Use of a nutritional composition for non-therapeutic purposes of improving brain development and promoting neural and / or cognitive development

Abstract

The present invention relates to the use of a nutritional composition for non-therapeutic purposes of improving brain development, promoting neural and / or cognitive development. The nutritional composition comprises medium and long-chain fatty acid triglycerides and human milk oligosaccharides, and the mass ratio of the medium and long-chain fatty acid triglycerides to the human milk oligosaccharides is 1:1 to 9:1. In this composition, the medium and long-chain fatty acid triglycerides and the human milk oligosaccharides have a synergistic effect in terms of the said use, significantly improving the effect of the composition in improving brain development, promoting neural and / or cognitive development. This composition can be used for preventing or improving brain developmental retardation, nervous system and / or cognitive developmental retardation; at the same time, it can also be used for preventing or improving impaired learning ability, impaired mental behavior, impaired memory or reduced attention span, etc., and has good application prospects.

Description

Technical Field

[0001] The present invention relates to the field of food, and particularly to the use of a nutritional composition for the non-therapeutic purpose of improving brain development, promoting nerve and / or cognitive development. Background Art

[0002] The brain is the high-level center of the nervous system, playing a role in controlling and regulating the functional activities of various systems of the whole body. Research shows that the brain weight of a human at birth is about 370 g, about 600 - 700 g at 6 months, reaches 900 - 1000 g at 2 years old, and exceeds three times the birth weight at 3 years old. Thus, it can be seen that brain development, nerve development, and / or cognitive development play an important role in subsequent intellectual development. Currently, products on the market for improving brain development, promoting nerve development, and / or cognitive development mostly use DHA, AA, vitamins, zinc, etc. as the main raw materials. Therefore, it is of great significance to research and find a nutritional composition that can improve brain development, promote nerve development, and / or cognitive development.

[0003] Early studies have shown that compositions containing one or more long-chain polyunsaturated fatty acids (LCPUFAs) and medium-chain triglycerides (MCTs) can enhance cognitive function, reduce or prevent decline in social interaction, reduce or prevent age-related behavioral changes, increase trainability, maintain optimal brain function, promote learning and memory, and reduce memory loss (BRPI0818301B1). However, administration of high doses of MCT can cause gastrointestinal discomfort, and there is a risk of ketoacidosis or ketonemia with long-term use of MCT. Medium- and long-chain fatty acid triglycerides (MLCTs) have one or two medium-chain fatty acids attached to the glycerol backbone, with the others being long-chain fatty acids, and medium- and long-chain fatty acid triglycerides account for approximately 30% of the total triglycerides in human milk. Early studies have shown that the fatty acid composition of MLCT is closer to that of human milk, which is beneficial for fat digestion and absorption, improves the absorption of lipid nutrients, inhibits the accumulation of body fat, and can provide energy quickly and stably (Cheng X, Jiang C, Jin J, Jin Q, Akoh CC, Wei W, Wang X. Medium- and Long-Chain Triacylglycerol: Preparation, Health Benefits, and Food Utilization. Annu Rev Food Sci Technol. 2024 Jan 18; Ting Lan, Wei Wei, Ye Xingwang, Liu Zhengdong, Yan Zhiyuan, Jin Qingzhe, Wang Xingguo. Research Progress of Medium-Chain Triglycerides in Human Milk [J]. Journal of Food Science and Biotechnology, 2022, 41(6):41-50.). In addition, when the overall fatty acid composition in human milk is the same, the structure of triglycerides is different, and there are also significant differences in their biological functions.For example, mouse studies have shown that compared with formula lipid diets containing physically mixed vegetable oils of LCT / MCT with the same fatty acid composition, formula lipid diets containing human milk structured lipid MLCT have the functions of regulating thermogenesis in mice, inhibiting visceral fat accumulation, altering the gut microbiota, and regulating lipid metabolism (Yuan T, Cheng X, Shen L, Liu Z, Ye X, Yan Z, Wei W, Wang X. Novel Human Milk Fat Substitutes Based on Medium- and Long-Chain Triacylglycerol Regulate Thermogenesis, Lipid Metabolism, and Gut Microbiota Diversity in C57BL / 6J Mice. J Agric Food Chem. 2024 Mar 27;72(12):6213-622.), while there are few reports on the effect of MLCT on brain cognitive development.

[0004] Human milk oligosaccharides (HMOs) have a rich composition. Currently, HMOs have different classification methods. Classified by pH, they are divided into neutral oligosaccharides and acidic oligosaccharides; neutral oligosaccharides can be further divided into fucose-free and fucose-containing oligosaccharides, accounting for about 70% of the mass fraction of human milk oligosaccharides; acidic oligosaccharides are oligosaccharides containing sialic acid and sulfate structures, accounting for about 30% of the mass fraction of human milk oligosaccharides. Classified by representative groups, they are divided into fucose-containing (such as 2′-fucosyllactose (fucosyllactose, 2’-FL)), sialic acid-containing (such as 6’-Sialyllactose (sialyllactose sodium salt, 6’-SL), 3’-Sialyllactose (sialyllactose sodium salt, 3’-SL)), and non-fucose non-sialic acid-containing (such as lacto-N-tetraose (lacto-N-tetraose, LNT), lacto-N-neotetraose (lacto-N-neotetraose, LNnT)).

