COMPOSITION FOR RELIEVING STRESS, PHARMACEUTICAL COMPOSITION AND FOOD AND DRINK COMPOSITION AND METHOD FOR RELIEVING STRESS USING THE COMPOSITION FOR RELIEVING STRESS

Abstract

A composition for relieving stress comprising a Bifidobacterium breve MCC 1274 (FERMBP-11175) as an active ingredient is provided. The composition for relieving stress according to the present technology can improve or prevent stress-induced anger, confusion, tension, or fatigue, or can improve vigor., stress can be assessed by POMS or POMS 2. The composition for relieving stress according to the present technology can be used for pharmaceutical compositions and food and drink compositions.

Description

This application claims priority under 35 U.S.C. § 119 to Japanese Patent Application No. 2018-062467, filed Mar. 28, 2018, the entirety of which is incorporated by reference herein.

BACKGROUND

General Field

The present technology relates to a composition for relieving stress and a pharmaceutical composition, a food and drink composition, and a method for relieving stress using the composition for relieving stress.

Brief Description of the Related Art

In recent years, situations of mental stress and anxiety in daily life and work have been increasing. Mental stress causes psychological changes such as anxiety, irritability and mental confusion, and if it is prolonged, there is a high possibility of causing depression and interfering with interpersonal relationships. In addition, appetite may be abnormally enhanced due to such mental stress, leading to obesity.

Until now, the use of chemical synthetic drugs such as tranquilizers, anti-anxiety agents and sleeping pills to relieve mental stress have also been suggested. However, not all drugs are suitable for daily or long-term use due to serious side effects and habits. As a way of coping with mental stress, coping methods such as mental training and mind control have been tried, but their effectiveness is limited.

In recent years, it has been clarified that the intestinal environment is involved in signal transmission from the intestine to the brain, and stress control originating in the intestine has been reported.

For example, JP2014-101288 discloses an effect of suppressing stress-induced enteropathy, which comprises a sterilized form of Lactobacillus gasseri CP 2305 as an active ingredient.

Neurosci Lett. 2005 discloses that the parasympathetic activity is enhanced upon administration of Lactobacillus johnsonii Lal to rats.

JP2015-96542 discloses a vagus nerve activator containing cells of Lactobacillus gasseri CP 2305 as an active ingredient. WO2014/132982 discloses a stress reducing agent containing Lactobacillus gasseri OLL 2809, a probiotic lactic acid bacterium, as an active ingredient, reduces “tension-anxiety” in psychological profile examination and reduces “fatigue” by combining with α-LA.

Bioscience of Microbiota, Food and Health, 2015/1/21 discloses that the lactic acid bacteria beverage containing Bifidobacterium B. Bifidum Y as an active ingredient significantly improves “irritability” (anger) and maintains “vigor” at a high level.

Journal of Bioengineering, Vol. 85, No. 12 521-526, 2007 reports that intake of a lactic acid bacteria fermented tea beverage of Lactobacillus brevis mh 4219 suppresses a decrease in “vigor” after stress load calculation.

Thus, although some improvement effects of psychological state by ingesting probiotics cells or fermentation products have been reported so far, probiotics are known to show different physiological effects in each strain; and hence, no consistent results have been obtained in the above report.

SUMMARY

Problems to be Solved

As mentioned above, although some improvement effects of psychological state by ingesting probiotics cells or fermentation products have been reported so far, probiotics are known to show different physiological effects in each strain; and hence, no consistent results have been obtained in the above report.

Therefore, in the present technology, the main object is to provide a novel composition for relieving stress.

Means for Solving the Problems

Firstly, the present technology provides a composition for relieving stress comprising a Bifidobacterium breve MCC 1274 (FERMBP-11175) as an active ingredient.

The composition for relieving stress according to the present technology can improve or prevent stress-induced anger, confusion, tension, or fatigue, or can improve vigor.

In the present technology, stress can be assessed by POMS or POMS 2.

The composition for relieving stress according to the present technology can be used for pharmaceutical compositions and food and drink compositions.

The present technology provides use of Bifidobacterium breve MCC 1274 (FERMBP-11175) in a stress relieving agent, a drug for stress relieving, or a food/beverage for stress relieving; a method for relieving stress, comprising administering Bifidobacterium breve MCC 1274 (FERMBP-11175) to a subject; the method for relieving stress comprising administering Bifidobacterium breve MCC 1274 (FERMBP-11175) to a subject with normal brain function; the method for relieving stress, comprising administering Bifidobacterium breve MCC 1274 (FERMBP-11175) to person over 35 years of age; the method for relieving stress, comprising administering Bifidobacterium breve MCC 1274 (FERMBP-11175) to a subject from a period of autumn to winter; and use of Bifidobacterium breve MCC 1274 (FERMBP-11175) for preventing, treating and/or improving stress-induced migraine, tension headache, chronic pain, dizziness, Meniere's disease, menopausal disorder, Seasonal Affective Disorder (SAD), hyperthyroidism, organ asthma, hyperventilation syndrome, chronic obstructive pulmonary disease (COPD), chronic urticaria, shingles (herpes), atopic dermatitis, alopecia areata, hyperhidrosis, hypertension, angina pectoris, myocardial infarction, arrhythmia, orthostatic hypotension, temporomandibular joint arthrosis, stomatitis, functional gastrointestinal disorder, functional dyspepsia, gastric pain, gastroenteritis, diarrhea and constipation, gastric ulcer, duodenal ulcer, irritable bowel syndrome, ulcerative colitis, psychogenic vomiting, colic, night terror, night crying, rheumatoid arthritis, low back pain, muscle contraction headache, spasmodic torticollis, writer's cramp, eye strain, essential blepharospasm, nocturnal enuresis, overactive cystitis, psychogenic impotence, eating disorder or hyperphagia.

The present technology further provides a method for preventing, treating and/or improving stress-induced migraine, tension headache, chronic pain, dizziness, Meniere's disease, menopausal disorder, Seasonal Affective Disorder (SAD), hyperthyroidism, organ asthma, hyperventilation syndrome, chronic obstructive pulmonary disease (COPD), chronic urticaria, shingles (herpes), atopic dermatitis, alopecia areata, hyperhidrosis, hypertension, angina pectoris, myocardial infarction, arrhythmia, orthostatic hypotension, temporomandibular joint arthrosis, stomatitis, functional gastrointestinal disorder, functional dyspepsia, gastric pain, gastroenteritis, diarrhea, constipation, gastric ulcer, duodenal ulcer, irritable bowel syndrome, ulcerative colitis, psychogenic vomiting, colic, night terror, night crying, rheumatoid arthritis, low back pain, muscle contraction headache, spasmodic torticollis, writer's cramp, eye strain, essential blepharospasm, nocturnal enuresis, overactive cystitis, psychogenic impotence, eating disorder or hyperphagia by administering Bifidobacterium breve MCC 1274 (FERMBP-11175) to the subject.

According to the present technology, a novel composition for relieving stress can be provided.

Note that, the effect described here is not necessarily limited, and may be any effect described in the present specification.

DESCRIPTION OF THE EXEMPLARY EMBODIMENTS

Hereinafter, exemplary embodiments for implementing the present technology will be described. Note that the embodiments described below show an example of a representative embodiment of the present technology, and the scope of the present technology is not narrowly interpreted by this.

