Use of nutritional compositions for non-therapeutic purposes of improving brain development, promoting neurological 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 neurological and / or cognitive development. The nutritional composition comprises medium-chain and long-chain fatty acid triglyceride and breast milk oligosaccharide, and the mass ratio of the medium-chain and long-chain fatty acid triglyceride to the breast milk oligosaccharide is 1: 1 to 9: 1. In the composition, the medium-chain and long-chain fatty acid triglyceride and the breast milk oligosaccharide have a synergistic effect in the aspect of application, and the effects of improving brain development and promoting nerve and / or cognitive development of the composition are remarkably improved. The composition can be used for preventing or improving brain development retardation, nervous system and / or cognitive development retardation; meanwhile, the composition can also be used for preventing or improving learning ability impairment, mental behavior impairment, memory impairment or attention breadth reduction and the like, and has a relatively good application prospect.

Description

Technical Field

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

[0002] The brain is the higher center of the nervous system, which plays a role in controlling and regulating the functional activities of various systems in the body. Studies have shown that the brain weight of humans is about 370 g at birth, about 600-700 g at 6 months, 900-1000 g at 2 years old, and more than 3 times the weight at birth at 3 years old. It can be seen that brain development, neural development and / or cognitive development play an important role in future intellectual development. Currently, products on the market that improve brain development, promote neural development and / or cognitive development mostly use DHA, AA, vitamins, zinc, etc. as main raw materials. Therefore, it is of great significance to study and find a nutritional composition that can improve brain development, promote neural development and / or cognitive development.

[0003] Early studies have shown that compositions containing one or more long-chain polyunsaturated fatty acids (LCPUFA) 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, high-dose MCT administration can cause gastrointestinal discomfort, and long-term use of MCTs carries the risk of ketoacidosis or ketonemia. Medium-chain triglycerides (MLCTs) have one or two medium-chain fatty acids attached to the glycerol backbone, while the rest are long-chain fatty acids. Medium-chain triglycerides account for about 30% of total triglycerides in breast milk. Early studies have shown that the fatty acid composition of MLCT is closer to breast milk, which is beneficial to fat digestion and absorption, improves the absorption of lipid nutrients, inhibits the accumulation of body fat, and can quickly and stably provide energy (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 on Medium and Long-Chain Triacylglycerols in Breast Milk [J]. Journal of Food and Biotechnology, 2022, 41(6): 41-50.). In addition, when the overall fatty acid composition in breast milk is the same, the structure of triglycerides is different and their biological functions are also very different.For example, studies on mice have shown that compared with feeding a formula lipid feed containing LCT / MCT physical mixed vegetable oil with the same fatty acid composition, feeding a formula lipid feed containing human milk structural fat MLCT has the function of regulating mouse thermogenesis, inhibiting visceral fat accumulation, changing intestinal flora, and regulating lipid metabolism (Yuan T, Cheng X, Shen L, Liu Z, Ye X, Yan Z, Wei W, Wang X. Novel Human Milk FatSubstitutes Based on Medium- and Long-Chain Triacylglycerol RegulateThermogenesis, Lipid Metabolism, and Gut Microbiota Diversity in C57BL / 6JMice. J Agric Food Chem. 2024 Mar 27;72(12):6213-622.), however, there are few reports on the effects of MLCT on brain cognitive development.

[0004] Human milk oligosaccharides (HMOs) are rich in components. Currently, HMOs can be classified in different ways. According to pH, they are divided into neutral oligosaccharides and acidic oligosaccharides. Neutral oligosaccharides can be further divided into fucosyl-free and fucosyl-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. According to the classification of representative groups, they are divided into fucosyl-containing (e.g. 2′-fucosyllactose (fucosyllactose, 2′-FL)), sialic acid-containing (e.g. 6′-Sialyllactose (sialyllactose sodium salt, 6′-SL), 3′-Sialyllactose (sialyllactose sodium salt, 3′-SL)), non-fucosyl and non-sialic acid groups (e.g. lacto-N-tetraose (lacto-N-tetraose, LNT), lacto-N-neotetraose (lacto-N-neotetraose, LNnT)).

