WO2019082430A1 - カロテノイド組成物を含有する脳機能低下抑制剤または脳機能低下予防剤 - Google Patents

カロテノイド組成物を含有する脳機能低下抑制剤または脳機能低下予防剤

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Publication number
WO2019082430A1
WO2019082430A1 PCT/JP2018/020051 JP2018020051W WO2019082430A1 WO 2019082430 A1 WO2019082430 A1 WO 2019082430A1 JP 2018020051 W JP2018020051 W JP 2018020051W WO 2019082430 A1 WO2019082430 A1 WO 2019082430A1
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Prior art keywords
carotenoid
mass
composition
astaxanthin
adonirubin
Prior art date
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Ceased
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PCT/JP2018/020051
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English (en)
French (fr)
Japanese (ja)
Inventor
卓 石橋
雅浩 林
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Eneos Corp
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JXTG Nippon Oil and Energy Corp
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Priority to US16/756,199 priority Critical patent/US20210186895A1/en
Priority to CA3079373A priority patent/CA3079373A1/en
Publication of WO2019082430A1 publication Critical patent/WO2019082430A1/ja
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Preparation or treatment thereof
    • 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
    • A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/03—Organic compounds
    • A23L29/045—Organic compounds containing nitrogen as heteroatom
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • 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
    • 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
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria

Definitions

  • the present invention relates to a brain function decrease inhibitor or a brain function decrease preventive agent containing a carotenoid composition.
  • dementia is a major social problem in developed countries facing an aging society.
  • One of the symptoms of dementia is forgetfulness, but forgetfulness can also occur in the normal brain aging phenomenon.
  • deterioration of brain function such as deterioration of memory ability and information processing ability due to aging is one of the aging phenomena that can occur to anyone.
  • carotenoids including astaxanthin are known to have various effects.
  • astaxanthin is known to have an antioxidative action to eliminate active oxygen and a retinopathy preventive action (Patent Document 1).
  • Patent Document 1 it has not been known that carotenoids such as adonirubin and adonixanthin have a suppressing or preventing effect on deterioration of brain functions such as verbal memory ability and information processing ability.
  • carotenoids have similar chemical structures, their effects are different depending on their specific structures, so their functions can not be estimated from their structural similarities.
  • zeaxanthin and lutein have a similar structure to astaxanthin, but zeaxanthin and lutein are accumulated around the macula of the eye, whereas astaxanthin reaches the blood vessels of the eye but does not accumulate.
  • various carotenoids produce different effects at different places depending on the binding protein, it is not possible to infer the effect by structural similarity alone. That is, if it is desired to identify the function of a certain carotenoid, it is necessary to carry out a test for that carotenoid.
  • Carotenoids are obtained by chemical synthesis and extraction from natural products such as animals, plants and microorganisms. In view of application to humans, it is desirable from the viewpoint of safety that the carotenoids are extracted from natural products.
  • a carotenoid composition containing astaxanthin, adonirubin and adonixanthin at a predetermined ratio reduced brain functions such as verbal memory ability and information processing ability It has been found that it has a preventive or suppressive action on That is, the present invention includes the following.
  • An inhibitor or preventive agent for cerebral dysfunction comprising a carotenoid composition containing astaxanthin, adonirubin and adonixanthin.
  • the carotenoid composition comprises 45 to 80% by weight of astaxanthin, 4 to 22% by weight of adonirubin and 4 to 20% by weight of adonixanthin, based on the total weight of the composition [1] ]
  • the agent as described in.
  • An inhibitor or preventive agent for cerebral dysfunction including a carotenoid preparation containing astaxanthin, adonirubin and adonixanthin.
  • the carotenoid preparation contains 0.5 to 20% by mass of astaxanthin, 0.01 to 4% by mass of adonirubin and 0.01 to 4% by mass of adonixanthin based on the mass of the whole preparation.