1. Composition for Relieving Stress

The composition for relieving stress of the present technology comprises a Bifidobacterium breve MCC 1274 (FERMBP-11175) as an active ingredient.

Bifidobacterium breve MCC 1274 is deposited with National Institute of Advanced Industrial Science and Technology Patent Microorganisms Depositary (Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan (Present IPOD National Institute of Technology and Evaluation—Patent Organism Depositary (NITE-IPOD): 2-5-8120, Kazusakamatari, Kisarazu, Chiba 292-0818, Japan)) on Aug. 25, 2009 under the accession number IPODFER MBP-11175, and is generally available from the above storage institution.

Note that the names of the bacteria exemplified above are not limited to the deposited strains which have been deposited or registered in a predetermined institution under the name of the bacteria, and include strains (also called “derivative” or “derivative strain”) substantially identical thereto. That is, “Bifidobacterium breve MCC 1274 (FERMBP-11175)” is not limited to the strain deposited in the above depository under the deposit number of MCC 1274 (FERMBP-11175), and includes substantially identical strains thereto.

With regards to the strain, “a strain substantially identical to the above deposited strain” means a strain which belongs to the same species as the above deposited strain and from which the sleep promoting effect, which is the effect, can be obtained. The strain substantially identical to the deposited strain may be, for example, a derivative having the deposited strain as a parent strain. Derivative includes a strain bred from the deposited strain or a strain naturally produced from the deposited strain.

The substantially identical strains and derivatives include the following strains.

(1) A strain determined to be identical to the strain Bifidobacterium breve MCC 1274 by RAPD method (Randomly Amplified Polymorphic DNA) and PFGE method (Pulsed-field gel electrophoresis) described in Probiotics in food/Health and nutritional properties and guidelines for evaluation 85 Page 43)(2) A strain that has only the gene derived from Bifidobacterium breve MCC1274, does not have a gene of foreign origin, and has 95% or more DNA identity with Bifidobacterium breve MCC1274
(3) A strain bred from Bifidobacterium breve MCC 1274 (including strain bred by genetic engineering modification, mutation, natural mutation) and having a trait with MCC 1274

Bifidobacterium breve is one of strains belonging to the genus Bifidobacterium. Bifidobacterium breve is mainly found in the large intestine of infants, and known as an infant type Bifidobacterium bacterium, along with Bifidobacterium longum subsp. Infantis and the like are among the strains belonging to the genus Bifidobacterium.

The composition for relieving stress of this technology is Bifidobacterium breve, the active ingredient of which predominantly resides in the large intestine of infants and toddlers. Therefore, it is highly safe and it is very useful because there is a lower risk of side effects even if it is continuously administered for a long period of time. Furthermore, it is highly safe even when used in combination with other drugs.

Here, “relief” in the present specification means recovery of symptoms or disease, prevention or delay of deterioration of symptoms or disease, reversal, prevention or delay of progression of symptoms or disease, or treatment of symptoms or disease, and the like. Furthermore, “relief” in the present specification also includes the meaning of prevention. “Prevention” means preventing or delaying the onset of symptoms or disease in a subject of application, or reducing the risk of onset of symptoms or disease in a subject of application or the like.

The composition for relieving stress of the present technology can relieve stress, particularly in situations where brain function is exposed to stress in a normal state. Specifically, stress-induced anger, confusion or tension can be improved or prevented.

In the present technology, stress can be assessed by POMS (Profile of Mood States) or POMS 2 (Profile of Mood States 2nd Edition). POMS and POMS 2 are registered trademarks of Multi-Health Systems Inc. Note that these psychological tests have different inspection methods depending on the target population, such as for adults and adolescents, and different number of question items at the time of examination, such as all items version and short version. However, the inspection method and the number of question items may be appropriately selected according to the situation of the object.

Specifically, for example, in POMS, the factors of “Anger-Hostility (AH)”, “Confusion (C)”, “Depression-Dejection (DD)”, “Fatigue (F)”, “Tension-Anxiety (TA)”, “Vigor (V) and “Total Mood Disturbance (TMD)” are measured.

In POMS 2, the factors of “Anger-Hostility (AH)”, “Confusion-Bewilderment (CB)”, “Depression-Dejection (DD)”, “Fatigue-Inertia (FI)”, “Tension-Anxiety (TA)”, “Vigor-Activity (VA)”, “Friendliness (F)”, and “Total Mood Disturbance (TMD)” are measured.

The composition for relieving stress according to the present technology can be used to prevent and/or treat symptoms and diseases that occur under stress by relieving stress. Examples of the symptoms and diseases that occur under stress include migraine, tension headache, chronic pain, dizziness, Meniere's disease, menopausal disorder, Seasonal Affective Disorder (SAD), hyperthyroidism, organ asthma, hyperventilation syndrome, chronic obstructive pulmonary disease (COPD), chronic urticaria, shingles (herpes), atopic dermatitis, alopecia areata, hyperhidrosis, hypertension, angina pectoris, myocardial infarction, arrhythmia, orthostatic hypotension, temporomandibular joint arthrosis, stomatitis, functional gastrointestinal disorder, functional dyspepsia, gastric pain, gastroenteritis, diarrhea and constipation, gastric ulcer, duodenal ulcer, irritable bowel syndrome, ulcerative colitis, psychogenic vomiting, colic, night terror, night crying, rheumatoid arthritis, low back pain, muscle contraction headache, spasmodic torticollis, writer's cramp, eye strain, essential blepharospasm, nocturnal enuresis, overactive cystitis, psychogenic impotence, eating disorder or hyperphagia and the like.

The composition for relieving stress according to the present technology can also be used to improve energy, vitality, concentration and the like by relieving stress. That is, the composition for relieving stress according to the present technology can also be used as an energy improver, a vitality improver, a concentration improver, and the like.

Furthermore, the composition for relieving stress according to the present technology can also relieve tension by relieving stress under specific conditions. Specifically, for example, it may be used to relieve tension of the athlete during competition or relieve tension during tests and maintain the mental aspect under the situation thereof, and exert ordinary abilities.

The subject of the composition for relieving stress according to the present technology is not particularly limited, and can be applied to animals including humans. Sex and age of the subjects are not particularly limited, but for example, in the case of humans, the composition can be used particularly effectively for a person in middle or old age such as 35 years old or above, preferably 40 years old or above, more preferably 45 years old or above. The composition can be used in infants and toddlers or children, in women during pregnancy period, perinatal period, lactation period and before and after menstruation.

Subjects to whom composition can be preferably administered are as follows:

(1) A person who tends to be depressed, such as a person who is punctual, serious, who has a strong sense of responsibility, is hardworking, has a strong sense of justice, who cannot refuse when asked, who dislikes fighting with people, who always cares about what other people think and the like
(2) A person who is weak to environmental changes
(3) A person who is sensitive to stress

The composition for relieving stress according to the present technology can be used anytime throughout the year, but can be effectively used particularly in the period from autumn to winter when stress is likely to occur, in the change of the season, and the like.

The composition for relieving stress according to the present technology may contain a culture containing Bifidobacterium breve MCC 1274 (FERMBP-11175) as its active ingredient Bifidobacterium breve MCC 1274 (FERMBP-11175).

The medium for culturing Bifidobacterium breve used is not particularly limited, and a medium usually used for culturing bacteria belonging to the genus Bifidobacterium can be used.

