Composition for improving work performance

Abstract

To provide a new functionality of Bifidobacteriumlongumsubsp. longum (Bifidobacteriumlongumsubsp. longum).SOLUTION: The composition for improving work performance contains a combination of one or more kinds selected from bacterial cells of Bifidobacterium longum subsp. longum, a cultured product of the bacteria and a treated product of the bacteria, and lactulose as active ingredients.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a composition for improving work performance, which contains Bifidobacterium longum subsp. longum and lactulose as active ingredients. [Background technology]

[0002] In recent years, attention has been drawn to the relationship between intestinal bacteria and health, and research is being conducted worldwide. "Probiotics," a term known for improving the intestinal environment, generally refers to microorganisms that have a beneficial effect on humans by improving the balance of intestinal flora. Furthermore, there are also "prebiotics" that are assimilated by such probiotics, which generally refer to substances that are not broken down or absorbed in the upper digestive tract, but serve as a selective nutrient source for beneficial bacteria that live symbiotically in the large intestine, promoting their proliferation and improving and maintaining a healthy balance of intestinal flora in the large intestine, thereby helping to promote and maintain human health. It has also been proposed to combine probiotics and prebiotics to create "synbiotics" that have even more beneficial effects on humans.

[0003] Bifidobacterium bacteria (also known as bifidobacteria) are one of the major probiotics. Bifidobacterium bacteria have been reported to have various beneficial effects on hosts such as humans, including the prevention of diarrhea, reduction of harmful bacteria and toxic compounds, immunomodulation, and anticarcinogenic activity (Non-Patent Documents 1 to 3). Various prebiotics are known, and one of them, lactulose, a disaccharide consisting of galactose and fructose, is known to promote the proliferation of beneficial intestinal bacteria such as Bifidobacterium bacteria and to have various effects such as regulating the intestines and improving liver function (Patent Documents 1 to 7). Although various functions are expected from Bifidobacterium bacteria as probiotics, the full picture has not yet been elucidated. The same is true for the functionality of synbiotics when they are combined with prebiotics such as lactulose.

[0004] In recent years, there has been a desire to improve not only the physical health but also the mental health of workers, and it has been proposed that the intake of fermented milk containing lactic acid bacteria (Lactococcus lactis subsp. lactis), a type of probiotic, can improve work performance (Patent Document 8). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent No. 3908513 [Patent Document 2] Patent No. 3920288 [Patent Document 3] Japanese Patent Application Publication No. 7-39318 [Patent Document 4] Japanese Patent Application Laid-Open No. 2009-167172 [Patent Document 5] Japanese Patent Application Publication No. 11-240837 [Patent Document 6] European Patent Publication No. 04664362 [Patent Document 7] Japanese Patent Application Publication No. 10-194975 [Patent Document 8] Japanese Patent Application Publication No. 2020-039308 [Non-patent literature]

[0006] [Non-Patent Document 1] S. Fukuda et al., Nature, 2011, 469, 543-547. [Non-patent document 2] S. Fanning et al., PNAS, 2012, 109 (6), 2108-2113. [Non-patent document 3] Sivan A. et al., Science. 2015, 350 (6264), 1084-1089. Summary of the Invention [Problem to be solved by the invention]

[0007] An objective of the present invention is to provide new functionality when Bifidobacterium longum subsp. longum is used as a probiotic. [Means for solving the problem]

[0008] As a result of intensive research to solve the above-mentioned problems, the present inventors discovered that relative presenteeism improved in humans who were administered a composition containing Bifidobacterium longum subsp. longum and lactulose, resulting in improved work performance, and thus completed the present invention.

[0009] That is, the present invention provides a composition for improving work performance, which contains lactulose and one or more substances selected from the group consisting of Bifidobacterium longum subsp. longum cells, a culture of the bacterium, and a processed product of the bacterium. In a preferred embodiment, the Bifidobacterium longum subsp. longum is Bifidobacterium longum subsp. longum BB536 The strain is (NITE BP-02621). In a preferred embodiment, the improved work performance is due to an improvement in relative presenteeism. In a preferred embodiment, the composition comprises 2 x 10 Bifidobacterium longum subsp. longum. 9Contains more than cfu / 100g. The compositions of the present invention are preferably administered to humans in their 40s of age. The composition of the present invention is preferably administered to a human who works 4 to 5 days per week. The compositions of the present invention are preferably administered to humans with a low diversity of intestinal flora. The composition of the present invention is preferably administered to a human having a high proportion of Bifidobacterium bacteria in the intestinal flora. The composition of the present invention preferably contains Bifidobacterium longum subsp. longum in an amount of 3×10 7 cfu / kg body weight / day or more. The composition of the present invention is preferably a food or drink, more preferably fermented milk. The composition of the present invention is preferably a pharmaceutical product. [Effects of the Invention]

[0010] The present invention provides new functionalities when Bifidobacterium longum subsp. longum is used as a probiotic, specifically, it is expected to improve work performance and contribute to improving the mental health of workers. DETAILED DESCRIPTION OF THE INVENTION

[0011] The present invention will now be described in detail. However, the present invention is not limited to the following embodiments and can be freely modified within the scope of the present invention.

