Composition for promoting development of brain function in infants

Abstract

To elucidate how disialyllacto-N-tetraose (DSLNT) and its constituent sugars affect infants, and to provide a composition capable of promoting development of a brain function in infants.SOLUTION: A composition for promoting development of a brain function in infants contains a component selected from a group consisting of DSLNT and its constituent sugars. The development of the brain function preferably should involve development in gross motor skills and personal-social areas.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a composition for promoting the development of brain functions in infants. The present invention is useful in the fields of infant and toddler development, health, and nutrition, as well as the production of foods and beverages therefor, etc. [Background technology]

[0002] Human milk oligosaccharides (HMOs) are the third most abundant solid components in breast milk, after lactose and lipids. The effect of breastfeeding duration on a child's intelligence has been reported (Non-Patent Document 1). In addition, it has been reported that 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL) from human milk oligosaccharides are positively correlated with the neurodevelopment of infants (Non-Patent Document 2).

[0003] Furthermore, with regard to HMOs and brain / nerve development, Patent Document 1 describes that HMOs increase the abundance of Akkermansia in the human gastrointestinal tract and can be used to treat or prevent brain / gastrointestinal disorders such as stress, anxiety, and depression-like behavior, and autism-like behavior. Patent Document 2 describes that fucosylated neutral HMOs, nonfucosylated neutral HMOs, sialylated HMOs, or any combination of the above, improve myelination to mature the prefrontal cortex region of non-infant brains, and are effective in treating Alzheimer's disease, depression, anxiety, schizophrenia, autism, dementia, and the like.

[0004] On the other hand, with regard to disialyllacto-N-tetraose (DSLNT), a type of HMO, it has been reported that the DSLNT content in breast milk from infants who developed necrotizing enterocolitis (NEC), one of the most common intestinal diseases in premature infants, was significantly lower than that from breast milk from infants who did not develop NEC, and that the DSLNT content in breast milk may be a non-invasive marker for identifying infants at risk of developing NEC and screening high-risk donor milk, and that DSLNT may also be useful in developing new treatments for NEC (Non-Patent Documents 3 and 4).

[0005] Patent Document 3 discloses a nutritional composition containing a spray-dried powder essentially consisting of 3'-SL and / or 6'-SL produced by microbial fermentation, and describes that DSLNT may be contained as an additional HMO. However, the function of DSLNT is not described. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] International Publication WO2019 / 106620 (Patent Publication No. 2021-504420) [Patent Document 2] International Publication WO2020 / 178774 (Patent Publication No. 2022-523560) [Patent Document 3] International Publication WO2019 / 110803 (Patent Publication No. 2021-505171) [Non-patent literature]

[0007] [Non-Patent Document 1] Hou, L., Li, X., Yan, P., Li, Y., Wu, Y., Yang, Q., Shi, X., Ge, L., and Yang, K.: Impact of the Duration of Breastfeeding on the Intelligence of Children: A Systematic Review with Network Meta-Analysis, Breastfeed Med (2021). [Non-Patent Document 2] Elena Oliveros , MJM, Francisco J Torres-Espinola: Human Milk Levels of 2´-Fucosyllactose and 6´-Sialyllactose are Positively Associated with Infant Neurodevelopment and are Not Impacted by Maternal BMI or Diabetic Status, J Nutr Food Sci, 4, 024 (2020). [Non-Patent Document 3] Autran CA, et al.: Human milk oligosaccharide composition predicts risk of necrotising enterocolitis in preterm infants, Gut 2017;0:1-7. [Non-Patent Document 4] Masi AC, et al. Human milk oligosaccharide DSLNT and gutmicrobiome in preterm infants predicts necrotising enterocolitis, Gut 2021;70:2273-2282. Summary of the Invention [Problem to be solved by the invention]

[0008] As mentioned above, DSLNT contained in breast milk is known to be associated with NEC, but the effect of DSLNT on the development of infant brain function was unknown. [Means for solving the problem]

