JP2022157465A - Defecation promoter for infants - Google Patents

Abstract

To provide an agent for promoting defecation of infants.SOLUTION: The present invention relates to a defecation promoter for infants that contains probiotics and is started to be administered to an infant on day 0-10 after birth so that the administration continues for at least two weeks.SELECTED DRAWING: None

Description

TECHNICAL FIELD The present invention relates to a defecation promoting agent for infants, a defecation promoting composition for infants, and a defecation promoting package for infants.

Since infants, especially newborns who have just been born, spend most of the day in a supine position, it is known that a lack of exercise causes a symptom of so-called constipation. In addition, infants whose defecation function is underdeveloped are at a higher risk of constipation when they start taking solid foods at the time when they start to take baby food. Constipation in infants can cause problems such as loss of appetite, malnutrition, and failure to develop defecation function. Therefore, there is a need for a method of promoting bowel movements in infants.

Here, probiotics, particularly bifidobacteria, are the predominant bacterial species in the intestinal tract of newborns (see, for example, Non-Patent Document 1), and in recent years, colonization of the intestinal tract with bifidobacteria has improved the intestinal function and immune function of infants. Furthermore, it is known to promote neurodevelopment and have a positive effect on the physical and psychomotor development of infants (Non-Patent Document 2). Therefore, the effect is particularly expected for infants, especially high-risk infants such as premature infants and low-birth-weight infants who have a high probability of being impaired in physical development or psychomotor development.

H. Tsuji, et al. Molecular monitoring the development of intestinal microbiota in Japanese infants. Beneficial Microbes, 3, 113-125, 2012 Goyal MS, et al. Feeding the brain and nurturing the mind: Linking nutrition and the gut microbiota to brain development. Proc Natl Acad Sci USA 2015;112:14105-14112.

However, until now, no detailed studies have been conducted on how probiotics promote defecation in infants. I have no knowledge.
Accordingly, an object of the present invention is to provide an agent for promoting defecation in infants.

As a result of intensive studies by the present inventors, the inventors have found that defecation in infants can be promoted by ingesting probiotics during a specific period in the early period of birth and continuously for a predetermined period, and have completed the present invention.

That is, the present invention is as follows.
1. A defecation stimulant for infants containing probiotics, which is used to start administration to infants on the 0th to 10th day of birth and continue to take it for 2 weeks or more.
2. 2. The defecation promoting agent for infants according to 1 above, wherein the probiotic is Bifidobacterium or Lactobacillus.
3. 3. The defecation promoting agent for infants according to 2 above, wherein the Bifidobacterium is Bifidobacterium bifidum.
4. 3. The defecation promoting agent for infants according to 2 above, wherein the Bifidobacterium is Bifidobacterium bifidum OLB6378 strain (Bifidobacterium bifidum, accession number: NITE BP-31).
5. 5. The defecation promoting agent for infants according to any one of 1 to 4 above, wherein the probiotics are live bacteria.
6. 6. The agent for promoting defecation for infants according to any one of 1 to 5 above, which is used so as to ingest the probiotic with a bacterial count of 1×10 ⁸ cfu or more per day.
7. 7. The defecation promoting agent for infants according to any one of 1 to 6 above, for promoting defecation in infants up to 18 months of age.
8. A defecation promoting composition for infants containing the defecation promoting agent for infants according to any one of 1 to 7 above.
9. 9. A package for promoting defecation for infants, wherein the defecation promoting composition for infants according to 8 above is packaged in a packaging material.

By starting the administration of the defecation promoting agent for infants of the present invention to infants at the early stage of birth and having them continue to ingest for a predetermined period, the defecation of infants can be promoted.

In the present invention, infants include infants and toddlers, more particularly infants, toddlers and newborns, more particularly infants, toddlers, newborns, premature infants, premature infants and low birth weight infants. An infant refers to a child in infancy, and infancy means the period when milk such as mother's milk is the main source of nutrition. Toddlers generally refer to children before school age (ages 6 to 7). A neonate refers to a child in the neonatal period, and the neonatal period means the period immediately after birth, and in the case of humans, usually within 4 weeks after birth corresponds to the neonatal period.