  • a pharmaceutical composition, a food composition or a drinking composition comprising the agent according to any one of [1] to [10].
  • a method for suppressing or preventing brain dysfunction comprising administering to a subject a carotenoid composition or a carotenoid preparation containing astaxanthin, adonirubin and adonixanthin.
  • the carotenoid composition comprises 45 to 80% by weight of astaxanthin, 4 to 22% by weight of adonirubin and 4 to 20% by weight of adonixanthin, based on the weight of the entire composition [12] ] The method as described in.
  • the carotenoid preparation contains 0.5 to 20% by mass of astaxanthin, 0.01 to 4% by mass of adonirubin and 0.01 to 4% by mass of adonixanthin based on the mass of the whole preparation.
  • the method described in [12]. [15] The method according to any one of [12] to [14], wherein the brain function is verbal memory ability or information processing ability.
  • the decrease in brain function is an age-related decrease in brain function.
  • a brain function hypoallergenic agent or a brain hypofunction inhibitor there is provided a brain function hypoallergenic agent or a brain hypofunction inhibitor.
  • a preventive agent for cerebral function decline with aging or an inhibitor for cerebral function decline with age is provided.
  • Example 1 of a language memory test and the comparative example 1 is shown.
  • the present invention relates to a preventive agent or an inhibitor for a decrease in brain function such as a decrease in verbal memory ability or a decrease in information processing ability, which comprises a carotenoid composition containing astaxanthin, adonirubin and adonixanthin in a predetermined ratio.
  • a preventive agent or an inhibitor for a decrease in brain function such as a decrease in verbal memory ability or a decrease in information processing ability, including a carotenoid preparation containing astaxanthin, adonirubin and adonixanthin at a predetermined ratio.
  • the present invention is based on the finding that a carotenoid composition or preparation containing astaxanthin, adonirubin and adonixanthin in a predetermined ratio has a preventive or suppressive action on the reduction of brain functions such as verbal memory ability and information processing ability. It is based.
  • the present inventors have ingested a food (carotenoid-containing food) containing carotenoids such as astaxanthin, adonirubin, adonixanthin for 4 weeks or more in healthy middle-aged and elderly 45-64-year-old men and women for four weeks
  • carotenoids such as astaxanthin, adonirubin, adonixanthin
  • the effects of contained foods on brain function were examined by word memory test, recall test and Stroop test.
  • the study was a randomized double-blind placebo-controlled parallel group comparison. Subjects were excluded those who had a history of cranial nerve disease and those who were suspected of having a low score on the intelligence rating scale.
  • the change amount at the 4th week of the subject group who received the carotenoid-containing food increased significantly as compared with the placebo group.
  • serum carotenoids (astaxanthin, adonirubin, adonixanthin) were all significantly increased in the carotenoid-containing food group as compared to the placebo group. From these results, it was found that when the carotenoid composition is ingested for 4 weeks or more in middle-aged and elderly people of 45 to 54 years of age, verbal memory ability is improved or improved. In addition, for example, it has been found that the information processing ability is improved in the test subject group aged 55 or older.
  • a carotenoid composition or preparation containing astaxanthin, adonirubin, adonixanthin and the like can be used as a brain function hypoallergenic agent or inhibitor.
  • the carotenoid composition or preparation according to the present invention can be said to be particularly effective in the suppression or prevention of cerebral function deterioration due to aging.
  • the carotenoid composition or formulation according to the present invention has an effect of improving verbal memory ability in a subject under 55 years of age
  • the carotenoid composition or formulation of the present invention Is particularly effective in the suppression or prevention of brain function decline in the early stage of aging.
  • the carotenoid composition or preparation according to the present invention has an effect of improving information processing ability in a subject aged 55 or over
  • the carotenoid composition or preparation according to the present invention It is particularly effective in the suppression or prevention of brain function deterioration after the early stage of aging.
  • the carotenoid compositions or formulations of the present invention comprise astaxanthin, adonirubin and adonixanthin.
