HK1260727A1 - Brain function-improving composition for newborns - Google Patents

Description

Composition for improving brain function for newborn

Cross Reference to Related Applications

The present application enjoys the benefit of priority from Japanese patent application 2016-.

Technical Field

The present invention relates to a composition for improving brain function for a newborn infant.

Background

As humans grow after birth, there is a need to develop brain function properly so that they adapt to and enjoy social life. Development of brain function in adulthood requires development of brain function during development, i.e., prior to adulthood.

Currently, among infant and child-oriented foods, foods containing functional ingredients such as eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) that can be expected to improve brain functions are commercially available. Furthermore, when the food is intended not only for infants and children but also for adults and elderly persons, not only eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) but also many food ingredients are known to have the effect of improving brain function.

Further, among probiotics that exhibit functionality due to ingestion of beneficial microorganisms, an edible composition containing bifidobacterium longum ATCC BAA-9 is known to inhibit a decrease in hippocampal BDNF (brain-derived neurotrophic factor) expression (patent document 1).

Documents of the prior art

Patent literature

Patent document 1: japanese Kohyo publication 2011-517568

Disclosure of Invention

Patent document 1 aims to treat or prevent anxiety and related disorders in adults, and since the effects on developed nerve tissue and the effects on developing nerve tissue cannot be equalized with each other, it cannot be applied to the improvement of brain functions represented by the improvement of nerve-undeveloped infants, particularly newborn infants immediately after birth. In addition, the examples of patent document 1 are directed to the phenomenon caused by infection with mouse whipworm using a mouse animal test system and the phenomenon caused when DSS is administered. In other words, this is a result under special conditions, and even under normal conditions, application to a fully developed healthy adult is difficult.

Since the subsequent growth of a newborn may be affected by side effects when a functional substance having an effect of improving the brain function of an adult is administered to a newborn, in particular, the development of the brain function has been promoted by improving the living environment by strengthening education and guidance.

The purpose of the present invention is to provide a composition for brain function and a brain function-improving agent for a newborn.

The present inventors have now found that the development index can be improved by orally feeding a newborn, particularly a newborn that is newly born, with lactic acid bacteria and/or bifidobacteria. The present invention is based on this finding.

That is, the present invention is as follows:

[1] a composition for improving brain function for a newborn and a brain function improving agent for a newborn, which contain lactic acid bacteria and/or bifidobacteria as an active ingredient (sometimes hereinafter, also referred to as "the composition and agent of the present invention").

[2] The composition and agent according to [1], wherein the effective ingredient is Bifidobacterium.

[3]According to said [1]Or [2]]The composition and agent, wherein the bifidobacteria is Bifidobacterium bifidum (b: (b)Bifidobacterium bifidum)。

[4]According to [1] above]～[3]The composition and agent of any one of, wherein the bifidobacterium is bifidobacterium bifidum OLB6378 strain (b: (b))Bifidobacterium bifidumThe preservation number is: NITE BP-31).

[5] The composition and agent according to any one of the above [1] to [4], wherein the Bifidobacterium is a heat-treated bacterial body.

[6]According to [1] above]～[5]The composition and agent for continuously feeding bacteria in an amount of 10 days ⁸ The number of the bifidobacteria is more than 1 month.

[7] The composition and the reagent according to any one of the above [1] to [6], which is a food.

[8] Use of lactic acid bacteria and/or bifidobacteria for the preparation of a composition for improving brain function for a newborn or a brain function-improving agent for a newborn.

[9] Lactic acid bacteria and/or bifidobacteria for improving neonatal brain function.

[10] A method of improving brain function in a newborn infant, comprising feeding or administering an effective amount of lactic acid bacteria and/or bifidobacteria to a subject in need thereof.

According to the composition and agent of the present invention, in a newborn, particularly, a newborn at birth, a brain function improving effect based on a developmental index improving effect can be expected. Since the lactic acid bacteria and/or bifidobacteria as the active ingredient of the present invention are bacteria contained in food materials that have been taken by humans for many years, the composition and agent of the present invention can improve the developmental index without side effects, and are advantageous in that the newborn can be effectively developed and grown.

Detailed Description

< lactic acid bacteria >

The kind and source of lactic acid bacteria used in the present invention are not limited. Specific examples thereof include Streptococcus such as Streptococcus thermophilus, Lactobacillus such as Lactobacillus bulgaricus, Lactobacillus gasseri, and Lactobacillus acidophilus, lactococcus lactis such as lactococcus lactis, Lactobacillus casei (クレモリス), and Lactobacillus diacetylactis (ジアセチルラクチス), and Leuconostoc.

