WO2022244727A1 - 認知機能を改善するための組成物 - Google Patents

認知機能を改善するための組成物 Download PDF

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Publication number
WO2022244727A1
WO2022244727A1 PCT/JP2022/020368 JP2022020368W WO2022244727A1 WO 2022244727 A1 WO2022244727 A1 WO 2022244727A1 JP 2022020368 W JP2022020368 W JP 2022020368W WO 2022244727 A1 WO2022244727 A1 WO 2022244727A1
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Prior art keywords
composition according
test
composition
subjects
improving
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PCT/JP2022/020368
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English (en)
French (fr)
Japanese (ja)
Inventor
正貴 河原▲崎▼
正樹 坂東
勝哉 岸川
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Ono Pharmaceutical Co Ltd
Maruha Nichiro Corp
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Ono Pharmaceutical Co Ltd
Maruha Nichiro Corp
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Priority to KR1020237038452A priority Critical patent/KR20240008846A/ko
Priority to JP2023522655A priority patent/JPWO2022244727A1/ja
Priority to CN202280033840.0A priority patent/CN117337186A/zh
Publication of WO2022244727A1 publication Critical patent/WO2022244727A1/ja
Anticipated expiration legal-status Critical
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/60—Fish, e.g. seahorses; Fish eggs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/322—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the nervous system or on mental function
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/18—Lipids
    • A23V2250/184—Emulsifier
    • A23V2250/1842—Lecithin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/20—Natural extracts
    • A23V2250/204—Animal extracts
    • A23V2250/2042—Marine animal, fish extracts

Definitions

  • Non-Patent Document 1 DHA and EPA derived from fish oil have been widely used.
  • orally ingesting salmon roe oil which is rich in DHA and EPA, is expected to increase the amount of REM sleep and improve the quality of sleep (Non-Patent Document 3).
  • Non-Patent Document 4 lecithin is one of the raw materials of acetylcholine, which is a neurotransmitter, and its intake is expected to improve cognitive function. It has also been suggested that DHA and EPA are beneficial for improving mental health in elderly people with MCI (Non-Patent Document 5).
  • the purpose of this disclosure is to provide new means for improving cognitive function.
  • compositions for improving cognitive function comprising fish egg lipid preparations.
  • the present disclosure provides new means for improving cognitive function.
  • test flow chart The process from allocation of test foods to analysis is shown as a test flow chart.
  • Fish egg lipid preparations are prepared, for example, from salmonid fish eggs.
  • Salmonidae includes the genus Atlantic salmon, the genus Atlantic salmon, the genus char, and the genus Ito, and more preferably the genus Atlantic salmon or the genus Atlantic salmon.
  • Atlantic salmon examples include chum salmon (Oncorhynchus keta), coho salmon (Oncorhynchus kisutch), pink salmon (Oncorhynchus gorbuscha), cherry salmon (Oncorhynchus masou masou), yamame trout (Oncorhynchus masou masou), Taiwan trout (Oncorhynchus masou formosanus), and salmon trout.
  • the fish egg lipid preparation is prepared from pink salmon (Oncorhynchus gorbuscha) fish eggs.
  • reference to fish egg lipid preparations also includes lipid preparations made from fish egg extracts, fish egg oils, purified fish egg oils, dried products of any of them, and the like.
  • the fish egg lipid preparation is prepared from sardine roe, salmon roe, or any processed product thereof, such as sardine roe extract, salmon roe extract, salmon roe oil, or refined salmon roe oil.
  • the extraction of the fish egg lipid preparation from the raw material can be carried out by mixing the raw material with a low-polarity organic solvent.
  • low polar solvents include one or more organic solvents selected from the group consisting of 60 to 99% hydrous ethanol, ethanol, hexane, isopropyl alcohol, ethyl acetate, acetone, ether, chloroform, and methanol.
  • the extraction temperature with the organic solvent is 0 to 90°C, preferably 30 to 70°C. It is known that manipulating the water content of hydrous ethanol can increase the content of phospholipids in the resulting extract (see Oleoscience Vol. 2, No. 2, pp.
  • Extraction of fish egg lipid preparations from raw materials, which are fish eggs or processed products thereof, can also be carried out by supercritical fluid extraction using carbon dioxide.
  • the fish egg lipid preparation may be one described in WO2021/132516, especially sarcoplasmic oil PL40.
  • Phospholipid In some embodiments, the phospholipid content of the fish egg lipid preparation is enhanced.
  • Phospholipids refer to lipids having phosphorus in the form of phosphate esters, and include glycerophospholipids and sphingophospholipids.
  • Representative glycerophospholipids include phosphatidylcholine (PC), ⁇ -glycerophosphocholine ( ⁇ -GPC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), 1-lysophosphatidylcholine (LPC-1), 2- Lysophosphatidylcholine (LPC-2), 2-lysophosphatidylethanolamine (LPE-2), representatives of sphingolipids are sphingomyelin (SM) and dihydrosphingomyelin (DHSM).
  • PC phosphatidylcholine
  • ⁇ -GPC phosphatidylethanolamine
  • PE phosphatidylinositol
  • PI 1-lysophosphatidylcholine
  • LPC-2 2- Lysophosphatidylcholine
  • LPE-2 2-lysophosphatidylethanolamine
  • representatives of sphingolipids are sphingomyelin (SM)
  • the phospholipid content of the fish egg lipid preparation is, for example, about 26% or more, may be about 30% or more, preferably about 35% or more, and more preferably about 37.5% or more. , more preferably about 40% or more.
  • the upper limit of the phospholipid content in the fish egg lipid preparation is not particularly limited, but the higher the phospholipid content, the higher the viscosity.
  • the fish egg lipid preparation contains at least one selected from the group consisting of ⁇ -GPC, SM and DHSM, and in preferred embodiments SM and DHSM.
  • the contents of ⁇ -GPC, SM and DHSM are not particularly limited.
  • the content of ⁇ -GPC in fish egg lipid preparations is, for example, about 0.050% to 0.60%.
  • the content of SM in fish egg lipid preparations is, for example, about 0.8% to 2.3%.
