Composition and its use

Abstract

To provide a novel composition containing DAGE and to provide a new use of DAGE.SOLUTION: There is provided a composition comprising A: a diacylglycerol ether (DAGE) represented by formula (I) (in formula (I), R1 is an aliphatic hydrocarbon group having 12 to 24 carbon atoms and an unsaturation degree of 0 to 2, R2 is an acyl group having 12 to 24 carbon atoms and an unsaturation degree of 0 to 6, and R3 is an acyl group having 12 to 24 carbon atoms and an unsaturation degree of 0 to 6), and B: squalene, wherein the mass ratio A:B is from 0.9 to 9:1.SELECTED DRAWING: None

Description

[Technical Field]

[0001] This invention relates to a composition containing diacylglyceryl ether (DAGE) and its use. [Background technology]

[0002] Diacylglyceryl ether (DAGE) is widely distributed in aquatic animal fats and oils, and is particularly abundant in fats derived from the livers of sharks and squid. Several functions of DAGE are known. For example, Patent Document 1 describes an oral preventive and therapeutic agent for skin damage caused by ultraviolet light, containing diacylglyceryl ether as an active ingredient. Patent Document 2 describes a composition for improving sleep quality, containing a fish roe lipid preparation and diacylglyceryl ether (DAGE).

[0003] Furthermore, regarding DAGE, it has been reported that it has an effect on circadian rhythms (Non-Patent Literature 1), and that when healthy individuals who temporarily experience dissatisfaction with their sleep consume DHA / EPA-containing salmon roe oil and DAGE-containing deep-sea shark liver oil, the proportion of deep sleep and REM sleep increases, improving sleep quality. It has also been reported that it alleviates anxiety, tension, and depression in individuals with low vitality, improving vitality and reducing daytime sleepiness (Non-Patent Literature 2, 3). In addition, the effects of consuming deep-sea shark liver oil-containing foods on the vitality of healthy Japanese individuals have been reported (Non-Patent Literature 4). [Prior art documents] [Patent Documents]

[0004] [Patent Document 1] International Publication WO2004 / 000301 (Patent No. 4417249) [Patent Document 2] International release WO2022 / 210856 [Non-patent literature]

[0005] [Non-Patent Document 1] Kobayashi, Rio et al., Journal of Chronobiology, Vol. 28, No. 2, p. 216, 2022. [Non-Patent Document 2] Iku Nakagawa et al., Verification of the sleep quality improvement and anti-stress effects of processed oils containing DHA derived from salmon roe oil, EPA derived from salmon roe oil, and DAGE derived from deep-sea shark liver oil in people dissatisfied with their sleep - A randomized, double-blind, placebo-controlled, parallel-group comparative study -, Jpn Pharmacol Ther (Pharmacology and Therapeutics), Vol.49, No.6, p977-990, 2021. [Non-Patent Document 3] Takada, Yuka et al., "The Cutting Edge of Functional Food Development for Fatigue, Stress, and Sleep: Effects of DHA, EPA, and DAGE (Diacylglyceryl Ether)-Containing Oil-Based Foods on Increasing REM and Deep Sleep," Monthly Fine Chemical, Vol. 52, No. 4, pp. 40-48, 2023. [Non-Patent Document 4] Yoshinaga, Yusei et al., The effect of consuming deep-sea shark liver oil-containing foods on the vitality of healthy Japanese individuals - A randomized, double-blind, placebo-controlled, double-blind, parallel-group comparative study -, Jpn Pharmacol Ther (Pharmacology and Therapeutics), Vol.46, No.9, p1399-1425, 2021. [Overview of the Initiative] [Problems that the invention aims to solve]

[0006] It is desirable to provide a novel composition containing DAGE that is highly effective. It is also desirable to provide new applications for DAGE. [Means for solving the problem]

[0007] The present invention provides the following: [1] A. Equation I:

[0008] [ka]

[0009] (In formula I, R 1 is an aliphatic hydrocarbon group having an unsaturation degree of 0 to 2 and 12 to 24 carbon atoms, and R 2 is an acyl group having an unsaturation degree of 0 to 6 and 12 to 24 carbon atoms, and R 3 is an acyl group having an unsaturation degree of 0 to 6 and 12 to 24 carbon atoms.) A diacylglyceryl ether (DAGE) represented by B. Squalene containing a composition wherein the mass ratio of A:B is 0.9 to 9:1. [2] The composition according to 1, formulated such that 400 mg or more of DAGE is ingested per day. [3] Formula I:

[0010]