The probiotics contained in the defecation promoting agent for infants of the present invention (hereinafter also referred to as the agent of the present invention) are bacteria that benefit the host animal by improving the balance of intestinal flora formed by intestinal microorganisms. means
Examples of probiotics in the present invention include, but are not limited to, lactic acid bacteria and bifidobacteria, and include, but are not limited to, Bifidobacterium genus, Lactobacillus genus, Streptococcus genus, Lactococcus genus ) and the like can be exemplified.

Bifidobacterium genus, for example, Bifidobacterium longum strain, Bifidobacterium infantis strain, Bifidobacterium breve strain , Bifidobacterium bifidum strain, Bifidobacterium adolescentis strain, and the like.

Preferred among these are Bifidobacterium bifidum strains, more preferably Bifidobacterium bifidum OLB6378 (Bifidobacterium bifidum, accession number: NITE BP-31).

The present applicant has deposited these strains with the National Institute of Technology and Evaluation Patent Microorganisms Depositary. Below is a description identifying the deposit.
(1) Depository name: Patent Microorganism Depositary Center, National Institute of Technology and Evaluation (2) Contact: 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818
(Currently: Room 122, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan)
Phone number 0438-20-5580
(3) Accession number: NITE BP-31
(4) Label for identification: Bifidobacterium bifidum OLB6378
(5) Date of original deposit: October 26, 2004 (6) Date of transfer to deposit under the Budapest Treaty: January 18, 2006

Bifidobacterium bifidum strain OLB6378 is a Gram-positive obligate anaerobic bacillus derived from human infant feces. When this bacterium is applied to a BL agar medium (Eiken Chemical Co., Ltd.) plate and cultured in an anaerobic state at 37°C for 48 hours using AnaeroPack Kenki (Mitsubishi Gas Chemical Co., Ltd.), an opaque circular hemispherical gloss is obtained. form colonies with

In addition, the Bifidobacterium bifidum OLB6378 strain is a Bifidobacterium bifidum specific primer (Intestinal Flora Symposium 8, Molecular Biological Detection and Identification of Intestinal Flora, Tomotari Mitsuoka, Takahiro Matsumoto (2001)), specifically used species-specific primers for the 16S rRNA region, BiBIF-1: CCA CAT GAT CGC ATG TGA TT (SEQ ID NO: 1), and BiBIF-2: CCG AAG GCT TGC TCC CAA A (SEQ ID NO: 2). A PCR product is observed in the PCR. It also has fermentability to galactose, glucose, fructose, lactose and gentiobiose.

The genus Lactobacillus includes, for example, Lactobacillus gasseri strain, Lactobacillus bulgaricus strain, and the like.
The genus Streptococcus includes, for example, Streptococcus thermophilus strains.

The probiotics in the present invention are not limited to these species, and these strains can be used singly or in combination of two or more.

As a medium for culturing probiotics used in the present invention, a medium commonly used for culturing probiotics can be used. That is, the medium that can be used in the present invention is not particularly limited, and any medium can be used as long as it contains a main carbon source, a nitrogen source, inorganic substances and other nutrients in amounts within a predetermined range.

Lactose, glucose, sucrose, fructose, starch hydrolysates, blackstrap molasses and the like can be used as the carbon source depending on the assimilation of the bacteria used. Organic nitrogen-containing substances such as casein hydrolysates, whey protein hydrolysates and soybean protein hydrolysates can be used as the nitrogen source. In addition, meat extract, fish extract, yeast extract and the like are used as growth promoters.

Cultivation is preferably performed under anaerobic conditions, and known techniques such as a method of culturing while aerated with carbon gas can be applied. It can also be cultured using other techniques such as. The culture temperature is preferably 25 to 50° C., particularly 35 to 42° C., but the present invention is not limited to this, and other temperature conditions may be used as long as the temperature allows the bacteria to grow.

The pH of the medium during cultivation is preferably maintained at 6.0 to 7.0, but other pH conditions may be used as long as the pH is such that the bacteria can grow. The culture time is preferably 3 to 48 hours, more preferably 8 to 24 hours, particularly preferably 10 to 20 hours, but other culture times may be used as long as the bacteria can grow.

