WO2017047777A1 - Agent améliorant une déficience en sérotonine pour une libération de charge post-stress - Google Patents

Agent améliorant une déficience en sérotonine pour une libération de charge post-stress Download PDF

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Publication number
WO2017047777A1
WO2017047777A1 PCT/JP2016/077519 JP2016077519W WO2017047777A1 WO 2017047777 A1 WO2017047777 A1 WO 2017047777A1 JP 2016077519 W JP2016077519 W JP 2016077519W WO 2017047777 A1 WO2017047777 A1 WO 2017047777A1
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WIPO (PCT)
Prior art keywords
serotonin deficiency
serotonin
stress load
lactobacillus
stress
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PCT/JP2016/077519
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English (en)
Japanese (ja)
Inventor
一仁 六反
憲生 西田
由紀 桑野
豪人 加藤
麻衣 高田
幸司 宮崎
光久 河合
一徳 須田
早川　弘子
Original Assignee
国立大学法人徳島大学
株式会社ヤクルト本社
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Application filed by 国立大学法人徳島大学, 株式会社ヤクルト本社 filed Critical 国立大学法人徳島大学
Priority to JP2017540018A priority Critical patent/JPWO2017047777A1/ja
Publication of WO2017047777A1 publication Critical patent/WO2017047777A1/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
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • 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
    • 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
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis

Definitions

  • the present invention relates to a serotonin deficiency improving agent after releasing stress load, which improves serotonin deficiency after stress load is released.
  • Serotonin is released into the brain when stress is applied to the body, but when it is released from stress and the amount of serotonin decreases, the brain becomes serotonin deficient, lethargy, sleep disorder, migraine, anxiety, depression, chronic fatigue, Symptoms such as feeling of light, overeating, anorexia, and hypersensitivity often occur.
  • Patent Document 1 a stress reducing agent containing Lactobacillus gasseri as an active ingredient
  • Patent Document 2 an anti-stress agent containing a fermented wort obtained by fermentation with Lactobacillus pentosas
  • Lactobacillus casei has never been known to improve serotonin deficiency after the stress load has been released.
  • the present invention relates to providing a serotonin deficiency ameliorating agent after releasing a stress load, which improves the serotonin deficiency after the stress load is released.
  • the inventor examined the pharmacological action of Lactobacillus lactic acid bacteria, and found that Lactobacillus casei has an action to improve serotonin deficiency that appears after release from mental stress.
  • the present invention provides the following [1] to [8].
  • [1] A serotonin deficiency ameliorating agent after releasing a stress load, comprising a bacterial body of Lactobacillus casei or a processed product thereof or a fermented product containing them as an active ingredient.
  • [2] The serotonin deficiency improving agent after release of stress load according to [1], wherein Lactobacillus casei is Lactobacillus casei YIT9029 (FERM BP-1366).
  • [3] The serotonin deficiency improving agent after release of stress load according to [1] or [2], wherein the symptoms caused by serotonin deficiency are sleep disorders.
  • a food for improving serotonin deficiency after releasing a stress load comprising as an active ingredient a bacterial body of Lactobacillus lactic acid bacteria or a processed product thereof or a fermented product containing them.
  • the present invention it is possible to improve the serotonin deficiency after the stress load is released, and for example, it is useful for improving sleep disorders that occur after the stress load is released.
  • Lactobacillus casei (L. casei) may be separable from nature, or may be available from a cell bank such as ATCC, but preferably, for example, Lactobacillus casei YIT 9018 (FERM BP-665), Lactobacillus casei YIT 9029 (FERM BP-1366), Lactobacillus casei YIT 10003 (FERM BP-7707), among which Lactobacillus casei YIT9029 (FERM BP-13 Is particularly preferred.
  • the said lactic acid strain may be used individually by 1 type, and may be used in combination of 2 or more type.
  • the bacterial cells of Lactobacillus casei may be either live cells or dead cells, but are preferably live cells. Bacteria can be produced in large quantities by culturing viable cells.
  • the medium may be either a liquid medium or a solid medium, but preferably contains a nitrogen source and a carbon source. Nitrogen sources include meat extract, peptone, gluten, casein, yeast extract, amino acids, etc., and carbon sources include glucose, xylose, fructose, inositol, maltose, water candy, soup, starch, bacus, bran, Molasses, glycerin and the like can be used.
  • Suitable media include MRS media, LBS media, Rogosa media, WYP media, GYP media and the like.
  • the culture conditions for viable cells may be those suitable for each lactic acid bacterium.
  • the culture temperature is usually 20 to 50 ° C., preferably 25 to 40 ° C., more preferably 35 to 38 ° C.
  • the culture time is usually 6 to 62 hours, preferably 12 to 48 hours, more preferably 15 to 30 hours.
  • the pH of the medium is usually 3 to 8, preferably 4 to 7, and more preferably 6 to 7. Cultivation may be performed in an incubator, or aeration and shaking may be performed during the cultivation.
  • the treated bacterial product refers to a product obtained by adding some treatment to Lactobacillus casei used, and the treatment is not particularly limited.
  • the treatment is not particularly limited.
  • cell lysates, etc. specifically, disrupted solution of Lactobacillus casei with ultrasonic waves, enzyme treatment solution of Lactobacillus casei, and separation by solid-liquid separation means such as filtration or centrifugation Solid residue and the like.
  • a nucleic acid-containing fraction obtained by dissolving Lactobacillus casei with a surfactant or the like and then precipitating with ethanol or the like is also included.
  • those obtained by further performing separation / purification treatment such as separation by various chromatography on the crushing solution of Lactobacillus casei using ultrasonic waves, the enzyme treatment solution of cells and the like are also included.
  • dead cells When dead cells are used, they can be obtained by, for example, heat treatment, treatment with drugs such as antibiotics, treatment with chemical substances such as formalin, treatment with ultraviolet rays, treatment with radiation such as ⁇ rays.
  • heat treatment treatment with drugs such as antibiotics
  • treatment with chemical substances such as formalin
  • treatment with ultraviolet rays treatment with radiation such as ⁇ rays.
  • ultrasonic treatment, enzyme treatment, and heat treatment are particularly preferable.
  • Such a Lactobacillus casei microbial cell or a processed product thereof is in the form of a fermented product containing the microbial cell or a processed product thereof from the viewpoint of ease of intake, continuity of intake, sleep quality improving effect, etc. Is more preferable.