< Bifidobacterium >

The species and source of bifidobacteria useful in the present invention are not limited. Specifically, for example, Bifidobacterium bifidum (B.bifidum) ((B.bifidum))Bifidobacterium bifidum) Bifidobacterium longum (b) andBifidobacterium longum) Bifidobacterium breve: (A), (B)B.breve) Bifidobacterium adolescentis (B.adolescentis) Bifidobacterium infantis (b.infantis)B.infantis) Bifidobacterium pseudolongum (b) ((b))B.pseudolongum) Bifidobacterium thermophilum (b)B.thermophilum) And so on.

Specifically, the bifidobacterium bifidum includes, for example, bifidobacterium bifidum OLB6378 strain (f) (b)Bifidobacterium bifidumThe preservation number is: NITE BP-31), by using the strain, the composition and the agent of the present invention can be provided.

The present inventors deposited this strain in the national institute of technology and evaluation, the patent microorganism Collection (independent administrative human culture value technical substrate microorganism fungal センター). The deposited content was identified as follows:

the inventors deposited Bifidobacterium bifidum OLB6378 strain (Bifidobacterium bifidum OLB6378)。

(1) The name of the depository institution: national institute of technology evaluation, center for patent deposit of microorganisms

(2) Contact address: 〒 292-0818-thousand-leaf county wood-Dajin-total Sickle foot 2-5-8 (telephone: 0438-20-5580)

(3) The preservation number is as follows: NITE BP-31

(4) Identification mark: bifidobacterium bifidum OLB6378 (C.) (Bifidobacterium bifidum OLB6378)

(5) Original preservation date: 2004, 10 months and 26 days

(6) Transfer to date on budapest treaty-based deposit: 2006, 1 month and 18 days

Bifidobacterium bifidum OLB6378 strain is a gram-positive obligate anaerobacter derived from human infant faeces. When this strain was spread on a BL agar medium (Roche chemical Co., Ltd.) plate and cultured at 37 ℃ for 48 hours under anaerobic conditions using AnaeroPack-Kenki (manufactured by MITSUISI HI GAS CHEMICAL COMPANY, INC.), an opaque round hemispherical glossy colony was formed. In addition, PCR products were observed in PCR using Bifidobacterium bifidumIs/are as followsSpecific primers (symposium of intestinal flora 8, molecular biological detection and identification of intestinal flora, photaoka sufficient, songbu Longwu), specifically, species-specific primers of the 16S rRNA region were used, namely 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). In addition, it has a fermentation ability to galactose, glucose, fructose, lactose and gentiobiose.

As a medium for culturing the strain of the present invention, a medium which is generally used as a medium for lactic acid bacteria and/or bifidobacterium can be used. That is, the medium usable in the present invention is not particularly limited, and any medium may be used as long as it contains a nitrogen source, inorganic substances, and other nutrients in amounts within a predetermined range in addition to the main carbon source. Lactose, glucose, sucrose, fructose, starch hydrolysate, blackstrap molasses, and the like can be used as the carbon source depending on the ability of the bacteria to utilize growth. Organic nitrogen-containing substances such as casein hydrolysate, whey protein hydrolysate, and soybean protein hydrolysate can be used as the nitrogen source. In addition, meat extract, fish meat extract, yeast extract, etc. can be used as a proliferation promoter.

In particular, the bifidobacterium is preferably cultured under anaerobic conditions, and a known technique such as a method of culturing while introducing carbon gas may be applied, but it may be cultured under microaerophilic conditions, batch culture conditions or the like by a conventional liquid static culture or the like. The culture temperature is 25 to 50 ℃, particularly preferably 35 to 42 ℃, but the present invention is not limited thereto, and other temperature conditions may be used as long as the bacteria can grow. The pH of the medium during the culture is preferably maintained at 6.0 to 7.0, but may be other pH conditions as long as the bacteria can grow. The culture time is preferably 3 to 48 hours, more preferably 8 to 24 hours, and particularly preferably 10 to 20 hours, but any other culture time may be used as long as the bacteria can grow.