[0012] The composition of the present invention contains, as active ingredients, one or more selected from the group consisting of Bifidobacterium longum subsp. longum cells, cultures of said bacteria, and processed products of said bacteria (these may be collectively referred to as "B. longum cells"), and lactulose.

[0013] Bifidobacterium longum subsp. longum includes, but is not limited to, Bifidobacterium longum BB536. Um longum BB536 was deposited at the National Patent Microorganism Depositary (NPMD) of the National Institute of Technology and Evaluation (Room 122, 2-5-8 Kazusa Kamatari, Kisarazu, Chiba 292-0818) on January 26, 2018, under the accession number NITE BP-02621, in accordance with the Budapest Convention. The same bacterium, Bifidobacterium longum subsp. longum ATCC BAA-999 (number: ATCC BAA-999), is available from the American Type Culture Collection (ATCC; 10801 University Boulevard, Manassas, VA 20110, United States of America) under the designation ATCC BAA-999 (see, for example, Japanese Patent Application Laid-Open No. 2012-22244). (See Publication No. 23134, etc.)

[0014] It should be noted that the Bifidobacterium longum subsp. longum BB536 strain in this specification is not limited to the strain itself that has been deposited or registered with a designated institution under that name of bacterium (hereinafter, for convenience of explanation, also referred to as the "deposited strain"), but also includes strains that are substantially equivalent thereto (also referred to as "derived strains" or "derived strains"). In other words, it is not limited to the strain itself that has been deposited with the depository institution under the above accession number, but also includes strains that are substantially equivalent thereto. With regard to bacteria, "strains that are substantially equivalent to the above deposited strain" means strains that belong to the same species as the above deposited strain, and further, the degree of similarity of the genome sequence (Average Nucleotide Identity value) with the above deposited strain is preferably It refers to a strain that has 99.0% or more, more preferably 99.5% or more, and even more preferably 100% identity, and preferably has the same bacteriological properties as the deposited strain. With regard to bacteria, a strain that is substantially equivalent to the deposited strain may be, for example, a derivative strain with the deposited strain as a parent strain. Derived strains include strains bred from the deposited strain and strains that have arisen naturally from the deposited strain. Breeding methods include modification by genetic engineering techniques and modification by mutation treatment. Mutation treatments include irradiation with X-rays, irradiation with ultraviolet light, and N-methyl-N'- Examples of such mutations include treatment with mutagens such as nitro-N-nitrosoguanidine, ethyl methanesulfonate, and methyl methanesulfonate. Strains naturally arising from the deposited strain include strains that arise naturally during use of the deposited strain. Such strains include mutant strains that arise naturally through culturing (e.g., subculturing) of the deposited strain. Derivative strains may be constructed by a single modification, or by two or more modifications.

[0015] The bacteria contained in the composition of the present invention may be commercially available products, may be obtained by appropriate manufacturing, or may be obtained by culturing the above-mentioned bacteria. The culture method is not particularly limited as long as it allows the bacteria to grow. For example, a method generally used for culturing lactic acid bacteria can be used as is, or with appropriate modifications. The culture temperature may be, for example, 25 to 50°C, and preferably 35 to 42°C. The culture can be preferably carried out under anaerobic conditions, for example, while aerating with anaerobic gas such as carbon dioxide. The culture can also be carried out under microaerobic conditions, such as liquid static culture. The culture can be carried out, for example, until the bacteria grow to a desired level.

