阅读说明：本技术 呼吸系统疾病预防或缓解用组合物 (Composition for preventing or alleviating respiratory diseases ) 是由 伊藤利洋 平工明里 高桥幸子 岩渊纪介 村田麻衣 于 2018-12-06 设计创作，主要内容包括：本发明提供一种安全性高、用于通过使妊娠期和/或哺乳期的母体摄取来预防该母体所生的婴幼儿的呼吸系统疾病的组合物。一种呼吸系统疾病预防用组合物,其以双歧杆菌属细菌为有效成分,该组合物被给予至妊娠期和/或哺乳期的母体,且用于预防该母体所生的婴幼儿的呼吸系统疾病。该组合物尤其适合用于降低由于所述母体处于大气污染环境下和/或暴露于二手烟的环境下而提高的、所述婴幼儿的所述呼吸系统疾病的罹患风险。(The present invention provides a composition which is highly safe and is intended for preventing respiratory diseases in infants born to the mother by ingestion to the mother during the gestation and/or lactation period. A composition for preventing respiratory diseases, which contains a bacterium belonging to the genus Bifidobacterium as an active ingredient, is administered to a mother during pregnancy and/or lactation and is used for preventing respiratory diseases in infants and young children born to the mother. The composition is particularly suitable for reducing the risk of developing said respiratory disease in said infant, which is increased by exposure of said mother to atmospheric pollution and/or to second-hand smoke.)

1. A composition for preventing or alleviating respiratory diseases, which comprises a bacterium belonging to the genus Bifidobacterium as an active ingredient,

the composition is administered to a mother during pregnancy and/or lactation, and is used for preventing or alleviating respiratory diseases in infants born to the mother.

2. The composition according to claim 1, wherein the respiratory disease is a respiratory disease mediated by natural lymphocytes of type 2.

3. The composition according to claim 1 or 2, wherein the disease is caused or exacerbated by one of the factors of the mother being in an atmosphere contaminated environment.

4. A composition according to any one of claims 1 to 3, wherein the respiratory disease is asthma.

5. The composition according to any one of claims 1 to 4, wherein the respiratory disease is steroid-resistant asthma.

6. The composition according to any one of claims 1 to 5, wherein the bacterium of the genus Bifidobacterium is Bifidobacterium breve.

7. The composition according to any one of claims 1 to 6, wherein the Bifidobacterium bacteria is Bifidobacterium breve M-16V (NITE BP-02622).

8. The composition according to any one of claims 1 to 7, wherein the composition is a food or beverage composition.

9. The composition of any one of claims 1 to 7, wherein the composition is a pharmaceutical composition.

Technical Field

The present invention relates to a composition for preventing or alleviating respiratory diseases.

Background

It is known that the living environment of a pregnant woman sometimes has an impact on the risk of respiratory diseases in the child after birth. For example, exposure of a pregnant mother to atmospheric pollution has been reported to aggravate asthma in the born child (non-patent document 1). In addition, it has been reported that a child born by a mother who has second-hand smoke in pregnancy is remarkably apt to develop asthma compared with a child born by a mother who has no second-hand smoke (non-patent document 2). Therefore, considering the risk of future respiratory diseases of the fetus, it is preferable that the pregnant woman live in an environment as clean as possible.

In addition, means are being developed to address the risk of diseases after birth of the fetus during the pregnancy stage. For example, patent document 1 below discloses a prophylactic agent for allergic diseases in infants, which is characterized by administering bacteria of the genus bifidobacterium to pregnant and lying-in women and their children.

Disclosure of Invention

Problems to be solved by the invention

As described above, it is preferable that the pregnant woman live in an environment as clean as possible, but it is not easy to change the living environment in many cases. In particular, it is often difficult to exclude environmental factors such as exposure to atmospheric pollution and exposure to second-hand smoke.

It is therefore an object of the present invention to provide a new means for addressing the risk of respiratory diseases in children.

Means for solving the problems

The present inventors have conducted intensive studies and, as a result, have found that the risk of respiratory diseases in infants and young children can be addressed by administering bacteria belonging to the genus bifidobacterium to the mother in pregnancy and/or lactation. Namely, the present invention provides the following inventions.

[1] A composition for preventing or alleviating respiratory diseases, which comprises a bacterium belonging to the genus Bifidobacterium as an active ingredient,

the composition is administered to a mother during pregnancy and/or lactation, and is used for preventing or alleviating respiratory diseases in infants born to the mother.

[2] The composition according to the above [1], wherein the respiratory disease is a respiratory disease mediated by natural lymphocyte type 2.