The obtained microbial cells can be contained in the composition and the agent of the present invention as a treated product of lactic acid bacteria and/or bifidobacteria to be treated as described below. The treated product of lactic acid bacteria and/or bifidobacteria includes a culture product which remains unchanged after completion of the culture, a culture product which is subjected to centrifugation or filtration or the like after completion of the culture, a concentrate thereof, a further processed product in the form of a paste, a dried product obtained by various methods (spray-dried product, freeze-dried product, vacuum-dried product, drum-dried product or the like), a liquid product dispersed in a medium, a diluted product obtained by a diluent, a heat-treated product (heat-treated bacterial cells) which has been heat-treated, a light-irradiated treated product (light-irradiated bacterial cells) obtained by treatment with ultraviolet rays and/or radioactive rays, a drug-treated product (drug-treated bacterial cells) obtained by treatment with a drug (bactericide, antibacterial agent, bacteriostatic agent), a pulverized product obtained by pulverizing the dried product with a mill or the like. Centrifugation, filtration and concentration are carried out by conventional techniques. The drying may be performed, for example, by vacuum drying, spray drying, freeze drying, drum drying, or the like. They are sometimes abbreviated as "lactic acid bacteria and/or bifidobacterium-treated matter" or "treated matter" in the present specification.

The lactic acid bacteria and/or bifidobacteria and the treated products thereof obtained by the above-mentioned methods may be contained in the composition and agent of the present invention as live bacteria as they are, or as heat-treated bacteria followed by being treated with pulverization or without pulverization, alone or as a mixture of plural kinds. If the bacteria are viable bacteria, the effect of proliferation in vivo (in the intestine) after feeding or administration can be expected. If the cells are heat-treated (for example, 0.1ml of a suspension (dispersion) of bifidobacteria after completion of heat treatment is sampled and applied to a petri dish containing a culture medium in which bifidobacteria can grow, and the cells are not formed in the form of colonies (colony) of bifidobacteria even when cultured under anaerobic conditions), it is not necessary to consider the property that bifidobacteria are difficult to survive in the presence of oxygen, and the range of application is expanded as the composition and the reagent of the present invention, which is preferable.

Among them, the bifidobacterium is particularly preferably a live bacterium. It is inferred that by continuously feeding or administering live bifidobacteria to a newborn as described below, the bifidobacteria will be immobilized in the intestine of the newborn and continuously provide the effects of the present invention.

In the present invention, when using a heat-treated bifidobacterium, the heating temperature is, for example, usually 60 to 300 ℃, preferably 60 to 200 ℃, more preferably 60 to 150 ℃, further preferably 60 to 140 ℃, further preferably 60 to 130 ℃, further preferably 60 to 120 ℃, further preferably 60 to 110 ℃, further preferably 60 to 100 ℃, further preferably 70 to 100 ℃, further preferably 80 to 100 ℃, and particularly preferably 85 to 95 ℃ as the heat treatment condition. The heat treatment conditions are preferably 60 ℃ or higher because the vegetative cells of bifidobacteria are killed. Further, the heat treatment conditions are preferably set to 300 ℃ or lower because the bifidobacteria are not carbonized and remain.

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, and particularly preferably 0.03 to 20 minutes. It is preferable to set the heat treatment time to 0.1 minute or more because the vegetative cells of bifidobacteria are killed. Further, it is preferable to set the heat treatment time to 120 minutes or less from the viewpoint of suppressing heat denaturation and effectively killing vegetative cells.

In the heat treatment at a low temperature (60 to 100 ℃), 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, further preferably 0.2 to 30 minutes, further preferably 0.2 to 25 minutes, and particularly preferably 0.2 to 20 minutes. In the heat treatment in the high temperature range (100 to 300 ℃), the optimum heat treatment time may be, for example, 0.01 to 0.5 minute, preferably 0.015 to 0.5 minute, more preferably 0.02 to 0.5 minute, further preferably 0.025 to 0.5 minute, further preferably 0.03 to 0.5 minute, and particularly preferably 0.03 to 0.5 minute. For example, the heat treatment is carried out at 90 ℃ for 15 minutes.

The heat treatment method is not particularly limited. For example, the obtained bacterial cells can be heated under predetermined conditions using a plate sterilizer, a tube sterilizer, a direct heating sterilizer, or a jacketed can heating sterilizer.

In order to exert the newborn-oriented brain function improving effect of the present invention, the amount of the lactic acid bacteria and/or bifidobacteria to be fed or administered is, for example, 10 per day ⁸ More than 10 ⁸ ～10 ¹² 5 x 10 of ⁸ ～5×10 ¹¹ 1, 10 ⁹ ～10 ¹¹ 5 x 10 pieces of ⁹ ～5×10 ¹⁰ 6 x 10 pieces ⁹ ～4×10 ¹⁰ Size 7X 10 ⁹ ～3×10 ¹⁰ And (4) respectively. Preferably 8X 10 ⁹ ～2×10 ¹⁰ More preferably 9X 10 ⁹ ～2×10 ¹⁰ And (4) respectively. Within the above range, the brain function improving effect based on the increase in the developmental index for the newborn can be effectively exhibited. Need to explainIt has been found that the compositions and agents of the present invention are components providing preventive and therapeutic effects, i.e., effective components, and the purpose of use thereof is not limited as long as the effects can be exerted.