[0009] The present invention provides the following: [1] A composition for promoting the development of a child's brain function, comprising any one selected from the group consisting of disialyllacto-N-tetraose (DSLNT) and its constituent sugars. [2] The composition described in 1, wherein the development of brain function is development in either the gross motor area or the personal / social area. [3] The composition described in 1 or 2, wherein the development of brain function is the development of brain function in children aged 11 months or older. [4] A composition described in any one of 1 to 3, for consumption by a child of 6 months of age or younger. [5] The composition described in any one of 1 to 4, which is in a form selected from the group consisting of powdered milk, liquid milk, and breast milk substitute food. [6] The composition described in any one of 1 to 5, wherein the concentration of DSLNT upon ingestion is 0.09 mg / mL or more. [7] The composition described in any one of 1 to 6, wherein the concentration of DSLNT upon ingestion is 0.153 mg / mL or more. [8] The composition described in any one of 1 to 7, which is in the form of a formula powder and contains 52.9 mg or more of DSLNT per 100 g. [9] The composition described in any one of 1 to 8, which is in the form of an infant formula and contains 90 mg or more of DSLNT per 100 g.

[0010]

[10] A method for promoting the development of a child's brain function, comprising the steps of: producing an artificial nutrition composition containing disialyllacto-N-tetraose (DSLNT) and any one selected from the group consisting of its constituent sugars; and administering the produced composition to a child in need of promoting the development of his or her brain function. A non-therapeutic method for promoting the development of a child's brain function, comprising the steps of: administering a composition containing DSLNT and any one selected from the group consisting of its constituent sugars to a child in whom promotion of brain function development is desirable. A composition containing DSLNT and any one selected from the group consisting of its constituent sugars for use in a method for promoting the development of a child's brain function. Use of a composition containing DSLNT and any one selected from the group consisting of its constituent sugars in the production of a composition for promoting the development of a child's brain function. Use of a composition containing DSLNT and any one selected from the group consisting of its constituent sugars to promote the development of a child's brain function.

[11] The method, composition, or use according to claim 10, wherein the development of brain function is development in either the gross motor domain or the personal-social domain.

[12] The method, composition, or use according to 10 or 11, wherein the development of brain function is the development of brain function in a child from 11 months of age onwards.

[13] The method, composition, or use according to any one of claims 10 to 12, for consumption by a child of 6 months of age or younger.

[14] The method, composition, or use according to any one of claims 10 to 13, wherein the composition is in a form selected from the group consisting of infant formula, infant liquid formula, and breast milk substitute food.

[15] The method, composition, or use according to any one of claims 10 to 14, wherein the concentration of DSLNT upon ingestion is 0.09 mg / mL or more.

[16] The method, composition, or use according to any one of claims 10 to 15, wherein the concentration of DSLNT upon ingestion is 0.153 mg / mL or more.

[17] The method, composition, or use according to any one of claims 10 to 16, wherein the composition is in the form of an infant formula and contains 52.9 mg or more of DSLNT per 100 g.

[18] The method, composition, or use according to any one of 10 to 17, wherein the composition is in the form of an infant formula and contains 90 mg or more of DSLNT per 100 g. Effect of the Invention

[0011] The composition of the present invention can promote the development of a child's brain functions and thereby contribute to the child's future healthy growth. Since DSLNT, the active ingredient of the composition of the present invention, is naturally contained in breast milk, the composition of the present invention can safely exert its intended effect on infants. Even when breast-feeding is not possible, a composition can be provided that promotes the development of brain function in a manner similar to that achieved by breast-feeding. The present invention provides information regarding the relationship between DSLNT ingested during infancy and the development of brain function. The composition of the present invention is expected to be applicable to the treatment of diseases or conditions related to brain function in children. The composition of the present invention is also expected to be applicable to the promotion of brain function development, improvement of nutritional status, and maintenance and promotion of health not only in infants but also in young children, children, adults, and the elderly. [Brief description of the drawings]

[0012] [Figure 1] Comparison of developmental scores between groups based on DSLNT concentrations in breast milk [Diagram 2] Distribution of DSLNT concentrations in breast milk from one month olds. The horizontal lines showing the distribution of DSLNT concentrations in the figure indicate, from lowest concentration, the minimum, first quartile, second quartile (median), third quartile, and maximum value. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] [Active ingredients] The composition of the present invention contains, as an active ingredient, any one selected from the group consisting of disialyllacto-N-tetraose (Neu5Acα2-3Galβ1-3(Neu5Acα2-6)Galβ1-4Glc, DSLNT) and its constituent sugars. "Any one" means that the number and type of any one may be selected.