[3] The composition according to the above [1] or [2], wherein the disease is developed or worsened by exposure of the mother to an atmosphere contaminated with the above-mentioned substance.

[4] The composition according to any one of the above [1] to [3], wherein the respiratory disease is asthma.

[5] The composition according to any one of the above [1] to [4], wherein the respiratory disease is steroid-resistant asthma.

[6] The composition according to any one of the above [1] to [5], wherein the bacterium belonging to the genus Bifidobacterium is Bifidobacterium breve.

[7] The composition according to any one of the above [1] to [6], wherein the bacterium belonging to the genus Bifidobacterium is Bifidobacterium breve M-16V (NITE BP-02622).

[8] The composition according to any one of the above [1] to [7], wherein the composition is a food or beverage composition.

[9] The composition according to any one of the above [1] to [7], wherein the composition is a pharmaceutical composition.

ADVANTAGEOUS EFFECTS OF INVENTION

According to the present invention, respiratory diseases in infants and young children born to the mother can be prevented or alleviated by administering bacteria belonging to the genus bifidobacterium to the mother during the gestation and/or lactation period.

The effects of the present invention are not limited to the effects described herein, and may be any of the effects described in the present specification.

Drawings

Fig. 1 is a graph showing the average value of the proportion of eosinophils in leukocytes in bronchoalveolar lavage fluid of the non-treated group, control group, and ingested group.

Fig. 2 is a graph showing the mucin scores of the control group and the ingested group.

FIG. 3 is a graph showing the proportion of ILC2 in Lin-CD45+ cells of the control group and the uptake group.

Detailed Description

Next, preferred embodiments of the present invention will be described. However, the present invention is not limited to the following preferred embodiments, and can be freely modified within the scope of the present invention. In the present specification, unless otherwise stated, percentages are expressed on a mass basis.

< composition for preventing or alleviating respiratory diseases >

The composition for preventing or alleviating a respiratory disease of the present invention contains a bacterium belonging to the genus bifidobacterium as an active ingredient. The composition is administered to a mother during pregnancy and/or lactation, and is used for preventing or alleviating respiratory diseases in infants born to the mother.

The composition for preventing respiratory diseases of the present invention can prevent respiratory diseases of infants born to the mother. Particularly, it is effective in reducing the respiratory diseases of the mother who has to live in an atmosphere polluted environment during pregnancy and/or lactation and the child who is born by the mother who is inevitably exposed to second-hand smoke.

The composition for preventing or alleviating respiratory diseases of the present invention can exert the preventing or alleviating effect only by being administered to the mother only during the pregnancy and/or lactation period. Therefore, the respiratory disease preventing or alleviating composition of the present invention may not be administered to children born by the mother. Administration of the composition to infants is time consuming. The composition of the present invention can be easily used because it is not administered to children born to the mother.

It is considered that the effect of the present invention is exerted by the fact that the intestinal flora and/or breast milk of a pregnant and/or lactating mother changes by ingestion of bacteria belonging to the genus bifidobacterium, and this change affects the constitution of the child born.

As to the influence of the intestinal flora of the mother and/or breast milk on the constitution of the born child, for example, the following influences are reported. Intestinal bacteria of pregnant mothers are reported to be associated with methylation of Diabetes-associated genes in children (Tachibana K et al J Diabetes investig.2017; 8(4): 550-. This is considered to be because metabolites and the like produced by intestinal bacteria of the mother affect epigenetic control in the development of the fetus via the placenta. It is also known that when born vaginally, a child inherits a portion of the mother's intestinal flora. Gradually knowing: the mother's intestinal flora, which may affect the infant's intestinal flora, affects the future development of obesity, diabetes, non-alcoholic fatty liver disease, allergic diseases, etc. of the child (Mulligan CM, Friedman JE, J endocrinol.2017; 235(1): R1-R12.). But also knows that: the mother's milk contains ingredients that prevent the child from suffering from allergies. The intake of probiotic bacteria by the lactating mother has been shown to affect the constitution of the child via breast milk (Munblit D et al. Clin Exp allergy.2015; 45(3): 583-. In conclusion, the intestinal flora and/or breast milk of the mother influences the constitution of the born child. In the present invention, it is also considered that the intestinal flora and/or breast milk of the mother affect the constitution of the child, and as a result, respiratory diseases can be prevented or alleviated.

In the present invention, "prevention" includes: preventing onset of disease, reducing the risk of onset of disease, and reducing the likelihood of onset of disease; and preventing the occurrence of at least one symptom of the disease, reducing the risk of the occurrence of at least one symptom of the disease, and reducing the likelihood of the occurrence of at least one symptom of the disease.

