WO2021100704A1 - Composition pour améliorer la qualité du sommeil - Google Patents

Composition pour améliorer la qualité du sommeil Download PDF

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Publication number
WO2021100704A1
WO2021100704A1 PCT/JP2020/042796 JP2020042796W WO2021100704A1 WO 2021100704 A1 WO2021100704 A1 WO 2021100704A1 JP 2020042796 W JP2020042796 W JP 2020042796W WO 2021100704 A1 WO2021100704 A1 WO 2021100704A1
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Prior art keywords
pharmaceutically acceptable
acceptable salt
astaxanthin
sleep
composition
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PCT/JP2020/042796
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English (en)
Japanese (ja)
Inventor
萌 鶴成
祐貴 川嶋
雅浩 林
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Ｅｎｅｏｓ株式会社
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Publication of WO2021100704A1 publication Critical patent/WO2021100704A1/fr

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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 COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • 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
    • 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
    • A61P25/20—Hypnotics; Sedatives
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P23/00—Preparation of compounds containing a cyclohexene ring having an unsaturated side chain containing at least ten carbon atoms bound by conjugated double bonds, e.g. carotenes

Definitions

  • the present invention relates to compositions for improving sleep quality, more particularly astaxanthin or a pharmaceutically acceptable salt thereof, adonylbin or a pharmaceutically acceptable salt thereof, and adonixanthin or a pharmaceutically acceptable salt thereof. Containing carotenoids containing acceptable salts in the composition for improving sleep quality.
  • astaxanthin, adonylvin, and adonixanthin are a type of carotenoid and are widely distributed in animals, plants, and microorganisms.
  • Patent Document 1 describes foods and drinks and pharmaceutical compositions having astaxanthin as an active ingredient and having a diurnal rhythm normalizing action.
  • Patent Document 2 describes a pet food having a sleep improving effect, which is characterized by containing astaxanthin.
  • Patent Document 3 describes a method for promoting sleep in an animal, which comprises a step of administering astaxanthin and melatonin together to the animal.
  • Patent Document 4 describes a sleep deprivation improving agent using an oily composition containing astaxanthins and a red wine extract.
  • Patent Document 5 describes a sleep improving agent containing crocin, which is a carotenoid, as an active ingredient.
  • An object of the present invention is to provide a new technical means for effectively improving the quality of sleep.
  • carotenoids including astaxanthin or a pharmaceutically acceptable salt thereof, adonylbin or a pharmaceutically acceptable salt thereof, and adonixanthin or a pharmaceutically acceptable salt thereof, are used for sleep. We have found that it shows an effective improvement in quality.
  • the present invention includes the following inventions.
  • a quality of sleep comprising astaxanthin or a pharmaceutically acceptable salt thereof, adonylbin or a pharmaceutically acceptable salt thereof, and a carotenoid containing adonixanthin or a pharmaceutically acceptable salt thereof.
  • Composition for improvement [2] The composition according to [1], wherein the improvement in sleep quality is an improvement in at least one selected from the group consisting of drowsiness when waking up, falling asleep and maintaining sleep, dreaming, and satisfaction of sleep time. Stuff. [3] The composition according to [1] or [2], wherein the carotenoid is a microbial, animal or plant-derived product or a chemically synthesized product.
  • composition according to [3], wherein the microorganism is Paracoccus carotinifaciens [5] The composition according to any one of [1] to [4] for humans. [6] The composition according to [5], wherein the human is a healthy person. [7] The composition according to [5] or [6], wherein the human has a depressed mood or a feeling of fatigue. [8] The composition according to any one of [1] to [7], wherein the composition is a food or drink or a food additive. [9] The composition according to any one of [1] to [8], wherein the composition is a functional food. [10] The composition according to any one of [1] to [5] and [7], wherein the composition is a pharmaceutical product.
  • a method comprising administering or ingesting an effective amount of a carotenoid, including a salt, to a subject in need thereof.
  • the sleep quality of the subject can be effectively improved.
  • the compositions of the present invention may also improve the quality of sleep exhibited by at least one selected from the group consisting of improved drowsiness when waking up, falling asleep and maintaining sleep, dreaming, and / or improving sleep time satisfaction. It is advantageous to be able to do it.
  • compositions for improving sleep quality of the present invention include astaxanthin or a pharmaceutically acceptable salt thereof, adonylbin or a pharmaceutically acceptable salt thereof, and adonixanthin or a pharmaceutically acceptable salt thereof. It is characterized by containing carotenoids containing salts. It is a surprising fact that carotenoids as described above can significantly improve sleep quality, as shown in Test Example 1 below.
