WO2011118468A1

WO2011118468A1 - Wake-time-extending agent

Info

Publication number: WO2011118468A1
Application number: PCT/JP2011/056192
Authority: WO
Inventors: 内田　勝幸; 成臣山田; 伊藤　裕之
Original assignee: 株式会社明治
Priority date: 2010-03-24
Filing date: 2011-03-16
Publication date: 2011-09-29
Also published as: JP2016028097A; JPWO2011118468A1; JP6049108B2; IN2012DN06612A; CN102933210A

Abstract

Disclosed is a food, beverage or medicinal material which is safe and readily available, does not undergo the deterioration in flavor when combined with another food material or material, is suitably applicable to foods, beverages and medicinal agents, and has a wake-time-extending activity. It is found that an oxidized carotene derivative derived from a terrestrial animal, a terrestrial plant or a microorganism has an activity of shortening a sleep time and extending a wake time.

Description

Awakening time extender

The present invention relates to a wakefulness-prolonging agent comprising a land animal, a land plant or a microorganism-derived carotene oxidant as an active ingredient.

Carotenoid is a general term for the hydrocarbons carotenes in which eight isoprenoid units are bonded. Carotenoids are natural pigments that are distributed in plants, microorganisms and animals, have a physiological effect as provitamin A, such as β-carotene, and the active ingredients of herbal medicines such as crocin and crocetin, and the coloring of foods containing these Some important fees are included. In plants and photosynthetic bacteria, it is known as an auxiliary enzyme in light energy transmission (Non-patent Document 1). Recently, many new actions have been found in carotenoids, so-called marine carotenoids contained in marine organisms such as seafood and seaweed.

For example, fucoxanthin, which is one of the fat-soluble substances contained in seaweeds such as hijiki and seaweed, has anti-obesity action (Non-patent Document 2), neutral fat absorption inhibitory action (Patent Document 1), and the like.

In addition, for example, astaxanthin, which is contained in crustaceans such as shrimp and crab and used as a red pigment, has an in vivo antioxidant action (Patent Document 3) and has an effect of improving liver function (patent) Document 4) has been found. Furthermore, astaxanthin has also been found to have an effect of improving muscle damage and disease (Patent Document 2).

On the other hand, lutein, a type of carotenoid, is a pigment present in plant leaves, flowers, fruits and egg yolks. Lutein has long been used as a food additive for coloring, but it has recently been used as a functional food material because it has effects such as eyestrain based on antioxidant action and suppression of cataract and age-related macular degeneration. Also attracting attention. For example, Patent Document 5 discloses a composition for eye strain containing lutein. Patent Document 6 discloses a nutritional supplement for treating macular degeneration containing lutein.

By the way, with the diversification of lifestyles, in the modern society with irregular life and stress, diseases related to circadian rhythm disorders such as sleep disorders are disturbed due to disturbed sleep-wake rhythm and balance based on the body clock. Is increasing rapidly. Moreover, in general, sleep is shallow in elderly people, and awakening is frequently observed on the way, and sleep disorders are likely to occur. Although there are various causes of sleep disorders, it is said that one of the causes is that the amount of exercise during the activity time is related to poor sleep. Therefore, there is a demand for materials that support life rhythms that can be active during active hours and, as a result, provide high quality sleep.

As means for solving these problems, Patent Document 7 discloses a circadian rhythm normalizing composition containing astaxanthin which is a kind of carotenoid and / or its ester as an active ingredient. The invention described in Patent Document 7 has an action in which astaxanthin effectively regulates the daily rhythm by increasing the utilization rate of melatonin in vivo, and is a rat sleep time zone in a rat experiment. This is based on the action of reducing the activity ratio of the light period with astaxanthin. That is, the circadian rhythm normalization composition described in Patent Document 7 affects sleep.

However, since the circadian rhythm normalizing composition described in Patent Document 7 affects sleep time, there remains a question as to whether it is possible to improve the poor sleep due to the small amount of exercise during the activity time. Further, astaxanthin, which is a circadian rhythm normalizing composition described in Patent Document 7, belongs to marine carotenoids. For example, when applied to food and drink such as dairy products, the odor derived from raw materials becomes a problem, and there is a problem in terms of flavor. It will remain.