  • the content of DHSM in fish egg lipid preparations is, for example, about 0.050% to 0.40%.
  • Phospholipids other than ⁇ -GPC, SM and DHSM contained in the fish egg lipid preparation are not particularly limited, and PC, PE, PI, LPC-2 and the like are preferably abundant.
  • the content of PC in the fish egg lipid preparation is, for example, about 24-45%, preferably about 26-43%, more preferably about 28-41%, still more preferably about 30-39%. is.
  • the content of PE in fish egg lipid preparations is, for example, about 0.90-2.3%.
  • the content of PI in fish egg lipid preparations is, for example, about 0.80-1.8%.
  • the content of LPC-2 in fish egg lipid preparations is, for example, about 0.60-3.0%.
  • PC is contained in a relatively large amount as a content in phospholipids.
  • the PC content in the phospholipid is, for example, about 74% or more, preferably about 80% or more.
  • the content of PC in phospholipids is higher. Therefore, in a preferred embodiment, the phospholipid content in the fish egg lipid preparation is about 35% or more, more preferably about 40% or more, and the PC content in the phospholipids is about 74%. % or more, preferably about 80% or more.
  • the composition ratio of DHA in the constituent fatty acids of the lipid of the fish egg lipid preparation is relatively high.
  • Fish eggs are known to contain DHA in the form of phospholipids or triglycerides (TG).
  • the composition ratio of DHA to the constituent fatty acids of the lipid of the fish egg lipid preparation is, for example, about 15% or more, preferably about 18% or more, and more preferably about 22% or more, More preferably, it is about 24% or more.
  • the upper limit of the composition ratio of DHA to the constituent fatty acids of the lipid in the fish egg lipid preparation is not particularly limited, but is, for example, about 46% or less, preferably about 40% or less, and more preferably about 35% or less.
  • composition ratio of a specific fatty acid to the constituent fatty acids of a lipid is expressed in %, it is based on the area of a chart obtained by analyzing the fatty acid composition by gas chromatography, unless otherwise specified.
  • the composition ratio of EPA in the constituent fatty acids of the lipid of the fish egg lipid preparation is relatively low, for example, about 25% or less, preferably about 23% or less, more preferably about 21% or less, and still more preferably. is about 19% or less.
  • the lower limit of the composition ratio of EPA to the constituent fatty acids of the lipid in the fish egg lipid preparation is not particularly limited. 0% or more, more preferably about 10% or more, and even more preferably about 11% or more or about 12% or more.
  • Fish egg lipid preparations contain, as constituent fatty acids, myristic acid (C14:0), palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1, n9c), eicosenoic acid (C20 :1), docosapentaenoic acid (DPA) (C22:5).
  • fatty acids include myristoleic acid (C14:1), pentadecenoic acid (C15:1), heptadecenoic acid (C17:1), docosenoic acid (C22:1), tetracosenoic acid (C24:1), linoleic acid ( C18:2n-6), ⁇ -linolenic acid (C18:3n-3), ⁇ -linolenic acid (C18:3n-6), eicosadienoic acid (C20:2n-6), eicosatrienoic acid (C20 :3n-6), arachidonic acid (C20:4n-6), docosadienoic acid (C22:2), and the like.
  • the fish egg lipid preparation contains a large amount of DHA-bound phospholipids.
  • the weight of DHA per 100 g of fish egg lipid preparation is, for example, about 10 g or more, preferably about 12 g or more, more preferably about 14 g or more, even more preferably about 15 g or more.
  • the upper limit of the weight of DHA per 100 g of the fish egg lipid preparation is not particularly limited, it is, for example, about 30 g or less, preferably about 25 g or less, more preferably about 22 g or less, and still more preferably about 20 g or less. be.
  • the weight of EPA per 100 g of fish egg lipid preparation is, for example, about 5.0 g or more, more preferably about 6.0 g or more.
  • the upper limit of the weight of EPA per 100 g of the fish egg lipid preparation is not particularly limited, it is, for example, about 20 g or less, preferably about 15 g or less.
  • PDPC palmito docosahexaenoyl phosphatidylcholine
  • PDPC is phosphatidylcholine (38:6) in which one of the acyl groups at C-1 and C-2 is hexadecanoyl (16:0) and the other is docosahexaenoyl (22:6).
  • SDPC stearoyl docosahexaenoyl phosphatidylcholine
  • Ether-type phospholipid refers to a phospholipid having a hydrocarbon chain formed by an ether bond, particularly a glycerophospholipid having a hydrocarbon chain formed by a vinyl ether bond at the sn-1 position and a fatty acid at the sn-2 position. are called plasmalogens.
  • the fish egg lipid preparation contains any one selected from the group consisting of DHA-bound ether-type phospholipids and EPA-bound ether-type phospholipids.
  • Fish egg lipid preparations may contain components other than lipids.
  • Components other than lipids include proteins, sodium, potassium, phosphorus and other inorganic substances.
  • a lipid is a biological substance that is soluble in a nonpolar solvent, and includes simple lipids, complex lipids, and derived lipids (fatty acids, terpenoids, steroids, carotenoids, etc.).
  • the content of components other than lipids in the fish egg lipid preparation is, for example, 10.0% or less, preferably 8.0% or less, more preferably 7.5% or less, and still more preferably 7.0%. % or less.
  • the fish egg lipid preparation may contain astaxanthin.
  • the content thereof in 100 g of the fish egg lipid preparation is, for example, about 0.7 mg or more, preferably about 1.0 mg or more, more preferably about 1.2 mg or more, and still more preferably about 1.5 mg or more. is.
  • the upper limit of the content of astaxanthin in 100 g of the fish egg lipid preparation is not particularly limited, it is, for example, about 23 mg or less, preferably about 20 mg or less, more preferably about 10 mg or less, and still more preferably about 5.0 mg. It is below.
  • compositions of the present disclosure improve cognitive function.
  • improvement of cognitive function includes maintenance of state, suppression of decline, maintenance of improved state, and suppression of decline from improved state.
