Oral composition for intestinal delivery

Abstract

The present invention provides an oral composition for intestinal delivery comprising one or more selected from the bacterium Bifidobacterium longum subspecies infantis MCC2042 (NITE PB-03068), a cultured product of this bacterium, and a treated product of this bacterium. The oral composition for intestinal delivery may demonstrate a bacterial survival rate of at least 80% after treatment for 60 minutes in a liquid with a pH of 3.0 at 37°C.

Description

Oral composition for intestinal delivery

[0001] The present invention relates to an oral composition for intestinal delivery. This application claims priority to Japanese Patent Application No. 2024-012669, filed on January 31, 2024, the contents of which are incorporated herein by reference.

[0002] In recent years, active research has been conducted into the prevention of disease occurrence or health promotion by actively ingesting bacteria that have a positive effect on animals (so-called beneficial bacteria, also known as "probiotics") to improve the intestinal environment. For example, Patent Document 1 discloses probiotics that have an immunomodulatory effect and are useful for treating pathologies associated with changes in the immune system.

[0003] Research is also being conducted to improve the intestinal flora, including beneficial bacteria, to suppress the occurrence of diseases or promote health. Improvement of the intestinal flora, mainly through the promotion of the proliferation of beneficial bacteria, is known to have beneficial effects on human health, such as regulating the intestines and preventing and improving inflammatory bowel disease (Non-Patent Documents 1 to 3).

[0004] Special Publication No. 2013-521335

[0005] Cannarella et al., “Mixture of probiotics reduces inflammatory biomarkers and improves the oxidative / nitrosative profile in people with rheumatoid arthritis”, Nutrition (Burbank, Los Angeles County, Calif.), vol. 89, 2021Kim et al., “Probiotic Supplementation Improves Cognitive Function and Mood with Changes in Gut Microbiota in Community-Dwelling Older Adults: A Randomized, 76, No. 1, 2021Gomi et al., “Bifidobacterium bifidum YIT 10347 fermented milk exerts beneficial effects on gastrointestinal discomfort and symptoms in healthy adults: A double-blind, randomized, placebo-controlled study”, Journal of Dairy Science, vol. 101, No. 6, 2018

[0006] Thus, further research and development of probiotics is required. The present invention aims to provide an oral composition for delivery to the intestines that allows bacteria to reach the intestines alive.

[0007] The present invention encompasses the following aspects. [1] An oral composition for intestinal delivery comprising one or more bacteria selected from the group consisting of Bifidobacterium longum subsp. infantis MCC2042 (NITE BP-03068), a culture of said bacteria, and a processed product of said bacteria. [2] The oral composition for intestinal delivery according to [1], in which the survival rate of said bacteria after treatment with a liquid having a pH of 3.0 at 37°C for 60 minutes is 80% or more. [3] The oral composition for intestinal delivery according to [1] or [2], further comprising human milk oligosaccharides. [4] The oral composition for intestinal delivery according to [3], in which the human milk oligosaccharides comprise at least one of 2'-fucosyllactose, 3'-fucosyllactose, lacto-N-tetraose, and lacto-N-neotetraose. [5] The oral composition for reaching the intestines according to [4], wherein the ratio of the total mass of the 2'-fucosyllactose, the 3'-fucosyllactose, the lacto-N-tetraose and the lacto-N-neotetraose to 100 parts by mass of the bacteria is 1 to 1,000,000 parts by mass. [6] The oral composition for reaching the intestines according to any one of [1] to [5], which is used for improving intestinal flora. [7] The oral composition for reaching the intestines according to any one of [1] to [6], wherein the oral composition for reaching the intestines does not substantially contain an acid-resistant protective agent.

[0008] According to the above-mentioned aspects, it is possible to provide an oral composition for delivery to the intestines that allows bacteria to reach the intestines alive, use of bacteria for improving intestinal flora, and a method for improving intestinal flora.

[0009] 1 is a graph showing the change in bacterial cell concentration (CFU / ml) of MCC2042 and JCM1222 over time in a test example. 2 is a graph showing the change in survival rate (%) of MCC2042 and JCM1222 over time in a test example.

[0010] Preferred embodiments for carrying out the present invention will be described below. Note that the embodiment described below shows an example of a typical embodiment of the present disclosure, and the scope of the present technology is not to be interpreted narrowly by this. Note that in this specification, when a numerical range is expressed as "lower limit value to upper limit value," it means that both the upper limit value and the lower limit value are included.

[0011] Bifidobacterium bacteria have been reported to have various physiological functions. These physiological functions are reportedly related to intestinal proliferation or substances produced by Bifidobacterium bacteria (e.g., acetic acid, etc.). Therefore, the Bifidobacterium bacteria of this embodiment are also highly safe and can be expected to have the efficacy commonly associated with Bifidobacterium bacteria across a wide range of age groups. For this reason, the Bifidobacterium bacteria of this embodiment can be used in a wide range of compositions, such as foods and beverages, functional foods, pharmaceuticals, and feed. Furthermore, since the Bifidobacterium bacteria of this embodiment can be expected to have probiotic effects, they can also be used for purposes such as health promotion, dietary improvement, and intestinal environment improvement (intestinal regulation).

[0012] <Bifidobacterium longum subsp. infantis MCC2042 (NITE BP-03068)> Bifidobacterium longum subsp. infantis MCC2042 (NITE BP-03068, hereinafter also referred to as "MCC2042") was deposited internationally as Bifidobacterium longum subsp. infantis MCC2042 (accession number: NITE BP-03068) at the National Institute of Technology and Evaluation, Patent Microorganisms Depositary (NPMD) (Address: Room 122, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818) on November 20, 2019. This bacterium is publicly available from the above-mentioned preservation institution. "Bifidobacterium infantis" has been reclassified as "Bifidobacterium longum subsp. infantis", which is synonymous with the term.

[0013] MCC2042 has a high survival rate in low pH environments, i.e., high acid resistance. Furthermore, ingestion of MCC2042 by animals is expected to have an intestinal regulating effect. As used herein, pH refers to the value measured at 25°C. As used herein, "high acid resistance" can be evaluated by calculating the survival rate in the test examples described below. MCC2042 is inoculated into 1 mL of artificial gastric fluid (pH 3.0) at 1 v / v% to obtain a mixed solution. The resulting mixed solution is maintained at 37°C. The time when the container containing the mixed solution is placed in an incubator is designated as 0 minutes, and aliquots of the mixed solution are taken at 0 minutes and 60 minutes, and subjected to pour plate culture for 72 hours, followed by measurement of CFU (colony forming units) for each time point. If the ratio (%) of CFUs in the pour plate culture after 60 minutes to the CFUs in the pour plate culture at 0 minutes is 80% or more, it is judged to have a "high survival rate in a low pH environment," i.e., "high acid resistance."

