Composition and use thereof

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] The present invention relates to a composition containing diacylglyceryl ether (DAGE) and uses thereof. [Background technology]

[0002] Diacylglyceryl ether (DAGE) is widely distributed in aquatic animal fats and oils, and is particularly abundant in fats and oils derived from shark and squid livers. DAGE has several known functions. For example, Patent Document 1 describes an oral agent for preventing and treating UV-induced skin damage, which contains diacylglyceryl ether as an active ingredient. Patent Document 2 also describes a composition for improving sleep quality, which contains a fish roe lipid preparation and diacylglyceryl ether (DAGE).

[0003] Furthermore, it has been reported that DAGE has an effect on circadian rhythms (Non-Patent Document 1), that when healthy individuals who are temporarily dissatisfied with their sleep habit take salmon roe oil containing DHA and EPA or deep-sea shark liver oil containing DAGE, the proportion of deep sleep and REM sleep increases, improving sleep quality, and that it relieves anxiety, tension, and depression in individuals with low vitality, improves vitality and energy, and reduces daytime sleepiness (Non-Patent Documents 2 and 3).Furthermore, the effect of consuming foods containing deep-sea shark liver oil on the vitality of healthy Japanese individuals has been reported (Non-Patent Document 4). [Prior art documents] [Patent documents]

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

[0005] [Non-Patent Document 1] Rio Kobayashi et al., Journal of Chronobiology, Vol. 28, No. 2, p. 216, 2022 [Non-patent document 2] Nakagawa, Iku, et al., Evaluation of the sleep quality improvement and anti-stress effects of processed oils containing salmon roe oil-derived DHA, salmon roe oil-derived EPA, and deep-sea shark liver oil-derived DAGE in people with poor sleep quality - A randomized, double-blind, placebo-controlled, parallel-group comparative study, Jpn Pharmacol Ther (Pharmacology and Therapeutics), Vol. 49, No. 6, p. 977-990, 2021 [Non-patent document 3] Yuka Takada et al., The forefront of development of functional foods related to fatigue, stress, and sleep: Increased REM and deep sleep by oil-processed foods containing DHA, EPA, and DAGE (diacylglyceryl ether), Monthly Fine Chemical, Vol. 52, No. 4, pp. 40-48, 2023 [Non-patent document 4] Yoshinaga, Y. et al., The effect of ingestion of foods containing deep-sea shark liver oil on vitality in healthy Japanese subjects - A randomized, double-blind, placebo-controlled, parallel-group comparative study -, Jpn Pharmacol Ther (Pharmacology and Therapy), Vol. 46, No. 9, p. 1399-1425, 2021 Summary of the Invention [Problem to be solved by the invention]

[0006] It would be desirable to provide a novel, highly effective composition containing DAGE, and it would also be desirable to provide a new use for DAGE. [Means for solving the problem]

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

[0008] [ka]

[0009] (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 R 2 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. Diacylglyceryl ether (DAGE) represented by the formula: B. Squalene Including, A composition in which the mass ratio of A:B is 0.9 to 9:1. [2] The composition described in 1, formulated so that 400 mg or more of DAGE is ingested per day. [3] Formula I:

[0010] [ka]

[0011] (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 R 2 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. A composition for improving at least one selected from negative mood states, anger, fatigue, lethargy, confusion, and mental health, comprising a diacylglyceryl ether (DAGE) represented by the formula: [4] A composition for improving a mood state by relieving at least one of anger, fatigue, lethargy, and confusion in a subject experiencing a negative mood state, comprising a DAGE as defined in 3. [5] The composition described in 3 or 4, wherein the composition further contains squalene. [6] The composition described in any one of 1 to 5, further comprising a triglyceride. [7] The composition described in any one of 1 to 6, intended for administration to a subject who is prone to stress or who is in a negative mood state. [8] The composition described in any one of items 1 to 7, for ingestion of 400 mg or more of DAGE per day for 12 weeks or more. [9] The composition described in any one of items 1 to 7, for continuous intake of 400 mg or more of DAGE per day for 12 weeks or more. [Effects of the Invention]