  • the carotenoids of the invention include astaxanthin or a pharmaceutically acceptable salt thereof, adonylbin or a pharmaceutically acceptable salt thereof, and adonixanthin or a pharmaceutically acceptable salt thereof.
  • Carotenoids containing may be referred to as a carotenoid mixture) include.
  • Astaxanthin belongs to the kind xanthophyll carotenoid red pigment, its chemical formula is 3,3'-dihydroxy- ⁇ , ⁇ - carotene-4,4'-dione (C 40 H 52 0 4, molecular weight 596.852) Yes, the structural formula is represented by the following formula.
  • adonirubin 3-hydroxy- ⁇ , ⁇ - carotene-4,4'-dione (C 40 H 52 0 3, molecular weight 580.853) and the structural formula is represented by the following formula.
  • adonixanthin is 3,3'-dihydroxy- ⁇ , ⁇ - carotene-4-one (C 40 H 54 0 3, molecular weight 582.869) and the structural formula is represented by the following formula.
  • the carotenoids of the present invention include one or more carotenoids selected from astaxanthin, adonylbin, adonixanthin and pharmaceutically acceptable salts thereof.
  • the carotenoid of the present invention includes a carotenoid containing astaxanthin as a main component.
  • the carotenoid of the present invention may be a free form or a fatty acid ester form. From the viewpoint of absorbability, it is preferable to use a free carotenoid.
  • the carotenoid of the present invention may be a stereoisomer such as an optical isomer or a cis-trans isomer.
  • the optical isomer of astaxanthin include at least one selected from the group consisting of 3S, 3'S-form, 3S, 3'R-form (meso-form), and 3R, 3'R-form. It can be, preferably a 3S, 3'S-form.
  • astaxanthin may be a conjugated double bond cis form in the center of the molecule, an isomer which is a trans form (all E-astaxanthin), or a combination thereof.
  • cis form examples include 9-cis form (9Z-astaxanthin), 13-cis form (13Z-astaxanthin), 15-cis form, Zisis form and combinations thereof. Astaxanthin is preferably a combination of cis and trans isomers.
  • the cis-trans isomer of adonylbin may be a cis isomer, a trans isomer or a combination thereof, and the cis isomer may be a 13-cis isomer.
  • the optical isomer of adonixanthine is at least one selected from the group consisting of 3S, 3'R-form, 3S, 3'S-form, 3R, 3'S-form and 3R, 3'R-form.
  • the cis-trans isomer of adonixanthine may be a cis isomer, a trans isomer or a combination thereof.
  • the cis-trans isomer of adonixanthine is preferably a combination of cis and trans isomers.
  • the carotenoid of the present invention is preferably used as an active ingredient.
  • astaxanthin or a pharmaceutically acceptable salt thereof, adonylbin or a pharmaceutically acceptable salt thereof, and adonixanthin or a pharmaceutically acceptable salt thereof in the carotenoid of the present invention is preferably from 1: 0.01 to. It is 10: 0.01 to 10, more preferably 1: 0.03 to 9: 0.03 to 9, and even more preferably 1: 0.05 to 8: 0.05 to 8.
  • astaxanthin or a pharmaceutically acceptable salt thereof and adonylbin or a pharmaceutically acceptable salt thereof and adonixanthin or a pharmaceutically acceptable salt thereof in the carotenoid of the present invention is preferably 1: 0.01. It is ⁇ 20, more preferably 1: 0.03 to 15, and even more preferably 1: 0.05 to 12.
  • the mass ratio of adonylbin or a pharmaceutically acceptable salt thereof to adonixanthine or a pharmaceutically acceptable salt thereof in the carotenoid of the present invention is preferably 1: 0.001 to 100, more preferably 1: 0.002 to 95, and even more preferably 1: It is 0.003 to 90.
  • the carotenoid may be in the form of pharmaceutically acceptable salts, and these salts are also included in the carotenoid in the present invention.
  • carotenoids may also form salts with acids or bases.
  • the pharmaceutically acceptable salt is not particularly limited as long as it forms a pharmaceutically acceptable salt with astaxanthin, adonylbin and / or adonixanthin.
  • hydrohalogenate for example, hydrofluoride salt, hydrochloride, hydrobromide, hydroiodide, etc.
  • inorganic acid salt for example, sulfate, nitrate, excess.
  • organic carboxylates eg, acetates, oxalates, maleates, tartrates, fuma
  • the carotenoid of the present invention may be a commercially available product, or is produced by a chemically synthesized product produced by a conventional chemical synthesis method, a fermentation method using a microorganism, or extraction and purification from a microorganism, an animal, a plant, or the like.
  • Microbial, animal or plant-derived products can be used.
  • Such microorganisms include bacteria, algae and yeast.