[0005] At present, the relevant studies on HMOs for cognition mainly focus on studies of piglets, mice and rats, and humans. Experimentally, they mainly focus on behavioral tests (novel object recognition, hole board experiment), gut microbiota, microbiomics, macromolecular and microscopic structures, studies related to 5HT receptors and solute carrier genes of 5HT transporters, myelination and myelin pathways, etc. Currently, there are no reports on the improvement of brain development and promotion of nerve and / or cognitive development (such as improvement of brain development and promotion of nerve and cognitive development) in the form of a composition formed by mixing HMOs and MLCT. Summary of the Invention

[0006] The present invention is made in view of the above problems existing in the prior art.

[0007] The present invention relates to a non-therapeutic use of a nutritional composition for improving brain development, promoting nerve and / or cognitive development (such as improving brain development, promoting nerve and cognitive development), wherein the nutritional composition comprises medium and long-chain fatty acid triglycerides and human milk oligosaccharides, and the mass ratio of the medium and long-chain fatty acid triglycerides to the human milk oligosaccharides is 1:1 to 9:1.

[0008] The inventors unexpectedly found in the research that when the medium and long-chain fatty acid triglycerides and human milk oligosaccharides are used in combination according to the defined mass ratio, the two can have a synergistic effect and synergistically improve brain development, promote nerve and / or cognitive development (such as improving brain development, promoting nerve and cognitive development). BRIEF DESCRIPTION OF THE DRAWINGS

[0009] To more clearly illustrate the technical solutions of the present invention, the drawings required for describing the embodiments will be briefly described below. It should be understood that these drawings are only for facilitating those skilled in the art to more easily understand the present invention, rather than intending to limit the scope of the present invention.

[0010] Figure 1 It is a schematic diagram of a plus maze (right figure) and the movement trajectory of zebrafish in the plus maze within 2 weeks (left figure). DETAILED DESCRIPTION OF THE EMBODIMENTS

[0011] In order to make the invention object, technical solutions and beneficial technical effects of the present invention clearer, the present invention will be described in detail below. It should be noted that the various aspects, features, embodiments, and their advantages described in the present invention can be compatible and / or combined together.

[0012] Unless otherwise specified, the meanings of the technical terms or scientific and technical terms in this specification are the same as those generally understood by those skilled in the art.

[0013] In this application, unless otherwise specified, the temperature is room temperature (25 °C), the atmosphere is air, and the pressure is atmospheric pressure.

[0014] In the present application, the term "medium-chain fatty acid" refers to fatty acids having 6 to 12 carbon atoms in the carbon chain, such as caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecanoic acid, lauric acid, etc.; the term "long-chain fatty acid" refers to fatty acids having more than 14 carbon atoms, generally 14 to 30 carbon atoms in the carbon chain, such as myristic acid, palmitic acid, oleic acid, linoleic acid, stearic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid, etc. The terms "medium-chain fatty acid triglyceride" and "long-chain fatty acid triglyceride" respectively refer to the esterification reaction products of "medium-chain fatty acid" and "long-chain fatty acid" with glycerol; the term "medium and long-chain fatty acid triglyceride" refers to triglycerides containing both medium-chain fatty acid residues and long-chain fatty acid residues in the molecular structure.

[0015] In the present application, the term "human milk oligosaccharide" is a class of complex oligosaccharides formed by connecting structural units such as monosaccharides and derivatives, sialic acid, etc. through glycosidic bonds.

[0016] In the present application, the term "non-therapeutic purpose" has its conventional meaning in the art, which includes, for example, nutritional and / or health care purposes, which may be, for example, for the preparation of foods such as ordinary foods, functional foods, or health foods, etc.

[0017] The present invention will be described in detail below.

[0018] The present invention relates to the use of a nutritional composition for non-therapeutic purposes of improving brain development, promoting nerve and / or cognitive development (such as improving brain development, promoting nerve and cognitive development), wherein the nutritional composition comprises or is medium and long-chain fatty acid triglyceride and human milk oligosaccharide, and the mass ratio of the medium and long-chain fatty acid triglyceride to the human milk oligosaccharide is 1:1 to 9:1.

[0019] The inventors unexpectedly found in the research that when medium and long-chain fatty acid triglyceride and human milk oligosaccharide are used in combination according to the defined mass ratio, the two can have a synergistic effect and synergistically improve brain development, promote nerve and / or cognitive development. It should be noted that in the present application, the expression "improving brain development, promoting nerve and / or cognitive development" can be understood as one or more of "improving brain development", "promoting nerve development", and "promoting cognitive development". For example, it can be understood as "improving brain development", or understood as "promoting nerve development", or understood as "promoting cognitive development", or understood as "improving brain development" and "promoting nerve development", or understood as "improving brain development" and "promoting cognitive development", or understood as "promoting nerve development" and "promoting cognitive development", or understood as "improving brain development", "promoting nerve development", and "promoting cognitive development".