In the present invention, "alleviating" includes: reducing the extent of the disease, slowing the progression of the disease, and arresting the progression of the disease; and, alleviating at least one symptom of the disease, slowing exacerbation of at least one symptom of the disease, and arresting at least one symptom of the disease. At the time of administering the composition of the present invention to a mother, the infant that the mother wants to live or the infant that the mother has born may not yet suffer from a respiratory disease to be alleviated by the present invention. By allowing a mother in pregnancy and/or lactation to ingest the composition of the present invention, the respiratory disease can be alleviated when the child to whom the mother wants to live or the child who has born the mother will suffer the respiratory disease in the future. That is, the composition of the present invention can be used to thus alleviate respiratory diseases of future onset.

In the present invention, the respiratory disease may preferably be a respiratory disease mediated by natural lymphocyte type 2 (Group2 lnnate lymphoidcell, hereinafter also referred to as "ILC 2"). The composition of the present invention is particularly suitable for the prevention or alleviation of the respiratory disease. The respiratory disease in the present invention may be, for example, asthma, bronchitis or pneumonia mediated by type 2 natural lymphocytes, and particularly asthma mediated by type 2 natural lymphocytes. Examples of asthma mediated by type 2 natural lymphocytes include steroid-resistant asthma.

In the present invention, the respiratory disease may be, for example, hyperplasia of airway epithelial goblet cells and/or a disease accompanied by eosinophilia in bronchi. The compositions of the present invention are particularly suitable for preventing or alleviating such diseases.

In the present invention, examples of respiratory diseases include, but are not limited to, asthma, bronchitis, environmental lung diseases, chronic bronchitis, COPD (chronic obstructive pulmonary disease), allergic pneumonia, and eosinophilic pneumonia.

In the present invention, the disease may be one which is caused to develop or worsen when the parent is in an atmosphere polluted environment. That is, the causative agent or the exacerbating agent of the disease may be only the causative agent or the exacerbating agent of the disease, or may be other than the causative agent or the exacerbating agent of the disease (for example, genetic agent, physical agent, dietary agent, etc.) of the disease.

In the invention, the parent body can be in an atmosphere pollution environment. That is, when the above-mentioned mother body is in an atmosphere polluted environment, the respiratory diseases of the infant born by the mother body can be prevented and/or alleviated by administering the composition of the present invention to the mother body. In the invention, the parent body is in an atmosphere pollution environment, and the parent body lives in the atmosphere pollution environment. The above-mentioned mother may live in an atmosphere-polluted environment during any period or the whole period in the gestational period, any period or the whole period in the lactation period, or the whole period in the gestational period and the lactation period, or may live in an atmosphere-polluted environment before the gestational period and live in an atmosphere-polluted environment during the gestational period and the lactation period. The composition may be administered in a state where the precursor is exposed to air pollution, or may be administered in a clean space (e.g., a clean room) in an air polluted environment.

< bacterium belonging to the genus Bifidobacterium >

The bacterium belonging to the genus bifidobacterium used in the present invention is not particularly limited as long as the effect of the present invention is not impaired, and known bacterium belonging to the genus bifidobacterium can be used.

Examples of the Bifidobacterium bacteria include Bifidobacterium breve (Bifidobacterium breve), Bifidobacterium longum subsp (Bifidobacterium longum subsp. longum), Bifidobacterium bifidum (Bifidobacterium bifidum), Bifidobacterium adolescentis (Bifidobacterium adolescentis), Bifidobacterium horn (Bifidobacterium anguum), Bifidobacterium odonum (Bifidobacterium bifidum), Bifidobacterium pseudocatenulatum (Bifidobacterium pseudocatenulatum), Bifidobacterium animalis (Bifidobacterium animalis subsp. lactis), Bifidobacterium pseudocatenulatum (Bifidobacterium pseudocatenulatum), Bifidobacterium pseudolongum (Bifidobacterium pseudolongum) and Bifidobacterium pseudolongum (Bifidobacterium bifidum). The bifidobacterium bacteria used in the present invention may be selected from 1 or more species from the above groups, and only 1 species may be used, or any two or more species may be used. Incidentally, Bifidobacterium longum subspecies longum may be simply referred to as Bifidobacterium longum.

Further, among the above-mentioned bacteria belonging to the genus Bifidobacterium, Bifidobacterium breve (Bifidobacterium breve) is preferable, and Bifidobacterium breve (Bifidobacterium breve) M-16V (NITE BP-02622) is more preferable.