  • cognitive function includes language ability in subjects with regular exercise habits. Exercise refers to physical activity that is carried out systematically and intentionally for the purpose of maintaining and improving physical strength, and means continuous activity, such as strength training, aerobic exercise, sports, walking and active Hobbies, specifically stretching, gymnastics, yoga, mountain climbing, hiking, dancing, golf, gateball and swimming (including underwater walking) are included in exercise.
  • compositions of the present disclosure improve language skills in subjects with regular exercise habits.
  • a regular exercise habit means exercising regularly, for example, every day, 3 times a week or more, 2 times a week or more, 1 time or more a week, 3 times a month or more, or 2 times a month or more, means to do
  • a regular exercise routine is performing exercise such as stretching, gymnastics, yoga, mountain climbing, hiking, dancing, golf, gateball, or swimming (including underwater walking) at least once a week.
  • Verbal ability means the ability to understand spoken words and written characters, and the ability to communicate using words. In one aspect, it refers to the ability to comprehend, remember, and accurately verbalize the meaning of sentences, which can be assessed, for example, by a Montreal Cognitive Assessment (MoCA) repetition score.
  • MoCA is available in various languages, including the Japanese version of MoCA (MoCA-J).
  • Compositions containing fish egg lipid preparations also improve mental health or mental aspects of QOL as assessed by the SF-36.
  • the improvement of mental health or mental aspects of QOL includes maintenance of the state, suppression of deterioration, maintenance of the improved state, and suppression of deterioration from the improved state.
  • SF-36 is a scale for measuring Health Related Quality of Life (HRQOL).
  • HRQOL Health Related Quality of Life
  • SF-36v2 which is an improved version of the original SF-36 (Japanese version is version 1.2)
  • the SF-36 consists of 36 items and consists of eight health concepts (physical function, daily role function (physical), body pain, overall well-being, vitality, social function, daily role function (mental), and mental health).
  • NBS scores scores by a scoring method based on national norms
  • component summary scores can be calculated from them, with higher scores indicating higher QOL.
  • improving mental health is improving at least one of nervousness, depression and depressed mood. In some embodiments, improving mental health is improving calm or joyful mood.
  • component summary score for example, 3 component summary scores (3MCS; physical aspects, mental aspects, social aspects) of factor coefficients based on the 2002 Japanese survey, 2 components of factor coefficients based on the 1995 US national survey - Summary score (2MCS; physical aspect, mental aspect), 2-component summary score (2MCS (Japanese version); physical aspect, mental aspect) based on the 1995 Japanese national survey.
  • 3MCS 3 component summary scores
  • 2MCS 2MCS (Japanese version)
  • the mental aspect of QOL is assessed by 3MCS or 2MCS (Japanese version).
  • the target is typically a human.
  • Subjects may or may not be cognitively impaired.
  • Cognitive impairment includes forgetfulness and mild cognitive impairment.
  • Forgetful subjects include those who have subjective symptoms of forgetfulness or those who have been told that a close relative also has forgetful symptoms.
  • the age of the subject is not limited, it can be middle-aged or older, specifically 45 years old or older, 50 years old or older, 55 years old or older, 60 years old or older, or 65 years old or older, and 95 years old or younger, 85 years old or younger, 80 years old or less than or equal to 75 years of age.
  • a composition of the present disclosure may be a pharmaceutical composition.
  • the administration method of the pharmaceutical composition is not particularly limited, and oral administration, transdermal administration or nasal administration is preferred, and oral administration is more preferred.
  • Dosage forms for oral administration include granules, fine granules, powders, coated tablets, tablets, powders, soft capsules, hard capsules, microcapsules, chewables, liquids, suspensions, emulsions, and the like.
  • Dosage forms for transdermal administration include patches, tapes, sprays, lotions, creams, ointments, liquids, emulsions, suspensions and the like.
  • Dosage forms for nasal administration include nasal drops, nasal sprays, and the like.
  • dosage forms are manufactured by formulating in a conventional manner. Furthermore, various pharmaceutically acceptable substances for formulation can be blended according to pharmaceutical needs. The substance for formulation can be appropriately selected depending on the dosage form of the formulation. Coating agents, lubricants, flavoring agents, sweeteners, solubilizers and the like are included.
  • the composition of the present disclosure may be a food composition.
  • the food composition can be in the form of a typical processed food.
  • it can be a solid food, or a liquid food such as a drink, a drink, a powdered drink, or a soup.
  • it can be consumed as, for example, juice, confectionery, jelly, tablet, dressing, seasoning, and the like.
  • Such foods may be provided as foods with health claims or dietary supplements.
  • Foods with health claims include, for example, foods for specified health uses, foods with nutrient claims, and foods with function claims. Foods with health claims can be labeled as being used for purposes such as improving cognitive function. The labeling may be directly on a package, container, label, tag, insert, etc. associated with the product, or indirectly through advertising activities.
  • Dietary supplements include, for example, dietary supplements and health supplements.
  • the intake of the composition of the present disclosure can be such that about 100 mg to 10000 mg of the fish egg lipid preparation is ingested per day, preferably about 300 mg to 5000 mg, more preferably about 500 mg to 2500 mg, more preferably about 500 mg to 2500 mg. is about 700 mg to 1500 mg, such as about 1000 mg.
  • the intake of the composition of the present disclosure can be an amount that provides about 20 mg or more of DHA per day, preferably about 50 mg or more, more preferably about 100 mg or more, and even more preferably about 150 mg or more. be.
  • the intake of the composition of the present disclosure can be an amount such that about 2000 mg or less of DHA is ingested per day, preferably about 1000 mg or less, more preferably about 750 mg or less, even more preferably about 500 mg or less, Even more preferably 300 mg or less or less than 300 mg, particularly preferably about 200 mg or less.
  • the intake of the compositions of the present disclosure is an amount that provides about 150 mg (eg, 135 mg-165 mg) or about 160 mg (eg, 144 mg-176 mg) of DHA per day.