  • fermented products include fermented milk, fermented soymilk, fermented fruit juice, fermented vegetable liquid, etc., but fermented milk is more preferable.
  • Fermented milk products include fermented milk, dairy lactic acid bacteria beverages, hard yoghurt, soft yoghurt, plain yoghurt and the like that are specified by ministerial ordinances.
  • the fermented Lactobacillus casei for example, is obtained by cultivating Lactobacillus casei in milk components such as cow milk, milk powder, whole milk powder, skim milk powder, etc. at a temperature of 30-40 ° C. for 5-24 hours. Can be obtained. Examples of the culture include standing, stirring, shaking, aeration and the like. More preferably, Lactobacillus casei is inoculated and cultured in a sterilized milk medium alone or simultaneously with other microorganisms, and this is homogenized to obtain a fermented milk base. Next, a separately prepared syrup solution may be added and mixed, homogenized with a homogenizer or the like, and then a flavor may be added to finish the final product.
  • milk components such as cow milk, milk powder, whole milk powder, skim milk powder, etc.
  • the culture include standing, stirring, shaking, aeration and the like.
  • Lactobacillus casei is inoculated and cultured in a sterilized milk medium alone or simultaneously with other
  • These fermented products if necessary, in addition to sweeteners such as syrup, various other food materials such as various sugars, thickeners, emulsifiers, various vitamins, antioxidants, stabilizers, etc. These optional components can be blended. Specific examples of these food materials include sugars such as sucrose, glucose, fructose, palatinose, trehalose, lactose, xylose, maltose, sorbitol, xylitol, erythritol, lactitol, palatinit, reduced starch syrup, reduced maltose starch syrup, etc.
  • High-sweetness sweeteners such as sugar alcohol, aspartame, thaumatin, sucralose, acesulfame K, stevia, agar, gelatin, carrageenan, guar gum, xanthan gum, pectin, locust bean gum, gellan gum, carboxymethylcellulose, soy polysaccharide, propylene glycol alginate, etc.
  • Various thickeners stable), sucrose fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, lecithin emulsifier, etc.
  • Milk fat such as cream, butter, sour cream
  • acidulants such as citric acid, lactic acid, acetic acid, malic acid, tartaric acid, gluconic acid
  • various vitamins such as vitamin A, vitamin B, vitamin C, vitamin E, calcium , Magnesium, zinc, iron, manganese and other minerals, yogurt, berry, orange, pear, perilla, citrus, apple, mint, grape, apricot, pair, custard cream, peach, Flavors such as melon, banana, tropical, herbal, tea and coffee can be mentioned.
  • microorganisms other than Lactobacillus casei can be used in combination.
  • Such microorganisms include, for example, Lactobacillus acidophilus, Lactobacillus plantarum, L. buchneri, L. gallinarum, Lactobacillus gallinarum, Lactobacillus Bacillus amylovorus, L. brevis, L. rhamnosus, L. kefir, L. curvatus, L. curvatus, Lactobacillus L. zeae, L. helveticus, L.
  • Lactobacillus gasseri Lactobacillus fermentum (L.fermentum), Lactobacillus reuteri (L.reuteri), Lactobacillus Kurisupatasu (L.crispatus), Lactobacillus Deruburukkyi subsp. Bulgaricus (L. delbrueckii b subsp. Bulgaricus), Lactobacillus delbrukki Subspecies. Lactobacillus bacteria such as L. delbschreibii subsp. Delbschreibii, L. johnsonii, Bifidobacterium breve, Bifidobacterium logum B. B. bifidum, B.
  • Lactobacillus casei it is preferable to produce a fermented product using at least one selected from other Lactobacillus bacteria, Streptococcus bacteria, and Lactococcus bacteria, because high palatability is obtained and ingestion is preferable. .
  • the fermented product containing Lactobacillus casei has an action of suppressing a decrease in the amount of serotonin that occurs when released from mental stress. Therefore, Lactobacillus casei cells or processed products thereof or fermented products containing them can be a serotonin deficiency ameliorating agent after releasing stress.
  • stress mainly means a state of distortion generated in the living body by a psychological / social stressor, and examples of the stress reaction caused thereby include decreased vitality, irritability, anxiety, and depression ( (Depressed mood, decreased interest).
  • “Serotonin deficiency” means a state in which the amount of serotonin in the body (intestine, brain, blood), particularly in the brain, is lower than the normal value. Improvement of serotonin deficiency means the amount of serotonin that has decreased from the normal value. Is restored to normal. Serotonin concentration in stool has been reported to correlate with blood serotonin concentration (or brain serotonin concentration) (Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, Nagler CR, Ismagilov RF, Mazmanian SK, Hsiao EY. Cell. 2015 Apr 9; 161 (2): 264-76.).
  • serotonin deficiency In the state of serotonin deficiency, it is known that sleep disorder, eating disorder, chronic pain syndrome, migraine, etc. develop. In the present invention, it is confirmed that serotonin deficiency occurs after release from the stress load, and sleep disorders occur, and Lactobacillus casei exhibits an effect on the sleep disorders that occur after the stress load is released.
  • the term “sleep disorder” means a disorder that causes abnormal behavior related to sleep, such as a disorder of falling asleep and a disorder of sleep retention, but a disorder of falling asleep, difficulty in continuing to sleep, sleep A typical example is insomnia, in which the pattern is disturbed (decrease in non-REM sleep) and presents with the symptoms that sufficient sleep cannot be obtained.