Bifidobacterium breve M-16V (NITE BP-02622) was subjected to International deposit based on the Budapest treaty at the national institute of technical evaluation, national institute of technology, 1/26.2018, patent microorganism Collection (NPMD) (postal code: 292-.

The bacterium belonging to the genus bifidobacterium used in the present invention may be a mutant of the bacterium belonging to the genus bifidobacterium as long as the bacterium has the characteristics that can achieve the object of the present invention. Such a mutant can be constructed by introducing a mutation into the bacterium belonging to the genus Bifidobacterium in a non-artificial manner. Alternatively, the bacterium may be constructed by introducing mutation into the bacterium by treatment with a mutagen such as UV, or may be constructed by introducing mutation into the bacterium by various genetic manipulation methods.

In the present invention, when the mutant is used as a bacterium belonging to the genus bifidobacterium, the mutant preferably has the same bacteriological properties as the bacterium belonging to the genus bifidobacterium and has an inhibitory effect on ILC2 production which is equal to or higher than that of the bacterium belonging to the genus bifidobacterium. Whether or not a certain mutant has "the same or greater ILC2 production inhibitory effect" as that of the bacterium belonging to the genus bifidobacterium "can be confirmed, for example, by measuring the proportion of ILC2 in lung tissue by the method described in the test examples described below.

The bacterium belonging to the genus bifidobacterium used in the present invention can be easily obtained by culturing the bacterium belonging to the genus bifidobacterium by a conventional method. The bacterium belonging to the genus Bifidobacterium of the present invention may be used in the form of the above-mentioned bacterium itself (cell body), a culture of the above-mentioned bacterium, a purified product isolated from the culture of the above-mentioned bacterium (for example, culture supernatant), or a treated product of the cell body of the above-mentioned bacterium.

That is, the bacterium belonging to the genus Bifidobacterium may be used as it is, or a culture obtained by culturing the bacterium belonging to the genus Bifidobacterium may be used as it is. The bacterium belonging to the genus bifidobacterium used in the present invention may be a live bacterium or a dead bacterium, or may contain both a live bacterium and a dead bacterium.

Examples of the treated product of the bacterial cells include a disrupted product of cells obtained by partially or completely disrupting cell walls and cell membranes of the bacterial cells by a conventional method such as ultrasonic treatment or homogenizer treatment. The disrupted cell product may be the whole or a part of the disrupted cell product, or may be a fraction obtained by centrifuging the supernatant after disruption, partially purifying the supernatant by treatment with ammonium sulfate, or the like, or a product obtained by concentrating the supernatant.

As shown in the examples, the bacteria belonging to the genus bifidobacterium used in the present invention have the following effects: the excessive production of ILC2 in lung tissue of a newborn infant is suppressed by allowing the mother to take the bacterium belonging to the genus Bifidobacterium during pregnancy or lactation. That is, by ingesting bacteria belonging to the genus bifidobacterium during pregnancy or lactation in accordance with the present invention, respiratory diseases caused by ILC2 in newborn infants can be effectively prevented or alleviated. ILC2 in lung tissue can be measured by the method described in the examples below.

Here, ILC2 refers to a natural lymphocyte type 2 (Group2 inacate lymphoidcell) which is one of lymphocytes, and is activated by IL-25 and IL-33 produced by airway epithelial cells stimulated by atmospheric pollutants, microorganisms, glycolipids, and the like to produce Th2 cytokines (IL-5 and IL-13). The Th2 cytokine triggers eosinophil activation and goblet cell proliferation, leading to asthma symptoms. The proliferation of goblet cells leads to an overproduction of mucin as airway mucus, leading to airway remodeling. Airway remodeling exacerbates the symptoms of chronic respiratory disease (Jantina c. de Groot et al, ERJOpen res, 2015, vol.1 (1)). The composition of the present invention can be used, for example, for preventing exacerbation of chronic respiratory disease. In addition, the compositions of the present invention may be used to prevent or alleviate airway remodeling. In addition, the compositions of the present invention may be used to prevent or alleviate mucin overproduction.

Since asthma symptoms accompanied by overproduction of ILC2 are not symptom-mediated by Th2 cells, conventional prevention or treatment of respiratory diseases based on activity control of Th2 cells is sometimes ineffective. Since the present invention can suppress overproduction of ILC2, it is effective in the prevention or treatment of respiratory diseases in which the prevention or treatment based on the activity control of Th2 cells does not effectively function.

In addition, activation or proliferation of ILC2 has been confirmed as a cause of steroid-resistant asthma (h.kabata et al, nat. commun.,2013,4: 2675). Steroid-resistant asthma is intractable and a serious disease requiring inhaled administration of large doses of steroids. It is also known that: in the case of asthma in children born to pregnant women who smoke, steroid agents used to treat asthma have poor therapeutic efficacy and are likely to become refractory asthma (Robyn T. Cohen et al., J. allergy Clin Immunol.,2010,126(3), 491-.