  • the microorganism, animal or plant-derived product is a product obtained from the microorganism, animal or plant, and is preferably a product derived from a Paracoccus genus microorganism.
  • examples of the Paracoccus genus microorganisms include Paracoccus carotinifaciens, Paracoccus marcusii, Paracoccus haeundaensis and Paracoccus haeundaensis and Paracoccus zeaxianthis. Is preferably used, and more preferably Paracoccus carotinifaciens.
  • Examples of specific strains of Paracoccus microorganisms include Paracoccus carotinifaciens E-396 strain and Paracoccus bacterium A581-1 strain (FERM BP-4671), and these mutant strains are also preferably used in the present invention. Be done.
  • Examples of the method for culturing Paracoccus microorganisms that is, the method for producing carotenoids from Paracoccus microorganisms
  • the methods for extracting and purifying carotenoids include the following methods.
  • the method for culturing a microorganism belonging to the genus Paracoccus is not particularly limited as long as it is a method capable of culturing such a microorganism, and can be carried out according to, for example, the method described in Example 1 of JP-A-2007-31901. It is briefly described below.
  • a medium containing glucose, meat extract, peptone, sodium chloride, etc. is placed in a test tube and sterilized by steam.
  • the E-396 strain (FERM BP-4283) is inoculated into this and subjected to reciprocating shaking culture. This culture solution is centrifuged and then freeze-dried to obtain dried cells containing carotenoids.
  • the method for extracting and purifying the carotenoid is not particularly limited as long as it can extract and purify the carotenoid, but can be carried out according to, for example, the method described in International Publication No. 2014/0546669. It is briefly described below.
  • ⁇ Ethanol extraction step> Ethanol is added to the dried cells of the Paracoccus microorganism containing carotenoids obtained above, and the carotenoids are extracted while stirring in a high-pressure container at about 90 ° C. in a nitrogen atmosphere. After cooling (for example, the liquid temperature is 65 ° C.), the pressure vessel is opened, the cells are removed from the extract by filtration, and the cell cake is further washed with ethanol to obtain a carotenoid-containing extract.
  • ⁇ Concentration and crystallization step of extract A part of ethanol was distilled off from the extract obtained in the above ethanol extraction step using a rotary evaporator in which the degree of reduced pressure was adjusted, and the solid content of the extract was concentrated. After that (for example, 1.25 to 20 times), the concentrated solution is aged overnight (for example, 30 ° C.) to precipitate crystals.
  • the carotenoid of the present invention is selected from the group consisting of canthaxanthin, asteroidenone, ⁇ -carotene, echinenone and 3-hydroxyechinenone in addition to astaxanthin, adonylvin and adonixanthin. It is preferable to further include at least one of these. Further, as the carotenoid of the present invention, it is more preferable to further contain canthaxanthin, asteroidenone, ⁇ -carotene, echinenone and 3-hydroxyechinenone in addition to astaxanthin, adonylvin and adonixanthin.
  • carotenoids extracted from dried cells of Paracoccus carotinifaciens include astaxanthin, adonylvin and adonixanthin. It further comprises at least one selected from the group consisting of canthaxanthin, asteroidenone, ⁇ -carotene, echinenone and 3-hydroxyechinenone.
  • the content of the carotenoid in the composition of the present invention is not particularly limited as long as it does not interfere with the effect of the present invention, but is, for example, 0.001 to 99.9% by mass, preferably 0. It is 005 to 99.8% by mass, more preferably 0.007 to 99.7% by mass, still more preferably 0.01 to 99.6% by mass.
  • the content of the carotenoid is, for example, the content of astaxanthin when the carotenoid is only astaxanthin, and when the carotenoid is a plurality of carotenoids (for example, astaxanthin, adonylbin and adonixanthin), a plurality of types. It is considered to be the total content of carotenoids.
  • Measurement of the content of astaxanthin, adonylbin and / or adonixanthin in the composition of the present invention is measured by a high performance liquid chromatography (HPLC) method.
  • HPLC high performance liquid chromatography
  • Such measurements are conveniently performed by using a commercially available HPLC apparatus (eg, Waters) and a column (eg, Luna, 5 ⁇ m, Silica (2), 100 ⁇ , (150 mm x ⁇ 4.6 mm) (Phenomenex)). be able to.
  • the measurement can be performed under the following conditions, for example.
  • composition of the present invention can be provided as a composition containing the above carotenoids and optionally an orally acceptable or pharmaceutically acceptable additive.
  • additives solvents, solubilizers, solubilizers, lubricants, emulsifiers, tonicity agents, stabilizers, preservatives, preservatives, surfactants, gelling agents, regulators, chelating agents, pH Examples include regulators, buffers, excipients, thickeners, colorants, fragrances, sweeteners or fragrances.
