Use of a nutritional composition

Abstract

This invention relates to the use of nutritional compositions, specifically to the non-therapeutic use of nutritional compositions in improving brain development and intelligence in infants and young children by promoting the proliferation, maturation, and myelination of oligodendrocyte precursor cells. The nutritional composition comprises: human milk oligosaccharides selected from 2'-fucosylated lactose; milk phospholipids; and choline and / or edible choline derivatives; wherein the mass ratio of human milk oligosaccharides to milk phospholipids is 1:0.15-2.5; and the mass ratio of human milk oligosaccharides to choline and / or edible choline derivatives, expressed as the ratio of the mass of human milk oligosaccharides to the total mass of converted choline, is 1:0.1-0.5. 2'-fucosylated lactose; milk phospholipids; and choline and / or edible choline derivatives synergistically promote neuronal maturation, synapsis, and myelination, and synergistically promote brain development and improve memory.

Description

[0001] This application is a divisional application of Chinese invention patent application No. 202111568623.5, filed on December 13, 2021. Technical Field

[0002] This invention generally relates to the food field. Specifically, it relates to a nutritional composition for improving brain development and intelligence in infants and young children, particularly promoting neuronal maturation, synapse formation, and myelination; a food comprising this nutritional composition; and the use of this nutritional composition. More specifically, it relates to a nutritional composition comprising neutral alginate-based human milk oligosaccharides (HMOs) selected from 2'-fucosylated lactose (2'-FL), 3'-fucosylated lactose (3'-FL), lactose-N-fucopentose I (LNFPI), lactose-N-difucohexose I (LNDFH I), and lactose-N-difucohexose II (LNDFH II), such as 2'-fucosylated lactose (2'-FL)), milk phospholipids, and choline and / or edible choline derivatives; a food comprising this nutritional composition; and the use of said nutritional composition for non-therapeutic purposes in improving brain development and intelligence in infants and young children, particularly promoting neurodevelopment. Background Technology

[0003] Oligodendrocyte precursor cells (OPCs) were first discovered by Raff and Miller in 1993 and have been extensively studied. Both developing and mature central nervous systems contain OPCs. Myelin-forming cells in the central nervous system originate from OPCs. The types of myelin proteins expressed by OPCs, such as myelin-associated glycoprotein (MAG) and myelin-binding protein (MBP), are associated with their maturation. Myelinated OPCs express MAG, and MAG expression gradually increases during OPC maturation. MAG is a sialic acid-binding immunoglobulin-like lectin; although it constitutes only a small portion of the total myelin protein content, it is primarily expressed in the peri-axonal region of the myelin sheath. It appears to play a crucial role in oligodendrocyte-axon interactions and mediates bidirectional signaling between axons and OPCs to support myelin formation. MBP is strongly expressed in mature myelinated OPCs and is one of the major components of myelin. MBP appears to play an active role in myelin formation and compaction. In fact, MBP is polymerizing and forming a sticky network of reticulum proteins, which is crucial for hopping currents.

[0004] Brain development is influenced by both genetic and environmental factors. Of the latter, maternal and early life nutrition plays a crucial role in neurodevelopment processes such as neuronal maturation, synapse formation, and myelination. Myelination, the process by which oligodendrocytes (OLs) in the central nervous system (CNS) form myelin sheaths around axons, is essential for normal brain connectivity. In humans, myelination begins in mid-pregnancy and peaks in the first few years of life. Environmental factors can influence myelination during human brain development. In particular, different nutrients exhibit varying effects on myelination, suggesting that early life nutrition may be a significant factor regulating myelination.

[0005] During the development of the central nervous system, oligodendrocyte precursor cells (OPCs) migrate from the cortex and generate an adult population of oligodendrocytes (OLs). Following mitosis, OPCs differentiate into myelinated OLs. These OLs then undergo numerous processes, establishing contact with axons of different neurons, initiating myelination—a process that enhances neuronal connectivity and supports the maturation of new cognitive functions.

[0006] In the central nervous system, each step of myelination, including OPC proliferation, differentiation and maturation of OPCs into myelinated OLs, and myelination itself, is highly regulated by both external and internal factors. In particular, different nutrients have varying effects on myelination, suggesting that early life nutrition may play a significant role in its regulation. Therefore, identifying early life nutrition factors that support myelination is crucial for optimal brain and cognitive development.

[0007] There is a need for a composition that can improve the brain development and intelligence of infants and young children, especially promoting neural development such as promoting neuronal maturation, synapse formation and myelination. Summary of the Invention

[0008] One object of the present invention is to provide a composition that can improve the brain development and intelligence of infants and young children, especially to promote neural development such as promoting neuronal maturation, synapse formation and myelination.

[0009] Another object of the present invention is to provide a food containing the nutritional composition.

[0010] Another object of the present invention is to provide the use of the nutritional composition or food for non-therapeutic purposes in improving brain development and intelligence in infants and young children, especially in promoting neurodevelopment such as neuronal maturation, synapsis and myelination, particularly in promoting the proliferation, maturation and differentiation of oligodendrocyte precursor cells into oligodendrocytes and / or myelination of oligodendrocytes.

[0011] The inventors have discovered that by combining human milk oligosaccharides (such as neutral alginate-based human milk oligosaccharides (HMOs) selected from 2'-fucosylvose (2'-FL), 3'-fucosylvose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexose I (LNDFH I), lactose-N-difucohexose II (LNDFH II), for example 2'-fucosylvose (2'-FL)), milk phospholipids, and choline and / or edible choline derivatives, it is possible to significantly promote neuronal maturation, synapsis, and myelination, thereby improving brain development and intelligence. In particular, the inventors have discovered that human milk oligosaccharides (HMOs) such as neutral Dunaliella salina-based HMOs selected from 2'-fucosylvose (2'-FL), 3'-fucosylvose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexose I (LNDFH I), and lactose-N-difucohexose II (LNDFH II), such as 2'-fucosylvose (2'-FL)), milk phospholipids, and choline and / or edible choline derivatives can synergistically promote neuronal development such as neuronal maturation, synapsis, and myelination, especially synergistically promote the proliferation, maturation, and differentiation of OPCs into mature OLs and / or the myelination properties of OLs; synergistically promote brain development and improve memory.

[0012] Specifically, the present invention is achieved by the following:

[0013] 1. A nutritional composition comprising:

[0014] Human milk oligosaccharides (HMOs), preferably neutral Dunaliella salina-based human milk oligosaccharides (HMOs), are preferably selected from one or more of 2'-fucosyllactose (2'-FL), 3'-fucosyllactose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexose I (LNDFH I), and lactose-N-difucohexose II (LNDFH II), with 2'-fucosyllactose being the most preferred;

[0015] - Milk phospholipids; and

[0016] - Choline and / or edible choline derivatives, preferably edible choline derivatives selected from choline chloride and / or choline tartrate.

[0017] 2. The nutritional composition as described in item 1, comprising: human milk oligosaccharides; milk phospholipids; and choline and / or edible choline derivatives.

[0018] 3. The nutritional composition as described in any one of items 1-2, wherein the human milk oligosaccharides are provided in the form of natural sources, and / or synthetic sources, and / or bacterial fermentation sources.

[0019] 4. A nutritional composition as described in any one of items 1-3, wherein:

[0020] Milk phospholipids are phospholipids derived from cow and / or sheep milk; and / or

[0021] Milk phospholipids are provided in the following forms: protein powder containing milk phospholipids, preferably wherein the milk phospholipid content in the protein powder is 6-25% by weight; and / or milk-derived phospholipids, preferably wherein the milk-derived phospholipid content is 9-60% by weight; and / or

[0022] The milk phospholipids contain at least sphingomyelin and phosphatidylcholine, and optionally further contain serine phospholipids and / or phosphatidylethanolamine, wherein sphingomyelin accounts for more than 10% by weight of the total milk phospholipids and phosphatidylcholine accounts for more than 15% by weight of the total milk phospholipids.

[0023] 5. The nutritional composition as described in any one of items 1-4, wherein the choline and / or edible choline derivative is choline chloride and / or choline tartrate.

[0024] 6. A nutritional composition as described in any one of items 1-5, wherein:

[0025] The mass ratio of human milk oligosaccharides to milk phospholipids is 1:0.01-500, preferably 1:0.02-100, preferably 1:0.05-50, preferably 1:0.1-10, and preferably 1:0.15-6; and

[0026] The mass ratio of human milk oligosaccharides to choline and / or edible choline derivatives, expressed as the ratio of the mass of human milk oligosaccharides to the total mass of choline converted to choline, is 1:0.001-100, preferably 1:0.002-20, preferably 1:0.005-5, preferably 1:0.01-1, and preferably 1:0.02-0.5.

[0027] Preferably, the mass ratio of human milk oligosaccharides, milk phospholipids, and choline and / or edible choline derivatives, calculated as the ratio of the mass of human milk oligosaccharides, the mass of milk phospholipids, and the total mass of choline converted to choline, is 1:0.01-500:0.001-100, preferably 1:0.02-100:0.002-20, preferably 1:0.05-50:0.005-5, preferably 1:0.1-10:0.01-1, and preferably 1:0.15-6:0.02-0.5.

[0028] 7. A food product comprising a nutritional composition as described in any one of entries 1-6.

[0029] 8. The food as described in item 7, wherein the food is in powder or liquid form.

[0030] 9. Foods described in any of items 7-8, such as infant formula, follow-up formula, toddler formula, such as infant formula milk powder, toddler formula milk powder; complementary foods for infants; nutritional or dietary supplements; or formula milk powder for pregnant women.

[0031] 10. The food product as described in any one of items 7-9, wherein the amount of said nutritional composition added is such that, relative to the total weight of said food product:

[0032] The weight content of human milk oligosaccharides is at least 0.01%, preferably at least 0.05%, preferably at least 0.1% and at most 10.0%, preferably at most 5.0%, and preferably at most 1.0%.

