composition

Abstract

To provide a technique for promoting assimilation of oligosaccharide such as HMO by enteric bacterium.SOLUTION: Provided is a composition in which a tocopherol is used as an active ingredient of the composition for promoting assimilation of oligosaccharide. The tocopherol includes one or more selected from the group consisting of β-tocopherol, γ-tocopherol and δ-tocopherol. The oligosaccharide to be assimilated is preferably human milk oligosaccharide. In the assimilation-promoting composition, the mass ratio (δ / β) of the content of δ-tocopherol to the content of β-tocopherol is preferably 5 or more, and the mass ratio (γ / δ) of the content of γ-tocopherol to the content of δ-tocopherol is preferably 8.8 or less.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a new use of tocopherol, specifically to a use for promoting the assimilation of oligosaccharides.

Background Art

[0002] In recent years, various studies have been conducted on human milk oligosaccharides (hereinafter also referred to as HMO), which is a general term for various oligosaccharides contained in human colostrum. Human milk oligosaccharides are calculated to be contained at 22 - 24 g / L in colostrum and 12 - 13 g / L in mature milk, and are the third solid component after lactose and lipids in breast milk. Human milk oligosaccharides are known to have functions such as infection defense and immune regulation. Also, it is considered that human milk oligosaccharides contribute to the health of the host by being assimilated by various bacteria in the intestine (Non-Patent Document 1). Regarding oligosaccharides other than HMO, their use as prebiotics that are assimilated by intestinal bacteria and promote their growth has been actively studied. Improving the ease of assimilation of oligosaccharides in the intestine is important for enhancing the health of humans including infants.

[0003] In addition, tocopherol has been attracting attention as a component to be formulated in nutritional compositions for infants. Patent Document 1 discloses a composition containing 2'-fucosyllactose, which is one of HMO, and α-tocopherol, and it is described that such a composition has an effect of improving at least one of cognition, learning, and memory. Regarding other isoforms of tocopherol other than α-tocopherol, the research is still in progress and there is not enough knowledge.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Non-Patent Documents

[0005] [Non-Patent Document 1] LW Chia et al., Microorganisms, 2020,8 (10), 1513 Summary of the Invention [Problem to be solved by the invention]

[0006] An objective of the present invention is to provide a technique for promoting the assimilation of oligosaccharides such as HMOs by intestinal bacteria. [Means for solving the problem]

[0007] As a result of intensive research conducted by the inventors to solve the above-mentioned problems, they discovered that one or more members selected from the group consisting of β-tocopherol, γ-tocopherol and δ-tocopherol promote the assimilation of oligosaccharides such as human milk oligosaccharides by intestinal bacteria, and thus completed the present invention.

[0008] That is, the present invention is a composition for promoting the assimilation of oligosaccharides, containing tocopherol, wherein the tocopherol comprises one or more selected from the group consisting of β-tocopherol, γ-tocopherol and δ-tocopherol. In the composition of the present invention, the ratio of δ-tocopherol to the content of β-tocopherol is The mass ratio of the contents (δ / β) is preferably 5 or more, and more preferably 10 or more. In the composition of the present invention, the mass ratio (γ / δ) of the content of γ-tocopherol to the content of δ-tocopherol is preferably 8.8 or less, and more preferably 3.9 or less. A more preferred use of the composition of the present invention is to promote the assimilation of oligosaccharides having 3 to 5 sugar residues. Another more preferred use of the composition of the present invention is to promote the assimilation of human milk oligosaccharides. In such a use, the human milk oligosaccharides whose assimilation is promoted preferably include one or more selected from the group consisting of lacto-N-neotetraose (also denoted as LNnT), 2'-fucosyllactose (also denoted as 2'-FL), 3'-sialyllactose (also denoted as 3'-SL), 6'-sialyllactose (also denoted as 6'-SL), difucosyllactose (DFL), and 3-fucosyllactose (3-FL). The composition of the present invention may further contain human milk oligosaccharides. In such an embodiment, it is preferably used for promoting the assimilation of human milk oligosaccharides containing lacto-N-tetraose (also denoted as LNT) and including 2'-fucosyllactose. The composition of the present invention is preferably a nutritional composition, and more preferably a prepared milk. The composition of the present invention may be used in a mode of being added to a composition containing human milk oligosaccharides. In such an embodiment, the composition containing the human milk oligosaccharides is preferably breast milk. Also, as another embodiment of the present invention, there is provided a nutritional composition containing oligosaccharides and tocopherol, wherein the oligosaccharides include lacto-N-tetraose and 2'-fucosyllactose, and the tocopherol includes one or more selected from the group consisting of β-tocopherol, γ-tocopherol, and δ-tocopherol (excluding breast milk). Also, as another embodiment of the present invention, there is provided a nutritional composition containing oligosaccharides and tocopherol, wherein the oligosaccharides include fructooligosaccharides and 6'-sialyllactose, and the tocopherol includes one or more selected from the group consisting of β-tocopherol, γ-tocopherol, and δ-tocopherol (excluding breast milk).