  • composition of the present invention can be prepared by a known method such as mixing, dissolving, dispersing and suspending the carotenoid and optionally an orally acceptable or pharmaceutically acceptable additive. Further, in the preparation of the composition of the present invention, as long as the effect of the present invention is not impaired, the mixture, solution, dispersion, suspension and the like prepared by the above method are subjected to homogenization treatment, sterilization treatment and drying treatment. May be applied.
  • composition of the present invention is not particularly limited as long as it does not interfere with the effects of the present invention, and is preferably solid, semi-solid (including paste, gel, jelly) or liquid (oily). , Including slurry).
  • the dosage form of the composition of the present invention is not particularly limited as long as the effect of the present invention is not impaired, but injections, tablets (for example, naked tablets, sugar-coated tablets, film-coated tablets, enteric coated tablets, sustained-release tablets, oral cavity).
  • tablets for example, naked tablets, sugar-coated tablets, film-coated tablets, enteric coated tablets, sustained-release tablets, oral cavity.
  • the dosage form of the composition of the present invention is preferably a dosage form for oral ingestion or administration, and is a tablet, capsule, pill, powder, powder, granule, syrup, dry syrup, emulsion, liquid, suspension.
  • examples include turbid agents, liquid agents, troche agents, jelly agents and the like.
  • the method for ingesting or administering the composition of the present invention is not particularly limited, but is limited to injections such as infusion, intravenous injection, intramuscular injection, subcutaneous injection, and intradermal injection, oral, transmucosal, transdermal, intranasal, and oral.
  • injections such as infusion, intravenous injection, intramuscular injection, subcutaneous injection, and intradermal injection, oral, transmucosal, transdermal, intranasal, and oral.
  • Ingestion or administration by intraperitoneal injection or intraperitoneal administration is preferable, and oral ingestion or oral administration is preferable.
  • composition of the present invention examples include foods and drinks such as foods and beverages, food and drink additives such as food additives, feeds, pharmaceuticals, quasi-drugs, and cosmetics. Goods are preferred.
  • the food or drink of the present invention is prepared by preparing the composition of the present invention as it is as a food or drink, various proteins, sugars, fats, trace elements, vitamins, other active ingredients (for example, lactic acid bacteria, Bacillus) and the like. Bacteria, fungi such as yeast, dietary fiber, DHA or EPA), etc. may be further blended, or the composition of the present invention may be in a liquid, semi-solid or solid form such as a solution, and the present invention may be used. The composition of the above may be added to general foods and drinks.
  • foods and drinks include instant foods such as instant noodles, retort foods, canned foods, microwave foods, instant soups / miso juices, and freeze-dried foods; soft drinks, fruit juice drinks, vegetable drinks, and soy milk.
  • the foods and drinks of the present invention include health foods, supplements, functional foods (including, for example, foods for specified health use, foods with nutritional function or foods with functional claims), nutritional supplements, foods for special purposes (for example, foods for the sick).
  • infant prepared milk powder, pregnant women, lactating women powdered milk or foods for people with swallowing / chewing difficulties) or infant liquid prepared milk (also referred to as infant liquid milk) are also included.
  • the composition of the present invention has an effect of improving sleep quality
  • foods and drinks for improving sleep quality are provided. That is, the food or drink of the present invention can be provided, for example, as a food or drink for a person who is very drowsy when waking up or for a person who has a sleep problem.
  • foods and drinks such as functional foods may be provided with labels such as "for those who sleep lightly and do not sleep soundly" and "for those who are concerned about the quality of sleep".
  • the intake or dose of the composition of the present invention is not particularly limited, and the formulation of the composition, the type and purity of the carotenoid, the type of the subject, the age or body weight of the subject, the symptoms, the intake or administration time, and the form of the composition It can be determined depending on the method of ingestion or administration, the combination of carotenoids or drugs other than the carotenoids of the present invention, and the like.
  • the composition of the present invention is preferably composed in the form of a daily intake unit so as to be an effective amount for improving the quality of sleep.
  • compositions of the present invention when taken orally, they include astaxanthin or a pharmaceutically acceptable salt thereof, adonylbin or a pharmaceutically acceptable salt thereof, and adonixanthin or a pharmaceutically acceptable salt thereof.
  • the carotenoid is added to the composition so that the intake or dose of the carotenoid is in the range of 0.01 to 1000 mg, preferably 0.05 to 100 mg, more preferably 0.1 to 50 mg per day for an adult weighing 60 kg. Can be blended.
  • Carotenoids or drugs other than the carotenoids of the present invention used in combination with the carotenoids of the present invention can also be appropriately determined based on the clinically used intake or dose, respectively.