[0016] The medium used for the culture is not particularly limited as long as it allows the bacteria to grow. For example, a medium generally used for culturing lactic acid bacteria can be used as is or after appropriate modification. Specifically, sugars such as galactose, glucose, fructose, mannose, cellobiose, maltose, lactose, sucrose, trehalose, starch, starch hydrolysates, and blackstrap molasses can be used as carbon sources depending on the assimilation ability. For example, ammonium salts such as ammonia, ammonium sulfate, ammonium chloride, and ammonium nitrate, as well as nitrates, can be used as nitrogen sources. Furthermore, inorganic salts such as sodium chloride, potassium chloride, potassium phosphate, and magnesium sulfate can be used. Examples of suitable media include calcium, calcium chloride, calcium nitrate, manganese chloride, and ferrous sulfate. Organic ingredients such as peptone, soybean flour, defatted soybean meal, meat extract, and yeast extract may also be used. Media commonly used for culturing Bifidobacterium longum subsp. longum include reinforced clostridial medium, de Man, Rogosa, and Sharpe medium (MRS medium), modified MRS medium (mMRS medium), TOSP medium (TOS propionate medium), and TOSP Mup medium. Examples of suitable medium include TOS propionate mupirocin medium, GAM (Gifu Anaerobic Medium), and YCFA (Yeast Extract-casein Hydrolysate Acid) medium.

[0017] The form of Bifidobacterium longum subsp. longum contained in the composition of the present invention may be any of bacterial cells, a bacterial culture, or a processed bacterial product. The bacterial cells may be live bacterial cells, dead bacterial cells, or a mixture of live and dead bacterial cells, but preferably contain live bacterial cells.

[0018] As the bacterial culture, for example, the culture obtained by culturing may be used as is, or the culture may be diluted or concentrated and used, or bacterial cells recovered from the culture may be used. Furthermore, the culture may be a culture supernatant or a culture fraction. When using a culture supernatant, for example, the supernatant of the culture solution obtained by culturing in GAM medium at 37°C for 16 hours can be preferably used. As the processed bacterial product, the bacterial cells or culture may be crushed, heated, dried, or diluted, dried, or fractionated. Heat-treated bacterial cells (heat-sterilized bacterial cells) can be obtained, for example, by treating the bacteria at 70 to 100°C for 10 to 40 minutes or at 90 to 150°C for 5 to 30 seconds. Pressure may be applied during the heat treatment. The temperature does not necessarily need to be constant during the heat treatment, as long as it is within the above temperature range for the specified time. The heat-sterilized bacteria may be used as is after the heat treatment, or may be subjected to a process such as crushing, heat drying, freeze drying, or spray drying before use.

[0019] The content of B. longum cells in the composition of the present invention is not particularly limited and is appropriately determined depending on the form of the composition. For example, the amount of the bacterial cells is 2×10 9 cfu / 100g or more, 2×10 10 cfu / 100g or more, 2×10 11 cfu / 100g or more is preferable, and the upper limit is not particularly limited, but 2 × 10 14 cfu / 100g or less, 2×10 13 cfu / 100g or less, 2×10 12 cfu / 100g or less. 9 cfu / 100mL or more, 2×10 10 cfu / 100mL or more, 2×10 11 It is preferable that the concentration is 2×10 cfu / 100 mL or more. The upper limit is not particularly limited, but it is preferably 2×10 14 cfu / 100mL or less, 2×10 13 cfu / 100mL or less, 2×10 12 It is acceptable to limit the number of cfu / 100 mL. In this specification, "cfu" stands for colony forming unit. Furthermore, when dead cells are included, cfu / g or cfu / mL may be interpreted as individual cells / g or individual cells / mL. When a culture supernatant is used as the bacterial culture, the content is preferably 0.1 to 100% by mass, more preferably 1 to 90% by mass, and even more preferably 10 to 80% by mass of the entire composition. In the composition of the invention, the content of B. longum fungal cells in the entire composition is preferably 0.001% by mass or more and less than 100% by mass, more preferably 0.005 to 95% by mass, and even more preferably 0.01 to 85% by mass. These may be in the range of contents typically used when distributed as oral compositions.

[0020] The composition of the present invention contains lactulose. Lactulose is a disaccharide consisting of fructose and galactose. In the present invention, lactulose may be anhydrous or hydrated.

[0021] Lactulose can be produced by known methods. For example, sodium hydroxide is added to a 10% aqueous solution of commercially available lactose, the mixture is heated at 70°C for 30 minutes, cooled, and the cooled solution is purified with an ion exchange resin, concentrated, cooled, crystallized, and unreacted lactose is removed to obtain an aqueous lactulose solution with a solids content of about 68% (about 79% lactulose in the solids). This solution is passed through an ion exchange resin column, and the lactulose-containing fraction is collected and concentrated to obtain a purified aqueous lactulose solution with a solids content of about 68% (about 86% lactulose in the solids) (the method described in JP 3-169888 A). Furthermore, the lactulose aqueous solution (syrup) obtained by the above method is concentrated to a solids content of about 72%, and the concentrate is cooled to 15°C. Lactulose trihydrate crystals are added as seed crystals, and the mixture is gradually cooled to 5°C over 7 days with stirring to produce crystals. After 10 days, the solids content of the supernatant liquid has decreased to about 61%, and the crystals are separated from the liquid containing the crystals using a filter cloth centrifuge, washed with cold water at 5°C, and dried to obtain lactulose crystals with a purity of 95% or more (the method described in Japanese Patent Laid-Open No. 6-228179). Alternatively, commercially available lactulose can be used, such as "Milk Oligosaccharide MLS (registered trademark)-50" and "Milk Oligosaccharide MLC (registered trademark)-97" (both manufactured by Morinaga Milk Industry Co., Ltd.).

