Use of nutritional compositions
Through the combination of medium- and long-chain fatty acid triglycerides and breast milk oligosaccharides, the problem of intestinal development and nutritional absorption efficiency is solved, and the promotion of intestinal development and improvement of nutritional absorption is achieved.
Patent Information
- Application Number
- CN202510428665.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-08
- Publication Date
- 2025-05-16
- Estimated Expiration
- 2045-04-08
AI Technical Summary
The prior art is difficult to effectively promote intestinal development, improve intestinal secretion and nutrient absorption.
The combination of medium-long chain fatty acid triglycerides (MLCT) and breast milk oligosaccharides (HMO) is used in a specific proportion to promote intestinal development and improve nutrient absorption.
This combination can synergistically promote intestinal development, improve intestinal secretion and nutrient absorption in a specific proportion, and especially show significant synergistic effects in the ratio of small intestinal villus length to crypt depth.
Smart Images

Figure SMS_3 
Figure SMS_4 
Figure SMS_5
Abstract
Description
Technical Field
[0001] The present invention relates to the field of food, and in particular to the use of a nutritional composition for the non-therapeutic purpose of promoting intestinal development, improving intestinal secretion and / or nutrient absorption. Background Art
[0002] The intestine usually refers to the digestive tract from the pylorus of the stomach to the anus. It is the longest section of the digestive tract and also the most important section in terms of function. The intestine is about 7-8 meters long and is divided into two parts: the small intestine and the large intestine. As the main organ for digesting food and absorbing nutrients required for the development of the body, the intestine is divided into three parts: the small intestine, the cecum, and the colon. Among them, the small intestine is the main place for the body to absorb nutrients. The small intestinal villi it possesses significantly expand the internal surface area of the small intestine and play a key role in nutrient absorption. The longer the small intestinal villi, the larger the contact area with food, which is more conducive to the absorption of nutrients. The depth of the crypt reflects the rate of intestinal cell generation. Usually, a shallower crypt depth means a higher cell maturation rate and stronger secretory function. Intestinal villus length / crypt depth (V / C) is an important parameter for evaluating the absorption capacity of the small intestine. A higher V / C usually indicates a stronger absorption capacity and may be related to the rapid renewal of epithelial cells. Unlike the small intestine, the colon only has crypts but no villi. The colon crypts contain goblet cells and intestinal epithelial cells, which have secretory and absorptive functions.
[0003] The intestine is not only the main part for the digestion and absorption of nutrients, but also an important immune organ and endocrine organ. The intestine is the main digestive organ of the human body. Most of the nutrients needed by the human body are digested and absorbed by the intestine, providing beneficial material nutrition for human growth and development and maintaining human vitality. More than 80% of the toxins in the human body are excreted from the intestine. The relationship between the complex microbial ecosystem of the intestine and the body's immune system is also very close. The intestine is responsible for more than 70% of the human body's immune function, and nearly 70% of the immune cells are distributed in the intestinal mucosa, which plays an important role in resisting bacteria and viruses and maintaining the stability of the intestinal environment.
[0004] The development of the intestine 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 inventor unexpectedly discovered in the study that medium-chain fatty acid triglycerides and human milk oligosaccharides, when used in combination in a specific ratio, can synergistically promote the development of the human intestine, improve intestinal secretion and / or nutrient absorption. In particular, the effect of the combination of medium-chain fatty acid triglycerides and human milk oligosaccharides is better than the effect of the same total amount of medium-chain fatty acid triglycerides alone, and is also better than the effect of the same total amount of human milk oligosaccharides alone. DETAILED DESCRIPTION
[0009] In order to make the invention purpose, technical solution and beneficial technical effect of the present application clearer, the present application will be described in detail below. It should be noted that the various aspects, features, implementation methods and advantages described in the present application may be compatible and / or may be combined together.
[0010] Unless otherwise specified, the meanings of the technical terms or scientific terms in this specification are the same as those generally understood by those skilled in the art.
[0011] In the present 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) for 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 the present application, unless otherwise specified, the temperature is room temperature (25° C.), the atmosphere is air, and the pressure is atmospheric pressure.
