Use of a nutritional composition

Through the specific ratio combination of medium and long-chain fatty acid triglycerides and breast milk oligosaccharides, the problem of promoting intestinal development and nutritional absorption in infants and young children is solved, significantly improving intestinal functional indicators and promoting growth and development.

CN119999922BActive Publication Date: 2025-08-05INNER MONGOLIA MENGNIU DAIRY IND (GROUP) CO LTD +1
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Patent Information

Application Number
CN202510428665.0
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2025-04-08
Publication Date
2025-08-05
Estimated Expiration
2045-04-08

AI Technical Summary

Technical Problem

There is a lack of effective nutritional compositions in the prior art for solutions to promote intestinal development, improve intestinal secretion and nutrient absorption in infants and young children.

Method used

Nutritional compositions that combine medium-long chain fatty acid triglycerides and breast milk oligosaccharides in a specific ratio are 0.1:1 to 100:1 to synergistically promote intestinal development and nutrient absorption.

Benefits of technology

Significantly improve indicators such as the length of small intestine villus, depth of crypts, and number of goblet cells, enhance the absorption and secretion function of the intestine, and promote the growth and development of infants and young children.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention relates to the use of a nutritional composition, and more specifically to the use of the nutritional composition for non-therapeutic purposes of promoting intestinal development, improving intestinal secretion and / or nutrient absorption. The nutritional composition comprises medium- and long-chain fatty acid triglycerides and human milk oligosaccharides, wherein the weight ratio of the medium- and long-chain fatty acid triglycerides to the human milk oligosaccharides is 0.1:1 to 100:1.
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Description

Technical Field

[0001] The present invention relates to the field of food, and in particular to a nutritional composition for promoting intestinal development, improving intestinal secretion and / or nutrient absorption for non-therapeutic purposes. Background Art

[0002] The intestine generally refers to the digestive tract from the pylorus to the anus. It is the longest section of the digestive tract and also its most functionally important. The intestine is approximately 7-8 meters long and is divided into the small intestine and the large intestine. As the primary organ for digesting food and absorbing nutrients necessary for development, the intestine is divided into three parts: the small intestine, the cecum, and the colon. The small intestine is the primary site for nutrient absorption. Its villi significantly increase its internal surface area, playing a key role in nutrient absorption. Longer villi increase the contact area with food, facilitating nutrient absorption. Crypt depth reflects the rate of intestinal cell formation. Generally, shallower crypt depth indicates a higher rate of cell maturation and enhanced secretory function. The ratio of villus length to crypt depth (V / C) is an important parameter for assessing the absorptive capacity of the small intestine. A higher V / C ratio generally indicates greater absorptive capacity and may be related to the rapid turnover of epithelial cells. Unlike the small intestine, the colon has only crypts without villi. Colonic crypts contain goblet cells and enterocytes, which perform both secretory and absorptive functions.

[0003] The intestines are not only the primary site for nutrient digestion and absorption, but also a crucial immune and endocrine organ. As the body's primary digestive organ, the intestines digest and absorb the majority of nutrients needed, providing beneficial nutrients for growth and development and maintaining vitality. Over 80% of toxins are excreted from the body through the intestines. The intestinal tract's complex microbial ecosystem is closely linked to the body's immune system. The intestines are responsible for over 70% of the body's immune function, with nearly 70% of immune cells located in the intestinal mucosa. These cells play a crucial role in defending against bacteria and viruses and maintaining a stable intestinal environment.

[0004] Intestinal development is very important for infants. It not only helps to improve the infant's immune system, reduce gastrointestinal infections, respiratory infections and other diseases, and promote the growth and development of infants, but also promotes the development of the infant's nervous system and contributes to their all-round development.

[0005] Therefore, it is of great significance to study and find a nutritional composition that can be used to promote intestinal development, improve intestinal secretion and / or nutrient absorption. 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 nutritional composition for the non-therapeutic purpose of promoting intestinal development, improving intestinal secretion and / or nutrient absorption. The nutritional composition comprises medium- and long-chain triacylglycerol (MLCT) and human milk oligosaccharides (HMO), and the weight ratio of the medium- and long-chain triacylglycerol to the human milk oligosaccharides is 0.1:1 to 100:1.