[0014] MCC2042 is not limited to the bacterium itself deposited and registered with the institution under that name (hereinafter, for convenience of explanation, also referred to as the "deposited bacterium"), but also includes bacteria substantially equivalent thereto (also referred to as "derived strains" or "derived strains"). With regard to bacteria, "bacteria substantially equivalent to the deposited bacterium" means bacteria that belong to the same species as the deposited bacterium and have acid resistance equivalent to or greater than that of the deposited bacterium. Bacteria substantially equivalent to the deposited bacterium may be, for example, a derived strain of the deposited bacterium. Derivative strains include bacteria bred from the deposited bacterium and bacteria that naturally arise from the deposited bacterium.

[0015] In this embodiment, a bacterium substantially equivalent to MCC2042 refers to, for example, a bacterium of the same genus, in which the base sequence of the 16S rRNA gene has preferably 99.9% or more, more preferably 100%, homology with the base sequence of the 16S rRNA gene of MCC2042, and preferably has the same bacteriological properties as MCC2042.

[0016] In this embodiment, MCC2042 also includes mutant strains of MCC2042, as long as they have the properties of MCC2042 (e.g., a high survival rate in low pH environments). Furthermore, it is preferable that this mutant strain is a bacterium that has the same bacteriological properties as MCC2042 and has a survival rate in low pH environments equal to or higher than that of MCC2042. Whether a certain mutant strain has a "high survival rate in low pH environments equal to or higher than that of MCC2042" can be confirmed, for example, by the method of the test example described below.

[0017] Such mutant strains may be constructed by non-artificially introducing mutations into MCC2042. Alternatively, they may be constructed by introducing mutations into the bacterium by treatment with a mutagen such as UV, or by various genetic engineering techniques.

[0018] Substantially equivalent bacteria and derived strains include the following: (1) Bacteria determined to be the same bacteria by the Randomly Amplified Polymorphic DNA method or the Pulsed-field gel electrophoresis method (described in Probiotics in food / Health and nutritional properties and guidelines for evaluation 85, page 43) (2) Bacteria that contain only genes derived from the deposited bacteria, do not contain genes of foreign origin, and have a DNA identity of 95% or more (preferably 98% or more) (3) Bacteria that have the same characteristics as bacteria bred from the bacteria (including genetic engineering modifications, mutations, or natural mutations)

[0019] MCC2042 can be grown by culturing the bacterium. The culturing method is not particularly limited as long as it allows MCC2042 to grow, and methods commonly used for culturing Bifidobacterium bacteria can be used with appropriate modifications as necessary. For example, the culture temperature may be 30 to 50°C, preferably 35 to 45°C. The culture is preferably carried out under anaerobic conditions, for example, while aerating with anaerobic gas such as carbon dioxide. Culture may also be carried out under microaerobic conditions, such as liquid static culture.

[0020] The culture medium for growing MCC2042 is not particularly limited, and media typically used for culturing Bifidobacterium bacteria can be used with appropriate modifications as needed. For example, sugars such as galactose, glucose, fructose, arabinose, mannose, cellobiose, maltose, lactose, sucrose, trehalose, starch, starch hydrolysates, and blackstrap molasses can be used as carbon sources. In particular, MCC2042 has excellent assimilation ability for 2'-fucosyllactose, 3'-fucosyllactose, lacto-N-tetraose, and lacto-N-neotetraose, with OD600 values ​​of 0.3 or higher for each, as determined by the method for determining assimilation ability of sugar sources described below.

[0021] <Method for determining sugar source assimilation> 1 mL of MRS (de Man-Rogosa-Sharpe) liquid medium containing a sugar source is inoculated with 1 v / v % of each strain and cultured at 37°C under anaerobic conditions. After 16 hours of culture, the turbidity (OD600) is measured, and the turbidity of a control medium cultured in the same manner but without the strain is subtracted. The value obtained is used to determine the presence or absence of assimilation and the degree of assimilation ability in accordance with the following criteria. An OD600 difference from the control of 0.3 or higher is considered to indicate "good assimilation."

[0022] Examples of nitrogen sources that can be used include ammonium salts and nitrates such as ammonia, ammonium sulfate, ammonium chloride, and ammonium nitrate. Examples of inorganic salts that can be used include sodium chloride, potassium chloride, potassium sulfate, magnesium sulfate, calcium chloride, calcium nitrate, manganese chloride, and ferrous sulfate. Organic components such as soybean flour, defatted soybean meal, meat extract, and yeast extract may also be used. Examples of prepared media that can be used include MRS medium.

[0023] <Oral Composition for Intestinal Delivery Containing MCC2042> The oral composition for intestinal delivery of this embodiment contains one or more selected from the bacterium MCC2042, a culture of said bacterium, and a processed product of said bacterium. Oral compositions for intestinal delivery include food and beverage compositions, pharmaceutical compositions, and the like. Since MCC2042 is derived from humans, it has few side effects and is highly safe, allowing animals to ingest it continuously over a long period of time. Therefore, it can be used in products with a wide range of applications, such as food and beverage compositions and pharmaceutical compositions.

[0024] When animals ingest the oral composition for delivery to the intestines of this embodiment, the intestinal regulating effect can be expected. MCC2042 can be used by mixing live or sterilized cells with a usual carrier or diluent that is physiologically, pharmaceutically, or food- and beverage-acceptable.

[0025] The term "cultured product of MCC2042" refers to a culture obtained after culturing by the above-mentioned method. The term "treated product of MCC2042" refers to cells that have been cultured by the above-mentioned method and then subjected to additional treatments such as heating, drying, crushing, and sterilization. These treatments can be used in combination as appropriate. The oral composition for delivery to the intestines contains at least live cells and may also contain killed cells.

[0026] Examples of drying methods include spray drying and freeze drying. Examples of sterilization methods include retort sterilization, UHT (Ultra High Temperature) sterilization, pressure sterilization, high-pressure steam sterilization, dry heat sterilization, circulating steam disinfection, electromagnetic wave sterilization, electron beam sterilization, high-frequency sterilization, radiation sterilization, ultraviolet sterilization, ethylene oxide gas sterilization, hydrogen peroxide gas plasma sterilization, and chemical sterilization (specifically, alcohol sterilization, formalin fixation, and electrolyzed water treatment).

[0027] MCC2042 can be in the form of, for example, a bacterial cell concentrate, freeze-dried bacterial cells, spray-dried bacterial cells, sterilized bacterial cells, heat-sterilized bacterial cells, or crushed bacterial cells.

[0028] In the oral composition for delivery to the intestines of this embodiment, the survival rate of the bacteria after treatment for 60 minutes with a liquid having a pH of 3.0 at 37° C. is preferably 80% or more, and more preferably 90% or more. If the survival rate is 80% or more, it can be determined that the bacteria have a "high survival rate in a low pH environment," that is, have "high acid resistance," and it can be said that MCC2042 can reach the intestines alive.