In addition, the compositions and agents of the invention may also be fed or administered continuously in newborns, especially newborns born, due to their low side effects. In order to exert the brain function improving effect on the newborn, the feeding or administration period of the lactic acid bacteria and/or bifidobacteria of the present invention is, for example, 1 month or more, 1 to 12 months, 1 to 10 months, 1 to 9 months, 1 to 8 months, or 2 to 7 months. Within the above range, the brain function improving effect for the newborn can be effectively exerted. In particular, it is preferable that the number of bacteria to be continuously applied is 10 per day ¹⁰ More than one lactic acid bacteria and/or bifidobacteria for more than 1 month. In addition, in terms of the weight of the newborn, the feeding or administration period of the Bifidobacterium of the present invention is, for example, a period until the weight of the newborn reaches 1.5kg or more, a period until the weight of the newborn reaches 1.5 to 5kg, a period until the weight of the newborn reaches 1.7 to 5kg, a period until the weight of the newborn reaches 1.8 to 5kg, a period until the weight of the newborn reaches 1.9 to 5kg, a period until the weight of the newborn reaches 2 to 4kg, or a period until the weight of the newborn reaches 2 to 3 kg. Within the above range, the brain function improving effect for the newborn can be effectively exerted.

In the present specification, a neonate refers to an infant that has just been born, more specifically including healthy neonates, immature infants, premature infants and low birth weight infants. In the present invention, unless otherwise specified, the species of the neonate includes a human.

Furthermore, neonates refer to children in the neonatal period, which refers to the period immediately after birth, and in humans, typically within 4 weeks after birth.

As shown in the following examples, the compositions and agents of the present invention demonstrate brain function improving effects based on increasing developmental index by starting feeding or administration to a newborn, particularly an newborn right after birth, and continuing feeding or administration thereafter. In particular, it was demonstrated that the developmental index can be significantly improved, especially for newborns with birth weights above 1000g, compared to the situation without feeding or administering the compositions and agents of the invention. That is, by feeding or administering the composition and agent of the present invention, a developmental index-improving effect is imparted to the newborn right after birth without side effects or the like, which can be expected even in subsequent growth. That is, inconvenience and anxiety of life forced to promote development of brain function by enhancing living environment through strengthening educational coaching or the like can be eliminated and/or alleviated.

The nerves of the newborn at the time of birth are in an undeveloped state, and at this time, by feeding or administering the composition and agent of the present invention containing lactic acid bacteria and/or bifidobacteria as an effective ingredient, a brain function improving effect based on an increase in development index is obtained, and thus a significant development of brain function in the subsequent growth process can be expected. Furthermore, in addition to feeding and administration of the composition and agent of the present invention, enhancement of living environment by enhancing education counseling or the like can promote development of brain function, and further improvement of development index can be expected. In the present invention, "improvement of brain function" is used to include the meaning of increasing developmental index and promoting or accelerating development of brain function. The newborn right after birth is, for example, 0 to 60 days, 0 to 50 days, 0 to 40 days, 0 to 30 days, 0 to 20 days, 0 to 15 days, or 0 to 10 days after birth. In addition, the term "low birth weight infant" as used herein refers to an infant with a birth weight of 300 to 3000g, 350 to 2900g, 400 to 2800g, 450 to 2700g, 500 to 2600g or 500 to 2500g in the case of human. In addition, the term "low birth weight infant with a birth weight of 1000g or more" as used herein means that the infant has a birth weight of 1000 to 3000g, 1000 to 2900g, 1000 to 2800g, 1000 to 2700g, 1000 to 2600g or 1000 to 2500g in the case of human.

The lactic acid bacteria and/or bifidobacteria may be used alone or in combination with other components in the composition and agent of the present invention. The amount of the lactic acid bacteria and/or bifidobacteria to be incorporated in the composition and agent of the present invention may be arbitrarily determined depending on the purpose, use, form, formulation, symptom, body weight, etc., but the present invention is not limited thereto, and the amount may be incorporated in a range of 0.1 to 90% (w/w), and more preferably 0.1 to 50%, relative to the total weight. This is because, by being within the range, feeding or administration becomes easy. In the present invention, the agent of the present invention may be designed as an agent containing lactic acid bacteria and/or bifidobacteria, and the composition of the present invention may be designed as a composition containing lactic acid bacteria and/or bifidobacteria and other ingredients.