  • the serotonin deficiency improving agent after releasing stress load of the present invention may be a drug, quasi drug or food for improving serotonin deficiency after releasing stress load, or the drug, quasi drug or food. It may be a material or a preparation used in combination.
  • the food includes specific health foods, functional display foods, and the like, which are based on the concept of improving serotonin deficiency after release of stress load, and indicate that as necessary.
  • the administration form of the above pharmaceuticals and quasi drugs may be either oral administration or parenteral administration, but oral administration is preferred.
  • the composition containing the active ingredient is mixed with a solid or liquid non-toxic pharmaceutical carrier suitable for administration methods such as oral administration, rectal administration and injection, and administered in the form of a conventional pharmaceutical preparation.
  • a solid or liquid non-toxic pharmaceutical carrier suitable for administration methods such as oral administration, rectal administration and injection
  • administration methods such as oral administration, rectal administration and injection
  • administration methods such as oral administration, rectal administration and injection
  • administered in the form of a conventional pharmaceutical preparation be able to.
  • Such preparations include solid preparations such as tablets, granules, dispersions and capsules, liquid preparations such as solutions, suspensions and emulsions, and freeze-dried preparations. These preparations can be prepared by conventional means on the preparation.
  • non-toxic pharmaceutical carrier examples include glucose, lactose, sucrose, starch, mannitol, dextrin, fatty acid glyceride, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid ester, amino acid, gelatin, albumin , Water, physiological saline and the like.
  • conventional additives such as stabilizers, wetting agents, emulsifiers, binders, isotonic agents, excipients and the like can be appropriately added as necessary.
  • Examples of food forms include beverages such as soft drinks, fruit juice drinks, milk drinks, carbonated drinks, dairy products such as yogurt, cheese, butter and milk, processed flour foods, processed rice foods, and confectionery. And various food compositions such as processed soybean foods, but dairy products such as milk drinks and yogurt are preferred.
  • the intake / dosage of the serotonin deficiency improving agent after releasing the stress load of the present invention is not particularly limited as long as the effect is obtained.
  • the intake / dose may vary according to the subject's condition, weight, sex, age or other factors, but the daily dose or intake per adult (60 kg) may be Lactobacillus lactic acid bacteria
  • the (viable cell count) is preferably 10 5 cfu or more, more preferably 10 8 cfu or more, further preferably 10 9 cfu or more, and particularly preferably 10 11 cfu or more.
  • the number of intake days is preferably 5 days or more, more preferably 2 weeks or more, further preferably 4 weeks or more, and particularly preferably 8 weeks or more.
  • Production Example 1 Production of fermented milk containing Lactobacillus casei
  • a syrup was mixed with skim milk powder solution inoculated with Lactobacillus casei strain YIT 9029, fermented at 37 ° C., added with fragrance, then homogenized and filled into a container to obtain a fermented product.
  • the number of Lactobacillus casei bacteria in 100 mL of this fermented product was 10 11 cfu.
  • a placebo the unfermented thing which did not contain Lactobacillus casei and adjusted the flavor by adding lactic acid equivalent to a fermented product was used.
  • about another composition it is the same as a fermented material.
  • Test example 1 the drinking effect of lactic acid bacteria on the stress response associated with the academic test was evaluated by a double-blind placebo-controlled parallel group comparison test.
  • Fermented milk (LcS group) prepared in Production Example 1 divided into 2 groups of 51 healthy 4th grade medical students under 30 years of age who have no smoking habits and are not preparing for national exams (scientific examinations) for entering fifth graders )
  • a placebo drink (placebo group) was ingested every day from 8 weeks before the academic test (before the start of drinking) to 8 weeks until the day before the academic test.
  • the serotonin concentration in the stool further decreased in the placebo group, but increased in the LcS group and tended to be higher than in the placebo group. That is, after the academic test, it was confirmed that the LcS group exhibited an action of suppressing and increasing the decrease in serotonin concentration after release from the stress due to the academic test.
  • Test example 2 The effect of drinking lactic acid bacteria on student sleep under academic test stress was evaluated by a double-blind, placebo-controlled, parallel group comparative study.
  • the OSA sleep questionnaire MA version Yamamoto Yuka et al., Brain and Psychiatric Medicine, Volume 10 , No.
  • OSA sleep questionnaire factor I: wakefulness at sleep, factor II: sleep onset and sleep maintenance, factor III: dream, factor IV: fatigue
  • the average value of 5 factors (recovery, factor V: sleep time) and the clearness of the head were lower in both groups than before the start of drinking, and there was no difference between the groups.
  • the LcS group showed significantly higher mean values of the OSA sleep questionnaire and a clear head feeling compared to the placebo group. That is, it was confirmed that LcS has a significant improving effect on the worsening of sleep after release from stress by an academic test.