[0014] In the context of the present invention, the abbreviations and structures of human milk oligosaccharides are as follows: Nutr Rev. 2017 Nov 1;75(11):920-933. doi: 10.1093 / nutrit / nux044. and Nutrients 2021, 13(8), 2737; https: / / doi.org / 10.3390 / nu13082737. In case of any discrepancy between these documents, the latter shall prevail.

[0015] In the present invention, the term "constituent sugar of DSLNT" refers to the sugar constituting DSLNT (sugar resulting from decomposition of DSLNT) excluding glucose having a reducing end and galactose added thereto, unless otherwise specified. It is known that HMO is decomposed by intestinal bacteria present in the human large intestine after ingestion (J Pediatr. 1998 Jul;133(1):95-8. doi: 10.1016 / s0022-3476(98)70185-4). Examples of the constituent sugar of DSLNT include lacto-N-biose (LNB), N-acetylglucosamine (GlcNAc), N-acetylneuraminic acid (Neu5Ac), and galactose. The constituent sugar of DSLNT used in the composition is not particularly limited as long as it has the desired effect. In addition, the DSLNT and the constituent sugar of DSLNT used in the composition may be one type or a combination of two or more types.

[0016] DSLNT and its constituent sugars can be produced by various methods, including synthesis, extraction from natural products containing the substance, and cultures of yeast and the like.

[0017] The composition of the present invention contains, as an active ingredient, any one selected from the group consisting of disialyllacto-N-tetraose (Neu5Acα2-3Galβ1-3(Neu5Acα2-6)Galβ1-4Glc, DSLNT) and its constituent sugars. "Any one" means that the number and type of any one may be selected.

[0018] [Application] (Function / Action) The composition of the present invention can be used to promote the development of brain function in children. The development of brain function includes those that can be evaluated by various existing tests. Examples of existing tests include developmental screening (questionnaires), such as Ages & Stages Questionnaires (registered trademark), Third Edition (ASQ (registered trademark)-3), its translated version, Tojoji Infant Analytical Development Test, Denver Developmental Screening Test (DDST), its Japanese version (JDDST); individual developmental tests, such as the new version of K-type Developmental Test, etc.

[0019] In a preferred embodiment, the composition is used to promote development in any of the five areas of development: communication (babbling, vocalization, listening and understanding), gross motor (arm, leg and whole body movements), fine motor (hand and finger movements), problem solving (learning and playing with toys), and personal and social (social play, playing with toys and other children).

[0020] In one embodiment, the composition is used to promote development in the area of ​​gross motor development. In another embodiment, the composition is used to promote development in any one of the five areas, including at least one of the gross motor area and the personal / social area. In another embodiment, the composition is used to promote development in any one of the five areas, including both the gross motor area and the personal / social area.

[0021] The promotion of development in the gross motor domain is specifically shown by the use of arms and legs when moving, playing, etc., and the ability to move them in a coordinated manner. Thus, in a more specific embodiment, the composition is used to promote the use of arms and legs, and the ability to move them in a coordinated manner. The promotion of development in the personal and social domain is specifically shown by the extent to which a child can take care of themselves (reach into their sleeves when dressing, lift their legs when putting on pants, etc.), and the ability to interact with others (give something when asked, interact with others by throwing or rolling a ball, etc.). Thus, in a more specific embodiment, the composition is used to promote the ability to take care of themselves and the ability to interact with others.

[0022] Development in the five areas can be assessed with the Ages & Stages Questionnaires®, Third Edition (ASQ®-3) and its Japanese version. When using the ASQ®-3, the questionnaire is selected based on the exact age of the child. The Japanese version is available for 6, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months of age. If the child was born before 37 weeks and 0 days of gestation, and is under 2 years old at the time of evaluation, the questionnaire is selected based on corrected age. The questionnaire is usually completed by the parent or caregiver. The completed scores are tallied, adjusted if necessary, and the developmental status of each area can be evaluated using a graph showing the cutoff values ​​for each area.

[0023] In one embodiment, the composition is used to promote the development of brain function in infants aged 11 months or older. According to the study by the present inventors, a high correlation has been observed between the amount of DSLNT in breast milk ingested by infants aged 1 to 6 months and the development evaluated by the Japanese version of the ASQ-3 24-Month Basic Information Form (target age: 11 months 0 days to 12 months 30 days).