Chemical formula

[0011] (In formula I, R 1 is an aliphatic hydrocarbon group having an unsaturation degree of 0 to 2 and 12 to 24 carbon atoms, and R 2 is an acyl group having an unsaturation degree of 0 to 6 and 12 to 24 carbon atoms, and R 3 is an acyl group having an unsaturation degree of 0 to 6 and 12 to 24 carbon atoms.) A composition for improving at least one selected from a negative mood state, anger, fatigue, listlessness, confusion, and mental health, containing the diacylglyceryl ether (DAGE) represented by [4] A composition for alleviating at least one selected from anger, fatigue, listlessness, and confusion of a subject in a negative mood state, and improving the mood state, containing the DAGE defined in 3. [5] The composition according to 3 or 4, wherein the composition further contains squalene. [6] The composition according to any one of 1 to 5, wherein the composition further contains triglyceride. [7] The composition according to any one of 1 to 6, for ingestion by a subject who is prone to feeling stress on a daily basis or a subject in a negative mood state. [8] The composition according to any one of items 1 to 7 for causing ingestion of 400 mg or more of DAGE per day for 12 weeks or more. [9] The composition according to any one of items 1 to 7 for causing continuous ingestion of 400 mg or more of DAGE per day for 12 weeks or more.

Effect of the Invention

[0012] According to one aspect of the present invention, a composition containing diacylglyceryl ether and squalene is provided. According to another aspect, a composition containing diacylglyceryl ether (DAGE) for improving at least one selected from the group consisting of general mood state, anger-hostility, fatigue-apathy, confusion-perplexity, and mental health is provided.

Modes for Carrying Out the Invention

[0013] Regarding the present invention, the numerical range x to y includes the values x and y at both ends. Regarding the present invention, numerical values of ratios and proportions are based on mass unless otherwise specified.

[0014] [Composition] The first embodiment of the present invention relates to a composition containing diacylglyceryl ether (DAGE) and squalene.

[0015] (Diacylglyceryl Ether) The composition of this embodiment contains diacylglyceryl ether (DAGE) represented by formula I. DAGE may also be referred to as alkyl diacyl glycerol. DAGE has a structure in which fatty acids are ester-bonded to two of the three hydroxyl groups of glycerol (glycerin), and a hydrocarbon is ether-bonded to one, and is represented by the following formula I.

[0016]

Chemical Formula

[0017] In formula I, R 1 is an aliphatic hydrocarbon group with an unsaturation degree of 0 to 2 and a carbon number of 12 to 24, and R2 is an acyl group with an unsaturation degree of 0 to 6 and a carbon number of 12 to 24, and R 3 is an acyl group with an unsaturation degree of 0 to 6 and a carbon number of 12 to 24.

[0018] R 1 Examples of the aliphatic hydrocarbon group represented by are those represented by a carbon number: unsaturation degree of 24:1, 22:1, 20:1, 18:2, 18:1, 18:0, 16:1, 16:0, 14:0, or 12:0. Those with a carbon number: unsaturation degree of 18:1, 18:0, 16:1, or 16:0 are particularly preferred.

[0019] R 2 Examples of the acyl group represented by include those represented by a carbon number: unsaturation degree of 24:1 (derived from nervonic acid), 22:6 (derived from docosahexaenoic acid), 22:1 (derived from erucic acid), 20:5 (derived from eicosapentaenoic acid), 20:4 (derived from arachidonic acid), 20:1 (derived from gadoleic acid), 18:3 (derived from α-linolenic acid, γ-linolenic acid), 18:2 (derived from linoleic acid), 18:1 (derived from oleic acid, octadecenoic acid), 18:0 (derived from stearic acid), 16:1 (derived from palmitoleic acid), 16:0 (derived from palmitic acid), 14:0 (derived from myristic acid), 12:0 (derived from lauric acid), etc.

[0020] Those with a carbon number: unsaturation degree of 24:1 (derived from nervonic acid), 22:6 (derived from docosahexaenoic acid), 22:1 (derived from erucic acid), 20:5 (derived from eicosapentaenoic acid), 20:1 (derived from gadoleic acid), 18:1 (derived from oleic acid, octadecenoic acid), and 16:0 (derived from palmitic acid) are particularly preferred.

[0021] R 3Examples of acyl groups represented by this formula include those with carbon number:unsaturation ratios of 24:1 (derived from nervonic acid), 22:6 (derived from docosahexaenoic acid), 22:1 (derived from erucic acid), 20:5 (derived from eicosapentaenoic acid), 20:4 (derived from arachidonic acid), 20:1 (derived from gadoleic acid), 18:3 (derived from α-linolenic acid and γ-linolenic acid), 18:2 (derived from linoleic acid), 18:1 (derived from oleic acid and octadecenoic acid), 18:0 (derived from stearic acid), 16:1 (derived from palmitoleic acid), 16:0 (derived from palmitic acid), 14:0 (derived from myristic acid), and 12:0 (derived from lauric acid).

[0022] Carbon number: Particularly preferred are those with an unsaturation ratio of 24:1 (derived from nervonic acid), 22:6 (derived from docosahexaenoic acid), 22:1 (derived from erucic acid), 20:5 (derived from eicosapentaenoic acid), 20:1 (derived from gadoleic acid), 18:1 (derived from oleic acid and octadecenoic acid), and 16:0 (derived from palmitic acid).