Advantages of the Invention

[0009] According to the present invention, there is provided a composition capable of promoting the assimilation of oligosaccharides such as HMO by intestinal bacteria. Such a composition can be in the form of an oral composition such as a food or drink product or a pharmaceutical product, or can be contained in a food or drink product or a pharmaceutical product in the form of an additive or the like. By ingesting the composition of the present invention, an effect of improving the intestinal flora can be obtained, and it is expected to be useful for maintaining the health of the consumer, particularly infants.

Mode for Carrying Out the Invention

[0010] Next, the present invention will be described in detail. However, the present invention is not limited to the following embodiments and can be freely changed within the scope of the present invention.

[0011] The composition of the present invention contains tocopherol as an active ingredient. The tocopherol includes one or more selected from the group consisting of β-tocopherol, γ-tocopherol, and δ-tocopherol. Preferably, it includes all three of β-tocopherol, γ-tocopherol, and δ-tocopherol. Further, the composition of the present invention may further contain α-tocopherol.

[0012] In the composition of the present invention, the mass ratio (δ / β) of the content of δ-tocopherol to the content of β-tocopherol is preferably 5 or more, more preferably 10 or more. Also, the upper limit of δ / β is not particularly limited, but is usually 200. By setting δ / β within the above range, the effect of promoting the assimilation of oligosaccharides by intestinal bacteria can be more easily obtained.

[0013] In the composition of the present invention, the mass ratio (γ / δ) of the content of γ-tocopherol to the content of δ-tocopherol is preferably 8.8 or less, more preferably 3.9 or less. Also, the lower limit of γ / δ is not particularly limited, but is usually 0.1. By setting γ / δ within the above range, the effect of promoting the assimilation of oligosaccharides by intestinal bacteria can be more easily obtained.

[0014] In the composition of the present invention, the total content of β-tocopherol, γ-tocopherol, and δ-tocopherol with respect to the entire composition (per solid content) is not particularly limited. In the composition of the present invention, the total amount of β-tocopherol, γ-tocopherol, and δ-tocopherol is preferably 0.001 to 0.2, more preferably 0.004 to 0.2, and even more preferably 0.01 to 0.2 in terms of mass ratio with respect to the amount of the oligosaccharide whose assimilation is to be promoted. The total content is adjusted or applied accordingly.

[0015] In the composition of the present invention, β-tocopherol, γ-tocopherol, and / or δ-tocopherol act as active ingredients, and can promote the direct or indirect assimilation of the oligosaccharide by intestinal bacteria. Normally, intestinal bacteria that have assimilated oligosaccharides produce various useful substances. Since the composition of the present invention promotes such production, it can contribute to enhancing the health of the host of the intestinal bacteria. In general, intestinal bacteria assimilate oligosaccharides and grow. When the assimilation of oligosaccharides is promoted, as a result, the intestinal bacteria whose growth is promoted by oligosaccharides become dominant in the intestine. Therefore, the composition of the present invention can also assist and enhance the effect of oligosaccharides as prebiotics.