  • the intake of the composition of the present disclosure can be an amount such that about 10 mg or more of EPA is ingested per day, preferably about 30 mg or more, more preferably about 50 mg or more, and even more preferably about 60 mg or more. be. Also, the intake of the composition of the present disclosure can be an amount that provides about 500 mg or less of EPA per day, preferably about 300 mg or less, more preferably about 150 mg or less. In some embodiments, the intake of the compositions of the present disclosure is about 60 mg (eg, 54 mg to 66 mg), about 100 mg (eg, 90 mg to 110 mg), or about 110 mg (eg, 99 mg to 121 mg) of EPA per day. is the amount
  • the daily intake of each component may be contained in one composition, or may be dispersed and contained in a plurality of compositions to be ingested per day.
  • the daily intake of each component of the composition may be dispersed in 2 to 15, preferably 3 to 10, eg, 4 capsules to be taken daily.
  • compositions of the present disclosure may be taken once or multiple times. When taking multiple times, for example, once to several times a day, for example, once, twice or three times a day, every day or every few days, for example, 1 day, 2 days, 3 days or Can be taken every 7 days.
  • the period of ingestion is not limited, for example, until cognitive function, mental health or mental QOL is improved, for example, 1 week or more, preferably 1 month or more, more preferably 2 months or more, particularly preferably 3 months. It can be taken continuously for months or longer. There may be periods during which the intake is discontinued.
  • the compositions of this disclosure are taken daily for at least 12 weeks.
  • compositions of the present disclosure can be used alone or in combination with one or more additional ingredients.
  • “Combining" the ingredients includes not only the use of dosage forms containing all of the ingredients and the use of combinations of dosage forms containing each ingredient separately, but also the use of each ingredient at the same time so long as they are used for the same purpose. , or delayed ingestion of any component.
  • a combination of two or more additional components is also possible.
  • compositions containing one or more additional ingredients may be used.
  • ingredients suitable for combined use include astaxanthin.
  • the daily intake of astaxanthin can be about 50 ⁇ g or more, preferably about 100 ⁇ g or more, more preferably about 200 ⁇ g or more, and can be about 1000 ⁇ g or less, preferably about 400 ⁇ g or less, for example about 200 ⁇ g (e.g., 180 ⁇ g to 220 ⁇ g).
  • Astaxanthin may be included in the fish egg lipid composition, but astaxanthin from yet another source may be used.
  • astaxanthin extracted from natural products such as krill, salmon, trout, adonis, red yeast, and Haematococcus algae or a synthetic product can be used, and astaxanthin is preferably contained in Haematococcus algae pigment.
  • the extraction solvent for obtaining astaxanthin from natural products may be either an aqueous solvent or an organic solvent.
  • Methanol, ethanol, isopropanol, acetone, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, ethyl acetate, ether, hexane and the like can be used as organic solvents.
  • Carbon dioxide in a supercritical state can also be used.
  • These solvents may be used alone, or two or more of them may be mixed and used.
  • astaxanthin acts to protect and stabilize DHA and EPA from peroxidation.
  • Haematococcus algae specifically, Haematococcus pluvialis, Haematococcus lacustris, Haematococcus capensis, Haematococcus droebakensis, Haematococcus ginseng Babiensis (Haematococcus zimbabwiensis) and the like.
  • commercially available Haematococcus algae extracts can be used, for example, ASTOTS-S, -5O, -10O, etc. manufactured by Fuji Film Co., Ltd., AstaReal Oil 50F, 5F, etc.
  • krill-derived astaxanthin examples include Astax-S manufactured by Marine Daio Co., Ltd., and the like.
  • lecithin is a generic term for lipid products containing phospholipids and can include phospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, phosphatidic acid.
  • Lecithins include, for example, soybean lecithin, enzymatically decomposed soybean lecithin, hydrogenated soybean lecithin, egg yolk lecithin, hydrogenated phospholipids, milk-derived phospholipids, lysolecithin, phosphatidylcholine and phosphatidylserine, preferably plant lecithin, particularly soybean lecithin.
  • Soy lecithin can be produced as a by-product of the degumming process when manufacturing soybean oil. Further decolorization and purification may be carried out.
  • lecithins can be used, and examples thereof include purified soybean lecithin manufactured by Nisshin OilliO, purified egg yolk lecithin manufactured by Asahi Kasei Pharma, and egg yolk lecithin PL-100M manufactured by Kewpie.
  • the content of PC contained in the composition is, for example, about 24-45%, preferably about 26-43%, more preferably It is about 28-41%, more preferably about 30-39%.
  • the content of PE contained in the composition is, for example, about 0.90-3.5%.
  • the content of PI contained in the composition is, for example, about 0.80-2.5%.
  • the content of LPC-2 contained in the composition is, for example, about 0.60-3.0%.
  • the content of SM contained in the composition is, for example, about 0.8% to 2.3%.
  • the content of phosphatidic acid contained in the composition is, for example, about 0.10-1.0%.
  • the content of DHSM contained in the composition is, for example, about 0.050% to 0.40%.
  • the content of phospholipids in the present composition is about 35% or more, more preferably about 40% or more, and the content of PC in the phospholipids is about 74% or more, preferably about 77%. That's it.
  • agents for improving cognitive function comprise a fish egg lipid preparation.
  • methods of improving cognitive function comprising ingesting a fish egg lipid preparation to a subject in need of improved cognitive function.
  • fish egg lipid preparations are provided for improving cognitive function.
  • use of fish egg lipid preparations to improve cognitive function is provided.
  • use of the fish egg lipid preparation in the manufacture of a composition for improving cognitive function is provided.
  • a mental health or mental QOL improving agent comprising a fish egg lipid preparation.
  • maintaining, enhancing and/or improving mental health or mental QOL comprising ingesting a fish egg lipid preparation to a subject in need of improved mental health or mental QOL.
  • a method is provided.
  • fish egg lipid preparations for improving mental health or psychological aspects of QOL are provided.
  • the use of fish egg lipid preparations for improving mental health or psychological aspects of QOL is provided.
  • a composition for improving cognitive function comprising a fish egg lipid preparation.
  • the composition according to item 1 wherein the cognitive function is language ability in a subject with a regular exercise habit.