[0023] DAGE is known to be abundant in the liver oil of sharks, especially deep-sea sharks. In addition to sharks, it is also known to be found in squid (liver), some fish (muscle), cattle, humans (milk), and chimaeras (silver shark, Chimaera phantasma). The raw material for DAGE used in the composition of this embodiment is not particularly limited. In this embodiment, shark liver oil may be used as DAGE, or concentrated, crude, or refined shark liver oil may be used. It may be produced by microorganisms or a synthetic product may be used.

[0024] In one embodiment, DAGE may be contained in deep-sea shark liver oil. Deep-sea shark liver oil is an oil extracted from the livers of sharks that can inhabit the deep sea, such as dogfish, night heron, and horned dogfish. Liver oil can be extracted by conventionally known methods. For example, the liver of a shark can be removed, finely crushed in a crushing device, left to stand for 1 to 4 days to separate the oil from the solids, and the oil can be extracted to obtain liver oil. The liver oil may be further filtered to remove fine solids and refined. Alternatively, commercially available deep-sea shark liver oil can be used. Furthermore, there are reports regarding the immune-activating function of alkylglycerols contained in shark liver oil (Mar. Drugs 2010, 8, 2267-2300; doi:10.3390 / md8082267, and Lipids Health Dis. 2014 Nov 27:13:178. doi: 10.1186 / 1476-511X-13-178).

[0025] (Squalene) The composition of this embodiment contains squalene. Squalene (sometimes written as squalene; IUPAC name: 2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene) is an oily substance belonging to the triterpene group.

[0026] Squalene is abundant in shark liver oil and is also found in vegetable oils such as olive oil, rice bran oil, wheat germ oil, sesame oil, and soybean oil. Algae that produce squalene are also known (Patent No. 6265407, Patent No. 5942197).

[0027] The raw material for squalene used in this embodiment is not particularly limited. In one embodiment, the above-mentioned oil may be used as squalene, or a concentrate, crude refined product, or refined product of the above-mentioned oil may be used. Squalene has been reported to have antioxidant properties, and the inclusion of squalene in the composition is expected to support the action of DAGE during ingestion and in the body.

[0028] (mass ratio, content) The mass ratio of A (DAGE) to B (squalene) in the composition of this embodiment can be set as appropriate. In one embodiment, A:B can be 0.1 to 10:1, for example 0.8 to 10:1, or 0.1 to 9:1, preferably 0.9 to 9:1, more preferably 1 to 8:1, more preferably greater than 1 to 7.5:1 (DAGE-rich), and even more preferably 2 to 7:1. It should be noted that the A:B ratio in commercially available functional foods containing DAGE is analyzed to be 0.07 to 0.77:1.

[0029] The DAGE content in the composition of this embodiment can be set as appropriate. In one embodiment, it can be 38 g or more per 100 g (or per 100 g of mass including the coating if formulated as a capsule, etc.; the same applies hereinafter), preferably 39 g or more, more preferably 40 g or more, even more preferably 41 g or more, and may be 42 g or more, 43 g or more, 44 g or more, or 45 g or more. The DAGE content in the composition can be analyzed as total alkoxyglycerol after saponification of DAGE. In one embodiment, the DAGE content per 100 g of the composition can be 14 g or more, 15 g or more, 16 g or more, 17 g or more, or 18 g or more as total alkoxyglycerol after saponification.

[0030] In another embodiment, the amount of DAGE in the composition can be 1 to 50 g per 100 g, preferably 16 to 40 g, more preferably 18 to 35 g, and even more preferably 20 to 30 g.

[0031] The squalene content in the composition of this embodiment can be set as appropriate. In one embodiment, it can be 1 to 50 g per 100 g, preferably 2 to 40 g, more preferably 3 to 30 g, and even more preferably 5 to 20 g.

[0032] (others) In one embodiment, the composition may contain components other than DAGE and squalene. An example of such a component is triglycerides. Triglycerides (sometimes written as triglycerides) are compounds in which three molecules of fatty acids are ester-bonded to one molecule of glycerol, and are also called triacylglycerol or triacylglyceride. In another embodiment, when DAGE in the composition is analyzed by saponification, alkoxyglycerols (e.g., chymyl alcohol, batyl alcohol, ceracyl alcohol) are found.

[0033] If the composition contains triglycerides, the amount can be adjusted as appropriate. In one embodiment, it can be 1 to 50 g per 100 g, preferably 2 to 40 g, more preferably 3 to 30 g, and even more preferably 5 to 30 g.

[0034] In one embodiment, the total amount of alkoxyglycerols when DAGE in the composition is analyzed by saponification is 14.5 to 50 g per 100 g of the composition, preferably 14 to 40 g, more preferably 15 to 35 g, and even more preferably 16 to 30 g. Specifically, the amount of chimyl alcohol is 2 to 18 g per 100 g, preferably 2.2 to 16 g, more preferably 2.6 to 13 g, and even more preferably 3 to 10 g. The amount of batyl alcohol is 1.5 to 18 g per 100 g, preferably 1.7 to 16 g, more preferably 1.9 to 13 g, and even more preferably 2.1 to 10 g. The amount of cerakyl alcohol is 6.4 to 18 g per 100 g, preferably 6.7 to 16 g, more preferably 7 to 13 g, and even more preferably 7.3 to 10 g.

