD)," "Fatigue-Inertia (FI)," "Tension-Anxiety (TA)," "Vigor-Activity (VA)," "Friendliness (F)," and "Total Mood Disturbance (TMD)" are measured, and the mood state over a predetermined time frame is evaluated. The "confusion-perplexity" score is made up of subitems such as "I feel confused, overwhelmed, insecure, unsure, and unable to concentrate."

[0025] The STAI measures the factors of "state anxiety (anxiety state that changes from moment to moment)" and "trait anxiety (personality tendency to be prone to anxiety)."

[0026] The DAMS measures the factors "positive mood," "depressed mood," and "anxious mood."

[0027] PMS measures the factors "relaxed mood," "friendly mood," "pleasant mood," and "focused mood."

[0028] Examples of POMS2 include the "Profile of Mood States 2nd Edition-Adult (POMS2-A)" and the "Profile of Mood States 2nd Edition-Adult Short (POMS2-A)" (Heuchert, J. P. et al., Japanese version: translated and supervised by Kazuhito Yokoyama, Kaneko Shobo, 2015). The confusion and / or bewilderment state in the present invention can be assessed using either the full version or the short version.

[0029] The Mood Profile Test using the "POMS2 Adult Full Version" and "POMS2 Adult Short Version" is a test that uses a questionnaire to objectively measure mood states at the time of the survey. It is a test that is used internationally in a variety of fields, including medicine, the workplace, education, and sports instruction, to measure the progress of treatment for mental disorders (depression, anxiety disorders, etc.), group mental health screening in hospitals and workplaces, and the effects of exercise and relaxation.

[0030] In the "POMS2 Adult Full Version," subjects answer questions consisting of 65 items, and in the "POMS2 Adult Short Version," subjects answer questions consisting of 35 items, and the results are expressed as scores for the above factors (also called scales). "Confusion-Bewilderment" in POMS2 can reflect the subject's low cognitive efficiency or anxious state. Specifically, it can be evaluated by items such as lack of mental clarity, decreased attention, confusion, feeling at a loss, instability, lack of confidence, inability to concentrate, inability to organize thoughts, forgetfulness, lack of certainty, and inability to think logically. Definitions of the other factors are as described in the POMS2 manual, etc.

[0031] There are several reports of subjective evaluation of the effects of GABA intake using POMS / POMS2 (for example, references 1 to 4 in Table 1 below).

[0032] These studies reported studies in which subjects ingested 25-100 mg of GABA, and found that the fatigue (F) and vitality (V) scores of the POMS / POMS2 scale were significantly improved compared to placebo. However, there were no reports of improvement in the confusion and / or bewilderment (CB) score. Furthermore, Applied Pharmacology 72 (3 / 4) 51-56 (2007) reported that the intake of 180 g of soy milk rich in natural GABA (30 mg of GABA) did not affect the confusion and / or bewilderment (CB) score of the POMS scale (Figure 4).

[0033] On the other hand, evaluations of the effects of GABA intake on concentration and relaxation are available in Japanese Patent Application Laid-Open Nos. 2005-013127, 2006-061088, and 2005-348656. In Japanese Patent Application Laid-Open No. 2005-013127, subjects ingested GABA-containing chocolate and performed word processing input tasks and calculation tests to evaluate concentration, but no subjective evaluation was conducted using POMS / POMS2. In Japanese Patent Application Laid-Open No. 2006-061088, subjects ingested GABA and performed golf tee shots and calculation tests to evaluate concentration, but no subjective evaluation was conducted using POMS / POMS2. In JP 2005-348656 A, the relaxation effect of GABA was measured, and as indicators of relaxation, electroencephalogram (EEG), salivary chromogranin A, and STAI (State-Trait Anxiety Scale) were used, and subjective evaluation was performed, but no subjective evaluation was performed using POMS / POMS2. Furthermore, in "GABA suppresses stress on a suspension bridge for men and women with acrophobia, URL: <https: / / web.archive.org / web / 20230921144250 / http: / / www.gabastress.jp / effect / 04-2>," it is described that GABA intake resulted in calming of confusion, depression, and tension and anxiety compared to when GABA was not taken, but there is no description that GABA intake can improve or prevent confusion and / or bewilderment in subjects.