  • the carotenoid composition or preparation according to the present invention comprises one or more carotenoids selected from the group consisting of ⁇ -carotene, equinenone, 3-hydroxyechinone, canthaxanthin and asteroidenone in addition to astaxanthin, adonirubin and adonixanthin. May be further contained.
  • terminal hydroxy groups of carotenoids may be esterified with saturated fatty acids or unsaturated fatty acids to form monoesters or diesters.
  • the carotenoids in the present invention such as astaxanthin, adonirubin or adonixanthin, are more preferably carotenoids having no ester structure.
  • the ester form of the carotenoid is deesterified in the process of blood transfer, while the carotenoid having no ester structure does not have a deesterification step and has good absorbability.
  • Carotenoids produced by microorganisms belonging to the genus Paracoccus have no ester structure.
  • the carotenoid composition of the present invention is The lower limit value of astaxanthin is preferably 45% by mass or more, more preferably 50% by mass or more or 55% by mass, and most preferably 60% by mass or more based on the total mass (100%) of the composition.
  • % As upper limit, preferably 80% by mass or less, more preferably 75% by mass or less, most preferably 73% by mass or less
  • the lower limit value of adonirubin, based on the total mass (100%) of the composition is preferably 4% by mass or more, more preferably 6% by mass or more, and most preferably 8% by mass or more, preferably 22% by mass as the upper limit.
  • the lower limit value of adonixanthin is preferably 4% by mass or more, more preferably 7% by mass or more, and most preferably 10% by mass or more, based on the total mass (100%) of the composition.
  • the content is 20% by mass or less, more preferably 15% by mass or less, and most preferably 13% by mass or less.
  • the lower limit value and the upper limit value can be arbitrarily combined, for example, the carotenoid composition of the present invention is 45 to 80% by weight astaxanthin, 4 to 22% by weight adnirubin and 4 to 25% by weight based on the weight of the whole composition. It contains ⁇ 20% by weight of adonixanthin.
  • the carotenoid composition of the present invention may be a commercial product, or may be one produced by a conventional chemical synthesis method, and each carotenoid of chemical synthesis or natural origin is within the above composition range. It may be manufactured by mixing. When administered to humans, from the viewpoint of safety, it is more preferable to be a carotenoid derived from a natural product.
  • the carotenoid composition of the present invention may be of natural origin produced by a fermentation method using a microorganism or an extraction and purification method from animals, plants and the like.
  • those produced by extraction and purification from a microorganism belonging to the genus Paracoccus such as Paracoccus carotinifaciens can be used.
  • the carotenoid composition of the present invention can be produced according to the method described in JP-A-2009-50237. Specifically, a carotenoid eluate is prepared by extracting a dried product of a microorganism belonging to the genus Paracoccus with ethanol at 90-100 ° C. for 15 minutes or more. The bacterial residue is removed from the carotenoid eluate by hot filtration (60 to 70 ° C.). The filtrate (extract) is cooled to 30 ° C., the degree of vacuum is adjusted so that the temperature of the can becomes 30 ° C., and the solution is concentrated to 1 ⁇ 5. After concentration, it is heated at 60 ° C. for 2 to 4 hours, and then aged at 30 ° C. for 10 to 20 hours.
  • the carotenoid composition containing astaxanthin, adonixanthin and adonirubin is recovered by filtration and dried by heating at 100 ° C. under vacuum.
  • a carotenoid composition extracted from a microorganism belonging to the genus Paracoccus (such as Paracoccus carotinifaciens etc.) can be obtained by the production method described in this example.
  • the brain function decrease inhibitor or preventive agent according to the present invention can be produced using the carotenoid composition described above.
  • a carotenoid composition can be used as it is for the brain function decrease inhibitor or preventive agent according to the present invention, it can be used as a pharmaceutically acceptable carrier, a food acceptable carrier, or a beverage besides a carotenoid composition.