[0024] A composition promoting the development of brain function means that, compared to a composition that does not contain DSLNT and its constituent sugars or that contains a lower concentration of DSLNT and its constituent sugars, the composition not only accelerates development in any of the five areas (resulting in a higher score calculated on the ASQ (registered trademark)-3), but also helps the development of any of the five areas to progress smoothly, and when the level of development in any of the five areas is within the range requiring observation, brings the development closer to the level of smooth development.

[0025] The composition of the present invention can also be used to treat diseases or conditions related to brain function that are expected to improve by promoting the development of brain function. Examples of such diseases or conditions include developmental disorders. Developmental disorders are disorders related to the development of brain function. Developmental disorders include autism, Asperger's syndrome and other pervasive developmental disorders, learning disabilities, attention deficit hyperactivity disorder, Tourette's syndrome, and stuttering.

[0026] The compositions of the present invention can also be used to maintain healthy brain function and to support good development of brain function.

[0027] In the present invention, the term "treatment" for a disease or condition includes reducing the risk of onset, delaying onset, prevention, treatment, and stopping or delaying progression. Treatment includes medical procedures performed by doctors for the purpose of treating a disease, and non-medical procedures performed by people other than doctors, such as nutritionists, registered dietitians, public health nurses, midwives, nurses, clinical laboratory technicians, food manufacturers, and food sellers. Treatment also includes recommendations for administration or intake of specific foods, dietary guidance, health guidance, nutritional guidance (including nutritional guidance required for the medical treatment of injured or sick people, and nutritional guidance for maintaining and promoting health), school meal management, and guidance required for nutritional improvement regarding school meals. The subjects of treatment in the present invention include humans (individuals) and non-human mammals (companion animals, etc.).

[0028] (subject) The composition of the present invention is suitable for administration to subjects for whom it is desirable or necessary to promote the development of brain function, including infants (under 1 year old, including newborns up to 1 month old), toddlers (1 year to 6 years old), children (6 years to 15 years old), adults (15 years old or older), middle-aged and elderly people (40 years to 65 years old), elderly people (65 years old or older), pregnant women, postpartum women, people who are sick or recovering from illness, men, and women.

[0029] In one embodiment, the composition is used for feeding to infants (infants, toddlers, and children), preferably for feeding to infants or toddlers, more preferably for feeding to infants (e.g., 6 months of age or younger). In another embodiment, the composition is suitable for feeding to subjects who desire or require formula feeding rather than breast feeding.

[0030] [Composition] (Dosage form / shape) The composition of the present invention can be prepared in any form, such as a solid, liquid, mixture, suspension, emulsion, gel, sol, etc. The composition of the present invention can be a synthetic nutritional composition prepared by mixing various ingredients.

[0031] In a particularly preferred embodiment, the composition of the present invention is in the form of an infant formula, a liquid formula, or a breast milk substitute. The term "infused formula" refers to raw milk, cow's milk, special cow's milk, or a food product made from these ingredients, which is processed or used as the main ingredient, to which nutrients necessary for infants are added, and which is made into a powder. The term "liquid formula" refers to raw milk, cow's milk, special cow's milk, or a food product made from these ingredients, which is processed or used as the main ingredient, to which nutrients necessary for infants are added, and which is made into a liquid.

[0032] Formulated powdered milk, formula liquid milk, or breast milk substitutes can be for infants, follow-up, low birth weight infants, children, adults, the elderly, allergies, lactose intolerance, and congenital metabolic disorders. In Japan, follow-up refers to products that provide a balanced intake of nutrients necessary for infants and toddlers from the weaning period around 9 months of age until around 3 years of age.

[0033] In one embodiment, the prepared powdered milk is used after being dissolved to a concentration of 5 to 17%, preferably 8 to 16%, and more preferably 12 to 15%. The prepared powdered milk can be packaged in a stick or cube shape for one serving (e.g., the amount required to prepare 200 ml of milk by dissolving in hot water).