[0034] L-theanine, hemp seed extract, and hop extract are also known to have relaxing effects. While there are no known reports that L-theanine and hop extract significantly improve POMS / POMS2 CB scores, they are known to suggest a tendency for improvement. There are no known reports on hemp seed extract's POMS / POMS2 CB scores.

[0035] Specifically, regarding L-theanine, a notification (Notification No. I603) for a functional food containing L-theanine as a functional ingredient discloses that ingesting 200 mg of theanine reduced CB scores. Furthermore, Figure 4 of the literature (J Physiol Anthropol 31, 28 (2012)) adopted in the notification shows that there was no significant difference in the change in CB(C) scores, and the change was small. Furthermore, Figure 6 of JP-A-2019-520806 shows that a green tea extract containing tenian, procyanidins, and catechins improves the POMS CB score. Furthermore, Table 3 of JP-A-2007-31309 shows that the combined intake of tryptophan, L-theanine, and GABA improved all POMS2 scores, including the CB score, but no improvement in CB(C) scores was confirmed with the combination of tryptophan, L-theanine, and GABA.

[0036] Regarding hop extracts, Table 5 of International Publication WO2019 / 181058 reports that ingestion of hop oxidation products tends to improve the POMS2 CB score.

[0037] As described above, the effect of GABA intake on improving the POMS2 CB (confusion-bewilderment) score in subjects, the effect of GABA intake on improving concentration during simple tasks, the relaxation effect, and the inhibitory effect of GABA intake on confusion, depression, and tension anxiety caused by high-altitude stress, etc., can be said to be effects exerted in vivo by different mechanisms. Without being bound by theory, for example, a suspension bridge (high-altitude stress) and an MPG (Mobalytics Proving Ground) game (parallel processing task) share the same stress on the organism, but in terms of details, they have different characteristics, namely, situation-dependent stress (high-altitude stress) and cognitive load-type stress (parallel processing task). Specifically, the confusion, depression, tension anxiety, etc. caused by a suspension bridge (high-altitude stress) are emotional responses primarily due to environmental stressors (high altitude and fearful stimuli). In the case of such reactions, physiological stress responses, including the amygdala and sympathetic nervous system, play a major role in suppressing them (Mental Health Journal (2010) Vol. 112, No. 8, pp. 797-805). On the other hand, stress associated with parallel tasks (parallel processing work) in which multiple operations are performed simultaneously creates cognitive load, which can be assessed, for example, by the CB score of the POMS2. When dealing with such stress, efficient allocation of working memory and attention resources, centered on the prefrontal cortex, is important, which improves cognitive performance and task processing ability, and this is reflected in the improvement of the CB score.

[0038] Furthermore, the criteria for success in resolving stress associated with simple tasks or high altitude stress differ from those for stress associated with parallel tasks (parallel processing tasks). In the former, the goal is emotional stability, such as overcoming fear and tension, while in the latter, measurable cognitive outcomes, such as task accuracy and efficiency, are the criteria. This difference is thought to support the idea that the two phenomena are confirmed through different mechanisms. Therefore, stress associated with simple tasks or high altitude stress and stress associated with parallel tasks (parallel processing tasks) can be said to be stress responses resulting from different aspects, namely, emotions and cognition, and each is caused by a different mechanism. Therefore, the concentration-improving and relaxing effects of GABA intake for simple tasks, as well as the inhibitory effect of GABA intake on confusion, depression, and tension anxiety caused by high altitude stress, and the effect of GABA intake on improving POMS2 CB scores in subjects, can be said to be effects exerted in vivo by different mechanisms, corresponding to the differences in the mechanisms of stress generation.

[0039] In one embodiment of the present disclosure, the GABA-containing composition of the present disclosure can suppress and / or prevent an increase in confusion and / or bewilderment, or an increase in the confusion and / or bewilderment rating score. As described above, the effect of GABA intake on confusion and / or bewilderment (CB) was unknown until now. However, in the present invention, as shown in the Examples, it has been found that intake of a GABA-containing composition suppresses or improves an increase in the POMS2 CB (confusion-bewilderment) score. Therefore, in one embodiment of the present disclosure, a composition for suppressing and / or preventing an increase in confusion and / or bewilderment, or an increase in the confusion and / or bewilderment rating score in a subject, is provided, which contains γ-aminobutyric acid (GABA) as an active ingredient.