[0033] The weight content of milk phospholipids is at least 0.01%, preferably at least 0.05%, preferably at least 0.1% and at most 5.0%, preferably at most 1.0%, and preferably at most 0.6%.

[0034] The weight content of choline or edible choline, wherein the weight of edible choline converted to choline is at least 0.01%, preferably at least 0.05%, preferably at least 0.1% and at most 3.0%, preferably at most 1.0%, and preferably at most 0.3%.

[0035] 11. The use of the nutritional composition as described in any one of items 1-6 or the food as described in any one of items 7-10 for non-therapeutic purposes in improving brain development and intelligence in infants and young children, especially in promoting neurodevelopment such as neuronal maturation, synapsis and myelination, particularly in promoting the proliferation, maturation and differentiation of oligodendrocyte precursor cells into oligodendrocytes and / or oligodendrocytes. Detailed Implementation

[0036] Unless otherwise specified, the technical terms in this specification have the same meaning as those generally understood by those skilled in the art; however, in case of any conflict, the definitions in this specification shall prevail.

[0037] As used herein, the following terms have the following meanings.

[0038] The term "infant" refers to a person aged 0 to 6 months.

[0039] The term "older baby" refers to people aged 6 to 12 months.

[0040] The term "infant" refers to a person aged 12 to 36 months.

[0041] The term "infant" refers to people aged 0-36 months.

[0042] The term "infant formula" as used in this article encompasses infant formula, follow-up formula, and toddler formula. Generally, infant formula is used as a breast milk substitute from birth, follow-up formula is used from 6-12 months after birth, and toddler formula is used from 12-36 months after birth.

[0043] The term "infant formula" refers to liquid or powdered products made primarily from milk and milk protein products or soy and soy protein products, with the addition of appropriate amounts of vitamins, minerals, and / or other ingredients, produced and processed solely using physical methods. It is suitable for consumption by healthy infants, and its energy and nutrient content can meet the normal nutritional needs of infants aged 0-6 months.

[0044] The term "follow-up formula" refers to liquid or powdered products made primarily from milk and milk protein products or soy and soy protein products, with the addition of appropriate amounts of vitamins, minerals, and / or other ingredients, produced and processed solely using physical methods. These products are suitable for older infants, and their energy and nutrient content can meet some of the nutritional needs of normal older infants aged 6-12 months.

[0045] The term "infant formula" refers to liquid or powdered products made primarily from milk and milk protein products or soybeans and soy protein products, with the addition of appropriate amounts of vitamins, minerals, and / or other ingredients, produced and processed using only physical methods. These products are suitable for infants and their energy and nutrient content can meet some of the nutritional needs of normal infants aged 12-36 months.

[0046] The term "breast milk" should be understood as the mother's breast milk or colostrum.

[0047] The term "infant or toddler exclusively breastfed" has the common meaning of referring to an infant whose nutrients and / or energy are derived primarily from human breast milk.

[0048] The term "infants / followers / toddlers primarily fed with infant formula" has a general meaning, referring to infants or toddlers whose nutrients and / or energy are primarily derived from infant formula, follow-up milk, or growth milk produced by physical methods. The term "primarily" means at least 50%, for example, at least 75%, of those nutrients and / or energy.

[0049] Furthermore, in the context of this invention, the terms "comprising" or "including" do not exclude other possible elements. The compositions of this invention (including the various embodiments described herein) may comprise, consist of, or consist substantially of the following elements: the essential elements and necessary limitations of the invention as described herein, and any other or optional ingredients, components, or limitations as described herein or as otherwise desired.

[0050] The individuals described in this invention are applicable to normal humans, including infants and / or older infants, and / or toddlers, and / or children, and / or young adults, and / or middle-aged adults, and / or the elderly. More preferably, they are human infants and young children fed with formula.

[0051] Unless otherwise specified, all percentages are by weight.

[0052] The invention will now be described in more detail. It should be noted that the various aspects, features, implementation methods, embodiments, and advantages described herein are compatible and / or can be combined together.

[0053] This invention relates to a nutritional composition for improving brain development and intelligence in infants and young children, particularly promoting neuronal maturation, synapsis, and myelination, a food comprising the nutritional composition, and the use of the nutritional composition for non-therapeutic purposes in improving brain development and intelligence in infants and young children, particularly promoting neuronal maturation, synapsis, and myelination, especially the proliferation, differentiation, or maturation of oligodendrocyte precursor cells (OPCs) into oligodendrocytes (OLs).

[0054] The present invention will be described in detail below.

[0055] Nutritional composition

[0056] In one aspect, the present invention provides a nutritional composition comprising:

[0057] - Human milk oligosaccharides (HMOs), preferably neutral Dunaliella salina-based human milk oligosaccharides (HMOs), which are preferably selected from one or more of 2'-fucosyllactose (2'-FL), 3'-fucosyllactose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexose I (LNDFH I), and lactose-N-difucohexose II (LNDFH II), with 2'-fucosyllactose (2'-FL) being the most preferred;

[0058] - Milk phospholipids; and

[0059] - Choline and / or edible choline derivatives.

[0060] Human milk oligosaccharides (HMOs) are a collective term for oligosaccharides with a degree of polymerization ≥3 naturally found in human milk. They are formed by modifying the terminal position of a lactose molecule with five monomers: glucose (Glc), galactose (Gal), N-acetylglucosamine (GlcNAc), fucose (Fuc), and N-acetylneuraminic acid (Neu5Ac). Each HMO molecule contains 3 to 32 monosaccharides linked by different glycosidic bonds, contributing to the diversity and complexity of HMOs. Based on their core structure, HMOs can be classified into three types: neutral fucosylated HMOs (containing fucose at the terminal position), neutral non-fucosylated HMOs (containing N-acetylglucosamine at the terminal position), and acidic or sialylated HMOs (containing sialic acid at the terminal position). Their proportions in human milk oligosaccharides are typically 35-50%, 42-55%, and 12-14%, respectively.

[0061] 2'-Fucosyllactose (2'-FL) is a neutral trisaccharide composed of L-fucose, D-galactose, and D-glucose units, in which the monosaccharide L-fucose is linked to the disaccharide D-lactose via an α(1→2) bond. Its molecular formula is C2. 18 H 31 O 15 It has a molecular weight of 488.439 g / mol and the following molecular structure.

[0062]

[0063] 3'-Fucosyllactose (3'-FL) is a neutral trisaccharide composed of L-fucose, D-galactose, and D-glucose units, in which the monosaccharide L-fucose is linked to D-glucose via an α(1→3) bond. Its molecular formula is C2. 18 H 32 O 15 It has a molecular weight of 488.44 g / mol and the following molecular structure.

[0064]

[0065] Lactose-N-fucopentose I (LNFP I) is a neutral pentasaccharide composed of L-fucose, D-glucose, two molecules of D-galactose, and N-acetylglucosamine units. The monosaccharide L-fucose is linked to D-glucose via an α(1→3) bond. Its molecular formula is C1. 32 H 55 NO 25 It has a molecular weight of 853.77 g / mol and the following molecular structure.

[0066]

[0067] Lactose-N-difucohexasaccharide I (LNDFH I) is a neutral hexasaccharide composed of two molecules of L-fucose, D-glucose, D-galactose, and N-acetylglucosamine. The monosaccharide L-fucose is linked to D-galactose and N-acetylglucosamine via α(1→2) and α(1→4) bonds, respectively. Its molecular formula is C1. 38 H 65 NO 29 It has a molecular weight of 999.91 g / mol and the following molecular structure.

[0068]

[0069] Lactose-N-difucohexasaccharide II (LNDFH II) is a neutral hexasaccharide composed of two molecules of L-fucose, D-glucose, D-galactose, and N-acetylglucosamine. The monosaccharide L-fucose is linked to D-glucose and N-acetylglucosamine via α(1→3) and α(1→4) bonds, respectively. Its molecular formula is C2. 38 H 65 NO 29 It has a molecular weight of 999.91 g / mol and the following molecular structure.

[0070]

[0071] Sphingomyelin is a sphingolipid composed of phosphocholine (or phosphoethanolamine) linked to the C-1 hydroxyl group of ceramide. Its molecular structure is as follows:

[0072]

[0073] Phosphatidylethanolamine, 1,2-dipalmitoyl-SN-glycerol-3-phosphatidylethanolamine, has the following molecular structure:

[0074]

[0075] Choline is a positively charged tetravalent base, a component of all biological membranes, and a precursor of acetylcholine in cholinergic neurons. Its chemical formula is C5H12H2O. 14 ON + .

[0076] In this article, edible choline derivatives refer to substances that can be broken down in the human or animal body to form choline and have no biotoxicity. They meet the relevant national standards for consumption.

[0077] The inventors have surprisingly discovered that when human milk oligosaccharides (HMOs) (preferably one or more neutral alginate-sylated human milk oligosaccharides selected from 2'-fucosylvose (2'-FL), 3'-fucosylvose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexose I (LNDFH I), lactose-N-difucohexose II (LNDFH II), preferably 2'-fucosylvose (2'-FL)), milk phospholipids, and choline and / or edible choline derivatives are used in combination, they can synergistically promote neurodevelopment such as neuronal maturation, synapsis, and myelination, and in particular, can synergistically promote the proliferation, maturation, and differentiation of OPCs into mature OLs and / or the myelination properties of OLs.

[0078] In one embodiment, the nutritional composition comprises: human milk oligosaccharides (HMOs), preferably neutral Dunaliella salina-based human milk oligosaccharides (HMOs), which are preferably selected from one or more of 2'-fucosyllactose (2'-FL), 3'-fucosyllactose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexose I (LNDFH I), and lactose-N-difucohexose II (LNDFH II), preferably 2'-fucosyllactose (2'-FL); milk phospholipids; and choline and / or edible choline derivatives.

[0079] In one embodiment, the human milk oligosaccharide is a neutral Dunaliella salina-based human milk oligosaccharide (HMO), preferably selected from one or more of the following: 2'-fucosylated lactose (2'-FL), 3'-fucosylated lactose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexose I (LNDFH I), and lactose-N-difucohexose II (LNDFH II).