[0034] The composition of the present invention may be a composition that is a food or a medicine other than a formula milk powder, a formula liquid milk, or a breast milk substitute food. The food or medicine includes not only those for humans but also those for animals other than humans, unless otherwise specified. The food includes general food, functional food, food for infants, and nutritional compositions, as well as therapeutic food (food that serves the purpose of treatment. Food prepared based on a menu prepared by a nutritionist or the like according to a doctor's meal prescription), dietary therapy food, ingredient-adjusted food, nursing care food, and food for medical support, unless otherwise specified. The food includes not only solids but also liquids, such as beverages, drinks, liquid foods, and soups, unless otherwise specified. Functional foods refer to foods that can provide a specific functionality to the living body, and include all types of health foods, such as foods for specified health uses (including conditional FOSHU [specified health foods]), foods with functional claims, health functional foods including foods with nutrient functions, foods for special dietary uses, dietary supplements, dietary supplements, supplements (for example, tablets, coated tablets, sugar-coated tablets, capsules, liquids, and other dosage forms), and beauty foods (for example, diet foods). In the present invention, "functional foods" also includes health foods to which a health claim based on the food standards of Codex Alimentarius (the Joint FAO / WHO Food Standards Commission) is applied. Cosmetics include medicated cosmetics.

[0035] When the composition is a food, it can be in any form such as a supplement, confectionery, beverage, drink, seasoning, dairy product, processed food, side dish, soup, etc. Specifically, the composition of the present invention can be in the form of gummies, tablets, drink, fermented milk, dairy drink, milk drink, soft drink, ice cream, cheese, bread, biscuits, crackers, pizza crust, modified milk powder, liquid food, food for sick people, nutritional food, frozen food, processed food, etc., and can also be in the form of granules, powder, paste, thick liquid, etc. for mixing with beverages or foods or for diluting to prepare beverages, etc., specifically, it can be in the form of a syrup for adding to milk.

[0036] When the composition is a pharmaceutical product, examples of specific forms include chewable tablets, sublingual tablets, tablets, pills, capsules, granules, powders, liquids, suspensions, emulsions, syrups, liniments, lotions, gels, aerosols, sprays, ointments, creams, tapes, poultices, eye drops, nasal drops, and suppositories.

[0037] (Content / dose / concentration) The content and concentration of the active ingredient in the composition may be any amount that can produce the desired effect, and can be appropriately set in consideration of various factors such as the age, body weight, and desired effect of the subject. In addition, when the content of DSLNT in the composition and the concentration of DSLNT at the time of ingestion are shown in relation to the present invention, the content and concentration of DSLNT are shown unless otherwise specified. In other words, when any of the constituent sugars of DSLNT is included as the active ingredient, the constituent sugar is used in an equimolar content and equimolar concentration with the DSLNT at the indicated content and concentration. This conversion can be easily performed by those skilled in the art. In addition, when there are multiple active ingredients, for example, when DSLNT and one of its constituent sugars are included, the indicated content and concentration are the total content and concentration after necessary conversion.

[0038] When the composition is liquid, for example, a liquid milk preparation, the DSLNT concentration of the composition is preferably 0.05 mg / mL or more, more preferably 0.07 mg / mL or more, from the viewpoint of promoting development in any of the above-mentioned five areas, and is preferably 0.09 mg / mL or more, more preferably 0.153 mg / mL or more, even more preferably 0.399 mg / mL or more, and even more preferably 0.485 mg / mL or more, from the viewpoint of promoting development in any of the above-mentioned five areas, including at least the gross motor area.

[0039] When the composition is liquid, for example, when it is a liquid preparation, the upper limit of the DSLNT concentration of the composition can be appropriately set, for example, to 5.0 mg / mL or less, or may be 4.0 mg / mL or less, or 3.0 mg / mL or less, or may be 2.0 mg / mL or less, or may be 1.0 mg / mL or less. From the viewpoint of being within the range of the amount normally contained in breast milk, the concentration of DSLNT is preferably 0.90 mg / mL or less, and may be 0.71 mg / mL or less.

[0040] When the composition is solid, for example, in the form of powdered milk, the amount of DSLNT per 100 g of the composition is preferably 20 mg or more, more preferably 40 mg or more, from the viewpoint of promoting development in any of the above-mentioned five areas, including at least the gross motor area, preferably 52.9 mg or more, more preferably 90 mg or more, even more preferably 234 mg or more, and even more preferably 285 ...

[0041] When the composition is solid, for example, in the form of powdered milk, the upper limit of the amount of DSLNT per 100 g of the composition can be appropriately set, for example, to 60 mg or less, or may be 50 mg or less, 40 mg or less, 30 mg or less, or may be 20 mg or less. From the viewpoint of being within the range of the amount normally contained in breast milk, the amount of DSLNTs per 100 g of the composition is preferably 1420 mg or less, and may be 418 mg or less.