  • the daily intake or dose of the composition of the present invention is appropriately selected according to the formulation of the composition and the like, similarly to the intake or dose of the composition described above.
  • the daily intake or dose of the composition of the present invention may be, for example, one or more times to be ingested or administered to the subject, but one to five times to be ingested or administered to the subject. Is preferable. Therefore, the number of times of ingestion or administration of the composition of the present invention per day is 1 to 5 times a day, preferably 1 to 3 times a day, and more preferably 1 to 2 times a day. Times.
  • the subject to which the composition of the present invention is applied is not particularly limited as long as it does not interfere with the effects of the present invention, but is preferably a mammal, and more preferably a primate such as a human. , Dogs, cats.
  • the subject may be a healthy person (healthy animal) or a patient (patient animal).
  • an object to which the composition of the present invention is applied includes a person in a depressed mood.
  • the depressed mood includes a state of depression such as sadness, vainness, depression, depression, and depression.
  • POMS Profile of Mood States
  • Such a depressed mood preferably means that the T score of the Japanese version of POMS2 [Depression-Depression (DD)] is higher than 65 points.
  • DD Depression-Depression
  • 92 points can be mentioned, preferably 91 points, and more preferably 90 points.
  • an object to which the composition of the present invention is applied includes a person having a feeling of fatigue.
  • a person having a feeling of fatigue for example, a person having a feeling of fatigue VAS of 70 mm or more in the fatigue feeling VAS (Visual Analogue Scale) test of the anti-fatigue clinical evaluation guideline 5th edition of the Japanese Society of Fatigue can be mentioned.
  • VAS Visual Analogue Scale
  • Examples of the upper limit value of the fatigue feeling VAS include 100 mm, preferably 99 mm, and more preferably 98 mm.
  • the "sleep quality" in the present invention means how much the body and brain are able to rest by sleep, that is, the degree of good sleep, and the sleep quality of anxiety patients with sleep disorders is Be excluded. Therefore, according to a preferred embodiment of the present invention, the "sleep quality" is the sleep quality of a healthy person.
  • the quality of sleep is, for example, sleepiness on rising (may be referred to as sleepiness when waking up), initiation and maintenance of sleep (eg, smooth sleep onset and maintenance of sleep), or Satisfaction with falling asleep quickly and staying stable without awakening), frequent dreaming (for example, not having frequent dreams or night dreams), and sleep length It is indicated by at least one selected from the group consisting of sensations (which may be referred to as satisfaction with sleep time) (eg, sleep without feeling of lack of time). Of these, sleep quality is preferably indicated by drowsiness when waking up. Sleep quality can be evaluated using sleep quality VAS, as shown in the test examples. In addition, sleep onset during wake-up, sleep onset and sleep maintenance, dreaming, and satisfaction with sleep time can be evaluated using the OSA wake-up sleep sensation questionnaire (MA version) as shown in the test example.
  • MA version OSA wake-up sleep sensation questionnaire
  • the quality of sleep can be improved, preferably at least one selected from the group consisting of wake-up drowsiness, sleep onset and sleep maintenance, dreams, and sleep time satisfaction. Can be improved. Therefore, according to the composition of the present invention, it is possible to improve the quality of sleep. Therefore, according to one aspect of the invention, the composition of the invention is provided as a composition for improving sleep quality.
  • "improvement of sleep quality” preferably means the above-mentioned improvement or improvement of sleep quality. Improvements in sleep quality include, for example, improved drowsiness when waking up (eg, waking up comfortably), improved sleep onset and sleep maintenance (eg, falling asleep and deep sleep), and dreaming (dreaming).
  • the composition of the present invention contains astaxanthin together with adonylbin and adonixanthin to cause drowsiness when waking up, sleep onset and sleep maintenance, dreaming, and sleep time. It is advantageous in being able to improve all of the satisfaction of.
  • a method of improving the sleep quality of a subject, astaxanthin or a pharmaceutically acceptable salt thereof, adonylbin or a pharmaceutically acceptable salt thereof, and adonixanthin or A method comprising administering or ingesting an effective amount of a carotenoid containing its pharmaceutically acceptable salt to a subject in need thereof.
  • carotenoids comprising astaxanthin or a pharmaceutically acceptable salt thereof, adonylbin or a pharmaceutically acceptable salt thereof, and adonixanthin or a pharmaceutically acceptable salt thereof.
  • methods of improving the sleep quality of a subject comprising administering or ingesting a composition comprising an effective amount to the subject.
  • the improvement in sleep quality is preferably at least one selected from the group consisting of wake-up drowsiness, sleep onset and sleep maintenance, dreams, and sleep time satisfaction.