[0080] In one embodiment, the human milk oligosaccharide is 2'-fucosylated lactose (2'-FL).

[0081] In one embodiment, the human milk oligosaccharide (HMO) (e.g., a neutrally alginate-based human milk oligosaccharide (HMO) selected from 2'-fucosylvose (2'-FL), 3'-fucosylvose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexose I (LNDFHI), and lactose-N-difucohexose II (LNDFH II), such as 2'-fucosylvose (2'-FL)) can be provided from natural sources, and / or synthetic sources, and / or bacterial fermentation sources. For example, for 2'-fucosylvose, the 2'-fucosylvose content in each source can typically be 60-99.9%.

[0082] In one embodiment, milk phospholipids may be provided in the following form or may be derived from: protein powder containing milk phospholipids, and / or milk-derived phospholipids. The milk phospholipid content in the protein powder containing milk phospholipids is typically 6-25% by weight, for example 7-15% by weight. The milk phospholipid content in the milk-derived phospholipids is typically 9-60% by weight. The milk phospholipids contain at least sphingomyelin and phosphatidylcholine, and optionally further contain serine phospholipids and / or phosphatidylethanolamine, wherein sphingomyelin accounts for more than 10% by weight of the total milk phospholipids, and phosphatidylcholine accounts for more than 15% by weight of the total milk phospholipids. In one embodiment, the proportions of each phospholipid component in the total phospholipids of the milk phospholipids are: sphingomyelin (SM) 15-36%, phosphatidylcholine (PC) 20-40%, phosphatidylethanolamine (PE) 20-38%, serine phospholipids (PS) 5-18%, and phosphatidylinositol (PI) 3-11%.

[0083] In one embodiment, the edible choline derivative is choline chloride or choline tartrate. The choline chloride described herein meets the requirements of GB 1903.36, the standard for food fortifier choline chloride, and the choline tartrate described herein meets the requirements of GB 1903.54-2021, the standard for food fortifier choline tartrate.

[0084] In one embodiment, the mass ratio of human milk oligosaccharides (e.g., neutral alginate-based human milk oligosaccharides (HMOs) selected from 2'-fucosylated lactose (2'-FL), 3'-fucosylated lactose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexose I (LNDFH I), and lactose-N-difucohexose II (LNDFH II), such as 2'-fucosylated lactose (2'-FL)) to milk phospholipids in the nutritional composition can be 1:0.01-500, preferably 1:0.02-100, preferably 1:0.05-50, preferably 1:0.1-10, preferably 1:0.15-6, for example, 1:0.01, 1:0.015, 1:0.02, etc. 1:0.025, 1:0.03, 1:0.04, 1:0.05, 1:0.06, 1:0.07, 1:0.08, 1:0.09, 1:0.1, 1:0.15, 1:0.2, 1:0.25, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1.0, 1:1.5, 1: 2.0, 1:2.5, 1:3.0, 1:3.5, 1:4.0, 1:4.5, 1:5.0, 1:5.5, 1:6.0, 1:7.0, 1:8.0, 1:9.0, 1:10.0, 1:11.0, 1:12.0, 1:13.0, 1:14.0, 1:15.0, 1:16.0, 1:17.0, 1:18.0, 1:19.0, 1:20.0, 1:2 1.0, 1:22.0, 1:23.0, 1:24.0, 1:25.0, 1:26.0, 1:27.0, 1:28.0, 1:29.0, 1:30.0, 1:31.0, 1:32.0, 1:33.0, 1:34.0, 1:35.0, 1:36.0, 1:37.0, 1:38.0, 1:39.0, 1:40.0, 1:41.0, 1:42.0 1:43.0, 1:44.0, 1:45.0, 1:46.0, 1:47.0, 1:48.0, 1:49.0, 1:50.0, 1:51.0, 1:52.0, 1:53.0, 1:54.0, 1:55.0, 1:56.0, 1:57.0, 1:58.0, 1:59.0, 1:60.0, 1:61.0, 1:62.0, 1:63.0, 1: 64.0, 1:65.0, 1:66.0, 1:67.0, 1:68.0, 1:69.0, 1:70.0, 1:71.0, 1:72.0, 1:73.0, 1:74.0, 1:75.0, 1:76.0, 1:77.0, 1:78.0, 1:79.0, 1:80.0, 1:81.0, 1:82.0, 1:83.0, 1:84.0, 1:85.0, 1:86.0, 1:87.0, 1:88.0, 1:89.0, 1:90.0, 1:91.0, 1:92.0, 1:93.0, 1:94.0, 1:95.0, 1:96.0, 1:97.0, 1:98.0, 1:99.0, 1:100, 1:110, 1:120, 1:130, 1:140, 1:150, 1:160, 1:170, 1:180, 1:190, 1:200, 1:210, 1:220, 1:230, 1:24 0, 1:250, 1:260, 1:270, 1:280, 1:290, 1:300, 1:310, 1:320, 1:330, 1:340, 1:350, 1:360, 1:370, 1:380, 1:390, 1:400, 1:410, 1:420, 1:430, 1:440, 1:450, 1:460, 1:470, 1:480, 1:490, 1:500, or a range defined by any two of these values, and any values ​​and subranges encompassed within that range.

[0085] In one embodiment, the nutritional composition contains human milk oligosaccharides (e.g., selected from 2'-fucosylated lactose (2'-FL), 3'-fucosylated lactose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexasose I (LNDFH I), lactose-N-difucohexasose II (LNDFH II)). II) The mass ratio of neutral Dunaliella salina-based human milk oligosaccharides (HMOs), such as 2'-fucosylated lactose (2'-FL) to choline or edible choline, expressed as the mass ratio of HMOs to converted choline, can be 1:0.001-100, preferably 1:0.002-20, preferably 1:0.005-5, preferably 1:0.01-1, preferably 1:0.02-0.5, for example, 1:0.001, 1:0.002, 1:0.003, 1:0.00 4, 1:0.005, 1:0.006, 1:0.007, 1:0.008, 1:0.009, 1:0.01, 1:0.02, 1:0.03, 1:0.04, 1:0.05, 1:0.06, 1:0.07, 1:0.08, 1:0.09, 1:0.1, 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1.0, 1:1.5, 1: 2.0, 1:2.5, 1:3.0, 1:3.5, 1:4.0, 1:4.5, 1:5.0, 1:6.0, 1:7.0, 1:8.0, 1:9.0, 1:10.0, 1:11.0, 1:12.0, 1:13.0, 1:14.0, 1:15.0, 1:16.0, 1:17.0, 1:18.0, 1:19. 0, 1:20.0, 1:21.0, 1:22.0, 1:23.0, 1:24.0, 1:25.0, 1:26.0, 1:27.0, 1:28.0, 1:29.0, 1:30.0, 1:31.0, 1:32.0, 1:33.0, 1:34.0, 1:35.0, 1:36.0, 1:37.0, 1:38. 0, 1:39.0, 1:40.0, 1:41.0, 1:42.0, 1:43.0, 1:44.0, 1:45.0, 1:46.0, 1:47.0, 1:48.0, 1:49.0, 1:50.0, 1:51.0, 1:52.0, 1:53.0, 1:54.0, 1:55.0, 1:56.0, 1:57. 0, 1:58.0, 1:59.0, 1:60.0, 1:61.0, 1:62.0, 1:63.0, 1:64.0, 1:65.0, 1:66.0, 1:67.0, 1:68.0, 1:69.0, 1:70.0, 1:71.0, 1:72.0, 1:73.0, 1:74.0, 1:75.0, 1:76.0, 1:77.0, 1:78.0, 1:79.0, 1:80.0, 1:81.0, 1:82.0, 1:83.0, 1:84.0, 1:85.0, 1:86.0, 1:87.0, 1:88.0, 1:89.0, 1:90.0, 1:91.0, 1:92.0, 1:93.0, 1:94.0, 1:95.0, 1:96.0, 1:97.0, 1:98.0, 1:99.0, 1:100, or a range defined by any two of these values, and any values ​​and subranges encompassed within that range.

[0086] In one embodiment, the nutritional composition contains human milk oligosaccharides (e.g., selected from 2'-fucosylated lactose (2'-FL), 3'-fucosylated lactose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexasose I (LNDFH I), lactose-N-difucohexasose II (LNDFH II)). II) Neutral alginate-sylated human milk oligosaccharides (HMOs), such as 2'-fucosylated lactose (2'-FL), phospholipids, and choline and / or edible choline derivatives, in a mass ratio of HMOs, phospholipids, and converted choline, can be 1:0.01-500:0.001-100, preferably 1:0.02-100:0.002-20, preferably 1:0.05-50:0.005-5, preferably 1:0.1-10:0.01-1, preferably 1:0.15-6:0.02-0.5, or by adjusting the above ratios for HMOs (e.g., selected from 2'-fucosylated lactose (2'-FL), 3'-fucosylated lactose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexasose I (LNDFH)). I) The mass ratio of neutral alginate-based human milk oligosaccharides (HMOs) of lactose-N-difucohexose II (LNDFH II), such as 2'-fucosylated lactose (2'-FL) to milk phospholipids and the mass ratio of human milk oligosaccharides (e.g., selected from 2'-fucosylated lactose (2'-FL), 3'-fucosylated lactose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexose I (LNDFH I), lactose-N-difucohexose II (LNDFH II) to choline or edible choline (converted to choline) is obtained by any combination of the ratios described above.