JP 2009-173597 A JP-T-2001-514215 JP-A-2-49091 JP-A-9-124470 JP 2007-308396 A Japanese Patent No. 3672554 International Publication No. WO01 / 087291

The present invention has been made in view of the above situation, and the problem to be solved by the present invention is that it is safe and easy to obtain, and does not cause a problem of flavor even when combined with other foods and ingredients. It is to provide a time extender, and at the same time, to provide a food / beverage product, a food composition, and a pharmaceutical composition using the awakening time extender.

In view of the above-mentioned conventional problems, the present inventors conducted extensive research and found that the action of extending the awakening time to carotenylated derivatives derived from terrestrial animals, terrestrial plants or microorganisms was found.

That is, the present invention relates to the following [1] to [24].
[1] An awakening time prolonging agent comprising a caroten-oxidized derivative derived from a land animal, a land plant or a microorganism as an active ingredient.
[2] The awakening time extending agent according to [1], wherein the terrestrial animal, land plant or microorganism-derived carotene oxidation derivative contains at least one of a hydroxyl group, a carbonyl group, and an ether group.
[3] The above terrestrial animal, terrestrial plant or microorganism-derived carotene oxidation derivative is lutein, zeaxanthin, crocin, spheroidene, violaxanthin, torularhodinaldehyde ), Torularhodin, capsanthin, crocetin, bixin, azafrin, β-carotenone, beta-carotenone, eschscholtzxanthin, rhodoxanthin, cap The awakening time extending agent according to [1] or [2], wherein at least one of (decaprenoxanthin) is an active ingredient.
[4] The awakening time according to any one of [1] to [3], wherein an effective amount of the carotene oxidation derivative derived from a land animal, a land plant or a microorganism is 0.1 to 1500 mg / 60 kg body weight. Extender.
[5] A pharmaceutical composition for prolonging wakefulness, comprising 0.01 to 95% by weight of the wakefulness extending agent according to any one of [1] to [4].
[6] A food / beverage product for prolonging the arousal time, comprising 0.0001 to 10% by mass of the awakening time extending agent according to any one of [1] to [4].
[7] A method for extending awakening time, comprising a step of administering to a subject a pharmaceutically effective amount of a carotenylated derivative derived from a land animal, a land plant or a microorganism.
[8] The method according to [7], wherein the carotene oxidation derivative derived from a land animal, a land plant, or a microorganism includes at least one of a hydroxyl group, a carbonyl group, and an ether group.
[9] The above-mentioned terrestrial animal, terrestrial plant or microorganism-derived carotene oxidation derivative is selected from the group consisting of lutein, zeaxanthin, crocin, spheroidene, violaxanthin, torularhodinaldehyde ), Torularhodin, capsanthin, crocetin, bixin, azafrin, β-carotenone, beta-carotenone, eschscholtzxanthin, rhodoxanthin, cap [7] or [8], wherein at least one of (decaprenoxanthin) is an active ingredient.
[10] The method according to any one of [7] to [9], wherein an effective amount of the carotene oxidation derivative derived from land animals, land plants, or microorganisms is 0.1 to 1500 mg / 60 kg body weight.
[11] A method for producing a pharmaceutical composition effective for extending awakening time, comprising the step of blending 0.01 to 95% by weight of the awakening time extending agent according to any one of [1] to [4] .
[12] A method for producing a food or drink effective for extending awakening time, comprising the step of adding 0.0001 to 10% by mass of the awakening time extending agent according to any one of [1] to [4].
[13] Use of carotene-oxidized derivatives derived from terrestrial animals, terrestrial plants or microorganisms in the production of awakening time prolonging agent.
[14] The use according to [13], wherein the carotene oxidation derivative derived from a land animal, a land plant, or a microorganism contains at least one of a hydroxyl group, a carbonyl group, and an ether group.
[15] The carotenylated derivatives derived from terrestrial animals, terrestrial plants or microorganisms are lutein, zeaxanthin, crocin, spheroidene, violaxanthin, torularhodinaldehyde ), Torularhodin, capsanthin, crocetin, bixin, azafrin, β-carotenone, beta-carotenone, eschscholtzxanthin, rhodoxanthin, cap The use according to [13] or [14], wherein at least one of (decaprenoxanthin) is an active ingredient.
[16] The use according to any one of [13] to [15], wherein an effective amount of the carotenylated derivative derived from a land animal, land plant or microorganism is 0.1 to 1500 mg / 60 kg body weight.
[17] Use of the agent for extending wakefulness according to any one of [1] to [4] in the production of a pharmaceutical composition effective for prolonging wakefulness.
[18] Use of the awakening time extending agent according to any one of [1] to [4] in the production of a food or drink effective for extending the awakening time.
[19] A carotene-oxidized derivative derived from a land animal, a land plant, or a microorganism for use in extending awakening time.
[20] The carotene-oxidized derivative according to [19], which contains at least one of a hydroxyl group, a carbonyl group, and an ether group.
[21] lutein, zeaxanthin, crocin, spheroidene, violaxanthin, torularhodinaldehyde, torularhodin, capsanthin, crocetin , Bixin, azafrin, beta-carotenone, eschscholtzxanthin, rhodoxanthin, decaprenoxanthin, and decaprenoxanthin [19] or [20].
[22] The carotene-oxidized derivative according to any one of [19] to [21], wherein an effective amount for use in extending awakening time is 0.1 to 1500 mg / 60 kg body weight.
[23] The agent for extending wakefulness according to any one of [1] to [4] for use in the production of a pharmaceutical composition effective for prolonging wakefulness.
[24] The agent for extending awakening time according to any one of [1] to [4], which is used for producing a food or drink effective for extending awakening time.