[0035] The composition of this embodiment can be used for the applications of the second embodiment described below.

[0036] [Application] A second embodiment of the present invention relates to a composition comprising DAGE as an active ingredient for improving at least one selected from overall mood state, anger-hostility, fatigue-apathy, confusion-embarrassment, and mental health.

[0037] (Active ingredients) The active ingredient in this embodiment is DAGE. Regarding DAGE, the matters described in the first embodiment also apply to this embodiment. A combination of DAGE and squalene may also be used as the active ingredient. Regarding squalene, the matters described in the first embodiment also apply to this embodiment.

[0038] (Effect / Function) The composition of this embodiment can be used to improve at least one selected from negative mood states, anger, fatigue, lethargy, confusion, and mental health. Here, anger can also be expressed as irritability (a state of anger), hostility or antagonism, fatigue or lethargy as fatigue or lethargy (a state of exhaustion), and confusion as bewilderment or perplexity (a state of being unable to organize one's thoughts), and negative mood states comprehensively represent a state of depressed mood or mental distress such as anger, hostility, fatigue, lethargy, confusion, bewilderment, tension, anxiety (a state of being restless), depression (a state of being depressed), and sadness (a state of being depressed).

[0039] Negative mood states, anger, fatigue (apathy), and confusion can be evaluated, respectively, as General Mood State (TMD), Anger-Hostility (AH), Fatigue-Inertia (FI), and Confusion-Bewilderment (CB), along with Tension-Anxiety (TA), Depression-Dejection (DD), Vigor-Activity (VA), and Friendliness (F), using the "POMS® 2 Japanese Edition" (Kaneko Shobo Co., Ltd.) and the "POMS 2 Japanese Edition Manual" (Kaneko Shobo Co., Ltd.). POMS2 assesses mood states within a given time frame using seven scales—anger-hostility, fatigue-apathy, confusion-embarrassment, tension-anxiety, depression-depression, vitality-energy, and friendliness—along with a "TMD score" that comprehensively represents negative mood states.

[0040] Specifically, for each item, participants answer 6 to 12 predetermined questions on a 5-point scale from 0 to 4. The sum of the scores for each item is used as the raw score to evaluate each item. Additionally, the TMD score is calculated by subtracting the raw VA score from the sum of the raw scores for AH, CB, DD, F, and TA to evaluate the TMD. AH (Anger-Hostility) indicates anger and hostility towards others, intense anger, as well as inner resentment and a desire to be mean to others. CB (Confusion-Bewilderment) indicates bewilderment and low cognitive efficiency, a state of confusion and inability to organize thoughts. DD (Depression-Dejection) indicates a loss of self-confidence, such as feeling worthless, having no hope, or feeling guilty. FI (Fatigue-Apathy) indicates fatigue and a state of decreased awareness and vitality. TA (Tension-Anxiety) represents heightened tension and anxiety, characterized by nervousness and restlessness. VA (Vitality) represents energy, dynamism, and high levels of vitality. F (Friendliness) represents a positive mood state and the influence of interpersonal relationships.

[0041] Mental health (MH) can be assessed using the MOS Short-Form 36-Item Health Survey (SF36v2) Japanese version (distributed by Qualitest Co., Ltd.).

[0042] Specifically, mental health can be assessed by answering questions on a 5-point scale (1-5) in a prescribed questionnaire regarding how individuals perceive their own health. The questions relate to health status; current health status compared to one year ago; difficulty in daily activities; physical or psychological problems in performing work or regular activities (such as housework) in the past month; whether social interactions with colleagues were hindered by physical or psychological reasons; physical pain and whether it interfered with their usual work (J Clin Epidemiol Vol. 51, No. 11, pp. 1037-1044, 1998. J Clin Epidemiol Vol. 51, No. 11, pp. 1045-1053, 1998).

[0043] In one embodiment, the composition is suitable for use in alleviating at least one selected from anger, fatigue, lethargy, and confusion in an object with a negative mood state, i.e., at least one selected from anger-hostility, fatigue-lethargy, and confusion-embarrassment in an object with a depressed mood state, and for improving the mood state. The negative mood state or depressed mood state may be temporary or persistent, but functionally, when the composition is used as a food, it is preferably temporary.

[0044] In one embodiment, the composition can be used to improve at least two or more selected from overall mood state, anger-hostility, fatigue-apathy, confusion-embarrassment, and mental health. In a preferred embodiment, the composition can be used to improve three or more, or four or more, selected from those. In a particularly preferred embodiment, the composition can be used to improve all of them.