[0087] In this document, unless otherwise stated, the mass ratio of choline and / or edible choline derivatives to other substances, and the mass content of choline and / or edible choline in the composition, are calculated by converting the edible choline derivatives into the mass of choline. That is, when only choline is present and no edible choline derivatives are present, the mass ratio and mass content refer to the mass ratio of choline to other substances and the percentage of choline mass relative to the total mass of the composition, respectively; when only edible choline derivatives are present and no choline is present, the mass ratio and mass content refer to the ratio of the mass of choline converted to or corresponding to the edible choline derivative to the mass of other substances and the percentage of the converted or corresponding choline mass relative to the total mass of the composition, respectively; when choline and edible choline derivatives are present, the mass ratio and mass content refer to the ratio of the sum of the mass of choline and the sum of the mass of choline converted to or corresponding to the edible choline derivatives to the mass of other substances and the percentage of the sum of the masses relative to the total mass of the composition, respectively.

[0088] When the mass ratio of human milk oligosaccharides (e.g., neutral alginate-based human milk oligosaccharides (HMOs) selected from 2'-fucosylvose (2'-FL), 3'-fucosylvose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexose I (LNDFH I), lactose-N-difucohexose II (LNDFH II), such as 2'-fucosylvose (2'-FL)), milk phospholipids, and choline or edible choline (converted to choline) in the nutritional composition is within the above range, it can more significantly promote neurodevelopment such as neuronal maturation, synapsis, and myelination, especially in promoting the proliferation, maturation, and differentiation of OPCs into mature OLs and / or the myelination properties of OLs, and the synergistic effect between the components in this regard is more significant.

[0089] food

[0090] In another aspect, the present invention also relates to food comprising the said nutritional composition.

[0091] The food product of this invention can be in powder form or liquid form.

[0092] The food products of the present invention may be infant formula foods (e.g., baby formula, follow-up formula, toddler formula), such as infant formula milk powder (e.g., baby formula milk powder, toddler formula milk powder), baby complementary foods, nutritional or dietary supplements, or formula milk powder for pregnant women.

[0093] In one embodiment, the nutritional composition is added in such a way that, relative to the total weight of the food, the weight content of human milk oligosaccharides (e.g., neutral alginate-based human milk oligosaccharides (HMOs) selected from 2'-fucosylated lactose (2'-FL), 3'-fucosylated lactose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexose I (LNDFH I), lactose-N-difucohexose II (LNDFH II), such as 2'-fucosylated lactose (2'-FL)) is at least 0.01%, preferably at least 0.05%, preferably at least 0.1% and at most 10.0%, preferably at most 5.0%, and preferably at most 1.0%. For example, the weight content of 2'-fucosyl lactose (2'-FL) relative to the total weight of the food product can be 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%. %, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4% 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, 5.0%, 5.1%, 5.2%, 5.3%, 5.4%, 5.5%, 5.6%, 5.7%, 5.8%, 5.9%, 6.0%, 6.1%, 6.2%, 6.3%, 6.4%, 6.5%, 6.6%, 6.7%, 6.8%, 6.9%, 7.0%, 7.1%, 7.2%, 7.3%, 7.4%, 7.5%, 7.6%, 7.7%, 7.8%, 7.9%, 8.0%, 8.1%, 8.2%, 8.3%, 8.4%, 8.5%, 8.6%, 8.7%, 8.8%, 8.9%, 9.0%, 9.1%, 9.2%, 9.3%, 9.4%, 9.5%, 9.6%, 9.7%, 9.8%, 9.9%, 10.0%, or a range defined by any two of these values, and any value and subrange encompassed within that range.

[0094] In one embodiment, the nutritional composition is added in such a way that, relative to the total weight of the food, the weight content of milk phospholipids is at least 0.01%, preferably at least 0.05%, preferably at least 0.1% and at most 5.0%, preferably at most 1.0%, and preferably at most 0.6%. For example, the weight content of milk phospholipids relative to the total weight of the food can be 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, or 2.0%. 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, 5.0%, or a range defined by any two of these values, and any value and subrange encompassed within that range.

[0095] In one embodiment, the nutritional composition is added in such a way that, relative to the total weight of the food, the weight content of choline and / or edible choline derivatives (converted to choline) is at least 0.01%, preferably at least 0.05%, preferably at least 0.1% and at most 3.0%, preferably at most 1.0%, preferably at most 0.3%. For example, the weight content of choline relative to the total weight of the food can be 0.01%, 0.015%, 0.02%, 0.025%, 0.03%, 0.035%, 0.04%, 0.045%, 0.05%, 0.055%, 0.06%, 0.065%, 0.07%, 0.075%, 0.08%, 0.085%, 0.09%, 0.095%, 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%, 0.31%, 0.32%, 0.33%, 0.34%, 0.35%, 0.36%, 0.37%, 0.38%, 0.39%, 0.40%, 0.41%, 0.42%, 0.43%, 0.44%, 0.45%, 0.46%, 0.47%, 0.48%, 0.49%, 0.50%, 0.51%, 0.52%, 0.53%, 0.5 4%, 0.55%, 0.56%, 0.57%, 0.58%, 0.59%, 0.60%, 0.61%, 0.62%, 0.63%, 0.64%, 0.65%, 0.66%, 0.67%, 0.68%, 0.69%, 0.70%, 0.71%, 0.72%, 0.73%, 0.74%, 0.75%, 0.76%, 0.77%, 0.78%, 0.79%, 0.80%, 0.81%, 0.82%, 0.83%, 0.84%, 0.85%, 0.86%, 0.87%, 0.8 8%, 0.89%, 0.90%, 0.91%, 0.92%, 0.93%, 0.94%, 0.95%, 0.96%, 0.97%, 0.98%, 0.99%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3.0%, or a range defined by any two of these values, and any value and subrange encompassed within that range.As described above, the mass (weight) content of choline and / or edible choline derivatives in the composition is calculated by converting the edible choline derivatives into the mass of choline; that is, when only choline is present and no edible choline derivatives are present, the mass content refers to the percentage of choline relative to the total mass of the composition; when only edible choline derivatives are present and no choline is present, the mass content refers to the percentage of the mass of choline converted into or corresponding to the edible choline derivatives relative to the total mass of the composition; when both choline and edible choline derivatives are present, the mass content refers to the percentage of the sum of the mass of choline and the mass of choline converted into or corresponding to the edible choline derivatives relative to the total mass of the composition.

[0096] In addition to the components described above in the nutritional composition, the food may also contain other ingredients, such as other proteins, carbohydrates, fats, vitamins, minerals, etc., which are commonly found in formulated foods such as infant formula, like milk powder.

[0097] use

[0098] In another aspect, the present invention relates to the use of the above-mentioned nutritional composition or the above-mentioned food for non-therapeutic purposes in improving the brain development and intelligence of infants and young children, especially in promoting neurodevelopment (e.g., neuronal maturation, synapsis and myelination, such as promoting the proliferation, maturation and differentiation of OPCs into mature OLs and / or OLs).

[0099] Example

[0100] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention. Unless otherwise specified, the reagents, methods, and equipment used in this invention are conventional in the art.

[0101] raw material

[0102] In the following examples, unless otherwise stated, the raw materials used are as follows.

[0103] 2'-Fucose-based lactose (2'-FL): GlyCare™ 2'-FL 9000, 2'-fucosylated lactose content 96.0% by mass

[0104] Milk phospholipid powder (phospholipid 12.3%): Tatua of New Zealand PLC1

[0105] Choline: Choline chloride from Beijing Jinkangpu Food Technology Co., Ltd., with a choline content of 72.5% by mass.

[0106] In the following sections, unless otherwise stated, choline chloride is referred to simply as choline, and when referring to the parts by mass and ratios of the ingredients in the nutritional composition, the parts by mass refer to the parts by mass of 2'-fucosylated lactose (2'-FL), phospholipids and choline as active ingredients, and the ratios refer to the mass ratios between 2'-fucosylated lactose (2'-FL), phospholipids and choline as active ingredients, i.e., all choline chloride has been converted to choline for calculation.

[0107] Various nutritional compositions were formulated by mixing 2'-fucosylated lactose (2'-FL), milk phospholipids and choline raw materials in the proportions shown in the following examples, the composition of which is shown in Table 1.

[0108] Table 1. Composition of the nutritional composition

[0109]

[0110] Cell Experiment Examples

[0111] Current research on brain development is limited to passive memory studies using animal experiments, without exploring the development of neuronal cells or investigating the effects of specific dosages of the composition on early brain development. This invention uses an in vitro model of primary cell culture containing neurons and OPCs to evaluate the effects of a nutrient mixture on myelin formation and neurons. By experimentally studying the effects of components containing different proportions of 2'-FL, lactalofop-p-ethyl, and choline on brain nerve cell development, this method systematically and intuitively evaluates the impact on early brain development, and has profound significance for guiding the application of the composition.

[0112] 1. Materials and Methods

[0113] 1.1 Instruments, Reagents, and Consumables

[0114] Cell culture incubator; laser confocal fluorescence microscope; centrifuge; electronic balance; vortex mixer; water bath; tissue homogenizer.

[0115] Nerve cell culture medium; antibodies such as A2B5, MAG, and MBP.

[0116] 1.2 Experimental Methods

[0117] 1.2.1 Obtaining primary neural cells

[0118] All experiments were ethically approved. Primary co-culture of neurons and OL cells was performed according to the following steps. In short, the forebrain of newborn rats was dissociated at 37°C for 20 minutes using trypsin (Trypsin EDTA 1X, PAN BIOTECH). The reaction was stopped after adding Dulbecco modified Eagle medium (DMEM, PAN BIOTECH) containing DNase Grade II (0.1 mg / ml, PAN BIOTECH) and 10% fetal bovine serum (FCS, GIBCO). Cells were mechanically separated three times using 10 ml pipettes, and then centrifuged at 515 g for 10 minutes at 4°C.

[0119] Live cells were seeded into 96-well plates (20,000 cells / well) pre-coated with poly-L-lysine (BD Falcon) and laminin (Sigma). The culture medium consisted of Neurobasal (GIBCO) supplemented with 2% B27 (GIBCO), 2 mM L-glutamine (L Glu, PAN BIOTECH), 2% P / S solution (PAN BIOTECH), 1% FCS, and 10 ng / ml platelet-derived growth factor (PDGF-AA, PAN BIOTECH). The 96-well plates were stored in a humidified incubator at 37°C in an environment of 95% air and 5% CO2.