[0022] The amount of lactulose in the composition of the present invention may be appropriately determined depending on the embodiment of the composition and is not particularly limited, but is, for example, preferably 0.01% by mass or more, more preferably 0.1% by mass or more, of the total composition. The upper limit of the lactulose content is not particularly limited, but may be, for example, 100% by mass or less. Furthermore, when the composition of the present invention is in the form of a food or beverage, the amount of lactulose per 100 kcal of the composition of the present invention is preferably 100 mg or more, more preferably 1000 mg or more, and even more preferably 5000 mg or more. There is no particular upper limit, but the content per 100 kcal of the composition may be 10,000 mg or less, or even 8,000 mg or less. Note that, when lactulose is a hydrate, these values ​​are values ​​converted to anhydrous form. The same applies to the following description.

[0023] The composition of the present invention has the effect of improving work performance in humans to whom it is administered, and is therefore used to achieve such an effect. The compositions and agents of the present invention are intended to be used to improve work performance. In the present invention, "work performance" refers to work productivity, for example, the work productivity of workers such as office workers. Work performance can be evaluated using presenteeism as an index using the HPQ used in the test examples described below, and more preferably, relative presenteeism (assessment by comparison with others) is used as an index. When presenteeism improves significantly compared to the control, it can be determined that work performance has improved. Here, "presenteeism" refers to a state of reduced work performance. Improvement in presenteeism leads to improvement in work performance.

[0024] In the present invention, "improving work performance" means raising work performance from the current level and is used in a sense that includes improving work performance. Here, "improving work performance" includes recovering work performance that has once declined and preventing a decline in work performance.

[0025] The subject to which the composition of the present invention is administered (ingested) is not particularly limited as long as it is an animal, but is usually a mammal, preferably a human, and there is no particular limitation on the sex. Furthermore, the age of subjects to whom the composition of the present invention is administered (ingested) is preferably in their 40s, in terms of humans, as this is likely to produce an effect. Furthermore, the subjects to whom the composition of the present invention is administered (ingested) are usually working people, and people who work 4 to 5 days a week are preferred as they are more likely to obtain the effects. Furthermore, the composition of the present invention is preferably administered (ingested) to humans with low intestinal microbiota diversity, as this is likely to be effective. The diversity of intestinal microbiota refers to the varying levels of various bacteria contained in the intestinal microbiota. Low diversity may mean that the diversity is lower than the median value of the intestinal microbiota diversity in the general population, when using diversity indicators known in the art, such as Observed ASV, Chao1, Evenness, Shannon, and Faith pd. Furthermore, the composition of the present invention is preferably administered (ingested) to humans with a high proportion of Bifidobacterium bacteria in their intestinal flora, as this is likely to be effective. Here, "prevalence" can also be rephrased as "occupancy rate" of the entire bacterial group detected in the intestinal flora. A high proportion of Bifidobacterium bacteria in the intestinal flora may be higher than the median proportion of Bifidobacterium bacteria in the intestinal flora of the general population.

[0026] Another aspect of the present invention is the use of B. longum cells and lactulose in the manufacture of a composition for improving work performance. Another aspect of the present invention is the use of B. longum cells and lactulose in improving work performance. Another aspect of the present invention is a combination of B. longum cells and lactulose for use in improving work performance. Another aspect of the invention is a method for improving work performance comprising administering to a subject B. longum cells and lactulose.

[0027] Note that "administering B. longum fungal cells and lactulose to a subject" may be synonymous with "allowing a subject to ingest B. longum fungal cells and lactulose." The ingestion may be voluntary (ad libitum intake) or forced (forced intake). That is, the administration step may specifically be, for example, a step of incorporating B. longum fungal cells into food, drink, or feed and supplying the mixture to a subject, thereby allowing the subject to ad libitum ingest the B. longum fungal cells.