[0014] In the present application, the term "medium-chain fatty acid" refers to fatty acids with 6-12 carbon atoms in the carbon chain, such as caproic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, dodecanoic acid, etc.; the term "long-chain fatty acid" refers to fatty acids with more than 14 carbon atoms, generally 14-30 carbon atoms, in the carbon chain, such as myristic acid, palmitic acid, oleic acid, linoleic acid, stearic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, etc. The terms "medium-chain fatty acid triglyceride" and "long-chain fatty acid triglyceride" refer to the esterification reaction products of "medium-chain fatty acid" and "long-chain fatty acid" with glycerol, respectively; the term "medium-long chain fatty acid triglyceride" refers to triglycerides containing both medium-chain fatty acid residues and long-chain fatty acid residues in the molecular structure.
[0015] In the present application, the term "human milk oligosaccharides", also known as "human milk oligosaccharides", is a type of complex oligosaccharides composed of monosaccharides and their derivatives, sialic acid and other structural units connected by glycosidic bonds.
[0016] The present invention relates to a use of a nutritional composition for non-therapeutic purposes of promoting intestinal development, improving intestinal secretion and / or nutrient absorption. In particular, the present invention relates to a use of a nutritional composition for non-therapeutic purposes of promoting intestinal development, improving intestinal secretion and / or nutrient absorption, the nutritional composition comprising medium-chain fatty acid triglycerides (MLCT) and human milk oligosaccharides (HMO), and the weight ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides is 0.1:1 to 100:1.
[0017] The inventor unexpectedly discovered in the study that medium-chain fatty acid triglycerides and human milk oligosaccharides (particularly 2'-fucosyllactose, 3'-sialyl lactose and / or lactose-N-neotetraose) can synergistically promote the development of the human intestine, improve intestinal secretion and / or nutrient absorption, such as promoting the development of the intestine of infants and young children, and improving intestinal secretion and / or nutrient absorption when used in combination in a specific ratio. The intestinal development, improvement of intestinal secretion and / or nutrient absorption can be reflected, for example, by indicators such as the length of small intestinal villi, the depth of small intestinal crypts, the ratio of small intestinal villi length to small intestinal crypt depth, the depth of colonic crypts, the number of small intestinal goblet cells, and the number of colonic goblet cells. Therefore, when medium-chain fatty acid triglycerides and human milk oligosaccharides are used in combination in a specific ratio, they can synergistically improve one, two, three, four, five or six of the indicators of small intestinal villus length, small intestinal crypt depth, ratio of small intestinal villus length to small intestinal crypt depth, colonic crypt depth, number of small intestinal goblet cells and number of colonic goblet cells, especially at least improve the ratio of small intestinal villus length to small intestinal crypt depth. Those skilled in the art will understand that the more indicators that are synergistic, the stronger the synergistic effect.
[0018] The length of the villi and the depth of the crypts in the small intestine reflect the intestinal function and development. The small intestine is the main place for the body to absorb nutrients. The villi in the small intestine significantly expand the internal surface area of the intestine. The villi are rich in capillaries and lymphatic capillaries, which play a key role in nutrient absorption. The longer the villi in the small intestine, the larger the contact area with food, which is more conducive to the absorption of nutrients.
[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 in the small intestinal crypts continuously divide to produce new intestinal epithelial cells. The proliferating cells push the neighboring cells to gradually migrate to the top of the villi and eventually squeeze into the intestinal cavity to undergo apoptosis, thus keeping the small intestinal villi in a state of continuous self-renewal. Intestinal villus length / crypt depth (V / C) is an important parameter for evaluating the absorption capacity of the small intestine. A higher V / C usually means a stronger absorption capacity and may be related to the rapid renewal of epithelial cells. A lower V / C indicates mucosal damage and decreased nutrient absorption capacity.
[0021] Unlike the small intestine, the colon has only crypts but no villi. The colon crypts contain goblet cells and intestinal epithelial cells, which have secretory and absorptive functions. The greater the colon crypt depth value, the stronger the secretory and absorptive functions.
[0022] Goblet cells are a special type of epithelial cell that are shaped like a goblet that is larger at the top and smaller at the bottom. Goblet cells mainly synthesize and secrete mucin, and participate in the formation of the mucus layer, i.e. the intestinal mucus barrier. The mucus layer provides lubrication for the surface of the intestinal mucosa, protects the tissue from invasion by pathogenic bacteria, and maintains symbiotic homeostasis and the stability of the intestinal environment. The more goblet cells there are, the more stable the intestinal environment is.
[0023] The present invention has no special requirements for the human milk oligosaccharides used, and the human milk oligosaccharides commonly used in the art can be used. The human milk oligosaccharides can be used in a pure form or in an impure form rich in human milk oligosaccharides.
