[go: up one dir, main page]

WO2015133122A1 - Agent de réglage autonome pour sédation, et agent d'amélioration de rythme quotidien - Google Patents

Agent de réglage autonome pour sédation, et agent d'amélioration de rythme quotidien Download PDF

Info

Publication number
WO2015133122A1
WO2015133122A1 PCT/JP2015/001098 JP2015001098W WO2015133122A1 WO 2015133122 A1 WO2015133122 A1 WO 2015133122A1 JP 2015001098 W JP2015001098 W JP 2015001098W WO 2015133122 A1 WO2015133122 A1 WO 2015133122A1
Authority
WO
WIPO (PCT)
Prior art keywords
milk
yeast
lactic acid
fermented
acid bacteria
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2015/001098
Other languages
English (en)
Japanese (ja)
Inventor
恭輔 川口
恵 小谷
征一 水野
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Asahi Soft Drinks Co Ltd
Original Assignee
Calpis Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Calpis Co Ltd filed Critical Calpis Co Ltd
Priority to JP2016506135A priority Critical patent/JP6471145B2/ja
Publication of WO2015133122A1 publication Critical patent/WO2015133122A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/20Milk; Whey; Colostrum
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/02Drugs for disorders of the nervous system for peripheral neuropathies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/20Hypnotics; Sedatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/10Preparation or pretreatment of starting material
    • A61K2236/19Preparation or pretreatment of starting material involving fermentation using yeast, bacteria or both; enzymatic treatment