[0120] 1.2.2 Nerve Cell Culture

[0121] Place the same number of cells in a 48-well plate and incubate for 12, 18, or 30 DIVs, changing half of the medium every other day, adding the mixture or individual nutrients (the above-prepared nutrient composition containing 2'-FL, choline, and / or milk phospholipids) to the fresh medium.

[0122] 1.2.3 Immunohistochemical experiment

[0123] Cells were fixed at 12, 18, and 30 DIV sites after treatment with a cold mixture of 95% ethanol and acetic acid (5%) for 5 minutes. Then, nonspecific sites were blocked at room temperature for 15 minutes with phosphate-buffered saline (PBS) containing 0.1% saponin (Sigma) and 1% FCS (GIBCO).

[0124] At 12 DIV, nerve cells were co-incubated with mouse monoclonal antibody A2B5 (dilution: 1 / 200, Millipore, MAB312RX) at room temperature for 2 h, followed by co-incubation with neurofilament protein antibody (dilution: 1 / 500, Sigma, N4142) at room temperature for 2 h. Finally, they were co-incubated with goat anti-rabbit antibody (dilution: 1 / 400, SIGMA, SAB4600084) at room temperature for 1 h.

[0125] At 18 DIV, nerve cells were co-incubated for 2 h with mouse monoclonal antibody MAG (dilution: 1 / 400, Millipore, MAB1567) and neurofilament antibody (dilution: 1 / 500, Sigma, N4142). They were then incubated at room temperature for 1 h with secondary antibodies: goat anti-rabbit antibody (dilution: 1 / 400, Sigma, SAB4600042) and goat anti-rabbit antibody (dilution: 1 / 400, SIGMA, SAB4600084).

[0126] At 30 DIV, nerve cells were co-incubated for 2 h with mouse monoclonal antibody MBP (dilution: 1 / 1000, Novus, NBP1-05204) and neurofilament antibody (dilution: 1 / 500, Sigma, N4142). Then, they were co-incubated at room temperature for 1 h with secondary antibodies: goat anti-mouse antibody (dilution: 1 / 800, Sigma, SAB4600042) and goat anti-rabbit antibody (dilution: 1 / 400, SIGMA, SAB4600084).

[0127] 1.2.4 Microscopic photography

[0128] 20x magnification was achieved using ImageXpress, equipped with LED lights (360 / 480 / 565 excitation and 460 / 535 / 620 emission). All images were acquired using the same settings.

[0129] Under 12 DIV conditions, the number of OPCs was calculated by quantifying the number of A2B5-expressing cells, and the result is expressed as the average number of A2B5-expressing cells per well per image.

[0130] OPC differentiation into OL was assessed by counting the number of MAG-positive cells in cell culture. Results are expressed as per image and average cell count per well. Morphological maturity of MAG-positive cells was assessed by measuring the average surface area (μm / image / well) of MAG-positive cells in 18 DIV wells.

[0131] At 30 DIVs, the maturity of OLs was estimated by calculating the number of MBP-positive cells (average number of cells per image, per well) and the average surface area of ​​MBP-positive cells at 30 DIVs (μm, per image, per well).

[0132] 1.3 Cell Experiment Grouping

[0133] Cells were seeded in 96-well plates and cultured for a certain period of time. Half of the culture medium was replaced every other day. Different concentrations of mixed or single 2'-FL mixtures were added to fresh primary cell culture medium (added at 12, 18, and 30 days). Each sample was tested in six replicates. Olesoxime (300 nM, proven to accelerate OL maturation and myelination in vitro and in vivo) was used as a positive control. The blank control group, positive control group, and sample intervention group were compared. Immunohistochemistry (MBP, NF, A2B5) was used to determine the effects of single or mixed milk phospholipids, 2'-FL, and choline on OPC population, OL maturation and differentiation, myelin formation, and neurite growth. Specific experimental dosages are shown in Table 2 below.

[0134] Table 2. Dosage for Cell Experiments

[0135]

[0136] 1.4 Statistical Analysis

[0137] Results are expressed as mean ± standard error. SPSS software was used to perform T-tests and one-way ANOVA. A p-value < 0.05 was considered statistically significant.

[0138] 2. Experimental Results

[0139] 2.1 Effects of each sample on nerve cells

[0140] To measure the effect of mixed or individual nutrient treatments on OPC, we assessed the number of A2B5-labeled positive cells after 12 DIVs to estimate the number of OPCs. The mean number of A2B5-positive cells per well is shown in Table 3.

[0141] Table 3. Effects of different nutrient compositions containing 2'-FL, milk phospholipids, and / or choline on the number of A2B5 positive cells.

[0142]

[0143] The sample processing results showed that, compared with the blank control group (Cell Experiment Example 1), 2'-FL, milk phospholipids, and choline could all increase the number of A2B5 positive cells, indicating that these three components all contribute to the proliferation of oligodendrocyte precursor cells.

[0144] However, the inventors have discovered that when any two of the three components are used in combination, there is a strong antagonistic effect.

[0145] In particular, as can be seen from cell experiment examples 12-14:

[0146] In terms of the components and amounts used, Cell Experiment Example 12 is equivalent to a combination of Cell Experiment Examples 4 and 6. Compared to the blank control group (Cell Experiment Example 1), Cell Experiment Examples 4 and 6 increased the number of A2B5 positive cells by 39.33 and 51.33, respectively, while Cell Experiment Example 12 increased the number of A2B5 positive cells by 24. This increase is not only much smaller than the sum of the former two (90.66) (the difference from the sum of the former two is Δ1 = 66.66), but also smaller than each of the former two.

[0147] Cell Experiment Example 13 is equivalent to a combination of Cell Experiment Examples 4 and 10. Compared to the blank control group (Cell Experiment Example 1), Cell Experiment Examples 4 and 10 increased the number of A2B5 positive cells by 39.33 and 109, respectively, while Cell Experiment Example 13 increased the number of A2B5 positive cells by 21.83, which is not only much smaller than the sum of the former two (148.33) (the difference from the sum of the former two is Δ2 = 126.5), but also smaller than each of the former two.

[0148] Cell Experiment Example 14 is equivalent to a combination of Cell Experiment Examples 6 and 10. However, compared to the blank control group (Cell Experiment Example 1), Cell Experiment Examples 6 and 10 increased the number of A2B5 positive cells by 51.33 and 109, respectively, while Cell Experiment Example 14 increased the number of A2B5 positive cells by 19. This increase is not only much smaller than the sum of the former two (160.33) (the difference from the sum of the former two is Δ3 = 141.33), but also smaller than each of the former two.

[0149] This indicates that when any two of 2'-FL, lactophospholipids, and choline are used in combination, there is a strong antagonistic effect in terms of the number of A2B5 positive cells and therefore the proliferation of oligodendrocyte precursor cells, and the combined effect is less than the effect of using any one of the components alone.

[0150] The inventors further discovered that when 2'-FL, lactophospholipids, and choline are used in combination, the antagonistic effect between the components can be significantly reduced, the number of A2B5 positive cells can be synergistically increased, and the proliferation of oligodendrocyte precursor cells can be reduced accordingly.

[0151] Specifically, in terms of the components and amounts used, Cell Experiment Example 16 is equivalent to a combination of Cell Experiment Examples 7 and 13, or a combination of Cell Experiment Examples 4, 7, and 10. Compared to Cell Experiment Example 1, Cell Experiment Examples 4, 7, 10, 13, and 16 increased the number of A2B5 positive cells by 39.33, 14.66, 109, 21.83, and 167, respectively. The increase in the number of A2B5 positive cells in Cell Experiment Example 16 (167) is greater than the sum of the increases in Cell Experiment Examples 7 and 13 (36.49), and also greater than the sum of the increases in Cell Experiment Examples 4, 7, and 10 (162.99).

[0152] Furthermore, in terms of the components and amounts used, Cell Experiment Example 17 is equivalent to a combination of Cell Experiment Examples 5, 8, and 11. Compared to Cell Experiment Example 1, Cell Experiment Examples 5, 8, and 11 increased the number of A2B5 positive cells by 18.33, -10.34, and -9, respectively, while Cell Experiment Example 17 increased the number of A2B5 positive cells by 180.33, which is greater than the sum of the previous three (-1.01).

[0153] Furthermore, in terms of the components and amounts used, Cell Experiment Example 20 is equivalent to a combination of Cell Experiment Examples 9 and 12, or a combination of Cell Experiment Examples 4, 6, and 9. Compared to Cell Experiment Example 1, Cell Experiment Examples 4, 6, 9, 12, and 20 increased the number of A2B5 positive cells by 39.33, 51.33, 50.66, 24, and 97.83, respectively. The increment achieved in Cell Experiment Example 20 (97.83) is greater than the sum of the increments of Cell Experiment Examples 9 and 12 (74.66), but less than the sum of the increments of Cell Experiment Examples 4, 6, and 9 (141.32) (difference Δ4 = 43.69, less than Δ1 = 66.66).

[0154] Furthermore, in terms of the components and amounts used, Cell Experiment Example 21 is equivalent to a combination of Cell Experiment Examples 7 and 13, or a combination of Cell Experiment Examples 4, 7, and 10. Compared to Cell Experiment Example 1, Cell Experiment Examples 4, 7, 10, 13, and 21 increased the number of A2B5 positive cells by 39.33, 14.66, 109, 21.83, and 123.52, respectively. The increment achieved in Cell Experiment Example 21 (123.52) is greater than the sum of the increments of Cell Experiment Examples 7 and 13 (36.49), but less than the sum of the increments of Cell Experiment Examples 4, 7, and 10 (162.99) (difference Δ5 = 39.47, less than Δ2 = 126.5).