[0040] In one embodiment of the present disclosure, confusion and / or bewilderment may be caused by cognitive load on a subject. Cognitive load refers to the total amount of mental activity imposed on working memory and attention resources at any given time, e.g., the mental effort or demands required for a subject to understand or learn some information or complete some task, and is distinct from emotional responses. Cognitive load also depends on the limited capacity of a subject's working memory and attention resources and the subject's ability to process new information. Examples of cognitive load include, but are not limited to, mental activity imposed on working memory and attention resources due to multiple factors, such as long working hours, intellectual labor, e-sports, VDT work, digital work, and gaming (TV games, PC games, mobile games, etc.).

[0041] In one embodiment of the present disclosure, the state of confusion and / or bewilderment may be caused by single-tasking or multitasking. In one embodiment, multitasking includes a subject simultaneously performing multiple tasks, movements, assignments, and / or tasks. For example, in the case of VDT work, the following tasks and movements can be cited as single-tasking and multitasking, respectively. <Single-tasking> - Typing games (repeated simple data entry) - Shooting PC games where you only shoot targets (simply left-clicking the mouse with one hand. Games that do not involve switching weapons using the keyboard, switching the field of view, moving forward, backward, left, right, jumping, crouching, or other movements, or reloading bullets) <Multitasking> - Shooting games Tasks that involve shooting while simultaneously switching weapons, reloading bullets, moving forward, backward, left, right, switching the field of view, and checking the map, etc. - Racing games Simultaneous acceleration, braking, and determining left and right directions, etc.

[0042] In another embodiment, in the case of tasks other than VDT ​​work, the following tasks and actions can be listed as single tasks and multitasks: <Single task> Kraepelin test (repeated simple addition), etc. <Multitask> Driving a car: steering, turning signals, etc., operating footwork, making decisions based on other cars, traffic lights, and people, etc. Playing the piano: different movements with the left and right, operating footwork, etc.

[0043] E-sports refers to competitive computer games and video games (games that can be played on any device, including personal computers (PCs), home game consoles, mobile applications, and VR). E-sports include, for example, gamified versions of actual sports competitions and newly created virtual sports competitions that are controlled by human players (in the case of competitive competitions, the opponent may be a computer simulation). Virtual sports refer to virtual sports competitions that mimic actual sports competitions or newly created virtual sports competitions that are played virtually under certain rules and algorithms through computer simulation. Virtual sports are configured so that virtual players based on data that mimic athletes in actual sports competitions, or virtual players based on data generated by users under certain rules, compete through computer simulation.

[0044] In one embodiment, the game genre of e-sports is not particularly limited and may be any game genre. For example, it may be a fighting game, a sports game, a shooting game, a racing game, a puzzle game, a word game, a card game, a board game, a role-playing game, or a simulation game. Furthermore, e-sports may be individual or team competitions. Furthermore, it may be a competition between humans as players, or a competition between humans and a computer (e.g., AI or a robot).

[0045] VDT work refers to work using VDT (Visual Display Terminals) such as displays and keyboards. Digital work refers to work primarily using computers and the Internet. VDT work and digital work involve looking at a screen for long periods of time, which can cause eye fatigue and stress. The composition of the present invention can improve or prevent confusion and / or bewilderment caused by fatigue and / or stress in a subject.

[0046] In one embodiment, games include those played on any electronic device, such as TV games, PC games, and mobile games. The game genre is not particularly limited and may be, for example, a fighting game, a sports game, a shooting game, a racing game, a puzzle game, a word game, a card game, a board game, a role-playing game, or a simulation game. The composition of the present invention can improve or prevent confusion and / or embarrassment that occurs when a subject plays e-sports, thereby enabling the subject to improve their score or achieve efficient progress in the game.

[0047] In one embodiment, the composition of the present invention is ingested before a subject performs a task so as to achieve the effects of the composition of the present invention. The composition of the present invention may be ingested at least about 5 hours to about 1 minute before, or immediately before, the subject performs the task. The upper limit (maximum time) of the intake timing may be, for example, at least about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, or about 7 hours before the subject performs the task. The lower limit (minimum time) of the intake timing may be, for example, at least about 50 minutes, about 45 minutes, about 40 minutes, about 35 minutes, about 30 minutes, about 25 minutes, about 20 minutes, about 15 minutes, about 10 minutes, about 5 minutes, about 4 minutes, about 3 minutes, about 2 minutes, about 1 minute, or immediately before the subject performs the task. The intake timing may be within any range between these lower and upper limits. Ingestion of the composition of the present invention before performing a task can improve or prevent confusion and / or bewilderment that occurs when a subject performs the task. In one embodiment, the time at which the composition of the present invention should be ingested before performing a task can be determined appropriately depending on the type, content, or difficulty of the task, the condition or nature of the subject, or the degree of confusion and / or bewilderment.