[0028] The administration (ingestion) timing and duration of the composition of the present invention are not particularly limited. Preferably, the composition is administered continuously for at least 3 days, at least 1 week, at least 2 weeks, or at least 1 month. Here, "continuously" means daily administration. It is desirable to start administration of the composition of the present invention, for example, before the expected date and time of improvement in work performance, and the start time can be 3 days, preferably 5 days, and more preferably 10 days before the expected date and time. It is also desirable to administer the composition of the present invention, for example, for as long a period as possible before the expected date and time of improvement in work performance, and the end time of administration can be determined from this perspective, and can be, for example, 3 days, 2 days, 1 day, or the same day as the expected date and time.

[0029] The composition of the present invention may be in the form of a food or drink, a medicine, or the like, or may be in the form of being contained in a food or drink, a medicine, or the like as an additive. The composition of the present invention may be administered orally or parenterally, but is usually administered orally. Parenteral administration includes transdermal, intravenous, rectal, and inhalation routes.

[0030] The amount of the composition of the present invention to be administered (ingested) is appropriately selected depending on the age (months), sex, condition, and other conditions of the subject to be administered (ingested). The dosage (ingestion) of the composition of the present invention is, for example, 1.0 × 10 as the dosage (ingestion) of Bifidobacterium longum subsp. longum according to the present invention. 6 ~5.0 x10 9 cfu / kg body weight / day is preferred, 5.0 × 10 6 ~5.0×10 9 cfu / kg body weight / day is more preferable, and 1.0 × 10 7 ~3.3×10 9 cfu / kg body weight / day is more preferred. Furthermore, the dosage (ingestion) of the composition of the present invention is preferably set to an amount in the range of, for example, 0.01 to 40.0 g / day, more preferably 0.05 to 20.0 g / day, and even more preferably 0.1 to 5.0 g / day, in terms of the dosage of lactulose. Regardless of the amount or period of administration (ingestion), the composition of the present invention can be administered (ingested) once a day or in divided doses multiple times a day.

[0031] When the composition of the present invention is intended to be orally administered, it is preferably in the form of a food or drink. There are no particular restrictions on the form or properties of the food and beverage products as long as they do not impair the effects of the present invention and can be administered orally.Except for containing B. longum cells and lactulose, they can be produced by conventional methods using ingredients normally used in food and beverage products.

[0032] Food and drink should be selected appropriately depending on the subject, but may be in any form, such as liquid, paste, gel-like solid, or powder, including tablet confectionery; liquid food (nutritional food for tube feeding); wheat flour products such as bread, macaroni, spaghetti, noodles, cake mix, fried chicken powder, and breadcrumbs; instant noodles, cup noodles, retort / prepared foods, canned foods, microwave foods, instant soup / stew, instant miso soup / cleaning liquid, canned soup, freeze-dried foods, and other instant foods. processed agricultural products such as canned agricultural products, canned fruit, jams and marmalades, pickles, boiled beans, dried agricultural products, and cereals (processed grain products); processed seafood products such as canned seafood, fish ham and sausage, fish paste products, seafood delicacies, and tsukudani (simmered fish dishes); processed livestock products such as canned livestock paste, livestock ham and sausage; processed milk, milk drinks, yogurt (fermented milk), lactic acid bacteria drinks, cheese, ice cream, cream, and other dairy products; fats and oils such as butter, margarines, and vegetable oils; Basic seasonings such as soy sauce, miso, sauces, processed tomato seasonings, mirin, vinegars, etc.; complex seasonings and foods such as cooking mixes, curry bases, sauces, dressings, noodle soups, spices, and other complex seasonings; frozen foods such as frozen ingredients, semi-cooked frozen foods, and cooked frozen foods; caramel, candy, chewing gum, chocolate, cookies, biscuits, cakes, pies, snacks, crackers, Japanese sweets, rice snacks, bean snacks, desserts, jellies, and other sweets. and other confectioneries; carbonated drinks, natural fruit juices, fruit juice drinks, soft drinks with fruit juice, fruit pulp drinks, fruit drinks with fruit pieces, vegetable drinks, soy milk, soy milk drinks, coffee drinks, tea drinks, powdered drinks, concentrated drinks, sports drinks, nutritional drinks, alcoholic drinks, and other beverages; other commercially available foods such as baby food, furikake, and ochazuke nori seaweed; nutritional compositions such as supplements and infant formula (including powdered milk, liquid milk, etc.); enteral nutritional foods; and functional foods (foods for specified health uses, foods with nutrient functions).

[0033] Among these, fermented milk is preferred. Examples of "fermented milk" include solid (standing) yogurt (e.g., plain yogurt, yogurt with added flavor, solid yogurt with added flavor), solid (stirred) yogurt (e.g., soft yogurt), liquid yogurt (e.g., drinkable yogurt), and frozen yogurt (e.g., frozen yogurt). The fermented milk may contain sweeteners such as sucrose, pectin, fruit juice, fruit preserve (fruit or fruit pulp cooked in sugar), agar, gelatin, oils and fats, flavorings, coloring agents, stabilizers, reducing agents, etc., as needed. The fermented milk may also be packed in a suitable container.