  • the "effective amount” means astaxanthin or a pharmaceutically acceptable salt thereof, adonylbin or a pharmaceutically acceptable salt thereof, and adonixanthin or a pharmaceutically acceptable salt thereof in a daily intake unit. It can be set in the same manner as the content of carotenoids containing possible salts.
  • the above-mentioned method for improving sleep quality is a non-therapeutic method excluding medical treatment for humans when the subject is a healthy person.
  • the medical practice for a human means an act of ingesting (administering) a drug to a human, requiring a prescription from a doctor or the like.
  • the method of improving the quality of sleep of the present invention can be carried out for the composition of the present invention in accordance with the contents described herein.
  • astaxanthin or a pharmaceutically acceptable salt thereof for improving the quality of sleep.
  • adonylbin or a pharmaceutically acceptable salt thereof for improving the quality of sleep.
  • adonixanthin or a pharmacy thereof for improving the quality of sleep.
  • the use of carotenoids containing qualibly acceptable salts is provided.
  • the improvement in sleep quality is preferably at least one selected from the group consisting of wake-up drowsiness, sleep onset and sleep maintenance, dreams, and sleep time satisfaction.
  • astaxanthin or a pharmaceutically acceptable salt thereof, adonylbin or a pharmaceutically acceptable salt thereof, and adoni as a composition for improving the quality of sleep.
  • the use of carotenoids containing xanthine or a pharmaceutically acceptable salt thereof is provided.
  • the improvement in sleep quality is preferably at least one selected from the group consisting of wake-up drowsiness, sleep onset and sleep maintenance, dreams, and sleep time satisfaction.
  • astaxanthin or a pharmaceutically acceptable salt thereof adonylbin or a pharmaceutically acceptable salt thereof, and an ad in the production of a composition for improving sleep quality.
  • the use of carotenoids containing astaxanthin or a pharmaceutically acceptable salt thereof is provided.
  • the improvement in sleep quality is preferably at least one selected from the group consisting of wake-up drowsiness, sleep onset and sleep maintenance, dreams, and sleep time satisfaction.
  • astaxanthin or a pharmaceutically acceptable salt thereof for improving the quality of sleep.
  • Carotenoids containing qualibly acceptable salts are provided.
  • the improvement in sleep quality is preferably at least one selected from the group consisting of wake-up drowsiness, sleep onset and sleep maintenance, dreams, and sleep time satisfaction.
  • the obtained upper layer was made up to 50 mL with an HPLC mobile phase to obtain a diluted solution.
  • 5 mL of the obtained diluted solution was collected in a new 50 mL volumetric flask, and the injection solution obtained by measuring up to 50 mL with the HPLC mobile phase was used for HPLC analysis.
  • Astaxanthin (mg / g) (astaxanthin concentration in standard solution (mg / L)) / (peak area of astaxanthin standard solution) x (astaxanthin peak area in sample) / (sample mass (mg)) x coefficient * 1 ⁇ C * 2 ... (2)
  • Other carotenoid concentrations were calculated according to equation (3).
  • Step 1 Culturing step of E-396 strain E-396 strain (FERM BP-4283) is cultured according to the method described in Example 1 of JP-A-2007-31901, and the culture is contained in 1 g. Dried cells containing a carotenoid containing about 17 mg of astaxanthin were obtained.
  • Step 2 Ethanol extraction step 2200 kg of ethanol was added to 100 kg of dried cells obtained in step 1 of this preparation example, and carotenoids containing astaxanthin were extracted while stirring in a high-pressure container at 90 ° C. for 15 minutes. went. After cooling the liquid temperature to 65 ° C., open the pressure vessel, remove the cells from the extract by filtration, and wash the cell cake with ethanol to make astaxanthin 0.07% (wt / wt), carotenoid weight. 2200 kg of an extract having a concentration of 0.1% (wt / wt) was obtained.
  • Step 3 Concentration, heat treatment (incubation) and crystallization step of the extract
  • the extract obtained in step 2 of this preparation example is adjusted to a reduced pressure so that the can temperature becomes 30 ° C., and a rotary evaporator is used.
  • a part of ethanol was distilled off, and the solid content concentration was concentrated to 5 times that of the extract (astaxanthin weight concentration 0.35% (wt / wt), carotenoid weight concentration 0.5% (wt / wt)). Then, this concentrated solution was heated (incubated) at 60 ° C. for 4 hours in a nitrogen atmosphere, and then aged overnight at a can temperature of 30 ° C. to precipitate crystals.
  • Step 4 Crystal filtration, washing and drying steps Crystals were recovered by filtration from the liquid containing the crystals obtained in step 3 of this preparation example. The crystals were dried under reduced pressure at 100 ° C. for 2 hours to obtain 1700 g of dried crystals.
  • Steps 1 to 4 were repeated, and the obtained dried crystals were mixed into one and put together.