  • a preparation (carotenoid preparation) containing an acceptable carrier and the like can also be used.
  • the carotenoid preparation of the present invention is The lower limit value of astaxanthin is preferably 0.5% by mass or more, more preferably 0.7% by mass or more, and most preferably 0.9% by mass or more, based on the total mass (100%) of the preparation. As 20% by weight or less, or 10% by weight or less, more preferably 5% by weight or less, and most preferably 3% by weight or less, The lower limit value of adonirubin is preferably 0.01% by mass or more or 0.05% by mass or more, more preferably 0.10% by mass or more, most preferably 0.1% by mass or more, based on the mass (100%) of the whole preparation.
  • adonixanthin is preferably 0.01% by mass or more, more preferably 0.03% by mass or more, and most preferably 0.04% by mass or more, based on the total mass (100%) of the preparation.
  • the upper limit thereof is preferably 4% by mass or less, more preferably 1% by mass or less or 0.5% by mass or less, and most preferably 0.2% by mass or less or 0.1% by mass or less.
  • the lower limit value and the upper limit value can be arbitrarily combined, and, for example, the carotenoid preparation of the present invention is 0.5 to 20% by mass astaxanthin, 0.01 to 4% by mass adonirubin based on the mass of the whole preparation. And 0.01 to 4% by mass of adonixanthin.
  • the carriers used in the present invention may be excipients, diluents, binders, fillers, lubricants, disintegrants, stabilizers, wetting agents, emulsifiers, buffers, suspending agents, preservatives or antioxidants.
  • diluents binders
  • fillers lubricants, disintegrants, stabilizers, wetting agents, emulsifiers, buffers, suspending agents, preservatives or antioxidants.
  • lubricants disintegrants
  • stabilizers wetting agents
  • emulsifiers emulsifiers
  • buffers emulsifiers
  • suspending agents preservatives or antioxidants.
  • sugars such as starches, dextrose, lactose, sucrose, glucose, sugar alcohols such as mannitol, xylitol, erythritol, sorbitol, maltitol, gum acacia, gum arabic, gelatin, magnesium aluminometasilicate, hydrotalcite, Inorganic compounds such as anhydrous calcium phosphate, calcium carbonate, calcium silicate and light anhydrous silicic acid, polyvinyl pyrrolidone, hydroxypropyl methyl cellulose, microcrystalline cellulose, talc, silica, magnesium stearate, sodium starch glycolate, sodium lauryl sulfate, cellulose derivative, Methyl-p-hydroxybenzoate, sorbic acid, water, mineral oils and the like can be mentioned.
  • carriers that can be used in the present invention are not limited to these examples, and examples include gum arabic, maltodextrin, tocopherol, medium-chain fatty acid and
  • the form of the cerebral function decrease inhibitor or preventive agent according to the present invention is not particularly limited.
  • a dosage form for oral administration or parenteral administration (intravenous, intraarterial, intraperitoneal, intrarectal, subcutaneous, intramuscular, sublingual, intranasal, intravaginal etc.)
  • parenteral administration intravenous, intraarterial, intraperitoneal, intrarectal, subcutaneous, intramuscular, sublingual, intranasal, intravaginal etc.)
  • Such a dosage form is not particularly limited, and examples thereof include solutions, tablets, intraoral fast disintegrating tablets, powders, granules, capsules, syrups, injections, suppositories, sprays, ointments, bops, etc. , Drink agents and the like.
  • the brain function decrease inhibitor or preventive agent according to the present invention is added to or enclosed in any form such as tablets, capsules, granules, tablets, jellies, gummi, gums, drinks, plastic bottles, or substantially carotenoids
  • the brain function decrease inhibitor or preventive agent according to the present invention can be made into a food composition or a drinking composition.