[0016] The fact that the oligosaccharide has been assimilated can be confirmed, for example, by the decrease in the amount of the oligosaccharide over time when culturing intestinal bacteria in the presence of the oligosaccharide. More specifically, it can be confirmed by the small residual rate of the amount of the oligosaccharide in the culture system after any lapse of time with respect to the amount of the oligosaccharide in the culture system at a predetermined time point (such as at the start of culturing, etc.). In this specification, "promotion of assimilation" means that when the composition of the present invention is applied, the degree of assimilation of oligosaccharides is greater than when it is not applied. In other words, it means that the residual rate of oligosaccharides after a predetermined period of time is small. The degree of decrease in such a residual rate is not particularly limited, but it is preferably 0.9 times or less, more preferably 0.8 times or less, and even more preferably 0.7 times or less of the residual rate when the composition of the present invention is not applied. Alternatively, the residual rate 7 hours, 10 hours, or 24 hours after the start of culture with respect to the start of culture may preferably be 70% by mass or less, more preferably 50% by mass or less, and even more preferably 20% by mass or less. Also, "promotion of assimilation" may mean that the rate of decrease in the amount of oligosaccharides assimilated and decreased is increased when the composition of the present invention is applied compared to when it is not applied. The degree of increase in such a rate is not particularly limited, but it is preferably 10% or more, more preferably 20% or more, and even more preferably 50% or more greater than the rate of decrease when the composition of the present invention is not applied. The increase in the rate of decrease can be confirmed, for example, by the fact that the time required for the residual rate to reach an arbitrary value with respect to the start of culture is shorter when the composition of the present invention is applied compared to when it is not applied. Alternatively, when the culture time required for the residual rate to be 20% by mass or less with respect to the start of culture is preferably 24 hours or less, more preferably 18 hours or less, and preferably 12 hours or less, it may be considered that assimilation is promoted.

[0017] Also, the fact that oligosaccharides have been assimilated can also be confirmed by the promotion of the growth of intestinal bacteria when the intestinal bacteria are cultured in the presence of oligosaccharides. Here, the "growth" of intestinal bacteria includes an increase in the absolute number of bacteria, and the "promotion of growth" means that the degree of such increase is greater when the composition of the present invention is applied than when it is not applied. That is, it means that the number of intestinal bacteria when the composition of the present invention is applied increases compared to when it is not applied. The degree of increase in such bacterial count is not particularly limited, but is preferably 1.1 times or more, more preferably 1.5 times or more, and even more preferably 3 times or more the bacterial count compared to the number of intestinal bacteria when the composition of the present invention is not applied. Such an increase in bacterial count can be confirmed not only by directly measuring the bacterial count, but also, for example, by measuring the turbidity (absorbance) of the digestive tract contents of animals such as humans who have ingested a medium or composition in which intestinal bacteria have been cultured or the amount of short-chain fatty acids such as acetic acid and finding that the value increases, or by measuring the pH in the medium and finding that the value decreases.

[0018] Also, the "promotion of growth" may be an increase in the rate at which the absolute number of intestinal bacteria increases. The degree of increase in such rate is not particularly limited, but is preferably 10% or more, more preferably 20% or more, and even more preferably 50% or more greater than the growth rate of intestinal bacteria when the composition of the present invention is not applied. An increase in the growth rate can be confirmed, for example, by the fact that the time required to reach an arbitrary bacterial count is shorter when the composition of the present invention is applied than when it is not applied.

[0019] The oligosaccharides whose assimilation is promoted in the present invention are those that can be assimilated by intestinal bacteria. Such intestinal bacteria include bacteria of the genus Bifidobacterium, Enterococcus bacteria of the genus Enterococcus, bacteria of the genus Streptococcus, Esch eria bacteria of the genus Escherichia, bacteria of the genus Staphylococcus, Tur icibacter bacteria of the genus Turicibacter, bacteria of the genus Clostridium, Lumin Bacteria belonging to the genus Ruminococcus, bacteria belonging to the genus Veillonella, Bacteroides (Bacteria belonging to the genus Bacteroides, bacteria belonging to the genus Parabacteroides, bacteria belonging to the genus Lacticaseibacillus, bacteria belonging to the genus Lactiplantibacillus, bacteria belonging to the genus Limosilactobacillus, bacteria belonging to the genus Levilactobacillus, bacteria belonging to the genus Ligilactobacillus, bacteria belonging to the genus Latilactobacillus, bacteria belonging to the genus Blautia, etc. can be mentioned.)

[0020] The oligosaccharides whose assimilation is promoted in the present invention are not particularly limited. Here, the oligosaccharide refers to an oligosaccharide of saccharides in which two or more sugars are linked by a glycosidic bond. As the oligosaccharide in the present invention, the number of sugar residues linked to each other by a glycosidic bond is 2 or more, preferably 2 or more and 10 or less, and particularly preferably 3 or more and 5 or less.) Specific examples of the oligosaccharide include raffinose, lactulose, maltotriose, stachyose, galactooligosaccharide, fructooligosaccharide, kestose, nystose, soy oligosaccharide, lactulose oligosaccharide, xylooligosaccharide, isomaltooligosaccharide, coffee bean manno-oligosaccharide, gluconic acid, polydextrose, inulin, etc.) Among these, as oligosaccharides having 3 or more and 5 or less sugar groups, maltotriose, stachyose, galactooligosaccharide, fructooligosaccharide, kestose, nystose, and human milk oligosaccharide are preferably mentioned.)