  • a fish egg lipid preparation prepared so that the daily intake is about 100 mg or more and less than 300 mg (preferably about 100 mg to 200 mg, more preferably about 150 mg to 200 mg) of DHA.
  • a composition for improving cognitive function comprising: said cognitive function is language ability in a subject with a regular exercise habit.
  • a composition for improving mental health or mental aspects of QOL comprising a fish egg lipid preparation.
  • composition of paragraph 4 or 5 for improving mental health.
  • the composition according to any one of items 4 to 6, wherein improving mental health is improving at least one of nervousness, depression and depressed mood.
  • the composition according to any one of items 4 to 6, wherein improving mental health is improving to calm mood or happy mood.
  • the phospholipid contains about 74% or more of PC.
  • the composition according to Item 18, wherein the lecithin is soybean lecithin.
  • EPA eicosapentaenoic acid
  • DHA Daily intake of DHA of about 100 mg to less than 300 mg (preferably about 100 mg to 200 mg, more preferably about 150 mg to 200 mg), about 30 mg to 300 mg (preferably about 60 mg to 300 mg, more preferably about 60 mg) ⁇ 150 mg) of eicosapentaenoic acid (EPA) and from about 50 mg to 500 mg (preferably from about 60 mg to 300 mg, more preferably from about 70 mg to 150 mg) of soy lecithin are prepared for ingestion.
  • EPA eicosapentaenoic acid
  • soy lecithin are prepared for ingestion.
  • the composition according to item 23 further comprising about 100 ⁇ g to 1000 ⁇ g (preferably about 200 ⁇ g to 1000 ⁇ g, more preferably about 200 ⁇ g to 400 ⁇ g) of astaxanthin.
  • composition of paragraph 23 wherein the composition is prepared as [27] The composition according to item 25 or 26, which is further adjusted so that about 200 ⁇ g (or 180 ⁇ g to 220 ⁇ g) of astaxanthin is ingested. [28] About 150 mg (or 135 mg to 165 mg) of DHA, about 60 mg (or 54 mg to 66 mg) of EPA, and about 100 mg (or 90 mg to 110 mg) of soy lecithin are taken as a daily intake. 24. The composition of paragraph 23, wherein the composition is prepared as [29] The composition according to Item 28, which is further adjusted so that about 200 ⁇ g (or 180 ⁇ g to 220 ⁇ g) of astaxanthin is ingested.
  • a cognitive function improving agent comprising a fish egg lipid preparation.
  • a method of improving cognitive function comprising ingesting a fish egg lipid preparation to a subject in need of cognitive improvement.
  • Fish egg lipid preparations for improving cognitive function [39] Use of fish egg lipid preparations to improve cognitive function.
  • Use of a fish egg lipid preparation in the manufacture of a composition for improving cognitive function [41] A mental health or mental quality of life improving agent comprising a fish egg lipid preparation.
  • a method for improving mental health or mental QOL comprising ingesting a fish egg lipid preparation to a subject in need of improved mental health or mental QOL.
  • Fish egg lipid preparations for improving mental health or mental aspects of QOL [44] Use of fish egg lipid preparations to improve mental health or psychological aspects of QOL.
  • a fish egg lipid preparation was produced according to the method described in WO2021/132516. Specifically, hydrous ethanol (150 L) was added to raw sarcomas (15 kg) of frozen and pulverized pink salmon (Oncorhynchus gorbuscha) for extraction, and the residue was separated by filtration. In addition, the residue was returned to the extractor and extracted again by adding ethanol (75 L). The solvent was distilled off from the obtained filtrate under reduced pressure to produce a composition (40PL) containing about 40% phospholipid in the red oily substance (Tables 1 and 2).
  • the quantitative value is the amount of fatty acids constituting the total lipid.
  • ONO-SR/AST-SOYPC were as shown in the table below.
  • Subjects were 100 men and women aged 60 to 85 who had subjective symptoms of forgetfulness or who were pointed out to have forgetfulness symptoms in close relatives (some were diagnosed with MCI). include).
  • Prior to conducting the study we provided the subjects with written informed consent, fully explained the purpose and content of the study, and obtained written consent from the subjects based on their free will. Subjects who did not meet the following exclusion criteria were selected from the preliminary test results of subjects who were able to obtain consent.
  • Subjects who regularly use health foods rich in DHA, EPA, astaxanthin, and soybean lecithin (2) Drugs, health foods, foods for specified health uses, foods with nutrient function claims, and functional claims that contain ingredients that have cognitive function improvement effects, antioxidant effects, or blood flow improvement effects that may affect research results. Subjects who continuously take food more than once a week. (3) Subjects who have difficulty in performing cognitive function tests due to poor eyesight, or who have been diagnosed with amblyopia or blindness. (4) Subjects who have difficulty in conducting cognitive function tests due to their low hearing, or who have been diagnosed with hearing loss or deafness. (5) Those who have a history or current disease of mental disorder, dementia, cranial nerve disease, cerebrovascular disease.
  • Those who have an existing disease of menopause (7) Taking drugs that may affect the research results (dyslipidemia drugs, antipsychotic drugs, antianxiety drugs, antidepressants/congestive drugs, antiparkinsonian drugs, antiepileptic drugs, anticoagulants, etc.) those who are (8) Subjects with a history of serious disease requiring medication (malignant tumor, diabetes, liver disease (hepatitis), renal disease, heart disease, etc.). (9) Subjects with a history of drug dependence or alcohol dependence or a current medical history. (10) Subjects who are suspected of having dementia based on a cognitive function test as a preliminary test or an interview with a doctor. (11) Subjects whose daily life becomes irregular several times during the study period due to night work, etc.
  • the cognitive function test should be started at the same time as the preliminary (cognitive) test. The morning or afternoon should be the same, and the start time of the preliminary (cognitive) cognitive function test should be within ⁇ 2 hours. (18) Live in such a way that the working conditions before the pre-test (cognitive) test and before the test on the day of the test do not change significantly.
  • the test food contained 1000 mg of salmon roe oil (containing 150 mg of DHA and 60 mg of EPA) in 4 grains, which is the daily intake.