Definitions

  • the present invention relates to a sedative autonomic nerve regulator and a diurnal rhythm improving agent. More specifically, a fermented milk-derived component obtained by fermenting milk with lactic acid bacteria and yeast is used as an active ingredient, and the active ingredient is allowed to act on the sense of smell. It relates to an improving agent.
  • Patent Document 1 an aroma composition obtained by fermenting a plant material using yeast acts on the sense of smell and has an autonomic nerve regulating action.
  • Patent Document 1 The effect of the aromatic composition obtained by fermentation and the diurnal rhythm improving action of the aromatic composition have not been reported.
  • nonpatent literature 1 the effect given to the disorder of an autonomic nerve or a circadian rhythm is not reported.
  • Astaxanthin and arachidonic acid have been reported as excellent compounds that have a safe and effective diurnal rhythm-improving effect, but in order to obtain the effect, it is necessary to ingest the ingredients (in the body), and the usage is limited (Patent Documents 3 and 4).
  • the problem of the present invention is that it does not require ingestion (administration), and acts on the olfaction, thereby providing an agent that has an autonomic nerve adjustment effect, a diurnal rhythm improvement effect, and a scented product (fragrance, cosmetic, food, Pharmaceuticals, feed additives, textile detergents, textiles, etc.).
  • the inventors have intensively studied to solve the above problems, and have found that the odor of a fermented milk-derived component obtained by fermentation with lactic acid bacteria and yeast has an autonomic nerve adjusting action and a diurnal rhythm improving action.
  • the present invention relates to the following [1] to [15].
  • a sedative autonomic nervous regulator characterized by using as an active ingredient a component derived from fermented milk obtained by fermenting milk with lactic acid bacteria and yeast;
  • the diurnal rhythm improving agent according to any one of [7] to [11], wherein the milk is skim milk; [13] A method for producing a sedative autonomic nerve regulator that acts on the olfactory sense, wherein the milk is fermented with lactic acid bacteria and then fermented with yeast; [14] A method for producing a diurnal rhythm improving agent that acts on the sense of smell, wherein the milk is fermented with lactic acid bacteria and then fermented with yeast; [15] A scented composition containing a fermented milk-derived component obtained by fermenting milk with lactic acid bacteria and yeast.
  • the balance of autonomic nerves due to stress or the like (autonomous ataxia), and the disturbance of diurnal rhythm are improved, or sleep, body temperature, blood pressure, hormone secretion, feeding, metabolism, resulting from these, It is possible to alleviate, prevent, or treat disorders of physiological activities such as mental activity or various symptoms and diseases such as obesity and depression.
  • the autonomic nerve adjusting agent and the diurnal rhythm improving agent of the present invention do not need to be ingested (administered) into the body, and have an effect by acting on the olfaction, and thus are highly safe. Therefore, it can be used widely and can be used by adding to various products such as fragrances, cosmetics, foods, pharmaceuticals, feed additives, detergents for textiles, textiles and the like.
  • FIG. 1 shows changes in rat adrenal sympathetic nerve activity (rate of change (%) when the start time is 100) due to odor stimulation of fermented milk A fermented with lactic acid bacteria and yeast.
  • FIG. 2 shows changes in rat gastric parasympathetic nerve activity (rate of change (%) when the start time is 100) due to odor stimulation of fermented milk A fermented with lactic acid bacteria and yeast.
  • FIG. 3 shows the total activity of rats after odor stimulation of fermented milk A fermented with lactic acid bacteria and yeast.
  • FIG. 4 shows the light activity rate of rats after odor stimulation of fermented milk A fermented with lactic acid bacteria and yeast.
  • FIG. 5 shows the total activity of rats after odor stimulation of fermented milk B fermented with lactic acid bacteria.
  • FIG. 6 shows the total activity of rats after odor stimulation of fermented milk C fermented with yeast.
  • FIG. 7 shows the total activity of rats after odor stimulation of skim milk.
  • FIG. 8 shows the light activity rate of rats after odor stimulation of fermented milk B fermented with lactic acid bacteria.
  • FIG. 9 shows the light activity rate of rats after odor stimulation of fermented milk C fermented with yeast.
  • FIG. 10 shows the light activity rate of rats after odor stimulation of skim milk.
  • FIG. 11 shows the light period activity ratio of the fermented milk A, fermented milk B, fermented milk C, and skim milk to the control after odor stimulation.
  • the autonomic nerve consists of two nervous systems, the sympathetic nerve and the parasympathetic nerve. It is generally known that when sympathetic nerve activity is enhanced or parasympathetic nerve activity is suppressed, it is in a stress state (excitement). In addition, it is generally known that the state is relaxed (sedated) when sympathetic nerve activity is suppressed or parasympathetic nerve activity is increased.
  • the “autonomic nerve regulator” of the present invention uses fermented milk-derived components obtained by fermenting milk with lactic acid bacteria and yeast as active ingredients, and adjusts the autonomic nerves by causing the active ingredients to act on the sense of smell, thereby reducing the sedative effect. Demonstrate.