The composition for preventing or alleviating a respiratory disease of the present invention can suppress the overproduction of ILC2, and therefore is effective for preventing intractable asthma which is steroid-resistant in a respiratory disease.

The bacterium belonging to the genus bifidobacterium used in the present invention is contained in the composition as an active ingredient, and can be used in a wide range of products such as medicines, foods, drinks, feeds, etc. because of its high safety. These products can be produced by using any components for each application as appropriate, and by a known production method suitable for each application.

The bacterium belonging to the genus bifidobacterium used in the present invention may be used as it is, or may be used by mixing with a conventional carrier or diluent acceptable in physiological, pharmaceutical or food and drink.

The bacterium belonging to the genus Bifidobacterium used in the present invention can be used for the production of the above-mentioned various preparations and various compositions.

The bacterium belonging to the genus Bifidobacterium used in the present invention can be used for the prevention or alleviation of allergic diseases. That is, the bacterium belonging to the genus bifidobacterium may be contained as an active ingredient for preventing or alleviating respiratory diseases in infants and young children born to the mother, which is administered to the mother during pregnancy and/or lactation for preventing or alleviating allergic diseases.

< subject to whom composition is administered and administration period >

The subject to which the respiratory disease preventive composition of the present invention is applied is a pregnant and/or lactating mother, and particularly, a pregnant and/or lactating mother that must live in an atmosphere contaminated with air and/or exposed to second-hand smoke may be preferably used. That is, the composition for preventing or alleviating respiratory diseases of the present invention is particularly suitable for reducing the risk of the respiratory diseases of the infant, which is increased by exposure of the mother to the atmosphere and/or the second-hand smoke.

In the present invention, a maternal body refers to a mammal in pregnancy and/or lactation, which is preferably a human being or a pet, more preferably a human being.

Further, the intake of the respiratory disease preventing or alleviating composition of the present invention is preferably continued for a certain period of pregnancy and/or a certain period of lactation. Particularly preferably, the intake of the composition of the present invention is more preferably continued for a certain period in both the gestation period and the lactation period. Preferably the composition of the invention is taken continuously at least during pregnancy, more preferably during pregnancy and during lactation. Desirably, the compositions of the present invention are ingested daily.

For example, the composition for preventing or alleviating respiratory diseases of the present invention is preferably taken from at least 6 days before, more preferably 4 weeks before, further preferably 2 months before, 3 months before, 4 months before, 6 months before, or 8 months before the expected term of delivery to the day of production. In addition, the compositions of the present invention may be taken throughout the pregnancy. Moreover, the intake during the lactation period after birth is preferably continued for 30 days from birth, more preferably 2 months, 3 months, 4 months, 6 months or 8 months, and further preferably 1 year. In addition, the composition of the present invention can be taken throughout lactation.

The composition for preventing or alleviating respiratory diseases of the present invention is administered to a mother only during pregnancy and/or lactation, and can be administered to or ingested by a baby born to the mother. Administration of the composition to infants is time consuming. The composition of the present invention can exert its effect without administering it to children born to the mother, and thus can be easily utilized.

As described above, the respiratory disease preventing or alleviating composition of the present invention can be administered to a mother in pregnancy and/or in lactation who has to live in an atmosphere polluted environment, to reduce the risk of the infant from suffering from the respiratory disease, which is increased by the mother being in the atmosphere polluted environment and/or being exposed to second-hand smoke.

Here, the atmospheric pollution environment in the present specification means: the atmosphere is polluted by the atmospheric pollutants such as particulate matter PM2.5 and the like. Specific examples of the environmental conditions relating to air pollution include the standards specified in article 1 of article 16 of the basic environmental act of japan. With respect to the environmental conditions, the terms specify: formulated as a hope of being maintained in protecting human health and maintaining a living environmentThe reference of (1). As the expected standard, regarding air pollution, the annual average concentration of particulate matter PM2.5 in the atmosphere is specified to be 15 μ g/m³The average concentration at 24 hours was 35. mu.g/m³The following environmental benchmarks. An environment exceeding the environmental standard can be exemplified as the air pollution environment in the present invention.