[0020] In the present application, the mass ratio of the medium- and long-chain fatty acid triglyceride to the human milk oligosaccharide may be from 1:1 to 9:1. As an example, the mass ratio of the medium- and long-chain fatty acid triglyceride to the human milk oligosaccharide may be 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or a range defined by any two of them.

[0021] In some embodiments, the mass ratio of the medium- and long-chain fatty acid triglyceride to the human milk oligosaccharide may be from 2:1 to 9:1; within this range, the synergistic effect between the medium- and long-chain fatty acid triglyceride and the human milk oligosaccharide in terms of improving brain development and promoting nerve and / or cognitive development (such as improving brain development and promoting nerve and cognitive development) is more significant.

[0022] The present invention has no particular requirements for the human milk oligosaccharide used, and the human milk oligosaccharide conventionally used in the art can be used. The human milk oligosaccharide can be used in the form of a pure product or in a non-pure form rich in human milk oligosaccharide.

[0023] Human milk oligosaccharides (also known as milk oligosaccharides or human milk oligosaccharides, Human Milk Oligosaccharides) are the third largest solid component in breast milk, second only to lactose and fat, and have important biological activities. Classified according to representative groups, human milk oligosaccharides can be divided into fucosylated human milk oligosaccharides (such as 2'-fucosyllactose), sialylated human milk oligosaccharides (such as 3'-sialyllactose), and non-fucosylated and non-sialylated human milk oligosaccharides (such as lacto-N-neotetraose).

[0024] In some embodiments, the human milk oligosaccharide is selected from one or more of the following: fucosylated human milk oligosaccharides, sialylated human milk oligosaccharides, non-fucosylated and non-sialylated human milk oligosaccharides. For example, the human milk oligosaccharide may be: one or more fucosylated human milk oligosaccharides; one or more sialylated human milk oligosaccharides; one or more non-fucosylated and non-sialylated human milk oligosaccharides; one or more fucosylated human milk oligosaccharides and one or more sialylated human milk oligosaccharides; one or more fucosylated human milk oligosaccharides and one or more non-fucosylated and non-sialylated human milk oligosaccharides; one or more sialylated human milk oligosaccharides and one or more non-fucosylated and non-sialylated human milk oligosaccharides; one or more fucosylated human milk oligosaccharides, one or more sialylated human milk oligosaccharides, and one or more non-fucosylated and non-sialylated human milk oligosaccharides.

[0025] In some embodiments, the fucosylated human milk oligosaccharide may be selected from one or more of the following: 2'-fucosyllactose (2'-FL), 3-fucosyllactose, lacto-N-fucopentaose I, lacto-N-difucohexaose I, lacto-N-difucohexaose II, lacto-bifucosyltetraose.

[0026] In some embodiments, the sialylated human milk oligosaccharide may be selected from one or more of the following: 3'-sialyllactose (3'-SL), 6'-sialyllactose.

[0027] In some embodiments, the non-fucosylated and non-sialylated human milk oligosaccharide is selected from one or more of the following: lacto-N-tetraose (LNnT), lacto-N-neotetraose, lacto-N-triose II, lacto-N-disaccharide.

[0028] In some preferred embodiments, the human milk oligosaccharide may be selected from one of the following: 2'-fucosyllactose; 3'-sialyllactose; lacto-N-neotetraose; 2'-fucosyllactose and 3'-sialyllactose; 2'-fucosyllactose and lacto-N-neotetraose; 3'-sialyllactose and lacto-N-neotetraose; 2'-fucosyllactose, 3'-sialyllactose and lacto-N-neotetraose. When the human milk oligosaccharide is selected from the above components or combinations, it can more significantly improve brain development and promote neural and / or cognitive development (such as improving brain development and promoting neural and cognitive development).

[0029] In some preferred embodiments, the human milk oligosaccharide is selected from 2'-fucosyllactose or lacto-N-neotetraose, and the ratio of the medium-chain and long-chain fatty acid triglyceride to the total mass of the human milk oligosaccharide is from 5:1 to 9:1; in some preferred embodiments, the human milk oligosaccharide is selected from 3'-sialyllactose, and the mass ratio of the medium-chain and long-chain fatty acid triglyceride to 3'-sialyllactose is from 2:1 to 5:1; in some preferred embodiments, the human milk oligosaccharide is selected from any two of 2'-fucosyllactose, 3'-sialyllactose and lacto-N-neotetraose, and the ratio of the mass of the medium-chain and long-chain fatty acid triglyceride to the total mass of the human milk oligosaccharide is from 5:1 to 7:1; in some preferred embodiments, the human milk oligosaccharide is 2'-fucosyllactose, 3'-sialyllactose and lacto-N-neotetraose, and the ratio of the mass of the medium-chain and long-chain fatty acid triglyceride to the total mass of the human milk oligosaccharide is from 1:1 to 3:1. The inventors found in the study that in the above preferred embodiments, when the mass ratio of the medium-chain and long-chain fatty acid triglyceride to the human milk oligosaccharide is within the preferred mass ratio range defined above, the synergistic effect of the nutritional composition in improving brain development and promoting nerve and / or cognitive development (such as improving brain development and promoting nerve and cognitive development) is more significant.