[0008] The inventors unexpectedly discovered during their research that medium- and long-chain fatty acid triglycerides and human milk oligosaccharides, when used in combination at specific ratios, can synergistically promote intestinal development, improve intestinal secretion, and / or nutrient absorption. In particular, the combined effect of medium- and long-chain fatty acid triglycerides and human milk oligosaccharides is superior to the effect of the same total amount of medium- and long-chain fatty acid triglycerides alone, and also superior to the effect of the same total amount of human milk oligosaccharides alone. DETAILED DESCRIPTION

[0009] In order to make the invention objectives, technical solutions and beneficial technical effects of this application clearer, this application will be described in detail below. It should be noted that the various aspects, features, implementation methods and advantages described in this application may be compatible and / or combinable.

[0010] Unless otherwise specified, the technical terms or scientific terms in this specification have the same meanings as those generally understood by those skilled in the art.

[0011] In this application, the "promoting intestinal development, improving intestinal secretion and / or nutrient absorption" refers to one of the following situations: 1. Promoting intestinal development; 2. Improving intestinal secretion; 3. Improving nutrient absorption; 4. Promoting intestinal development and improving intestinal secretion; 5. Promoting intestinal development and improving nutrient absorption; 6. Promoting intestinal development, improving intestinal secretion and nutrient absorption.

[0012] The non-therapeutic purpose (non-medical therapeutic purpose such as nutrition and / or health care purpose) of promoting intestinal development, improving intestinal secretion and / or nutrient absorption is, for example, for preparing food (such as functional food or health food) for promoting intestinal development, improving intestinal secretion and / or nutrient absorption.

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

[0014] In this application, the term "medium-chain fatty acids" refers to fatty acids with 6-12 carbon atoms in the carbon chain, such as hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, and dodecanoic acid; the term "long-chain fatty acids" refers to fatty acids with 14 or more 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. The terms "medium-chain fatty acid triglycerides" and "long-chain fatty acid triglycerides" refer to the esterification reaction products of "medium-chain fatty acids" and "long-chain fatty acids," respectively, with glycerol; the term "medium- and long-chain fatty acid triglycerides" refers to triglycerides containing both medium- and long-chain fatty acid residues in their molecular structure.

[0015] In this application, the term "human milk oligosaccharide", also known as "human milk oligosaccharide", is a type of complex oligosaccharide composed of monosaccharides and their derivatives, sialic acid and other structural units connected by glycosidic bonds.

[0016] The present invention relates to the use of a nutritional composition for the non-therapeutic purpose of promoting intestinal development, improving intestinal secretion and / or nutrient absorption. In particular, the present invention relates to the use of a nutritional composition for the non-therapeutic purpose of promoting intestinal development, improving intestinal secretion and / or nutrient absorption, wherein the nutritional composition comprises medium-chain fatty acid triglycerides (MLCT) and human milk oligosaccharides (HMO), wherein the weight ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides is 0.1:1 to 100:1.

[0017] The inventors unexpectedly discovered in their research that medium- and long-chain fatty acid triglycerides and human milk oligosaccharides (particularly 2'-fucosyllactose, 3'-sialyllactose, and / or lactose-N-neotetraose), when used in combination in specific ratios, can synergistically promote intestinal development, improve intestinal secretion, and / or nutrient absorption in humans, for example, in infants and young children. Such intestinal development, improved intestinal secretion, and / or nutrient absorption can be reflected, for example, by indicators such as small intestinal villus length, small intestinal crypt depth, the ratio of small intestinal villus length to small intestinal crypt depth, colonic crypt depth, the number of small intestinal goblet cells, and the number of colonic goblet cells. Therefore, when medium- and long-chain fatty acid triglycerides and human milk oligosaccharides are used in combination at a specific ratio, they can synergistically improve one, two, three, four, five, or six of the following indicators: small intestinal villus length, small intestinal crypt depth, the ratio of small intestinal villus length to small intestinal crypt depth, colonic crypt depth, small intestinal goblet cell number, and colonic goblet cell number, particularly improving at least the ratio of small intestinal villus length to small intestinal crypt depth. Those skilled in the art will appreciate that the greater the number of synergistic indicators, the stronger the synergistic effect.

[0018] The length of the villi and the depth of the crypts in the small intestine reflect intestinal function and development. The small intestine is the primary site for nutrient absorption. The villi significantly increase the intestinal surface area. The villi are rich in capillaries and lymphatic vessels, which play a key role in nutrient absorption. Longer villi increase the contact area with food, facilitating nutrient absorption.