The awakening time extender of the present invention is useful as a food or drink or a medicine for shortening the sleeping time and prolonging the awakening time. And the food / beverage / beverage-drink material or the drug / drug material having an arousal action in which the agent for extending the arousal time of the present invention is blended comprises a land animal, a land plant or a microorganism-derived carotene oxidation derivative as an active ingredient. It is safe because it has abundant dietary experience and few side effects. Furthermore, the odor derived from the raw material is much less than the conventional odor and is excellent in flavor. Also, by ingesting, taking, or administering the wakefulness extending agent of the present invention, for example, by spending longer wakefulness during the day and becoming active, it is possible to have good quality sleep during the sleeping hours. Obtainable.

It is a figure which shows the awakening time in the dark period at the time of olive oil administration and lutein administration for each rat. It is a figure which shows the Non-REM sleep time in the dark period at the time of olive oil administration and lutein administration by rat individual. It is a figure which shows the REM sleep time in the dark period at the time of olive oil administration and lutein administration for every rat individual. In each rat, increase or decrease in awakening time, non-REM sleep time, and REM sleep time in the dark period after lutein administration based on wakefulness time, Non-REM sleep time, and REM sleep time based on olive oil administration in each rat Is an average value. (*) In the figure indicates that there is a significant difference at a risk rate of 10% or less compared to when olive oil is administered (p <0.1, t test), and * indicates that when lutein is administered compared to when olive oil is administered. It shows that there is a significant difference at a risk rate of 5% or less (p <0.05, t test).

Hereinafter, the present invention will be described in detail, but the present invention is not limited to the individual forms described below.

The carotenylated derivatives derived from land animals, land plants or microorganisms in the present invention are not particularly limited as long as they are carotenylated derivatives derived from, for example, vegetables, fruits and microorganisms containing carotenoids. The carotene oxidized derivative of the present invention can contain at least one of a hydroxyl group, a carbonyl group, and an ether group.
As an example of the carotene-oxidized derivative of the present invention, lutein is given and described below.