That is, examples of a carbon source that can be used according to assimilability include saccharides such as glucose, galactose, lactose, arabinose, mannose, sucrose, starch, starch hydrolysate, molasses and the like. Examples of a nitrogen source that can be used include ammonium salts and nitrates such as ammonia, ammonium sulfate, ammonium chloride, ammonium nitrate and the like. Further, examples of the inorganic salts that can be used include sodium chloride, potassium chloride, potassium phosphate, magnesium sulfate, calcium chloride, calcium nitrate, manganese chloride, ferrous sulfate and the like. In addition, organic components such as peptone, soybean powder, defatted soybean meal, meat extract, and yeast extract may be used.

The culture conditions are not particularly limited as long as the effects of the present technology are not impaired. For example, the culture temperature is usually from 25 to 50° C., and preferably from 35 to 42° C. Moreover, culture is preferably cultivated under anaerobic conditions, for example, culture can be cultivated while ventilating an anaerobic gas such as carbon dioxide gas. Further, the culture may be cultivated under slightly aerobic conditions such as liquid stationary culture.

The culture obtained after culturing Bifidobacterium breve used may be used as it is, or may be used after dilution or concentration, or cells collected from the culture may be used.

For present cells, the culture obtained after culturing may be used as it is, or may be used after dilution or concentration, or cells collected from the culture may be used. In addition, various additional operations such as heating and lyophilization can be performed after the culturing as long as the effects are not impaired. In addition, the present cells may be live bacteria or dead bacteria. In the case of live bacteria, it is preferable to treat by the bacterial culture freezing method, the spray drying method, the lyophilization method, and the oil drop method. The dead bacteria include dead bacteria which are sterilized by heating, lyophilization and the like. Other methods for preparing dead cells include a spray drying method, retort sterilization method, lyophilization method, UHT sterilization method, pressure sterilization method, high pressure steam sterilization method, dry heat sterilization method, flow steam sterilization method, electromagnetic wave sterilization method, electron beam sterilization method, microwave sterilization method, radiation sterilization method, ultraviolet ray sterilization method, gaseous ethylene oxide sterilization method, gaseous hydrogen peroxide plasma sterilization method, chemical sterilization method (alcohol sterilization method, formalin fixation method, electrolytic water treatment method) and the like. Also, the present cells may be crushed product. The crushed product may be one obtained by crushing live bacteria or one obtained by crushing dead bacteria, or may be one subjected to heating or lyophilization after crushing. Further, crushing can be selected by, for example, physical crushing, enzymatic dissolution treatment, chemical treatment, autolysis treatment and the like using methods and equipment known in the technical field.

Physical crushing may be performed either in the form of a cell suspension or in the form of a cell powder. As an example of physical crushing, crushing by stirring using ultrasonic homogenizer, homogenizer, ball mill, bead mill, dyno mill, planetary mill and the like; crushing by pressure using a jet mill, French press, cell homogenizer and the like; or crushing by damaging the cells by filter filtration can be selected.

As the enzymatic dissolution treatment, for example, an enzyme such as lysozyme can be used to destroy the cell structure of the lactic acid bacterial cell.

As the chemical treatment, surfactants such as soybean phospholipid and glycerin fatty acid ester can be used to destroy the cell structure of the lactic acid bacterial cell.

As the autolysis treatment, lactic acid bacterial cells can be dissolved by some enzymes of lactic acid bacteria themselves.

Note that, physical crushing is preferable because it is not necessary to add other chemicals or compounds.

In the present specification, “culture” is a concept including culture supernatant.

The composition for relieving stress according to the present technology may consist only of the active ingredient or may be a composition in which the active ingredient and an optional ingredient other than the active ingredient are blended.

The optional ingredient is not particularly limited, and additives (for example, a pharmaceutical carrier or the like described later) which has been conventionally blended in pharmaceuticals can be blended.

2. Specific Form of Composition for Relieving Stress According to the Present Technology

The composition for relieving stress according to the present technology can be used in the form of food and drink, pharmaceutical, quasi-drug, feed and the like.

Note that the application of the present embodiment may be therapeutically or non-therapeutically used.

“Non-therapeutic” is a concept that does not include medical practice, i.e., treatment of the human body by medical treatment. Examples thereof include health promotion, beauty practice and the like.

“Improvement” refers to the recovery from a disease, symptom or condition; prevention or delay of deterioration of a disease, symptom or condition; reversal, prevention or delay of the progression of a disease or symptom.

“Prevention” refers to preventing or delaying the onset of disease or symptom in a subject of application, or reducing the risk of disease or symptom in a subject of application or the like.

<Food and Drink>

The composition for relieving stress according to the present technology can be prepared by adding it to known food and drink, or can be mixed into the raw material of food and drink to produce new food and drink.

The food and drink using the composition for relieving stress according to the present technology may be in any form such as liquid, paste, solid, powder, and the like. In addition to tablet confectionery, liquid food and the like, examples include wheat flour products, instant foods, processed agricultural products, processed marine products, processed meat products, milk and dairy products, oils and fats, basic seasonings, combined seasonings and foods, frozen foods, confectionery, beverages, and other commercially available products and the like.

Examples of wheat flour products include bread, macaroni, spaghetti, noodles, cake mix, fried flour and bread crumbs and the like.

Examples of instant foods include instant noodles, cup noodles, retorts, cooked foods, cooked cans, microwave foods, instant soups and stews, instant miso soup and clear soup, soup cans, freeze-dried foods, and other instant foods and the like.

Examples of processed agricultural products include canned agricultural products, canned fruits, jams and marmalades, pickles, boiled beans, dried agricultural products and cereals (grain processed food products) and the like.

Examples of processed marine products include canned marine products, fish ham/sausages, seafood paste products, fish delicacies, tsukudani and the like.

Examples of processed meat products include meat cans/pastes, meat ham and sausages, and the like.

Examples of milk and dairy products include fermented milk such as yogurt, processed milk, milk drink, lactic acid bacteria drinks, cheese, ice creams, modified milk powders, cream, modified milk powder for infants, nutritional supplementary food for infants, milk for pregnant women and lactating women, other dairy products and the like.

Examples of fats and oils include butter, margarine, vegetable oil and the like.

Examples of basic seasonings include soy sauce, miso, sauces, tomato processed seasoning, mirins, and vinegars and the like. Examples of combined seasonings and foods include cooking mixes, curry ingredients, sauces, dressings, noodles, spices, and other combined seasonings and the like.

Examples of frozen foods include raw frozen food, semi-cooked frozen food, cooked frozen food and the like.

Examples of confectionery include caramel, candy, chewing gum, chocolate, cookies, biscuits, cakes, pies, snacks, crackers, Japanese confectionery, rice cakes, bean sweets, dessert sweets, other sweets and the like.

Examples of beverages include carbonated beverages, natural juices, fruit juices, soft drinks containing fruit juice, fruit pulp drinks, fruit drinks containing granules, vegetable drinks, soy milk, soy milk drinks, coffee drinks, tea drinks, powdered drinks, concentrated drinks, sports drinks, nutritional drinks, alcoholic beverages, other favorite beverages and the like.