[0155] Furthermore, in terms of the components and amounts used, Cell Experiment Example 22 is equivalent to a combination of Cell Experiment Examples 4 and 14, or a combination of Cell Experiment Examples 6 and 13, or a combination of Cell Experiment Examples 10 and 12, or a combination of Cell Experiment Examples 4, 6, and 10. This is relative to the blank control group (Cell Experiment Example 1).

[0156] - Cell experiment example 22 increased the number of A2B5 positive cells by 131.44.

[0157] - Cell experiments Examples 4 and 14 increased the number of A2B5 positive cells by 39.33 and 19, respectively, for a total of 58.33, which is less than the increase (131.44) achieved in Cell Experiment Example 22.

[0158] - Cell experiments Examples 6 and 13 increased the number of A2B5 positive cells by 51.33 and 21.83, respectively, for a total of 73.16, which is less than the increase (131.44) achieved in Cell Experiment Example 22.

[0159] - Cell experiments 10 and 12 increased the number of A2B5 positive cells by 109 and 24, respectively, for a total of 133, slightly larger than the increase (131.44) achieved in cell experiment 22. The difference, Δ6 = 1.56, is much smaller than Δ1 = 66.66.

[0160] - Cell experiment examples 4, 6, and 10 increased the number of A2B5 positive cells by 39.33, 51.33, and 109, respectively, with a sum of 199.66, which is greater than the increment (131.44) achieved in cell experiment example 22. The difference Δ7 = 68.22 is much smaller than Δ2 = 126.5 and Δ3 = 141.33.

[0161] Therefore, it can be seen that when 2'-FL, lactophospholipids and choline are used in combination, the antagonistic effect between the components can be significantly reduced. There is a synergistic effect among the three components, which can synergistically increase the number of A2B5 positive cells and thus reduce the proliferation of oligodendrocyte precursor cells.

[0162] 2.2 Effects of each sample on myelination of OPC cells

[0163] To measure the effect of mixed or single nutrient treatments on myelination of OPC cells, we assessed the number of MAG-labeled positive cells after 18 DIVs. The mean number of MAG-positive cells per well is shown in Table 4.

[0164] Table 4. Effects of different nutrient compositions containing 2'-FL, milk phospholipids, and / or choline on the number of MAG-positive cells.

[0165]

[0166] The sample processing results showed that, compared with the blank control group (Cell Experiment Example 1), 2'-FL, milk phospholipids, and choline could all increase the number of MAG positive cells, indicating that these three components all contribute to the myelination of oligodendrocyte precursor cells.

[0167] However, the inventors have discovered that when any two of the three components are used in combination, there is a strong antagonistic effect.

[0168] In particular, as can be seen from cell experiment examples 12-14:

[0169] In terms of the components and amounts used, Cell Experiment Example 12 is equivalent to a combination of Cell Experiment Examples 4 and 6. Compared to the blank control group (Cell Experiment Example 1), Cell Experiment Examples 4 and 6 increased the number of MAG-positive cells by 35.66 and 29.66, respectively, while Cell Experiment Example 12 increased the number of MAG-positive cells by 25.83, which is not only much smaller than the sum of the former two (65.32) (the difference from the sum of the former two Δ1 = 39.49), but also smaller than each of the former two.

[0170] Cell Experiment Example 13 is equivalent to a combination of Cell Experiment Examples 4 and 10. Compared to the blank control group (Cell Experiment Example 1), Cell Experiment Examples 4 and 10 increased the number of MAG-positive cells by 35.66 and 53.33, respectively, while Cell Experiment Example 13 increased the number of MAG-positive cells by 24.5, which is not only much smaller than the sum of the former two (88.99) (the difference from the sum of the former two is Δ2 = 64.49), but also smaller than each of the former two.

[0171] Cell Experiment Example 14 is equivalent to a combination of Cell Experiment Examples 6 and 10. However, compared to the blank control group (Cell Experiment Example 1), Cell Experiment Examples 6 and 10 increased the number of MAG-positive cells by 29.66 and 53.33, respectively, while Cell Experiment Example 14 increased the number of MAG-positive cells by 21.83, which is not only much smaller than the sum of the former two (82.99) (the difference from the sum of the former two is Δ3 = 61.16), but also smaller than each of the former two.

[0172] This indicates that when any two of 2'-FL, lactophospholipids, and choline are used in combination, there is a strong antagonistic effect in terms of the number of MAG-positive cells and therefore myelination of oligodendrocyte precursor cells, and the combined effect is less than the effect of any one of the components used alone.

[0173] The inventors further discovered that when 2'-FL, lactophospholipids, and choline are used in combination, the antagonistic effect between the components can be significantly reduced, the number of MAG-positive cells can be synergistically increased, and myelination of oligodendrocyte precursor cells can be achieved.

[0174] Specifically, in terms of the components and amounts used, Cell Experiment Example 16 is equivalent to a combination of Cell Experiment Examples 7 and 13, or a combination of Cell Experiment Examples 4, 7, and 10. Compared to Cell Experiment Example 1, Cell Experiment Examples 4, 7, 10, 13, and 16 increased the number of MAG-positive cells by 35.66, 18, 53.33, 24.5, and 61.66, respectively. The increase in the number of MAG-positive cells in Cell Experiment Example 16 (61.66) is greater than the sum of the increases in Cell Experiment Examples 7 and 13 (42.5), but less than the sum of the increases in Cell Experiment Examples 4, 7, and 10 (106.99) (difference Δ4 = 45.33, less than Δ2 = 64.49).

[0175] Furthermore, in terms of the components and amounts used, Cell Experiment Example 17 is equivalent to a combination of Cell Experiment Examples 5, 8, and 11. Compared to Cell Experiment Example 1, Cell Experiment Examples 5, 8, and 11 increased the number of MAG-positive cells by 21.33, 1.66, and 40.66, respectively, while Cell Experiment Example 17 increased the number of MAG-positive cells by 83.33, which is greater than the sum of the previous three (63.65).

[0176] Furthermore, in terms of the components and amounts used, Cell Experiment Example 20 is equivalent to a combination of Cell Experiment Examples 9 and 12, or a combination of Cell Experiment Examples 4, 6, and 9. Compared to Cell Experiment Example 1, Cell Experiment Examples 4, 6, 9, 12, and 20 increased the number of MAG-positive cells by 35.66, 29.66, 25.66, 25.83, and 68.36, respectively. The increment achieved in Cell Experiment Example 20 (68.36) is greater than the sum of the increments of Cell Experiment Examples 9 and 12 (51.49), but less than the sum of the increments of Cell Experiment Examples 4, 6, and 9 (90.98) (difference Δ5 = 22.62, less than Δ1 = 39.49).

[0177] Furthermore, in terms of the components and amounts used, Cell Experiment Example 21 is equivalent to a combination of Cell Experiment Examples 7 and 13, or a combination of Cell Experiment Examples 4, 7, and 10. Compared to Cell Experiment Example 1, Cell Experiment Examples 4, 7, 10, 13, and 21 increased the number of MAG-positive cells by 35.66, 18, 53.33, 24.5, and 76.16, respectively. The increment achieved in Cell Experiment Example 21 (76.16) is greater than the sum of the increments of Cell Experiment Examples 7 and 13 (42.5), but less than the sum of the increments of Cell Experiment Examples 4, 7, and 10 (106.99) (difference Δ6 = 30.83, less than Δ2 = 64.49).

[0178] Furthermore, in terms of the components and amounts used, Cell Experiment Example 22 is equivalent to a combination of Cell Experiment Examples 4 and 14, or a combination of Cell Experiment Examples 6 and 13, or a combination of Cell Experiment Examples 10 and 12, or a combination of Cell Experiment Examples 4, 6, and 10. This is relative to the blank control group (Cell Experiment Example 1).

[0179] - Cell experiment Example 22 increased the number of MAG-positive cells by 80.91.

[0180] - Cell experiments Examples 4 and 14 increased the number of MAG-positive cells by 35.66 and 21.83, respectively, for a total of 57.49, which is less than the increase (80.91) achieved in Cell Experiment Example 22.

[0181] - Cell experiments Examples 6 and 13 increased the number of MAG-positive cells by 29.66 and 24.5, respectively, for a total of 54.16, which is less than the increase (80.91) achieved in Cell Experiment Example 22.

[0182] - Cell experiments Examples 10 and 12 increased the number of MAG-positive cells by 53.33 and 25.83, respectively, for a total of 79.16, which is less than the increase (80.91) achieved in Cell Experiment Example 22.

[0183] - Cell experiment examples 4, 6, and 10 increased the number of MAG-positive cells by 35.66, 29.66, and 53.33, respectively, with a sum of 118.65, which is greater than the increment (80.91) achieved in cell experiment example 22. The difference Δ7=37.74 is less than Δ1=39.49, Δ2=64.49, and Δ3=61.16.

[0184] Therefore, when 2'-FL, lactophospholipids, and choline are used in combination, the antagonistic effect between the components can be significantly reduced. There is a synergistic effect among the three components, which can synergistically increase the number of MAG-positive cells and thus myelinate oligodendrocytes.

[0185] 2.3 Effects of different samples on OPC cell maturation

[0186] To measure the effect of mixed or single nutrient treatments on OPC cell maturation, we assessed the number of MBP-labeled positive cells after 30 DIV. The mean number of MBP-positive cells per well is shown in Table 5.

[0187] Table 5. Effects of different nutrient compositions containing 2'-FL, milk phospholipids, and / or choline on the number of MBP-positive cells.

[0188]

[0189] The sample processing results showed that, compared with the blank control group (Cell Experiment Example 1), 2'-FL, milk phospholipids, and choline could all increase the number of MBP-positive cells, indicating that these three components all contribute to the maturation of oligodendrocyte precursor cells.

[0190] However, the inventors have discovered that when any two of the three components are used in combination, there is a strong antagonistic effect.