[0029] The oral composition for intestinal delivery of this embodiment has high acid resistance, and therefore, when ingested as live bacterial cells, it can reach the intestine as live bacterial cells without being killed by gastric acid. It is generally known that ingested food remains in the stomach for approximately two hours. MCC2042 can reach the intestine after ingestion without being killed by gastric acid. As a result, MCC2042 can exert beneficial effects on the human body, such as intestinal regulation, while remaining alive in the intestine. In this embodiment, the intestine refers to the duodenum, small intestine, or large intestine. When ingested as live bacterial cells, the oral composition for intestinal delivery of this embodiment allows 35% by mass or more, preferably 40% by mass or more, more preferably 50% by mass or more, even more preferably 60% by mass or more, even more preferably 70% by mass or more, even more preferably 80% by mass or more, even more preferably 90% by mass or more, and even more preferably 95% by mass or more of the ingested amount of MCC2042 to reach the intestine as live bacterial cells.

[0030] The oral composition for delivery to the intestine of this embodiment may further contain human milk oligosaccharides. The human milk oligosaccharides are not particularly limited as long as they are oligosaccharides normally contained in human milk, but may include 2'-fucosyllactose, 3-fucosyllactose, 3'-fucosyllactose, lactodifucotetraose, 2',3-difucosyllactose, lacto-N-triose II, lacto-N-tetraose, lacto-N-neotetraose, lacto-N-fucopentaose I, lacto-N-neofucopentaose, lacto-N-fucopentaose II, lacto-N-fucopentaose III, lacto-N Preferred examples of such oligosaccharides include neutral human milk oligosaccharides such as 2'-fucosyllactose V, lacto-N-neofucopentaose V, lacto-N-difucohexaose I, lacto-N-difucohexaose II, 6'-galactosyllactose, 3'-galactosyllactose, lacto-N-hexaose, and lacto-N-neohexaose, and acidic human milk oligosaccharides such as 3'-sialyllactose, 6'-sialyllactose, 3-fucosyl-3'-sialyllactose, and disialyl-lacto-N-tetraose. Of these, 2'-fucosyllactose, 3'-fucosyllactose, lacto-N-tetraose, and lacto-N-neotetraose are particularly preferred.

[0031] The oral composition for intestinal delivery of this embodiment preferably contains at least one of 2'-fucosyllactose, the 3'-fucosyllactose, the lacto-N-tetraose, and the lacto-N-neotetraose. In the oral composition for intestinal delivery, the ratio of the total mass of 2'-fucosyllactose, the 3'-fucosyllactose, the lacto-N-tetraose, and the lacto-N-neotetraose to 100 parts by mass of the bacteria is preferably 1-1,000,000 parts by mass, and more preferably 10-10,000 parts by mass. When the ratio of the total mass of 2'-fucosyllactose, the 3'-fucosyllactose, the lacto-N-tetraose, and the lacto-N-neotetraose to 100 parts by mass of the bacteria is 1-1,000,000 parts by mass, MCC2042 is likely to proliferate in the body after ingestion of the oral composition for intestinal delivery.

[0032] The oral composition for intestinal delivery of this embodiment preferably does not substantially contain an acid-resistant protective agent. "Substantially not containing an acid-resistant protective agent" means that an acid-resistant protective agent may be contained to the extent that it does not exhibit acid resistance. More specifically, the content of the acid-resistant protective agent is preferably 1% by mass or less, more preferably 0.05% by mass or less, and even more preferably 0.001% by mass or less, relative to the total mass of the oral composition for intestinal delivery. In particular, it is preferable that the oral composition for intestinal delivery does not contain an acid-resistant protective agent. The acid-resistant protective agent may be a substance that is substantially stable in an acidic environment and substantially unstable in a near-neutral to alkaline environment, or a substance that is substantially stable in gastric juice. Examples of the acid-resistant protective agent include, but are not limited to, shellac, sugar coating, fatty acids, waxes, plastics, carboxymethylcellulose, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, hydroxypropyl methylcellulose acetate succinate, cellulose acetate trimellitate, and hypromellose hydroxypropyl methylcellulose. As described above, MCC2042 has high acid resistance, and therefore can reach the intestine alive even if the oral composition for intestinal delivery does not substantially contain an acid-resistant protective agent.

[0033] The content of MCC2042 in the entire oral composition for intestinal delivery of this embodiment is not particularly limited, but may be, for example, 10 ２ CFU / g or mL or more, 10 ３ CFU / g or mL or more, 10 ４ CFU / g or mL or more, 10 ５ CFU / g or mL or more, or 10 ６ CFU / g or mL or more, １２ CFU / g or mL or less, 10 １１ CFU / g or mL or less, or 10 １０ CFU / g or mL or less, or 10 ９ The content of MCC2042 in the oral composition for intestinal delivery of this embodiment may be 10 CFU / g or mL. ２ CFU / g or mL ~10 ９ CFU / g or mL,３ CFU / g or mL ~10 １２ CFU / g or mL, ４ CFU / g or mL ~10 １１ CFU / g or mL, ５ CFU / g or mL or more to 10 １０ It may be in CFU / g or mL.

[0034] An oral composition for intestinal delivery containing MCC2042 can be used for the purpose of improving the intestinal flora. An oral composition for intestinal delivery containing MCC2042 may be used for therapeutic or non-therapeutic purposes. "Non-therapeutic purposes" is a concept that does not include medical procedures, i.e., treatment of the human body through therapy. Examples include health promotion or cosmetic procedures. "Improvement" refers to the improvement of a disease, symptom, or condition; the prevention or delay of the worsening of a disease, symptom, or condition; or the reversal, prevention, or delay of the progression of a disease or symptom. "Prevention" refers to the prevention or delay of the onset of a disease or symptom in a subject, or the reduction of the risk of a disease or symptom in a subject.

[0035] When the oral composition for intestinal delivery of the present invention is used for non-therapeutic purposes, it can be administered to healthy subjects. A healthy subject may mean a subject who has a healthy intestinal flora and who is not suffering from a disease caused by a disruption of the intestinal flora. Examples of diseases caused by a disruption of the intestinal flora include diarrhea and constipation. When the oral composition for intestinal delivery of the present invention is used for non-therapeutic purposes, it can be used to further improve the healthy intestinal flora of a healthy subject, and in particular, it can be used to grow MCC2042 in the intestines of a healthy subject.

[0036] When the oral composition for intestinal access of the present invention is used for non-therapeutic purposes, it may include the prevention of physical or mental conditions associated with intestinal flora disturbance. When the oral composition for intestinal access of the present invention is used for non-therapeutic purposes, it is possible to regulate the intestinal flora in healthy individuals, prevent diarrhea and constipation, increase appetite, and improve beauty.