Examples of commercially available food other than the above include baby food, Furikake (dried food sprinkled over rice), dried seasoning for rice with tea and the like. The food and drink composition can be manufactured by adding the present cells to the raw material of ordinary food and drink, and can be manufactured in the same manner as ordinary food and drink without adding the present cells. The present cells may be added at any stage of the process of manufacturing the food and drink composition. Moreover, the food and drink composition may be manufactured through the fermentation process with the added cells. Examples of such food and drink composition include a lactic-acid-bacteria drink, fermented milk and the like.

As a raw material of the food and drink composition, the raw material used for ordinary food and drink can be used. The manufactured food and drink composition can be taken orally.

Further, for example, for newborns or infants, it is also possible to adopt a method of adding the present cells to milked breast milk and orally ingested or ingested through a naso-gastric feeding tube or the like.

In addition, the food and drink composition may use a component having a probiotic effect known or to be found in the future or a component that supplements a probiotic effect as long as the effect is not impaired. For example, the food and drink composition can be produced by blending present cells with components such as various proteins such as whey protein, casein protein, soybean protein, or pea protein or mixtures and decomposition products thereof; amino acids such as leucine, valine, isoleucine or glutamine; vitamins such as vitamin B6 or vitamin C; creatine; citric acid; fish oil; or oligosaccharides such as isomaltooligosaccharides, galactooligosaccharides, xylooligosaccharides, soybean oligosaccharides, fructooligosaccharides, lactulose, and human milk oligosaccharides (HMO). Examples of the human milk oligosaccharide that can be used include neutral human milk oligosaccharides such as 2′-fucosyllactose, 3-fucosyllactose, 2′, 3-difucosyllactose, lacto-N-triose II, lacto-N-tetraose, lacto-N-neotetraose, lacto-N-fucopentaose I, lacto-N-neofucopentaose, 1-N-fucopentaose II, lacto-N-fucopentaose III, lacto-N-fucopentaose V, lacto-N-neofucopentaose V, lacto-N-difucohexaose I, lacto-N-difucohexaose II, 6′-galactosyl lactose, 3′-galactosyl lactose, lacto-N-hexaose and lacto-N-neohexaose; acidic human milk oligosaccharides such as 3′-sialyllactose, 6′-sialyllactose, 3-fucosyl-3′-sialyllactose, disialyl-lacto-N-tetraose and the like.

As the food and drink according to the present technology, modified milk powder can be mentioned. Modified milk powder refers to a modified milk powder for children of 0 to 12 months, a follow-up milk for infants after 6 to 9 months and young children (up to 3 years old), a low birth weight modified milk powder for newborns weighing less than 2500 g at birth (low birth weight infants), various therapeutic milks used for the treatment of a child with a pathological condition such as milk allergy or lactose intolerance and the like. Furthermore, the composition can be applied to health functional foods and foods for patients. The health functional food system was established not only for ordinary foods but also for food in the form of tablets, capsules and the like, based on internal and external trends and consistency with the conventional food system for specified health use. It consists of two types; a special health food (individual permission type) and a nutrition functional food (standard type).

Food and drink according to the present technology may include nutritional supplementary food and milk for mothers during pregnancy and lactation. Milk for mothers refers to milk and the like which is balancedly blended with the nutrition necessary for pregnancy and lactation.

Specifically, the formula milk can be produced, for example, by the following method.

In other words, a method is provided for producing a powdered milk for infants or a milk for mothers which comprises mixing a prebiotic and/or powdered milk with a cell powder containing Bifidobacterium bacteria to obtain a powdered milk for stress relief

Specifically, for example, a method of producing powdered milk for stress relief is provided, which comprises the following steps (A) to (C):

(A) Culturing the Bifidobacterium bacteria in a medium containing a milk component to obtain a culture;

(B) Subjecting the culture to spray drying and/or lyophilization to obtain cell powder; and

(C) Mixing the cell powder with prebiotics and/or powdered milk to obtain powdered milk for stress relief.

Further, the food composition may specifically be, for example, a powdered milk supplement for stress relief. For example, a powdered milk supplement for stress relief can be produced by the following method.

That is, a method is provided for producing a powdered milk supplement for stress relief which comprises the following steps (A) and (B):

(A) Mixing the prebiotics, Bifidobacterium bacteria, and an excipient to obtain a mixture; and

(B) Tableting the resulting mixture.

The content of Bifidobacterium breve MCC 1274 (FERMBP-11175) in food and drink according to the present technology can be freely set as long as the effects of the present technology are not impaired., the content of Bifidobacterium breve MCC 1274 (FERMBP-11175) in food and drink is particularly preferably 1×10³ to 1×10¹² cfu/g with respect to the final composition of food and drink. The daily dose is at least 1×10³ cfu/day or more, more preferably 1×10⁶ cfu/day or more, more preferably 1×10⁸ cfu/day or more, furthermore preferably 2×10¹⁰ cfu/day or more, or it is preferable to add more than the aforementioned dose. “cfu” represents colony forming unit. When the cells are dead, cfu/g or cfu/ml can be replaced with individual cell/g or individual cell/ml. When the present cell is a crushed product, it can be displayed in terms of weight from the number of cells (individual cell/g) before crushing.

Functional Indication Food and Drink

In addition, the food and drink as defined can be provided and sold as a food and drink for which a specific application (in particular, health application) or a function is displayed.

“Display” act includes all acts to inform consumers about the application, and if it is an expression that can recall or analogize the application, regardless of the purpose of the display, the content of the display, the target object or medium to be displayed and the like, all fall under the “display” act of the present technology.

Moreover, it is preferable that “display” is expressed so that the consumer recognizes the said application directly. Specifically, examples thereof include an act to assign, deliver, display for the purpose of assignment or delivery, and import goods or packages of goods relating to the food and drink described by the application, an act to describe, display or distribute the above application in an advertisement, price list or transaction document concerning goods, or to describe the above application in information containing them and provide it by an electromagnetic (internet or the like) method and the like.

On the other hand, it is preferable that the display content is a display approved by the administration or the like (for example, a display which is approved based on various systems defined by the administration and performed in a mode based on such an approval). In addition, it is preferable to affix such display contents to advertising materials at sales sites such as packaging, containers, catalogs, pamphlets, POPs, and other documents.

In addition, “display” also includes display of health food, functional food, food for patients, enteral nutrition food, special purpose food, health functional food, special health food, functional display food, functional nutritional food, quasi-drugs and the like. Among these, examples of the display approved by the Consumer Affairs Agency include the display approved by the Special health food system, the Functional display food system, the system similar to these and the like. More specifically, the display as special health food, the display as conditional special health food, the display as functional display food, the display of effects on the structure and function of the body, display of reducing disease risk and the like can be mentioned. Among these, typical examples include the special health food specified by Health Promotion Act Enforcement Regulations (Apr. 30, 2003, Ministry of Health, Labor and Welfare Ordinance No. 86 of Japan) (particularly display of the use of health), the functional display food specified by Food Labelling Law (2013 Law No. 70) and the display similar to these.

Note that the expression used in the display as described above is not limited to only the expression of stress relief and the like. Even if other expression is used, it is included in the scope of the present technology as long as it indicates the effect of preventing, treating and/or improving various diseases and symptoms related to stress relief. As such an expression, for example, it is also possible to display “to those who are tired” and “to those who are stressed” based on various applications that make the consumer recognize the effect of stress relief

<Pharmaceuticals, Quasi-Drugs>

The composition for relieving stress according to the present technology can be prepared by adding it to a known pharmaceutical or quasi-drug (hereinafter, also referred to as “pharmaceutical or the like”), or it can be mixed with raw materials such as pharmaceutical or the like to produce new pharmaceutical and the like.