The compositions and agents of the invention may be administered in any form, either orally or non-orally (intramuscular, subcutaneous, intravenous, suppository or transdermal, etc.). In addition, the compositions and agents of the present invention can be administered without being affected by side effects resulting from drug administration. In particular Bifidobacterium bifidum OLB6378(NITE BP-31) of the present invention is considered to have no side effects even if administered to newborn infants just after birth and to be safe (Totsu et al, (2014) PEDIATRICSINTERNATIONAL Vol.56, No.5, pp.714-719). In addition, the composition and agent of the present invention improve diarrhea, improve constipation, inhibit proliferation of harmful bacteria in the intestine, produce vitamin B group, promote digestive absorption by lactose degradation, and at the same time, provide brain function improving effect based on improvement of developmental index.

Specifically, the composition and agent of the present invention can be utilized in any form of a drug or food and drink. For example, it is expected that the brain function improving effect is exerted by direct administration as a medicine or by direct feeding as a special-purpose food such as a specific health food or a nutritional food. In addition, examples of special purpose foods and nutritional foods include foods such as formula milk powder, liquid diet, patient food, infant milk powder, foods such as milk powder for lactating women, supplements, nutrition-enriched foods, and the like.

When the composition and the reagent of the present invention are used as a medicament, the form thereof includes, for example, oral administration in the form of tablets, coated tablets, capsules, granules, powders, solutions, syrups, emulsions and the like. These various preparations can be prepared into the pharmaceutical compositions and agents of the present invention by using, as a main ingredient, the cells and/or treated matters of the present invention as known adjuvants conventionally used in the field of pharmaceutical preparations, such as dispersing agents, excipients, binders, disintegrating agents, lubricants, coloring agents, flavoring agents, solubilizing agents, suspending agents, coating agents, and the like, according to conventional methods.

The compositions and agents of the present invention are preferably used as a composition mixed with a dispersant. Examples of the dispersant include milk proteins such as casein, soybean protein, peptides, amino acids, starch, dextrin, xylan, oligosaccharides, saccharides (glucose, lactose, sucrose, galactose, and maltose), sugar alcohols (trehalose, xylitol, erythritol, palatinose, trehalose, and xylose), and the like. Among the dispersing agents, dextrin is particularly preferable. This is because the powder can be granulated by using dextrin as a dispersant, and because handling such as dispersion and dissolution of dextrin is easy, and also can be stored for a long period of time.

The dextrin is preferably in the form of granules. This is because the granules have high solubility and high filling property, and thus can be dispensed in a small amount. In addition, the following advantages in preparation are also provided: only the packaging material is required to be put into the packaging material for subpackage, and accurate subpackage can be realized without mass distribution change.

In the composition and the agent of the present invention, the mass ratio of the lactic acid bacteria and/or bifidobacteria as the active ingredient to the dispersant is preferably 1:100 to 1:2, more preferably 1:100 to 1:10, and still more preferably 1:100 to 1: 20. This is because, by setting the content within the above range, the effective ingredient can be effectively dispersed.

For example, in the case of orally feeding or orally administering the composition and agent of the present invention containing lactic acid bacteria and/or bifidobacteria and dextrin as effective ingredients, the composition and agent of the present invention may be divided into portions each having a predetermined amount and packaged in a packaging material to make a package, followed by feeding or administration. In the present invention, it is preferably packaged in 1-time use amount, or in a plurality of 1-time use amounts, and particularly preferably in 1-time use amount.

When the composition and agent of the present invention are added to a food composition having no side effects, they can be added to various foods and drinks (milk, refreshing drink, fermented milk, yogurt, cheese, bread, biscuit, cracker, pizza crust, formula milk, liquid diet, food such as patient food, infant milk powder, food such as milk powder for lactating women, nutritional food, etc.) and fed. The composition and the agent of the present invention can be used as they are, or mixed with other foods or food ingredients, etc., according to conventional methods in conventional food compositions. In addition, as for the shape thereof, it may be in the state of usual foods and drinks, such as any of solid (powder, granule, etc.), paste, liquid and suspension. By taking this form, the compositions and agents of the present invention can be fed without causing psychological disorders.

The composition and the agent of the present invention may be used as a composition containing water, protein, carbohydrate, lipid, vitamins, minerals, organic acids, organic bases, fruit juices, flavors, and the like, without causing any side effects. Examples of the protein include animal and plant proteins such as whole milk powder, skim milk powder, partially skim milk powder, casein, whey powder, whey protein concentrate, whey protein isolate, α -casein, β -casein, κ -casein, β -lactoglobulin, α -lactalbumin, lactoferrin, soybean protein, egg protein, and meat protein, and hydrolysates thereof; butter, milk minerals, cream, whey, non-protein nitrogen, sialic acid, phospholipids, lactose, and other milk-derived components. All ingredients which have no side effects and which have been used as medicaments or food and beverage products are suitable. Further, 2 or more of these components may be used in combination.