[0005] At present, the research on HMO for cognition mainly tends to be on piglets, mice and humans, and the experiments mainly focus on behavioral tests (new object recognition, hole plate test), intestinal flora, microbiome and macromolecular structure and microstructure, 5HT receptor and 5HT transporter protein solute carrier gene-related research, myelination and myelination pathways, etc. At present, there are no reports of HMO and MLCT in the form of a combination to improve brain development, promote neural and / or cognitive development (e.g., improve brain development, promote neural and cognitive development). 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 use of a nutritional composition for the non-therapeutic purpose of improving brain development, promoting neural and / or cognitive development (e.g., improving brain development, promoting neural and cognitive development), wherein the nutritional composition comprises medium-chain fatty acid triglycerides and human milk oligosaccharides, and the mass ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides is 1:1 to 9:1.

[0008] The inventors unexpectedly discovered during their research that when medium- and long-chain fatty acid triglycerides and human milk oligosaccharides are used in combination at a specified mass ratio, the two can act synergistically to synergistically improve brain development, promote neural and / or cognitive development (e.g., improve brain development, promote neural and cognitive development). BRIEF DESCRIPTION OF THE DRAWINGS

[0009] In order to more clearly illustrate the technical solution of the present invention, the following will briefly describe the drawings required for describing the embodiments. It should be understood that these drawings are only for the convenience of technicians to understand the present invention more easily, and are not intended to limit the scope of the present invention.

[0010] Figure 1 Schematic diagram of the plus maze (right) and the movement trajectory of zebrafish in the plus maze over a 2-week period (left). DETAILED DESCRIPTION

[0011] In order to make the invention purpose, technical solution and beneficial technical effect 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 advantages described in the present invention may be compatible and / or may be combined together.

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

[0013] In the present 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 with 6-12 carbon atoms in the carbon chain, such as caproic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, dodecanoic acid, etc.; the term "long-chain fatty acid" refers to fatty acids with more than 14 carbon atoms, generally 14-30 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" refer to the esterification reaction products of "medium-chain fatty acid" and "long-chain fatty acid" with glycerol, respectively; the term "medium-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 oligosaccharides" refers to a class of complex oligosaccharides composed of monosaccharides and their derivatives, sialic acid and other structural units connected by glycosidic bonds.

[0016] In the present application, the term "non-therapeutic purpose" has the conventional meaning in the art, which includes, for example, nutritional and / or health purposes, which can be used for preparing 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 the non-therapeutic purpose of improving brain development, promoting neural and / or cognitive development (e.g., improving brain development, promoting neural and cognitive development), wherein the nutritional composition comprises or is medium-chain fatty acid triglycerides and human milk oligosaccharides, and the mass ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides is 1:1 to 9:1.

[0019] The inventor unexpectedly discovered in the study that when medium- and long-chain fatty acid triglycerides and human milk oligosaccharides are used in combination according to a defined mass ratio, the two can act synergistically to synergistically improve brain development and promote neural and / or cognitive development. It should be noted that in the present application, the expression "improving brain development, promoting neural and / or cognitive development" can be understood as "improving brain development", "promoting neural development" and "promoting cognitive development" One or more, for example, it can be understood as "improving brain development", or as "promoting neural development", or as "promoting cognitive development", or as "improving brain development" and "promoting neural development", or as "improving brain development" and "promoting cognitive development", or as "promoting neural development" and "promoting cognitive development", or as "improving brain development" and "promoting cognitive development", or as "promoting neural development" and "promoting cognitive development", or as "improving brain development", "promoting neural development" and "promoting cognitive development".

[0020] In the present application, the mass ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides may be 1: 1 to 9: 1. As an example, the mass ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides 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-chain fatty acid triglycerides to the human milk oligosaccharides can be 2:1 to 9:1; within the range, the synergistic effect between the medium-chain fatty acid triglycerides and human milk oligosaccharides in improving brain development, promoting neural and / or cognitive development (e.g., improving brain development, promoting neural and cognitive development) is more significant.

[0022] The present invention has no special requirements for the human milk oligosaccharides used, and the human milk oligosaccharides conventionally used in the art can be used. The human milk oligosaccharides can be used in a pure form or in an impure form rich in human milk oligosaccharides.

[0023] Human milk oligosaccharides (also known as human milk oligosaccharides or human milk oligosaccharides) are the third largest solid component in breast milk, second only to lactose and fat, and have important biological activity. According to the representative groups, human milk oligosaccharides can be divided into human milk oligosaccharides containing fucosyl groups (such as 2'-fucosyllactose), human milk oligosaccharides containing sialic acid groups (such as 3'-sialyllactose) and non-fucosyl and non-sialic acid human milk oligosaccharides (such as lactose-N-neotetraose).