The obtained microbial cells can be contained in the agent of the present invention as a probiotics-processed product subjected to the following treatments. Probiotics processed products include cultures as they are after completion of cultivation, cultures that have been centrifuged or filtered after completion of cultivation, their concentrates, pastes, and dried products by various methods. (spray-dried, freeze-dried, vacuum-dried, drum-dried, etc.), liquid dispersed in a medium, diluted with a diluent, heat-treated (heat-treated fungus), ultraviolet light and/or Light-irradiated products treated with radiation (light-irradiated bacteria), chemical-treated products (medicine-treated bacteria) treated with drugs (sterilizers, antibacterial agents, bacteriostatic agents), crushed by crushing dried products with a mill, etc. things, etc.

Centrifugation, filtration, concentration, crushing, and the like are carried out by commonly used methods. Drying can be performed by, for example, vacuum drying, spray drying, freeze drying, drum drying, and the like. In addition, conventionally known ones can be appropriately selected and used for the medium, diluent, drug (bactericide, antibacterial agent, bacteriostatic agent) and the like.
These may be abbreviated herein as "probiotics processed" or "processed".

The probiotics and/or processed product obtained by the above method can be used directly as live bacteria or heat-treated bacteria, and then crushed or unpulverized as a processed product, either alone or as a mixture of multiple types, of the present invention. It can be contained in an agent.

If it is a viable bacterium, it can be expected to have effects such as proliferating in the body (in the intestine) after ingestion. In addition, if the bacteria are heat-treated, it is not necessary to consider the characteristic of probiotics that it is difficult to survive in the presence of oxygen, and the application range of the agent of the present invention is expanded.

Furthermore, probiotics can be used after removing the medium by centrifugation or the like from probiotics grown in a medium by culturing or the like. At this time, the defecation-promoting effect of the agent of the present invention can be further enhanced by allowing the medium components to remain unwashed so that the probiotic culture is included.

As the conditions for the heat treatment, for example, the heating temperature is usually 60 to 300°C, preferably 60 to 200°C, more preferably 60 to 150°C, still more preferably 60 to 140°C, further preferably 60 to 130°C, More preferably 60 to 120°C, more preferably 60 to 110°C, still more preferably 60 to 100°C, still more preferably 70 to 100°C, still more preferably 70 to 90°C, particularly preferably 75 to 85°C.

A heat treatment condition of 60° C. or higher is preferable because the nutrient cells of the probiotics are sterilized. In addition, it is preferable to set the heat treatment condition to 300° C. or lower because the probiotics remain without being carbonized.

The heat treatment time is usually 0.01 to 120 minutes, preferably 0.015 to 60 minutes, more preferably 0.02 to 40 minutes, still more preferably 0.025 to 30 minutes, still more preferably 0.03. to 25 minutes, more preferably 0.03 to 20 minutes. Heating for 5 minutes or more is particularly preferred. A heat treatment time of 5 minutes or longer kills the nutrient cells of the probiotics. In addition, it is preferable to set the heat treatment time to 120 minutes or less because heat denaturation can be suppressed and vegetative cells can be efficiently sterilized.

The optimum heat treatment time is, for example, 0.2 to 120 minutes, preferably 0.2 to 60 minutes, more preferably 0.2 to 40 minutes for heat treatment in a low temperature range (60 to 100 ° C.). , more preferably 0.2 to 30 minutes, more preferably 0.2 to 25 minutes, particularly preferably 0.2 to 20 minutes.

In addition, the optimum heat treatment time for heat treatment in a high temperature range (100 to 300 ° C.) is, for example, 0.01 to 0.5 minutes, preferably 0.015 to 0.5 minutes, more preferably It can be 0.02 to 0.5 minutes, more preferably 0.025 to 0.5 minutes, still more preferably 0.03 to 0.5 minutes, particularly preferably 0.03 to 0.5 minutes.

For example, the heat treatment of probiotics is preferably carried out at 80°C for 10 minutes or at 90°C for 15 seconds.

A heat treatment method is not particularly limited. For example, the obtained cells can be heated under predetermined conditions using a heat sterilizer such as a plate sterilizer, a tubular sterilizer, a direct heating sterilizer, and a jacketed tank.