  • the “autonomic nerve modulating agent” of the present invention suppresses sympathetic nerve activity such as adrenal sympathetic nerve and exerts effects such as stress relaxation / reduction, blood pressure lowering and blood sugar lowering action. It also enhances parasympathetic nerves such as gastric parasympathetic nerves, and improves gastrointestinal tract function and accompanying relaxation.
  • Daily rhythm improving agent “daily rhythm” is a daily rhythm that appears as a cycle of day and night, and is also referred to as a daily rhythm.
  • the bright period is the active period
  • the dark period is the dormant period (in the rat, the light period is the dormant period and the dark period is the active period, which is the opposite of humans).
  • the daily rhythm is disturbed.
  • the “daily rhythm improving agent” of the present invention improves the daily rhythm by using as an active ingredient a fermented milk-derived component obtained by fermenting milk with lactic acid bacteria and yeast, and causing the effective component to act on the sense of smell (normal) ).
  • the “daily rhythm improving agent” of the present invention reduces the stress state and improves the daily rhythm, resulting in sleep, body temperature, blood pressure, hormone secretion, feeding, metabolism, mental activity, etc. It exhibits the effect of improving various physiological activities such as obesity, depression, and other symptoms and diseases.
  • Fermented milk-derived component which is the "active ingredient” of the autonomic nervous regulator and diurnal rhythm improving agent of the present invention, is the odor component of the fermented milk, that is, usually used at around room temperature or higher. It is a volatile component at a certain temperature.
  • the fermented milk-derived component exerts an effect (function) as an autonomic nerve regulator and a diurnal rhythm improving agent by acting on the olfaction. That is, “acting on olfaction” means that the odor component of fermented milk, which is an active ingredient, volatilizes and stimulates the olfaction. In this way, the smell of fermented milk stimulates the sense of smell and is transmitted to the brain as a signal, thereby adjusting the disturbance of the autonomic nerve and the disturbance of the daily rhythm.
  • the action on the sense of smell is included in the scope of the present invention whether it is an orthonasal route through which the odor is inhaled or a retronasal route through which the odor contained in the oral cavity enters the nasal cavity.
  • Fermented milk “Fermented milk” used in the present invention is acidic milk obtained by fermenting milk using lactic acid bacteria and yeast into a liquid or pasty form, and includes fermented milk, lactic acid bacteria beverages, and the like specified by a ministerial ordinance.
  • Milk is preferred, and skim milk made from milk is particularly preferred.
  • Non-fat milk means milk from which fat (generally fat and fat-soluble vitamins) has been completely removed (less than 0.5% milk fat) or partially.
  • the skim milk may be reduced milk obtained by reducing skim milk powder.
  • Examples of the “lactic acid bacterium” used in the present invention include microorganisms belonging to the genus Lactobacillus, Streptococcus, Bifidobacterium, Enterococcus, Leuconostoc, Lactococcus, Pediococcus, and Weissella. In particular, Lactobacillus is preferable.
  • Lactobacillus '' Lactobacillus helveticus, Lactobacillus delbrukki Subspecies Bulgaricus, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus amyloborus, Lactobacillus gasseri, Lactobacillus paracasei, lacto Bacillus zeae, Lactobacillus rhamnosus, Lactobacillus reuteri, Lactobacillus crispatas, Lactobacillus gallinarum, Lactobacillus brevis, Lactobacillus fermentum, Lactobacillus plantarum, Lactobacillus johnsonii etc.
  • Lactobacillus helveticus L. helveticus
  • Lactobacillus helveticus can be preferably used.
  • yeast used in the present invention include microorganisms belonging to the genus Saccharomyces, Schizosaccharomyces, Tigosaccharomyces, and Krivellomyces, and the genus Saccharomyces is particularly preferable.
  • Saccharomyces microorganisms include, but are not limited to S. cerevisiae can be preferably used.
  • the present invention is a method for producing a sedative autonomic nerve regulator or a diurnal rhythm improving agent that acts on the olfactory sensation as described above, wherein the milk is fermented with lactic acid bacteria and then fermented with yeast. Also provided is a method for producing an autonomic nerve regulator or a diurnal rhythm improving agent.
  • the above-mentioned production method is a sterilization process, a formulation process, such as propylene glycol, glycerin, and fats and oils that are used as a kind of retention agent in order to enhance the action on olfaction.
  • a formulation process such as propylene glycol, glycerin, and fats and oils that are used as a kind of retention agent in order to enhance the action on olfaction.
  • additives and substances, and a step of adding additives and substances such as vitamin E and various plant extracts that reduce odor deterioration and loss in the heat treatment step and the like may be included.
  • the process of attaching to the exterior of a product the indication to the effect that it acts on an olfactory sense that it is an autonomic nerve regulator for sedation or a diurnal rhythm improving agent may be included.