When the composition for relieving stress according to the present technology is blended in a pharmaceutical or the like, the pharmaceutical or the like can be appropriately formulated into a desired dosage form according to an administration method such as oral administration or parenteral administration. The dosage form is not particularly limited, but in the case of oral administration, examples include solid preparations such as powders, granules, tablets, troches and capsules; and liquids such as solutions, syrups, suspensions and emulsions. In the case of parenteral administration, examples include suppositories, sprays, inhalants, ointments, patches, injections and the like., it is preferable to formulate into a dosage form for oral administration.

Note that formulation can be carried out by known methods as appropriate depending on the dosage form.

At the time of formulation, the formulation may be prepared by appropriately blending a formulation carrier. In addition to the composition for relieving stress of the present technology, it is possible to use components such as excipients, pH adjusters, coloring agents, and flavoring agents that are generally used for formulation. Furthermore, it is also possible to use components in combination which have an effect of preventing, improving and/or treating diseases or symptoms known or to be found in the future, according to the purpose.

Formulation carriers including various organic or inorganic carriers can be used depending on the dosage form. Examples of the carrier in the case of solid preparation include excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents and the like.

Examples of the excipient include sugar derivatives such as lactose, sucrose, glucose, mannitol, sorbite, and the like; starch derivatives such as corn starch, potato starch, α-starch, dextrin, carboxymethyl starch and the like; cellulose derivatives such as crystalline cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethylcellulose, carboxymethylcellulose calcium and the like; gum arabic; dextran; pullulan; silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, magnesium aluminometasilicate and the like; phosphate derivatives such as calcium phosphate; carbonate derivatives such as calcium carbonate; sulfate derivatives such as calcium sulfate and the like.

Examples of the binder include, in addition to the above-mentioned excipients, gelatin; polyvinyl pyrrolidone; macrogol and the like.

Examples of the disintegrant include, in addition to the above-mentioned excipients, chemically modified starch or cellulose derivatives such as croscarmellose sodium, sodium carboxymethyl starch and crosslinked polyvinyl pyrrolidone.

Examples of the lubricant include talc; stearic acid; metal stearates such as calcium stearate, magnesium stearate and the like; colloidal silica; waxes such as pea gum and spermaceti wax; boric acid; glycols; carboxylic acids such as fumaric acid and adipic acid; sodium salt of carbonic acid such as sodium benzoate; sulfates such as sodium sulfate; leucine; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acids such as anhydrous silicic acid and silicic acid hydrate; starch derivatives and the like.

Examples of the stabilizer include p-hydroxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalkonium chloride; acetic anhydride; sorbic acid and the like.

Examples of the flavoring agent include sweetening agents, acidulants, perfumes and the like.

Carrier to be used in the case of liquid drug for oral administration includes solvents such as water, flavoring agents and the like.

The content of Bifidobacterium breve MCC 1274 (FERMBP-11175) in the pharmaceutical and the like according to the present technology can be freely set as long as the effects of the present technology are not impaired., the content of Bifidobacterium breve MCC 1274 (FERMBP-11175) in the pharmaceutical and the like is particularly preferably 1×10³ to 1×10¹² cfu/g with respect to the final composition of the pharmaceutical and the like. The daily dose is at least 1×10³ cfu/day or more, more preferably 1×10⁶ cfu/day or more, more preferably 1×10⁸ cfu/day or more, furthermore preferably 2×10¹⁰ cfu/day or more, or the dose is preferably more than the aforementioned dose.

<Feed>

The composition for relieving stress according to the present technology can be prepared by adding it to a known feed, or can be mixed into raw material of feed to produce new feed.

In the case of adding the composition for relieving stress according to the present technology to feed, examples of the raw material of the feed include cereals such as corn, wheat, barley, rye; bran such as fusuma, wheat bran, rice bran, defatted rice bran; manufactured meals such as corn gluten meal, corn jam meal and the like; animal feeds such as skimmed milk powder, whey, fish meal, bone meal; yeast such as beer yeast; mineral feeds such as calcium phosphate and calcium carbonate; oils and fats; amino acids; saccharides and the like. Moreover, the form of the feed includes the feed for pets (pet food and the like), livestock feed, fish feed and the like.

The content of Bifidobacterium breve MCC 1274 (FERMBP-11175) in the feed according to the present technology can be freely set according to the weight and the like as long as the effect of the present technology is not impaired., the content of Bifidobacterium breve MCC 1274 (FERMBP-11175) in the feed is particularly preferably 1×10³ to 1×10¹² cfu/g with respect to the final composition of feed. The daily dose is at least 1×10³ cfu/day or more, more preferably 1×10⁶ cfu/day or more, more preferably 1×10⁸ cfu/day or more, furthermore preferably 2×10¹⁰ cfu/day or more, or the dose is preferably more than the aforementioned dose.

The present technology can also adopt the following configuration.

[1] A composition for relieving stress comprising a Bifidobacterium breve MCC 1274 (FERMBP-11175) as an active ingredient.

[2] The composition for relieving stress according to [1], which improves or prevents stress-induced anger, confusion, tension or fatigue, or improves vigor.

[3] The composition for relieving stress according to [2], wherein the stress is evaluated by POMS (Profile of Mood States) or POMS 2 (Profile of Mood States 2nd Edition).

[4] The composition for relieving stress according to any one of [1] to [3] is a pharmaceutical composition.

[5] The composition for relieving stress according to any one of [1] to [3] is a food and drink composition.

[6] Use of Bifidobacterium breve MCC 1274 (FERMBP-11175) as a stress relieving agent, a drug for stress relief, or a food/drink for stress relief.

[7] A method for relieving stress, comprising the administration of Bifidobacterium breve MCC 1274 (FERMBP-11175) to a subject.

[8] The method for relieving stress comprising the administration of Bifidobacterium breve MCC 1274 (FERMBP-11175) to a subject with normal brain function.

[9] The method for relieving stress, comprising the administration of Bifidobacterium breve MCC 1274 (FERMBP-11175) to person over 35 years of age.

[10] The method for relieving stress, comprising the administration of Bifidobacterium breve MCC 1274 (FERMBP-11175) to a subject from period of autumn to winter.

[11] Use of Bifidobacterium breve MCC 1274 (FERMBP-11175) for preventing, treating and/or improving stress-induced migraine, tension headache, chronic pain, dizziness, Meniere's disease, menopausal disorder, Seasonal Affective Disorder (SAD), hyperthyroidism, organ asthma, hyperventilation syndrome, chronic obstructive pulmonary disease (COPD), chronic urticaria, shingles (herpes), atopic dermatitis, alopecia areata, hyperhidrosis, hypertension, angina pectoris, myocardial infarction, arrhythmia, orthostatic hypotension, temporomandibular joint arthrosis, stomatitis, functional gastrointestinal disorder, functional dyspepsia, gastric pain, gastroenteritis, diarrhea and constipation, gastric ulcer, duodenal ulcer, irritable bowel syndrome, ulcerative colitis, psychogenic vomiting, colic, night terror, night crying, rheumatoid arthritis, low back pain, muscle contraction headache, spasmodic torticollis, writer's cramp, eye strain, essential blepharospasm, nocturnal enuresis, overactive cystitis, psychogenic impotence, eating disorder or hyperphagia.