[0030] In the present application, when the human milk oligosaccharide is a mixture of any two or more kinds, the ratio between the components of the human milk oligosaccharide is not particularly limited and can be appropriately selected in consideration of other effects of each specific human milk oligosaccharide; for example, the mass ratio between any two specific human milk oligosaccharides can be between 20:1 and 1:20, for example 15:1 to 1:15.

[0031] For example, when the human milk oligosaccharide includes fucosylated human milk oligosaccharide (such as 2'-FL) and sialylated human milk oligosaccharide (such as 3'-SL), the mass ratio of the fucosylated human milk oligosaccharide / sialylated human milk oligosaccharide, for example the 2'-FL / 3'-SL mass ratio, can be 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, 12:1, 11:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, or the range defined by any two of them.

[0032] For example, when the human milk oligosaccharides include fucosylated human milk oligosaccharides (such as 2'-FL) and non-fucosylated and non-sialylated human milk oligosaccharides (such as LNnT), the mass ratio of fucosylated human milk oligosaccharides to non-fucosylated and non-sialylated human milk oligosaccharides, for example, the 2'-FL / LNnT mass ratio, can be 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, 12:1, 11:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, or a range defined by any two of them.

[0033] For example, when the human milk oligosaccharides include sialylated human milk oligosaccharides (such as 3'-SL) and non-fucosylated and non-sialylated human milk oligosaccharides (such as LNnT), the mass ratio of sialylated human milk oligosaccharides to non-fucosylated and non-sialylated human milk oligosaccharides, for example, the 3'-SL / LNnT mass ratio, can be 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, 12:1, 11:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, or a range defined by any two of them.

[0034] For example, when the human milk oligosaccharides include fucosylated human milk oligosaccharides (such as 2'-FL), sialylated human milk oligosaccharides (such as 3'-SL), and non-fucosylated and non-sialylated human milk oligosaccharides (such as LNnT), the mass ratio of fucosylated human milk oligosaccharides / sialylated human milk oligosaccharides, such as the 2'-FL / 3'-SL mass ratio, the mass ratio of fucosylated human milk oligosaccharides / non-fucosylated and non-sialylated human milk oligosaccharides, such as the 2'-FL / LNnT mass ratio, and the mass ratio of sialylated human milk oligosaccharides / non-fucosylated and non-sialylated human milk oligosaccharides, such as the 3'-SL / LNnT mass ratio, can each independently be 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, 12:1, 11:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, or a range defined by any two of them.

[0035] Medium-chain triglycerides (MLCT) are a type of structural lipid in which triglyceride molecules contain both medium-chain fatty acids and long-chain fatty acids. They have different physical and chemical properties, metabolic characteristics, and nutritional values from long-chain triglycerides (LCT) or medium-chain triglycerides (MCT). Research (see, for example, Yuan Tinglan, Composition and Metabolic Characteristics of Medium-chain Triglycerides in Human Milk Fat [D], Jiangnan University, 2021) shows that medium-chain triglycerides (MLCT) are not simply equivalent to a physical mixture of long-chain triglycerides (LCT) and medium-chain triglycerides (MCT) (certainly not equivalent to a simple mixture of long-chain fatty acids and medium-chain fatty acids), and the latter do not possess the physical and chemical properties, metabolic characteristics, and nutritional values of the former.

[0036] The present invention has no particular requirements for the medium-chain triglycerides used, and medium-chain triglycerides commonly used in the art can be used. The medium-chain triglycerides can be used in pure form or in a non-pure form rich in medium-chain triglycerides.

[0037] In some embodiments, the medium-chain triglycerides of the present invention contain C6-C 12 (such as C6, C7, C8, C9, C 10 , C 11 , C 12 , or a range defined by any two of them) fatty acid residues and C 14 -C 30(such as C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , C 24 , C 25 , C 26 , C 27 , C 28 , C 29 , C 30 , or the range defined by any two of them) fatty acid residues, wherein: the C6-C 12 fatty acid residues are derived from one or more of the following: caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecanoic acid, lauric acid, etc., preferably caproic acid, caprylic acid, capric acid and lauric acid; and / or the C 14 -C 30 fatty acid residues are derived from one or more of the following: myristic acid, palmitic acid, margaric acid, oleic acid, linoleic acid, stearic acid, nonadecanoic acid, eicosapentaenoic acid, heneicosanoic acid, docosatetraenoic acid, docosahexaenoic acid, tricosanoic acid, tetracosenoic acid, pentacosenoic acid, docosahexaenoic acid, arachidonic acid, etc., preferably myristic acid, palmitic acid, oleic acid, linoleic acid, stearic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid.