[0034] Fermented milk is produced by fermenting raw milk material using microorganisms. It is possible. The milk raw material is not particularly limited as long as it is a raw material derived from milk and can be fermented using a microorganism to produce fermented milk, and examples include milk or its fractions or processed products, such as cow's milk, skim milk, fresh cream, butter, whole milk powder, and skim milk powder, or mixtures, dissolutions, or suspensions of these in water. Before fermentation, the raw milk material may be subjected to sterilization, homogenization, cooling, etc. according to conventional methods.

[0035] The microorganisms used for fermentation are not particularly limited, but are preferably Bifidobacterium bacteria, and more preferably Bifidobacterium longum subsp. longum. When Bifidobacterium bacteria are used, the amount of Bifidobacterium bacteria to be inoculated into the milk raw material is not particularly limited, but is preferably 10 5 ~10 9 cfu, more preferably 10 7 ~10 8 cfu. Usually, the bacteria are viable at the time of inoculation.

[0036] When the composition of the present invention is in the form of a supplement, it can be formulated into solid preparations such as powders, granules, tablets, capsules, etc.; liquid preparations such as solutions, syrups, suspensions, emulsions, etc. When preparing such preparations, the components, carriers, and methods for formulating pharmaceuticals described below can be used in accordance with the description.

[0037] Furthermore, one aspect of the food and drink product may be feed, such as pet food, livestock feed, and fish feed. The form of the feed is not particularly limited, and may contain, in addition to B. longum fungal bodies and lactulose, for example, grains such as corn, wheat, barley, rye, and milo; vegetable oil cakes such as soybean oil cake, rapeseed oil cake, palm oil cake, and linseed oil cake; bran such as wheat bran, wheat bran, rice bran, and defatted rice bran; manufacturing residues such as corn gluten meal and corn jam meal; animal feeds such as fish meal, skim milk powder, whey, yellow grease, and tallow; yeasts such as torula yeast and brewer's yeast; mineral feeds such as calcium phosphate and calcium carbonate; oils and fats; simple amino acids; and sugars.

[0038] When the composition of the present invention is in the form of a food or drink (including feed), it can be provided and sold as a food or drink labeled for use in improving work performance. Furthermore, the B. longum cells and lactulose described herein can be used to produce such a food or drink.

[0039] Such "indication" acts include all acts for informing consumers of the aforementioned uses, and any expression that can recall or infer the aforementioned uses falls under the category of "indication" acts in this invention, regardless of the purpose of the indication, the content of the indication, the object or medium on which it is displayed, etc. Furthermore, it is preferable that the "labeling" be done in an expression that allows consumers to directly recognize the intended use. Specifically, this includes acts of transferring, delivering, displaying for the purpose of transferring or delivering, or importing food and beverage products or product packaging on which the intended use is stated, displaying or distributing advertisements, price lists, or transaction documents related to the products and including the intended use, or providing information containing the above-mentioned content by electromagnetic means (such as the Internet).

[0040] On the other hand, it is preferable that the content of the labeling be one approved by the government, etc. (for example, a labeling approved based on various systems established by the government and made in a manner based on such approval.) It is also preferable that such content of the labeling be affixed to promotional materials at the point of sale, such as packaging, containers, catalogs, pamphlets, POP displays, and other documents.

[0041] "Labeling" also includes labeling as health food, functional food, enteral nutrition food, special dietary food, health functional food, food for specified health uses, food with nutrient functions, food with functional claims, quasi-drugs, etc. Among these, labeling approved by the Consumer Affairs Agency, for example, labeling as a food for specified health uses, Examples of such labels include those approved under systems related to foods, functional foods, or functional food labeling, or similar systems. Specifically, examples include labeling as a food for specified health uses, labeling as a conditional food for specified health uses, labeling that claims to affect the structure or function of the body, labeling that claims to reduce disease risk, and labeling of functionality based on scientific evidence. More specifically, typical examples include labeling as a food for specified health uses (especially labeling of health uses) and similar labeling as defined in the Cabinet Office Ordinance on Permission for Labeling for Special Uses Provided for in the Health Promotion Act (Cabinet Office Ordinance No. 57 of August 31, 2009). Examples of such displays include "To motivate yourself at work," "For those who want to work efficiently," "To improve presenteeism," "For those who want to increase labor productivity," etc.