[0048] In one embodiment of the present invention, the content of GABA in the composition of the present invention is not particularly limited as long as the concentration or weight is such that the effect of the composition of the present invention can be obtained, depending on the administration method, etc. The content of GABA in the composition of the present invention is preferably about 10 to about 1000 mg, and the lower limit of the content may be, for example, about 10 mg or more, about 30 mg or more, about 50 mg or more, about 70 mg or more, about 100 mg or more, about 150 mg or more, about 200 mg or more, about 300 mg or more, about 400 mg or more, about 500 mg or more, or about 700 mg or more, and the upper limit of the content may be, for example, about 1000 mg or less, about 800 mg or less, about 700 mg or less, about 600 mg or less, about 500 mg or less, about 400 mg or less, about 300 mg or less, about 200 mg or less, or about 100 mg or less, and the content may be in any numerical range between these lower and upper limits.

[0049] In one embodiment of the present invention, the composition of the present invention can contain, in addition to GABA, any additives or any components that can be used in ingestible compositions, depending on its form.Examples of these additives and components include, but are not limited to, vitamins including vitamin E, vitamin C, etc., minerals, nutritional components, physiologically active ingredients such as flavorings, excipients, binders, emulsifiers, tonicity agents (isotonicity agents), buffers, solubilizers, preservatives, stabilizers, antioxidants, colorants, coagulants, or coating agents that are added during formulation.

[0050] In one embodiment of the present invention, the form of the composition of the present invention is not particularly limited as long as it contains GABA, and it can be, for example, a pharmaceutical composition, a food or drink (including functional foods such as foods for specified health uses, foods with nutrient function claims, and foods with functional claims, health supplements, health foods, and supplements), a food additive, a quasi-drug, or a pharmaceutical. Examples of functional claims that can be adopted include claims such as "contains GABA as an active ingredient, and prevents, alleviates, or improves states of confusion and bewilderment," or "improves or prevents states of mental sluggishness and / or decreased attention span," and the composition can be provided as a food with such claims affixed to its packaging.

[0051] In one embodiment of the present invention, the composition of the present invention can be taken orally, and when used as an oral preparation, its form can be, for example, a tablet (including coated tablets), capsule, powder, granule, powder, liquid, suspension, emulsion, granule, powder, pill, paste, cream, caplet, gel, chewable, stick, etc. Furthermore, it can be prepared into a form that is easy to incorporate, such as a powder or granule, and then used as a raw material for other pharmaceuticals.

[0052] In one embodiment of the present invention, the composition of the present invention can be used for non-therapeutic purposes, and ingesting the composition of the present invention can be used as a non-therapeutic method for improving or preventing a state of confusion and / or bewilderment in a subject. Such a method does not include therapeutic or medical treatment, and the subject is not particularly limited, but is preferably a healthy individual. By having such a healthy individual ingest the composition of the present disclosure, the state of confusion and / or bewilderment can be improved or prevented. Furthermore, when used as a pharmaceutical or quasi-drug, efficacy such as improvement or prevention of a state of confusion and / or bewilderment can be promoted.

[0053] The compositions of the present invention can be used for therapeutic purposes, and therefore, in another aspect of the present invention, there is provided a method for ameliorating a state of confusion and / or bewilderment in a subject, the method comprising the step of administering to the subject a composition containing γ-aminobutyric acid (GABA) as an active ingredient.

[0054] In one embodiment of the present invention, the daily or single intake of GABA contained in the composition of the present invention can be appropriately set depending on the form of the composition, the intake method, the purpose of use, and the age, weight, symptoms, etc. of the subject. For example, from the viewpoint of more significantly exerting the effect of GABA contained in the composition of the present invention, it is preferable to take the GABA contained in the composition of the present invention so that the daily intake is about 10 mg / day or more, more preferably about 25 mg / day or more, about 50 mg / day or more, about 60 mg / day or more, about 80 mg / day or more, about 100 mg / day or more, about 120 mg / day or more, about 150 mg / day or more, about 180 mg / day or more, about 200 mg / day or more, about 300 mg / day or more, about 400 mg / day or more, about 500 mg / day or more, about 800 mg / day or more, or about 1000 mg / day or more. There is no particular upper limit to the daily intake amount of GABA contained in the composition of the present invention, as long as it is within the range in which the composition of the present invention can exert its effect of improving or preventing confusion and / or bewilderment.