[0038] In some embodiments, in the medium-chain triglyceride, the mass ratio of the C6-C 12 fatty acid residues to the C 14 -C 30 fatty acid residues is 0.124 to 2.000. As an example, the mass ratio of the C6-C 12 fatty acid residues to the C 14 -C 30 fatty acid residues can be 0.124, 0.125, 0.130, 0.140, 0.150, 0.160, 0.170, 0.180, 0.190, 0.200, 0.300, 0.400, 0.500, 0.600, 0.700, 0.800, 0.900, 1.000, 1.100, 1.200, 1.300, 1.400, 1.500, 1.600, 1.700, 1.800, 1.900, 2.000, or the range defined by any two of them.

[0039] In some embodiments, the nutritional composition of the present invention can be composed of medium-chain fatty acid esters and human milk oligosaccharides.

[0040] In some embodiments, the nutritional composition may be used in the form of a food product thereof. In some embodiments, the food product is an infant food such as an infant formula.

[0041] In some embodiments, based on the total mass of the food product, the content of human milk oligosaccharide may be from 0.01 to 6% by mass. As an example, based on the mass of the food product, the content may be 0.01, 0.02, 0.05, 0.1, 0.2, 0.5, 1, 2, 3, 4, 5, 6% by mass, or a range defined by any two of them. The content of medium and long-chain fatty acid triglycerides may be converted based on the ratio to human milk oligosaccharide.

[0042] In some embodiments, based on the total mass of the food product, the content of medium and long-chain fatty acid triglycerides may be from 0.1 to 30% by mass. As an example, based on the mass of the food product, the content of medium and long-chain fatty acid triglycerides may be 0.1, 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30% by mass, or a range defined by any two of them.

[0043] In some embodiments, the food product may be a general food or a special food. As an example, the food product may be selected from dairy products, candies, beverages, breads, and biscuits. For example, the food product may be selected from milk powder or fermented foods. In some embodiments, the milk powder is an infant formula milk powder.

[0044] In some embodiments, the food product may be, for example, a functional food or a health food.

[0045] In addition, it is easily understood by those skilled in the art that in addition to the nutritional composition of the first aspect of the present invention, the food product further includes one or more selected from the following: raw cow milk, demineralized whey powder, concentrated whey protein, lactose, edible vegetable blended oil, fructooligosaccharide, galactooligosaccharide, nucleotides, choline, vitamins, minerals, DHA, and taurine.

[0046] For example, when the food product is milk powder, in addition to the nutritional composition, the milk powder may further include proteins such as α-lactalbumin and milk fat globule membrane protein; saccharides such as lactose; lipids; minerals such as calcium, iron, phosphorus, etc.; vitamins; and other additives such as whey powder, choline bitartrate, docosahexaenoic acid, arachidonic acid, walnut oil, etc.

[0047] The food product may be produced by a preparation method commonly used in the art, which will not be elaborated herein.

[0048] In some embodiments, when the nutritional composition is used for oral administration to humans, the dosage is such that the dosage of the human milk oligosaccharide is 0.05 to 25 g / day, preferably 0.1 to 25 g / day. As an example, the dosage of the human milk oligosaccharide can be 0.05, 0.10, 0.50, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10.0, 11.0, 12.0, 13.0, 14.0, 15.0, 16.0, 17.0, 18.0, 19.0, 20.0, 21.0, 22.0, 23.0, 24.0, 25.0 g / day, or within the range defined by any two of them. The dosage of the medium- and long-chain fatty acid triglyceride can be converted according to the ratio to the human milk oligosaccharide.

[0049] In some embodiments, when the nutritional composition is used for oral administration to humans, the dosage is such that the dosage of the medium- and long-chain fatty acid triglyceride is 0.1 to 30 g / day, preferably 1.7 to 30 g / day. As an example, the dosage of the medium- and long-chain fatty acid triglyceride can be 0.10, 0.50, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10.0, 11.0, 12.0, 13.0, 14.0, 15.0, 16.0, 17.0, 18.0, 19.0, 20.0, 21.0, 22.0, 23.0, 24.0, 25.0, 26.0, 27.0, 28.0, 29.0, 30.0 g / day, or within the range defined by any two of them.

[0050] In some embodiments, the use involved in the present invention is particularly for non-therapeutic purposes of improving brain development, promoting nerve and / or cognitive development (such as improving brain development, promoting nerve and cognitive development) in infants, children or adolescents, especially for non-therapeutic purposes of improving brain development, promoting nerve and / or cognitive development (such as improving brain development, promoting nerve and cognitive development) in infants and / or children.

[0051] Examples

[0052] In order to make the objectives, technical solutions and advantages of the present invention clearer, the present invention will be further described in detail below in conjunction with examples. It should be understood that the specific examples described herein are only used to explain the present invention and are not used to limit the present invention.