  • the fermentation process may be performed by a fermentation method used for normal fermented milk production, and examples thereof include stationary fermentation, stirring fermentation, shake fermentation, and aeration fermentation. Since the production method of the present invention is characterized by passing through a step of fermenting milk with lactic acid bacteria and then a step of fermenting with yeast, it is possible to appropriately set a fermentation temperature, a fermentation time, and a fermentation promotion product, which will be described later. preferable.
  • the lactic acid bacteria or yeast cell cultures or dried cell bodies such as dried cells are added to the milk as a starter, and the fermentation is performed under known fermentation conditions.
  • a mixed starter may be used, or individual starters may be used.
  • the timing which inoculates a starter in milk is not specifically limited, You may inoculate simultaneously and may inoculate individually.
  • the obtained fermented milk can be subjected to known sterilization treatments such as filtration sterilization, radioactive sterilization, heating sterilization, and pressure sterilization.
  • sterilization treatments such as filtration sterilization, radioactive sterilization, heating sterilization, and pressure sterilization.
  • high-temperature treatment for example, 80 to 150 ° C.
  • a certain time for example, about 1 second to 1 hour.
  • the fermentation temperature is 20 ° C. to 50 ° C. for lactic acid bacteria, preferably 25 ° C. to 45 ° C., more preferably 30 ° C. to 40 ° C., and for yeast, 5 ° C. to 40 ° C., preferably 8 ° C. 30 ° C, more preferably 10 ° C to 25 ° C.
  • the temperature condition can be adjusted by a thermostatic bath, a mantle heater, a jacket, or the like.
  • Fermentation time is not particularly limited, but lactic acid bacteria fermentation is 3 hours to 96 hours, preferably 6 hours to 72 hours, more preferably 12 hours to 48 hours, yeast fermentation is 3 hours to 192 hours, preferably 6 hours to 96 hours, more preferably 12 to 72 hours.
  • the milk may contain additives that promote fermentation of lactic acid bacteria and yeast, for example, amino acids such as glutamic acid, sugars such as glucose and sucrose, minerals, vitamins, yeast extract and the like.
  • the addition amount of the lactic acid bacteria is not particularly limited, and when adding the bacterial cell culture as a starter, the bacterial cell culture containing 1 ⁇ 10 7 (cells / mL) or more of the lactic acid bacteria is preferably 1 to 10% by mass, preferably Is added in an amount of 1.5 to 7% by mass, more preferably 2 to 5% by mass.
  • the amount of yeast to be added is not particularly limited, and 1 to 10% by mass, preferably 1.5 to 7% by mass, more preferably 2 to 5% of a cell culture containing 1 ⁇ 10 5 (units / mL) or more of yeast. Add mass%.
  • the autonomic nervous regulator and diurnal rhythm improving agent of the present invention may be used as it is in the form of a suspension of the fermented milk obtained after the fermentation, as long as the object of the present invention is not impaired. Etc. may be performed.
  • the dosage form may be in the form of capsules, granules, powders, powders, dry syrups, etc. used by dissolving or adding at the time of use in addition to liquids.
  • the autonomic nervous regulator and diurnal rhythm improving agent of the present invention include excipients, disintegrants, binders, wetting agents, stabilizers, buffering agents, lubricants, preservatives commonly used in medicines, foods and drinks, etc.
  • additives such as surfactants, sweeteners, flavoring agents, fragrances, acidulants, and coloring agents may be blended.
  • collagen polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, sodium alginate, water-soluble dextran, water-soluble dextrin, carboxymethyl starch sodium, pectin, xanthan gum, gum arabic, casein, gelatin, agar, glycerin, propylene glycol, polyethylene glycol Vaseline, paraffin, stearyl alcohol, stearic acid, human serum albumin, mannitol, sorbitol, lactose, a surfactant acceptable as a pharmaceutical additive, and the like can be blended.
  • the autonomic nervous regulator and the diurnal rhythm improving agent of the present invention include various oils and fats (for example, vegetable oils such as soybean oil, corn oil, safflower oil, olive oil, animal oils such as beef tallow and sardine oil), crude drugs ( For example, royal jelly, carrots, etc.), amino acids (eg, glutamine, cysteine, leucine, arginine, etc.), polyhydric alcohols (eg, ethylene glycol, polyethylene glycol, propylene glycol, glycerin, sugar alcohols such as sorbitol, erythritol, xylitol, maltitol) , Mannitol, etc.), natural polymers (such as gum arabic, agar, water-soluble corn fiber, gelatin, xanthan gum, casein, gluten or gluten hydrolyzate, lecithin, starch, dextrin, etc.), vitamins (such as vitamin C, Tamine group B), minerals (eg calcium, magnesium, magnesium
  • the present invention is a method for producing a sedative autonomic nerve regulator or a diurnal rhythm improving agent that acts on the olfactory sensation described above, and is characterized in that after fermenting milk with lactic acid bacteria, it is fermented with yeast.
  • a method for producing a nerve modifier is also provided.
  • the above-mentioned production method is a sterilization process, a formulation process, such as propylene glycol, glycerin, and fats and oils that are used as a kind of retention agent in order to enhance the action on olfaction.