[0021] Human milk oligosaccharide is particularly preferably mentioned as the oligosaccharide whose assimilation is promoted in the present invention.) The human milk oligosaccharide is not particularly limited as long as it is an oligosaccharide usually contained in human milk, and examples include fucosylated oligosaccharide, sialylated oligosaccharide, acetylated oligosaccharide, galactosyllactose, etc.) Examples of fucosylated oligosaccharides include 2'-fucosyllactose, lacto-N-fucopentaose-I, lacto-N-fucopentaose-II, lacto-N-fucopentaose-III, and the like. Examples of sialylated oligosaccharides include 3'-sialyllactose, 6'-sialyllactose, difucosyllactose, 3-fucosyllactose, lactodifucotetraose, difucosyllacto-N-tetraose, sialyllacto-N-tetraose a, sialyllacto-N-tetraose b, sialyllacto-N-tetraose c, disialyllacto-N-tetraose, and the like. Examples of acetylated oligosaccharides include lacto-N-neotetraose, lacto-N-hexaose, and the like. Examples of galactosyllactose include 3'-galactosyllactose, 4'-galactosyllactose, 6'-galactosyllactose, and the like. Among these, from the viewpoint of the effect of promoting assimilation, one or more selected from lacto-N-neotetraose, 2'-fucosyllactose, 3'-sialyllactose, 6'-sialyllactose, difucosyllactose, and 3-fucosyllactose are particularly preferred.

[0022] The composition of the present invention may further contain human milk oligosaccharides. Examples of human milk oligosaccharides include the above-mentioned fucosylated oligosaccharides, sialylated oligosaccharides, acetylated oligosaccharides, and the like. From the viewpoint of the effect of promoting assimilation, one or more selected from lacto-N-neotetraose, lacto-N-tetraose, 2'-fucosyllactose, 3'-sialyllactose, 6'-sialyllactose, difucosyllactose, and 3-fucosyllactose are more preferred. In particular, the composition of the present invention preferably contains lacto-N-tetraose together with a predetermined tocopherol. In such a case, since the assimilation of 2'-fucosyllactose can be further promoted, it is particularly preferably applicable to the use of promoting the assimilation of human milk oligosaccharides containing 2'-fucosyllactose. That is, as one of the particularly preferred embodiments of the present invention, there is provided a composition for promoting the assimilation of human milk oligosaccharides, which contains tocopherol and lacto-N-tetraose, wherein the tocopherol contains one or more selected from the group consisting of β-tocopherol, γ-tocopherol and δ-tocopherol, and the human milk oligosaccharides contain 2'-fucosyllactose. Further, as another aspect of a particularly preferred embodiment of the present invention, there is provided a nutritional composition containing an oligosaccharide and a tocopherol, wherein the oligosaccharide contains lacto-N-tetraose and 2'-fucosyllactose, and the tocopherol contains one or more selected from the group consisting of β-tocopherol, γ-tocopherol and δ-tocopherol (however, excluding breast milk itself). The human milk oligosaccharides contained in the composition of the present invention may be purified or a mixture as long as the effects of the present invention are not impaired.

[0023] The composition of the present invention may further contain oligosaccharides other than human milk oligosaccharides. Examples of such oligosaccharides include those described above, and it is particularly preferable to contain fructooligosaccharide together with a predetermined tocopherol. In such a case, since the assimilation of 6'-sialyllactose can be further promoted, it can be particularly preferably applied to the use of promoting the assimilation of human milk oligosaccharides containing 6'-sialyllactose. That is, as one of the particularly preferred embodiments of the present invention, there is provided a composition for promoting the assimilation of human milk oligosaccharides, which contains tocopherol and fructooligosaccharide, wherein the tocopherol contains one or more selected from the group consisting of β-tocopherol, γ-tocopherol and δ-tocopherol, and the human milk oligosaccharide contains 6'-sialyllactose. Further, as another aspect of a particularly preferred embodiment of the present invention, there is provided a nutritional composition containing an oligosaccharide and tocopherol, wherein the oligosaccharide contains fructooligosaccharide and 6'-sialyllactose, and the toc A nutritional composition (excluding breast milk itself) is disclosed, wherein the tocopherol contains one or more selected from the group consisting of β-tocopherol, γ-tocopherol and δ-tocopherol.

