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

Abstract

The present invention relates to a nutritional composition, food and pharmaceutical products comprising the nutritional composition, and uses thereof. The nutritional composition comprises medium and long chain fatty acid triglycerides and breast milk oligosaccharides, and the weight ratio of the medium and long chain fatty acid triglycerides to the breast milk oligosaccharides is 1: 1 to 9: 1. The nutritional composition disclosed by the invention can play a role in synergistically promoting skeletal development and particularly improving bone mineral density.

Description

Technical Field

[0001] The present invention relates to the field of food, in particular to a nutritional composition, food and medicine comprising the nutritional composition, and uses thereof. Background Art

[0002] Bone is a highly active connective tissue that can repair its own micro-damage through bone metabolism and bone remodeling, and maintain the homeostatic balance of bone structure, load and calcium content. At the same time, bone also regulates metabolic processes as an endocrine organ and is an important organ for maintaining human life. From the neonatal period, bone mass increases with age until the bone matures and reaches its peak in adolescence. Studies have found that paying attention to increasing bone mass during adolescence can achieve individual peak bone mass in adolescence. Therefore, the growth and development of bones during adolescence is crucial to bone maturation. Studies have pointed out that bone mineral density (BMD) during adolescence determines the peak bone mass and subsequent bone loss rate in adulthood. Reduced BMD can lead to insufficient bone mass, thereby causing a series of bone diseases such as rickets and osteomalacia, which seriously affects the bone health of adolescents. During this period, nutritional supplementation is an important factor affecting the peak bone mass. Intake of nutrients can increase the peak bone mass and promote bone formation. Therefore, seeking a natural functional nutrient to improve adolescent BMD and increase bone formation is of great significance for increasing bone mass, preventing adolescent fractures and bone diseases such as osteoporosis in middle-aged and elderly people, and maintaining bone health.

[0003] Bone consists of an extracellular protein matrix (osteoid) in which osteocytes are interspersed and a mineral component consisting of calcium salts and other minerals is located within the extracellular matrix. Bone undergoes remodeling by a resorption process in which bone is degraded by osteoclasts and then replaced (reformed) by osteoblasts. Remodeling occurs to regulate calcium homeostasis, repair bone damaged by daily stresses, and to shape bone as growth or mechanical stress patterns change. Osteoclasts degrade bone in specific areas and then undergo apoptosis. Osteoblasts rebuild new bone and mediate its remineralization. During remineralization, some osteoblasts are encased in calcified material and then become osteocytes.

[0004] Once peak bone mass has been reached during infancy through early adulthood, the resorption process is almost entirely accompanied by re-formation. However, as humans age, the remodeling system becomes less effectively regulated. With the onset of menopause in women, the two processes may become out of sync, with resorption dominating. In addition, with aging there is a loss of bone mineral density, disruption of bone microarchitecture, and other changes that contribute to an increased risk of fracture. The process of bone loss is often gradual, with no obvious symptoms present until the disease is well advanced. Therefore, it is important to maintain bone mass and density over time so that bones do not become more fragile with aging.

[0005] Therefore, there is a need to provide a nutritional composition that can promote bone development, especially can promote bone development in infants and children. Summary of the invention

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

[0007] In a first aspect, the present invention relates to a nutritional composition comprising:

[0008] Medium and long chain fatty acid triglycerides; and

[0009] Human milk oligosaccharides,

[0010] The weight ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides is 1:1 to 9:1.

[0011] The inventors unexpectedly discovered during their research that when medium- and long-chain fatty acid triglycerides and human milk oligosaccharides are used in combination at a certain weight ratio, the two can work synergistically to promote bone development, especially to increase bone density.

[0012] In a second aspect, the present invention relates to a food product comprising the nutritional composition according to the first aspect.

[0013] In a third aspect, the present invention relates to a medicament comprising the nutritional composition according to the first aspect.

[0014] In a fourth aspect, the present invention relates to use of the nutritional composition according to the first aspect or the food according to the second aspect for the non-therapeutic purpose of promoting bone development, in particular improving bone density.

[0015] In a fifth aspect, the present invention relates to use of the nutritional composition according to the first aspect in preparing a medicine for promoting bone development, in particular improving bone density. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the technical solution of the present invention, the following will briefly describe the drawings required for describing the embodiments. It should be understood that these drawings are only for the convenience of technicians to understand the present invention more easily, and are not intended to limit the scope of the present invention.

[0017] Figure 1 A typical graph showing the fluorescence intensity of a zebrafish skull after sample processing.

[0018] Figure 2 A bar graph showing the fluorescence intensity of zebrafish skulls after sample treatment. Compared with the normal control group: * indicates p < 0.05, ** indicates p < 0.01, *** indicates p < 0.001. DETAILED DESCRIPTION

[0019] 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.

[0020] 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.

[0021] In the present application, unless otherwise specified, the temperature is room temperature (25° C.), the atmosphere is air, and the pressure is atmospheric pressure.