In order to exert a defecation promoting effect on infants, the number of probiotic bacteria to be ingested is, for example, 1×10 ⁸ cfu or more per day, 1×10 ⁸ to 1×10 ¹² cfu, 1× 10 ⁸ to 1×10 ¹¹ cfu, 5×10 ⁸ to 5×10 ¹¹ cfu, 1×10 ⁹ to 1×10 ¹¹ cfu, 1×10 ⁹ to 1×10 ¹⁰ cfu, 5×10 ⁹ to 5×10 ¹⁰ cfu, 6×10 ⁹ to 4×10 ¹⁰ cfu, 7×10 ⁹ to 3×10 ¹⁰ cfu, 8×10 ⁹ to 2×10 ¹⁰ cfu, 9×10 ⁹ to 2×10 ¹⁰ cfu.

In addition, the period of continuous intake of the agent of the present invention shall be two weeks or longer. Preferably, it is 3 weeks or more. The period of continuous intake of the agent of the present invention is preferably 2 weeks or more and less than 8 weeks, more preferably 3 weeks or more and less than 8 weeks, further preferably 3 weeks or more and less than 6 weeks, and particularly preferably 3 weeks or more and less than 5 weeks. .

When the period of ingestion of the agent of the present invention is within the above range, a higher defecation promoting effect is exhibited in infants. In particular, it is preferable to continuously ingest probiotics with a bacterial count of 1×10 ⁸ cfu or more per day for 2 weeks or more, and to continue ingesting 1×10 ⁸ cfu or more and 1×10 ¹¹ cfu or less per day for 2 weeks or more. is more preferable, and it is even more preferable to continuously ingest 1×10 ⁹ cfu or more and 1×10 ¹⁰ cfu or less per day for 2 weeks or longer.

The agent of the present invention is administered to infants from 0 to 10 days after birth. Preferably, administration is initiated in infants between 3 and 7 days of life, more preferably between 4 and 6 days of age.

In addition, the agent of the present invention exhibits a defecation-promoting effect on infants by starting administration to infants soon after birth and then continuing administration. The effect continues, for example, from the start of administration until 12 months after birth, more preferably from the start of administration until 18 months after birth.

The agent of the present invention can be used alone, or can be used as a defecation promoting composition for infants of the present invention (hereinafter also referred to as the composition of the present invention) by mixing with other ingredients. can. The compounding amount of the agent of the present invention in the composition of the present invention can be arbitrarily determined according to its purpose, use, form, dosage form, symptoms, body weight, and the like.

The agent of the present invention can be blended, for example, in a content of 0.001 to 90% (w/w), more preferably in a content of 0.001 to 50% (w/w), based on the entire composition of the present invention. can be blended with

The agent of the present invention or the composition of the present invention can be administered either orally or parenterally (intramuscular, subcutaneous, intravenous, suppository, transdermal, etc.).

The agent of the present invention or the composition of the present invention can be used in the form of pharmaceuticals or food and drink. For example, direct administration as a pharmaceutical or direct ingestion as a food for special dietary use such as a food for specified health use or as a nutritional food is expected to exert a defecation-promoting effect on infants. Examples of foods for special uses and nutritious foods include powdered milk, liquid food, food for the sick, powdered milk for infants, powdered milk for infants, powdered milk for lactating women, supplements, and nutrient-enriched foods.

When the agent of the present invention or the composition of the present invention is used as a pharmaceutical, examples of forms include oral administration in formulations such as tablets, coated tablets, capsules, granules, powders, solutions, syrups, and emulsions. be able to. These various preparations are prepared according to a conventional method by adding dispersants, excipients, binders, disintegrants, lubricants, coloring agents, flavoring agents, solubilizers, Oral preparations can be prepared by formulating with known adjuvants that are commonly used in the technical field of pharmaceutical formulations, such as suspending agents and coating agents.

Above all, it is preferable to use the agent of the present invention as a composition mixed with a dispersant. Examples of dispersants include milk proteins such as casein, soybean proteins, peptides, amino acids, starch, dextrin, xylan, oligosaccharides, sugars (glucose, lactose, sucrose, galactose, maltose), sugar alcohols (trehalose, xylitol, erythritol, palatinose, trehalulose, xylose) and the like. Among dispersants, dextrin is particularly preferred. This is because the use of dextrin as a dispersing agent enables powder to be granulated, facilitates handling such as dispersing and dissolving, and enables long-term storage.