[12] A method for preventing, treating and/or improving stress-induced migraine, tension headache, chronic pain, dizziness, Meniere's disease, menopausal disorder, Seasonal Affective Disorder (SAD), hyperthyroidism, organ asthma, hyperventilation syndrome, chronic obstructive pulmonary disease (COPD), chronic urticaria, shingles (herpes), atopic dermatitis, alopecia areata, hyperhidrosis, hypertension, angina pectoris, myocardial infarction, arrhythmia, orthostatic hypotension, temporomandibular joint arthrosis, stomatitis, functional gastrointestinal disorder, functional dyspepsia, gastric pain, gastroenteritis, diarrhea, constipation, gastric ulcer, duodenal ulcer, irritable bowel syndrome, ulcerative colitis, psychogenic vomiting, colic, night terror, night crying, rheumatoid arthritis, low back pain, muscle contraction headache, spasmodic torticollis, writer's cramp, eye strain, essential blepharospasm, nocturnal enuresis, overactive cystitis, psychogenic impotence, eating disorder or hyperphagia by administering Bifidobacterium breve MCC 1274 (FERMBP-11175) to the subject.

EXAMPLES

Hereinafter, the present technology will be described in more detail based on examples. Note that the examples described below show an example of a representative embodiment of the present technology, and the scope of the present technology is not narrowly interpreted.

Example 1

<Preparing Test Sample>

The culture solution of Bifidobacterium breve MCC 1274 (FERMBP-11175) was concentrated and dried to obtain a live bacteria dry matter. The live bacteria dry matter was mixed with starch, and filled 345 mg into 1 capsule to prepare a test sample.

On the other hand, a placebo capsule was prepared by filling only 345 mg of starch into a capsule, and used as a control sample.

It was confirmed that the test sample and the control sample were indistinguishable in appearance, color and taste.

<Subject>

Healthy subjects of 20 years or older (BMI of 25 or more and less than 30) were enrolled in the clinical trial as subjects. Furthermore, persons who did not violate the following exclusion criteria (1) to (7) were analyzed by body composition measurement, blood test, and interview by consent.

(1) Person taking treatment for serious illness or person who has a serious past history of illness

(2) Person suffering from gastrointestinal disease and taking medication

(3) Person receiving drug treatment for lifestyle-related diseases (diabetes, hypertension, dyslipidemia)

(4) Person who has a past history of drug allergy or serious food allergy

(5) Those who are pregnant, who intend to become pregnant during the trial period, those who are breastfeeding

(6) Person who is heavy smoker, heavy drinker, and has irregular lifestyle

(7) Person who is judged to be unsuitable as a subject by the examination doctor or study doctor based on the subject's background, physical findings, and interview results

Specific subject's background factors are shown in Table 1 below. No significant difference was found in the age of the control group and the test group.

	TABLE 1
			Difference
	Control group	Test group	between groups
No. of subjects	40	40	N.S.
(Person)
Age (years old)	45.6 ± 8.5	45.4 ± 9.8	N.S.

<Test Method>

A randomized, double-blind, placebo-controlled, parallel-group comparison study was conducted. After a two-week pre-observation period, the subjects were assigned to a group receiving a control sample (hereinafter sometimes referred to as “control group”) and a group receiving a test sample (hereinafter sometimes referred to as “test group”). The subjects in both groups received the test sample or the control sample once a day for 12 weeks together with water within 30 minutes after meals. That is, the daily intake of the test group was 20 billion live bacteria of Bifidobacterium breve MCC 1274 (FERMBP-11175).

Before intake, at 12 weeks after intake, in order to evaluate the temporary mood state, the examination by “POMS 2 adult short version”, which is a mood profile examination, was carried out. As a result, the total scores were converted into T scores according to the Japanese manual thereof. At the same time, for the test group, before intake and at 12 weeks after intake, the total score of seven factors: sleep quality, sleep onset time, sleep duration, sleep efficiency, sleep difficulty, sleep medication use, and daytime awakening difficulties, were calculated using the Pittsburgh Sleep Quality Index (PSQI).

<Statistical Analysis>

The blind results were reviewed before the key open and analyzed excluding those who did not meet the analysis criteria defined in advance (i.e. those who meet less than 80% of the criteria, those who violate prohibited food or taking medicine, and others who seriously violate or deviate from the study protocol). However, there were no such individuals in this study, so all 80 subjects were analyzed for efficacy.

<Results>

The results of the examination by “POMS 2 adult short version” are shown in Table 2 below. The average value and the variation of the overall score of the Pittsburgh Sleep Quality Index (PSQI) in the test group are shown in Table 3 below.

	TABLE 2
	Control group	Test group
	Before	At 12	p	Before	At 12	p
	intake	weeks	value*	intake	weeks	value*
Anger-Hostility	44.6 ± 6.1	46.9 ± 6.8	0.031	45.2 ± 6.6	46.3 ± 7.7	0.311
(AH)
Confusion-	44.0 ± 6.7	47.1 ± 7.4	0.004	46.6 ± 8.7	46.6 ± 8.7	1.000
Bewilderment
(CB)
Depression-	45.2 ± 5.7	46.8 ± 7.5	0.063	46.1 ± 7.5	47.0 ± 8.3	0.275
Dejection (DD)
Fatigue-Inertia	43.6 ± 6.2	45.1 ± 6.9	0.189	44.7 ± 8.5	46.0 ± 8.6	0.077
(FI)
Tension-Anxiety	43.7 ± 5.4	45.4 ± 5.9	0.055	46.7 ± 9.7	46.8 ± 8.7	0.948
(TA)
Vigor-Activity	49.4 ± 8.9	50.4 ± 8.0	0.358	52.6 ± 10.1	53.1 ± 11.0	0.673
(VA)
Friendliness (F)	49.3 ± 8.6	51.9 ± 9.1	0.086	52.0 ± 10.4	52.4 ± 11.4	0.767
Total Mood	44.3 ± 5.9	46.3 ± 6.7	0.032	45.3 ± 8.4	46.0 ± 9.0	0.408
Disturbance
(TMD)
Result is shown in mean value and standard deviation.
*Intergroup comparison of mean value for before intake by unpaired t test

TABLE 3
Before intake	After intake	Variation
3.1	2.9	−0.2

Values of “Anger-Hostility (AH)”, “Confusion-Bewilderment (CB)”, “Depression-Dejection (DD)”, “Tension-Anxiety (TA)” and “Total Mood Disturbance (TMD)” shown in Table 2 were significantly increased at 12 weeks compared to before intake in the control group, while these values remained low in the test group.

From these results, Bifidobacterium breve MCC 1274 (FERMBP-11175) was shown to be effective in improving mood profile of “Anger-Hostility (AH)”, “Confusion-Bewilderment (CB)”, “Depression-Dejection (DD)”, “Tension-Anxiety (TA)” and “Total Mood Disturbance (TMD)”.

In addition, as shown in Table 3, the PSQI overall score was decreased by −0.20 after intake for 12 weeks compared to before intake of the test substance, and sleep quality, sleep onset time, sleep duration, sleep efficiency, sleep difficulty, sleep medication use, and daytime awakening difficulties were improved in a comprehensive manner.