Examples of the carbohydrate include saccharides, processed starch (soluble starch other than dextrin, british starch, oxidized starch, starch ester, starch ether, and the like), dietary fiber, and the like. Examples of the lipid include animal fats and oils such as lard and fish oil, fractionated oils thereof, hydrogenated oils thereof, and transesterified oils thereof; palm oil, safflower oil, corn oil, rapeseed oil, coconut oil, fractionated oil thereof, hydrogenated oil thereof, and vegetable oils and fats such as transesterified oil thereof. Examples of the vitamins include vitamin a, carotenes, vitamin B group, vitamin C, vitamin D group, vitamin E, vitamin K group, vitamin P, vitamin Q, nicotinic acid, pantothenic acid, biotin, inositol, choline, and folic acid, and examples of the minerals include calcium, potassium, magnesium, sodium, copper, iron, manganese, zinc, and selenium. Examples of the organic acid include malic acid, citric acid, lactic acid, and tartaric acid. All ingredients which have been used as medicaments or food and drink without side effects can be used. Further, 2 or more of these components may be used in combination.

When the composition and agent of the present invention are provided as food or medicine, the preparation method can be carried out by a method known to those skilled in the art. Those skilled in the art can appropriately combine the steps of mixing the bifidobacterium or the treated product of the present invention with other components, molding, sterilization, fermentation, calcination, drying, cooling, granulation, packaging, and the like to produce a desired food or drug.

Further, the composition and the reagent of the present invention can also be applied to health functional foods and patient foods. In view of the domestic and foreign trends and the consistency with the conventional specific health food system, the health functional food system is established not only for general foods but also for foods formed into a tablet, capsule, etc. shape, and includes 2 types of specific health foods (individually approved type) and nutritional functional foods (standard type). The brain function improving effect is expected to be exhibited by directly feeding the composition and the agent of the present invention as a food for special use such as a specific health food or a nutritional functional food.

Examples of forms of the composition and the agent of the present invention to be added to a formula include oral compositions for improving brain function for newborn infants, such as a formula for newborn infants, a peptide milk powder (ペプチドミルク), a follow-up milk powder (フォローアップミルク), a growing-up milk powder (グローイングアップミルク), a formula for low-birth-weight infants, a lactose-free milk powder, a low-sodium special milk powder, and a powder to be added to a mother's milk, and the forms are not particularly limited as long as the effects and efficacies of the present invention can be expected.

For example, when docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), arachidonic acid (ARA), cholesterols, etc., which promote the development and growth of a newborn, are incorporated in an appropriate amount to produce and provide a formula for a newborn containing the lactic acid bacteria and/or bifidobacteria of the present invention close to the composition of breast milk, further effective development and growth of a newborn can also be expected.

Further, when a newborn formula containing the lactic acid bacterium and/or bifidobacterium of the present invention in which beta-lactoglobulin having a strong allergy property is removed or reduced, a newborn formula containing the lactic acid bacterium and/or bifidobacterium of the present invention in which a nucleic acid or a nucleotide having an immunoregulatory function is incorporated in an appropriate amount, a newborn formula containing the lactic acid bacterium and/or bifidobacterium of the present invention in which soybean lecithin is not contained as an emulsifier are prepared and provided, it is expected that the newborn allergy can be effectively avoided while the brain function improvement effect of the newborn can be expected.

Further, when a formulated milk powder for a newborn containing the lactic acid bacterium and/or bifidobacterium of the present invention for enhancing milk lectin having an infection protective function is prepared and provided and at least one or more of fructo-oligosaccharide, nucleoside or nucleotide, taurine, and zinc for enhancing immunity is incorporated in an appropriate amount in the formulated milk powder for a newborn containing the lactic acid bacterium and/or bifidobacterium of the present invention, it is expected that the brain function improvement effect of the newborn can be expected and the immunity of the newborn can be effectively enhanced.

Further, when a milk powder formula for neonates containing the lactic acid bacterium and/or the bifidobacterium of the present invention that selectively decomposes poorly digestible and absorbable β -lactoglobulin and a milk powder formula for neonates containing the lactic acid bacterium and/or the bifidobacterium of the present invention that enhances α -lactalbumin with good digestibility are prepared and provided, it is expected that the brain function improvement effect of the neonates can be expected and that the digestive absorption ability in the digestive tract of the neonates can be effectively improved.