[0037] When the oral composition for reaching the intestine of the present invention is used for therapeutic purposes, it may include the treatment or prevention of diseases caused by disruption of the intestinal flora. When the oral composition for reaching the intestine of the present invention is used for therapeutic purposes, it may be administered to unhealthy subjects. Examples of unhealthy subjects include those suffering from diseases caused by disruption of the intestinal flora.

[0038] When the oral composition for delivery to the intestines of the present invention is used for therapeutic purposes, it is possible to regulate the intestines of unhealthy people, and improve, prevent, and treat diarrhea and constipation.

[0039] When the oral composition for delivery to the intestine of the present invention is used for therapeutic purposes, it can be used to improve the intestinal flora of unhealthy individuals, and in particular, can be used to grow MCC2042 in the intestines of unhealthy individuals.

[0040] The oral composition for delivery to the intestines containing MCC2042 may be used for humans or non-human animals (preferably mammals), preferably humans and pets, more preferably humans. Furthermore, the target population of the present technology is not particularly limited as long as it is anyone desiring a probiotic effect, and examples include infants, children, adults, middle-aged and elderly people, the elderly, healthy individuals, and individuals with poor intestinal environments. Of these, the present technology is preferably used for infants, adults, the elderly, and individuals with poor intestinal environments.

[0041] The oral composition for intestinal delivery containing MCC2042 is preferably administered or ingested continuously for at least one week, more preferably at least four weeks. During the administration or ingestion period of MCC2042, it is desirable to ingest MCC2042 daily.

[0042] The amount of MCC2042 used is not particularly limited because it is highly safe. For example, ４ ~1 x 10 ９ CFU / kg body weight / day is preferred, 1 x 10 ５ ~1 x 10 １２ CFU / kg body weight / day is preferred, 1 x 10 ７ ~1 x 10 １１ CFU / kg body weight / day is more preferred, 1 x 10 ８ ~1 x 10 １０CFU / kg body weight / day is more preferable. Alternatively, the amount used (in other words, the dosage) per individual (body weight) is 10 ６ CFU / day ~10 １１ CFU / day is preferred, 10 ７ ~10 １４ CFU / day is preferred, 10 ８ ~10 １３ CFU / day is more preferred, 10 ９ ~10 １２ More preferably, it is CFU / day. If MCC2042 is sterile, CFU can be replaced with cells.

[0043] The amount of MCC2042 used is not particularly limited because it is highly safe, but is preferably 0.001 to 50 mg / kg body weight / day, more preferably 0.01 to 10,000 mg / kg body weight / day, more preferably 0.01 to 1,000 mg / kg body weight / day, and even more preferably 0.1 to 100 mg / kg body weight / day, in terms of dry weight of the bacterial cells. The amount of MCC2042 used is not particularly limited because it is highly safe, but is preferably 0.0001 to 5 mL / kg body weight / day, more preferably 0.001 to 100 mL / kg body weight / day, and even more preferably 0.1 to 10 mL / kg body weight / day.

[0044] <Pharmaceutical Composition> The oral composition for delivery to the intestine of this embodiment may be a pharmaceutical composition. The pharmaceutical composition is not particularly limited as long as it contains MCC2042. The pharmaceutical composition can also be used as a composition for intestinal regulation containing MCC2042.

[0045] The pharmaceutical composition is used for the above-mentioned therapeutic purposes in unhealthy individuals.

[0046] The dosage form of the pharmaceutical composition of this embodiment is not particularly limited. Specific examples of dosage forms of the pharmaceutical composition include tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, syrups, suppositories, injections, ointments, patches, eye drops, and nasal drops. Furthermore, additives commonly used as pharmaceutical carriers, such as excipients, binders, disintegrants, lubricants, stabilizers, flavorings, diluents, surfactants, and injection solvents, can be used in the formulation.

[0047] Furthermore, when formulating, the pharmaceutical composition according to this embodiment can contain ingredients such as excipients, pH adjusters, colorants, and flavoring agents that are commonly used in formulations. Furthermore, as long as the effects of the present invention are not impaired, the pharmaceutical composition according to this embodiment can also contain ingredients that have the effect of preventing, ameliorating, and / or treating known or future diseases or symptoms related to this embodiment. Additionally, formulation can be carried out by known methods as appropriate depending on the dosage form. When formulating, a pharmaceutical carrier may be added as appropriate.

[0048] The content of MCC2042 in the pharmaceutical composition is appropriately determined depending on the dosage form, dosage method, age and sex of the patient, type of disease, severity of disease, and other conditions, but is usually 1 x 10 ４ ~1 x 10 １１ CFU / g or 1 x 10 ４ ~1 x 10 １１ CFU / mL, preferably in the range of 1 x 10 ５ ~1 x 10 １２ CFU / g or 1 x 10 ５ ~1 x 10 １２ CFU / mL, preferably in the range of 1 x 10 ６ ~1 x 10 １２ CFU / g or 1 x 10 ６ ~1 x 10 １２ If MCC2042 is a fungicide, CFU / g or CFU / mL can be substituted with cells / g or cells / mL.

[0049] The timing of administration of the pharmaceutical composition of this embodiment is not particularly limited, and can be appropriately selected according to the treatment method for the target symptom or disease. It may also be administered prophylactically or for maintenance therapy. The dosage form is preferably determined depending on the formulation, the patient's age, sex, other conditions, or the severity of the patient's symptoms. In either case, the pharmaceutical composition of this embodiment can be administered once a day or multiple times a day, or may be administered once every few days or weeks.

[0050] <Food and drink composition> The oral composition for delivery to the intestine of this embodiment may be a food and drink composition. The food and drink composition is not particularly limited as long as it contains MCC2042, and may be a probiotic composition, a nutritional composition, or a general food and drink composition.

[0051] The dosage form of the food or drink composition is not particularly limited, and may be powder, granules, paste, emulsion, oil drops, capsules, tablets, or the like.

[0052] The food and beverage composition may be produced by adding MCC2042 to a known food or beverage, or by mixing MCC2042 into the ingredients of a food or beverage to produce a new food or beverage composition. Because MCC2042 has high acid resistance, the food and beverage composition of this embodiment exhibits a high survival rate even when combined with acidic food ingredients, and therefore can be applied to a wide variety of food and beverage compositions.

[0053] Furthermore, the food and beverage composition may be a probiotic composition containing a component having a probiotic effect or a component that supports the probiotic effect, as long as the effect of the present invention is not impaired. For example, the food and beverage composition in this embodiment can be prepared by combining MCC2042 with components such as carbohydrates such as human milk oligosaccharides; various proteins such as whey protein, casein protein, soy protein, and pea protein (pea protein), or mixtures or hydrolysates thereof; amino acids such as leucine, valine, isoleucine, and glutamine; vitamins such as vitamin B6 and vitamin C; creatine; citric acid; or fish oil.