  • forms of food composition or drinking composition include functional food, health food, supplement, confectionery (jelly, yoghurt, pudding, biscuit or cookies, chocolate, candy, cake, ice cream, chewing gum), retort It includes, but is not limited to, food, soup, juices, teas, jelly drinks, powdered drinks, dairy products and the like.
  • a sweetener, a seasoning, an emulsifier, a suspending agent, a preservative, etc. can be added to a food composition or a drinkable composition as needed.
  • the food composition or the drinkable composition according to the present invention can be used as a food additive.
  • the dose of the carotenoid composition or preparation used for suppression or prevention of brain function reduction according to the present invention varies depending on factors such as the patient's age, weight, sex, condition and the like.
  • the daily dose of the brain function decrease inhibitor or preventive agent according to the present invention is 2 to 24 mg / day, preferably 4 to 12 mg / day, as calculated as astaxanthin, but is not limited to this range. If necessary, the above dose may be divided and administered once or several times a day, for example, 2 to 3 times.
  • the brain function decrease inhibitor or preventive agent according to the present invention can also be administered to a subject in combination with other brain function decrease inhibitors or preventive agents. Astaxanthin conversion means that the dose of the carotenoid contained in the carotenoid composition or preparation is represented by the amount of astaxanthin contained therein.
  • the present invention also relates to a method for preventing or suppressing brain dysfunction, comprising administering a carotenoid composition or preparation to a patient.
  • the method for preventing or suppressing the brain function decrease conforms to the description of the brain function decrease inhibitor or preventive agent according to the present invention.
  • brain functions include verbal memory ability or information processing ability. Therefore, the brain function decrease inhibitor or preventive agent according to the present invention can also be used to suppress or prevent the decline in speech memory ability, or to suppress or prevent the decrease in information processing ability.
  • the brain function depression to be suppressed or prevented in the present invention may be age-related brain function depression.
  • the subjects tested in this example are middle-aged and elderly people excluding those who have a history of cranial nerve disease and those who are suspected of having a low score on the intelligence evaluation scale. Therefore, it can be said that the brain function decrease inhibitor or preventive agent according to the present invention is effective for suppressing or preventing brain function decrease due to aging.
  • the effectiveness evaluation of the cerebral function depression inhibitor or preventive agent according to the present invention can be performed, for example, in the word memory test, recall test or Stroop test described in the following examples.
  • the brain function decrease inhibitor or preventive agent according to the present invention can be judged to have a brain function decrease inhibitory action or a preventive action.
  • the suppressive action and the preventive action of the brain dysfunction include improvement of the brain function, maintenance of the brain function, reduction of the degree of brain function decline, and reduction of the rate of the brain function decline.
  • Language memory ability is the ability to memorize language, and it is known that the ability to memorize language has short-term ability and long-term ability.
  • the word memory test is a test to confirm short-term verbal memory ability
  • the recall test is considered to be a test to confirm long-term verbal memory ability. Therefore, the preventive or suppressive effect of the decline in verbal memory ability can be confirmed by the memory test and recall test of the words tested in the examples.
  • Information processing ability is the ability of the brain to process information, and affects the amount of information that the brain can process and the speed at which the brain processes information.
  • the Stroop test is known to be a test for confirming selective attention, information processing speed, and the like. Therefore, the prevention or suppression effect of the decrease in information processing ability can be confirmed by the Stroop test tested in the examples.
  • Subject selection Criteria and Exclusion Criteria Subjects are males and females who are 45 to 64 years old at the time of obtaining consent, who do not violate the following exclusion criteria. In addition, those who excluded subjects who fall under the following analysis exclusion criteria were included in the analysis.
  • brain function was evaluated using a test for evaluating memory ability and recall (word memory test and recall test), and a Stroop test for evaluating information processing ability and attention function.
  • the amount of carotenoids (astaxanthin, adonirubin, adonixanthin) in serum was measured to confirm that carotenoids were absorbed after intake of the carotenoid-containing food.