[0042] The content of DSLNT in the composition may be designed taking into consideration the amount of DSLNT per day. The daily amount of DSLNT may be 5 mg or more, and may be 10 mg or more. From the viewpoint of promoting development in at least one of the above-mentioned five areas, including the area of ​​gross motor skills, the daily amount of DSLNT is preferably 9 mg or more, more preferably 15.3 mg or more.

[0043] The upper limit of the daily amount of DSLNT can be set appropriately, for example, 500 mg or less, 400 mg or less, 300 mg or less, 200 mg or less, or 100 mg or less. From the viewpoint of being within the range of the amount normally contained in breast milk, the daily amount of DSLNT is preferably 900 mg or less, and may be 71 mg or less. Such a daily amount may be divided into multiple portions, for example, 3 to 7 portions so as to be suitable for ingestion 3 to 7 times a day.

[0044] The composition may be taken at any time of day. When the composition is a powdered milk formula, liquid milk formula, or breast milk substitute, the composition of the present invention can be used to breast-feed the baby in the same manner as breast-feeding.

[0045] (Other ingredients, additives) The composition of the present invention may contain other nutritional components acceptable as foods or pharmaceuticals, in addition to DSLNT and its constituent sugars. For example, when the composition is in the form of an infant formula, an infant liquid formula, or a breast milk substitute, the components other than DSLNT and its constituent sugars may include proteins, lipids, cholesterol, carbohydrates, niacin, pantothenic acid, biotin, vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, folic acid, zinc, sodium, potassium, calcium, selenium, iron, copper, magnesium, phosphorus, lactadherin, α-lactalbumin, β-lactoglobulin, ARA (arachidonic acid), DHA (docosahexaenoic acid), linoleic acid, α-linolenic acid, phospholipids, fructooligosaccharides, inositol, β-carotene, chlorine, carnitine, taurine, nucleotides, etc.

[0046] The composition may also contain, in addition to DSLNT and its constituent sugars, other active ingredients or nutritional ingredients that are acceptable as foods or pharmaceuticals.

[0047] The composition may further contain additives that are acceptable for use as food or medicine. Examples of such additives include inert carriers (solid or liquid carriers), excipients, surfactants, binders, disintegrants, lubricants, solubilizers, suspending agents, coating agents, colorants, preservatives, buffers, pH adjusters, emulsifiers, stabilizers, sweeteners, antioxidants, flavors, acidulants, and natural products.

[0048] (Usage) The composition of the present invention is used orally. It may also be administered parenterally, for example, via a tube (gastrostomy or enterostomy) or nasally, but is preferably used orally.

[0049] The composition can be repeatedly ingested by a subject, and can be continuously ingested by a subject for a long period of time. The period is not particularly limited, but in order to fully observe the effect, it is preferable to continuously ingest the composition for a relatively long period of time, for example, one week or more, two weeks or more, one month or more, three months or more, six months or more, or one year or more. Since the active ingredient DSLNT and its constituent sugars are substances that have a long history of dietary experience, and DSLNT is originally contained in breast milk, the composition of the present invention is particularly suitable for long-term ingestion.

[0050] (others) The composition of the present invention can be used together with the intake of other ingredients, the intake of health foods and supplements, exercise, normal diet, etc. The composition of the present invention may also be used together with a therapy that promotes the development of brain function. Examples of therapies that promote the development of brain function include inclusive therapy, music therapy, occupational therapy, social skills training, cognitive behavioral therapy, and therapeutic education.

[0051] Those skilled in the art can appropriately produce the composition of the present invention by using existing facilities, etc. In producing the composition, the stage of blending DSLNT and its constituent sugars is not particularly limited, so long as the properties of DSLNT and its constituent sugars are not significantly impaired.

[0052] The composition of the present invention can be produced according to a conventional method even when it is in the form of a formula, a formula liquid, or a breast milk substitute food. For example, a formula can be produced as follows. A processed whey protein, casein, a processed soy protein, sugars (lactose, oligosaccharides), minerals, vitamins, and fats and oils (including fatty acids such as ARA, DHA, linoleic acid, and α-linolenic acid) are blended, dissolved, mixed, and purified, and then sterilized, concentrated, homogenized, spray-dried, or otherwise dried to obtain a formula. In this case, the blending step of DSLNT and its constituent sugars is not particularly limited as long as it does not significantly impair the properties of DSLNT and its constituent sugars.