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Abstract

La présente invention concerne un agent améliorant une déficience en sérotonine pour une libération de charge post-stress, qui améliore des déficiences en sérotonine après libération d'une charge liée au stress. L'agent améliorant une déficience en sérotonine pour une libération de charge post-stress possède, en tant que composant efficace associé à celui-ci, une bactérie Lactobacillus casei, un produit traité associé, ou un produit fermenté contenant ceux-ci.
PCT/JP2016/077519 2015-09-18 2016-09-16 Agent améliorant une déficience en sérotonine pour une libération de charge post-stress WO2017047777A1 (fr)

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JP2017540018A JPWO2017047777A1 (ja) 2015-09-18 2016-09-16 ストレス負荷解放後のセロトニン欠乏改善剤

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Cited By (5)

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JP2019112328A (ja) * 2017-12-22 2019-07-11 キリン株式会社 概日リズム改善用組成物
JP2020039308A (ja) * 2018-09-12 2020-03-19 キリンホールディングス株式会社 労働パフォーマンスの向上用組成物
JP2021504441A (ja) * 2017-11-30 2021-02-15 アジュ ユニバーシティー インダストリー−アカデミック コーオペレイション ファウンデーションＡｊｏｕ Ｕｎｉｖｅｒｓｉｔｙ Ｉｎｄｕｓｔｒｙ−Ａｃａｄｅｍｉｃ Ｃｏｏｐｅｒａｔｉｏｎ Ｆｏｕｎｄａｔｉｏｎ シソ発酵抽出物を含む睡眠障害の予防、改善または治療用組成物
JP2021506867A (ja) * 2017-12-19 2021-02-22 デュポン ニュートリション バイオサイエンシーズ エーピーエス 認知的及び精神的健康のためのプロバイオティクス
CN116138457A (zh) * 2022-12-14 2023-05-23 温州医科大学 一种具有缓解抑郁样症状作用的复合营养组合物

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Cited By (8)

* Cited by examiner, † Cited by third party
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JP2021504441A (ja) * 2017-11-30 2021-02-15 アジュ ユニバーシティー インダストリー−アカデミック コーオペレイション ファウンデーションＡｊｏｕ Ｕｎｉｖｅｒｓｉｔｙ Ｉｎｄｕｓｔｒｙ−Ａｃａｄｅｍｉｃ Ｃｏｏｐｅｒａｔｉｏｎ Ｆｏｕｎｄａｔｉｏｎ シソ発酵抽出物を含む睡眠障害の予防、改善または治療用組成物
JP7346406B2 (ja) 2017-11-30 2023-09-19 アジュ ユニバーシティー インダストリー－アカデミック コーオペレイション ファウンデーション シソ発酵抽出物を含む睡眠障害の予防、改善または治療用組成物
JP2021506867A (ja) * 2017-12-19 2021-02-22 デュポン ニュートリション バイオサイエンシーズ エーピーエス 認知的及び精神的健康のためのプロバイオティクス
JP7303811B2 (ja) 2017-12-19 2023-07-05 デュポン ニュートリション バイオサイエンシーズ エーピーエス 認知的及び精神的健康のためのプロバイオティクス
JP2019112328A (ja) * 2017-12-22 2019-07-11 キリン株式会社 概日リズム改善用組成物
JP7041508B2 (ja) 2017-12-22 2022-03-24 キリンホールディングス株式会社 概日リズム改善用組成物
JP2020039308A (ja) * 2018-09-12 2020-03-19 キリンホールディングス株式会社 労働パフォーマンスの向上用組成物
CN116138457A (zh) * 2022-12-14 2023-05-23 温州医科大学 一种具有缓解抑郁样症状作用的复合营养组合物

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