[0012] One aspect of the present invention provides a composition comprising a diacylglyceryl ether and squalene. Another aspect provides a composition comprising a diacylglyceryl ether (DAGE) for improving at least one selected from overall mood state, anger-hostility, fatigue-apathy, confusion-bewilderment, and mental health. DETAILED DESCRIPTION OF THE INVENTION

[0013] In the present invention, the numerical range x to y includes the end values ​​x and y. In the present invention, ratios and percentages are based on mass unless otherwise specified.

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

[0015] (diacylglyceryl ether) The composition of this embodiment contains diacylglyceryl ether (DAGE) represented by formula I. DAGE is also called alkyl diacylglycerol. DAGE has a structure in which a fatty acid is ester-bonded to two of the three hydroxyl groups of glycerol (glycerin) and a hydrocarbon is ether-bonded to the remaining group, and is represented by formula I below.

[0016] [ka]

[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 the formula (I) include those in which the ratio of carbon number to degree of unsaturation is 24:1, 22:1, 20:1, 18:2, 18:1, 18:0, 16:1, 16:0, 14:0, or 12:0. Those in which the ratio of carbon number to degree of unsaturation is 18:1, 18:0, 16:1, or 16:0 are particularly preferred.

[0019] R 2 Examples of acyl groups represented by the formula (I) include those with a carbon number: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), 20:4 (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).

[0020] Particularly preferred are those with a carbon number: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, octadecenoic acid), and 16:0 (derived from palmitic acid).

[0021] R 3Examples of acyl groups represented by the formula (I) include those with a carbon number: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), 20:4 (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] Particularly preferred are those with a carbon number: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, octadecenoic acid), and 16:0 (derived from palmitic acid).

[0023] DAGE is known to be found in large amounts in the liver oil of sharks, particularly deep-sea sharks. In addition to sharks, DAGE is also known to be found in squid (liver), some fish (muscle), cows, humans (milk), and the silver shark (Chimaera phantasma). The source of DAGE used in the composition of this embodiment is not particularly limited. Furthermore, in this embodiment, shark liver oil may be used as DAGE, or a concentrate, crude product, or purified product of shark liver oil may also be used. DAGE produced by a microorganism or a synthetic product may also be used.

[0024] In one embodiment, DAGE can be contained in deep-sea shark liver oil. Deep-sea shark liver oil is oil extracted from the liver of sharks that live in the deep sea, such as the scleractinian shark, the blue shark, and the dogfish. Liver oil can be extracted by conventional methods. For example, the shark liver is removed, finely crushed in a crusher, and left to stand for 1 to 4 days to separate the oil and solid components, and the oil can be extracted to obtain liver oil. The liver oil may be further refined by filtering to remove fine solid components. Alternatively, commercially available deep-sea shark liver oil can be used. In addition, alkylglycerols contained in shark liver oil have been reported to have immune-activating functions (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 (IUPAC name: 2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene) is an oily substance that belongs to the triterpene group.

[0026] Squalene is found in large amounts in shark liver oil, and is also found in vegetable oils such as olive oil, rice bran oil, wheat germ oil, sesame oil, soybean oil, etc. Algae that produce squalene are also known (Patent Nos. 6265407 and 5942197).

[0027] The raw material of squalene used in this embodiment is not particularly limited. In one aspect, the above-mentioned oils may be used as squalene, or concentrates, crude products, or purified products of the above-mentioned oils may be used. Squalene has been reported to have antioxidant properties, and its inclusion 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 adjusted appropriately. In one aspect, 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. The A:B ratio in commercially available functional foods containing DAGE is analyzed to be 0.07 to 0.77:1.