[0055] In one embodiment of the present invention, the frequency of application of the method of the present invention or the frequency of ingestion of the composition of the present invention may be one or more times a day within the desired intake range, and the ingestion period may also be appropriately set within a range in which the composition of the present invention can exert its effect of improving or preventing confusion and / or bewilderment.

[0056] In one embodiment, ingestion of the compositions of the present invention improves or prevents confusion and / or bewilderment in a subject, thereby improving scores or achieving efficient progress when performing a task.

[0057] In another embodiment, the compositions of the present invention can be provided to suppress and / or prevent an increase in confusion and / or bewilderment in a subject, or an increase in the score of confusion and / or bewilderment in a subject. By ingesting the compositions of the present invention, scores can be improved or progress can be made more efficiently when working on a task.

[0058] As used herein, "or" is used when "at least one or more" of the items listed in the text can be employed. The same applies to "alternative." When "within the range of" two values ​​is specified herein, the range includes the two values ​​themselves. References cited herein, such as scientific literature, patents, patent applications, etc., are incorporated herein by reference in their entirety to the same extent as if each were specifically set forth.

[0059] The present disclosure has been described above by showing preferred embodiments for ease of understanding. The present disclosure will be described below based on examples. However, the above description and the following examples are provided for illustrative purposes only and are not intended to limit the present disclosure. Therefore, the scope of the present disclosure is not limited to the embodiments or examples specifically described herein, but is limited only by the scope of the claims.

[0060] (Example 1: Study Design A (Multitasking)) Whether POMS2 scores improve with GABA intake under the condition of multitasking as a task was evaluated. The study design is as follows. For EEG measurement, an analysis algorithm of an EEG analysis application (Sports Sensibility, KANSEI) provided by Little Software was used.

[0061] <Study Design A (Multitasking)> ・Test subjects: 9 people (1 excluded, 8 analyzed) ・Equipment used: Simple electroencephalograph ・Sample: GABA (200 mg) or placebo (dextrin) + 30 ml of water ・Measurement items: EEG, short version of POMS2, MPG (game task) score ・Double-blind crossover study (washout period: 1 week)

[0062] MPG (Mobalytics Proving Ground) is a game that measures the basic skills of esports players. It can be played at https: / / pg.mobalytics.gg / . The game involves simultaneously performing three tasks: shooting targets (MECHANICS), switching weapons (BG PROCESSING), and checking the map (MAP AWARENESS). The score for each task, as well as an overall score calculated from the three tasks, are displayed.

[0063] Details of the game score obtained from MPG are as follows. In the analysis below, only the major items marked with * were used. 1. Total score (n)* 2. Mechanics ability (the ability to operate the mouse and keyboard in response to sensory stimuli) (n)* Number of target hits (n) Accuracy (%) Precision (%) Ignored targets (n) Total points lost (n) Center hits (n) Center hits out of all hits (n) Points from center hits (n) Middle hits (n) Middle hits out of all hits (n) Points from center hits (n) Border hits (n) Border hits out of all hits (n) Number of points from border hits (n) Average click latency (s) Number of actions per minute (n) Center points missed (n) Number of target hits (n) 3. Background processing ability (n)* Number of target hits (n) Accuracy (%) Precision (%) Ignored targets (n) 4. Map awareness (n)* Score (n) Time stuck (s) Points lost (n) Average time per obstacle (s)

[0064] The study subjects were nine healthy male university students with no memory impairment symptoms and no drug therapy treatment for any illness (age: 20.10 ± 1.10 years, height: 178.71 ± 6.96 cm, weight: 60.9 ± 12.90 kg, mean ± standard deviation). All study subjects had experience playing League of Legends (23.31 months ± 11.81 months), average weekly gameplay time was 3.33 hours ± 1.25, and weekly play frequency was 3.33 ± 1.63 times. This study was approved by the Little Software Institutional Review Board (No. 2023-0001, February 28, 2022). Study subjects were informed that they could withdraw from the study at any time, and the purpose, content, and methods of the study were explained. Written consent was obtained. Study subject ID9 was taking hay fever medication and was therefore excluded from the analysis data. Therefore, valid data was available for eight subjects.