[0042] The composition of the present invention can also be in the form of a pharmaceutical product. The route of administration of pharmaceuticals may be either oral or parenteral, with oral being preferred. Parenteral administration (ingestion) includes transdermal, intravenous, rectal, and inhalation routes. The pharmaceutical form can be formulated into a desired dosage form depending on the administration method. For example, in the case of oral administration, it can be formulated into solid preparations such as powders, granules, tablets, and capsules; or liquid preparations such as solutions, syrups, suspensions, and emulsions. It can also be made into an enteric-coated preparation by enteric coating. In the case of parenteral administration, it can be formulated into suppositories, ointments, injections, and the like. In preparing the formulation, in addition to B. longum cells and lactulose, ingredients commonly used in formulations, such as excipients, pH adjusters, colorants, and flavoring agents, can be used. It is also possible to use other medicinal ingredients or ingredients that are known or will be discovered in the future to have an intestinal flora-improving effect. In addition, formulation can be carried out by a known method as appropriate depending on the dosage form. When formulating, carriers commonly used in formulations may be appropriately blended to form the formulation. Such carriers include excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, etc.

[0043] Examples of excipients include sugar derivatives such as lactose, sucrose, glucose, mannitol, and sorbitol; starch derivatives such as corn starch, potato starch, α-starch, dextrin, and carboxymethyl starch; cellulose derivatives such as crystalline cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose, and carboxymethyl cellulose calcium; gum arabic; dextran; pullulan; silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, and magnesium aluminometasilicate; phosphate derivatives such as calcium phosphate; carbonate derivatives such as calcium carbonate; and sulfate derivatives such as calcium sulfate.

[0044] Examples of binders include gelatin, polyvinylpyrrolidone, macrogol, and the like, in addition to the above-mentioned excipients.

[0045] Examples of disintegrants include the above-mentioned excipients, as well as chemically modified starch or cellulose derivatives such as croscarmellose sodium, carboxymethyl starch sodium, and cross-linked polyvinylpyrrolidone.

[0046] Examples of lubricants include talc; stearic acid; metal stearates such as calcium stearate and magnesium stearate; colloidal silica; waxes such as veegum and gaelt; boric acid; glycol; carboxylic acids such as fumaric acid and adipic acid; sodium carboxylates 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 silicic anhydride and silicic acid hydrate; and starch derivatives.

[0047] Examples of stabilizers include paraoxybenzoic 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.

[0048] Examples of flavoring agents include sweeteners, acidulants, and fragrances. In the case of a liquid preparation for oral administration, examples of the carrier to be used include solvents such as water.

[0049] The timing of administration of the pharmaceutical agent of the present invention is not particularly limited, and may be before meals, after meals, between meals, or before going to bed. [Example]

[0050] The present invention will be explained in more detail below using examples, but the present invention is not limited to these examples.

[0051] <Production Example> Production of fermented milk containing B. longum BB536 strain and lactulose Fermented milk was prepared using the ingredients listed in Table 1. Specifically, the ingredients other than pectin and dissolving water were mixed and dissolved using a mixer. The mixture was then homogenized using a homogenizer, heat-sterilized, and cooled to the fermentation temperature. A commercially available lactic acid bacteria starter, Bifidobacterium longum subsp. longum BB536 strain (NITE BP-02621), was added to the mixture and fermented. After cooling and homogenization, a sterilized pectin aqueous solution was added to obtain a drinkable fermented milk. The fermented milk was stored at 10°C or below until administration. The amount of Bifidobacterium longum subsp. longum BB536 strain (NITE BP-02621) contained in the fermented milk was measured by a conventional method, and the number was 2 × 10 9 It was confirmed that the strain contained more than 100 cfu / 100 g of lactulose.

[0052] [Table 1]

[0053] <Test Example> Examination of the effect of fermented milk administration on work performance (1) Test method A single-group open-label study was conducted with 201 subjects aged between 18 and 74 years old. After registration, there was a two-week observation period and a four-week administration (ingestion) period. During the study period, subjects were instructed not to make any major changes to their lifestyle. This study was conducted by the Suda Healthcare Center of Hakusuikai Medical Corporation. The study was conducted after being reviewed and approved by the Clinic Institutional Review Board. The test food was Bifidobacterium longum subsp. longum B. B536 strain (NITE BP-02621) at 2 × 10 9 Contains 4g of lactulose The subjects were instructed to take 100 g of the fermented milk obtained in the above-mentioned Production Example once a day after a meal during the administration period. They were then asked to answer questionnaires before and after the administration period.