[0191] In particular, as can be seen from cell experiment examples 12-14:

[0192] In terms of the components and amounts used, Cell Experiment Example 12 is equivalent to a combination of Cell Experiment Examples 4 and 6. Compared to the blank control group (Cell Experiment Example 1), Cell Experiment Examples 4 and 6 increased the number of MBP-positive cells by 42.34 and 44.34, respectively, while Cell Experiment Example 12 increased the number of MBP-positive cells by 20.17, which is not only much smaller than the sum of the former two (86.68) (the difference from the sum of the former two Δ1 = 66.51), but also smaller than each of the former two.

[0193] Cell Experiment Example 13 is equivalent to a combination of Cell Experiment Examples 4 and 10. Compared to the blank control group (Cell Experiment Example 1), Cell Experiment Examples 4 and 10 increased the number of MBP-positive cells by 42.34 and 71.34, respectively, while Cell Experiment Example 13 increased the number of MBP-positive cells by 18.5, which is not only much smaller than the sum of the former two (113.68) (the difference from the sum of the former two is Δ2 = 95.18), but also smaller than each of the former two.

[0194] Cell Experiment Example 14 is equivalent to a combination of Cell Experiment Examples 6 and 10. However, compared to the blank control group (Cell Experiment Example 1), Cell Experiment Examples 6 and 10 increased the number of MBP-positive cells by 44.34 and 71.34, respectively, while Cell Experiment Example 14 increased the number of MBP-positive cells by 16, which is not only much smaller than the sum of the former two (115.68) (the difference from the sum of the former two is Δ3 = 99.68), but also smaller than each of the former two.

[0195] This indicates that when any two of 2'-FL, lactophospholipids, and choline are used in combination, there is a strong antagonistic effect in terms of the number of MBP-positive cells and therefore the maturation of oligodendrocyte precursor cells, and the combined effect is less than the effect of any one of the components used alone.

[0196] The inventors further discovered that when 2'-FL, lactophospholipids, and choline are used in combination, the antagonistic effect between the components can be significantly reduced, the number of MBP-positive cells can be synergistically increased, and the maturation of oligodendrocyte precursor cells can be promoted.

[0197] Specifically, in terms of the components and amounts used, Cell Experiment Example 16 is equivalent to a combination of Cell Experiment Examples 7 and 13, or a combination of Cell Experiment Examples 4, 7, and 10. Compared to Cell Experiment Example 1, Cell Experiment Examples 4, 7, 10, 13, and 16 increased the number of MBP-positive cells by 42.34, 29.67, 71.34, 18.5, and 78.34, respectively. The increase in MBP-positive cells in Cell Experiment Example 16 (78.34) is greater than the sum of the increases in Cell Experiment Examples 7 and 13 (48.17), but less than the sum of the increases in Cell Experiment Examples 4, 7, and 10 (143.35) (difference Δ4 = 65.01, less than Δ2 = 95.18).

[0198] Furthermore, in terms of the components and amounts used, Cell Experiment Example 17 is equivalent to a combination of Cell Experiment Examples 5, 8, and 11. Compared to Cell Experiment Example 1, Cell Experiment Examples 5, 8, and 11 increased the number of MBP-positive cells by 20.67, -10, and 5.67, respectively, while Cell Experiment Example 17 increased the number of MBP-positive cells by 94, which is greater than the sum of the previous three (16.34).

[0199] Furthermore, in terms of the components and amounts used, Cell Experiment Example 20 is equivalent to a combination of Cell Experiment Examples 9 and 12, or a combination of Cell Experiment Examples 4, 6, and 9. Compared to Cell Experiment Example 1, Cell Experiment Examples 4, 6, 9, 12, and 20 increased the number of MBP-positive cells by 42.34, 44.34, 51, 20.17, and 74.07, respectively. The increment achieved in Cell Experiment Example 20 (74.07) is greater than the sum of the increments of Cell Experiment Examples 9 and 12 (71.17), but less than the sum of the increments of Cell Experiment Examples 4, 6, and 9 (137.68) (difference Δ5 = 63.61, less than Δ1 = 66.51).

[0200] Furthermore, in terms of the components and amounts used, Cell Experiment Example 21 is equivalent to a combination of Cell Experiment Examples 7 and 13, or a combination of Cell Experiment Examples 4, 7, and 10. Compared to Cell Experiment Example 1, Cell Experiment Examples 4, 7, 10, 13, and 21 increased the number of MBP-positive cells by 42.34, 29.67, 71.34, 18.5, and 93.25, respectively. The increment achieved in Cell Experiment Example 21 (93.25) is greater than the sum of the increments of Cell Experiment Examples 7 and 13 (48.17), but less than the sum of the increments of Cell Experiment Examples 4, 7, and 10 (143.35) (difference Δ6 = 50.1, less than Δ2 = 95.18).

[0201] Furthermore, in terms of the components and amounts used, Cell Experiment Example 22 is equivalent to a combination of Cell Experiment Examples 4 and 14, or a combination of Cell Experiment Examples 6 and 13, or a combination of Cell Experiment Examples 10 and 12, or a combination of Cell Experiment Examples 4, 6, and 10. This is relative to the blank control group (Cell Experiment Example 1).

[0202] - Cellular experiment Example 22 increased the number of MBP-positive cells by 99.45%.

[0203] - Cell experiments Examples 4 and 14 increased the number of MBP-positive cells by 42.34 and 16, respectively, for a total of 58.34, which is less than the increase (99.45) achieved in Cell Experiment Example 22.

[0204] - Cell experiments Examples 6 and 13 increased the number of MBP-positive cells by 44.34 and 18.5, respectively, for a total of 62.84, which is less than the increase (99.45) achieved in Cell Experiment Example 22.

[0205] - Cell experiments Examples 10 and 12 increased the number of MBP-positive cells by 71.34 and 20.17, respectively, for a total of 91.51, which is less than the increase (99.45) achieved in Cell Experiment Example 22.

[0206] - Cell experiment examples 4, 6, and 10 increased the number of MBP-positive cells by 42.34, 44.34, and 71.34, respectively, with a sum of 158.02, which is greater than the increment (99.45) achieved in cell experiment example 22. The difference Δ7 = 58.57 is less than Δ1 = 66.51, Δ2 = 95.18, and Δ3 = 99.68.

[0207] Therefore, it can be seen that when 2'-FL, lactophospholipids and choline are used in combination, the antagonistic effect between the components can be significantly reduced, and there is a synergistic effect among the three components, which can synergistically increase the number of MBP-positive cells and thus the maturation of oligodendrocyte precursor cells.

[0208] This invention provides a study on the research of human milk oligosaccharides (preferably neutral Dunaliella salina-based human milk oligosaccharides (HMOs), preferably selected from one or more of 2'-fucosylvose (2'-FL), 3'-fucosylvose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexose I (LNDFH I), lactose-N-difucohexose II (LNDFH II), preferably 2'-fucosylvose (2'-FL)), milk phospholipids, choline or edible choline in brain development, especially in neural development, particularly in the proliferation, differentiation or maturation of oligodendrocyte precursor cells (OPCs) into oligodendrocytes (OLs) and myelin properties of oligodendrocytes (OLs), providing new ideas for the development of future functional foods. Human milk oligosaccharides (preferably neutral Dunaliella salina-based human milk oligosaccharides (HMOs), preferably selected from one or more of 2'-fucosylvose (2'-FL), 3'-fucosylvose (3'-FL), lactose-N-fucopentose I (LNFP I), lactose-N-difucohexose I (LNDFH I), and lactose-N-difucohexose II (LNDFH II), with 2'-fucosylvose (2'-FL)) , milk phospholipids, choline, or edible choline show great promise in improving memory and brain development. Studies have found that the extracellular environment plays an important role in regulating brain homeostasis and controlling myelin formation during central nervous system development. Deficiencies in key nutrients can significantly affect brain development. Our research shows that, in in vitro models, brain cell cultures treated with a combination of 2'-FL, lactophospholipids, choline, or edible choline increased the number of OPCs, their differentiation or maturation into OLs, and the myelin properties of OLs, with good synergistic effects among the components.

[0209] Application Examples

[0210] In the following application examples, "parts" refers to parts by weight, and the percentage content of ingredients refers to percentage content by weight.

[0211] In addition, in the following application examples, unless otherwise stated, the sources of the following raw materials are as follows.

[0212] Raw milk: Heilongjiang Feihe Dairy Co., Ltd.

[0213] Whole milk powder: Heilongjiang Feihe Dairy Co., Ltd.

[0214] Skim milk powder: Kerry from Ireland

[0215] 2'-Fucosyllactose (2'-Fucosyllactose 96.0%): GlyCare™ 2'-FL 9000

[0216] Whey protein concentrate rich in phospholipids (7% phospholipids): Lacprodan® MFGM-10 from Denmark

[0217] Milk phospholipid powder (phospholipid 12.3%): Tatua of New Zealand PLC1

[0218] Choline chloride (choline content 72.5%): Beijing Jinkangpu Food Technology Co., Ltd.

[0219] Demineralized whey powder: Eurosorum (Red Bird), France

[0220] Galacto-oligosaccharides: Baolingbao Biotechnology Co., Ltd.

[0221] Blended vegetable oils: Cargill Oils & Grains (Nantong) Co., Ltd.

[0222] Mixed vegetable oil (containing 1,3-dioleoyl-2-palmitoylglycerol triglyceride): Bungelords (Xiamen) Oils & Fats Technology Co., Ltd.

[0223] Compound Vitamins: DSM Vitamins (Shanghai) Co., Ltd.

[0224] Compound Minerals: DSM Vitamins (Shanghai) Co., Ltd.

[0225] Solid corn syrup: Baolingbao Biotechnology Co., Ltd.

[0226] Fructooligosaccharides: Baolingbao Biotechnology Co., Ltd.

[0227] Isomaltooligosaccharide: Baolingbao Biotechnology Co., Ltd.