[0065] The test flow is as follows: (i) 0 to 5 minutes after the start of the test: MPG content explanation, pre-implementation, sensitivity setting (ii) 5 to 15 minutes after the start of the test: resting state (iii) 15 to 18 minutes after the start of the test: EEG measurement at rest (iv) 18 to 22 minutes after the start of the test: POMS2 implementation (before sample intake) (v) 22 to 23 minutes after the start of the test: sample (GABA or placebo) intake (vi) 23 to 55 minutes after the start of the test: game task implementation (32 minutes) and EEG measurement (a total of three times in the first, middle, and final stages) (vii) 55 to 59 minutes after the start of the test: POMS2 implementation (after sample intake)

[0066] In (vi), participants were asked to play the game multiple times with breaks in between. Test Results The results of POMS2 are shown in Figure 1. In Test Design A (multitasking), the CB (confusion-bewilderment) score after completing the game task was significantly lower in the GABA intake group compared to the placebo group. This was the first time that it was revealed that taking GABA (200 mg) significantly improved the POMS2 CB (confusion-bewilderment) score under conditions of high load, such as performing multiple tasks simultaneously.

[0067] The results of the game scores are shown in Figure 2. In test design A (multitasking), the total score in the GABA intake group was significantly higher than in the placebo group.

[0068] (Example 2: Study Design B (Single Task)) With a single task given as the task, we evaluated whether GABA intake would improve the POMS2 score. The study design was as follows. For EEG measurement, we used the analysis algorithm of an EEG analysis application (Sports Sensibility, KANSEI) provided by Little Software.

[0069] <Study Design B (Single Task)> ・Test subjects: 10 (0 excluded, 10 analyzed) ・Equipment used: Simple EEG meter ・Sample: GABA (200 mg) or placebo (dextrin) + 30 ml of water ・Measurement items: EEG, short version of POMS2, AIM LAB (game task) score ・Double-blind crossover study (washout period: 1 week)

[0070] AIM LAB is a game that measures the basic skills of esports players. The game only involves shooting targets, and displays four items: Total Score, Acc Total Score (total accuracy (%)), rt Total Score (total reaction time (%)), and kill Total Score (number of kills).

[0071] The study subjects were 10 healthy male university students with no memory impairment symptoms and no drug therapy for any illness (age: 21.00 ± 3.55 years, height: 169.85 ± 3.54 cm, weight: 71.0 ± 19.89 kg, mean ± standard deviation). All study subjects had experience playing Valorant (23.4 months ± 12.71 months), average weekly gameplay time was 3.9 hours ± 1.76, and weekly play frequency was 2.70 ± 0.98 times. This study was approved by the Little Software Institutional Review Board (No. 2023-0001, February 28, 2022). Study subjects were informed that they could withdraw from the study at any time, and the purpose, content, and methods of the study were explained, and written consent was obtained.

[0072] The test flow is as follows: (i) 0 to 5 minutes after the start of the test: AIM LAB explanation, pre-test, sensitivity setting (ii) 5 to 15 minutes after the start of the test: resting state (iii) 15 to 18 minutes after the start of the test: EEG measurement at rest (iv) 18 to 22 minutes after the start of the test: POMS2 implementation (before sample intake) (v) 22 to 23 minutes after the start of the test: sample (GABA or placebo) intake (vi) 23 to 55 minutes after the start of the test: game task implementation (32 minutes) and EEG measurement (a total of 3 times in the first, middle, and final stages) (vii) 55 to 59 minutes after the start of the test: POMS2 implementation (after sample intake)

[0073] In (vi), the participants were asked to play the game multiple times with breaks in between.

[0074] Test Results The results of POMS2 are shown in Figure 3. In test design B (single task), no significant change in scores was observed between the GABA intake group and the placebo group.

[0075] The results of the game scores are shown in Figures 4A and 4B. In Study Design B (single task), no significant change in scores was observed between the GABA intake group and the placebo group.