  • a formulation process such as propylene glycol, glycerin, and fats and oils that are used as a kind of retention agent in order to enhance the action on olfaction.
  • additives and substances, and a step of adding additives and substances such as vitamin E and various plant extracts that reduce odor deterioration and loss in the heat treatment step and the like may be included.
  • the process of attaching to the exterior of a product the indication to the effect that it acts on an olfactory sense that it is an autonomic nerve regulator for sedation or a diurnal rhythm improving agent may be included.
  • the autonomic nervous regulator and diurnal rhythm improving agent of the present invention is an extract obtained by extracting a volatile odor component from fermented milk at a temperature near or above normal temperature using a steam distillation method, a vacuum distillation method, a solvent extraction method, or the like.
  • the concentrate which concentrated fermented milk and the extract using the evaporation method, the membrane concentration method, etc., and the form which formulated those extracts and concentrates may be sufficient. Further, it may be used by adding to fragrances, cosmetics, pharmaceuticals, foods, feed additives, textile detergents, textiles and the like.
  • a beverage or food that stays in the oral cavity for a certain period of time may act on the olfactory sense through the retronasal route.
  • the present invention also provides a “scented composition” containing a fermented milk-derived component obtained by fermenting milk with lactic acid bacteria and yeast.
  • the scented composition of the present invention is an extract obtained by extracting a volatile odor component from a fermented milk at a temperature near or above normal temperature using a steam distillation method, a vacuum distillation method, a solvent extraction method, etc.
  • a concentrate obtained by concentrating the product using an evaporation method, a membrane concentration method, etc., and a fragrance etc. in which the extract or concentrate is formulated, a fragrance, a cosmetic, a pharmaceutical, a food, a feed additive, Used by adding to detergents for textiles, textiles, etc.
  • Example 1 Autonomic nerve adjustment action by fermented milk fermented with lactic acid bacteria and yeast Material / Method 1.1 Preparation of Fermented Milk A (Lactic Acid Bacteria + Yeast) 100% by mass of sterilized skim milk is inoculated with 3% by mass of a mixed starter containing lactic acid bacteria (L. helveticus) and yeast (S. cerevisiae). Fermentation was carried out at 24 ° C. for 24 hours. Thereafter, sucrose was added and fermentation was performed at 25 ° C. for 24 hours, followed by heat sterilization treatment to prepare fermented milk A.
  • Fermented Milk A Fermented Milk A (Lactic Acid Bacteria + Yeast) 100% by mass of sterilized skim milk is inoculated with 3% by mass of a mixed starter containing lactic acid bacteria (L. helveticus) and yeast (S. cerevisiae). Fermentation was carried out at 24 ° C. for 24 hours. Thereafter, sucrose was added and fermentation was
  • Test sample Fermented milk A, water (control)
  • Test method On the day of the test, after fasting for 3 hours, the rats were laparotomized under urethane anesthesia (1 g / kg urethane aqueous solution was intraperitoneally administered), and the change in electrical activity was measured for the distal branch of each autonomic nerve.
  • centrifugal branches of each autonomic nerve of an opened rat were picked up with a silver recording electrode under a stereomicroscope.
  • the electrode was previously sufficiently immersed in a mixture of liquid paraffin and petroleum jelly.
  • the obtained nerve electrical activity was amplified with a condenser-type differential amplifier, monitored with an oscilloscope, and recorded on a magnetic tape. All neural activity was analyzed after converting the raw data into standard pulses using a slicer and window discriminator to separate it from background noise.
  • the discharge frequency was displayed on the pen recorder by a late meter with a reset time of 5 seconds.
  • a tube was inserted into the trachea from the start of surgery to the end of the experiment to secure the airway, and the body temperature (rat rectal temperature) was maintained at 35 ° C. ⁇ 0.5 ° C. with a heat retaining device.
  • Scent stimulation is cut by injecting 4 mL of 100-fold diluted water or water of fermented milk A into pharmaceutical cut cotton (4 cm x 4 cm x 0.5 cm) in the bottom of a plastic container (diameter 4.5 cm, height 5 cm) It was soaked in cotton, and the mouth of the container was applied to the nostril of the rat for 10 minutes.
  • the data was analyzed by the average value of the firing frequency (pulse / 5s) per 5 seconds every 5 minutes, and the value immediately before the odor stimulation (0 minute value) was shown as a percentage of 100%.
  • Statistical test for significant difference was performed by analysis of variance (ANOVA) with repeated measures.
  • Example 2 Diurnal rhythm improvement effect by fermented milk fermented with lactic acid bacteria and yeast Materials / Method 1.1 Preparation of Fermented Milk A (Lactic Acid Bacteria + Yeast) Fermented milk A was prepared by the method described in Example 1.
  • Test sample Fermented milk A, water (control)