[0045] Subjects exhibiting a depressed mood state are, for example, those whose TMD score is greater than 50, more preferably 52 or higher, and even more preferably 55 or higher, as assessed by POMS2.

[0046] (subject) The composition of this embodiment is suitable for administration to subjects who have a low score in at least one of the following: negative mood states, anger, fatigue, lethargy, confusion, and mental health, which is desirable or necessary for improvement.

[0047] In one embodiment, the composition is suitable for administration to individuals who are prone to fatigue and stress on a daily basis. In another embodiment, it is suitable for administration to individuals with a relatively high POMS2 TMD score.

[0048] The subject may be a human or an animal other than a human. In one embodiment, it is preferable that the subject is healthy (for example, not diagnosed with an illness by a doctor). Being healthy may mean, for example, excluding those who fall under the following categories. • Individuals currently receiving treatment for or with a history of malignant tumors, heart failure, or myocardial infarction. • Individuals with implanted pacemakers or cardioverter-defibrillators • Individuals currently receiving treatment for any of the following chronic diseases Arrhythmia, liver damage, kidney damage, cerebrovascular disease, rheumatism, diabetes, dyslipidemia, hypertension, and other chronic diseases Individuals with a history of mental illness such as depression or attention deficit hyperactivity disorder (ADHD) • Individuals undergoing treatment for chronic fatigue syndrome or menopausal symptoms.

[0049] Being healthy can be defined as excluding those who fall under any of the following categories, in addition to those mentioned above. • Those who regularly use pharmaceuticals (including herbal medicines) or supplements. • Individuals who regularly consume Foods for Specified Health Uses or Foods with Function Claims. • Individuals with allergies (to pharmaceuticals or related foods) • Pregnant or breastfeeding women • Individuals with irregular sleep schedules and sleep habits due to night shifts, etc. • Individuals with irregular lifestyles (eating habits, exercise habits, sleep habits, etc.) • Persons engaged in manual labor such as transporting heavy objects

[0050] In one embodiment, the composition may be used non-therapeutically. Non-therapeutic means not intended to treat a disease.

[0051] The target populations mentioned above include adults (15 years of age or older in humans), middle-aged and elderly individuals, and the elderly (65 years of age or older in humans). In a preferred embodiment, the composition is suitable for consumption by individuals aged 30 to under 70 years in humans.

[0052] (others) The composition of this embodiment may contain components other than DAGE, which is the active ingredient. Examples of components other than DAGE include squalene and triglycerides. The matters described for the first embodiment also apply to squalene and triglycerides.

[0053] [Form of composition, etc.] (Food composition, pharmaceutical composition) The composition of the first embodiment and the composition of the second embodiment (hereinafter, both together may be referred to as "the Composition") may be a food composition or a pharmaceutical composition. Unless otherwise specified, food includes general foods, functional foods, and nutritional compositions. Unless otherwise specified, food also includes not only solids but also liquids, such as beverages, drinks, and soups. Functional foods refer to foods that utilize the function of their ingredients and include all types of health foods, such as Foods for Specified Health Uses, Foods with Function Claims, Foods with Nutrient Function Claims, Foods for Special Dietary Uses, Nutritional Supplements, Health Supplements, Beauty Foods, etc.

[0054] (Route of administration) This composition can be taken orally. In relation to the present invention, "ingestion" is used not only when giving a food composition to a subject, but also when administering a pharmaceutical composition to a subject. "Ingestion" can be read as "administration."

[0055] (Content and dosage of active ingredients) The amount of active ingredient in this composition is sufficient to produce the desired effect. The amount of active ingredient in this composition can be appropriately determined by considering various factors such as the age, weight, and symptoms of the person receiving the composition.

[0056] In one embodiment, the composition can be formulated so that the daily intake of the active ingredient is, for example, 50 mg or more, and may be 100 mg or more, 150 mg or more, 200 mg or more, 250 mg or more, 300 mg or more, or 350 mg or more. In a preferred embodiment, the composition can be formulated so that the daily intake of the active ingredient is 360 mg or more, and more preferably 400 mg or more. The upper limit can be set as appropriate, and the lower limit may be, in any case, 1800 mg or less, 1000 mg or less, or 500 mg or less. One unit of the composition can be administered to the subject once a day, or it may be administered to the subject multiple times a day, for example, three times. In one embodiment, if the composition also contains squalene in addition to the active ingredient, the composition can be formulated so that the daily intake of squalene is, for example, 5 mg or more, and may be 10 mg or more, 20 mg or more, 50 mg or more, 100 mg or more, or 150 mg or more. The upper limit can be set as appropriate, and the lower limit can be set to, for example, 1000 mg or less, or 500 mg or less, regardless of the case.