  • Word memory test (verification test of language memory ability)
  • the "word memory test” is a test that evaluates the capacity of immediate memory and short time memory as well as its retention / reproduction ability. The procedure was carried out with reference to Imamura's test method (Yoko Imamura: Clinical Higher Brain Function Evaluation Manual 2000, Second Revised Edition, Emerging Medicine Publisher, 2001). Specifically, 7 words were given to the subject one by one and then repeated, and immediately after recalling the seventh word, these words were recalled ("immediate self-probable number"). For words that were not able to be used for immediate self-exploration, they were given a hint of a prefix or category and recalled, and the number of recalled words was defined as the “number of recalled CUEs”.
  • the interference task (recollection test) was carried out.
  • the word was reproduced 5 minutes after the immediate self-provocation ("the number of spontaneous reproduction after 5 minutes").
  • a hint of a prefix or category was given and reproduced, and the number of CUE reproductions that could be reproduced "the number of spontaneous reproductions after 5 minutes + the number of CUE reproductions" was recorded.
  • an increase in the measured value indicates that verbal memory has improved or improved.
  • Recall test (verification test of language memory ability)
  • the "recollection test” is a test that evaluates the ability to recall memory. The procedure was carried out with reference to Imamura's test method (Yoko Imamura: Clinical Higher Brain Function Evaluation Manual 2000, Second Revised Edition, Emerging Medicine Publisher, 2001). For example, as a recall test for "vegetables”, he taught “Please say the name of vegetables in 1 minute as much as possible”, and wrote out words that could be listed in 60 seconds after the first was listed. The number of words that could be listed excluding the duplicates was recorded. The recall test for "words beginning with” A "” and "animal” was also conducted.
  • the order of the recall test was changed at each of the preintake test, the 4th week test, and the 8th week test. Each was evaluated by the number of words that could be listed. In the recall test, an increase in the measured value indicates that the verbal memory has improved or improved.
  • Stroop test (verification test of information processing ability)
  • the Stroop test is a test that evaluates the identification and processing ability of two different types of information that simultaneously enter the brain: verbal information and color vision information. It carried out according to the test
  • inspection implementation procedure of new stroop test II (Yuji Hakata, Megumi Watanabe: new Stroop test II, Toyo Physical, Inc., http://www.toyophysical.co.jp/sinnsutoru-pu1.htm).
  • the Stroop test consists of substeps of four steps of “step 1”, “step 2”, “step 3” and “step 4”, and the degree of difficulty increases as the steps progress.
  • the number of achievements (number of correct answers + number of incorrect answers), the number of correct answers and the number of incorrect answers (errors) were evaluated.
  • An increase in measured values in the number of achievements and the number of correct answers indicates that the information processing ability has improved or improved.
  • the decrease in the measured value in the number of incorrect answers indicates that the information processing ability has been improved or improved.
  • a carotenoid eluate was prepared by extracting the dried product of the microorganism belonging to the genus Paracoccus with ethanol at 90 ° C. for 20 minutes.
  • the cell residue was removed from the carotenoid eluate by hot filtration at 65 ° C.
  • the filtrate (extract) was cooled to 30 ° C., the degree of vacuum was adjusted so that the temperature of the can became 30 ° C., and the solution was concentrated to 1 ⁇ 5 of the solution volume. After concentration, it was heated at 60 ° C. for 3 hours and then aged at 30 ° C. for 12 hours.
  • the carotenoid composition containing astaxanthin, adonixanthin and adonirubin was recovered by filtration and dried by heating at 100 ° C. under vacuum.
  • the composition of the resulting carotenoid composition is shown in Table 3 below.
  • a carotenoid preparation (containing 1% by mass of astaxanthin, 0.14% by mass of adonirubin, and 0.05% by mass of adonixanthin).