[0054] The food and beverage composition can be a probiotic composition. The food and beverage composition of this embodiment can contain food ingredients in addition to MCC2042. Examples of food ingredients 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 calcium carboxymethyl cellulose; 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.

[0055] The food and drink composition usually contains 1 x 10 MCC2042 per total dry weight of the food and drink composition. ２ CFU / g ~ 1 x 10 １０ CFU / g, and can contain 1 x 10 ３ CFU / g ~ 1 x 10 １２ CFU / g, more preferably 1 x 10 ５ CFU / g ~ 1 x 10 １１ It is possible to include CFU / g.

[0056] When the food or beverage composition is liquid, MCC2042 is added to the total volume of the liquid. ２ CFU / mL~1×10 １０ CFU / mL, and can contain 1 x 10 ３ CFU / mL~1×10 １２ CFU / mL, more preferably 1 x 10 ５ CFU / mL~1×10 １１ It may contain CFU / mL.

[0057] The food and beverage composition of this embodiment is not particularly limited as long as it contains MCC2042. Examples of food and beverage compositions include beverages such as soft drinks, carbonated drinks, nutritional drinks, fruit juice drinks, and lactic acid bacteria drinks (including concentrated concentrates and powders for preparation of these beverages); frozen desserts such as ice cream, sherbet, and shaved ice; sweets such as candy, candy, gum, chocolate, tablet sweets, snacks, biscuits, jelly, jam, cream, and baked goods; dairy products such as processed milk, milk drinks, fermented milk, yogurt drinks, and butter; and bread. The food and beverage composition may also be a supplement, for example, a tablet supplement. When it is a supplement, MCC2042 can be ingested without being affected by other foods in terms of daily food intake and calorie intake.

[0058] Furthermore, the food and beverage composition defined in this embodiment can be used as a probiotic composition. That is, the food and beverage composition of this embodiment can be provided or sold as a food or beverage labeled with a use (including health use) such as a probiotic. Furthermore, the food and beverage can be provided or sold with a label indicating the intended users of the food and beverage, such as "those who wish to live with Bifidobacterium bacteria," "those who wish to improve their intestinal environment," "those who wish to regulate their stomach condition," "those who wish to create a healthy intestinal environment," or "those who wish to ingest Bifidobacteria that reach the intestines alive." The act of "labeling" includes all acts for informing consumers of the intended use, and any expression that can evoke or infer the intended use falls under the "labeling" act of the present invention, regardless of the purpose of the labeling, the content of the labeling, the object and medium on which it is displayed, etc.

[0059] 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 (specifically, the Internet, etc.).

[0060] On the other hand, the content of the labeling is preferably a labeling 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.) Furthermore, it is preferable that such a labeling content be attached to promotional materials at the point of sale, such as packaging, containers, catalogs, pamphlets, and POP (Point of Purchase) notices, as well as other documents.

[0061] "Labeling" also includes labeling as health food, functional food, enteral nutritional food, special dietary food, health functional food, food for specified health uses, food with nutrient functions, or food with functional claims. Among these, labeling approved by the Consumer Affairs Agency in Japan, such as labeling approved under systems related to foods for specified health uses, foods with nutrient functions, or foods with functional claims, or similar systems, can be cited. Specific examples include labeling as a food for specified health uses, labeling as a conditional food for specified health uses, labeling claiming to affect the structure or function of the body, labeling claiming disease risk reduction, and labeling claiming functionality based on scientific evidence. More specifically, typical examples include labeling as a food for specified health uses (especially labeling for health uses) and similar labeling as defined in the Cabinet Office Ordinance on Permission for Labeling for Special Uses Provided in the Health Promotion Act (Cabinet Office Ordinance No. 57 of August 31, 2009).

[0062] The probiotic composition of the present embodiment can be administered to any subject, including unhealthy individuals, but when it is made into a food or beverage product labeled for a specific use (particularly for health purposes) or function, it is used for the above-mentioned non-therapeutic purposes.

[0063] The food and drink composition can be used as a nutritional composition. In this embodiment, "nutritional composition" refers to a food and drink that is orally ingested primarily for the purpose of ingesting nutrition. The type of nutritional composition that can be used in this embodiment is not particularly limited, but is preferably formula, baby food, liquid food (enteral nutrition, porridge, etc.), sports drinks, etc., and more preferably formula. The subject of intake may be an infant, a toddler, a child, or an adult, but is preferably an infant or a toddler.

[0064] Formulated milk includes formulated powdered milk and formulated liquid milk. Formulated powdered milk is defined herein as "a powdered product obtained by processing or using as the main ingredient raw milk derived from cows, raw goat's milk, raw sheep's milk, pasteurized goat's milk, cow's milk, special cow's milk, or foods produced using these as raw ingredients, and adding nutrients necessary for infants." Formulated liquid milk is defined herein as "a liquid product obtained by processing or using as the main ingredient raw milk derived from cows, raw goat's milk, raw sheep's milk, pasteurized goat's milk, cow's milk, special cow's milk, or foods produced using these as raw ingredients, and adding nutrients necessary for infants."

[0065] The formula of this embodiment may further contain the above-mentioned human milk oligosaccharides. The above-mentioned descriptions can be applied to the human milk oligosaccharides contained in the formula.

[0066] Formulated milk is a blend of nutritional ingredients such as various proteins, fats and oils, carbohydrates, minerals, and vitamins, and includes formulas processed into powder or liquid form. The nutritional ingredients can be any of the nutritional ingredients described above. Formulated milk also includes "powdered infant formula," "liquid infant formula," and "powdered milk for pregnant and nursing women," which are foods for special dietary uses as defined by the Health Promotion Act. Formulated milk also includes powdered infant formula for infants aged 0 to 12 months, follow-up milk for infants aged 6 to 9 months and older and young children (up to 3 years of age), powdered milk for low birth weight infants weighing less than 2500 g at birth (low birth weight infants), allergy formula used to treat infants with pathological conditions such as cow's milk allergy or lactose intolerance, powdered milk for lactose intolerance, powdered milk for inborn errors of metabolism, powdered milk for infants, nutritional powder for adults, and nutritional powder for the elderly.

[0067] The formula of this embodiment can be administered to any subject, including healthy and unhealthy individuals. When administered to healthy individuals, the formula of this embodiment can be used as infant formula, follow-on milk, formula for low birth weight babies, formula for young children, nutritional powder for adults, or nutritional powder for the elderly, and can be used for the above-mentioned non-therapeutic purposes.

[0068] When the formula of this embodiment is administered to unhealthy individuals, it can be used as a formula for allergies, lactose intolerance, or congenital metabolic disorders, and can be used for the above-mentioned therapeutic purposes.

[0069] The nutritional composition according to this embodiment can be applied to foods with health claims and foods for the sick. The health claim food system was established based on domestic and international trends and consistency with the existing system of foods for specified health uses, and covers not only ordinary foods but also foods in the form of tablets or capsules, etc., and is categorized into two types: foods for specified health uses, which are individually approved, and foods with nutrient functions, which are standardized.