[0057] The amount of active ingredient per unit of the composition (e.g., per capsule) can be, for example, 10 mg or more, 20 mg or more, 30 mg or more, 40 mg or more, 50 mg or more, preferably 60 mg or more, more preferably 80 mg or more, and even more preferably 100 mg or more. The upper limit can be set as appropriate, and the lower limit may be, in any case, 500 mg or less, 400 mg or less, or 300 mg or less. One unit of the composition can be administered to a subject in the form of several units per day or as a single dose, for example, 1 to 9 units, 2 to 8 units, 3 to 7 units, or 4 to 6 units, and may be administered to the subject multiple times a day, for example, 3 times.

[0058] Since this composition is derived from natural products with a history of consumption, it can be administered repeatedly or over a long period of time, for example, for 3 days or more, 1 week or more, 2 weeks or more, preferably 4 weeks or more, more preferably 8 weeks or more, for example 12 weeks. Repeated or long-term administration should preferably be done continuously every day without interruption.

[0059] (Other ingredients, additives) This composition may contain ingredients that are acceptable as food or pharmaceuticals. Examples of ingredients that are acceptable as food or pharmaceuticals include lipids, proteins, amino acids, vitamins (e.g., vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, biotin, folic acid, pantothenic acid, and nicotinic acid), minerals (e.g., copper, zinc, iron, cobalt, manganese), and astaxanthin. Astaxanthin has the effect of protecting and stabilizing DAGE and squalene from peroxidation.

[0060] This composition may further contain additives that are acceptable as food or pharmaceuticals. Examples of such additives include excipients, surfactants, binders, disintegrants, lubricants, solubilizers, suspending agents, coatings, colorants, preservatives, buffers, pH adjusters, emulsifiers, stabilizers, sweeteners, antioxidants, flavorings, and acidulants.

[0061] (Dosage form / form) In one embodiment, the composition can be in any form, such as soft capsules, hard capsules, tablets, coated tablets, sugar-coated tablets, or drinks.

[0062] (others) In the manufacture of this composition, the stage of compounding the active ingredient can be selected as appropriate. The compounding stage is not particularly limited as long as it does not significantly impair the properties of the active ingredient.

[0063] In one embodiment, the composition may display its intended use, the function of the active ingredient, and how to use it based on that function.

[0064] Specific examples of its effects include: alleviating temporary anxiety, tension, fear, and anger in the workplace and at home, and helping to maintain mental health; alleviating temporary mood swings caused by anger, hostility, confusion, bewilderment, and lethargy, and supporting the maintenance of mental health; improving mood swings caused by temporary anxiety, fatigue, and lethargy; improving temporary anxiety, fatigue, and lethargy, and helping to maintain mental health; and supporting the reduction of temporary, recognizable states of confusion (inability to organize thoughts), lethargy (exhaustion), depression (melancholy), irritability (anger), and anxiety (restlessness) in people who are prone to feeling tired (or stressed) on a daily basis.

[0065] In one embodiment, the composition is labeled with a recommendation for administration to a specific target. Examples of targets are as described above.

[0066] Display can be explicit or implicit. Examples of explicit display include direct markings on tangible objects such as the product itself, packaging, containers, labels, and tags. Examples of implicit display include advertising and promotional activities by place or means, such as websites, stores, brochures, exhibitions, seminars, books, newspapers, magazines, television, radio, mail, email, and audio.

[0067] The present invention will be described in more detail below using examples. [Examples]

[0068] [Example 1: Evaluation of DAGE's functionality] I. Method 1. Purpose This study will examine the anti-psychological stress effects of consuming the test food in healthy individuals for 12 weeks.

[0069] 2. Examination Design Test objective: Efficacy and safety Study type: Intervention Basic design: Parallel group comparison Randomization: Randomization Blinding: Double-blind Control: Placebo control Number of test groups: 2 groups Number of tests: 3 (screening and before intake, 6 weeks after intake, 12 weeks after intake) Number of screening cases (*): 88 Target number of cases: 44 Number of cases treated: 48 *Screening case count: The minimum number of cases to participate in the screening test to select the target number of cases and the number of cases to be implemented.

[0070] 3. Eligibility Criteria (1) Selection Criteria This examination selected candidates from among those who met the following criteria i-v, based on criterion vi. i. Japanese ii. Both men and women iii. Ages 30 to under 70 iv. Healthy individuals v. People who are prone to feeling tired or stressed on a regular basis vi. Participants who agreed to participate in the study and had a relatively high TMD score on POMS2.

[0071] Subjects who did not meet the following exclusion criteria were considered healthy. i. Individuals currently receiving treatment for or with a history of malignant tumors, heart failure, or myocardial infarction. ii. Individuals with implanted pacemakers or cardioverter-defibrillators. iii. Individuals currently receiving treatment for any of the following chronic diseases Arrhythmia, liver damage, kidney damage, cerebrovascular disease, rheumatism, diabetes, Dyslipidemia, hypertension, and other chronic diseases iv. Individuals who regularly consume Foods for Specified Health Uses or Foods with Function Claims. v. Individuals who regularly use pharmaceuticals (including herbal medicines) or supplements. vi. Individuals with allergies (to pharmaceuticals, test foods, or related foods) vii. Pregnant, breastfeeding, or intending to become pregnant during the examination period. viii. Individuals who have participated in other clinical trials within the 28 days prior to the date of obtaining informed consent, or who are scheduled to participate in other clinical trials during the trial period. ix. Individuals with a history of mental illness such as depression or attention deficit hyperactivity disorder (ADHD). x. Individuals whose sleep duration and sleep habits are irregular due to night shifts, etc. xi. Individuals with irregular lifestyles (e.g., eating habits, exercise habits, sleep habits) xii. Individuals undergoing treatment for chronic fatigue syndrome or menopausal disorders. xiii. Persons engaged in manual labor such as transporting heavy objects. xiv. Other persons whom the principal investigator deems unsuitable to be included in this study.