[0019] The depth of the crypt reflects the rate of intestinal cell generation. Generally, a shallower crypt depth means a higher cell maturation rate and stronger secretory function.

[0020] Stem cells deep within the small intestinal crypts continuously divide to produce new intestinal epithelial cells. These proliferating cells push neighboring cells to gradually migrate to the villus tips, ultimately squeezing into the intestinal lumen and undergoing apoptosis, thus keeping the small intestinal villi in a state of continuous self-renewal. The ratio of villus length to crypt depth (V / C) is an important parameter for assessing the absorptive capacity of the small intestine. A higher V / C generally indicates greater absorptive capacity and may be related to rapid epithelial cell turnover. A lower V / C indicates mucosal damage and decreased nutrient absorption.

[0021] Unlike the small intestine, the colon has only crypts and no villi. Within the colonic crypts are goblet cells and enterocytes, which have secretory and absorptive functions. A greater colonic crypt depth generally indicates greater secretory and absorptive function.

[0022] Goblet cells are specialized epithelial cells that resemble a goblet, larger at the top and narrower at the bottom. They primarily synthesize and secrete mucin, contributing to the formation of the mucus layer, or intestinal mucus barrier. This layer lubricates the intestinal mucosal surface, protecting the tissue from pathogenic bacteria while maintaining symbiotic homeostasis and maintaining a stable intestinal environment. A greater number of goblet cells generally indicates a more stable intestinal environment.

[0023] The present invention has no particular requirements for the human milk oligosaccharides used, and human milk oligosaccharides commonly used in the art can be used. Human milk oligosaccharides can be used in pure form or in an impure form enriched with human milk oligosaccharides.

[0024] In some embodiments, the human milk oligosaccharide can be selected from one or more of fucosyl-containing human milk oligosaccharides, sialic acid-containing human milk oligosaccharides, and non-fucosyl and non-sialic acid human milk oligosaccharides.

[0025] In some embodiments, the fucosyl-containing human milk oligosaccharide is, for example, 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 is, for example, selected from one or more of the following: 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL).

[0027] In some embodiments, the non-fucosyl and non-sialic acid human milk oligosaccharides are selected from one or more of the following: lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), lacto-N-triose II and lacto-N-diose.

[0028] In some embodiments, the human milk oligosaccharide is, for example, selected from one of the following: 2'-fucosyllactose; 3'-sialyllactose; lactose-N-neotetraose; 2'-fucosyllactose and 3'-sialyllactose; 2'-fucosyllactose and lactose-N-neotetraose; 3'-sialyllactose and lactose-N-neotetraose; 2'-fucosyllactose and 3'-sialyllactose and lactose-N-neotetraose.

[0029] In some embodiments, the human milk oligosaccharide is, for example, selected from one of the following: 2'-fucosyllactose; lactose-N-neotetraose; 2'-fucosyllactose and lactose-N-neotetraose.

[0030] When human milk oligosaccharides are a mixture of any two or more, the ratio between the components is not particularly limited and can be appropriately selected taking into account the other functions 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, 14:1, 15:1, 16:1, 17 ... 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.

[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, such as 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, 14:1, 15 ... 2:1, 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 limited 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, such as 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, 14:1, 15 ... 2:1, 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 limited 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, such as the 2'-FL / 3'-SL mass ratio, the mass ratio of fucosyl-containing human milk oligosaccharide / non-fucosyl non-sialic acid human milk oligosaccharide, such as the 2'-FL / LNnT mass ratio and the mass ratio of sialic acid-containing human milk oligosaccharide / non-fucosyl non-sialic acid human milk oligosaccharide, such as the 3'-FL / 3'-SL mass ratio, are used. The -SL / LNnT mass ratio may be each 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. For example, when the human milk oligosaccharide is a combination of fucosyl-containing human milk oligosaccharides, sialic acid-containing human milk oligosaccharides and non-fucosyl non-sialic acid human milk oligosaccharides, based on 4 parts by weight of non-fucosyl non-sialic acid human milk oligosaccharides, the weight range of the fucosyl-containing human milk oligosaccharides is 1 to 12, preferably 4 to 12, and / or the weight range of the sialic acid-containing human milk oligosaccharides is 1 to 12, preferably 1 to 4. Alternatively, when the human milk oligosaccharide is a combination of fucosyl-containing human milk oligosaccharide, sialic acid-containing human milk oligosaccharide and non-fucosyl non-sialic acid human milk oligosaccharide, based on 4 parts by weight of non-fucosyl non-sialic acid human milk oligosaccharide, the weight range of fucosyl-containing human milk oligosaccharide is 8 to 28, preferably 16 to 24, and / or the weight range of sialic acid-containing human milk oligosaccharide is 1 to 8, preferably 1 to 4.