  • Test method The animals were raised under constant temperature conditions of 24 ° C. under a light / dark cycle every 12 hours (lighted for 12 hours from 8 o'clock), and food and water were freely ingested. The first week was a period of odor stimulation for water as a control, and the next week was a period of odor stimulation for fermented milk A.
  • Odor stimulation was performed for 30 minutes every day from 14:00, and the amount of spontaneous activity was measured by measuring the number of times the animal crossed infrared rays. Spontaneous activity was measured over time, and daily activity, light (daytime) activity, dark activity, etc. were calculated. From these values, the light activity rate [light activity amount ⁇ 100 / daily activity amount] and the dark activity rate [dark activity amount ⁇ 100 / daily activity amount] were calculated.
  • water or 50 mL of 1000-fold diluted solution of fermented milk A was bubbled using a pump, and a wind containing the odor of the liquid was blown into each animal breeding cage. Statistical test for significant difference was performed by Wilcoxon signed-rank test.
  • the bright period is the active period and the dark period (dark period) is the dormant period, but in the rat, the light period is the dormant period and the dark period is the active period, which is the opposite of humans. .
  • Comparative Example 1 Diurnal rhythm improving action by fermented milk of lactic acid bacteria, fermented milk of yeast, and skim milk Materials / Methods 1.1 Preparation of Fermented Milk B (Lactic Acid Bacteria), Fermented Milk C (Yeast), Nonfat Milk 100% by mass of sterilized skim milk is inoculated with 3% by mass of L. helveticus starter at 37 ° C, After fermentation for 24 hours, heat sterilization was performed to prepare fermented milk B. Sterilized skim milk 100% by mass was inoculated with 3% by mass of a yeast (S. cerevisiae) starter, sucrose was added, and fermentation was performed at 25 ° C. for 24 hours. Then, the heat sterilization process was performed and the fermented milk C was prepared. A commercially available skim milk powder was dissolved in 9% (w / w) and then heat sterilized to prepare skim milk.
  • Fermented Milk B Lactic Acid Bacteria
  • Fermented Milk C Yeast
  • Test sample fermented milk B, fermented milk C, skim milk, water (control)
  • Test method According to Example 2, the diurnal rhythm improving effect by odor stimulation to rats was evaluated.
  • Example 3 Relaxation effect by fermented milk fermented with lactic acid bacteria and yeast (sensory evaluation) 1.
  • Materials / Methods 1.1 Preparation of Fermented Milk A (Lactic Acid Bacteria + Yeast), Fermented Milk B (Lactic Acid Bacteria), and Nonfat Milk Fermented milk A, fermented milk B, and nonfat milk were prepared according to the above Examples and Comparative Examples.
  • a ′ (Lactic Acid Bacteria + Yeast) 100% by mass of sterilized skim milk is inoculated with 3% by mass of a starter of lactic acid bacteria (L. helveticus CM4 accession number: FERM BP-6060) at 37 ° C., 24 Lactic acid fermentation was performed to prepare lactic acid bacteria fermented milk. Next, 3% by mass of yeast (S. cerevisiae strain JCM7255) starter was inoculated into the obtained lactic acid bacteria fermented milk, sucrose was added, and fermentation was performed at 25 ° C for 24 hours, followed by heat sterilization treatment. A ′ was prepared.
  • Test sample fermented milk A, fermented milk A ', fermented milk B, skim milk
  • Subjects 10 trained analytical panelists
  • Test method 30 mL of each test sample was placed in a 50 mL plastic cup and presented to the subject, and sensory evaluation was performed on the naturally exposed odor.
  • the Visual Analogue Scale (VAS) method was used for odor evaluation.
  • the smell of fermented milk obtained by fermenting with lactic acid bacteria and yeast has an autonomic nerve adjusting action (sedation action), a diurnal rhythm improving action, and a human relaxing effect.
  • the said effect is not recognized in lactic-acid-bacteria fermented milk, yeast fermented milk, and skim milk, and is unique to fermented milk obtained by fermenting with lactic acid bacteria and yeast.
  • the autonomic nerve adjusting agent and the diurnal rhythm improving agent of the present invention improve the balance of autonomic nerves due to stress and the disturbance of the diurnal rhythm, resulting in an increase in blood pressure and blood glucose, abnormal gastrointestinal function, sleep disorder It is useful for the alleviation, prevention and treatment of various symptoms and diseases.
  • the autonomic nerve adjusting agent and diurnal rhythm improving agent of the present invention do not need to be ingested (administered) into the body, and have an effect by acting on the olfaction, and thus have high safety, fragrance, cosmetics, It can be used as a fragrance composition added to various products such as foods, pharmaceuticals, feed additives, detergents for textile products, textile products and the like.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Diabetes (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Emergency Medicine (AREA)
  • Developmental Biology & Embryology (AREA)
  • Obesity (AREA)
  • Endocrinology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Anesthesiology (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Hematology (AREA)
  • Immunology (AREA)
  • Virology (AREA)
  • Zoology (AREA)
  • Epidemiology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Detergent Compositions (AREA)
  • Fats And Perfumes (AREA)
  • Dairy Products (AREA)
  • Cosmetics (AREA)