[0024] When the composition of the present invention contains an oligosaccharide (including human milk oligosaccharide), its total content is preferably 0.05 to 10% by mass, more preferably 0.1 to 10, and still more preferably 0.2 to 10, based on the whole composition (per solid content). Also, when the composition of the present invention contains an oligosaccharide (including human milk oligosaccharide), the mass ratio of the total content of β-tocopherol, γ-tocopherol and δ-tocopherol to the content of the oligosaccharide is preferably 0.001 to 0.2, more preferably 0.004 to 0.2, and still more preferably 0.01 to 0.2.

[0025] The present invention can be rephrased as the use of one or more tocopherols selected from the group consisting of β-tocopherol, γ-tocopherol and δ-tocopherol in the production of a composition for promoting the assimilation of oligosaccharides. The present invention can also be paraphrased as the use of one or more tocopherols selected from the group consisting of β-tocopherol, γ-tocopherol, and δ-tocopherol in promoting the assimilation of oligosaccharides. The present invention can also be paraphrased as one or more tocopherols selected from the group consisting of β-tocopherol, γ-tocopherol, and δ-tocopherol, which are used to promote the assimilation of oligosaccharides.

[0026] The present invention can also be paraphrased as a method for promoting the assimilation of oligosaccharides, which includes administering one or more tocopherols selected from the group consisting of β-tocopherol, γ-tocopherol, and δ-tocopherol to a subject. In such a method, it is preferable to administer oligosaccharides to the subject simultaneously with or before or after the administration of tocopherols. Here, the subject is not particularly limited as long as it is an animal, but is usually a human. Note that "administering to a subject" may be synonymous with "causing a subject to ingest". The ingestion may be voluntary (free ingestion) or forced (forced ingestion). That is, specifically, the administration step may be, for example, a step of formulating one or more tocopherols selected from the group consisting of β-tocopherol, γ-tocopherol, and δ-tocopherol in food or drink or feed and supplying it to the subject, so that the subject freely ingests the food or drink or feed.

[0027] The ingestion (administration) timing of the composition of the present invention is not particularly limited and can be appropriately selected according to the state of the administration subject.

[0028] The ingestion (administration) amount of the composition of the present invention is appropriately selected according to the age, sex, state, and other conditions of the ingestion (administration) subject. Note that regardless of the amount and period of ingestion (administration), the drug can be administered once a day or divided into multiple times.

[0029] The composition of the present invention may be in the form of food and drink products, pharmaceuticals, etc. by itself, or may be in the form of being contained in food and drink products, pharmaceuticals, etc. as an additive. The intake (administration) route of the composition of the present invention may be either oral or parenteral, but is usually oral. Also, examples of parenteral intake (administration) include rectal administration.

[0030] The composition of the present invention is preferably in the form of a food and drink product. As for food and drink products, as long as they do not impair the effects of the present invention, the form and properties are not particularly limited, and they can be produced by ordinary methods using raw materials usually used in food and drink products.

[0031] Note that the form of so-called additives used by adding to food and drink products and pharmaceuticals is also included in the composition of the present invention. Examples of such forms include additives added to compositions containing oligosaccharides such as human milk oligosaccharides. Preferred examples of compositions containing human milk oligosaccharides include freshly expressed breast milk, formula milk, etc., and it is assumed that the milk after adding the composition of the present invention is ingested by newborns and infants. Here, "adding" may mean "mixing". Also, it may include either adding the composition of the present invention to food and drink products and pharmaceuticals, or adding food and drink products and pharmaceuticals to the composition of the present invention.

[0032] Food and drink products are usually ingested orally, but are not limited thereto. For example, those ingested nasally, or those ingested through a gastrostomy or enterostomy may also be acceptable. For example, it is assumed that for newborns and infants, formula milk which is the composition of the present invention described later, or breast milk added with the composition of the present invention, is ingested through a nasogastric feeding tube or the like.