[0053] Raw materials

[0054] The sources and specifications of the raw materials used in the following examples are as follows: Medium-chain and long-chain fatty acid triglycerides: sourced from medium-chain and long-chain fatty acid edible oil, with a purity of 69.8% by mass, provided by Qingdao Haizhiyuan Life Science Co., Ltd., batch number Y1501-23070101; 2'-fucosyllactose: provided by DSM Vitamins Trading (Shanghai) Co., Ltd., SHANGHAI, with a purity of 99.2% by mass, batch number: 21107002; 3'-sialyllactose: provided by DSM Vitamins Trading (Shanghai) Co., Ltd., SHANGHAI, with a purity of 95.2% by mass, batch number: DK21294101; Lacto-N-neotetraose: provided by DSM Vitamins Trading (Shanghai) Co., Ltd., DTL Duty Paid. Shanghai, with a purity of 100.5% by mass, batch number: 20454001; Ginkgo biloba and cistanche tablets: Amway Nutrilite Ginkgo biloba and cistanche tablets, batch number 3313N903, provided by Amway (China) Daily Necessities Co., Ltd., specification: 480 mg / tablet; Wild-type AB strain zebrafish: reproduced and provided by the fish breeding center of Hangzhou Huante Biotechnology Co., Ltd., experimental animal use license number: SYXK(Zhe)2022-0004.

[0055] In the research on improving brain development and promoting neural and cognitive development, traditionally, animal experiments (piglets, mice, and rats) and human experiments have been mostly used. In recent years, zebrafish experiments have increasingly gained the favor of researchers. This is because zebrafish experiments have the following multiple advantages in the efficacy evaluation experiments of improving brain development, promoting neural development, and / or cognitive development (such as improving brain development, promoting neural and cognitive development): (1) Compared with traditional animal models, the brain development of zebrafish occurs earlier. Neural development can be studied in embryos 24 hours after fertilization. This allows researchers to directly observe the developing nervous system at an early stage, enabling earlier discovery and evaluation of the effects of improving brain development, promoting neural development, and / or cognitive development (such as improving brain development, promoting neural and cognitive development). (2) The small and transparent embryos and larvae of zebrafish are convenient for microscopy imaging, and researchers can clearly observe the activities of each cell. This transparency and high-resolution imaging technology provide great convenience for studying brain development, neural development, and / or cognitive development (such as brain development, neural and cognitive development). (3) Zebrafish have a high degree of genetic similarity to humans and are suitable for gene manipulation techniques such as gene knockout and knock-in. The application of these techniques enables researchers to more precisely study the effects of specific genes on brain development, neural development, and / or cognitive development (such as brain development, neural and cognitive development). (4) Zebrafish have strong reproductive capabilities, develop quickly, and have a short sexual maturity cycle, making them very suitable for high-throughput experiments. High-throughput experiments can greatly accelerate the research process and improve experimental efficiency. (5) The zebrafish model also has strong translational relevance, meaning that its research results are more easily generalized to humans. This makes zebrafish have important application value in the efficacy evaluation of improving brain development, promoting neural development, and / or cognitive development (such as improving brain development, promoting neural and cognitive development).

[0056] The maze is one of the important devices for evaluating different phenomena (such as learning and memory, anxiety, preference, etc.) in the neurological disease model of zebrafish. Various cognitive tasks often use color cues in the maze to study the learning and memory of zebrafish. Color preference tests are mostly used in the evaluation of cognitive impairment in zebrafish. Zebrafish like colors with short wavelengths, such as blue. Compared with other colors (such as red, yellow, and green), zebrafish show a strong preference for blue. As brain development, neural development, and / or cognitive development (such as brain development, neural and cognitive development) improve, the preference of zebrafish for blue becomes more obvious. Figure 1 The right figure in shows a schematic diagram of a plus maze, where the blue area is the preferred area of zebrafish.

[0057] The degree of improvement / promotion of the studied nutritional composition on the brain development, neural and / or cognitive development (such as brain development, neural and cognitive development) of zebrafish is evaluated by analyzing and comparing the proportion of the movement trajectories of zebrafish in the blue area. According to the statistical significance test method, the statistical differences between the normal control group without any nutritional composition and the experimental group with the studied nutritional composition are compared, and are represented by the p-value, where p>0.05 indicates no statistical difference, p<0.05 indicates a statistical difference, p<0.01 indicates a significant statistical difference, and p<0.001 indicates an extremely significant statistical difference. Therefore, it can be understood that when the p-value situations of the two experimental groups are different, it means that there are significant statistical differences in the technical effects of these two groups. Therefore, the synergistic effect between the components in the corresponding experimental group formula can be judged according to the p-value difference between the experimental group formula and the control group formula.

[0058] Experimental protocol

[0059] The following experiments were conducted to study the effects of medium- and long-chain fatty acid triglycerides and different types of human milk oligosaccharides on the brain development, neural and / or cognitive development (such as brain development, neural and cognitive development) of zebrafish respectively.

[0060] 1. Detection materials

[0061] 1.1. Sample preparation information

[0062] MLCT, 2’-FL, LNnT, 3’-SL, and the solvent is standard dilution water.

[0063] Positive control: Amway Nutrilite Ginkgo and Cistanche Tablets (hereinafter referred to as Ginkgo and Cistanche Tablets), brown tablets, batch number 3313N903, Amway (China) Daily Necessities Co., Ltd., and the solvent is standard dilution water.