Lutein is abundant in vegetables, fruits and plants. In particular, it is one of carotenoids widely present in the plant world, such as green-yellow vegetables such as kale, brussels sprouts, spinach, broccoli, and yellow flowers such as marigold. Among them, the petals of the Asteraceae are contained in high concentrations in petals and have been used since ancient times as feed for enhancing the coloration of egg yolks in poultry, and in recent years as food colorings that take advantage of their clear yellow color. in use. Lutein is also known to improve eye diseases such as age-related macular degeneration and cataracts. Lutein has a CAS No. of 127-40-2, and lutein is also known as (3R, 3'R, 6'R) -β, ε-carotene-3,3'-diol ((3R, 3'R , 6'R) -β, ε-carotene-3,3'-diol), (3R, 3'R, 6'R) -3,3'-dihydroxy-β, ε-carotene ((3R, 3 ' R, 6′R) -3,3′-Dihydroxy-β, ε-carotene) or narrowly defined xanthophyll. Lutein belongs to the alcohol derivative of carotene, and lutein 20S (containing 20% by mass of lutein, Kyowa Hakko Bio Co., Ltd.) is commercially available. Lutein 20S is a reddish brown heat-softening paste containing 20% lutein derived from marigold petals.

Extraction of lutein is carried out by impregnating the above-mentioned plants and microorganisms with a solvent at room temperature or in a heated state, or by using a distillation device such as steam distillation in addition to solvent extraction performed using an extraction device such as a Soxhlet extractor. Extraction method, supercritical extraction method using carbon dioxide gas in a supercritical state, or pressing method to obtain an extract by pressing, freeze-dried, and distilled water is added to remove the residue to obtain a supernatant A method or the like can be used. In addition, fruit juice or the like can be used after being subjected to treatment such as spray drying.

As the extraction solvent used for the above-mentioned extraction, either a polar solvent or a nonpolar solvent can be used, and these can also be mixed and used. For example, water; alcohols such as methanol, ethanol, propanol and butanol; polyhydric alcohols such as ethylene glycol, propylene glycol and butylene glycol; ketones such as acetone and methyl ethyl ketone; esters such as methyl acetate and ethyl acetate; tetrahydrofuran Linear and cyclic ethers such as diethyl ether; polyethers such as polyethylene glycol; halogenated hydrocarbons such as dichloromethane, chloroform and carbon tetrachloride; hydrocarbons such as hexane, cyclohexane and petroleum ether; benzene and toluene Aromatic hydrocarbons such as; pyridines; supercritical carbon dioxide; oils, waxes, other oils, and the like. These can be used alone or in combination of two or more, and can be repeated by changing the solvent. In . Of these, water, ethanol, propylene glycol, butylene glycol and the like are preferably used, and a water / ethanol mixed solution is more preferably used.

In addition, examples of the means for separating and purifying the extract include activated carbon treatment, liquid-liquid distribution, column chromatography, liquid chromatography, gel filtration, and precision distillation.