  • a carotenoid preparation (containing 8 mg of astaxanthin, 1.12 mg of adonirubin, 0.4 mg of adonixanthin), add 896 mg of a pH adjuster, 4,092 mg of a sweetener, 630 mg of a gelling agent, 200 mg of a fragrance, and 33,382 mg of water, A carotenoid-containing food was produced. 40 g of the carotenoid-containing food thus produced was packaged in 4 bags of 10 g jelly.
  • a non-carotenoid placebo (raw material: 2 mg of food pigment, 896 mg of pH adjuster, 4,092 mg of sweetener, 630 mg of gelling agent, 200 mg of flavor, 34, 180 mg of water) was produced.
  • Carotenoid-containing food was ingested 4 bags in total 2 bags each after breakfast and dinner twice daily for subjects under the age of 55 (carotenoid intake per day: 8 mg of astaxanthin, 1.12 mg of adonirubin, 0.4 mg of adonixanthin). The time of intake was not specified. Those who did not eat breakfast had a carotenoid-containing food by 8 am. The carotenoid-containing food was also consumed on the day of the examination. The carotenoid-containing food was stored in a refrigerator.
  • a word memory test was performed on a group of subjects 4 weeks after the start of intake.
  • the transition of the measured value of each item and the amount of change from before intake are shown in Table 4.
  • the measurement values of “the number of immediate self-concepts + the number of CUE recalls” before intake and 4 weeks after intake start are shown in FIG.
  • Comparative Example 1 A placebo was ingested as in Example 1 to a group of subjects younger than 55 years. A word memory test was performed on a group of subjects 4 weeks after the start of intake. The transition of the measured value of each item and the amount of change from before intake are shown in Table 4. The measurement values of “the number of immediate self-concepts + the number of CUE recalls” before intake and 4 weeks after intake start are shown in FIG.
  • Example 1 Comparison of Example 1 and Comparative Example 1
  • the measured values of "the number of immediate self-concept generation + the number of CUE recalls” of Example 1 and the measured values of "the number of immediate self-concepts creation + the number of CUE recalls” of Comparative Example 1 before intake and 4 weeks after intake start are shown in FIG. .
  • Four weeks after the start of administration the variation of the three items of "instant self-conceptual occurrence number + CUE recall number", “Spontaneous regeneration number after 5 minutes” and “Spontaneous regeneration number after 5 minutes + CUE regeneration number” of Example 1 are comparative examples.
  • Example 2 With respect to a group of subjects under the age of 55, a carotenoid-containing food was ingested as in Example 1, and a recall test was performed. In Example 2, the intake period was 8 weeks. Table 5 shows the transition of measured values of each item and the amount of change from before intake.
  • Comparative Example 2 For the group of subjects younger than 55 years of age, a placebo containing no carotenoid was taken in the same manner as in Comparative Example 1, and a recall test was performed. In Comparative Example 2, the intake period was 8 weeks. Table 5 shows the transition of measured values of each item and the amount of change from before intake.
  • Example 2 shows the number of recalled words
  • the amount of change of D is 1 to 2 more than the amount of change of Comparative Example 2. From these results, it was demonstrated that when subjects under 55 years of age, that is, 45-54-year-old men and women with carotenoid-containing food for four weeks or longer, improve word recall. That is, it was shown that intake of a carotenoid-containing food from the early stage of aging is useful for preventing, maintaining or improving the reduction in word recall.
  • a Stroop test was performed on a subject group of 55 years old or older (55 to 64 years old) by taking a carotenoid-containing food as in Example 1.
  • the results of the achieved numbers are shown in Table 6, the results of the number of correct answers are shown in Table 7, and the results of the incorrect number are shown in Table 8.
  • Comparative Example 3 A Stroop test was performed on a group of subjects aged 55 years or older (55 to 64 years), taking a placebo as in Comparative Example 1. The results of achieved numbers are shown in Table 6, the results of correct answers are shown in Table 7, and the results of incorrect numbers are shown in Table 8.