The particulate matter PM2.5 is fine particles having a particle diameter of 2.5 μm or less suspended in the atmosphere. As PM2.5, there may be mentioned: directly discharged due to combustion of matter, etc.; gaseous atmospheric pollutants such as sulfur oxides (SOx), nitrogen oxides (NOx), and Volatile Organic Compounds (VOC) are mainly formed into particles by chemical reactions in the ambient atmosphere. As the generation source of PM2.5, there can be mentioned: soot from boilers, incinerators, and the like; dust from coke ovens, mineral dumps, etc.; exhaust gas of automobiles, ships, aircrafts, and the like. In addition, PM2.5 is also produced in nature such as soil, ocean, volcano, and the like. In addition, tobacco smoke is also typical of PM 2.5.

When health damage due to PM2.5 is studied in animal models, as shown in examples described below, the air pollution environment due to PM2.5 can be reproduced using petroleum burning ash (ROFA) containing nickel, vanadium, and zinc as main components (non-patent document 1).

< pharmaceutical composition >

The composition for preventing or alleviating respiratory diseases of the present invention can be used as a pharmaceutical composition. The pharmaceutical composition of the present invention can be used for preventing or alleviating respiratory diseases in infants and young children born to a mother by administering to the mother in pregnancy and/or lactation. As respiratory diseases, bronchial asthma and steroid-resistant asthma can be exemplified.

In addition, since the pharmaceutical composition of the present invention contains, as an active ingredient, a bacterium belonging to the genus bifidobacterium and/or a culture of the bacterium (for example, a culture supernatant of the culture of the bacterium and/or a treated cell product of the bacterium) which has been used as an oral composition for many years, it can be administered to patients suffering from various diseases with great care. In addition, bacteria belonging to the genus bifidobacterium are also present in the intestinal tract of animals, and therefore the following effects can be expected in the present invention: even if administered continuously for a long period of time, the composition is not likely to cause side effects. Therefore, the composition of the present invention can be taken with care even during pregnancy or lactation.

When the composition for preventing or alleviating respiratory diseases of the present invention is used as a pharmaceutical composition, the pharmaceutical composition can be administered by either oral administration or non-oral administration, and can be appropriately prepared into a desired dosage form according to the administration method. For example, in the case of oral administration, it can be formulated into solid preparations such as powder, granule, tablet, capsule, etc.; liquid preparations such as solutions, syrups, suspensions, and emulsions. In addition, in the case of parenteral administration, the composition of the present invention may be administered, for example, via a gastric fistula.

In addition, in the case of formulation, ingredients such as excipients, pH adjusters, colorants, flavors, and the like, which are generally used in formulation, may be used in the pharmaceutical composition of the present invention. In addition, a component known or discovered in the future that has an effect of preventing, ameliorating and/or treating a respiratory disease or a symptom thereof may be used in the pharmaceutical composition of the present invention as long as the effect of the present invention is not impaired.

The formulation may be carried out by a known method according to the dosage form. In the preparation, the preparation can be carried out by appropriately compounding a preparation carrier.

The amount of the pharmaceutical composition of the present invention to be ingested or administered can be suitably selected depending on the dosage form, and for example, the amount of the bacterium belonging to the genus Bifidobacterium is preferably 1 × 10 per 1 day of 1kg body weight⁵～1×10¹²CFU/kg body weight/day, more preferably 1 × 10⁷～1×10¹¹CFU/kg body weight/day, more preferably 1 × 10⁸～1×10¹⁰CFU/kg body weight/day. Alternatively, the amount of intake or administration per individual (Body weight) is preferably 10⁶～10¹⁴CFU/day, more preferably 10⁸～10¹³CFU/day, more preferably 10⁹～10¹²CFU/day.

The intake amount or administration amount of a culture of bacteria belonging to the genus Bifidobacterium, a purified product (for example, culture supernatant) derived from the culture of the bacteria, or a processed product of the bacteria is preferably an intake amount or administration amount in terms of the intake amount or administration amount of the bacteria belonging to the genus Bifidobacterium.

Further, it is preferable to take the pharmaceutical composition of the present invention in pregnancy and/or lactation in the above-mentioned intake amount or administration amount. In addition, it is preferably taken from at least 6 days before, more preferably 4 weeks before, further preferably 2 months before, 3 months before, 4 months before, 6 months before or 8 months before the predicted term of labor to the day of labor. In addition, the pharmaceutical composition of the present invention may be taken throughout the pregnancy. Moreover, the intake during the lactation period after birth is preferably continued for 30 days from the day of production, more preferably 2 months, 3 months, 4 months, 6 months or 8 months, and further preferably 1 year. In addition, the pharmaceutical composition of the present invention can be taken throughout lactation.