[0228] Application Example 1

[0229] Infant formula containing 2'-fucosylated lactose, milk phospholipids, and choline is prepared per 1000 servings of infant formula from the following components by weight:

[0230] The raw materials used in the milk powder of this invention are: 195 parts of raw milk (on a dry basis) (each part containing 0.10% choline and 0.20% phospholipids), 28.5 parts of concentrated whey protein powder rich in phospholipids (each part containing 7% phospholipids), 10.42 parts of 2'-fucosylated lactose (each part containing 96.0% 2'-fucosylated lactose), 0.3 parts of choline chloride (each part containing 72.5% choline), and 400 parts of demineralized whey powder (each part containing 0.15% choline). ), lactose 83.78 parts, galactooligosaccharides 37 parts, mixed vegetable oil 200 parts, arachidonic acid oil powder (10%) 16 parts, docosahexaenoic acid oil powder (7%) 14 parts, sodium citrate 2 parts, potassium chloride 2 parts, calcium citrate 6 parts, compound vitamins 3 parts, compound minerals 2 parts; after the above raw materials are mixed evenly, they are pasteurized, homogenized, evaporated and concentrated and spray dried into powdered semi-finished products. The milk powder after being mixed evenly is packaged with nitrogen to obtain the final product.

[0231] Application Example 2

[0232] Infant formula containing 2'-fucosylated lactose, milk phospholipids, and choline is prepared per 1000 servings of infant formula from the following components by weight:

[0233] The raw materials used in the milk powder of this invention are: 220 parts of raw milk (on a dry basis) (each part containing 0.10% choline and 0.20% phospholipids), 15 parts of concentrated whey protein powder rich in phospholipids (each part containing 7% phospholipids), 10.42 parts of 2'-fucosylated lactose (each part containing 96.0% 2'-fucosylated lactose), 3.1 parts of choline chloride (each part containing 72.5% choline), and 400 parts of demineralized whey powder (each part containing 0.15% choline). 74.48 parts lactose, 37 parts galactooligosaccharides, 195 parts mixed vegetable oil, 16 parts arachidonic acid oil powder (10%), 14 parts docosahexaenoic acid oil powder (7%), 2 parts sodium citrate, 2 parts potassium chloride, 6 parts calcium citrate, 3 parts compound vitamins, and 2 parts compound minerals; after the above raw materials are mixed evenly, they are pasteurized, homogenized, evaporated and concentrated and spray-dried into a powdered semi-finished product. The milk powder after being mixed evenly is then packaged with nitrogen to obtain the final product.

[0234] Application Example 3

[0235] Infant formula containing 2'-fucosylated lactose, milk phospholipids, and choline is prepared from the following components in parts by weight per 1000 servings:

[0236] The raw materials used in the milk powder of this invention are: 220 parts of raw milk (on a dry basis) (each part containing 0.10% choline and 0.20% phospholipids), 15 parts of concentrated whey protein powder rich in phospholipids (each part containing 7% phospholipids), 10.42 parts of 2'-fucosylated lactose (each part containing 96.0% 2'-fucosylated lactose), 1.5 parts of choline chloride (each part containing 72.5% choline), 380 parts of demineralized whey powder (each part containing 0.15% choline), and 120 parts of skim milk powder (each part containing 0.14% choline). The ingredients are: 72.43 parts lactose, 40 parts galacto-oligosaccharides, 120 parts mixed vegetable oil (containing 1,3-dioleoyl-2-palmitoylglycerol triglyceride), 4.5 parts arachidonic acid oil powder (10%), 6.5 parts docosahexaenoic acid oil powder (7%), 5 parts calcium citrate, 3 parts compound vitamins, 1 part compound minerals, and 0.65 parts compound nucleotides. After the above ingredients are mixed evenly, they are pasteurized, homogenized, evaporated and concentrated, and spray-dried into a powdered semi-finished product. The milk powder is then packaged with nitrogen to obtain the final product.

[0237] Application Example 4

[0238] This modified milk powder, containing 2'-fucosylated lactose, milk phospholipids, and choline, is suitable for pregnant women. Each 1000 servings of modified milk powder is made from the following components in parts by weight:

[0239] The raw materials used in the milk powder of this invention are: 436 parts of whole milk powder (each part contains 0.10% choline and 0.2% phospholipids), 40.65 parts of phospholipid powder (each part contains 12.3% phospholipids), 10.42 parts of 2'-fucosylated lactose (each part contains 96.0% 2'-fucosylated lactose), 2.5 parts of choline chloride (each part contains 72.5% choline), 200 parts of skim milk powder (each part contains 0.14% choline), 73.93 parts of lactose, 165 parts of maltodextrin, 60 parts of isomaltooligosaccharide, 7 parts of DHA powder (calculated as 7%), 3.5 parts of compound vitamins, and 1 part of compound minerals. After the above raw materials are mixed evenly, they are pasteurized, homogenized, evaporated and concentrated, and spray-dried into a powdered semi-finished product. The evenly mixed milk powder is then packaged with nitrogen to obtain the final product.

[0240] Application Example 5

[0241] This modified milk powder, containing 2'-fucosylated lactose, milk phospholipids, and choline, is suitable for pregnant women. Each 1000 servings of modified milk powder is made from the following components in parts by weight:

[0242] The raw materials used in the milk powder of this invention are: 436 parts of raw milk (on a dry basis) (each part contains 0.10% choline and 0.2% milk phospholipids), 5 parts of milk phospholipid powder (each part contains 12.3% milk phospholipids), 10.42 parts of 2'-fucosylated lactose (each part contains 96.0% 2'-fucosylated lactose), 1.8 parts of choline chloride (each part contains 72.5% choline), 250 parts of skim milk powder (each part contains 0.14% choline), 78.28 parts of lactose, 137 parts of maltodextrin, 70 parts of isomaltooligosaccharide, 7 parts of DHA powder (7%), 3.5 parts of compound vitamins, and 1 part of compound minerals. After the above raw materials are mixed evenly, they are pasteurized, homogenized, evaporated and concentrated, and spray-dried into a powdered semi-finished product. The evenly mixed milk powder is then packaged with nitrogen to obtain the final product.

[0243] Application Example 6

[0244] This modified milk powder, containing 2'-fucosylated lactose, milk phospholipids, and choline, is suitable for pregnant and postpartum women. Each 1000 servings of modified milk powder is made from the following components in parts by weight:

[0245] The raw materials used in the milk powder of this invention are: 436 parts of whole milk powder (each part contains 0.10% choline and 0.2% phospholipids), 35 parts of phospholipid powder (each part contains 12.3% phospholipids), 10.42 parts of 2'-fucosylated lactose (each part contains 96.0% 2'-fucosylated lactose), 3.1 parts of choline chloride (each part contains 72.5% choline), 210 parts of skim milk powder (each part contains 0.14% choline), 65.98 parts of lactose, 168 parts of maltodextrin, 60 parts of isomaltooligosaccharide, 7 parts of DHA powder (calculated as 7%), 3.5 parts of compound vitamins, and 1 part of compound minerals. After the above raw materials are mixed evenly, they are pasteurized, homogenized, evaporated and concentrated, and spray-dried into a powdered semi-finished product. The evenly mixed milk powder is then packaged with nitrogen to obtain the final product.

[0246] The above description is merely an exemplary embodiment of the present invention. It should be noted that those skilled in the art can make improvements without departing from the inventive concept of the present invention, and all such improvements fall within the protection scope of the present invention.

Claims

1. The use of a nutritional composition for non-therapeutic purposes in enhancing brain development and intelligence in infants and young children by promoting the proliferation, maturation, and myelination of oligodendrocyte precursor cells, wherein said nutritional composition comprises the following: - Human milk oligosaccharides, selected from 2'-fucosylated lactose; - Milk phospholipids; and - Choline and / or edible choline derivatives, preferably edible choline derivatives selected from choline chloride and / or choline tartrate; in: The mass ratio of human milk oligosaccharides to milk phospholipids is 1:0.15-2.5; The mass ratio of human milk oligosaccharides to choline and / or edible choline derivatives, expressed as the ratio of the mass of human milk oligosaccharides to the total mass of choline converted to choline, is 1:0.1-0.

5.

2. The use as described in claim 1, wherein the human milk oligosaccharide is provided in the form of a natural source, and / or a synthetic source, and / or a bacterial fermentation source.

3. The use as described in claim 1, wherein: Milk phospholipids are phospholipids derived from cow and / or sheep milk; and / or Milk phospholipids are provided in the following forms: protein powder containing milk phospholipids, preferably wherein the milk phospholipid content in the protein powder is 6-25% by weight; and / or milk-derived phospholipids, preferably wherein the milk-derived phospholipid content is 9-60% by weight; and / or The milk phospholipids contain at least sphingomyelin and phosphatidylcholine, and optionally further contain serine phospholipids and / or phosphatidylethanolamine, wherein sphingomyelin accounts for more than 10% by weight of the total milk phospholipids and phosphatidylcholine accounts for more than 15% by weight of the total milk phospholipids.

4. The use as described in any one of claims 1-3, wherein the choline and / or edible choline derivative is choline chloride and / or choline tartrate.

5. The use as described in any one of claims 1-3, wherein: The mass ratio of human milk oligosaccharides to milk phospholipids is 1:0.2-2.5; and The mass ratio of human milk oligosaccharides to choline and / or edible choline derivatives, expressed as the ratio of the mass of human milk oligosaccharides to the total mass of choline converted to choline, is 1:0.2-0.

4.

6. The use as described in any one of claims 1-3, wherein the nutritional composition is provided in the form of a food comprising the composition, the food being, for example, a powder or a liquid, the food being, for example, an infant formula.

7. The use of claim 6, wherein, The infant formula food is selected from one of the following: infant formula milk powder, toddler formula milk powder, infant complementary food, or nutritional or dietary supplements.

8. The use as claimed in claim 6, wherein the amount of the nutritional composition added is such that, relative to the total weight of the food, the weight content of human milk oligosaccharides is at least 0.01% and at most 10.0%, and the weight content of milk phospholipids is at least 0.01% and at most 5.0%.

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