In addition to lutein, examples of carotene oxidation derivatives of the present invention include carotene alcohol derivatives (zeaxanthin etc.), glycosides (crocin etc.), ether derivatives (spheroidene etc.), epoxide derivatives (violaxanthin etc.), aldehyde derivatives ( Tolralozinaldehyde, etc.) and carboxylic acid derivatives (tolralodine, etc.), as well as apocarotenoids (crocetin, bixin, azafrine, etc.), secocarotenoids (β-carotenone, etc.), retro carotenoids (such as eschertxanthin, rhodoxanthin, etc.), higher carotenoids ( Carotenylated derivatives belonging to decaprenoxanthin and the like, and those derived from land animals, land plants or microorganisms. For example,
Zeaxanthin (also called (3R, 3'R) -β, β-carotene-3,3'-diol, CAS No. 144-68-3, distributed in corn seeds, physalis, etc., Fluka, EXTRASYNTHESE SA Etc.)
Crocin (8,8'-Diapo-ψ, ψ-carotene-8,8'-dioic acid bis (6-O-β-D-glucopyranosyl-β-D-glucopyranosyl) ester, CAS No, 42553 -65-1, distributed in saffron stigma, gardenia fruit, etc., available at Sigma / EXTRASYNTHESE SA etc.),
Spheroidene (also known as spheroidene, 3,4-Didehydro-1,2,7 ', 8'-tetrahydro-1-methoxy-ψ, ψ-carotene, CAS No. 13836-61-8, Rhodopseudomonas spheroides, etc.) distribution),
Violaxanthin (also called violaxanthin, 5α, 6α: 5'α, 6'α-Bisoxy-5,5 ', 6,6'-tetrahydro-β, β-carotene-3β, 3β'-diol, CAS No. 126 -29-4, petals of sansikisumire, distributed in many green leaves and fruits, available at CaroteNature, etc.),
Torralodin aldehyde (also called torularhodinaldehyde, distributed in Rhodotorula genus yeast),
Torralodin (also called torularhodin, 3 ', 4'-Didehydro-β, ψ-caroten-16'-oic acid, CAS No. 514-92-1, distributed in Rhodotorula genus yeast, etc., available at CaroteNature, etc.),
Crocetin (also referred to as crocetin, 8,8'-Diapo-ψ, ψ-carotene-8,8'-dioic acid, CAS No, 27876-94-4, saffron stigma, etc., available at EXTRASYNTHESE SA, etc.) ,
Bixin (also referred to as (9Z) -6,6'-Diapo-ψ, ψ-carotene-6,6'-dioic acid 6-methyl ester, CAS No. 6983-79-5, akinoki fruit) , Available at CaroteNature / ChromaDex, Inc., etc.)
Azafrin (5R, 6R) -5,6-Dihydro-5,6-dihydroxy-10'-apo-β, ψ-carotenoic acid, CAS No. 507-61-9・ Distributed to roots)
β-Carotenone (also known as β-carotenone, 5,6,5 ', 6'-Diseco-β, β-caroten-5,6,5', 6'-tetrone, distributed in Murraya exotica, etc., CaroteNature Etc.)
Eschscholtzxanthin (3S, 3'S) -4 ', 5'-Didehydro-4,5'-retro-β, β-carotene-3,3'-diol, CAS No. 472-73-1 , Distributed in petals etc.)
Rhodoxanthin (also known as rhodoxanthin, 4 ', 5'-Didehydro-4,5'-retro-β, β-carotene-3,3'-dione, CAS No. 116-30-3, yew fruit) , Available at CaroteNature, etc.),
Decaprenoxanthin (decaprenoxanthin, (2R, 2'R, 6R, 6'R) -2,2'-Bis [(E) -4-hydroxy-3-methyl-2-butenyl] -ε, ε-carotene CAS No. 28368-06-1, Flavobacterium dehydrogenans (bacteria), Arthrobacter glacialis (bacteria), etc.), but are not limited to these examples.

The terrestrial animal, terrestrial plant or microorganism-derived carotene oxidation derivative used in the wakefulness prolonging agent of the present invention is the extract obtained by the method exemplified above or the separated fraction as it is, or appropriately diluted with a solvent. It can be used as a diluting solution, or can be made into a concentrated extract or dry powder, or can be prepared as a paste.

The awakening time extending agent of the present invention has an action of extending the awakening time.

On the other hand, the awakening time extending agent of the present invention has an action of shortening the sleeping time.

The terrestrial animal, terrestrial plant or microorganism-derived carotene oxidation derivative of the present invention has an action of shortening the sleep time and prolonging the awakening time, as shown in Examples below. Therefore, the terrestrial animal, land plant or microorganism-derived carotene-oxidized derivative of the present invention can be used not only as a wakefulness extending agent but also as a sleeping time shortening agent. Furthermore, in order to produce a drug (or a pharmaceutical composition, the same shall apply hereinafter) and a food or drink effective for extending the awakening time, the wakefulness extending agent of the present invention is combined with other additives or food and drink materials. Can be used.