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

[0025] In some embodiments, the fucosyl-containing human milk oligosaccharide can be selected from one or more of the following: 2'-fucosyllactose (2'-FL), 3-fucosyllactose, lactose-N-fucopentaose I, lactose-N-difucohexaose I, lactose-N-difucohexaose II, and lactose-bifucosyltetrose.

[0026] In some embodiments, the sialic acid-containing 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-fucosyl and non-sialic acid human milk oligosaccharides are selected from one or more of the following: lactose-N-tetraose (LNnT), lactose-N-neotetraose, lactose-N-triose II, and lactose-N-disaccharide.

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

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

[0030] In the present application, when human milk oligosaccharides are a mixture of any two or more, the ratio between the components of human milk oligosaccharides is not particularly limited and can be appropriately selected taking into account the 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, such as 15:1 to 1:15.

[0031] For example, when the human milk oligosaccharide includes a fucosyl-containing human milk oligosaccharide (e.g., 2'-FL) and a sialic acid-containing human milk oligosaccharide (e.g., 3'-SL), the mass ratio of the fucosyl-containing human milk oligosaccharide / the sialic acid-containing 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, 1 1:1, 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.

[0032] For example, when the human milk oligosaccharide includes fucosyl-containing human milk oligosaccharide (e.g., 2'-FL) and non-fucosyl non-sialic acid human milk oligosaccharide (e.g., LNnT), the mass ratio of fucosyl-containing human milk oligosaccharide / non-fucosyl non-sialic acid human milk oligosaccharide, for example, the mass ratio of 2'-FL / LNnT can be 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, 12:1, 14:1, 15:1, 16:1, 17 ... :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 oligosaccharide includes sialic acid-containing human milk oligosaccharide (e.g., 3'-SL) and non-fucosyl non-sialic acid human milk oligosaccharide (e.g., LNnT), the mass ratio of sialic acid-containing human milk oligosaccharide / non-fucosyl non-sialic acid human milk oligosaccharide, for example, the mass ratio of 3'-SL / LNnT can be 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, 12:1, 14:1, 15:1, 16:1, 17 ... :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 oligosaccharide includes fucosyl-containing human milk oligosaccharide (e.g., 2'-FL), sialic acid-containing human milk oligosaccharide (e.g., 3'-SL) and non-fucosyl non-sialic acid human milk oligosaccharide (e.g., LNnT), the mass ratio of fucosyl-containing human milk oligosaccharide / sialic acid-containing human milk oligosaccharide, e.g., 2'-FL / 3'-SL mass ratio, the mass ratio of fucosyl-containing human milk oligosaccharide / non-fucosyl non-sialic acid human milk oligosaccharide, e.g., 2'-FL / LNnT mass ratio, and the mass ratio of sialic acid-containing human milk oligosaccharide / non-fucosyl non-sialic acid human milk oligosaccharide, e.g., 3'-SL mass ratio. The SL / LNnT mass ratio may be independently 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 structural lipids that contain both medium-chain fatty acids and long-chain fatty acids in the triglyceride molecule. They have different physical and chemical properties, metabolic characteristics and nutritional value from long-chain triglycerides (LCT) or medium-chain triglycerides (MCT). Studies (see, for example, Yuan Tinglan, Medium-chain triglyceride composition and metabolic characteristics of breast milk fat [D], Jiangnan University, 2021) show that medium-chain triglycerides (MLCT) are not simply equivalent to a physical mixture of long-chain triglycerides (LCT) and medium-chain triglycerides (MCT) (of course, they are not equivalent to a simple mixture of long-chain fatty acids and medium-chain fatty acids), and the latter does not have the physical and chemical properties, metabolic characteristics and nutritional value of the former.

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

[0037] In some embodiments, the medium-chain fatty acid triglycerides of the present invention contain C6-C 12 (e.g. C6, C7, C8, C9, C 10 , C 11 , C 12 , or the range defined by any two thereof) fatty acid residues and C 14 -C 30(For example, 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 thereof) fatty acid residues, wherein: the C6-C 12 The fatty acid residue is derived from one or more of the following: caproic acid, heptanoic acid, caprylic acid, nonanoic acid, capric acid, undecanoic acid, dodecanoic acid, etc., preferably caproic acid, caprylic acid, capric acid and lauric acid; and / or the C 14 -C 30 The fatty acid residue is derived from one or more of the following: myristic acid, palmitic acid, heptadecanoic acid, oleic acid, linoleic acid, stearic acid, nonadecanoic acid, eicosapentaenoic acid, heneicosanoic acid, docosatetraenoic acid, docosahexaenoic acid, tricosanoic acid, tetracosenoic acid, eicosapentaenoic acid, hexacoshexaenoic 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, the C6-C 12 The fatty acid residues on the C 14 -C 30 The mass ratio of the fatty acid residues is 0.124 to 2.000. As an example, the C6-C 12 The fatty acid residues on the C 14 -C 30 The mass ratio of the fatty acid residues may 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 a range defined by any two of them.