Abstract

La présente invention concerne un agent qui a un effet de réglage autonome et un effet d'amélioration de rythme quotidien ; et un produit parfumé. En particulier, la présente invention concerne un agent de réglage autonome pour sédation et un agent d'amélioration de rythme quotidien, qui sont caractérisés par : la fourniture d'un constituant dérivé de lait fermenté comme principe actif, ledit constituant dérivé de lait fermenté étant obtenu par fermentation du lait avec des bactéries d'acide lactique et des levures ; et le principe actif agissant sur l'odorat.
PCT/JP2015/001098 2014-03-04 2015-03-03 Agent de réglage autonome pour sédation, et agent d'amélioration de rythme quotidien Ceased WO2015133122A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2016506135A JP6471145B2 (ja) 2014-03-04 2015-03-03 鎮静用の自律神経調整剤及び日周リズム改善剤

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2014-041728 2014-03-04
JP2014041728 2014-03-04

Publications (1)

Publication Number Publication Date
WO2015133122A1 true WO2015133122A1 (fr) 2015-09-11

Family

ID=54054938

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2015/001098 Ceased WO2015133122A1 (fr) 2014-03-04 2015-03-03 Agent de réglage autonome pour sédation, et agent d'amélioration de rythme quotidien

Country Status (3)

Country Link
JP (1) JP6471145B2 (fr)
TW (1) TWI667029B (fr)
WO (1) WO2015133122A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016104802A (ja) * 2016-02-15 2016-06-09 三基商事株式会社 睡眠改善剤
JP2020152685A (ja) * 2019-03-20 2020-09-24 株式会社ヤクルト本社 ストレス緩和及び/又は集中力維持用組成物
CN111919887A (zh) * 2019-05-13 2020-11-13 株式会社明治 用于改善植物性神经功能的发酵乳
JPWO2022196488A1 (fr) * 2021-03-15 2022-09-22
JP7566600B2 (ja) 2020-12-03 2024-10-15 日清食品ホールディングス株式会社 時計遺伝子の発現を制御するビフィズス菌

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5115676A (en) * 1974-07-25 1976-02-07 Meiji Milk Prod Co Ltd Hatsukonyoru chiizufureebaano seizohoho
JPH0775521A (ja) * 1993-09-06 1995-03-20 Asahi Chem Ind Co Ltd 果実風味増強剤および風味が増強された果実飲料
WO1998005343A1 (fr) * 1996-08-07 1998-02-12 Calpis Co., Ltd. Medicaments anti-stress et aliments fonctionnels ayant des effets anti-stress
WO2005094849A1 (fr) * 2004-03-31 2005-10-13 Calpis Co., Ltd. Aliment fonctionnel pour améliorer le rythme de sécrétion de mélatonine endogène et aliment fonctionnel pour améliorer le rythme circadien
WO2013073424A1 (fr) * 2011-11-14 2013-05-23 株式会社明治 Lait fermenté liquide et procédé pour produire celui-ci

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5115676A (en) * 1974-07-25 1976-02-07 Meiji Milk Prod Co Ltd Hatsukonyoru chiizufureebaano seizohoho
JPH0775521A (ja) * 1993-09-06 1995-03-20 Asahi Chem Ind Co Ltd 果実風味増強剤および風味が増強された果実飲料
WO1998005343A1 (fr) * 1996-08-07 1998-02-12 Calpis Co., Ltd. Medicaments anti-stress et aliments fonctionnels ayant des effets anti-stress
WO2005094849A1 (fr) * 2004-03-31 2005-10-13 Calpis Co., Ltd. Aliment fonctionnel pour améliorer le rythme de sécrétion de mélatonine endogène et aliment fonctionnel pour améliorer le rythme circadien
WO2013073424A1 (fr) * 2011-11-14 2013-05-23 株式会社明治 Lait fermenté liquide et procédé pour produire celui-ci