[0022] 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.

[0023] 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.

[0024] In the present application, the term "non-therapeutic purpose" has the conventional meaning in the art, which includes, for example, nutritional and / or health purposes, which can be used, for example, for preparing foods such as ordinary foods, functional foods, special foods (including, for example, infant formula, foods for special medical purposes and health foods), etc.

[0025] The present invention relates to a nutritional composition, a food and a medicine comprising the nutritional composition, and uses thereof.

[0026] The present invention will be described in detail below.

[0027] Nutritional composition

[0028] In a first aspect, the present invention relates to a nutritional composition comprising 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 9: 1. As an example, the mass ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides may be 1: 1, 2: 1, 3: 1, 4: 1, 5: 1, 6: 1, 7: 1, 8: 1, 9: 1, or a range defined by any two of them.

[0029] The inventors unexpectedly discovered in their research that medium-chain fatty acid triglycerides and human milk oligosaccharides (particularly 2'-fucosyllactose, 3'-sialyllactose and / or lactose-N-neotetraose) can synergistically promote bone development when used in combination in a specific ratio. The bone development may include, for example, improving bone density.

[0030] In some embodiments, the mass ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides may be 2:1 to 9:1; within the range, the nutritional composition can more significantly synergistically promote bone development, such as improving bone density.

[0031] 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.

[0032] Human milk oligosaccharides (also known as human milk oligosaccharides or human milk oligosaccharides) are the third largest solid component in breast milk, second only to lactose and fat, and have important biological activity. According to the representative groups, human milk oligosaccharides can be divided into human milk oligosaccharides containing fucosyl groups (such as 2'-fucosyllactose), human milk oligosaccharides containing sialic acid groups (such as 3'-sialyllactose) and non-fucosyl and non-sialic acid human milk oligosaccharides (such as lactose-N-neotetraose).

[0033] In some embodiments, the human milk oligosaccharide is selected from one or more of the following: fucosyl-containing human milk oligosaccharides, sialic acid-containing human milk oligosaccharides, and non-fucosyl and non-sialic acid human milk oligosaccharides. For example, the human milk oligosaccharides may be: one or more fucosyl-containing human milk oligosaccharides; one or more sialic acid-containing human milk oligosaccharides; one or more non-fucosyl and non-sialic acid human milk oligosaccharides; one or more fucosyl-containing human milk oligosaccharides, and one or more sialic acid-containing human milk oligosaccharides; one or more fucosyl-containing human milk oligosaccharides, and one or more non-fucosyl and non-sialic acid human milk oligosaccharides; one or more sialic acid-containing human milk oligosaccharides, and one or more non-fucosyl and non-sialic acid human milk oligosaccharides; one or more fucosyl-containing human milk oligosaccharides, one or more sialic acid-containing human milk oligosaccharides, and one or more non-fucosyl and non-sialic acid human milk oligosaccharides.

[0034] 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.

[0035] 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).

[0036] 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.

[0037] 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.

[0038] 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.

[0039] For example, in some preferred embodiments, the human milk oligosaccharides are 2'-fucosyllactose, 3'-sialyllactose and lactose-N-neotetraose, and the weight ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides is 3:1 to 9:1; in some preferred embodiments, the human milk oligosaccharides are any two selected from 2'-fucosyllactose, 3'-sialyllactose and lactose-N-neotetraose, and the weight ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides is 5:1 to 7:1; in some preferred embodiments, the human milk oligosaccharides are 2'-fucosyllactose, and the weight ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides is 5:1 to 9:1; within the above preferred range, the synergistic effect of the nutritional composition in promoting bone development, especially improving bone density, is more significant.

[0040] 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.

[0041] For example, when the human milk oligosaccharide includes a fucosyl-containing human milk oligosaccharide (e.g., 2'-FL) and a sialic acid-containing human milk oligosaccharide (e.g., 3'-SL), the mass ratio of the fucosyl-containing human milk oligosaccharide / the sialic acid-containing human milk oligosaccharide, for example, the 2'-FL / 3'-SL mass ratio, can be 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, 12:1, 1 1:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, or a range defined by any two of them.

[0042] For example, when the human milk oligosaccharide includes fucosyl-containing human milk oligosaccharide (e.g., 2'-FL) and non-fucosyl non-sialic acid human milk oligosaccharide (e.g., LNnT), the mass ratio of fucosyl-containing human milk oligosaccharide / non-fucosyl non-sialic acid human milk oligosaccharide, for example, the mass ratio of 2'-FL / LNnT can be 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, 12:1, 14:1, 15:1, 16:1, 17 ... :1, 11:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, or a range defined by any two of them.

[0043] For example, when the human milk oligosaccharide includes sialic acid-containing human milk oligosaccharide (e.g., 3'-SL) and non-fucosyl non-sialic acid human milk oligosaccharide (e.g., LNnT), the mass ratio of sialic acid-containing human milk oligosaccharide / non-fucosyl non-sialic acid human milk oligosaccharide, for example, the mass ratio of 3'-SL / LNnT can be 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, 12:1, 14:1, 15:1, 16:1, 17 ... :1, 11:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, or a range defined by any two of them.