[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 non-sialic acid human milk oligosaccharide is, for example, selected from one or more of the following: lactose-N-tetraose (LNT), lactose-N-neotetraose (LNnT), lactose-N-triose II and lactose-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 effects of each specific human milk oligosaccharide; for example, the mass ratio between any two specific human milk oligosaccharides can be between 20:1 and 1:20, such as 15:1 to 1:15.
[0031] For example, when the human milk oligosaccharide includes a fucosyl-containing human milk oligosaccharide (e.g., 2'-FL) and a sialic acid-containing human milk oligosaccharide (e.g., 3'-SL), the mass ratio of the fucosyl-containing human milk oligosaccharide / the sialic acid-containing human milk oligosaccharide, e.g., the 2'-FL / 3'-SL mass ratio, can be 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, 12:1, 11:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, or 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 2'-FL / LNnT mass ratio, can be 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, 14:1, 15:1, 16:1, 17 ... 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 defined by any two of them.
[0033] For example, when the human milk oligosaccharide includes sialic acid-containing human milk oligosaccharide (e.g., 3'-SL) and non-fucosyl non-sialic acid-containing human milk oligosaccharide (e.g., LNnT), the mass ratio of sialic acid-containing human milk oligosaccharide to non-fucosyl non-sialic acid-containing human milk oligosaccharide is, for example, 3'-SL The mass ratio of / LNnT can be 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, 12:1, 11:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, or a range defined by any two of them.
[0034] For example, when the human milk oligosaccharide includes fucosyl-containing human milk oligosaccharide (e.g., 2'-FL), sialic acid-containing human milk oligosaccharide (e.g., 3'-SL) and non-fucosyl non-sialic acid human milk oligosaccharide (e.g., LNnT), the mass ratio of fucosyl-containing human milk oligosaccharide / sialic acid-containing human milk oligosaccharide, e.g., 2'-FL / 3'-SL mass ratio, the mass ratio of fucosyl-containing human milk oligosaccharide / non-fucosyl non-sialic acid human milk oligosaccharide, e.g., 2'-FL / LNnT mass ratio and the mass ratio of sialic acid-containing human milk oligosaccharide / non-fucosyl non-sialic acid human milk oligosaccharide, e.g., 3'-SL mass ratio, are preferably selected from the group consisting of fucosyl-containing human milk oligosaccharide and non-fucosyl non-sialic acid human milk oligosaccharide. The SL / LNnT mass ratio may be independently 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, 12:1, 11:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, or a range defined by any two of them. 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 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 8 to 28, preferably 16 to 24, and / or the weight range of the sialic acid-containing human milk oligosaccharides 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, which have different physicochemical properties, metabolic characteristics and nutritional value from long-chain triglycerides (LCT) or medium-chain triglycerides (MCT). Studies (see, for example, Yuan Tinglan, Medium-chain triglyceride composition and metabolic characteristics of breast milk fat [D], Jiangnan University, 2021) show that medium-chain triglycerides (MLCT) are not simply equivalent to a physical mixture of long-chain triglycerides (LCT) and medium-chain triglycerides (MCT) (of course, they are not equivalent to a simple mixture of long-chain fatty acids and medium-chain fatty acids), and the latter does not have the physicochemical properties, metabolic characteristics and nutritional value of 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 triglycerides used, and the medium-chain triglycerides commonly used in the art can be used. The medium-chain triglycerides can be used in pure form or in an impure form rich in medium-chain triglycerides. In some embodiments, the medium-chain triglycerides of the present invention contain C6-C 12 (e.g. C6, C7, C8, C9, C 10 , C 11 , C 12 or the range defined by any two thereof) fatty acid residues and C 14 -C 30 (For example, C 14 , C 15 , C 16 , C 17 , C 18 , C 19 , C 20 , C 21 , C 22 , C 23 , C 24 , C 25 , C 26 , C 27 , C 28 , C 29 , C 30 or the range defined by any two thereof) fatty acid residues, wherein: the C6-C 12 The fatty acid residue is derived from one or more of the following: caproic acid, heptanoic acid, caprylic acid, nonanoic acid, capric acid, undecanoic acid, dodecanoic acid, etc., preferably caproic acid, caprylic acid, capric acid and lauric acid; and / or the C 14 -C 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, hexacoshexaenoic acid, arachidonic acid, etc., preferably myristic acid, palmitic acid, oleic acid, linoleic acid, stearic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid.
[0037] In some embodiments, the C6-C 12 The 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 The 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 of them.