The pharmaceuticals and foods and drinks of the present invention include “pharmaceutical compositions or foods and beverages that extend awakening time”, “pharmaceutical compositions or foods and beverages that are used to extend awakening time”, and “pharmaceutical compositions that shorten sleep time” It can also be referred to as “food or drink” or “pharmaceutical composition or food or drink used to shorten sleep time”.

The awakening time extender of the present invention is an additive for human or veterinary drugs, quasi-drugs, foods, functional foods, foods for the sick, and foods for specified health use that exert the action of extending the awakening time. It can be used. In addition, the present invention can be applied as a human or veterinary drug, a quasi drug, a food, a functional food, a food for a sick person, or a food for specified health, which indicates that the awakening time is extended. In addition, those who perform driving operations, those who assist driving operations, medical workers, construction workers, etc., who are not allowed to sleep while working and may threaten the life of the person or others, normal time for sleeping It can be used to deal with all people including athletes as well as those who work (eg at night), lack of exercise, middle-aged, and bed rest.

The wakefulness extending agent of the present invention, for example, makes it possible to obtain a good quality sleep during the sleeping hours by spending more wakefulness during the day and becoming more active. In addition, since the awakening time can be longer, it is possible to prevent bedridden elderly people and long-term caregivers, and to extend the awakening state of those who are required to be in an awakening state. Can be arranged freely.

In the present invention, when the wakefulness extending agent is used for treatment or prevention, it is desirable to administer the wakefulness extending agent of the present invention to the subject. The subject of administration of the awakening time prolonging agent of the present invention may be a person who performs driving operation, a person who assists driving operation, a medical worker, or a construction worker, etc. Examples include, but are not limited to, those who are not allowed, those who work normally during sleep (such as at night), those who are under exercise, those who are middle-aged and elderly, and those who are bed rests. It is not a thing.

Examples of the dosage form when the awakening time extender of the present invention is used as a pharmaceutical product or quasi-drug include oral administration by tablet, capsule, granule, powder, syrup or the like, injection, suppository, inhalant, Examples include parenteral administration using transdermal absorption agents, external preparations and the like. In order to prepare such various dosage forms, the carotene-oxidized derivative of the present invention (for example, lutein) alone or other pharmaceutically acceptable excipients, binders, extenders, Disintegrants, surfactants, lubricants, dispersants, buffers, preservatives, flavoring agents, fragrances, coating agents, carriers, diluents, and the like can be used in appropriate combinations. Of these dosage forms, the preferred form is oral administration. For example, when preparing an oral liquid preparation, it can be produced by a conventional method with the addition of a flavoring agent, a buffering agent, a stabilizer and the like. .

Foods and drinks effective for extending the awakening time of the present invention are not limited to categories and types, and may be functional foods and drinks, specified health foods and drinks, health foods and drinks, nursing foods and drinks, confectionery, lactic acid bacteria beverages, It may be a dairy product such as cheese or yogurt, a seasoning or the like. There is no restriction | limiting also about the shape of food / beverage products, It can take all the food / beverage product forms which can distribute | circulate normally, such as solid, liquid, liquid food form, jelly form, gummy form, tablet form, granule form, and capsule form. The above-mentioned food and drink can be produced by ordinary methods of those skilled in the art, but carbohydrates, proteins, lipids can be used as long as they do not hinder the awakening time-extending action of the land animal, land plant or microorganism-derived carotene-oxidized derivative of the present invention. Dietary fiber, vitamins, biologically essential trace metals (manganese sulfate, zinc sulfate, magnesium chloride, potassium carbonate, etc.), fragrances and other compounds can also be added.

Moreover, the food / beverage products which mix | blend the awakening time extension agent of this invention, specifically, various food / beverage products, food-drinks composition (For example, milk, milk drink, soft drink, fermented milk, yogurt, cheese, bread, Biscuits, crackers, pizza crusts, formula milk, liquid foods, foods for the sick, foods such as infant milk powder, foods such as infant milk powder, nutritional foods, etc.) It can be produced by adding an awakening time extending agent comprising a carotene oxide derivative as an active ingredient. Moreover, you may ingest the food / beverage products with which these awakening time extension agents were mix | blended.