[0033] Food and drink products include, regardless of their form such as liquid, paste, gel-like solid, powder, etc., for example, confectionery; wheat flour products such as bread, macaroni, spaghetti, noodles, cake mix, tempura flour, breadcrumbs, etc.; instant foods such as instant noodles, cup noodles, retort foods, canned cooked foods, microwave foods, instant soups and stews, instant miso soup and drinks, canned soups, freeze-dried foods, and other instant foods; agricultural processed products such as canned agricultural products, canned fruits, jams and marmalades, pickles, boiled beans, dried agricultural products, cereals (grain processed products), etc.; fishery processed products such as canned fishery products, fish ham and sausage, fish paste products, seafood delicacies, tsukudani, etc.; livestock processed products such as canned livestock products and pastes, livestock meat ham and sausage, etc.; milk and dairy products such as processed milk, milk beverages, yogurts, lactic acid bacteria beverages, cheese, ice creams, cream, and other dairy products; fats and oils such as butter, margarines, vegetable oils, etc.; basic seasonings such as soy sauce, miso, sauces, processed tomato seasonings, mirin, vinegars, etc.; compound seasonings and foods such as cooking mixes, curry bases, sauces, dressings, noodle soups, spices, and other compound seasonings; frozen foods such as raw material frozen foods, semi-cooked frozen foods, cooked frozen foods, etc.; confectionery such as caramel, candy, chewing gum, chocolate, cookies, biscuits, cakes, pies, snacks, crackers, Japanese confectionery, rice confectionery, bean confectionery, dessert confectionery, jelly, and other confectionery; preferred beverages such as carbonated beverages, natural fruit juices, fruit juice beverages, fruit-flavored soft drinks, pulp beverages, fruit drinks with fruit pieces, vegetable-based beverages, soy milk, soy milk beverages, coffee beverages, tea beverages, powdered beverages, concentrated beverages, sports beverages, nutritional beverages, alcoholic beverages, and other preferred beverages; other commercially available foods such as baby food, furikake, nori for ochazuke, etc.; nutritional compositions such as prepared milk (including powdered milk, liquid milk, etc.), liquid foods, supplements, etc.; functional foods (foods for specified health use, foods with nutritional function), etc.

[0034] Among these, nutritional compositions are preferably mentioned. In the present invention, the "nutritional composition" is not particularly limited as one aspect of food and drink products, but is preferably prepared milk, liquid food, supplement, etc., and more preferably prepared milk. The intake targets include infants, toddlers, children, and adults, but are preferably infants and toddlers. Prepared milk includes prepared powdered milk and prepared liquid milk. In the ordinance of the Ministry of Health, Labour and Welfare regarding the ingredient standards of milk and dairy products (Ordinance on Milk etc.), prepared powdered milk is defined as "raw milk, cow milk, special cow milk, or foods manufactured using these as raw materials, processed, or with these as the main raw material and nutrients necessary for infants added and made into a powder form." In the said ordinance, prepared liquid milk is defined as "raw milk, cow milk, special cow milk, or foods manufactured using these as raw materials, processed, or with these as the main raw material and nutrients necessary for infants added and made into a liquid form." Also, prepared milk is a product in which various nutritional components such as proteins, fats and oils, carbohydrates, minerals, vitamins, etc. are blended, and includes those processed into a powder or liquid form. Furthermore, prepared milk further includes "prepared powdered milk for infants", "prepared liquid milk for infants", and "powdered milk for pregnant and lactating women" among the foods for special purposes defined by the Health Promotion Act, and also includes forms such as prepared powdered milk for infants, nutritional powder for adults, nutritional powder for the elderly, etc.

[0035] 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. In such formulation, it can follow the explanations of the components, carriers, and methods related to the formulation of pharmaceuticals described later.

[0036] Also, it can be used as a feed as an aspect of food and drink. Examples of feeds include pet food, livestock feed, fish feed, etc. The form of the feed is not particularly limited. For example, it may contain grains such as corn, wheat, barley, rye, and millet; vegetable oil cakes such as soybean oil cake, rapeseed oil cake, coconut oil cake, and linseed oil cake; bran such as bran, wheat bran, rice bran, and defatted rice bran; production by-products such as corn gluten meal and corn germ meal; animal feeds such as fish meal, skimmed milk powder, whey, yellow grease, and tallow; yeasts such as torula yeast and brewer's yeast; mineral feeds such as tricalcium phosphate and calcium carbonate; oils and fats; single amino acids; sugars, etc.

[0037] When the composition of the present invention is in the form of food or drink (including feed), it can be provided and sold as a food or drink product labeled with the use of promoting the assimilation of oligosaccharides by intestinal bacteria.

[0038] Such "labeling" acts include all acts for informing consumers of the above use. As long as it is an expression that can evoke or analogize the above use, regardless of the purpose of labeling, the content of labeling, the object / media to be labeled, etc., it all falls within the "labeling" acts of the present invention. Also, the "labeling" is preferably carried out by an expression that allows consumers to directly recognize the above use. Specifically, it includes the acts of transferring, delivering, displaying for transfer or delivery, importing a product related to food or drink or its packaging labeled with the above use, advertising related to the product, displaying, distributing, or publishing a price list or transaction document labeled with the above use, or providing information containing these by electromagnetic (such as the Internet) means with the above use described therein.