[0038] In an embodiment, the weight ratio of the medium-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 the length of small intestinal villi, the depth of small intestinal crypts, the ratio of the length of small intestinal villi to the depth of small intestinal crypts, the depth of colonic crypts, the number of small intestinal goblet cells, and the number of colonic goblet cells have a synergistic effect; in particular, at least in terms of the ratio of the length of small intestinal villi to the depth of small intestinal crypts, a synergistic effect is presented. As an example, the weight ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides may 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, at least in terms of the length of small intestinal villi and the ratio of the length of small intestinal villi to the depth of small intestinal crypts, a synergistic effect is shown. 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 the length of small intestinal villi, the depth of small intestinal crypts, the ratio of the length of small intestinal villi to the depth of small intestinal crypts, the depth of colonic crypts, the number of small intestinal goblet cells, and the number of colonic goblet cells is more (at least four), and at least in terms of the length of small intestinal villi, the ratio of the length of small intestinal villi to the depth of small intestinal crypts, and the number of small intestinal goblet cells, a synergistic effect is shown. 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 thereof. In some embodiments, the food is an infant food such as an infant formula.
[0041] In some embodiments, the content of medium-chain fatty acid triglycerides can be 0.1 to 30% by weight based on the weight of the food. As an example, the content of medium-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, 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 in the range defined by any two of them.
[0042] In some embodiments, the content of human milk oligosaccharides may be 0.01 to 20% by weight based on the weight of the food. As an example, the content of human milk oligosaccharides may 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. %, 18, 18.5, 19, 19.5, 20 wt %, or 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 special food. As an example, the food can be selected from dairy products, candies, beverages, bread and biscuits, for example, the food can be selected from milk powder or fermented food. In some embodiments, the milk powder is infant formula milk powder.
[0045] In this application, "special food" refers to special types of food 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 easily understood by those skilled in the art that, in addition to the nutritional composition of the first aspect of the present invention, the food 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, 11.5, 12 .0, 12.5, 13.0, 13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, 20.5, 21.0, 21.5, 22.0, 22.5, 23.0, 23.5, 24.0, 24.5, 25.0, 25.5, 26.0, 26.5, 27.0, 27.5, 28.0, 28.5, 29.0, 29.5, 30.0 g / day or the range defined by any two of them), and in a further embodiment, the dosage of human milk oligosaccharides is calculated according to 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, 0065, 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, 5.0, 5.5, 6. , 21.0, 21.5, 22.0, 22.5, 23.0, 23.5, 24.0, 24.5, 25.0 g / day, or a range defined by any two of them).
[0051] Example
[0052] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.
[0053] 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'-sialyl lactose: 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 Paid. Shanghai, purity 100.5%, batch number: 20454001; mice: SPF grade male C57BL / 6, purchased from Beijing Weitonglihua Experimental Animal Technology Co., Ltd.
[0054] Dosage design
[0055] 1. Based on the content of HMO and MLCT in breast milk and the doses used in related studies, the design is based on 0.9g (HMO + MLCT) / kg.BW (infant) per day. Assuming that the weight of a 6-month-old infant is 8kg, the total dose of HMO + MLCT is 7.2g / d.
[0056] 2. Calculate according to the formula "AI values for children and adolescents are extrapolated from the corresponding values for adults" and the growth coefficient in the "Roadmap and Reference Values" document of the Recommended Dietary Nutrients for Chinese Residents 2023.
[0057] Formula for AI 7-12m =AI Adult (weight 7-12m / weight adult) 0.75 (1+growth coefficient).
[0058] *The growth coefficient for 0.5 to 4 years old is 0.3.
[0059] 3. According to the above formula, the daily HMO+MLCT intake of 7.2 g / d for a 6-month-old infant is equivalent to the daily HMO+MLCT intake of 25 g / 60 kg.BW for a 60 kg adult, which is equivalent to 418 mg / kg.BW (for adults).
[0060] 4. Based on the relevant documents published by the US FDA, the dose conversion of human and animal test substances is based on body surface area per square meter (BSA, m 2 ) of body weight (kg), that is, the conversion factor Km (kg / m 2 ) to convert, Km 小鼠 / Km 成人 =12.3, that is, the conversion factor from the human test dose (mg / kg.BW) to the mouse test dose is 12.3.