[0035] Medium-chain triglycerides (MLCT) are structural lipids that contain both medium-chain fatty acids and long-chain fatty acids in a class of triglyceride molecules. They have different physicochemical properties, metabolic characteristics, and nutritional values from long-chain triglycerides (LCT) or medium-chain triglycerides (MCT). Studies (see, for example, Yuan Tinglan, Composition of medium-chain triglycerides in breast milk fat and its metabolic characteristics [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). The latter does not have the physicochemical properties, metabolic characteristics, and nutritional value possessed by the former. Based on the unique properties of medium-chain triglycerides, they have received widespread attention in the field of weight loss compositions in recent years.

[0036] The present invention has no special requirements for the medium-chain fatty acid triglycerides used, and the medium-chain fatty acid triglycerides commonly used in the art can be used. The medium-chain fatty acid triglycerides can be used in pure form or in an impure form rich in medium-chain fatty acid triglycerides. 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: hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, dodecanoic acid, etc., preferably hexanoic acid, octanoic acid, decanoic acid and lauric acid; and / or the C 14 -C 30The 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, hexacosahexanoic 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.

[0037] In some embodiments, the C6-C 12 Fatty acid residues on the C 14 -C 30 The weight ratio of fatty acid residues is 0.124 to 2.000. As an example, the C6-C 12 Fatty acid residues on the C 14 -C 30 The weight 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 within the range defined by any two thereof.

[0038] In an embodiment, the weight ratio of the medium- and long-chain fatty acid triglycerides to the human milk oligosaccharides in the nutritional composition is 0.1:1 to 100:1; within the range, one or more (e.g., one, two, three, four, five, or six) indicators (e.g., at least three indicators) of the indicators such as small intestinal villus length, small intestinal crypt depth, the ratio of small intestinal villus length to small intestinal crypt depth, colonic crypt depth, small intestinal goblet cell number, and colonic goblet cell number have a synergistic effect; in particular, a synergistic effect is shown at least in terms of the ratio of small intestinal villus length to small intestinal crypt depth. As an example, the weight ratio of the medium- and long-chain fatty acid triglycerides to the human milk oligosaccharides can be 0.1:1, 0.5:1, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 15:1, 20:1, 50:1, 100:1, or within the range defined by any two of them. Preferably, the weight ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides in the nutritional composition is 0.1:1 to 10:1; within the preferred range, a synergistic effect is exhibited at least in terms of the length of small intestinal villi and the ratio of small intestinal villus length to small intestinal crypt depth. Further preferably, the weight ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides in the nutritional composition is 0.1:1 to 7:1; within the further preferred range, relative to the weight ratio outside this range, the number of synergistic indicators such as small intestinal villus length, small intestinal crypt depth, the ratio of small intestinal villus length to small intestinal crypt depth, colonic crypt depth, small intestinal goblet cell number, and colonic goblet cell number is greater (at least four), and a synergistic effect is exhibited at least in terms of small intestinal villus length, the ratio of small intestinal villus length to small intestinal crypt depth, and the number of small intestinal goblet cells. The synergistic effect is stronger.

[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. In some embodiments, the food is an infant food such as an infant formula.

[0041] In some embodiments, the content of medium and long chain fatty acid triglycerides can be 0.1 to 30% by weight based on the weight of the food. For example, the content of medium and long chain fatty acid triglycerides can be 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 %, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, 20, 20.5, 21, 21.5, 22, 22.5, 23, 23.5, 24, 24.5, 25, 25.5, 26, 26.5, 27, 27.5, 28, 28.5, 29, 29.5, 30 wt % or the range defined by any two of them.

[0042] In some embodiments, the content of human milk oligosaccharides may be 0.01 to 6 wt % based on the weight of the food. As an example, the content of human milk oligosaccharides 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, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6 weight % based on the weight of the food, or within the range defined by any two of them.