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

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

[0041] In some embodiments, based on the total mass of the food, the content of human milk oligosaccharides may be 0.01 to 20% by mass. As an example, based on the mass of the food, it may be 0.01, 0.02, 0.05, 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% by mass, or a range defined by any two of them, and the content of medium and long chain fatty acid triglycerides may be converted based on the ratio with human milk oligosaccharides.

[0042] In some embodiments, based on the total mass of the food, the content of medium and long-chain fatty acid triglycerides may be 0.1 to 30 mass %. As an example, based on the mass of the food, 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 mass %, or a range defined by any two of them.

[0043] In some embodiments, the food can be a common food or a special food. As an example, the food can be selected from dairy products, candies, beverages, bread and biscuits, for example, the food can be selected from milk powder or fermented food. In some embodiments, the milk powder is infant formula milk powder.

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

[0045] In addition, it is easy for those skilled in the art to understand that, in addition to the nutritional composition of the first aspect of the present invention, the food also includes one or more selected from the following: raw milk, desalted whey powder, concentrated whey protein, lactose, edible vegetable blending oil, oligofructose, oligogalactose, nucleotides, choline, vitamins, minerals, DHA and taurine.

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

[0047] The food can be produced by a preparation method commonly used in the art, which will not be described in detail here.

[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 may 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 triglycerides may be converted according to the ratio with human milk oligosaccharides.

[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-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-chain fatty acid triglyceride may 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 any two of them within the range defined.

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

[0051] Example

[0052] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments 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 fatty acid triglycerides: derived from medium-chain fatty acid edible oil, purity 69.8% by mass, provided by Qingdao Haizhiyuan Life Science Technology Co., Ltd., batch number Y1501-23070101; 2'-fucosyllactose: provided by DSM Vitamins Trading (Shanghai) Co. Ltd. SHANGHAI, purity 99.2% by mass, batch number: 21107002; 3'-sialyllactose: provided by DSM Vitamins Trading (Shanghai) Co. Ltd. SHANGHAI, purity 95.2% by mass, batch number: DK21294101; lactose-N-neotetraose: provided by DSM Vitamins Trading (Shanghai) Co. Ltd. DTL Duty Paid. Provided by Shanghai, purity 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 Products Co., Ltd., specification: 480 mg / tablet; Wild-type AB strain zebrafish: bred and provided by the fish breeding center of Hangzhou Huante Biotechnology Co., Ltd., the experimental animal use license number is: SYXK (Zhejiang) 2022-0004.

[0055] In the study of improving brain development and promoting neural and cognitive development, animal experiments (piglets, mice and rats) and human experiments have traditionally been used. In recent years, zebrafish experiments have become increasingly popular among researchers. This is because zebrafish experiments have the following advantages in the evaluation of the efficacy of improving brain development, promoting neural development and / or cognitive development (e.g., improving brain development, promoting neural and cognitive development): (1) Compared with traditional animal models, zebrafish brain development takes place earlier, and neural development studies can be performed on embryos after 24 hours. This allows researchers to directly observe the developing nervous system at an early stage, thereby discovering and evaluating the effects of improving brain development, promoting neural development and / or cognitive development (e.g., improving brain development, promoting neural and cognitive development) earlier. (2) The small and transparent embryos and larvae of zebrafish are easy to image under microscope, and researchers can clearly observe the activity of each cell. This transparency and high-resolution imaging technology provide great convenience for studying brain development, neural development and / or cognitive development (e.g., brain development, neural and cognitive development). (3) Zebrafish have a high degree of genetic similarity with humans and are suitable for genetic manipulation techniques, such as gene knockout and knock-in. The application of these technologies allows researchers to more accurately study the effects of specific genes on brain development, neural development and / or cognitive development (e.g., brain development, neural and cognitive development). (4) Zebrafish have strong reproductive capacity, rapid development, and a short sexual maturity period, which makes them very suitable for high-throughput experiments. High-throughput experiments can greatly speed up the research process and improve experimental efficiency. (5) The zebrafish model also has strong translational relevance, that is, its research results are more easily extended to humans. This makes zebrafish have important application value in the evaluation of the efficacy of improving brain development, promoting neural development and / or cognitive development (e.g., improving brain development, promoting neural and cognitive development).