[0070] <Method for producing oral composition for intestinal delivery> The method for producing an oral composition for intestinal delivery of this embodiment will be described below. In the method for producing an oral composition for intestinal delivery of this embodiment, the step of adding MCC2042 may be carried out at any stage in the process for producing the oral composition for intestinal delivery.

[0071] The method for producing an oral composition for intestinal delivery includes at least a step of mixing MCC2042 with raw materials. The MCC2042 described above can be used. The raw materials include the raw materials for the food and beverage compositions described above, components having probiotic effects, components that supplement the probiotic effects, and pharmaceutical carriers. In the case of a method for producing a composition for food and beverage, the raw materials include at least the raw materials for the food and beverage compositions described above. In the case of a method for producing a composition for food and beverage, the raw materials may include at least one of the components having probiotic effects, components that supplement the probiotic effects, and pharmaceutical carriers.

[0072] When mixing MCC2042 with raw materials, the content of MCC2042 is 1 x 10 ２ ~1 x 10 １０ It is preferable to mix so that the CFU / g is 1 x 10 ３ ~1 x 10 １２ It is preferable to mix so that the CFU / g is 1 x 10 ５ ~1 x 10 １１ It is more preferable to mix so that the concentration is CFU / g.

[0073] The method for producing an oral composition for intestinal delivery may further include a step of drying a mixture of MCC2042 and raw materials. The drying method is not particularly limited as long as it does not impair the effects of this embodiment. Specific drying methods include spray drying and freeze-drying. The method for producing an oral composition for intestinal delivery may further include a step of sterilizing a mixture of MCC2042 and raw materials. The sterilization method is not particularly limited as long as it does not impair the effects of this embodiment, and examples include retort sterilization, freeze-drying, UHT sterilization, autoclaving, high-pressure steam sterilization, dry heat sterilization, circulating steam disinfection, electromagnetic wave sterilization, electron beam sterilization, high-frequency sterilization, radiation sterilization, ultraviolet sterilization, ethylene oxide gas sterilization, hydrogen peroxide gas plasma sterilization, and chemical sterilization (specifically, alcohol sterilization, formalin fixation, and electrolyzed water treatment).

[0074] The method for producing an oral composition for intestinal delivery may further include at least one of the steps of mixing a prebiotic with the mixture and further mixing MCC2042 or a milk component with the mixture.

[0075] The method for producing an oral composition intended to reach the intestines may further include a step of mixing at least one type of probiotic bacteria such as Bifidobacterium bacteria other than MCC2042 and lactic acid bacteria.

[0076] The milk component is preferably in powder form, and more preferably mixed with MCC2042 bacterial powder.

[0077] The milk component is not particularly limited as long as it does not impair the effects of this embodiment. For example, milk components include cow's milk, buffalo milk, sheep's milk, goat's milk, horse's milk, skim milk, concentrated skim milk, skim milk powder, concentrated milk, whole milk powder, cream, butter, buttermilk, condensed milk, and milk proteins, and one or more selected from the group consisting of these can be used. Furthermore, the milk protein is not particularly limited, and examples thereof include whey, casein, and hydrolysates thereof, and one or more selected from the group consisting of these can be used. Milk-derived components are preferred.

[0078] The hydrolysate can be produced by hydrolyzing the milk component (preferably milk protein), such as whey hydrolysate or casein hydrolysate. Examples of hydrolysis include acid or alkali hydrolysis and enzymatic hydrolysis. Among these, enzymatic hydrolysis is preferred. Protease is preferred as the enzyme used for enzymatic hydrolysis. Examples of protease include protease, trypsin, chymotrypsin, plasmin, pepsin, papain, peptidase, and aminopeptidase. The pH during the hydrolysis reaction can be adjusted appropriately to the optimum pH for the enzyme used, for example, at a pH of 2 to 6. The temperature during the hydrolysis reaction is not particularly limited, and is typically preferably in the range of 30 to 60°C. The reaction time is preferably 2 to 10 hours.

[0079] Furthermore, when producing a supplement or tablet as the oral composition for delivery to the intestine of the present invention, the method for producing the oral composition for delivery to the intestine of this embodiment can include a step of mixing a culture containing MCC2042 with a pharmaceutical carrier or the like to obtain a mixture, and a step of molding the mixture into a predetermined shape for the supplement or tablet. Examples of the molding step include tableting. An example of tableting is compression molding a mixture of powder or granules to obtain a tablet.

[0080] Furthermore, an example of a method for producing an oral composition for delivery to the intestines of this embodiment is a method for producing a fermented food or drink (preferably fermented milk) containing MCC2042. A step of adding a dried mixture of MCC2042 and raw materials to a fermented milk raw material to obtain fermented milk containing MCC2042 is carried out. Alternatively, a step of mixing a dried mixture of MCC2042 and raw materials with fermented milk to obtain fermented milk containing MCC2042 is carried out. The fermentation conditions and blending amounts are adjusted so that the bacterial cell amount of MCC2042 in the composition is the above-mentioned bacterial cell amount. This allows for the provision of a fermented food or drink containing MCC2042, preferably fermented milk or a fermented product.

[0081] <Method for improving intestinal flora and use of bacteria for improving intestinal flora> The method for improving intestinal flora of the present invention involves administering Bifidobacterium longum subsp. infantis MCC2042 (NITE BP-03068) at an intake of 1 × 10 ２ ~1 x 10 １０ Preferably 1 x 10 CFU / day ３ ~1 x 10 １２ The method includes administering to a recipient a dose of 1000 CFU / day of the vaccine.

[0082] In the method for improving intestinal flora of this embodiment, MCC2042 can be administered to any subjects, including healthy and unhealthy subjects. ２ ~1 x 10 １０ Preferably 1 x 10 CFU / day ３ ~1 x 10 １２ When administered to a patient suffering from intestinal problems such as constipation or diarrhea, it is expected to improve the intestinal flora. It is preferable that the patient takes MCC2042 continuously.

[0083] In other words, one or more selected from the bacterium Bifidobacterium longum subsp. infantis MCC2042 (NITE BP-03068), a culture of the bacterium, and a processed product of the bacterium can be used to improve the intestinal flora of a subject to administration. In one aspect, the present invention may relate to the use of one or more selected from the bacterium Bifidobacterium longum subsp. infantis MCC2042 (NITE BP-03068), a culture of the bacterium, and a processed product of the bacterium for improving the intestinal flora. In another aspect, the present invention may relate to the use of one or more selected from the bacterium Bifidobacterium longum subsp. infantis MCC2042 (NITE BP-03068), a culture of the bacterium, and a processed product of the bacterium for the manufacture of a composition for improving the intestinal flora.