Furthermore, when a newborn formula containing the lactic acid bacterium and/or bifidobacterium of the present invention, which incorporates fructo-oligosaccharides or nucleosides or nucleotides that promote the formation of an appropriate intestinal flora in an appropriate amount, and a newborn formula containing the lactic acid bacterium and/or bifidobacterium of the present invention, which incorporates lactose that promotes the formation of an appropriate intestinal flora in an appropriate amount, are prepared and provided, it is expected that the fecal characteristics of the newborn can be effectively improved while the brain function improvement effect of the newborn can be expected.

As for the pharmaceutical composition, a food, a drink, which has been consumed and can be expected to have little side effect, or a composition that can be expected to have a brain function improving effect such as a developmental index improving effect, lactic acid bacteria and/or bifidobacteria as an active ingredient of the present invention may be used as an additive, and may be orally taken or fed or administered through a tube.

The lactic acid bacteria and/or bifidobacteria as the active ingredients of the present invention have the above-described excellent effects and efficacies not only on humans but also on mammals (mammals) other than humans. Thus, according to the present invention, there are provided a feed and a feed additive, particularly a milk powder and a milk powder additive for feeding mammals, containing lactic acid bacteria and/or bifidobacteria as an effective ingredient.

The development index mentioned in the present invention is demonstrated by a new version of the K-type development test 2001, which is one of mental exercise development evaluation methods. Specifically, the method is to calculate the developmental index by observing the activities and responses of the infant in a predetermined examination scene when the newborn who has been fed or administered a test sample such as the composition and the reagent of the present invention reaches 1.5 years old. In detail, the method is to observe the postural-motor (P-M), cognitive-adaptation (C-a), language-society (L-S) domains to deduce the developmental age and developmental index of all domains. That is, the ratio (percentage) of the development age to the actual age obtained by this examination corresponds to the development index, and it is understood that, for example, when the development index is 100, the development age and the actual age are equal. It should be noted that the above-described psychomotor development evaluation method includes various techniques, and even when the development of a young child is verified by a method other than the new K-type development test 2001 and the same effect as the improvement of the development index demonstrated by the new K-type development test 2001 is obtained, it is of course the same meaning as the improvement of the development index mentioned in the present invention.

According to the present invention, there is provided a method for improving brain function in a newborn infant, which comprises feeding or administering an effective amount of lactic acid bacteria and/or bifidobacteria or a composition containing the same to a subject in need thereof. The feeding or administration subject is a newborn, preferably a human newborn, of a mammal comprising a human. The methods of the invention can be practiced in accordance with the description to which the compositions and reagents of the invention are directed.

Furthermore, according to the present invention, there is provided the use of a lactic acid bacterium and/or a bifidobacterium or a composition containing the same for the preparation of a composition for improving brain function for newborn infants. Further, according to the present invention, there is provided a use of a lactic acid bacterium and/or a bifidobacterium or a composition containing the same for the preparation of a brain function improving agent for a newborn infant. Further, according to the present invention, there is provided a use of lactic acid bacteria and/or bifidobacteria or a composition containing the same for improving neonatal brain function. Further, according to the present invention, there is provided lactic acid bacteria and/or bifidobacteria or a composition containing the same for improving neonatal brain function. The use of the invention and the lactic acid bacteria, bifidobacteria and compositions of the invention can be carried out according to the description referred to for the compositions and agents of the invention.

Examples

The present invention will be described more specifically based on the following examples, but the present invention is not limited to these examples.

Example 1: preparation of test and control diets

120g of crude bacterial powder (viable cell count: 3.9X 10) of Bifidobacterium bifidum (Bifidobacterium bifidum) OLB6378 strain (accession number: NITE BP-31) ¹¹ cfu/g, trade name "mingzbi bright (mingzhi ビフィピュア) (registered trademark)", mingzhi food materials corporation) and 2880g of granular dextrin (songgu chemical corporation) were uniformly mixed and dispensed in 1g portions as test foods (viable bacteria).

In place of the test food, 3000g of granular dextrin (pine grain chemical Co., Ltd.) was dispensed in 1g portions as a control food (placebo).

Test example 1

In test example 1, the group of subjects fed with the test food (live bacteria) was referred to as "test food (live bacteria) feeding group", and the group of subjects fed with the control food (placebo) was referred to as "control food (placebo) feeding group". The subject groups selected newborns (88 with a birth weight of more than 1000g and 80 with a birth weight of less than 1000 g), test food (live bacteria) fed group selected 89 persons (49 with a birth weight of more than 1000g and 40 with a birth weight of less than 1000 g), control food (placebo) fed group selected 79 persons (39 with a birth weight of more than 1000g and 40 with a birth weight of less than 1000 g), each group was fed 1 test food (live bacteria) or control food (placebo) per 1 day, the feeding period was the day until the weight of the newborn reached 2 kg.