The content of bacteria belonging to the genus Bifidobacterium in the pharmaceutical composition of the present invention can be appropriately selected based on the above-mentioned intake amount or administration amount, and is set to 1 × 10, for example³～1×10¹³CFU/g or 1 × 10³～1×10¹³CFU/mL, preferably set to 1 × 10⁷～1×10¹¹CFU/g or 1 × 10⁷～1×10¹¹CFU/mL, more preferably 1 × 10⁸～1×10¹⁰CFU/g or 1 × 10⁸～1×10¹⁰CFU/mL. In the case where the bacterium is a dead bacterium, the CFU may be replaced with a cell number (cells).

The content of the culture of bacteria belonging to the genus Bifidobacterium, the isolated and purified product (for example, culture supernatant) derived from the culture of the bacteria, and the processed product of the cells of the bacteria is preferably the above content in terms of the content of the bacteria belonging to the genus Bifidobacterium.

As the formulation vehicle, various organic or inorganic vehicles can be used depending on the formulation. Examples of the carrier in the case of a solid preparation include an excipient, a binder, a disintegrant, a lubricant, a stabilizer, a flavoring agent, and the like.

Examples of the excipient include: sugar derivatives such as lactose, white sugar, 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 methylcellulose, carboxymethyl cellulose, and calcium carboxymethyl cellulose; acacia gum; (ii) a glucan; pullulan; silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, magnesium aluminate metasilicate, etc.; phosphate derivatives such as calcium phosphate; carbonate derivatives such as calcium carbonate; sulfate derivatives such as calcium sulfate, and the like.

Examples of the binding agent include, in addition to the above excipients: gelatin; polyvinylpyrrolidone; polyethylene glycol, and the like.

As the disintegrant, in addition to the above excipients, for example: chemically modified starch or cellulose derivatives such as croscarmellose sodium, sodium carboxymethyl starch, and crospolyvinylpyrrolidone.

Examples of the lubricant include: talc; stearic acid; metal stearates such as calcium stearate and magnesium stearate; colloidal silicon dioxide; waxes such as magnesium aluminum silicate (Veegum), spermaceti; boric acid; a dihydric alcohol; carboxylic acids such as fumaric acid and adipic acid; sodium carboxylates such as sodium benzoate; sulfates such as sodium sulfate; leucine; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acids such as silicic anhydride and silicic acid hydrate; starch derivatives, and the like.

Examples of the stabilizer include: parabens such as methyl paraben and propyl paraben; alcohols such as chlorobutanol, benzyl alcohol, and phenethyl alcohol; benzalkonium chloride; acetic anhydride; sorbic acid, and the like.

Examples of the taste-modifying and deodorizing agent include: sweetening agents, acidulants, flavors, and the like.

In the case of a liquid preparation for oral administration, carriers include: solvents such as water, and flavoring agents.

< food and drink composition >

Further, the composition for preventing or alleviating respiratory diseases of the present invention can be used as a food or beverage composition. The food or beverage composition of the present invention can be produced by adding a bacterium belonging to the genus bifidobacterium and/or a culture of the bacterium (for example, a culture supernatant of the culture of the bacterium and/or a treated cell product of the bacterium) to a known food or beverage, or can be produced as a novel food or beverage composition by mixing a bacterium belonging to the genus bifidobacterium and/or a culture of the bacterium (for example, a culture supernatant of the culture of the bacterium and/or a treated cell product of the bacterium) with a raw material for a food or beverage.

The food or drink composition of the present invention may be in any form such as liquid, paste, solid, powder, etc., and examples thereof include: wheat flour products, instant foods, processed agricultural products, processed marine products, processed livestock products, milk/dairy products, fats and oils, base seasonings, compound seasonings/foods, frozen foods, snacks, beverages, and other commercial products.

The food or drink composition defined in the present invention can be provided/sold in the form of a food or drink indicating the following uses (including health care uses): preventing respiratory diseases of infants by maternal intake, reducing the risk of respiratory diseases of infants, relieving symptoms of respiratory diseases of infants, and/or treating respiratory diseases of infants. In addition, "a pregnant woman", "a lactating mother", "a person who is concerned about the risk of respiratory diseases of a fetus or an infant", "a person who is concerned about the risk of asthma of a fetus or an infant", "a person who is concerned about the living environment in pregnancy or lactation", "a person who is concerned about the air in pregnancy or lactation", and the like can be indicated as the objects of ingestion of food and drink and provided and sold.

The "marking" behavior includes all behaviors for notifying a user of the above-described use, and all of them belong to the "marking" behavior of the present invention regardless of the purpose of marking, the content of marking, the object/medium of marking, and the like, as long as they can evoke and analogize the above-described use.