[0039] On the other hand, the content of the label is preferably a label approved by the administration or the like (for example, a label approved based on various systems determined by the administration and carried out in a manner based on such approval). Also, it is preferable to attach such label content to packaging, containers, catalogs, pamphlets, promotional materials at the point of sale such as POP, and other documents.

[0040] In addition, "display" also includes displays as health foods, functional foods, enteral nutritional foods, special-purpose foods, health-functional foods, foods with specified health claims, nutrient-functional foods, foods with functional claims, quasi-drugs, etc. Among these, in particular, displays approved by the Consumer Affairs Agency, such as displays approved under systems related to foods with specified health claims, nutrient-functional foods, or foods with functional claims, or displays approved under systems similar thereto, can be mentioned. Specifically, displays as foods with specified health claims, displays as conditional foods with specified health claims, displays indicating an impact on the structure and function of the body, disease risk reduction displays, functional displays based on scientific evidence, etc. can be mentioned. More specifically, displays as foods with specified health claims (particularly displays of health uses) and displays similar thereto as defined in the Cabinet Office Ordinance (Cabinet Office Ordinance No. 57 of August 31, 2009) regarding permission for special-purpose displays specified in the Health Promotion Act are typical examples. Examples of such displays include displays such as "for efficient use of prebiotics", "to assist the function of oligosaccharides useful for the health of babies", "for the health of the stomach of infants", etc.

[0041] When the composition of the present invention is in the form of a pharmaceutical, the administration route may be either oral or parenteral, but oral administration is preferred. In addition, examples of parenteral intake (administration) include rectal administration, etc. As the form of the pharmaceutical, it can be formulated into a desired dosage form as appropriate according to the administration method. For example, in the case of oral administration, it can be formulated into solid preparations such as powders, granules, tablets, capsules, etc.; liquid preparations such as solutions, syrups, suspensions, emulsions, etc. In addition, in the case of parenteral administration, it can be formulated into suppositories, ointments, injections, etc. When formulating, components such as excipients, pH adjusters, coloring agents, flavoring agents, etc. that are usually used in formulation can be used. In addition, it is also possible to use in combination other medicinal components and known or future-discovered prebiotics, etc. Preferred examples of known prebiotics include inulin, gluconic acid, polydextrose, etc., which are to be contained in the composition of the present invention. In addition, the formulation can be carried out by a method known per se according to the dosage form. When formulating, a formulation carrier may be appropriately blended for formulation.

[0042] 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, hydroxypropyl methylcellulose, carboxymethyl cellulose, and carboxymethyl cellulose calcium; gum arabic; dextran; pullulan; silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, and magnesium metasilicate aluminate; phosphate derivatives such as calcium phosphate; carbonate derivatives such as calcium carbonate; sulfate derivatives such as calcium sulfate, and the like.

[0043] Examples of binders include, for example, in addition to the above excipients, gelatin; polyvinylpyrrolidone; macrogol, and the like.

[0044] Examples of disintegrants include, for example, in addition to the above excipients, chemically modified starches or cellulose derivatives such as croscarmellose sodium, carboxymethyl starch sodium, and crosslinked polyvinylpyrrolidone.

[0045] Examples of lubricants include, for example, talc; stearic acid; metal stearates such as calcium stearate and magnesium stearate; colloidal silica; waxes such as beeswax and carnauba wax; 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 anhydrous silicic acid and hydrated silicic acid; starch derivatives, and the like.

[0046] Examples of stabilizers include, for example, 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.

[0047] Examples of flavoring and odor-correcting agents include, for example, sweeteners, acidulants, fragrances and the like. In addition, examples of carriers used in the case of liquid preparations for oral administration include solvents such as water.

[0048] The timing of ingesting the pharmaceutical of the present invention is not particularly limited, for example, before meals, after meals, between meals, before bedtime, etc.

Examples

[0049] The present invention will be described more specifically below using examples, but the present invention is not limited to these examples.

[0050] <Test Example> Evaluation of the effect of promoting the assimilation of human milk oligosaccharides by fecal culture (1) Pretreatment of samples A fecal sample was obtained from one healthy infant at 7 months of age. It was collected immediately after defecation and immediately transferred to a temperature of 10°C or lower under anaerobic conditions. Within 8 hours after defecation, the collected feces were diluted with 10 times the volume of physiological saline and stored at -80°C until use.