  • Example 3 significantly increased as compared with Comparative Example 3 with respect to the variation of Step 4 of the number of achievements, Step 4 of 4, Step 8 of the correct answer, and Week 4 of Step 3 of the number of correct answers.
  • P ⁇ 0.1 the amount of change of Example 3 was larger than that of Comparative Example 3 with respect to the amount of change at the 8th week of Step 3 (p ⁇ 0.1). That is, in the Stroop test, in the carotenoid-containing food intake group over 55 years of age, improvement tendencies were seen in the number of Step 1 achieved, the number 1 of correct answers, 3 and the number 3 of incorrect numbers.
  • the composition or preparation of the present invention It has been shown that it is useful for the prevention, maintenance or improvement of memory ability and the prevention, maintenance or improvement of reduction in recall of words. Furthermore, it has been shown that the composition or preparation of the present invention is useful for preventing, maintaining, or improving the decrease in information processing ability in a subject layer of 55 years old or older, which is from the early stage of aging.
  • Carotenoids used in the examples of the present invention are derived from bacteria belonging to the genus Paracoccus, and include carotenoids such as adonirubin and adonixanthin in addition to astaxanthin.
  • carotenoids produced by Haematococcus algae are almost exclusively astaxanthin, and the brain function improving effect of the carotenoid composition derived from Haematococcus algae was examined.
  • significant differences were observed between the placebo group and the carotenoid composition administration group. (J Clin Biochem Nutr. 2012 Sep; 51 (2): 102-107.).
  • adonirubin and adonixanthin are transferred to the blood of a subject more efficiently than astaxanthin, and may be in or around the brain. It is also considered that they accumulated and exhibited their functions.
  • a brain function hypoallergenic agent or a brain hypofunction inhibitor there is provided a brain function hypoallergenic agent or a brain hypofunction inhibitor.
  • a preventive agent for cerebral function decline with aging or an inhibitor for cerebral function decline with age is provided.

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001002569A (ja) * 1999-06-18 2001-01-09 Itano Refrigerated Food Co Ltd 記憶力改善組成物
JP2007126455A (ja) * 2005-10-07 2007-05-24 Fuji Chem Ind Co Ltd 脳機能障害の改善剤
JP2012025712A (ja) * 2010-07-27 2012-02-09 Jx Nippon Oil & Energy Corp 抗不安組成物
WO2015114900A1 (ja) * 2014-01-30 2015-08-06 Ｊｘ日鉱日石エネルギー株式会社 虚血性疾患を予防するための薬剤

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001002569A (ja) * 1999-06-18 2001-01-09 Itano Refrigerated Food Co Ltd 記憶力改善組成物
JP2007126455A (ja) * 2005-10-07 2007-05-24 Fuji Chem Ind Co Ltd 脳機能障害の改善剤
JP2012025712A (ja) * 2010-07-27 2012-02-09 Jx Nippon Oil & Energy Corp 抗不安組成物
WO2015114900A1 (ja) * 2014-01-30 2015-08-06 Ｊｘ日鉱日石エネルギー株式会社 虚血性疾患を予防するための薬剤

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HAYASHI, M. ET AL.: "Effect of astaxantnin-rich extract derived from paracoccus carotinifaciens on cognitve funtion in middle-aged and older individuals", J. CLIN. BIOCHEM. NUTR, vol. 62, no. 2, 27 January 2018 (2018-01-27) - March 2018 (2018-03-01), pages 195 - 205, XP055597534, DOI: 10.3164/jcbn.17-100 *
KATAGIRI, M. ET AL.: "Effects of astaxanthin-rich Haematococcus pluvialis extract on cognitive function: a randomised, double-blind, placebo- controlled study", J. CLIN. BIOCHEM. NUTR., vol. 51, no. 2, 30 March 2012 (2012-03-30) - September 2012 (2012-09-01), pages 102 - 107, XP055597526, DOI: 10.3164/jcbn.D-11-00017 *

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