[0064] 1.2. Experimental animals

[0065] All zebrafish were raised in fish-raising water at 28°C (water quality: 200 mg of instant sea salt was added to every 1 L of reverse osmosis water, the conductivity was 450~550 μS / cm; the pH was 6.5~8.5; the hardness was 50~100 mg / L CaCO3), provided by the fish-raising center of our company, and the experimental animal use license number was: SYXK(Zhe)2022-0004. The feeding management met the requirements of international AAALAC accreditation (accreditation number: 001458), and the IACUC ethical review number was: IACUC-2024-9218-01.

[0066] 1.3. Instruments, consumables and reagents

[0067] Dissecting microscope (SZX7, OLYMPUS, Japan); CCD camera (VertA1, Shanghai Tusen Vision Technology Co., Ltd., China); Precision electronic balance (CP214, OHAUS, USA); Behavior analyzer (ZebraLab3.22.3.31, Viewpoint, France); 6-well plate (Zhejiang Beilanbo Biotechnology Co., Ltd., China); Ultrasonic cleaner (JP-010T, Shenzhen Jiemeng Cleaning Equipment Co., Ltd., China); Automatic sample rapid grinder (JXFSTPRP-24L, Shanghai Jingxin Experimental Equipment Science and Technology Department, China).

[0068] 2. Detection method

[0069] Wild-type AB strain zebrafish at 5 days post-fertilization (5 dpf) were randomly selected and placed in beakers. Each beaker (experimental group) was treated with 30 zebrafish. The samples were administered in aqueous solution. The positive control was Ginkgo biloba and Cistanche deserticola tablets at a concentration of 125 μg / mL. At the same time, a normal control group was set up. The capacity of each beaker was 20 mL. Among them, for the zebrafish in the experimental group (30 tails), they were fed daily according to the formula in Table 1-4 (in each experiment in Table 1-4, the sum of the dosages of MLCT and all human milk oligosaccharides (HMO) was 800 μg / mL; the ratio outside the brackets in the table was the mass ratio of MLCT to all human milk oligosaccharides, and the ratio inside the brackets was the mass ratio of 2’-FL:LNnT:3’-SL), and treated at 28°C for 1 day; for the zebrafish in the normal control group (30 tails), they were not fed any components and treated at 28°C for 1 day; for the zebrafish in the positive control group (30 tails), they were fed with 125 μg / mL of Ginkgo biloba and Cistanche deserticola tablets and treated at 28°C for 1 day.

[0070] After treatment at 28°C for 1 day, 5 zebrafish were randomly selected from each experimental group and placed in a "cross" module. The module was divided into four regions: yellow, blue, red, and green. Six modules were placed in each group. The behavior analyzer was used to collect data and analyze the percentage (%) of the total movement distance of the zebrafish in the blue region within the total movement distance of the entire region within 10 min. The statistical analysis results of this index were used to evaluate the efficacy of the sample in improving brain development and promoting nerve and / or cognitive development (such as improving brain development and promoting nerve and cognitive development). The statistical processing results were expressed as mean ± SE. SPSS 26.0 software was used for statistical analysis (between two groups). p < 0.05 indicated that the difference was statistically significant.

[0071] The dosages of each component in each batch and the analysis results were summarized in Table 1-4.

[0072] Table 1

[0073]

[0074] Table 2

[0075]

[0076] Table 3

[0077]

[0078] Table 4

[0079]

[0080] As can be seen from Tables 1 - 4, when MLCT is mixed with one or more human milk oligosaccharides in a mass ratio of 1:1 to 9:1, a synergistic effect occurs between MLCT and human milk oligosaccharides, synergistically improving brain development and promoting neural and / or cognitive development (such as improving brain development and promoting neural and cognitive development).

[0081] Specifically: The p - values of Formulas 7, 20, and 21 in which MLCT and 2'-FL are combined in a mass ratio of 2:1 to 9:1 (the same below, relative to the normal control group) are less than 0.05, while the p - values of Formulas 1 and 2 using MLCT or 2'-FL alone and Formula 14 with a mass ratio of MLCT to 2'-FL of 0.1:1 are greater than 0.05, indicating that when MLCT and 2'-FL are combined in a mass ratio of 2:1 to 9:1, the two can synergistically improve the efficacy of brain development and promote neural and / or cognitive development (such as improving brain development and promoting neural and cognitive development), and the effect when the mass ratio of MLCT to 2'-FL is 2:1 to 9:1 is better than that when the mass ratio is 0.1:1; The p - values of Formulas 6, 22, and 23 in which MLCT and LNnT are combined in a mass ratio of 2:1 to 9:1 are less than 0.05, while the p - values of Formula 1 using MLCT alone and Formula 16 using LNnT alone are greater than 0.05, indicating that when MLCT and LNnT are combined in a mass ratio of 2:1 to 9:1, the two can synergistically improve the efficacy of brain development and promote neural and / or cognitive development (such as improving brain development and promoting neural and cognitive development); The p - values of Formulas 5, 24, and 25 in which MLCT and 3'-SL are combined in a mass ratio of 2:1 to 9:1 are less than 0.05, while the p - values of Formula 1 using MLCT alone and Formula 17 using 3'-SL alone are greater than 0.05, indicating that when MLCT and 3'-SL are combined in a mass ratio of 2:1 to 9:1, the two can synergistically improve the efficacy of brain development and promote neural and / or cognitive development (such as improving brain development and promoting neural and cognitive development).