[0029] The content of DAGE in the composition of this embodiment can be adjusted appropriately. In one aspect, it can be 38 g or more per 100 g (in the case of formulations such as capsules, this is per 100 g of mass including the coating; the same applies below), preferably 39 g or more, more preferably 40 g or more, and 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 content of DAGE in the composition can be determined by saponifying DAGE and analyzing it as total alkoxyglycerol. In one aspect, the content of DAGE 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 when saponified.

[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 content of squalene in the composition of this embodiment can be adjusted appropriately, and in one aspect, 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. Examples of such components include triglycerides. Triglycerides (sometimes written as triglycerides) refer to one molecule of glycerol to which three molecules of fatty acid are ester-bonded, and are also called triacylglycerols or triacylglycerides. Furthermore, in one embodiment, when DAGE in the composition is saponified and analyzed, it is found to contain alkoxyglycerols (e.g., chimyl alcohol, batyl alcohol, and selachyl alcohol).

[0033] When the composition contains triglyceride, the amount can be adjusted appropriately. In one embodiment, the amount 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 in the composition, as determined by saponification and analysis of DAGE, is 14.5 to 50 g, preferably 14 to 40 g, more preferably 15 to 35 g, and even more preferably 16 to 30 g, per 100 g of the composition. Specifically, the amount of chimyl alcohol is 2 to 18 g, preferably 2.2 to 16 g, more preferably 2.6 to 13 g, and even more preferably 3 to 10 g, per 100 g. The amount of batyl alcohol is 1.5 to 18 g, preferably 1.7 to 16 g, more preferably 1.9 to 13 g, and even more preferably 2.1 to 10 g, per 100 g. The amount of selachyl alcohol is 6.4 to 18 g, preferably 6.7 to 16 g, more preferably 7 to 13 g, and even more preferably 7.3 to 10 g, per 100 g.

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

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

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

[0038] (Action / Function) The composition of the present embodiment can be used to improve at least one selected from negative mood states, anger, fatigue, lethargy, confusion, and mental health. Here, anger can refer to irritation (an angry state), hostility or hostility, fatigue or lethargy can refer to fatigue or lethargy (an exhausted state), and confusion can refer to bewilderment or confusion (a state of being unable to organize one's thoughts), etc., and the negative mood states collectively refer to depressed mood states or mental disorders such as anger, hostility, fatigue, lethargy, confusion, bewilderment, tension, anxiety (a restless state), depression (a depressed state), and dejectedness (a gloomy state).

[0039] Negative mood states, anger, fatigue (apathy), and confusion can be assessed as general mood state (TMD), Anger-Hostility (AH), Fatigue-Inertia (FI), and Confusion-Bewilderment (CB), respectively, along with Tension-Anxiety (TA), Depression-Dejection (DD), Vigor-Activity (VA), and Friendliness (F) using the POMS (registered trademark) 2 Japanese Edition (Kaneko Shobo Publishing Co., Ltd.) and the POMS 2 Japanese Edition Manual (Kaneko Shobo Publishing Co., Ltd.). POMS2 assesses mood states over a specified time frame using seven scales: anger-hostility, fatigue-apathy, confusion-bewilderment, tension-anxiety, depression-depression, vigor-vitality, and friendliness, as well as a "TMD score" that comprehensively represents negative mood states.

[0040] Specifically, participants answer six to twelve questions for each item on a five-point scale ranging from 0 to 4. The sum of the scores for each item is used as a raw score, which can be used to evaluate each item. TMD can also be evaluated by subtracting the raw score for VA from the sum of the raw scores for AH, CB, DD, F, and TA to calculate a TMD score. AH (Anger-Hostility) indicates anger and resentment toward others, intense anger, as well as inner resentment and a desire to be mean to others. CB (Confusion-Bewilderment) indicates bewilderment, low cognitive efficiency, and a state of confusion and inability to organize thoughts. DD (Depression-Dejection) indicates a loss of confidence, including feelings of worthlessness, hopelessness, and guilt. FI (Fatigue-Apathy) indicates fatigue and a state of decreased consciousness and energy. TA (Tension-Anxiety) indicates increased tension and anxiety, characterized by nervousness and restlessness. VA (Vibrancy) represents high energy, dynamism, and vitality. F (Friendship) represents a positive mood state and interpersonal influence.