Example 2

<Preparing Test Sample>

Fermented milk with or without Bifidobacterium breve strain MCC 1274 (FERMBP-11175) was produced according to the following procedure. Firstly, a milk raw material, water as needed, other components and the like were mixed, and subjected to the homogenization treatment and the heat sterilization treatment by a conventional method. Then, to the heat-sterilized modified milk liquid, a lactic starter and a freeze-dried powder of Bifidobacterium breve strain MCC1274 (FERMBP-11175) were added (inoculated) and fermented by maintaining at a predetermined fermentation temperature. When the pH reached to the target value, the curd formed was crushed by stirring and cooled to 10° C. or less to produce a fermented milk. This was used as a test sample.

On the other hand, in the same process, the fermented milk in which only the lactic starter was added (inoculated) to the modified milk liquid was produced. This was used as a control sample.

It was confirmed that the test sample and the control sample were indistinguishable in appearance, color and taste.

<Subject>

Healthy subjects between the ages of 20 and 65 at the time of consent (BMI 25 of or more and less than 30) were enrolled in the clinical trial as subjects. Furthermore, 140 persons who did not violate the following exclusion criteria (1) to (6) were selected as subjects according to body composition measurement, blood test, and interview by doctor.

(1) Person who has a past history such as serious disease

(2) Person receiving drug treatment for lifestyle-related diseases (diabetes, hypertension, dyslipidemia)

(3) Person who has drug allergy or serious food allergy

(4) Those who are pregnant, who intend to become pregnant during the trial period, those who are breastfeeding

(5) Person who is a heavy smoker and a heavy drinker

(6) Person who is judged to be unsuitable as a subject by the examination doctor or study doctor based on the subject's background, physical findings, and interview results

Specific subject's background factors are shown in Table 4 below. No significant difference was found in the age of the control group and the test group.

	TABLE 4
			Difference
	Control group	Test group	between groups
No. of subjects	70	70	N.S.
(Person)
Age (years old)	46.8 ± 8.7	47.6 ± 8.6	N.S.

<Test Method>

A randomized, double-blind, placebo-controlled, parallel-group comparison study was conducted. After a two-week pre-observation period, 140 subjects were assigned to a group receiving a control sample (hereinafter sometimes referred to as “control group”) and a group receiving a test sample (hereinafter sometimes referred to as “test group”). Each group had 70 subjects. The subjects in both groups received the test sample or the control sample once a day after meals irrespective of breakfast, lunch or dinner for 12 consecutive weeks. The viable count of Bifidobacterium breve MCC 1274 (FERMBP-11175) contained in the test sample was at least 100 million per day (one dose). That is, the daily intake of the test group was at least 100 million live bacteria of Bifidobacterium breve MCC 1274 (FERMBP-11175).

Before intake, at 12 weeks after intake, in order to evaluate the temporary mood state, the examination by “POMS 2 adult short version”, which is a mood profile examination, was carried out. As a result, the total scores were converted into T scores according to the Japanese manual thereof

<Statistical Analysis>

The blind results were reviewed before the key open and analyzed excluding those who did not meet the analysis criteria defined in advance (i.e. those who meet less than 80% of the criteria, those who violate prohibited food or taking medicine, and others who seriously violate or deviate from the study protocol). However, there were no such individuals in this study, so all 140 subjects were analyzed for efficacy.

<Results>

The results of the examination by “POMS 2 adult short version” are shown in Table 5 below.

TABLE 5
								TMD
T score	AH	CB	DD	FI	TA	VA	F	score
Test group	0.1	−0.3	0.1	−0.4	−0.5	1.2	0.3	−0.4
Control	1.7	1.9	1.1	0.6	1.8	−0.1	0.0	1.5
group
p value (t-	0.10	0.01	0.24	0.33	0.03	0.32	0.82	0.03
test)

Values of “Anger-Hostility (AH)”, “Confusion-Bewilderment (CB)”, “Depression-Dejection (DD)”, “Fatigue-Inertia (FI)”, “Tension-Anxiety (TA)” and “Total Mood Disturbance (TMD)” shown in Table 5 were lower in the test group compared to the control group. Particularly, “Confusion-Bewilderment (CB)”, “Tension-Anxiety (TA)” and “Total Mood Disturbance (TMD)” showed low value with a significant difference.

The values of “Vigor-Activity (VA)” and “Friendliness (F)” were high in the test group compared to the control group.

From these results, Bifidobacterium breve MCC 1274 (FERMBP-11175) was shown to be effective in improving all mood profiles of “Anger-Hostility (AH)”, “Confusion-Bewilderment (CB)”, “Depression-Dejection (DD)”, “Fatigue-Inertia (FI)”, “Tension-Anxiety (TA)”, “Total Mood Disturbance (TMD)”, “Vigor-Activity (VA)” and “Friendliness (F)”.

Preparation Example

The preparation example of the pharmaceutical composition and the food composition for stress relief is shown as follows.

Preparation Example 1

Bifidobacterium breve MCC 1274 (FERMBP-11175) was added to 3 mL of MRS liquid medium, anaerobically cultured at 37° C. for 16 hours. The culture solution was then concentrated, and freeze-dried to obtain freeze-dried powder of bacteria (bacterial cell powder). The bacterial cell powder, the whey protein concentrate (WPC), and the prebiotics (lactulose, raffinose and galactooligosaccharide) were homogeneously mixed to obtain a composition. 20 g of the composition was dissolved in 200 g of water to obtain a composition for relieving stress. Administration of the resulting composition can alleviate the stress.

Preparation Example 2

Bifidobacterium breve MCC 1274 (FERMBP-11175) was added to 3 mL of MRS liquid medium, and anaerobically cultured at 37° C. for 16 hours. The culture solution was then concentrated and freeze-dried to obtain freeze-dried powder of bacteria (bacterial cell powder). The bacterial cell powder, the dry powder of milk protein concentrate (MPC 480, manufactured by Fontera Co., 80 mass % protein content, casein protein:whey protein=about 8:2), and the prebiotics (lactulose, raffinose and galactooligosaccharide) were homogeneously mixed to obtain a composition. 20 g of the composition was dissolved in 200 g of water to obtain a composition for relieving stress. Administration of the resulting composition can alleviate the stress.

Preparation Example 3

Bifidobacterium breve MCC 1274 (FERMBP-11175) was added to 3 mL of MRS liquid medium, anaerobically cultured at 37° C. for 16 hours. The culture solution was then concentrated and freeze-dried to obtain freeze-dried powder of bacteria (bacterial cell powder). Next, prebiotics (lactulose, raffinose and galactooligosaccharide) and crystalline cellulose were charged into a stirring granulator and mixed. Thereafter, the purified water was added to granulate. Resulting granules were dried to obtain granules (pharmaceutical composition) containing an extract of bacteria and prebiotics and containing an excipient. Administration of the granules can alleviate the stress.

Preparation Example 4

The preparation method of fermented milk to which Bifidobacterium breve MCC 1274 (FERMBP-11175) was added is shown below.

Firstly, the milk raw material, the water as needed, other components and the like were mixed, and preferably subjected to homogenization treatment and heat sterilization treatment. The homogenization treatment and the heat sterilization treatment can be performed by a conventional method. Then, to the heat-sterilized modified milk liquid, a lactic starter was added (inoculated) and fermented by maintaining at a predetermined fermentation temperature to obtain a fermented product. The curd was formed by fermentation.