[0061] According to the above conversion factor, the adult test dose of 418mg / kg.BW is equivalent to the mouse test dose of 5141mg / kg, which is approximately equivalent to 100mg / 20g.BW (mouse)** based on a mouse weight of 20g. Assuming that the average daily feed intake of a 20g mouse is 4g, it is equivalent to adding 2.5g HMO+MLCT per 100g 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 feeds provided to each group (Table 1 and Table 2) for 3 weeks. The total content of MLCT and HMO in each group of feed was 100 mg / 20 g.BW (mouse), which was converted to 7.2 g / d for infants around 6 months old. The feeding conditions were: SPF animal room, temperature 23±2°C, 12h light / dark cycle, free drinking water and food intake. The weight of mice was recorded every week 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 method: The control group was fed with conventional feed AIN93G (Jiangsu Medison Biopharmaceutical Co., Ltd., China). The experimental group was mixed with HMO and MLCT in the mouse feed according to the proportion in Table 2, and the intervention method 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 treatment and sample collection after the experiment
[0072] After the intervention, the mice were fasted for 12 h, anesthetized, and killed. The following biological samples were collected: small intestine and colon tissues of mice were collected for morphological and other indicators.
[0073] Sample storage conditions: About 0.5 cm of small intestine and colon tissue were taken for paraffin embedding and stored at room temperature for subsequent sectioning and staining. The remaining small intestine and colon tissues were frozen in a -80℃ refrigerator.
[0074] Table 1: Content of MLCT and HMO (2'-FL, LNnT and 3'-SL) in each group of feeds
[0075]
[0076] Table 2: Weight ratio of MLCT and HMO (2'-FL, LNnT and 3'-SL) in each group of feeds
[0077]
[0078] Indicators and testing methods
[0079] HE staining of small intestine and colon
[0080] The paraffin-embedded small intestine and colon tissues were cut into 3 μm thick sections. The paraffin sections were immersed in environmentally friendly dewaxing solution (G1128, Saiweier, China) twice for 20 min each time, and then immersed in anhydrous ethanol twice and 75% ethanol once for 5 min each time to dewax the sections to water. The hematoxylin staining solution, differentiation solution, blueing solution and eosin staining solution in the hematoxylin-eosin (H&E) high-definition constant staining kit (G1076, Saiweier, China) were used for subsequent staining. After washing with tap water, the sections were stained in hematoxylin staining solution for 3-5 min, differentiated in differentiation solution, and blued in blueing solution, and rinsed with tap water between each step. Then, they were dehydrated with 95% ethanol for 1 min and then stained in eosin staining solution for 15 s. The stained sections were immersed in anhydrous ethanol for 3 times, n-butanol for 2 times, and xylene for 2 minutes each time to dehydrate and make the sections transparent. After the sections were transparent, they were sealed with neutral gum (10004160, Sinopharm Group, China). A digital pathology section scanner (KF-PRO-120-H1, Jiangfeng Bio, China) was used to collect images and analyze the intestinal morphology of the small intestine and colon, such as villus length, crypt depth, and the ratio of villus length to crypt depth.
[0081] AB-PAS staining of intestinal goblet cells
[0082] The above paraffin sections of small intestine and colon were immersed in environmentally friendly dewaxing solution (G1128, Saiweier, China) twice, each time for 20 min, and then immersed in anhydrous ethanol twice and 75% ethanol once, each time for 5 min, to dewax the sections to water. AB-PAS dye solution A, AB-PAS dye solution B and AB-PAS dye solution C in the AB-PAS dye solution set (G1049, Saiweier, China) were used for subsequent staining. After rinsing with tap water, the sections were immersed in AB-PAS dye solution C for 15 min, washed with tap water until colorless, and then placed in AB-PAS dye solution B for 15 min, washed with tap water, and washed twice with distilled water; AB-PAS dye solution A was taken out in advance and returned to room temperature. The washed sections were stained with AB-PAS dye solution A in the dark for 30 min and rinsed with running water for 5 min. The stained sections were immersed in anhydrous ethanol for 3 times and xylene for 2 times, each time for 5 min, to make the sections dehydrated and transparent. After transparency, the sections were sealed with neutral gum (10004160, Sinopharm Group, China). A digital pathology section scanner (KF-PRO-120-H1, Jiangfeng Bio, China) was used to collect images and analyze the number of goblet cells in the small intestine and colon.
[0083] The results of each indicator are summarized in Table 3.
[0084]
[0085] As can be seen from Table 3, in experimental groups 5-15 (MLCT:HMO=0.1:1 to 100:1), at least 3 of the six indicators tested were synergistic (i.e., better than the indicator effects when MCLT or HMO was used 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 4 of the six indicators tested were synergistic, and at least a synergistic effect was shown in 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.