[0082] Therefore, the above experiments show that for any one of 2’-FL, LNnT, and 3’-SL, when combined with MLCT at a specific ratio, there is a synergistic effect between human milk oligosaccharides and MLCT.

[0083] In addition, it can also be seen from Tables 1-4 that the p-values of Formulas 8 to 10 in which MLCT is combined with any two of 2’-FL, LNnT, and 3’-SL at a mass ratio of 5:1 to 7:1 are less than 0.05, while the p-values of Comparative Formulas 1, 2, 3, 16, and 17 using fewer components (not using MLCT and human milk oligosaccharides simultaneously) are all greater than 0.05, indicating that when MLCT is combined with any two of 2’-FL, LNnT, and 3’-SL at a specific mass ratio, they have a synergistic effect in improving brain development, promoting nerve development, and / or cognitive development (such as improving brain development, promoting nerve and cognitive development); the p-values of Formulas 11-12 in which MLCT, 2’-FL, LNnT, and 3’-SL are combined at an MLCT / HMO mass ratio of 1:1 to 3:1 are less than 0.05, while the p-values of Comparative Formulas 1, 2, 4, 16-17 and Formulas 13 and 15 with an MLCT / HMO mass ratio of 10:1 to 100:1 are all greater than 0.05, indicating that when MLCT, 2’-FL, LNnT, and 3’-SL are combined, they have a synergistic effect in improving brain development, promoting nerve development, and / or cognitive development (such as improving brain development, promoting nerve and cognitive development), and the effect is better than that when the MLCT / HMO mass ratio is 10:1 to 100:1.

[0084] The above description is only an exemplary embodiment of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the inventive concept of the present invention, improvements can still be made to the present invention, but these all fall within the protection scope of the present invention.

Claims

1. Use of a nutritional composition for non-therapeutic purposes of improving brain development and promoting neural and / or cognitive development, characterized in that The nutritional composition comprises medium and long chain triglycerides and human milk oligosaccharides, and the mass ratio of the medium and long chain triglycerides to the human milk oligosaccharides is from 1:1 to 9:

1. It is characterized in that the human milk oligosaccharides are selected from one of the following: 2'-fucosyllactose; 3'-sialyllactose; lacto-N-neotetraose; 2'-fucosyllactose and 3'-sialyllactose; 2'-fucosyllactose and lacto-N-neotetraose; 3'-sialyllactose and lacto-N-neotetraose; 2'-fucosyllactose, 3'-sialyllactose and lacto-N-neotetraose.

2. The use according to claim 1, characterized in that The mass ratio of the medium and long chain triglycerides to the human milk oligosaccharides is 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, or 9:

1.

3. The use according to claim 1, characterized in that The mass ratio of the medium and long chain triglycerides to the human milk oligosaccharides is from 2:1 to 9:

1.

4. The use according to claim 1, characterized in that The human milk oligosaccharides are 2'-fucosyllactose or lacto-N-neotetraose, and the ratio of the mass of the medium and long chain triglycerides to the total mass of the human milk oligosaccharides is from 5:1 to 9:

1.

5. The use according to claim 1, characterized in that The human milk oligosaccharides are selected from 3'-sialyllactose, and the mass ratio of the medium and long chain triglycerides to 3'-sialyllactose is from 2:1 to 5:

1.

6. The use according to claim 1, wherein The human milk oligosaccharides are selected from any two of 2'-fucosyllactose, 3'-sialyllactose and lacto-N-neotetraose, and the ratio of the mass of the medium and long chain triglycerides to the total mass of the human milk oligosaccharides is from 5:1 to 7:

1.

7. The use according to claim 1, characterized in that The human milk oligosaccharides are 2'-fucosyllactose, 3'-sialyllactose and lacto-N-neotetraose, and the ratio of the mass of the medium and long chain triglycerides to the total mass of the human milk oligosaccharides is from 1:1 to 3:

1.

8. The use according to any one of claims 1 to 7, characterized in that The nutritional composition is used in the form of a food comprising the same.

9. The use according to claim 8, characterized in that The food is an infant food.

10. The use according to claim 8, characterized in that The food is selected from dairy products, confectionery, beverages, bread and biscuits.

11. The use according to claim 10, characterized in that The food is milk powder or a fermented food.

12. The use according to claim 11, wherein The milk powder is infant formula milk powder.

13. The use according to claim 8, characterized in that The food further comprises one or more components selected from the following: raw cow milk, demineralized whey powder, concentrated whey protein, lactose, edible vegetable blend oil, fructooligosaccharide, galactooligosaccharide, nucleotides, choline, vitamins, minerals, DHA and taurine.

14. The use according to any one of claims 1-7, characterized in that The improvement of brain development and the promotion of nerve and / or cognitive development are for improving brain development and promoting nerve and / or cognitive development in infants and / or children.

15. The use according to claim 8, characterized in that The food is a health food.

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