The blending amount of the awakening time extender of the present invention for these foods and drinks or food / beverage product compositions varies depending on the form of use, but the case where the awakening time extender of the present invention is lutein is as follows. is there. In the form of food, it is usually 0.0001 to 10% by mass, more preferably 0.001 to 5% by mass, and particularly preferably 0.002 to 2% by mass. In the case of beverages, it is preferably 0.001 to 0.5% by mass, more preferably 0.005 to 0.25% by mass, and particularly preferably 0.01 to 0.1% by mass. In the case of food tablets and / or capsules such as tablets, it is preferable that lutein is contained in an amount of 0.1 to 95% by mass, further 1 to 90% by mass, particularly 5 to 50% by mass. In addition, about the property, the state of the food / beverage products normally used, for example, any of solid (powder, granule, etc.), paste, liquid, suspension or gel may be used.

In the case of pharmaceuticals other than the above, for example, oral solid preparations such as tablets, granules, capsules, and oral liquid preparations such as oral liquids and syrups, lutein is usually 0.01 to 95% by mass, Further, it is preferably 5 to 90% by mass, particularly 10 to 50% by mass.

Other ingredients are also not particularly limited, but when using the wakefulness extender comprising the terrestrial animal, land plant or microorganism-derived carotene oxidation derivative of the present invention as an active ingredient as a food or drink or food composition, water, protein Sugars, lipids, vitamins, minerals, organic acids, organic bases, fruit juices, flavors and the like can be used as main components. Examples of the protein include whole milk powder, skim milk powder, partially skim milk powder, casein, whey powder, whey protein, whey protein concentrate, whey protein isolate, α-casein, β-casein, κ-casein, β-lactoglobulin , Α-lactalbumin, lactoferrin, soy protein, chicken egg protein, meat protein, etc., and their hydrolysates; butter, whey minerals, cream, whey, non-protein nitrogen, sialic acid, phospholipid, lactose, etc. And various milk-derived components. Examples of the saccharide include general saccharides, modified starch (in addition to dextrin, soluble starch, British starch, oxidized starch, starch ester, starch ether, etc.), dietary fiber, and the like. Examples of the lipid include animal oils such as lard, fish oil, etc., fractionated oils, hydrogenated oil, transesterified oil, etc .; palm oil, safflower oil, corn oil, rapeseed oil, coconut oil, fractionated oils thereof, Examples include vegetable oils such as hydrogenated oils and transesterified oils. Examples of vitamins include vitamin A, carotenes, vitamin B group, vitamin C, vitamin D group, vitamin E, vitamin K group, vitamin P, vitamin Q, niacin, nicotinic acid, pantothenic acid, biotin, inositol, choline. And minerals include, for example, calcium, potassium, magnesium, sodium, copper, iron, manganese, zinc, selenium, and whey minerals. Examples of the organic acid include malic acid, citric acid, lactic acid, and tartaric acid. These components can be used alone or in combination of two or more, and synthetic products and / or foods containing a large amount thereof may be used.

The effective intake (dose) of the awakening prolonging agent of the present invention is preferably 0.1 to 1500 mg / 60 kg body weight per day, more preferably 1 to 1200 mg / 60 kg body weight, and particularly preferably 5 to 1000 mg / 60 kg body weight.

Note that all prior art documents cited in the present specification are incorporated herein by reference.

Hereinafter, the present invention will be described with reference to experimental examples and examples, but the present invention is not limited thereto. In addition, in this specification,% display shows mass%, when not showing clearly.