  • the carotenoid content was quantified by the above-mentioned "method for quantifying carotenoids such as astaxanthin". As a result, the carotenoid content was astaxanthin content 70%, adonylbin content 10%, and adonixanthin 16%.
  • Step 5 Preparation of Astaxanthin-Containing Powder
  • gum arabic, maltodextrin, tocopherol, medium-chain fatty acid and ascorbic acid were added, mixed, and dissolved in water. Then, it was emulsified and spray-dried to obtain an astaxanthin-containing powder.
  • the carotenoid content of the obtained powder was astaxanthin 1%, adonylbin 0.17% and adonixanthin 0.18%.
  • a control food was prepared in the same manner as the astaxanthin-containing food except that the food coloring (edible red No. 2, amaranth) and water were used instead of the astaxanthin-containing powder and the content of each component was as shown in Table 1. ..
  • Test Example 1 Examination of the effect of astaxanthin-containing food on sleep quality The outline of the test was as follows. ⁇ Target: Adult men and women aged 20 to 64 years ⁇ Number of subjects: 60 (30 people x 2 groups) The body weight (kg) of the subjects was as follows (mean ⁇ standard deviation). Astaxanthin-containing food intake group: 58.47 ⁇ 9.77 Control food intake group: 57.97 ⁇ 12.67 -Study design: Randomized, double-blind, placebo-controlled, parallel-group comparative study-Intake: Astaxanthin 12 mg / day-Intake: 2 times daily, 3 bags each after breakfast and dinner (30 g total) 6 bags in total ⁇ Ingestion period: 8 weeks
  • Selection Criteria Men and women aged 20 to 64
  • POMS2 Japanese version of [Depression-Depression] score is selected from the highest score.
  • Exclusion criteria (1) As a result of the investigation of subjective symptoms (VAS) at the time of pre-examination, those who "strength of feeling stress in daily life" is 0 mm (not felt at all) (2)
  • VAS subjective symptoms
  • Currently contains astaxanthin Those who regularly use health foods, supplements, non-medicinal products, and pharmaceuticals
  • Those who have a smoking habit (5) Those who go to bed after 2:00 (6) Those who drink more than 60 g of average daily pure alcohol (7) Those who are not engaged in regular labor (8) )
  • Those who have been irritated by surgical tape those who may have weak skin irritation, or those who are
  • Subject candidates are sent to the hospital for pre-examination, and in addition to physical condition confirmation / measurement / general clinical examination (blood collection / urine collection), lifestyle-related questionnaire, POMS2 Japanese version, survey of subjective symptoms (VAS (stress, sleep, feeling of fatigue) )) was filled out.
  • VAS stress, sleep, feeling of fatigue
  • BMI blood pressure and pulse
  • OSA sleep questionnaire MA version (OSA-MA)
  • OSA-MA OSA sleep questionnaire MA version
  • the selected subjects were sent to the hospital for the examination at the start of ingestion, and physical condition confirmation, blood sampling, POMS2 Japanese version, and VAS (stress, sleep, fatigue) were filled out.
  • a diary was distributed to the subjects who completed the test during the intake period, and the astaxanthin-containing food or the control food was ingested and the diary was started to be recorded during the intake period.
  • OSA sleep questionnaire MA version (OSA-MA)
  • OSA-MA OSA sleep questionnaire MA version
  • OSA sleep sensation questionnaire (MA version) for middle-aged and elderly people, Brain and Psychiatric Medicine, 1999, 10, 401-409.
  • the subjects were asked to fill out the OSA wake-up sleep sensation questionnaire according to the above method, and factor I (wake-up sleepiness), factor II (sleep onset and sleep maintenance), factor III (dream), factor IV (fatigue recovery), and factor V.
  • OSA_MAforZ.xls available from the sleep onset score conversion file (http://www.jobs.gr.jp/osa_ma.html) distributed by the Japan Sleep Improvement Council ), The Zc score (reaction scale value) was calculated.
  • the OSA wake-up sleep sensation questionnaire (MA version) has been verified for both reliability and validity of each factor, and the higher the score for any of the factors, the better.
  • the subjects were stratified and analyzed based on the DD (depression-depression) of POMS2 at the start of ingestion or the fatigue feeling VAS at the start of ingestion.
  • DD depression-depression
  • the subjects in each group were divided into a layer higher than the median DD of POMS2 of each group of 65 points and a layer of 65 points or less.
  • 12 people had a DD T-score of POMS2 higher than 65 points
  • 13 people had a DD T-score of 65 points or less.
  • the body weight (kg) (mean ⁇ standard deviation) of the astaxanthin-containing food intake group in the layer having a DD T score of POMS2 higher than 65 points was 61.33 ⁇ 8.75, and the control food in the layer.