  • a soft capsule containing astaxanthin, soybean lecithin, gelatin, glycerin, water, and caramel pigment was used as other ingredients.
  • the placebo was a soft capsule containing safflower oil instead of salmon roe oil.
  • the daily intake of 4 grains was packed in one bag so that the test food and placebo could not be distinguished from the exterior.
  • Study Design This study was a randomized, double-blind, placebo-controlled, parallel-group study with a 12-week intake period. An allocation manager who was not directly involved in the study created an allocation table using a random number table, and based on this, assigned an allocation number to the study foods. The randomization list was sealed by the person responsible for randomization and kept sealed until the randomization list was opened. The investigator responsible, subjects, medical facility staff, and all other staff involved in this study were blinded.
  • Each subject was given one bag of the randomly assigned research food, four tablets per day after meals, without chewing, with water or lukewarm water throughout the 12-week intervention period. During the intervention period, subjects were asked to record in a diary the intake of research foods, changes in their physical condition, and the intake of medicines.
  • MoCA-J was performed as the primary endpoint, and MMSE and SF-36 were performed as secondary endpoints. Both MoCA-J and MMSE are tests that allow multifaceted assessment of various areas of cognitive function. In addition, since both are used for screening for MCI, they were used for evaluation of cognitive function in this study targeting healthy subjects including the MCI region. Details of each test are described below.
  • MoCA-J MoCA-J includes Trail Making, visuospatial cognitive function (cube), visuospatial cognitive function (clock drawing), nomenclature, memory, attention (forward chant, reverse chant, vigilance, calculation), repetition, word recall, and abstract thinking. , delayed recall, and orientation, and is a test developed for the purpose of screening for MCI. MCI is suspected with a score of 25 or less out of a maximum score of 30, and has been reported to have a sensitivity of 80-100% and a specificity of 50-87% (Ziad S Nasreddine, et al. The Montreal Cognitive Assessment MoCA: a brief Screening tool for mild cognitive impairment.
  • the attention (calculation) of MoCA-J and the attention and calculation of MMSE are the same calculation task (repeating 7 in order from 100 and subtracting 5 times), but considering the time from memory to delayed recall of MoCA-J , MoCA-J also performed computational tasks, and the results of the MMSE were used for the scores.
  • MoCA-J orientation and MMSE orientation to time and orientation to place are performed only in MMSE as the date (year, month, day, day of the week) and place (city, building) tasks are identical
  • the scores were obtained from the MMSE. In both cases, the higher the score, the higher the cognitive function.
  • MMSE is a test consisting of a total of 11 items: orientation to time, orientation to place, memorization, attention and calculation, reproduction, naming, repetition, comprehension, reading, writing, and drawing. Out of a maximum of 30 points, a score of 23 or less suggests dementia (sensitivity 81%, specificity 89%), and a score of 27 or less suggests MCI (sensitivity 45-60%, specificity 65-90%).
  • SF-36 SF-36v2 Japanese version was used to evaluate health-related QOL (Health Related Quality of Life).
  • the SF-36 consists of 36 items and consists of eight health concepts (physical function, daily role function (physical), body pain, overall well-being, vitality, social function, daily role function (mental), and mental health).
  • NBS scores scores by scoring method based on national standard values
  • component summary scores three component summary scores of factor coefficients based on the 2002 Japanese survey (physical aspects, mental aspects, social 2-component summary score of factor coefficients based on the 1995 U.S. national survey (physical and mental aspects), 2-component summary score of factor coefficients based on the 1995 Japanese national survey (physical and mental aspects) aspect)) can be calculated. In both cases, the higher the score, the higher the QOL.
  • Hematological test (white blood cell count, red blood cell count, hemoglobin, hematocrit, platelet count), blood biochemical test (total protein, albumin, total bilirubin, direct bilirubin, indirect bilirubin, ALP, AST (GOT), ALT (GPT), LD, ⁇ -GT, total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, urea nitrogen, creatinine, uric acid, Na, K, CL, blood sugar, HbA1c (preliminary test only)), urinalysis (protein (qualitative ), sugar (qualitative), occult blood reaction (qualitative)).
  • blood biochemical test total protein, albumin, total bilirubin, direct bilirubin, indirect bilirubin, ALP, AST (GOT), ALT (GPT), LD, ⁇ -GT, total cholesterol, triglyceride, HDL-cholesterol, LDL-chol
  • test values of individual subjects are abnormal changes corresponding to adverse events is based on the reference values specified by the implementing medical institution, and the criteria for abnormal changes stipulated by the Japanese Society of Chemotherapy, CTCAE v5.0- Conducted by the responsible physician with reference to the JCOG and the Japanese Society of Ningen Dock judgment categories (revised on April 1, 2018, partially changed on December 14, 2018).
  • the investigator-in-chief investigated and considered the relationship with the study food, and determined whether each adverse event was a side effect of the study food.
  • the values before intervention (baseline) to compare the characteristics of each subject group, the measured values at each time point after ingestion, and the amount of change from the baseline were each shown as the mean ⁇ standard deviation (sex is the number of subjects ).
  • the chi- square test was used for between-group comparisons of sex at baseline.
  • the two-sample t-test was used to compare the amount of change from the baseline and the baseline at each time point after ingestion between groups.
  • a one-sample t-test was used for intra-group comparison of changes from baseline in measured values at each time point after ingestion.
  • the change at week 12 when the baseline was 0 was evaluated using the Wilcoxon signed rank sum test.
  • Table 8 shows the NBS scores and component summary scores of SF-36 during the intervention period.
  • the NBS score of mental health at the 12th week the mental aspect of the 2002 3-component summary score and the 1995 2-component summary score (Japanese version)
  • both groups significantly increased (improved) in the NBS score of daily role functioning (psychiatric) and the mental aspects of the 1995 2-component summary score (US version) compared to the baseline at 12 weeks.