[0051] (2) Fecal culture To simulate the environment in the large intestine, a culture experiment was conducted according to the following procedure. A Bio Jr.8 100 mL × 8 multi-culture device (BJR-25NA1S-8M manufactured by Biott Co., Ltd.) was used, and the operation was carried out according to the equipment manual. As the culture medium, 100 mL of YCFA medium with the composition shown in Table 1 was used. Medium components other than tocopherol and oligosaccharide were dissolved in purified water and sterilized by autoclaving. Tocopherol was dissolved in dimethyl sulfoxide (DMSO, manufactured by Fujifilm Wako Pure Chemical Corporation), and oligosaccharide was dissolved in purified water. After being filtered and sterilized respectively, they were added to the material after the above autoclaving. The culture temperature was set at 37 °C, and filtered sterilized CO2 was blown into each culture container to maintain an anaerobic state during the culture period. After adjusting the pH to 7.0, 100 μL (10 mg as feces) of a fecal sample diluted with physiological saline was added to start anaerobic culture. To simulate the pH in the large intestine of infants, when the pH dropped below 5.5 during the culture period, it was neutralized with 1M Na2CO3 to control the pH. The culture medium was collected 7, 10, and 24 hours after the start of culture, centrifuged at 8000 rmp, 3 min, and 4 °C, and the supernatant and precipitate were collected respectively.

[0052]

Table 1-1

[0053]

Table 1-2

[0054] (3) Analysis of the amount of oligosaccharide in the culture supernatant For the supernatant collected and diluted with 4 times the volume of water, an equal amount of acetonitrile was added, and centrifugation (21500 g, 15 minutes, 4 °C) was carried out. After filter filtration, it was diluted 100 times with 50% acetonitrile and subjected to LC-MS analysis of oligosaccharide. For UHPLC separation, a Vanquish Flex UHPLC (Thermo Fisher Scientific, Waltham, MA, U.S.A.) system and an ACQUITY UPLC Glycoprotein BEH amide column (1.7 μm, 2.1 mm ×150 mm, Waters, Milford, MA, USA) were used. The gradient elution solvent was buffer A (10 mmol / L ammonium formate, 0.1% formic acid) and buffer B ( 0.1% formic acid / acetonitrile), the flow rate was 0.35 ml / min, and the column temperature was set at 3 5 °C. For the 13.5-min gradient elution, buffer B was changed from 75% to 6 0% over 7.5 min, from 60% to 20% over 1 min, held at 20% for 1 min, then from 20% to 75% over 0.1 min, and finally held at 75% for 4.4 min. Mass spectrometry was performed in parallel reaction monitoring (PRM) mode using an Orbitrap mass spectrometry Q Exactive Focus with a heated electrospray ionization source (Thermo Fisher Scientific). Data analysis was performed using TraceFinder software (Thermo Fisher Scientific) and executed.

[0055] (4) Results Table 2 shows the residual rate of oligosaccharides in the culture supernatant as a value when the pre-culture level is set to 100%. 2'-Fucosyllactose remains in the supernatant without being assimilated at 7 hours after culture (Comparative Example 1), but when three types of tocopherols, β-, γ-, and δ-, are added, the residual rate decreases to about 70% (Example 1-1). Further, when lacto-N-tetraose (LNT) is added in addition to the three types of tocopherols, the residual rate after 10 hours of culture decreases to about 20% of that without LNT addition (Example 1-2). 6'-sialyllactose remains in the supernatant without being assimilated even after 24 hours of culture in the presence of fructooligosaccharide (Comparative Example 2), but when three types of tocopherols, β-, γ-, and δ-, are added, the residual rate decreases to about 20% (Example 2). Galactooligosaccharide shows a residual rate of 70% at 7 hours after culture (Comparative Example 3), but when three types of tocopherols, β-, γ-, and δ-, are added at different ratios, the residual rate of galactooligosaccharide is reduced to about 50% in each case (Examples 3-1 to 3-4). From these results, it was shown that three types of tocopherols, β-, γ-, and δ-, promote the assimilation of oligosaccharides such as human milk oligosaccharides.

[0056]

Table 2-1

[0057]

Table 2-2

[0058]

Table 2-3

[0059]

Table 2-4

Claims

[Claim 1] A composition for promoting assimilation of oligosaccharides, comprising tocopherol, The composition, wherein the tocopherol comprises one or more selected from the group consisting of β-tocopherol, γ-tocopherol and δ-tocopherol.

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