  • the body weight (kg) (mean ⁇ standard deviation) of the ingestion group was 59.15 ⁇ 13.88.
  • the DD T score (mean ⁇ standard deviation) of POMS2 in the astaxanthin-containing food intake group in the layer having a DD T score of POMS2 higher than 65 points was 71.8 ⁇ 4.2, which was a control in the layer.
  • the DD T score (mean ⁇ standard deviation) of POMS2 in the food intake group was 69.9 ⁇ 2.1.
  • the subjects in each group were divided into a layer having a fatigue VAS of 70 mm or more and a layer having a fatigue VAS of less than 70 mm.
  • 13 people had a fatigue VAS of 70 mm or more, and 12 people had a fatigue VAS of less than 70 mm.
  • the weight (kg) (mean ⁇ standard deviation) of the astaxanthin-containing food intake group in the layer with a fatigue feeling VAS of 70 mm or more is 58.74 ⁇ 7.73, and the weight of the control food intake group in the layer.
  • Kg (mean ⁇ standard deviation) was 61.27 ⁇ 15.35.
  • the fatigue VAS (mean ⁇ standard error) of the astaxanthin-containing food intake group in the layer with a fatigue VAS of 70 mm or more was 80.29 ⁇ 1.68 mm, and the fatigue VAS (mean value) of the control food intake group. ⁇ standard error) was 78.18 ⁇ 1.50 mm.
  • the change in VAS (sleep) in the astaxanthin-containing food intake group at 8 weeks was significant as compared with the change in the control food intake group in the layer in which the fatigue VAS was 70 mm or more. Decreased (improved).
  • the amount of change is the difference between the measured value at the 8th week and the measured value at the start of ingestion (measured value at the 8th week-measured value at the start of ingestion). The results are shown in Table 3.

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Abstract

La présente invention concerne une nouvelle composition pour améliorer la qualité du sommeil. Plus précisément, l'invention concerne une composition pour améliorer la qualité du sommeil, la composition contenant un caroténoïde qui contient : de l'astaxanthine ou un sel pharmaceutiquement acceptable de celui-ci ; de l'adonirubine ou un sel pharmaceutiquement acceptable de celui-ci ; et de l'adonixanthine ou un sel pharmaceutiquement acceptable de celui-ci.
PCT/JP2020/042796 2019-11-18 2020-11-17 Composition pour améliorer la qualité du sommeil WO2021100704A1 (fr)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001087291A1 (fr) * 2000-05-16 2001-11-22 Suntory Limited Compositions permettant de regulariser le rythme circadien
JP2012025712A (ja) * 2010-07-27 2012-02-09 Jx Nippon Oil & Energy Corp 抗不安組成物
WO2014054669A1 (fr) * 2012-10-02 2014-04-10 株式会社ダイセル Méthode de production d'une composition contenant un caroténoïde, et composition contenant un caroténoïde
WO2014054651A1 (fr) * 2012-10-03 2014-04-10 富士フイルム株式会社 Agent d'amélioration du sommeil, agent d'augmentation de la durée du sommeil lent, et agent sédatif
WO2017213176A1 (fr) * 2016-06-08 2017-12-14 アスタリール株式会社 Composition alimentaire contenant de l'astaxanthine
JP2019135242A (ja) * 2019-04-01 2019-08-15 Ｊｘｔｇエネルギー株式会社 カロテノイド含有組成物

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001087291A1 (fr) * 2000-05-16 2001-11-22 Suntory Limited Compositions permettant de regulariser le rythme circadien
JP2012025712A (ja) * 2010-07-27 2012-02-09 Jx Nippon Oil & Energy Corp 抗不安組成物
WO2014054669A1 (fr) * 2012-10-02 2014-04-10 株式会社ダイセル Méthode de production d'une composition contenant un caroténoïde, et composition contenant un caroténoïde
WO2014054651A1 (fr) * 2012-10-03 2014-04-10 富士フイルム株式会社 Agent d'amélioration du sommeil, agent d'augmentation de la durée du sommeil lent, et agent sédatif
WO2017213176A1 (fr) * 2016-06-08 2017-12-14 アスタリール株式会社 Composition alimentaire contenant de l'astaxanthine
JP2019135242A (ja) * 2019-04-01 2019-08-15 Ｊｘｔｇエネルギー株式会社 カロテノイド含有組成物

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
HAYASHI,M. ET AL.: "Effect of astaxanthin-rich extract derived from Paracoccus carotinifaciens on the status of stress and sleep in adults", J. CLIN. BIOCHEM. NUTR., vol. 66, no. 2, 14 February 2020 (2020-02-14), pages 92 - 102, XP055825823 *

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