[0072] 4. Intervention (1) Test food Test food group: Foods containing shark liver oil Placebo group: Placebo (2) Active ingredient Squalene, DAGE (Diacylglyceryl ether) (3) Examination period Intervention period: 12 weeks (4) Dosage and administration Test food group: Take 4 tablets daily with water or lukewarm water without chewing. Placebo group: Take 4 tablets daily with water or lukewarm water without chewing.

[0073] [Table 1]

[0074] 5. Measurement items (1) POMS2 Japanese Edition (Profile of Mood States 2nd Edition; POMS2) i. Implementation details: The current mood state of the test participants will be assessed using the Japanese version of POMS2. ii. Survey items: TMD (Total Mood Disturbance), Tension-Anxiety (TA), Depression-Dejection (DD), Anger-Hostility (AH), Vigor-Activity (VA), Fatigue-Inertia (FI), Confusion-Bewilderment (CB), Friendliness (F), and each questionnaire item. iii. Evaluation method: Measurements will be taken using screening / pre-ingestion tests, tests 6 weeks after ingestion, and tests 12 weeks after ingestion. iv. POMS2 is a test that can quickly assess not only relatively long-lasting emotional states but also fluctuating, transient emotions. It includes seven factors: AH, CB, DD, FI, TA, VA, and F, and a comprehensive mood index called TMD (= AH + CB + DD + FI + TA - VA). The standardized (T) scores used in the POMS2 assessment are values ​​that normalize the measurement criteria, with a mean of 50 and a standard deviation of 10. Lower T scores for TMD, AH, CB, DD, FI, and TA, which assess negative mood states, indicate a better state, while higher T scores for VA and F, which assess positive mood states, indicate a better state. (Heuchert JP, McNair DM. POMS2 Japanese Version Adult - Full Item Version. Kazuhito Yokoyama, editor. Tokyo: Kaneko Shobo; 2015)

[0075] (2) MOS Short-Form 36-Item Health. Survey (SF36v2) i. Implementation details: Health-related quality of life will be assessed using SF-36v2. ii. Survey item: Mental Health (MH) iii. Evaluation Method: Summary scores and subscales are calculated using scoring based on national standard values. Measurements are taken during screening / pre-intake testing and 6-week post-intake testing.

[0076] 6. Outcomes Effectiveness evaluation items i. Primary Outcomes TMD, TA, DD, AH, VA, FI, CB, F(POMS2) in tests conducted 6 weeks and 12 weeks after ingestion. ii. Secondary outcomes MH levels observed 6 weeks after ingestion

[0077] II. Results The results summary (MH results for POMS2 and SF36v2) is shown in the table below.

[0078] [Table 2]

[0079] [Table 3]

[0080] n: Number of cases / Mean: Mean value / SD: Standard deviation / Med: Median / Min: Minimum value / Max: Maximum value / EMM: Estimated marginal mean / Δ: Difference between groups (test food group - placebo group) / SE: Standard error / 95%CI-: Lower limit of 95% confidence interval / 95%CI+: Upper limit of 95% confidence interval / P: Significance probability / †: Primary outcome / VISIT1: Screening and pre-intake examination (baseline) / VISIT2: Examination 6 weeks after intake / VISIT3: Examination 12 weeks after intake / *: Welch's t-test / #: Linear mixed model with baseline value as covariate, time point, group, interaction between time point and group, interaction between baseline value and time point, and study participant as factors (Δ is the difference between groups of estimated marginal means) / Orange: Significantly significant difference (P < 0.05)

[0081] In summary, 12 weeks of consumption of the test food contributed to the reduction of mental stress with clinical significance, particularly improving negative mood states such as TMD (Mood Disorders, Affective or Psychological Distress, and a General Indicator of Subjective Well-being), AH (Anger and Resentment Towards Others), FI (Fatigue, Apathy, and Low Energy), and CB. Furthermore, 6 weeks of consumption of the test food was suggested to improve mental health.