The dispersant, especially the dextrin, is preferably in the form of granules. This is because the granules not only have high solubility, but also have high filling performance, so that they can be packaged in small amounts. It also has the manufacturing advantage of enabling accurate packaging with no variation in mass distribution just by dropping it on the packaging material and packaging it.

In the composition of the present invention, the mass ratio of the agent of the present invention to the dispersant is preferably 1:100 to 1:2, more preferably 1:100 to 1:10, still more preferably 1:100. ~1:20. This is because the infection-preventing agent of the present invention can be efficiently dispersed by setting the mass ratio of the agent of the present invention to the dispersant within the above range.

For example, when the composition of the present invention containing the agent of the present invention and dextrin is orally administered, the composition of the present invention is subdivided into predetermined amounts, packaged in packaging materials, and packaged (infant defecation promoting package) before administration. In the present invention, it is preferable to package each amount for one-time use, or to pack a plurality of items for one-time use, and it is particularly preferable to package one-time use amount.

When adding the agent and composition of the present invention to food compositions, various foods and drinks (milk, soft drinks, fermented milk, yogurt, cheese, bread, biscuits, crackers, pizza crust, powdered milk, liquid diet, disease food for infants, powdered milk for infants, food such as powdered milk for infants, food such as powdered milk for breastfeeding women, nutritional food, etc.) and ingested. The agents and compositions of the present invention can be used as they are or mixed with other foods or food ingredients, and can be used in accordance with conventional methods for food compositions.

Moreover, as for its properties, it may be in the form of food or drink that is commonly used, such as solid (powder, granules, etc.), paste, liquid or suspension. By taking such a form, the agent of the present invention can be ingested without feeling any psychological disturbance.

The agent or composition of the present invention can also be used as a composition in which water, proteins, carbohydrates, lipids, vitamins, minerals, organic acids, organic bases, fruit juices, flavors, etc. are mixed without side effects. can.

Examples of proteins include whole milk powder, skim milk powder, partially skim milk powder, casein, whey powder, whey protein, whey protein concentrate, whey protein isolate, α-casein, β-casein, κ-casein, β-lactoglobulin. , α-lactalbumin, lactoferrin, soy protein, chicken egg protein, meat protein and other animal and plant proteins, hydrolysates thereof; butter, milk minerals, cream, whey, non-protein nitrogen, sialic acid, phospholipids, lactose, etc. and various milk-derived components. Any drug, food or drink that has been used without side effects can be applied. Moreover, these components can be used in combination of 2 or more types.

Carbohydrates include, for example, saccharides, processed starch (dextrin, soluble starch, British starch, oxidized starch, starch ester, starch ether, etc.), dietary fiber, and the like.

Lipids include, for example, lard, fish oil, fractionated oils thereof, hydrogenated oils, transesterified oils and other animal fats; palm oil, safflower oil, corn oil, rapeseed oil, coconut oil, fractionated oils thereof; Vegetable oils such as hydrogenated oils and transesterified oils are included.

Examples of vitamins include vitamin A, carotene, vitamin B group, vitamin C, vitamin D group, vitamin E, vitamin K group, vitamin P, vitamin Q, niacin, nicotinic acid, pantothenic acid, biotin, inositol, choline. , and folic acid.

Minerals include, for example, calcium, potassium, magnesium, sodium, copper, iron, manganese, zinc, and selenium.

Organic acids include, for example, malic acid, citric acid, lactic acid, and tartaric acid. Any drug, food or drink that has been used without side effects can be applied. Moreover, these components can be used in combination of 2 or more types.

When providing the agent of the present invention or the composition of the present invention as a food or drug, the production method can be performed by a method well known to those skilled in the art. A person skilled in the art would understand the process of mixing the probiotics or processed product of the present invention with other ingredients, the molding process, the sterilization process, the fermentation process, the baking process, the drying process, the cooling process, the granulation process, the packaging process, etc. It is possible to produce a desired food or medicine by combining them appropriately.

Furthermore, the agent of the present invention or the composition of the present invention can be applied to foods with health claims and foods for sick people. The Foods with Health Claims System was established to cover not only ordinary foods but also foods in the form of tablets, capsules, etc., based on domestic and international trends and consistency with the existing Foods for Specified Health Uses system. It consists of two types: Food for Specified Health Uses (individual permission type) and Food with Nutrient Function Claims (standard type). By directly ingesting the agent or composition of the present invention as a food for special use such as a food for specified health use or as a food with nutrient function claims, it is expected that the agent or composition of the present invention will exhibit an infection-preventing effect.