[Experimental Example 1]
<Evaluation during the dark period>
Eight male 10-week-old SD rats were incised at the head under pentobarbital anesthesia, and an electroencephalograph (Data Science) was implanted in the top of the skull. Thereafter, rats were reared normally for 3 weeks and used for the experiments. It was divided into two groups: a control group (3 animals) and a lutein administration group (3 animals). 20% lutein lutein 20S (containing 20% by mass lutein, Kyowa Hakko Bio, reddish brown heat-softening paste containing 20% lutein from marigold petals) suspended in olive oil, 80mg / kg at 16:00 Rats were orally administered at a dose of 16 mg / kg of lutein equivalent. In the control group, olive oil was orally administered at the same time. Thereafter, the electroencephalogram of the rat was measured by a telemetry system for 16 hours from 17:00 to 2 9:00 including 2 hours before and after the dark period (19:00 to 7:00 on the next day), which is the activity time zone of the rat. The obtained electroencephalogram data was analyzed with dedicated analysis software (Somnologica Science, Medcare) to examine changes in arousal, Non-REM sleep, and REM sleep within the measurement time (Biological & Pharmaceutical Bulletin Vol.30 No .10, 2007 p.1895-1897).
After a drug holiday of 1 week or more, rats that were in the control group were administered lutein in the same manner as above as the lutein administration group, and those that were in the lutein administration group were given olive oil as the control group. The same measurement as described above was performed.

The awakening time, Non-REM sleep time, and REM sleep time in the dark period for each rat are shown in FIG. 1, FIG. 2, and FIG. 3, respectively. As for the awakening time, as shown in FIG. 1, compared to the target olive oil administration, the lutein administration extended the awakening time in most individuals, while the average awakening time in olive oil administration was 368 minutes, Lutein administration showed a tendency to extend the awakening time to 387 minutes. Regarding non-REM sleep time, as shown in Fig. 2, non-REM sleep time was reduced in most individuals by oral administration of lutein as compared to olive oil administration as a control. While sleep time was 249 minutes, non-REM sleep time tended to be shortened to 229 minutes with lutein administration. As for REM sleep time, as shown in FIG. 3, the average non-REM sleep time in the olive oil administration group was 101 minutes, whereas the lutein administration group was 102 minutes, and no difference was observed.

The difference of each measurement item value at the time of olive oil administration was calculated from the value of each measurement item at the time of lutein administration shown in FIGS. 1 to 3, and the average of the individual values is shown in FIG. . As is clear from FIG. 4, the administration of lutein showed a tendency to increase the arousal time by about 20 minutes compared with olive oil administration (p <0.10), and conversely, non-REM sleep time compared to olive oil administration. Was significantly shortened by about 20 minutes (p <0.05).

The wakefulness-prolonging agent comprising the terrestrial animal, terrestrial plant or microorganism-derived carotene oxidation derivative of the present invention as an active ingredient can prolong the wakefulness time. In addition, the awakening time extender of the present invention can be provided in various forms, and since it has less odor derived from raw materials, it can be easily used and provided as a food or drink or a drug that extends the awakening time. can do. Furthermore, since the present invention has no problem with respect to safety to the human body, the excellent effect can be easily and effectively utilized, and its utility value is high.

Claims

Awakening time extender containing terrestrial animals, terrestrial plants or microorganism-derived carotene oxidation derivatives as active ingredients.
2. The awakening time extending agent according to claim 1, wherein the terrestrial animal, terrestrial plant or microorganism-derived carotene oxidation derivative contains at least one of a hydroxyl group, a carbonyl group and an ether group.
The terrestrial animal, terrestrial plant or microorganism-derived carotene oxidation derivative is at least one of lutein, zeaxanthin, crocin, spheroidene, violaxanthin, torularhodinaldehyde, torularhodin, capsanthin, crocetin, bixin, azafrin, β-carotenone, eschscholtzxanthin, rhodoxanthin, decaprenoxanthin The wakefulness extending agent according to claim 1 or 2, wherein the active ingredient is a species or more.
4. The awakening time extending agent according to any one of claims 1 to 3, wherein an effective amount of the terrestrial animal, terrestrial plant or microorganism-derived carotene oxidation derivative is 0.1 to 1500 mg / 60 kg body weight.
A pharmaceutical composition for prolonging wakefulness, comprising 0.01 to 95% by weight of the wakefulness extending agent according to any one of claims 1 to 4.
A food and drink for extending the awakening time, comprising 0.0001 to 10% by mass of the awakening time extending agent according to any one of claims 1 to 4.