  • NBS scores for daily role functioning (physical), the social dimension of the 2002 3-component summary score and the physical dimension of the 1995 2-component summary score (Japanese version) compared to baseline in the placebo group at 12 weeks significantly increased (improved) in NBS scores for physical function, vitality and mental health, mental aspects of the 2002 3-component summary score and 1995 2-component summary score (Japanese version) were compared to baseline in the test food groups. significantly increased (improved) at 12 weeks of
  • Subgroup analysis Regarding the presence or absence of regular exercise habits, all subjects were divided into the group of subjects who exercised at least once a week during the intake period (group with regular exercise habits) and the group of subjects who exercised less than once a week (regular exercise group). No habit layer), and subgroup analysis was performed for each subject layer. In addition, the test was not performed for the items for which the baseline and the amount of change were the same for all the subjects in both groups.
  • the number of subjects in the placebo group and the test food group in the regular exercise group was 24 (11 men, 13 women) and 26 (15 men, 11 women), respectively, and the non-regular exercise group.
  • the number of subjects in the placebo group and the test food group was 26 (16 males, 10 females) and 24 (11 males, 13 females), respectively.
  • age male/female ratio, physical measurements, physical examination values, and MoCA-J total score
  • P 0.04 for both
  • Table 10 shows the total MoCA-J and the scores for each item during the intervention period in the group with regular exercise habits.
  • Safety Evaluation was performed on 50 subjects for safety analysis in each group (Fig. 1) for both adverse events, measured values, and test values. During the intervention period, 21 subjects in the placebo group (55 cases) and 13 subjects in the test food group (23 cases) had positive urine occult blood tests, diarrhea, arthralgia, nasal discharge, lumbago, and other adverse events. Adverse events other than a positive urinary occult blood test must have an identifiable cause other than the research food, or be mild and transient, and none of them are related to the research food, i.e., not a side effect of the research food. was judged by the responsible investigator.
  • the positive urinary occult blood reaction is thought to be caused by the subject's exercise habits, but cannot be identified, so the relationship with the research food is "probably not", but the investigator-in-charge determined that it was within a clinically acceptable range. was done. Measured values and test values were compared before and after ingestion in each group, and significant changes were observed in some items, but all were minor changes within the standard range or reference range. It was judged not to be a clinical problem.
  • the 2002 3-component summary score "Mental aspect” and the 1995 2-component summary score (Japanese version) "Mental aspect” The test food group showed significant improvement compared to the placebo group.
  • the 2-component summary score “mental aspects” consists of “overall health”, “social functioning”, “daily role functioning (mental)”, “vitality”, and “mental health”. , both of which are scores indicating the QOL of the mental aspect.
  • Exclusion Criteria (1) Those who regularly use health foods rich in DHA, EPA, astaxanthin, soybean lecithin, (2) Persons with serious diseases such as diabetes, liver disease, kidney disease, heart disease, etc., and those with a history of such diseases; (3) Subjects who are at risk of developing allergies related to the research, (4) Subjects who have a medical condition affecting the study, or who have a history of chronic disease or serious disease requiring medication, (5) Those who have a history of drug dependence or alcohol dependence or a current medical history, (6) Persons who are judged to be unsuitable as subjects based on the clinical test values and measured values of the preliminary examination, (7) Those who have participated in other clinical studies within one month of obtaining consent to participate in this study, or those who plan to participate in other clinical studies after obtaining consent to participate in this study; (8) Subjects who are pregnant, breast-feeding, or planning to become pregnant or breast-feeding during the research period; (9) Those who are judged to be unsuitable as subjects based on the results of
  • Test food One bag of the test food "ONO-SR/AST-SOYPC" (Ono Pharmaceutical Co., Ltd.) contains 1 g of salmon roe oil (DHA 150 mg, EPA 60 mg) per 4 tablets, astaxanthin 200 ⁇ g, soybean lecithin 100 mg, gelatin, glycerin, A soft capsule containing water and caramel color was used. Raw materials and nutritional components are shown in Table 11.
  • Test method The test was an open study. 1 bag (4 tablets) for the 1-fold intake group, 2 bags (8 tablets) for the 2-fold intake group, 5 bags (20 tablets) for the 5-fold intake group, followed by water after meals. Alternatively, they were given without chewing with lukewarm water. In addition, the intake time was not specified, and it was allowed to divide and drink multiple times in one day. The intake period was 4 weeks. During the test period, do not change your lifestyle such as drinking, eating, and sleeping as much as possible from before participating in the study, limit excessive exercise that greatly deviates from your daily range, diet and overeating, do not start new exercise, In addition, it was decided not to stop the exercise habits that had been continued until then.
  • Test 1 the subjects visited the hospital two weeks after taking the test food, and interviews (confirmation of physical condition), physical measurements, physical examinations, and fasting clinical examinations were performed. In addition, the subjects were instructed to keep a test diary every day during the test period, which describes the intake status of the test food, changes in physical condition, mood in daily life, sleep (falling asleep, sleep quality), drug intake status, etc.
  • the same test was planned to be conducted at the 4th week of intake and the 2nd week after the intake, but due to the declaration of a state of emergency for the new coronavirus infection, to ensure the safety of the subjects, the 4th week of intake and the end of intake. The patient was not admitted to the hospital for the second week. After the ingestion period ended, only the entries in the diary were continued for two weeks.
  • Test 2 the subjects visited the hospital in the 2nd and 4th weeks after taking the test food, and interviews (confirmation of physical condition), physical measurements, physical examinations, and fasting clinical examinations were performed.
  • the subjects were instructed to keep a test diary every day during the test period, which describes the intake status of the test food, changes in physical condition, mood in daily life, sleep (falling asleep, sleep quality), drug intake status, etc. After the end of the ingestion period, only the entries in the diary were continued for two weeks.
  • Examination items/Evaluation items Examination includes confirmation of physical condition as an interview, confirmation of the presence or absence of adverse events, physical measurement (height (preliminary examination only), weight, BMI), physical examination (systolic and diastolic blood pressure, pulse rate), Fasting clinical examination hematologic test (white blood cell count, red blood cell count, hemoglobin, hematocrit, platelet count), blood biochemical test (total protein, albumin, total bilirubin, direct bilirubin, indirect bilirubin, ALP, AST, ALT, LD , ⁇ -GT, total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, urea nitrogen, creatinine, uric acid, sodium, potassium, chloride, blood sugar, HbA1c (preliminary test only)), urinalysis (protein qualitative, sugar qualitative, occult blood reaction) were performed.