Examples of forms in which the agent and composition of the present invention are added to infant formula include infant formula, peptide milk, follow-up milk, growing-up milk, low birth weight infant formula, lactose-free powder, and low sodium. Examples include oral compositions for preventing infection for infants, such as special powdered milk and powders added to mother's milk, and are not particularly limited as long as the effects and efficacy of the present invention can be expected. The agent and composition of the present invention can be added to foods and drinks other than infant formula without limitation. For example, yogurt and confectionery.

The probiotics, which are the active ingredients of the present invention, may be used as additives for pharmaceutical compositions, foods and drinks that are expected to have few side effects due to dietary habits, or compositions that can be expected to protect against infection. , orally or by gavage.

The probiotics, which are the active ingredients of the present invention, exhibit the above-described excellent effects and efficacy not only for humans but also for mammals (mammals). Accordingly, the present invention also relates to feeds and feed additives containing probiotics as an active ingredient, in particular to milk powders and milk powder additives for feeding mammals.

The present invention will be described in more detail below with reference to examples. However, the present invention is not limited to these examples.

As a sample, a viable bacterial preparation containing Bifidobacterium bifidum OLB6378 strain (accession number: NITE BP-31) (trade name “Meiji Bifidobacterium OLB6378”; viable count of 5 × 10 ⁹ cfu per tube (0.5 g)) 0.5 g was used.
Subject patients were divided into two groups, a sample-administered group (n=15) and a non-administered group (n=15). In the administration group, administration of the sample was started at the age of 5 days after birth, and the sample was continuously administered once in the morning and evening (twice a day) every day until the age of 1 month after birth. The sample was dissolved in 2 mL of plain hot water, and 1 mL of the solution was orally administered using a dropper. On the other hand, no sample was administered to the non-administration group.

Both groups were examined at a hospital visit at 1 year of age (12 to 13 months old), and the percentage of days with defecation until 1 year of age was examined using the following formula. In addition, the same test was performed on patients who dropped out during the test, and n=15 for both the sample-administered group and the non-administered group.
Percentage of days with bowel movements (%)
= {number of days with bowel movements / (number of days with bowel movements + number of days without bowel movements)} x 100
Here, the number of days with defecation refers to the number of days with defecation from the start of the test to the age of 1 year, and the number of days without defecation refers to the number of days from the start of the test to the age of 1 year. Means the number of days without a bowel movement in between.

As a result of the test, the percentage of days with defecation was 84.0% in the non-administration group, while it was 92.4% in the administration group, which is significantly higher in the administration group than in the non-administration group. It became (p = 0.034). From these results, it was found that defecation can be promoted in infants by starting the administration of probiotics to infants on the 0th to 10th day of birth and continuing the intake for two weeks or more.

There was no significant difference between the sample administration group and the non-administration group in terms of the number of diarrhea episodes and the number of days with diarrhea. It turned out not to be the result.

Claims (9)

A defecation stimulant for infants containing probiotics, which is used to start administration to infants on the 0th to 10th day of birth and continue to take it for 2 weeks or more. 2. The defecation aid for infants according to claim 1, wherein said probiotic is Bifidobacterium or Lactobacillus. 3. The defecation aid for infants according to claim 2, wherein said Bifidobacterium is Bifidobacterium bifidum. The defecation promoting agent for infants according to claim 2, wherein the Bifidobacterium is Bifidobacterium bifidum OLB6378 strain (Bifidobacterium bifidum, accession number: NITE BP-31). The defecation promoting agent for infants according to any one of claims 1 to 4, wherein the probiotics are live bacteria. The defecation promoting agent for infants according to any one of claims 1 to 5, which is used so as to ingest the probiotic with a bacterial count of 1 x 10 ⁸ cfu or more per day. The defecation promoting agent for infants according to any one of claims 1 to 6, for promoting defecation in infants up to 18 months of age. A defecation promoting composition for infants containing the defecation promoting agent for infants according to any one of claims 1 to 7. A defecation-promoting package for infants, wherein the defecation-promoting composition for infants according to claim 8 is packaged in a packaging material.