Examples of the lactic starter that can be used include the lactic acid bacteria usually used for producing yogurt, such as Lactobacillus bulgaricus, Lactococcus lactis, Streptococcus thermophilus. When the pH reached the target value, the curd formed was crushed by stirring and cooled to 10° C. or less to produce a fermented product. This was used as a test sample. By cooling to 10° C. or less, the activity of lactic acid bacteria can be reduced to suppress the production of an acid.

Next, the fermented product obtained in the fermentation step was subjected to heat treatment to obtain a fermented product after heating (fermented product after heat treatment). By appropriately heating the fermented product, it is possible to suppress the production of acid by lactic acid bacteria in the fermented product after heating. Thus, it is possible to suppress a decrease in pH during the subsequent manufacturing step and/or during storage of the concentrated fermented milk containing Bifidobacterium; as a result, it is possible to improve the survivability of Bifidobacterium.

Thereafter, to the fermented product obtained in the heat treatment step after heating, Bifidobacterium breve MCC 1274 (FERMBP-11175) and prebiotics (lactulose, raffinose and galactooligosaccharide) were added. The amount of Bifidobacterium breve MCC 1274 (FERMBP-11175) added to the fermented product after heating is preferably from 1×10⁷ to 1×10¹¹ cfu/ml, more preferably from 1×10⁸ to 1×10¹⁰ cfu/ml. When Bifidobacterium breve MCC 1274 (FERMBP-11175) is dead, cfu/mL can be replaced with individual cells/mL.

The fermented product after heating was concentrated after adding Bifidobacterium breve MCC 1274 (FERMBP-11175) and prebiotics thereto. The concentration step can be performed using a known concentration method as appropriate. For example, centrifugation method or membrane separation can be used. In the centrifugation method, whey in the substance to be concentrated (fermented product after heating to which bifidobacteria and prebiotics have been added) is removed to obtain concentrated fermented milk containing bifidobacteria and prebiotics with an increased solid content concentration.

Administration of the fermented milk obtained as described above can alleviate stress.

Preparation Example 5

The preparation method of modified milk powder to which Bifidobacterium breve MCC 1274 (FERMBP-11175) was added is shown below.

10 kg of desalted milk whey protein powder (manufactured by Mirai), 6 kg of milk casein powder (manufactured by Fontera), 48 kg of lactose (manufactured by Mirai), 920 g of mineral mixture (manufactured by Tomita Pharmaceutical Co., Ltd), and 32 g of vitamin mixture (manufactured by Tanabe Seiyaku Co., Ltd.), 500 g of lactulose (manufactured by Morinaga Milk Industry Co., Ltd.), 500 g of raffinose (manufactured by Nippon Tensai Seito Co., Ltd.) and 900 g of galactooligosaccharide liquid sugar (manufactured by Yakult Pharmaceutical Co., Ltd.) were dissolved in 300 kg of warm water. The mixture was further heated at 90° C. for 10 minutes and dissolved and 28 kg of prepared fat (manufactured by Taiyo Yushi Co., Ltd.) was added and homogenized. Thereafter, the mixture was sterilized and concentrated and spray-dried to prepare about 95 kg of modified milk powder. To this, 100 g of bacterial cell powder (1.8×10¹¹ cfu/g, manufactured by Morinaga Milk Co., Ltd.) of Bifidobacterium breve MCC 1274 (FERMBP-11175) dispersed in starch was added, to prepare about 95 kg of Bifidobacterium-oligosaccharide-blended modified milk powder. When the modified milk powder was dissolved in water to form modified milk liquid having a total solid concentration of 14% (w/V), which is a standard milk formula concentration, the number of Bifidobacterium in the modified milk liquid obtained was 2.7×10⁹ cfu/100 mL. Administration of modified milk powder obtained as described above can alleviate stress.

Claims

1. A composition for relieving stress comprising a Bifidobacterium breve MCC 1274 (FERMBP-11175) as an active ingredient.

2. The composition for relieving stress according to claim 1, which improves or prevents stress-induced anger, confusion, tension or fatigue, or improves vigor.

3. The composition for relieving stress according to claim 1, wherein stress is evaluated by POMS (Profile of Mood States) or POMS 2 (Profile of Mood States 2nd Edition).

4. The composition for relieving stress according to claim 1 is a pharmaceutical composition.

5. The composition for relieving stress according to claim 1 is a food and drink composition.

6. Use of Bifidobacterium breve MCC 1274 (FERMBP-11175) as a stress relieving agent, a drug for stress relief, or a food/drink for stress relief.

7. A method for relieving stress, comprising the administration of Bifidobacterium breve MCC 1274 (FERMBP-11175) to a subject.

8. The method for relieving stress of claim 7, wherein the subject has normal brain function.

9. The method for relieving stress of claim 7, wherein said subject is a person over 35 years of age.

10. The method for relieving stress of claim 7, wherein said administering is to a subject from a period of autumn to winter.

11. Use of Bifidobacterium breve MCC 1274 (FERMBP-11175) for preventing, treating and/or improving stress-induced migraine, tension headache, chronic pain, dizziness, Meniere's disease, menopausal disorder, Seasonal Affective Disorder (SAD), hyperthyroidism, organ asthma, hyperventilation syndrome, chronic obstructive pulmonary disease (COPD), chronic urticaria, shingles (herpes), atopic dermatitis, alopecia areata, hyperhidrosis, hypertension, angina pectoris, myocardial infarction, arrhythmia, orthostatic hypotension, temporomandibular joint arthrosis, stomatitis, functional gastrointestinal disorder, functional dyspepsia, gastric pain, gastroenteritis, diarrhea and constipation, gastric ulcer, duodenal ulcer, irritable bowel syndrome, ulcerative colitis, psychogenic vomiting, colic, night terror, night crying, rheumatoid arthritis, low back pain, muscle contraction headache, spasmodic torticollis, writer's cramp, eye strain, essential blepharospasm, nocturnal enuresis, overactive cystitis, psychogenic impotence, eating disorder or hyperphagia.

12. A method for preventing, treating and/or improving stress-induced migraine, tension headache, chronic pain, dizziness, Meniere's disease, menopausal disorder, Seasonal Affective Disorder (SAD), hyperthyroidism, organ asthma, hyperventilation syndrome, chronic obstructive pulmonary disease (COPD), chronic urticaria, shingles (herpes), atopic dermatitis, alopecia areata, hyperhidrosis, hypertension, angina pectoris, myocardial infarction, arrhythmia, orthostatic hypotension, temporomandibular joint arthrosis, stomatitis, functional gastrointestinal disorder, functional dyspepsia, gastric pain, gastroenteritis, diarrhea, constipation, gastric ulcer, duodenal ulcer, irritable bowel syndrome, ulcerative colitis, psychogenic vomiting, colic, night terror, night crying, rheumatoid arthritis, low back pain, muscle contraction headache, spasmodic torticollis, writer's cramp, eye strain, essential blepharospasm, nocturnal enuresis, overactive cystitis, psychogenic impotence, eating disorder or hyperphagia by administering Bifidobacterium breve MCC 1274 (FERMBP-11175) to the subject.