[0043] In some embodiments, the food may be, for example, a functional food or a health food.

[0044] In some embodiments, the food is a common food or a specialty 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.

[0045] In this application, "special food" refers to special foods for specific groups of people, such as "the elderly, the young, and the sick", including three categories: health food, infant formula, and special medical purpose formula food.

[0046] In addition, it will be readily understood by those skilled in the art that, in addition to the nutritional composition of the first aspect of the present invention, the food further comprises one or more components selected from the following: raw cow's milk, desalted whey powder, concentrated whey protein, lactose, edible vegetable blending oil, oligofructose, oligogalactose, nucleotides, choline, vitamins, minerals, DHA and taurine.

[0047] For example, when the food is milk powder, in addition to the nutritional composition, the milk powder may also include the following components: proteins such as α-lactalbumin and 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.

[0048] The food can be produced by a preparation method commonly used in the art, which will not be described in detail here.

[0049] In some embodiments, when the nutritional composition or food is taken orally by humans, the dosage is such that: the dosage of the medium and long chain fatty acid triglycerides can be 0.1 to 30.0 g / day, preferably 2.5 to 30 g / day (e.g., 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0, 10.5, 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 , 28.0, 28.5, 29.0, 29.5, 30.0 g / day or a range defined by any two of them), and in a further embodiment, the dosage of human milk oligosaccharides is calculated based on the ratio.

[0050] In some embodiments, the dosage of human milk oligosaccharides can be 0.05 to 25 g / day, preferably 0.1 to 25 g / day (e.g., 0.05, 0.055, 0.06, 0.065, 0.07, 0.075, 0.08, 0.085, 0.09, 0.095, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, , 22.0, 22.5, 23.0, 23.5, 24.0, 24.5, 25.0 g / day, or a range bounded by any two of them).

[0051] Example

[0052] In order to make the purpose, technical solutions 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 intended to limit the present invention.

[0053] 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%, 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%, batch number: 21107002; 3'-sialyllactose: provided by DSM Vitamins Trading (Shanghai) Co., Ltd., SHANGHAI, purity 95.2%, batch number: DK21294101; lactose-N-neotetraose: provided by DSM Vitamins Trading (Shanghai) Co., Ltd., SHANGHAI, purity 95.2%, batch number: DK21294101; lactose-N-neotetraose: provided by DSM Vitamins Trading (Shanghai) Co., Ltd., DTL Duty Free Provided by Paid.Shanghai, purity 100.5%, batch number: 20454001; mice: SPF grade male C57BL / 6, purchased from Beijing Weitonglihua Laboratory Animal Technology Co., Ltd.

[0054] Dosage design

[0055] 1. Based on the HMO and MLCT content in breast milk and the doses used in related studies, a daily dose of 0.9g (HMO + MLCT) / kg body weight (infant) was designed. For a 6-month-old infant weighing 8kg, the combined HMO + MLCT dose is 7.2g / day.

[0056] 2. Calculate according to the formula and growth coefficient in the "Roadmap and Reference Values" of the relevant document "Recommended Dietary Nutrients for Chinese Residents 2023" regarding "AI values for children and adolescents are extrapolated from corresponding values for adults".

[0057] Formula for AI 7-12m =AI adult×(weight 7-12m / weight 成人 ) 0.75 ×(1+growth coefficient).

[0058] *The growth coefficient for children aged 0.5 to 4 years is 0.3.

[0059] 3. Using the above formula, a 6-month-old infant's daily HMO+MLCT intake of 7.2 g / day is equivalent to a 60 kg adult's daily HMO+MLCT intake of 25 g / 60 kg.BW, or 418 mg / kg.BW (for adults).

[0060] 4. Based on the relevant documents published by the U.S. FDA, the dose conversion of human and animal test substances is based on the body surface area per square meter (BSA, m 2 ) of body weight (kg), that is, the conversion factor Km (kg / m 2 ) for conversion, Km mouse / Km adult = 12.3, that is, the conversion factor from the human test dose (mg / kg.BW) to the mouse test dose is 12.3.

[0061] Based on the above conversion factors, the adult human dose of 418 mg / kg.BW is equivalent to the mouse dose of 5141 mg / kg. Based on a 20g mouse weight, this is approximately equivalent to 100 mg / 20g.BW (mouse)**. Assuming an average daily feed intake of 4g for a 20g mouse, this is equivalent to adding 2.5g of HMO + MLCT per 100g of feed.