[0054] (2) Evaluation method The results of the questionnaire before and at the end of the administration period were compiled to evaluate work performance. Note that the following questionnaire on work performance status is an index to evaluate the status for a certain period before the time of answering the questionnaire, so the results of the questionnaire before the administration period The questionnaire results at the end of the administration period evaluate the condition during the administration period. In addition, feces were collected before and after the administration period to determine the state of the intestinal flora for use in stratified analysis.

[0055] Work performance was assessed using the World Health Organization Health and Work Performance Questionnaire (https: / / www.hcp.med.harvard.edu / hpq / info.php, hereinafter referred to as "HPQ"). The HPQ is a questionnaire developed by the World Health Organization to subjectively evaluate worker performance, and is composed of two indicators: absenteeism and presenteeism. Absenteeism refers to absence from work, i.e., not being at work. Presenteeism refers to a state of reduced ability due to poor health, i.e., a state in which a person is unable to perform adequately due to physical or mental health problems despite being at work (see HPQ above).

[0056] Based on the subjects' responses, the following was assessed for four items: absolute absenteeism, relative absenteeism, absolute presenteeism, and relative presenteeism. The mean ± standard deviation was calculated using the formula. <Absenteeism: Absence from work> Absolute absenteeism: (regular working hours - actual working hours) Relative absenteeism: (regular working hours - actual working hours) / regular working hours Presenteeism: A state of reduced ability due to poor health Absolute presenteeism: Own performance evaluation Relative presenteeism: Own performance rating / average performance of others Performance evaluation A significant difference test was performed using a paired t-test between the values ​​before and at the end of the administration period. A p-value of 0.05 or less was considered to indicate a significant difference.

[0057] When analyzing the results, in order to investigate which subjects would be most affected by the test food in improving their work performance, the subjects were stratified by age, number of days worked, and state of intestinal flora, and a paired t-test was used to test for significance between the values ​​before and at the end of the administration period. The status of the intestinal flora was measured and analyzed using fecal samples by standard methods and stratified. Regarding the diversity of the intestinal flora, the intestinal flora before the administration period was classified into groups using the Shannon index, and the total number of subjects was 100. The median value of the subjects was used as the standard for determining whether the alpha diversity was high or low. The proportion (occupancy) of Bifidobacterium bacteria in the intestinal flora was determined based on the median value of all subjects.

[0058] (3) Results One subject was excluded because the administration rate of the test food during the administration period was unknown, leaving 200 subjects for analysis. The results for work performance in all subjects are shown in Table 2. Regarding the relative presenteeism score on the HPQ, a significant improvement was observed during the administration period compared to before the administration period (p<0.05), indicating an improvement in work performance, such as an improvement in the condition in which patients were unable to perform adequately due to physical or mental health issues despite attending work.

[0059] [Table 2]

[0060] Furthermore, the results of the stratified analysis of relative presenteeism are shown in Table 3. Regarding relative presenteeism on the HPQ, it was shown that the test food had a significant effect on improving work performance in people in their 40s, who worked 4-5 days per week, had low alpha diversity in their intestinal flora, or had a high proportion of bifidobacteria before and after administration.

[0061] [Table 3]

[0062] From the above results, it was found that Bifidobacterium longum subsp. longum was 2 × 10 9 Administration of fermented milk containing 4g of Bifidobacterium longum subsp. longum and lactulose improved relative presenteeism and work performance. This indicates that administration of a combination of Bifidobacterium longum subsp. longum and lactulose is effective in improving work performance.

Claims

1. A composition for improving work performance, comprising lactulose and one or more substances selected from the group consisting of Bifidobacterium longum subsp. longum cells, cultures of the bacteria, and processed products of the bacteria.

2. The composition according to claim 1, wherein the Bifidobacterium longum subsp. longum is Bifidobacterium longum subsp. longum strain BB536 (NITE BP-02621).

3. 10. The composition of claim 1, wherein the improved work performance is due to an improvement in relative presenteeism.

4. Bifidobacterium longum subsp. longum, 2 x 10 ９ The composition of claim 1 containing at least cfu / 100g.

5. The composition of claim 1 , wherein the composition is administered to a person in their 40s.

6. The composition of claim 1, which is administered to a human who works 4 to 5 days per week.

7. The composition of claim 1 , administered to a human with a low diversity of intestinal flora.

8. The composition according to claim 1, which is administered to a human having a high proportion of Bifidobacterium bacteria in the intestinal flora.

9. The dosage of Bifidobacterium longum subsp. longum was 3 x 10 ７ 10. The composition of claim 1, wherein the composition is administered at or above cfu / kg body weight / day.

10. The composition according to any one of claims 1 to 9, which is a food or drink.

11. The composition of claim 10 which is fermented milk.

12. The composition according to any one of claims 1 to 9, which is a pharmaceutical product.

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