[0053] Products containing the composition of the present invention may be labeled with their functions and intended use (applications), and may also be labeled with a recommendation for administration or ingestion to a specific subject. Labeling may be direct or indirect. Examples of direct labeling include descriptions on tangible objects such as the product itself, packaging, containers, labels, and tags, while examples of indirect labeling include advertising and promotional activities by place or means such as websites, storefronts, pamphlets, exhibitions, seminars such as media seminars, books, newspapers, magazines, television, radio, mailings, e-mails, and voice. Examples of the functions and intended use (applications) to be labeled include "helps develop brain function," "helps maintain brain function," "for babies up to 6 months of age," "for infants," and "for young children."

[0054] The present application also provides the following as another invention. [i] A composition for promoting the development of brain functions in the personal and social domains of a child, comprising any one selected from the group consisting of 6'-sialyllactose (Neu5Acα(2-6)Galβ(1-4)Glc, 6'-sialyllactose, 6'-SL) and its constituent sugar sialic acid. [ii] The composition described in A1, for the development of brain function in children aged 11 months and older. [iii] A composition described in i or ii, intended for consumption by children 6 months of age or younger. [iv] The composition described in any one of i to iii, which is in a form selected from the group consisting of powdered milk, liquid milk, and breast milk substitute food. [v] The composition according to any one of i to iv, wherein the concentration of 6'-SL at the time of ingestion is 0.01 mg / mL or more, preferably 0.34 mg / mL or more, more preferably 0.550 mg / mL or more, and even more preferably 0.631 mg / mL or more. In either case, the upper limit can be set appropriately, but from the viewpoint of being within the range of the amount normally contained in breast milk, the concentration of 6'-SL at the time of ingestion is preferably 0.7 mg / mL or less, and may be 0.65 mg / mL or less. [vi] The composition according to any one of items i to v, which is in the form of a powdered milk and contains 5.9 mg or more, preferably 200 mg or more, more preferably 320 mg or more, and even more preferably 370 mg or more of 6'-SL per 100 g. In either case, the upper limit can be set appropriately, but from the viewpoint of being within the range of the amount normally contained in breast milk, the amount of 6'-SL per 100 g is preferably 420 mg or less, and may be 390 mg or less. The description in this specification of the composition containing, as an active ingredient, any one selected from the group consisting of DSLNT and its constituent sugars also applies to each of the above inventions i to vi, unless it is inconsistent with the above inventions i to vi.

[0055] The present invention will now be described in more detail with reference to examples. EXAMPLES

[0056] [DSLNT promotes brain function development in children] Method 1 We investigated whether the future development of a child's brain function is promoted depending on the concentration of DSLNT in the breast milk that the child ingested. The specific method is as follows.

[0057] The study targeted 150 infants who were exclusively breastfed from 1 month to 6 months of age. The DSLNT concentration in the breast milk consumed by the infants at 1 month of age was measured by multiple reaction monitoring using LC-MS / MS and quantified by the external standard method. The infant's development score was evaluated at 12 months of age using ASQ (registered trademark)-3 (Japanese version of ASQ (registered trademark)-3 Infant Development Screening Questionnaire, Igaku-Shoin, 2021). ASQ-3 evaluates the child's brain function development in five areas: communication, fine motor, gross motor, personal-social, and problem solving. The relationship between these two indices was evaluated by ordinal logistic regression analysis. Gestational age, which is considered a factor that affects brain development in ASQ-3, was used to adjust the regression model. In addition, in order to align the conditions of HMOs related to brain function development that the infant ingests, information on the secretory types of 2-FL and 6'-SL was also used to adjust the regression model.

[0058] Result 1 Ordinal logistic regression analysis revealed a significant positive correlation between the gross motor domain of developmental scores at 12 months of age and breast milk DSLNT concentration at a risk level of less than 5% (table below).

[0059] [Table 1]

[0060] Method 2 The subjects were 150 infants who were exclusively breastfed from 1 to 6 months of age, and the concentrations of DSLNT and 6'-SL in the breast milk that the infants drank when they were 1 month old were measured by LC-MS / MS. DSLNT is the component examined in Method 1, and 6'-SL is one of the HMOs that has already been reported to be associated with brain function development. The infants' development scores were evaluated using the ASQ-3 at 12 months of age. To evaluate which of the two components, DSLNT and 6'-SL, contained in breast milk, is more effective in promoting brain function development, the 150 infants were divided into two groups: group 1, which drank breast milk with a high DSLNT concentration only, and group 2, which drank breast milk with a high 6'-SL concentration only, and the development scores of the two groups were compared.