[0086] The above description is only an exemplary embodiment of the present invention. It should be noted that, for those skilled in the art, without departing from the creative concept of the present invention, the present invention can also be improved, but these all belong to the protection scope of the present invention.
Claims
1. A nutritional composition for non-therapeutic purposes of promoting intestinal development, improving intestinal secretion and / or nutrient absorption, characterized in that The nutritional composition comprises medium-chain fatty acid triglycerides and human milk oligosaccharides, and a weight ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides is 0.1:1 to 100:
1.
2. The use according to claim 1, characterized in that The weight ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides is 0.1:1, 1:1, 3:1, 4:1, 5:1, 6:1, 7:1, 10:1 or 100:
1.
3. The use according to claim 1, characterized in that The weight ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides is 0.1:1 to 10:
1.
4. The use according to claim 1, characterized in that The weight ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides is 0.1:1 to 7:
1.
5. The use according to claim 1, characterized in that The human milk oligosaccharide is selected from one or more of the following: human milk oligosaccharides containing fucosyl, human milk oligosaccharides containing sialic acid, and human milk oligosaccharides containing neither fucosyl nor sialic acid.
6. The use according to claim 5, characterized in that The fucosyl-containing human milk oligosaccharide is selected from one or more of the following: 2'-fucosyllactose, 3-fucosyllactose, lactose-N-fucopentaose I, lactose-N-difucohexaose I, lactose-N-difucohexaose II, and lactose-bifucosyltetrose.
7. The use according to claim 5, characterized in that The sialic acid-containing human milk oligosaccharide is selected from one or more of the following: 3'-sialyllactose and 6'-sialyllactose.
8. The use according to claim 5, characterized in that The non-fucosyl and non-sialic acid human milk oligosaccharides are selected from one or more of the following: lactose-N-tetraose, lactose-N-neotetraose, lactose-N-triose II and lactose-N-disaccharide.
9. The use according to claim 1, characterized in that The human milk oligosaccharide is selected from one of the following: 2'-fucosyllactose; 3'-sialyl lactose; lactose-N-neotetraose; 2'-fucosyllactose and 3'-sialyl lactose; 2'-fucosyllactose and lactose-N-neotetraose; 3'-sialyl lactose and lactose-N-neotetraose; 2'-fucosyllactose and 3'-sialyl lactose and lactose-N-neotetraose.
10. 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.
11. The use according to any one of claims 1 to 10, characterized in that The human milk oligosaccharide is one selected from the following: 2'-fucosyllactose, 3'-sialyl lactose 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.
12. The use according to any one of claims 1 to 10, characterized in that The human milk oligosaccharide is any two selected from 2'-fucosyllactose, 3'-sialyl lactose 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.
13. The use according to any one of claims 1 to 10, 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.
14. The use according to any one of claims 1 to 10, 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.
15. The use according to any one of claims 1 to 10, characterized in that The nutritional composition is used in the form of a food comprising the same.
16. The use according to claim 15, characterized in that The food is infant food.
17. The use according to claim 15, characterized in that The food is selected from dairy products, candies, beverages, bread and biscuits.
18. The use according to claim 15, characterized in that The food is milk powder or fermented food.
19. The use according to claim 18, characterized in that The milk powder is infant formula milk powder.
20. The use according to claim 15, characterized in that The food further comprises one or more components selected from the following: raw cow milk, desalted whey powder, concentrated whey protein, lactose, edible vegetable blending oil, oligofructose, oligogalactose, nucleotides, choline, vitamins, minerals, DHA and taurine.
21. The use according to claim 15, characterized in that The food is a health food.
Citation Information
Patent Citations
Human Milk Oligosaccharides For Preventing Injury And / Or Promoting Healing Of The Gastrointestinal Tract
CN104023560A
Composition and method for promoting intestinal barrier healing
CN113194961A
Nutritional composition, food and pharmaceutical product comprising same, and use thereof
CN119699579A
Lacto-n-fucopentaose and b. infantis to protect from enteric pathogens
WO2024223918A1
Cited By
Composition for promoting intestinal development and application thereof
CN120226773A
Composition for promoting intestinal development and application thereof
CN120226773B
Nutritional composition, product comprising same and use thereof
CN121867419A
Nutritional composition for improving immunity and application thereof
CN122229185A