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

[0042] Specifically, mental health can be assessed by answering questions about how people view their own health on a 5-point scale (1 to 5) in a prescribed questionnaire. The questions include health status, current health status compared to one year ago, difficulty with daily activities, physical or psychological problems in the past month with work or usual activities (e.g., housework), whether social interactions with peers were hindered by physical or psychological reasons, and whether bodily pain interfered with 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 a subject experiencing a negative mood state, i.e., at least one selected from anger-hostility, fatigue-lethargy, and confusion-bewilderment in a subject experiencing a decreased mood state, thereby improving the mood state. The negative mood state or decreased mood state may be temporary or persistent, but when the composition is used as a food product, it is preferably temporary in terms of its function.

[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-bewilderment, and mental health. In a preferred embodiment, the composition can be used to improve three or more, or four or more selected from these. In a particularly preferred embodiment, the composition can be used to improve all of them.

[0045] A subject with a depressed mood state is one whose TMD is greater than 50, more preferably greater than 52, and even more preferably greater than 55, as assessed, for example, by POMS2.

[0046] (subject) The composition of this embodiment is suitable for administration to a subject for whom improvement in at least one selected from negative mood states, anger, fatigue, lethargy, confusion, and mental health is desirable or necessary, i.e., a subject who has a low rating in at least one selected from negative mood states, anger, fatigue, lethargy, confusion, and mental health.

[0047] In one embodiment, the composition is suitable for administration to subjects who tend to feel fatigue or stress on a daily basis, and in another embodiment, the composition is suitable for administration to subjects who have a relatively high TMD score on the POMS2.

[0048] The subject may be a human or a non-human animal. In one aspect, the subject is preferably healthy (e.g., not diagnosed with a disease by a doctor). A healthy subject may be, for example, a subject excluding any of the following: -Those currently undergoing treatment for or with a history of malignant tumor, heart failure, or myocardial infarction -People with pacemakers or implantable cardioverter defibrillators -Those currently undergoing treatment for the following chronic diseases Cardiac arrhythmia, liver damage, kidney damage, cerebrovascular disease, rheumatism, diabetes, dyslipidemia, hypertension, and other chronic diseases -Those with a history of mental illness such as depression or attention deficit hyperactivity disorder (ADHD) Those currently undergoing treatment for chronic fatigue syndrome or menopausal disorders

[0049] In addition to the above, being healthy may also mean excluding those who fall under the following categories: Those who regularly take medicines (including herbal medicines) or supplements Those who regularly consume foods for specified health uses or foods with functional claims -People with allergies (medicine / food-related) Pregnant or breastfeeding women Those who have irregular sleep hours and habits due to night shifts, etc. -People with irregular lifestyle habits (eating habits, exercise habits, sleeping habits, etc.) Those engaged in physical labor such as transporting heavy objects

[0050] In one embodiment, the composition can be used non-therapeutically, meaning not intended to treat a disease.

[0051] Such subjects include adults (humans aged 15 years or older), middle-aged and elderly people (humans aged 65 years or older), and in a preferred embodiment, the composition is suitable for consumption by a human subject aged 30 years or older but younger than 70 years.

[0052] (others) The composition of this embodiment may contain ingredients other than the active ingredient DAGE. Examples of ingredients other than DAGE include squalene and triglycerides. Regarding squalene and triglycerides, the same explanations as for the first embodiment also apply to this embodiment.