[0061] [Table 2]

[0062] Result 2 A comparison of the results of classification according to Method 2 is shown in Table 3. The developmental score (12 months, personal-social) of Group (1) was 4.0 points higher than that of Group (2). This difference corresponds to approximately one stage of the developmental score.

[0063] This indicates that DSLNT is more effective at promoting child development than 6'-SL.

[0064] [Table 3]

[0065] Method 3 We investigated the difference in the future brain function development of children depending on the concentration of DSLNT in the breast milk that the children ingested. The specific method is as follows.

[0066] In method 1, an association between breast milk DSLNT concentration and infant brain function development was found in an analysis adjusted for information on the categorical variables 2-FL secretion type and 6'-SL secretion type. Based on this, in the study using method 3, infants whose breast milk 2-FL concentration was less than 0.1 mg / ml or whose 6'-SL concentration was less than 0.05 mg / ml were excluded from the analysis. The 122 subjects were divided into three groups according to the breast milk DSLNT concentration, and the development scores were compared between the groups. The boundary concentrations for the three groups were set at 0.153 mg / ml (mean DSLNT concentration in 1-month breast milk - 1 x standard deviation) and 0.271 mg / ml (mean DSLNT concentration in 1-month breast milk). Specifically, an intergroup comparison was performed between three groups: the group with DSLNT concentration in the breast milk ≥ 0.271 mg / ml (high DSLNT group), the group with DSLNT concentration < 0.271 mg / ml and ≥ 0.153 mg / ml (medium DSLNT group), and the group with DSLNT concentration < 0.153 mg / ml (low DSLNT group).

[0067] Result 3 The developmental score (gross motor skills at 12 months) was 39.1 in the low DSLNT group, whereas it was 48.5 in the medium DSLNT group and 49.0 in the high DSLNT group, which were 9.4 and 9.9 higher, respectively (Figure 1). This difference corresponds to approximately two stages of developmental score.

[0068] This indicates that if the DSLNT concentration in breast milk is above 0.153 mg / ml, the lower limit of the medium DSLNT concentration group, the development of a child's brain function is promoted.

[0069] Method 4 The maximum amount of DSLNT in the composition that the child would ingest was confirmed. The specific method was as follows: A box plot showing the distribution of DSLNT concentrations in breast milk was created from the DSLNT content in breast milk shown in Method 1. From the distribution obtained, the maximum DSLNT concentration in breast milk was confirmed as the maximum amount of DSLNT in the composition ingested by the infant.

[0070] Result 4 The distribution of DSLNT concentrations in 150 breast milk samples drunk by infants at one month of age is shown in Figure 2. The minimum value was 0.09 mg / mL, and the maximum concentration was 0.71 mg / mL. This confirmed that the upper limit of DSLNT concentration ingested by infants at one month of age is 0.71 mg / mL. [Industrial Applicability]

[0071] According to the present invention, it is possible to provide a food composition and a method for producing the food that can promote the future development of brain functions in children. It is also expected that the present invention will improve the nutrition of various people, ensure healthy lives, and promote welfare.

Claims

1. A composition for promoting the development of a child's brain function, comprising any one selected from the group consisting of disialyllacto-N-tetraose (DSLNT) and its constituent sugars.

2. The composition according to claim 1 , wherein the development of brain function is development in either the gross motor domain or the personal / social domain.

3. The composition according to claim 1, wherein the development of brain function is the development of brain function in children aged 11 months or older.

4. 10. The composition of claim 1 for ingestion by children 6 months of age or younger.

5. The composition according to claim 1, which is in any form selected from the group consisting of infant formula, liquid infant formula, and breast milk substitute food.

6. The composition according to claim 1 , wherein the concentration of DSLNT upon ingestion is 0.09 mg / mL or more.

7. The composition according to claim 1 , wherein the concentration of DSLNT upon ingestion is 0.153 mg / mL or more.

8. 6. The composition according to claim 1, which is in the form of a formula powder and contains 52.9 mg or more of DSLNT per 100 g.

9. 6. The composition according to claim 1, which is in the form of an infant formula and contains 90 mg or more of DSLNT per 100 g.

Images