In addition, "marking" is preferably performed by allowing a person in need to directly recognize the expression for the above-described use. Specifically, there may be mentioned: articles in which the above-described uses are described in commodity of food or drink or packages of commodity, such as transfer, delivery, display for transfer or delivery, and import; and a behavior in which the above-mentioned usage is described in an advertisement, a price list, or a transaction document relating to a product, and is displayed or distributed, or the above-mentioned usage is described in information containing the above-mentioned usage, and is provided by an electromagnetic (network, etc.) method.

On the other hand, the content of the label is preferably a label based on a license such as an administration (for example, a label based on various systems defined by an administration to obtain a license and a label based on such a license). It is preferable that such a label is attached to a package, a container, a catalog, a brochure, a promotional material on a sales site such as a Point of purchase (POP), or other material.

Further, the "label" may be a label for a health food, a functional food, a nutritional food for enteral use, a food for special use, a functional food for health care, a food for special health care, a functional food for nutritional use, a functional label food, a quasi drug for drugs, or the like. Among them, there are, in particular, indications permitted by consumer halls, for example, indications permitted by a system for obtaining specific health foods, nutritional functional foods or functional labeled foods, or a system similar thereto. Specifically, a label as a specific health food with a condition, a label mainly indicating an influence on the structure or function of the body, a label for reducing a risk of a disease, a label based on a functionality based on a scientific basis, and the like are exemplified, and more specifically, a label as a specific health food (a label for health care use) and the like specified in a pavilion government (fifty-seventh pavilion government for a thirteen-day pavilion government for twenty-one year, thirty-one month, and the like regarding permission of a specific use label specified by health promotion law are exemplified.

The intake amount of the food or beverage composition of the present invention can be appropriately selected, and for example, the intake amount of bacteria belonging to the genus Bifidobacterium per 1 day of 1kg body weight is preferably 1 × 10⁵～1×10¹²CFU/kg body weight/day, more preferably 1 × 10⁷～1×10¹¹CFU/kg body weight/day, more preferably 1 × 10⁸～1×10¹⁰CFU/kg body weight/day. Alternatively, the amount of intake or administration per individual (Body weight) is preferably 10⁶～10¹⁴CFU/day, more preferably 10⁸～10¹³CFU/day, more preferably 10⁹～10¹²CFU/day. In the case where the bacterium is a dead bacterium, the CFU may be replaced with a cell number (cells).

The intake amount of the culture of bacteria belonging to the genus Bifidobacterium or the processed microbial cell of the bacteria is preferably the intake amount in terms of the intake amount of bacteria belonging to the genus Bifidobacterium.

Further, the food or drink composition of the present invention may be ingested in the above-described ingestion amount or administration amount during pregnancy or lactation, preferably before at least 6 days of the expected term of delivery, more preferably before 4 weeks, further preferably before 2 months, before 3 months, before 4 months, before 6 months, or before 8 months until the day of production. The food or beverage composition of the present invention can be taken throughout pregnancy. Moreover, it is ingested during lactation after birth, preferably continuously for 30 days from the day of production, more preferably for 2 months, 3 months, 4 months, 6 months or 8 months, and further preferably for 1 year. The food or beverage composition of the present invention can be taken throughout lactation.

The content of bacteria belonging to the genus bifidobacterium in the food or beverage composition of the present invention can be appropriately selected based on the above intake amount, and can be, for example, 1 × 10⁶～1×10¹²CFU/g or 1 × 10⁶～1×10¹²CFU/mL, preferably set to 1 × 10⁷～1×10¹¹CFU/g or 1 × 10⁷～1×10¹¹CFU/mL, more preferably 1 × 10⁸～1×10¹⁰CFU/g or 1 × 10⁸～1×10¹⁰CFU/mL. In the case where the bacterium is a dead bacterium, the CFU may be replaced with a cell number (cells).

The present invention also provides the following methods and materials.

[1]

A method for producing a composition for preventing or alleviating respiratory diseases by using a bacterium belonging to the genus Bifidobacterium,

the composition is administered to a mother during pregnancy and/or lactation, and is used for preventing or alleviating respiratory diseases in infants born to the mother.

[2]

A bacterium belonging to the genus Bifidobacterium for preventing or alleviating respiratory diseases,

the bacterium belonging to the genus Bifidobacterium is administered to a mother during pregnancy and/or lactation, and is used for preventing or alleviating respiratory diseases of infants born to the mother.

[3]

A method of preventing or ameliorating a respiratory disease in an infant born to the mother, comprising: bacteria of the genus Bifidobacterium are administered to the mother during pregnancy and/or lactation.