[0056] The maze is one of the important equipment for evaluating different phenomena (such as learning and memory, anxiety, preference, etc.) in zebrafish neurological disease models. Various cognitive tasks often apply color clues in the maze to study zebrafish learning and memory. Color preference tests are often used in the evaluation of cognitive disorders in zebrafish. Zebrafish prefer short-wavelength colors 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, zebrafish's preference for blue becomes more obvious. Figure 1 The right picture in the figure is a schematic diagram of the plus maze, where the blue area is the preferred area of ​​zebrafish.

[0057] By analyzing and comparing the proportion of the movement trajectory of zebrafish in the blue area, the improvement / promotion degree of the studied nutritional composition on the zebrafish brain development, nerve and / or cognitive development (such as brain development, nerve and cognitive development) is evaluated. According to the statistical significance verification method, the statistical difference between the normal control group without any nutritional composition and the experimental group to which the studied nutritional composition is applied is compared, and represented by the p value, wherein p>0.05 indicates that there is no statistical difference, p<0.05 indicates that there is a statistical difference, p<0.01 indicates that there is a significant statistical difference, and p<0.001 indicates that there is an extremely significant statistical difference. Therefore, it can be understood that when the p value of the two experimental groups is different, it means that there are statistically significant differences in the technical effects of the two groups, so it can be judged whether there is synergy between the components in the corresponding experimental group formula 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 investigate the effects of long-chain fatty acid triglycerides and different types of human milk oligosaccharides on brain development, neural and / or cognitive development (eg, brain development, neural and cognitive development) of zebrafish.

[0060] 1. Test materials

[0061] 1.1. Sample preparation information

[0062] For MLCT, 2'-FL, LNnT, and 3'-SL, the solvent was standard dilution water.

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

[0064] 1.2. Experimental animals

[0065] Zebrafish were raised in fish farming water at 28°C (water quality: 200 mg of instant sea salt was added to every 1 L of reverse osmosis water, conductivity was 450-550 μS / cm; pH was 6.5-8.5; hardness was 50-100 mg / L CaCO3), bred and provided by our company's fish farming center, the experimental animal use license number is: SYXK (Zhejiang) 2022-0004, and the breeding management complies with the requirements of the international AAALAC certification (certification number: 001458), and the IACUC ethics review number is: 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 Bellambo Biotechnology Co., Ltd., China); ultrasonic cleaner (JP-010T, Shenzhen Jiemeng Cleaning Equipment Co., Ltd., China); fully automatic sample rapid grinding machine (JXFSTPRP-24L, Shanghai Jingxin Experimental Equipment Technology Department, China).

[0068] 2. Detection Method

[0069] Wild-type AB zebrafish at 5 days post-fertilization (dpf) were randomly selected and placed in beakers, and 30 zebrafish were treated in each beaker (experimental group). The samples were given water-soluble, and the positive control Ginkgo biloba and Cistanche tablets were 125 μg / mL in concentration. A normal control group was also set up, and the capacity of each beaker was 20 mL. Among them, for the zebrafish in the experimental group (30 fish), they were fed daily according to the formula in Tables 1-4 (wherein the sum of the amounts of MLCT and all human milk oligosaccharides (HMO) in each experiment in Tables 1-4 was 800 μg / mL; the ratio outside the brackets in the table is the mass ratio of MLCT to all human milk oligosaccharides, and the ratio in the brackets is 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 fish), no component was fed, and treated at 28°C for 1 day; for the zebrafish in the positive control group (30 fish), 125 μg / mL of Ginkgo Biloba and Cistanche tablets were fed, and treated at 28°C for 1 day.