[0062] Animal experiment design

[0063] (1) Experimental animals: 160 3-week-old male C57BL / 6 mice.

[0064] (2) Experimental Grouping: After adaptive feeding, mice were randomly divided into 16 groups according to body weight, with 10 mice in each group. They were fed with the provided feed (Tables 1 and 2) for 3 weeks. The total content of MLCT and HMO in each group of feed was 100 mg / 20 g.BW (mouse), which is equivalent to 7.2 g / d for infants around 6 months old. The feeding conditions were: SPF animal room, temperature 23±2°C, 12 h light / dark cycle, free access to water and food. The body weight of mice was recorded weekly during the intervention period, and the food intake of mice was recorded. All animal experiments were approved by the Animal Ethics Committee of Sun Yat-sen University.

[0065] (3) Experimental model

[0066] Intervention: The control group was fed with conventional feed AIN93G (Jiangsu Medison Biopharmaceutical Co., Ltd., China). The experimental group was fed with HMO and MLCT in the proportions according to Table 2. The intervention was oral dietary exposure under free feeding.

[0067] Intervention duration: 21 days.

[0068] Intervention frequency: Daily ad libitum oral dietary exposure.

[0069] (4) Experiments and testing items during the feeding process

[0070] Mice were housed in an SPF-grade animal room at the Experimental Animal Center of Sun Yat-sen University at an ambient temperature of 25±0.5°C with a 12-h light / dark cycle. During the experiment, the mice were weighed every 3 days, and the weight change trend of the mice was analyzed later, and the food intake of the mice was recorded.

[0071] (5) Mouse handling and sample collection after the experiment

[0072] After the intervention, mice were fasted for 12 hours, anesthetized, and sacrificed. The following biological samples were collected: small intestine and colon tissues were collected for morphological analysis and other indicators.

[0073] Sample Storage Conditions: Samples of approximately 0.5 cm of each small intestine and colon tissue were paraffin-embedded and stored at room temperature for subsequent sectioning and staining. The remaining small intestine and colon tissues were frozen at -80°C.

[0074] Table 1: Contents of MLCT and HMO (2'-FL, LNnT and 3'-SL) in the feeds of each group

[0075]

[0076]

[0077] Table 2: Weight ratio of MLCT and HMO (2'-FL, LNnT and 3'-SL) in the feeds of each group

[0078]

[0079] Indicators and detection methods

[0080] HE staining of small intestine and colon

[0081] After paraffin embedding, the small intestine and colon tissues were cut into 3 μm thick sections. The paraffin sections were immersed in an environmentally friendly dewaxing solution (G1128, Saiweier, China) twice for 20 minutes each time, and then immersed in anhydrous ethanol twice and 75% ethanol once for 5 minutes each time to dewax the sections until they were hydrated. Subsequent staining was performed using the hematoxylin stain, differentiation solution, bluing solution, and eosin stain in the hematoxylin-eosin (H&E) high-definition constant staining kit (G1076, Saiweier, China). After washing with tap water, the sections were stained in hematoxylin stain for 3-5 minutes, then in differentiation solution for differentiation, and bluing solution for bluing, with tap water rinses between each step. Then, the sections were dehydrated with 95% ethanol for 1 minute and then stained in eosin stain for 15 seconds. The stained sections were immersed in anhydrous ethanol three times, n-butanol twice, and xylene twice for 2 minutes each time to dehydrate and make them transparent. After transparency, the sections were mounted with neutral gum (10004160, Sinopharm Group, China). Images were acquired using a digital pathology slide scanner (KF-PRO-120-H1, Jiangfeng Biotechnology, China) to analyze the intestinal morphology of the small intestine and colon, including villus length, crypt depth, and the ratio of villus length to crypt depth.