[0082] [Example 2: Analysis of DAGE] (1)Equipment / equipment Rotary evaporator Normal-phase solid-phase extraction column High-performance liquid chromatography system Charged particle detector

[0083] (2) Reagents 2,2,4-Trimethylpentane (isooctane, for high-performance liquid chromatography) tert-Butyl Methyl Ether (for high-performance liquid chromatography) Formic acid (for LC / MS) Chloroform (special grade) n-Hexane (for high-performance liquid chromatography)

[0084] (3) Operation 〇Standard product 1,2-dipalmitoyl-3-O-hexadecyl-rac-glycerol was used as the standard. This product was synthesized by the following method. Under a nitrogen atmosphere, 3-(hexadecyloxy)-1,2-propanediol (89.5 mg, 0.28 mmol) dissolved in anhydrous dichloromethane (6 mL) was mixed with palmitic acid (201.5 mg, 0.79 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (124.3 mg, 0.80 mmol), and 4-dimethylaminopyridine (8.0 mg, 0.066 mmol), and the mixture was stirred at room temperature for 1.5 hours. After concentrating the reaction mixture under reduced pressure, it was applied to a normal-phase silica gel column (5 g) and purified with hexane-ethyl acetate (50:1). The solvent was then removed by distillation to obtain a white solid (150.1 mg, 0.19 mmol, yield: 67%, purity: 97.63% (purity: quantitative NMR method)). The obtained 1,2-dipalmitoyl-3-O-hexadecyl-rac-glycerol was accurately weighed, dissolved in isooctane, and used as a standard for DAGE quantification. A calibration curve (quadratic equation y = ax) was created using the peak area values ​​and concentrations detected by HPLC-charged particle detector. 2 A regression equation (using + bx + c) was created.

[0085] ○ Method for preparing the sample solution (test food in Example 1) The capsule was cut open, approximately 10 mg of the contents were weighed out, hexane was added, and the volume was adjusted to 10 mL in a volumetric flask. The solution was further diluted 50-fold with hexane, and HPLC analysis was performed. The concentration of DAGE was calculated from the calibration curve of the standard substance.

[0086] 〇HPLC conditions ·HPLC equipment: Nexera X2 (Shimadzu) • Detection device: Charged particle detector (Thermo Fisher SCIENTIFIC) • Column: SunShell HILIC-S, 2.6 μm, 2.1 × 150 mm (ChromanNik Technologies Inc.) ·Mobile phase: A: 2,2,4-Trimethylpentane, B: 0.01% (v / v) formic acid added tert-Butyl Methyl Ether ·Flow rate: 0.6 mL / min • Gradient: B conc. 0.5% (0-1.5 min), 0.5-1.5% (1.5-1.51 min), 1.5-11% (1.51-7.5 min), 25% (7.5-10 min), 25-0.5% (10-10.5 min), 0.5% (10.5-20 min) • Column oven: 35℃ ·Injection volume: 1 μL

[0087] As a result, a peak was observed around 4.7 minutes of retention in the DAGE standard. A peak was also observed around 4.7 minutes of retention in the test food of Example 1.

[0088] [Example 3: Analysis of DAGE content in commercially available products] The DAGE content of commercially available products was measured using the method of Example 2. The results are shown in the table below.

[0089] [Table 4]

Claims

1. A. Formula I: 【Chemistry 1】 (In formula I, R １ R is an aliphatic hydrocarbon group with a degree of unsaturation of 0 to 2 and 12 to 24 carbon atoms. ２ R is an acyl group with a degree of unsaturation of 0 to 6 and 12 to 24 carbon atoms. ３ (This refers to an acyl group with a degree of unsaturation of 0 to 6 and 12 to 24 carbon atoms.) Diacylglyceryl ether (DAGE) represented by, and B. Squalene Includes, A composition in which the A:B (mass ratio) is greater than 1 to 7.5:

1.

2. The composition according to claim 1, formulated to ensure that 400 mg or more of DAGE is ingested per day.

3. A. Formula I: 【Chemistry 2】 (In formula I, R １ R is an aliphatic hydrocarbon group with a degree of unsaturation of 0 to 2 and 12 to 24 carbon atoms. ２ R is an acyl group with a degree of unsaturation of 0 to 6 and 12 to 24 carbon atoms. ３ (This refers to an acyl group with a degree of unsaturation of 0 to 6 and 12 to 24 carbon atoms.) Diacylglyceryl ether (DAGE) represented by, and B. Squalene Includes, The mass ratio A:B is greater than 1 to 7.5:

1. A composition for improving at least one of the following: negative mood states, anger, fatigue, lethargy, confusion, and mental health.

4. A composition for improving mood, comprising DAGE and squalene as defined in claim 3, wherein the DAGE:squalene (mass ratio) is greater than 1 to 7.5:1, and for alleviating at least one selected from anger, fatigue, lethargy, and confusion in a subject who is experiencing a negative mood state.

5. The composition according to claim 3, further comprising a triglyceride.

6. The composition according to claim 3, for administration to subjects who are prone to stress on a daily basis, or who are in a negative mood state or a depressed mood state.

7. A composition according to any one of claims 1 to 4, for administering 400 mg or more of DAGE per day for 12 weeks or more.

Images