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
KYOSUKE KAWAGUCHI ET AL.: "Hakkonyu no Shikosei Kojo ni Ataeru Nyusankin Oyobi Kobo no Yakuwari", JAPAN SOCIETY FOR BIOSCIENCE, BIOTECHNOLOGY, AND AGROCHEMISTRY TAIKAI KOEN YOSHISHU, vol. 2012, 2012, pages 2J15p11 *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016104802A (ja) * 2016-02-15 2016-06-09 三基商事株式会社 睡眠改善剤
JP2020152685A (ja) * 2019-03-20 2020-09-24 株式会社ヤクルト本社 ストレス緩和及び/又は集中力維持用組成物
CN111919887A (zh) * 2019-05-13 2020-11-13 株式会社明治 用于改善植物性神经功能的发酵乳
JP2020184906A (ja) * 2019-05-13 2020-11-19 株式会社明治 自律神経機能改善用の発酵乳
JP7369992B2 (ja) 2019-05-13 2023-10-27 株式会社明治 自律神経機能改善用の発酵乳
US12285449B2 (en) 2019-05-13 2025-04-29 Meiji Co., Ltd Fermented milk for improving autonomic nervous function
JP7566600B2 (ja) 2020-12-03 2024-10-15 日清食品ホールディングス株式会社 時計遺伝子の発現を制御するビフィズス菌
JPWO2022196488A1 (fr) * 2021-03-15 2022-09-22
WO2022196488A1 (fr) * 2021-03-15 2022-09-22 森永乳業株式会社 Composition pour améliorer la qualité de vie
JP7662767B2 (ja) 2021-03-15 2025-04-15 森永乳業株式会社 Qolを改善するための組成物

Also Published As

Publication number Publication date
JPWO2015133122A1 (ja) 2017-04-06
JP6471145B2 (ja) 2019-02-13
TWI667029B (zh) 2019-08-01
TW201620530A (zh) 2016-06-16

Similar Documents

Publication Publication Date Title
JP5923238B2 (ja) 迷走神経活性化剤
JP5770425B2 (ja) 副交感神経活動亢進作用を有する医薬組成物又は飲食物
JP6923883B2 (ja) 栄養状態改善に使用するための組成物
JP6471145B2 (ja) 鎮静用の自律神経調整剤及び日周リズム改善剤
CN111212575A (zh) 肌肉增量用组合物
CN100586297C (zh) 抗牙周病菌组合物
JP6669829B2 (ja) 茶発酵物
JP6894097B2 (ja) 腎性貧血改善用組成物
CN112553117A (zh) 一株能够抑制皮肤角质层增厚的罗伊氏乳杆菌及其应用
CN111263590A (zh) 具有体力提高作用及抗疲劳作用中的一种以上作用的组合物
JP7430312B2 (ja) 腸内短鎖脂肪酸産生促進用組成物及びこれを含む飲食品
JPWO2005094849A1 (ja) 内因性メラトニン分泌リズム改善用機能性食品、及び概日リズム改善用機能性食品
JP2010006757A (ja) 経口摂取用皮膚性状改善剤
JP5950993B2 (ja) 迷走神経活性化剤
EP2612673A1 (fr) Immunomodulateur intestinal
EP3479836B1 (fr) Composition facilitant la régénération du cartilage
KR102789055B1 (ko) 장내 미생물 또는 이로부터 유래된 세포밖 소포체를 유효성분으로 포함하는 수면장애의 예방, 개선 또는 치료용 조성물
JP2018174772A (ja) 乳酸菌の製造方法、及び免疫調節用組成物
EP4527919A1 (fr) Prevotella histicola
JP2007126399A (ja) グルタチオン増加用組成物
JP2023106626A (ja) 乳酸菌、及びセロトニン分泌促進剤
HK1215854A1 (zh) 应激减轻剂

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15758885

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2016506135

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 15758885

Country of ref document: EP

Kind code of ref document: A1