[0082] AB-PAS staining of intestinal goblet cells

[0083] The paraffin sections of the small intestine and colon were immersed in an environmentally friendly dewaxing solution (G1128, Saiweier, China) twice for 20 minutes each, followed by two immersions in anhydrous ethanol and one immersion in 75% ethanol for 5 minutes each to dewax the sections. Subsequent staining was performed using AB-PAS stain solutions A, B, and C from the AB-PAS staining solution set (G1049, Saiweier, China). The sections were rinsed with tap water, then stained in AB-PAS stain solution C for 15 minutes. After rinsing with tap water until colorless, the sections were then immersed in AB-PAS stain solution B for 15 minutes. After rinsing with tap water, the sections were washed twice with distilled water. AB-PAS stain solution A was removed and allowed to cool to room temperature. After washing, the sections were stained with AB-PAS stain solution A for 30 minutes in the dark and rinsed with running water for 5 minutes. The stained sections were immersed in anhydrous ethanol three times and xylene twice for 5 minutes each time to dehydrate and make them transparent. After transparency, the sections were mounted with neutral gum (10004160, Sinopharm Group, China). Images were acquired using a digital pathology slide scanner (KF-PRO-120-H1, Jiangfeng Biotechnology, China) and the number of goblet cells in the small intestine and colon was analyzed.

[0084] The results of each indicator are summarized in Table 3.

[0085]

[0086] As can be seen from Table 3, in experimental groups 5-15 (MLCT:HMO = 0.1:1 to 100:1), at least three of the six indicators tested showed synergy (i.e., the indicators were better than the effects of MCLT or HMO alone), and at least a synergistic effect was shown in the ratio of small intestinal villus length to small intestinal crypt depth; and in experimental groups 5-12 and 14 (MLCT:HMO = 0.1:1 to 7:1), at least four of the six indicators tested showed synergy, and at least a synergistic effect was shown in small intestinal villus length, the ratio of small intestinal villus length to small intestinal crypt depth, and the number of small intestinal goblet cells, and the synergistic effect was stronger.

[0087] The above description is only an exemplary embodiment of the present invention. It should be noted that, for those skilled in the art, improvements can be made to the present invention without departing from the inventive concept of the present invention, and these improvements all fall within the scope of protection of the present invention.

Claims

1. A nutritional composition for promoting intestinal development, improving intestinal secretion and / or nutrient absorption for non-therapeutic purposes, characterized in that The nutritional composition comprises medium-chain fatty acid triglycerides and human milk oligosaccharides, wherein the weight ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides is 1:1 to 10:1, and the human milk oligosaccharides are 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.

2. The use according to claim 1, characterized in that The weight ratio of the medium and long chain fatty acid triglycerides to the human milk oligosaccharides is 1:1, 3:1, 4:1, 5:1, 6:1, 7:1, or 10:

1.

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

4. The use according to any one of claims 1 to 2, characterized in that The human milk oligosaccharide is one selected from the following: 2'-fucosyllactose, 3'-sialyllactose and lactose-N-neotetraose, and the weight ratio of the medium-chain fatty acid triglyceride to the human milk oligosaccharide is 3:1 to 5:

1.

5. The use according to any one of claims 1 to 2, characterized in that The human milk oligosaccharide is any two selected from 2'-fucosyllactose, 3'-sialyllactose and lactose-N-neotetraose, and the weight ratio of the medium-chain fatty acid triglyceride to the human milk oligosaccharide is 5:1 to 7:

1.

6. The method according to any one of claims 1 to 3, characterized in that The promoting of intestinal development, improving intestinal secretion and / or nutrient absorption includes improving any one, two, three, four, five or six of the following indicators: small intestinal villus length, small intestinal crypt depth, the ratio of small intestinal villus length to small intestinal crypt depth, colonic crypt depth, small intestinal goblet cell number and colonic goblet cell number.

7. The use according to any one of claims 1 to 3, characterized in that The promoting of intestinal development, improving intestinal secretion and / or nutrient absorption includes improving the ratio of small intestinal villus length to small intestinal crypt depth.

8. The method according to any one of claims 1 to 3, characterized in that The nutritional composition is used in the form of a food comprising the same.

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

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

11. The use according to claim 8, characterized in that The food is milk powder or fermented food.

12. The use according to claim 11, characterized in that The milk powder is infant formula milk powder.

13. The use according to claim 8, characterized in that The food further comprises one or more components selected from the group consisting of raw cow's milk, demineralized whey powder, concentrated whey protein, lactose, edible vegetable blending oil, oligofructose, oligogalactose, nucleotides, choline, vitamins, minerals, DHA and taurine.

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

Citation Information

Patent Citations

  • Nutritional composition, food and pharmaceutical product comprising same, and use thereof

    CN119699579A