  • Test 1 each test was performed at the time of the pre-inspection, 2 weeks after ingestion, except for items that were to be tested only in the pre-treatment.
  • Test 2 each test was performed at the time of the pre-inspection, 2 weeks after the intake, 4 weeks after the intake, and 2 weeks after the completion of the intake, except for items that were inspected only before the intake.
  • the implementation of the clinical examination was entrusted to LSI Rulece Co., Ltd. (Shinagawa-ku, Tokyo).
  • the evaluation items were adverse events, measured values and test values, and adverse events were subjective symptoms in interviews and diaries, as well as abnormal changes in test values. Subjective symptoms and adverse events as objective findings were determined by the responsible physician.
  • abnormal changes in test values abnormal events
  • the criteria for abnormal changes stipulated by the Japanese Society of Chemotherapy and Adverse Event Common Terminology Criteria v5.0 Japanese translation are based on the reference values stipulated by the medical institution.
  • Adverse events were judged by the responsible physician by referring to the JCOG version (CTCAE v5.0-JCOG) and the judgment categories of the Japanese Society of Ningen Dock.
  • Test 1 Background of Subjects In Study 1, a preliminary examination was performed on 63 subjects who gave written consent to participate in the study. A total of 30 subjects, 15 males and 15 females, who met the inclusion criteria and did not meet the exclusion criteria based on the results of the preliminary examination, were selected as eligible subjects for this study. In some subjects, items exceeding the standard range (testing standard values of the laboratory performing the clinical testing) were found in some subjects. It was included in this study after it was determined that there was no
  • Test 2 1. Background of Subjects In Study 2, a preliminary examination was performed on 23 subjects who gave written consent to participate in the study. A total of 10 subjects, 5 males and 5 females, who met the inclusion criteria and did not meet the exclusion criteria, were selected as eligible subjects for this study based on the results of the preliminary examination.
  • the present disclosure relates to improving cognitive function and can be used in the medical or food fields.

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010053054A (ja) * 2008-08-27 2010-03-11 Nof Corp 睡眠の改善方法
JP2010531351A (ja) * 2007-06-26 2010-09-24 エヌ．ヴィ．ニュートリシア ミニメンタルステート検査２４〜２６点の被験者における記憶力改善
JP2014534225A (ja) * 2011-10-31 2014-12-18 エヌ．ブイ．・ヌートリシア 認知の改善
WO2015140545A1 (en) * 2014-03-20 2015-09-24 Isis Innovation Limited Combination therapy comprising an omega-3 fatty acid, a folate species and a vitamin b12 species
JP2015224193A (ja) * 2014-05-26 2015-12-14 キリン株式会社 記憶学習機能を向上する医薬、食品、組成物
JP2021505527A (ja) * 2017-12-04 2021-02-18 ハワード・ファウンデーション・ホールディングス・リミテッドＨｏｗａｒｄ Ｆｏｕｎｄａｔｉｏｎ Ｈｏｌｄｉｎｇｓ Ｌｉｍｉｔｅｄ 神経変性疾患の予防及び／又は治療
WO2021132516A1 (ja) * 2019-12-26 2021-07-01 マルハニチロ株式会社 多価不飽和脂肪酸が結合したリン脂質を含む魚卵脂質組成物

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010531351A (ja) * 2007-06-26 2010-09-24 エヌ．ヴィ．ニュートリシア ミニメンタルステート検査２４〜２６点の被験者における記憶力改善
JP2010053054A (ja) * 2008-08-27 2010-03-11 Nof Corp 睡眠の改善方法
JP2014534225A (ja) * 2011-10-31 2014-12-18 エヌ．ブイ．・ヌートリシア 認知の改善
WO2015140545A1 (en) * 2014-03-20 2015-09-24 Isis Innovation Limited Combination therapy comprising an omega-3 fatty acid, a folate species and a vitamin b12 species
JP2015224193A (ja) * 2014-05-26 2015-12-14 キリン株式会社 記憶学習機能を向上する医薬、食品、組成物
JP2021505527A (ja) * 2017-12-04 2021-02-18 ハワード・ファウンデーション・ホールディングス・リミテッドＨｏｗａｒｄ Ｆｏｕｎｄａｔｉｏｎ Ｈｏｌｄｉｎｇｓ Ｌｉｍｉｔｅｄ 神経変性疾患の予防及び／又は治療
WO2021132516A1 (ja) * 2019-12-26 2021-07-01 マルハニチロ株式会社 多価不飽和脂肪酸が結合したリン脂質を含む魚卵脂質組成物

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
FAIRBAIRN PAUL, TSOFLIOU FOTINI, JOHNSON ANDREW, DYALL SIMON C.: "Effects of a high-DHA multi-nutrient supplement and exercise on mobility and cognition in older women (MOBILE): a randomised semi-blinded placebo-controlled study", BRITISH JOURNAL OF NUTRITION, vol. 124, no. 2, 28 July 2020 (2020-07-28), UK , pages 146 - 155, XP093007137, ISSN: 0007-1145, DOI: 10.1017/S0007114520000719 *
SANNOU, HIROO ET AL. : "Effect of Oil-Processed Foods Containing Salmon Roe Oil-Derived DHA or Salmon Roe Oil-Derived EPA on Cognitive Function and Health-Related Quality of Life in the Elderly: A Randomized, Double-Blind, Placebo-Controlled Comparative Study", JAPANESE PHARMACOLOGY AND THERAPEUTICS, vol. 49, no. 8, 1 August 2021 (2021-08-01), JP , pages 1307 - 1324, XP009541378, ISSN: 0386-3603 *
TAMAI TADAKAZAU: "Utilization of Processed Foods Rich in Docosahexaenoic Acid: Clinical Trials Using Foods for Specific Health Purposes", JOURNAL OF LIPID NUTRITION, vol. 23, no. 1, 1 January 2014 (2014-01-01), pages 45 - 52, XP093007143 *

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