[0053] [Form of composition, etc.] (food compositions, pharmaceutical compositions) The composition of the first embodiment and the composition of the second embodiment (hereinafter, both may be collectively referred to as the present composition) can be a food composition or a pharmaceutical composition. Food includes general foods, functional foods, and nutritional compositions, unless otherwise specified. Food also includes not only solids but also liquids, such as beverages, health supplements, and soups, unless otherwise specified. Functional foods refer to foods that utilize the functions of ingredients, and include all health foods, such as foods for specified health uses, foods with functional claims, foods with nutrient functions, foods for special dietary uses, nutritional supplements, health supplements, supplements, and beauty foods.

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

[0055] (Active ingredient content and dosage) The content of the active ingredient in the composition may be any amount that achieves the desired effect. The content of the active ingredient in the composition can be appropriately determined taking into consideration various factors such as the age, weight, and symptoms of the subject to be ingested or administered.

[0056] In one embodiment, the composition can be formulated to provide a daily intake of the active ingredient of, 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 to provide a daily intake of 360 mg or more, and more preferably 400 mg or more. The upper limit can be set as appropriate, and regardless of the lower limit, it may be, for example, 1800 mg or less, 1000 mg or less, or 500 mg or less. One unit of the composition can be administered to a subject once a day, or multiple times a day, for example, three times a day. In one embodiment, when the composition contains squalene in addition to the active ingredient, the composition can be formulated to provide a daily intake of squalene of, 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 whatever the lower limit, it may be, for example, 1000 mg or less, or 500 mg or less.

[0057] The content of the active ingredient per unit of the composition (e.g., one 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 appropriately, and whatever the lower limit, it may be, for example, 500 mg or less, 400 mg or less, or 300 mg or less. One unit of the composition can be taken by a subject in several units, for example, 1 to 9, 2 to 8, 3 to 7, or 4 to 6, per day or as a single dose, and may be taken by a subject multiple times per day, for example, 3 times.

[0058] Since the composition is derived from natural products that have been consumed, it may be taken 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. It is preferable that repeated or long-term intake is continued every day without interruption.

[0059] (Other ingredients, additives) The composition may contain ingredients acceptable for use as food or medicine. Examples of ingredients acceptable for use as food or medicine 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 acids), minerals (e.g., copper, zinc, iron, cobalt, and manganese), astaxanthin, etc. Astaxanthin has the effect of protecting and stabilizing DAGE and squalene from peroxidation.

[0060] The composition may further contain additives acceptable for use as food or pharmaceuticals, such as excipients, surfactants, binders, disintegrants, lubricants, solubilizers, suspending agents, coating agents, colorants, preservatives, buffers, pH adjusters, emulsifiers, stabilizers, sweeteners, antioxidants, flavors, and acidulants.

[0061] (Dosage form / shape) In one embodiment, the composition can be in any form, such as a soft capsule, hard capsule, tablet, coated tablet, sugar-coated tablet, or drinkable preparation.

[0062] (others) In the production of the present composition, the stage of compounding the active ingredient can be appropriately selected, and there are no particular limitations on the stage of compounding as long as the properties of the active ingredient are not significantly impaired.

[0063] In one embodiment, the composition can be labeled with the intended use (application), the function of the active ingredient, and how to use it based on that function.

[0064] Specific examples of claims include: Relieves temporary anxiety, tension, fear, anger, etc. at work or at home, and helps maintain mental health; Relieves temporary low moods caused by anger, hostility, confusion, bewilderment, lethargy, etc., and supports maintaining mental health; Improves low moods caused by temporary anxiety, fatigue, and lethargy; Improves temporary anxiety, fatigue, and lethargy, and helps maintain mental health; Supports the reduction of temporary, self-conscious states of confusion (inability to think clearly), lethargy (exhaustion), depression (depression), irritability (anger), and anxiety (restlessness) in people who tend to feel tired (and stressed) on a daily basis; etc.

[0065] In one embodiment, the composition is labeled to recommend administration to a specific subject. Examples of subjects for which the labeling is provided are as described above for subjects.