[0084] MCC2042 has high acid resistance, and when orally ingested, it can maintain a high survival rate even when coexisting with gastric acid. As a result, when orally ingested, MCC2042 can reach the intestines with a high survival rate. All matters related to MCC2042 can conform to the above.

[0085] The present embodiment will be described in more detail below based on examples. Note that the examples described below are representative examples of the present embodiment, and should not be construed as narrowing the scope of the present invention.

[0086] [Test Example] (1) Objective This test example was carried out to evaluate the acid resistance of Bifidobacterium longum subsp. infantis MCC2042.

[0087] (2) Bacteria The following two types of bacteria were used: Bifidobacterium longum subsp. infantis MCC2042 (FERM BP-03068) Bifidobacterium longum subsp. infantis (JCM1222, Type stain)

[0088] JCM1222 is available from the Japan Collection of Microorganisms (JCM), Microbial Materials Development Division, BioResource Research Center, RIKEN, National Research and Development Agency. The address is 3-1-1 Takanodai, Tsukuba, Ibaraki Prefecture, 305-0074, Japan. (3) Preparation of Artificial Gastric Juice. Sodium chloride and pepsin (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) were added to ultrapure water to a final concentration of 0.2% by mass and 0.35% by mass, respectively, and mixed with a stirrer. The resulting mixture was adjusted to pH 3.0 using hydrochloric acid and then filtered using a 0.45 μm pore filter to obtain artificial gastric juice.

[0089] (4) Pre-culture of bacteria Two types of bacteria were anaerobically cultured in an MRS medium containing 0.05% by mass of cysteine ​​hydrochloride at 37°C for 16 hours.

[0090] (5) Acid Resistance Test Two types of bacteria were cultured in the presence of artificial gastric juice for 0, 30, 60 and 120 minutes, and the number of bacteria was counted over time.

[0091] (5-1) Cultivation time: 0 minutes The bacteria after pre-culture were diluted 10 times with physiological saline, and then diluted 100 times with physiological saline twice to obtain a 100% ... ５ A 10-fold diluted solution containing the bacterial cells was prepared. ５ The 2-fold diluted bacterial cell-containing solution was diluted 10-fold twice, resulting in 10 ６ 10-fold diluted bacterial cell-containing solution, and ７ These three kinds of diluted bacterial cell-containing solutions were used as samples with a reaction time of 0 minutes with the artificial gastric juice.

[0092] (5-2) Incubation time: 30 minutes, 60 minutes, 120 minutes. The bacteria after pre-incubation were diluted 10-fold with physiological saline, then 10-fold with artificial gastric juice, and reacted at 37°C using a heat block for 30 minutes, 60 minutes, or 120 minutes. After the reaction, the bacteria were diluted 10-fold with Mitsuoka buffer, and further diluted 10-fold with physiological saline four times. ５ 10x dilution ６ 10-fold dilution, and ７ The Mitsuoka buffer contained 4.5 g of potassium dihydrogen phosphate, 6.0 g of disodium hydrogen phosphate, 0.5 g of L-cysteine ​​hydrochloride, 0.5 g of Tween (registered trademark) 80, and 1.0 g of agar per 1 L of ultrapure water.

[0093] (5-3) Measurement of viable cell count Four types of diluted bacterial cell-containing solutions prepared at each incubation time (0 min, 30 min, 60 min, 120 min) were added to TOS medium (Yakult Pharmaceutical Co., Ltd.) at 100 μL ( / dish) and cultured under anaerobic conditions. After the pour culture, the mixture was cultured at 37°C for 72 hours. After the culture, colonies were counted and the bacterial cell concentration (CFU / ml) was calculated. The bacterial cell concentration was determined by repeating the steps (5-1) to (5-3) above for each diluted bacterial cell solution (10 ５ , 10 ６ , 10 ７The results were calculated by performing three replicates for each of the diluted bacterial cell-containing solutions (2-fold diluted bacterial cell-containing solutions) and determining the arithmetic mean value (n=3).

[0094] The survival rate of bacteria at each incubation time was calculated using the following formula: Survival rate (%) = bacterial cell concentration (CFU / ml) at any incubation time / bacterial cell concentration (CFU / ml) at 0 min incubation time × 100

[0095] (6) Results The results of the bacterial cell concentration when cultured in artificial gastric juice for 0, 30, 60, or 120 minutes are shown in Figure 1. MCC2042 was cultured at 10 ６ 10x dilution ７ The diluted bacterial solution, JCM1222, was 10 ６ As shown in Figure 1, the cell concentration of MCC2042 was almost unchanged from the cell concentration at 0 hours of culture even after 60 minutes of culture. ９ The bacterial cell concentration was maintained at about CFU / ml. On the other hand, the bacterial cell concentration of JCM1222 was 10 ９ CFU / ml, but after 60 minutes of incubation, ８ The number of CFU / ml was reduced to about 1.

[0096] The survival rates of MCC2042 cultured in artificial gastric juice for 0, 30, 60, and 120 minutes are shown in Figure 2. The survival rate was 100% when the culture time was 0 minutes. As shown in Figure 2, the survival rate of MCC2042 cultured for 60 minutes was 96%, and the survival rate of MCC2042 cultured for 120 minutes was 40%. On the other hand, the survival rate of JCM1222 cultured for 60 minutes was 3.9%, and the survival rate of JCM1222 cultured for 120 minutes was 0.9%.

[0097] From the above, it was revealed that MCC2042 has high acid resistance to artificial gastric juice.

[0098] [Production Examples] Production examples of the composition, pharmaceutical composition, fermented milk, modified milk powder, and food and drink composition of this embodiment are shown below, but the compositions of this embodiment are not limited to these.

[0099] [Production Example 1] MCC2042 was cultured in MRS liquid medium (Difco ＴＭThe bacteria was added to 3 mL of Lactobacillus MRS Broth (product number 288130) and cultured anaerobically at 32-39°C for 5-25 hours. The culture was then concentrated and freeze-dried to obtain a freeze-dried bacterial powder (i.e., bacterial powder). The bacterial powder and whey protein concentrate (WPC) were uniformly mixed to obtain a composition. 20 g of this composition was dissolved in 200 g of water to obtain a composition containing MCC2042.

[0100] [Production Example 2] MCC2042 was added to 3 mL of MRS liquid medium and cultured anaerobically at 32-39°C for 5-25 hours. The culture medium was then concentrated and freeze-dried to obtain a freeze-dried bacterial powder (i.e., bacterial powder). The bacterial powder and a dried powder of milk protein concentrate (MPC480, manufactured by Fonterra, protein content 80% by mass, casein protein:whey protein ratio approximately 8:2) were uniformly mixed to obtain a composition. 20 g of this composition was dissolved in 200 g of water to obtain a composition containing MCC2042.