Test example 2

In the test example 1, 89 persons in the group fed with the test food (live bacteria) and 79 persons in the group fed with the control food (placebo) were examined for development in the new K-type development test 2001, and the development index was confirmed by an applicable test method as appropriate, when they reached 1.5 years of age. Specifically, the postural-motor (P-M), cognitive-adaptation (C-a), language-society (L-S) fields are observed, and the developmental age and developmental index of all fields are deduced from a comprehensive perspective. The obtained percentage of developmental age to actual age corresponds to the developmental index and is classified below 70, 70 and above and below 85, 85 and above and below 100, 100 and above.

Of 89 subjects in the test food (live bacteria) feeding group, there were 12 persons with a developmental index of less than 70, 12 persons with a developmental index of 70 or more and less than 85, 25 persons with a developmental index of 85 or more and less than 100, and 40 persons with a developmental index of 100 or more. That is, in the test food (live bacteria) fed group (89 subjects), the ratio of the developmental index was 13% or less than 70, 13% or more than 70 and less than 85, 28% or more than 85 and less than 100, and 45% or more than 100.

On the other hand, of 79 subjects in the control food (placebo) feeding group, there were 15 persons with a development index of less than 70, 17 persons with a development index of more than 70 and less than 85, 23 persons with a development index of more than 85 and less than 100, and 24 persons with a development index of more than 100. That is, in the control food (placebo) feeding group (79 subjects), the proportion of the development index of less than 70 was 19%, the proportion of 70 or more and less than 85 was 22%, the proportion of 85 or more and less than 100 was 29%, and the proportion of 100 or more was 30%.

When the U-test was performed between the test food (live bacteria) feeding group and the control food (placebo) feeding group, P was 0.038, which was significantly different.

It was thus established that by feeding or administering the compositions and agents of the invention to the neonate during a predetermined period of time, the developmental index of 1.5 years was significantly improved.

Next, the developmental index obtained was recalculated for subjects with birth weights of 1000g or more (49 subjects on the test food (live bacteria) and 39 subjects on the control food (placebo)).

Among 49 subjects in the test food (live bacteria) feeding group, there were 3 persons with a developmental index of less than 70, 6 persons with a developmental index of 70 or more and 85 or more, 10 persons with a developmental index of 85 or more and less than 100, and 30 persons with a developmental index of 100 or more. That is, in the test food (live bacteria) feeding group (49 subjects), the ratio of the developmental index was 6% or less, the ratio of 70 or more and less than 85 was 12%, the ratio of 85 or more and less than 100 was 20%, and the ratio of 100 or more was 61%.

On the other hand, among 39 subjects in the control food (placebo) feeding group, there were 9 persons with a development index of less than 70, 6 persons with a development index of more than 70 and less than 85, 10 persons with a development index of more than 85 and less than 100, and 14 persons with a development index of more than 100. That is, in the control food (placebo) feeding group (39 subjects), the proportion of the developmental index lower than 70 was 23%, the proportion of 70 or more and lower than 85 was 15%, the proportion of 85 or more and lower than 100 was 26%, and the proportion of 100 or more was 35%.

When the U-test was performed between the test food (live bacteria) and control food (placebo) fed groups, P ═ 0.009, which were significantly different.

It was thus established that by feeding or administering the compositions and agents of the invention to the neonate during a predetermined period, especially in young children with a birth weight above 1000g, the developmental index of 1.5 years is significantly improved.

Sequence listing

<110> Mingzhi, Kyoho

<120> neonate-oriented composition for improving brain function

<130> 171002PX

<150> JP2016-80676

<151> 2016-04-13

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<170> PatentIn version 3.5

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<213> Artificial sequence

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Claims (5)

1. Bifidobacterium bifidum (b) ((b))Bifidobacteriumbifidum) The application of the preparation of the reagent for improving the brain function of the newborn is disclosed.

2. Use according to claim 1, wherein the Bifidobacterium bifidum is Bifidobacterium bifidum (b: (b)Bifidobacteriumbifidum) OLB6378 strain, accession number: NITE BP-31.

3. Use according to claim 1 or 2, wherein the Bifidobacterium bifidum is a heat-treated thallus.

4. Use according to claim 1, wherein the number of bacteria fed continuously is 10 per day ⁸ More than one of the agents for improving the brain function of the newborn is more than 1 month.

5. The use according to claim 1, wherein the agent for improving brain function in a newborn is a food.