[0066] Representation can be explicit or implicit. Examples of explicit representation are direct inscriptions on tangible objects such as the product itself, packaging, containers, labels, tags, etc. Examples of implicit representation (which can also be called implied) include advertising and promotional activities by place or means such as websites, storefronts, pamphlets, exhibitions, seminars, books, newspapers, magazines, television, radio, mail, email, and voice.

[0067] The present invention will now be described in more detail with reference to examples. [Example]

[0068] Example 1: Evaluation of the functionality of DAGE I. Method 1. Purpose The anti-psychotic stress effects of the test food will be verified when healthy individuals take it for 12 weeks.

[0069] 2. Study Design Study 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 times (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: 48 * Number of screening cases: The minimum number of cases participating 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 In this study, subjects were selected from those who met the following criteria i to v, based on criteria vi. i. Japanese ii. Both men and women iii. 30 years old or older but younger than 70 years old iv. Healthy individuals v. People who are prone to fatigue and stress vi. Subjects with relatively high TMD scores on POMS2 who agreed to participate in the study

[0071] Subjects who did not meet the following exclusion criteria were considered healthy. i. Those currently undergoing treatment for or with a history of malignant tumor, heart failure, or myocardial infarction ii. Persons with pacemakers or implantable cardioverter defibrillators iii.Those currently undergoing treatment for the following chronic diseases: Arrhythmia, liver damage, kidney damage, cerebrovascular disease, rheumatism, diabetes, Dyslipidemia, hypertension, and other chronic diseases iv. People who regularly consume foods for specified health uses or foods with functional claims v. Those who regularly take medicines (including herbal medicines) or supplements vi. People with allergies (medicines, test food-related foods) vii. Pregnant, breastfeeding, or intending to become pregnant during the study period viii. Those who have participated in other clinical trials within the 28 days prior to the date of consent acquisition, or those who plan to participate during the trial period. ix. Those with a history of mental illness such as depression or attention deficit hyperactivity disorder (ADHD) x. Persons who have irregular sleeping hours and habits due to night shifts, etc. xi. People with irregular lifestyle habits (eating habits, exercise habits, sleeping habits, etc.) xii. Those currently undergoing treatment for chronic fatigue syndrome or menopausal disorders xiii. Persons engaged in physical labor such as transporting heavy objects xiv. Any other person who the investigator deems inappropriate for this study

[0072] 4. Intervention (1) Test food Test food group: Shark liver oil-containing foods Placebo group: placebo (2) Involved components Squalene, DAGE (diacylglyceryl ether) (3) Examination period Intervention period: 12 weeks (4) Dosage and administration Test food group: Take 4 tablets a day 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 version (Profile of Mood States 2nd Edition; POMS2) i. Procedure: The current mood state of the study 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 question item iii. Evaluation method: Measurements will be made at screening and pre-intake tests, 6-week intake tests, and 12-week intake tests. 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 TMD (= AH + CB + DD + FI + TA - VA) as an indicator of overall mood state. The standardized (T) scores used in POMS2 assessment are calculated by normalizing the measurement standard, 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, and higher T-scores for VA and F, which assess positive mood states, indicate a better mood (Heuchert JP, McNair DM. POMS2 Japanese Version for Adults - Complete Edition. Yokoyama Kazuhito, editor. Tokyo: Kaneko Shobo; 2015).

[0075] (2) MOS Short-Form 36-Item Health. Survey (SF36v2) i. Procedure: Health-related QOL will be assessed using the SF-36v2. ii. Survey item: Mental Health (MH) iii. Evaluation method: Summary scores and subscale scores will be calculated based on national standards. These will be measured at the screening and pre-intake test and at the 6-week post-intake test.