[0076] Example 3: Effects of theanine, ornithine hydrochloride, and saffron extract on POMS2 CB scores. Using substances other than GABA, which are known to have a relaxing effect, we evaluated whether POMS2 CB scores would improve when participants were given multitasking, as in Example 1. The test substances used were theanine, ornithine hydrochloride, and saffron extract. The following are known examples of the relaxing effects of each substance. <Theanine> Eight weeks of L-theanine (250 mg / day) significantly improved depressive symptoms (HAMD-21 score) and anxiety (STAI score) (Hidese et al., 2019). <Ornithine hydrochloride> When healthy adults ingested L-ornithine (400 mg) after alcohol consumption, scores for "confusion" and "anger-hostility" (POMS) significantly decreased (Kokubo et al., 2013). In a randomized, double-blind, placebo-controlled study, healthy Japanese workers were given L-ornithine (400 mg / day) for eight weeks, and the results showed improvements in anger. Confusion was also reduced, although not significantly different (Miyake et al., 2014). <Saffron extract> In a clinical trial in which saffron extract was administered to adults, depression (POMS) was improved (Jackson et al., 2021).

[0077] The test design was as follows. Test subjects were asked to play the MPG game under the same conditions and procedures as in Example 1, except for the ingestion of GABA. Test subjects were asked to perform POMS2 before ingestion of the sample, and then ingest 250 mg of theanine (N=3), 400 mg of ornithine (N=3), or 30 mg of saffron extract (N=3). They then performed the game task, and POMS2 was performed after ingestion of the sample.

[0078] The results of the POMS2 CB score are shown in Figure 5. All results are the average of three subjects. As shown in Figure 5, none of theanine, ornithine hydrochloride, and saffron extract showed any improvement in the POMS2 CB score after ingestion of the sample ("Post" in the figure) compared to the POMS2 CB score before ingestion of the sample ("Pre" in the figure). This suggests that even substances known to have a relaxing effect do not have an effect of improving the state of confusion and bewilderment during MPG games. Therefore, it was suggested that the significant improvement in the CB (confusion-bewilderment) score by GABA shown in Example 1 is an effect different from a simple stress-reducing effect.

[0079] (Note) While the present disclosure has been illustrated using preferred embodiments thereof, it is understood that the scope of the present disclosure should be construed solely by the claims. It is understood that the patents, patent applications, and other documents cited in this specification are incorporated by reference into this specification in their entirety as if the contents themselves were specifically set forth herein. This application claims priority to Japanese Patent Application No. 2024-41315, filed on March 15, 2024, with the Japan Patent Office, the contents of which are incorporated by reference in their entirety as if they constitute the contents of this application.

[0080] According to the present invention, the ingestion of GABA can improve or prevent confusion and / or bewilderment in a subject, and is therefore useful in fields related to stress management, mental health, and the like.

Claims

1. A composition for ameliorating or preventing confusion and / or bewilderment in a subject, comprising gamma-aminobutyric acid (GABA) as an active ingredient.

2. The composition of claim 1, wherein the confusion and / or bewilderment state is assessed by POMS2 (Profile of Mood States 2nd Edition).

3. The composition of claim 1, which inhibits and / or prevents an increase in the evaluation score of the confusion and / or bewilderment state.

4. The composition of claim 1 for ameliorating or preventing confusion and / or bewilderment caused by cognitive load.

5. A composition for improving or preventing confusion and / or bewilderment caused by cognitive load in a subject, the composition comprising gamma-aminobutyric acid (GABA) as an active ingredient, and the confusion and / or bewilderment is assessed by POMS2 (Profile of Mood States 2nd Edition).

6. The composition described in claim 4 or 5, wherein the cognitive load is caused by e-sports.

7. The composition of claim 1, wherein the GABA content is from about 10 mg to about 1000 mg.

8. The composition of claim 7, wherein the GABA content is at least about 200 mg.

9. The composition of claim 1, which is taken orally.

10. The composition according to claim 1, which is a beverage, food, supplement, food additive, quasi-drug, or pharmaceutical.

11. The composition of claim 1 in the form of a liquid, powder, tablet, or capsule.

12. The composition of claim 1 for improving scores in games and / or e-sports.

13. The composition according to claim 1, which is a food product and the packaging of the food product is labeled as containing GABA as an active ingredient and for improving or preventing confusion and / or bewilderment.

14. The composition of claim 1 for improving or preventing mental sluggishness and / or decreased attention span.

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