[0101] [Production Example 3] MCC2042 was added to 3 mL of MRS liquid medium and cultured anaerobically at 32-39°C for 5-25 hours. The culture was then concentrated and freeze-dried to obtain a freeze-dried powder (i.e., bacterial powder) of bacteria containing Bifidobacterium longum subsp. infantis MCC2042 (NITE BP-03068). The bacterial powder and crystalline cellulose were then placed in a stirring granulator and mixed. Purified water was then added to the mixture, followed by granulation. The granules were then dried to obtain a granule (pharmaceutical composition) containing excipients. In this manner, a granule containing MCC2042 was obtained.

[0102] [Production Example 4] A method for producing fermented milk with added MCC2042 is described below. First, the raw milk ingredients, and optionally water and other ingredients, are mixed, and then preferably homogenized and heat sterilized. The homogenization and heat sterilization can be carried out by conventional methods. A lactic acid bacteria starter is added to the heat-sterilized sterilized milk preparation (i.e., inoculated), and the mixture is fermented at a predetermined fermentation temperature to obtain a fermented product. Curd is formed by fermentation.

[0103] As the lactic acid bacteria starter, for example, lactic acid bacteria commonly used in yogurt production, such as Lactobacillus bulgaricus, Lactococcus lactis, and Streptococcus thermophilus, can be used. When the pH reaches the target value, the formed curd is broken down by stirring and cooled to 10°C or below to obtain a fermented product. By cooling to 10°C or below, the activity of the lactic acid bacteria can be reduced, thereby suppressing acid production.

[0104] The fermented product obtained in the fermentation step is then heat-treated to obtain a heated fermented product. By moderately heating the fermented product, acid production by lactic acid bacteria in the heated fermented product can be suppressed. This prevents a decrease in pH during the subsequent production process and / or during storage of the concentrated fermented milk containing bifidobacteria. As a result, the survival rate of bifidobacteria can be improved.

[0105] Next, MCC2042 is added to the heated fermented product obtained in the heat treatment step. The amount of MCC2042 added is 1 x 10 ７ ~1 x 10 １１ CFU / mL is preferred, 1 x 10 ８ ~1 x 10 １０ CFU / mL is more preferred. If MCC2042 is a bacterial cell, CFU / mL can be substituted with cells / mL.

[0106] MCC2042 is added to the heated fermented product, which is then concentrated. The concentration step can be carried out using any known concentration method. For example, centrifugation or membrane separation can be used. In the centrifugation method, whey is removed from the product to be concentrated (i.e., the heated fermented product to which MCC2042 has been added), thereby obtaining concentrated fermented milk with an increased solids concentration.

[0107] Fermented milk containing the MCC2042 obtained as described above can be produced.

[0108] [Production Example 5] The method for producing modified powdered milk containing MCC2042 is shown below.

[0109] 10 kg of desalted milk whey protein powder (Mirai Co., Ltd.), 6 kg of milk casein powder (Fonterra), 48 kg of lactose (Mirai Co., Ltd.), 920 g of mineral mixture (Tomita Pharmaceutical Co., Ltd.), 32 g of vitamin mixture (Tanabe Pharmaceutical Co., Ltd.), 500 g of lactulose (Morinaga Milk Industry Co., Ltd.), 500 g of raffinose (Nippon Beet Sugar Co., Ltd.), and 900 g of galactooligosaccharide liquid sugar (Yakult Pharmaceutical Co., Ltd.) were dissolved in 300 kg of warm water, further heated and dissolved at 90°C for 10 minutes, and 28 kg of modified fat (Taiyo Yushi Co., Ltd.) was added and homogenized. The mixture was then sterilized, concentrated, and spray-dried to prepare approximately 95 kg of modified milk powder. To this was added 100 kg of MCC2042 bacterial cell powder (10%) dispersed in starch. ８ ~10 １１ CFU / g, manufactured by Morinaga Milk Industry Co., Ltd.) was added to prepare approximately 95 kg of bifidobacteria-oligosaccharide formulated powdered milk. The prepared powdered milk was dissolved in water to prepare a formula with a total solids concentration of 14% (w / V), which is the standard formula concentration. When the number of bifidobacteria in the formula was 10 ６ ~10 ９ CFU / 100 mL can be obtained.

[0110] By ingesting or administering the thus obtained powdered milk containing MCC2042, the intestinal environment of humans can be improved.

[0111] [Production Example 6] A method for producing an intestinal environment improving food containing MCC2042 is shown below.

[0112] MCC2042 is added to 3 mL of MRS liquid medium and cultured anaerobically at 32 to 39°C for 5 to 25 hours. The culture medium is then concentrated and freeze-dried to obtain a freeze-dried powder of the bacteria (i.e., bacterial powder), which is used to obtain the composition of the present embodiment. The bacterial powder of the present embodiment can also be added to foods containing a large amount of cellulose (e.g., vegetables or salads) and cooked, thereby obtaining the composition of the present embodiment.

[0113] Alternatively, the bacterial powder can be taken before, during, or after a meal. Since regular meals (meals with a staple food, side dish, and main dish) inevitably involve the intake of dietary fiber, taking the dried bacterial powder product of this embodiment together with meals can be expected to have an effect of improving the intestinal environment in adults.

[0114] If people who suffer from intestinal problems such as constipation or diarrhea continue to take the intestinal environment improving food of this embodiment, they can expect to see a greater improvement in their intestinal environment.

[0115] From the above, it can be seen that an oral composition for delivery to the intestines containing Bifidobacterium longum subsp. infantis MCC2042 (NITE BP-03068) can promote the proliferation of bacteria of the genus Bifidobacterium in the intestines and can be effectively used for forming a favorable intestinal flora and improving the intestinal bacterial flora.

Claims

1. An oral composition for delivery to the intestines, comprising one or more selected from the group consisting of the bacterium Bifidobacterium longum subsp. infantis MCC2042 (NITE BP-03068), a culture of said bacterium, and a processed product of said bacterium.

2. An oral composition for intestinal delivery according to claim 1, wherein the survival rate of the bacteria after treatment with a liquid having a pH of 3.0 at 37°C for 60 minutes is 80% or more.

3. An oral composition for intestinal delivery according to claim 1 or 2, further comprising human milk oligosaccharides.

4. An oral composition for intestinal delivery according to claim 3, wherein the human milk oligosaccharides include at least one of 2'-fucosyllactose, 3'-fucosyllactose, lacto-N-tetraose and lacto-N-neotetraose.

5. An oral composition for intestinal access according to claim 4, wherein the ratio of the total mass of 2'-fucosyllactose, 3'-fucosyllactose, lacto-N-tetraose and lacto-N-neotetraose to 100 parts by mass of the bacteria is 1 to 1,000,000 parts by mass.

6. An oral composition for delivery to the intestines according to claim 1 or 2, which is used to improve the intestinal flora.

7. An oral composition for intestinal access according to claim 1 or 2, which is substantially free of an acid-resistant protective agent.

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