[0070] After 1 day of treatment at 28℃, 5 zebrafish were randomly selected from each experimental group and placed in a "cross" module. The module was divided into four areas: yellow, blue, red and green. Six modules were placed in each group. Data were collected using a behavior analyzer to analyze the percentage (%) of the total movement distance of zebrafish in the blue area within 10 minutes to the total movement distance in the entire area. The statistical analysis results of this indicator were used to evaluate the efficacy of the sample in improving brain development, promoting neural and / or cognitive development (e.g., improving brain development, promoting neural and cognitive development). Statistical processing results were expressed as mean ± SE. SPSS26.0 software was used for statistical analysis (between the two groups), and p < 0.05 indicated that the difference was statistically significant.

[0071] The amount of each component in each batch and the analysis results are summarized in Tables 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 to synergistically improve brain development and promote neural and / or cognitive development (e.g., improve brain development, promote neural and cognitive development).

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

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

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

[0084] The above description is only an exemplary embodiment of the present invention. It should be noted that, for those skilled in the art, without departing from the creative concept of the present invention, the present invention can also be improved, but these all belong to the protection scope of the present invention.

Claims

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

1.

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

1.

4. The use according to claim 1, characterized in that The human milk oligosaccharide is selected from one or more of the following: human milk oligosaccharides containing fucosyl, human milk oligosaccharides containing sialic acid, and human milk oligosaccharides containing neither fucosyl nor sialic acid.

5. The use according to claim 4, characterized in that The fucosyl-containing human milk oligosaccharide is selected from one or more of the following: 2'-fucosyllactose, 3-fucosyllactose, lactose-N-fucopentaose I, lactose-N-difucohexaose I, lactose-N-difucohexaose II, and lactose-bifucosyltetrose.

6. The use according to claim 4, characterized in that The sialic acid-containing human milk oligosaccharide is selected from one or more of the following: 3'-sialyllactose and 6'-sialyllactose.

7. The use according to claim 4, characterized in that The non-fucosyl and non-sialic acid human milk oligosaccharides are selected from one or more of the following: lactose-N-tetraose, lactose-N-neotetraose, lactose-N-triose II, and lactose-N-disaccharide.

8. The use according to claim 1, characterized in that The human milk oligosaccharide is selected from one of the following: 2'-fucosyllactose; 3'-sialyl lactose; lactose-N-neotetraose; 2'-fucosyllactose and 3'-sialyl lactose; 2'-fucosyllactose and lactose-N-neotetraose; 3'-sialyl lactose and lactose-N-neotetraose; 2'-fucosyllactose and 3'-sialyl lactose and lactose-N-neotetraose.

9. The use according to claim 1, characterized in that The human milk oligosaccharide is 2'-fucosyllactose or lactose-N-neotetraose, and the ratio of the medium- and long-chain fatty acid triglycerides to the total mass of the human milk oligosaccharide is 5:1 to 9:

1.

10. The use according to claim 1, characterized in that The human milk oligosaccharide is selected from 3'-sialyllactose, and the mass ratio of the medium-chain fatty acid triglyceride to 3'-sialyllactose is 2:1 to 5:

1.

11. The use according to claim 1, characterized in that The human milk oligosaccharide is selected from any two of 2'-fucosyllactose, 3'-sialyl lactose and lacto-N-neotetraose, and the ratio of the mass of the medium-chain fatty acid triglyceride to the total mass of the human milk oligosaccharide is 5:1 to 7:

1.

12. The use according to claim 1, characterized in that The human milk oligosaccharides are 2'-fucosyllactose, 3'-sialyl lactose and lactose-N-neotetraose, and the ratio of the mass of the medium- and long-chain fatty acid triglycerides to the total mass of the human milk oligosaccharides is 3:1 to 9:

1.

13. The use according to any one of claims 1 to 12, characterized in that The nutritional composition is used in the form of a food comprising the same.

14. The use according to claim 13, characterized in that The food is infant food.

15. The use according to claim 13, characterized in that The food is selected from dairy products, candies, beverages, bread and biscuits.

16. The use according to claim 15, characterized in that The food is milk powder or fermented food.

17. The use according to claim 16, characterized in that The milk powder is infant formula milk powder.

18. The use according to claim 13, characterized in that The food further comprises one or more components selected from the group consisting of raw cow milk, desalted whey powder, concentrated whey protein, lactose, edible vegetable blending oil, oligofructose, oligogalactose, nucleotides, choline, vitamins, minerals, DHA and taurine.

19. The use according to any one of claims 1 to 12, characterized in that The improving brain development and promoting nerve and / or cognitive development refers to improving brain development and promoting nerve and / or cognitive development for infants and / or children.

20. The use according to claim 13, characterized in that The food is a health food.

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