[0076] 6. Outcomes Efficacy endpoints i. Primary outcome TMD, TA, DD, AH, VA, FI, CB, F (POMS2) at 6-week and 12-week examinations ii. Secondary outcomes MH in the test 6 weeks after intake

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

[0078] [Table 2]

[0079] [Table 3]

[0080] n: number of subjects / 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: probability of significance / †: primary outcome / VISIT1: screening and pre-intake test (baseline) / VISIT2: test at 6 weeks after intake / VISIT3: test at 12 weeks after intake / *: Welch's t-test / #: linear mixed model with baseline value as covariate, time point, group, time point and group interaction, baseline value and time point interaction, and study participant as factors (Δ is the between-group difference in estimated marginal means) / orange: significant difference (P < 0.05)

[0081] These results suggest that 12-week intake of the test food contributes to a clinically significant reduction in mental stress, and in particular improves TMD (a general indicator of mood disorders, emotional or psychological distress, and subjective well-being), AH (a state of anger and hostility toward others), FI (fatigue, lethargy, and decreased energy), and CB, which indicate negative mood states. It also suggests that 6-week intake of the test food improves mental health.

[0082] Example 2: Analysis of DAGE (1)Equipment / device Rotary evaporator Normal Phase Solid Phase Extraction Columns 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 The standard used was 1,2-dipalmitoyl-3-O-hexadecyl-rac-glycerol, which was synthesized as follows. 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) were added to 3-(hexadecyloxy)-1,2-propanediol (89.5 mg, 0.28 mmol) dissolved in dehydrated dichloromethane (6 mL) under a nitrogen atmosphere and stirred at room temperature for 1.5 hours. The reaction mixture was concentrated under reduced pressure and then applied to a normal-phase silica gel column (5 g). The mixture was purified with hexane-ethyl acetate (50:1). The solvent was evaporated to give a white solid (150.1 mg, 0.19 mmol, yield: 67%, purity: 97.63% (purity: quantitative NMR)). The resulting 1,2-dipalmitoyl-3-O-hexadecyl-rac-glycerol was precisely weighed, dissolved in isooctane, and used as a standard for DAGE quantification. A calibration curve (quadratic equation y = ax 2 + bx + c) was created.

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

[0086] 〇HPLC conditions ·HPLC equipment: Nexera X2 (Shimadzu) Detector: Charged Aerosol 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 concentration 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 at a retention time of approximately 4.7 minutes in the DAGE standard product and in the test food of Example 1.

[0088] Example 3: Analysis of DAGE content in commercially available products The DAGE content of the 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 is an aliphatic hydrocarbon group having an unsaturation degree of 0 to 2 and a carbon number of 12 to 24, and R ２ is an acyl group having an unsaturation degree of 0 to 6 and a carbon number of 12 to 24, and R ３ is an acyl group having an unsaturation degree of 0 to 6 and a carbon number of 12 to 24. Diacylglyceryl ether (DAGE) represented by the formula: B. Squalene Including, A composition in which the mass ratio of A:B is 0.9 to 9:

1.

2. The composition of claim 1, formulated to provide a daily intake of 400 mg or more of DAGE.

3. Formula I: 【Chemistry 2】 (In formula I, R １ is an aliphatic hydrocarbon group having an unsaturation degree of 0 to 2 and a carbon number of 12 to 24, and R ２ is an acyl group having an unsaturation degree of 0 to 6 and a carbon number of 12 to 24, and R ３ is an acyl group having an unsaturation degree of 0 to 6 and a carbon number of 12 to 24. A composition for improving at least one selected from negative mood states, anger, fatigue, lethargy, confusion, and mental health, comprising a diacylglyceryl ether (DAGE) represented by the formula:

4. A composition for improving a mood state by relieving at least one selected from anger, fatigue, lethargy and confusion in a subject experiencing a negative mood state, comprising DAGE as defined in claim 3.

5. The composition of claim 3 , wherein the composition further comprises squalene.

6. The composition of claim 3 , wherein the composition further comprises a triglyceride.

7. The composition according to claim 3, intended to be taken by a subject who is prone to stress or who is in a negative mood state.

8. The composition according to any one of claims 1 to 7, for ingesting 400 mg or more of DAGE per day for 12 weeks or more.

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