[0044] For example, when the human milk oligosaccharide includes fucosyl-containing human milk oligosaccharide (e.g., 2'-FL), sialic acid-containing human milk oligosaccharide (e.g., 3'-SL) and non-fucosyl non-sialic acid human milk oligosaccharide (e.g., LNnT), the mass ratio of fucosyl-containing human milk oligosaccharide / sialic acid-containing human milk oligosaccharide, e.g., 2'-FL / 3'-SL mass ratio, the mass ratio of fucosyl-containing human milk oligosaccharide / non-fucosyl non-sialic acid human milk oligosaccharide, e.g., 2'-FL / LNnT mass ratio, and the mass ratio of sialic acid-containing human milk oligosaccharide / non-fucosyl non-sialic acid human milk oligosaccharide, e.g., 3'-SL mass ratio. The SL / LNnT mass ratio may be independently 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, 12:1, 11:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, or a range defined by any two of them. For example, in one embodiment, 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 (e.g., LNnT), the amount of fucosyl-containing human milk oligosaccharides (e.g., 2'-FL) ranges from 8 to 28, preferably 16 to 24 parts by weight, and / or the amount of sialic acid-containing human milk oligosaccharides (e.g., 3'-SL) ranges from 1 to 8, preferably 1 to 4 parts by weight.

[0045] Medium-chain triglycerides (MLCT) are structural lipids that contain both medium-chain fatty acids and long-chain fatty acids in the triglyceride molecule. They have different physical and chemical properties, metabolic characteristics and nutritional value from long-chain triglycerides (LCT) or medium-chain triglycerides (MCT). Studies (see, for example, Yuan Tinglan, Medium-chain triglyceride composition and metabolic characteristics of breast milk fat [D], Jiangnan University, 2021) show that medium-chain triglycerides (MLCT) are not simply equivalent to a physical mixture of long-chain triglycerides (LCT) and medium-chain triglycerides (MCT) (of course, they are not equivalent to a simple mixture of long-chain fatty acids and medium-chain fatty acids), and the latter does not have the physical and chemical properties, metabolic characteristics and nutritional value of the former.

[0046] 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:

[0047] 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

[0048] The C 14 -C 30 The fatty acid residue is derived from one or more of the following: myristic acid, palmitic acid, heptadecanoic acid, oleic acid, linoleic acid, stearic acid, nonadecanoic acid, eicosapentaenoic acid, heneicosanoic acid, docosatetraenoic acid, docosahexaenoic acid, tricosanoic acid, tetracosenoic acid, eicosapentaenoic acid, hexacoshexaenoic acid, arachidonic acid, etc., preferably myristic acid, palmitic acid, oleic acid, linoleic acid, stearic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid.

[0049] 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 12The 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.

[0050] In some embodiments, the nutritional composition of the present invention may consist of medium- and long-chain fatty acid esters and human milk oligosaccharides.

[0051] food

[0052] In a second aspect, the present invention relates to a food product comprising the nutritional composition according to the first aspect.

[0053] In some embodiments, the food is an infant food such as an infant formula.

[0054] In some embodiments, based on the weight of the food, the content of medium and long-chain fatty acid triglycerides can be 0.1 to 30% by weight. As an example, based on the weight of the food, the content of medium and long-chain fatty acid triglycerides can be 0.1, 0.2, 0.5, 0.8, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30% by weight, or within the range defined by any two of them.

[0055] In some embodiments, based on the weight of the food, the content of human milk oligosaccharides may be 0.01 to 20% by weight. As an example, based on the weight of the food, the content of human milk oligosaccharides may be 0.01, 0.02, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20% by weight, or within the range defined by any two of them.

[0056] In some embodiments, the food may be, for example, functional food and special food (infant formula, food for special medical purposes, or health food).

[0057] 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.

[0058] In some embodiments, the milk powder is infant formula milk powder.

[0059] In addition, it is easy for those skilled in the art to understand that, in addition to the nutritional composition of the first aspect of the present invention, the food also includes one or more selected from the following: raw milk, desalted whey powder, concentrated whey protein, lactose, edible vegetable blending oil, oligofructose, oligogalactose, nucleotides, choline, vitamins, minerals, DHA and taurine.

[0060] For example, when the food is milk powder, in addition to the nutritional composition, the milk powder may also include proteins such as α-lactalbumin, milk fat globule membrane protein; carbohydrates such as lactose; lipids; minerals such as calcium, iron, phosphorus, etc.; vitamins; other additives such as whey powder, choline bitartrate, docosahexaenoic acid, arachidonic acid, walnut oil, etc.

[0061] The food can be produced by a preparation method commonly used in the art, which is well known to those skilled in the art and will not be described in detail here.

[0062] All the above descriptions about the nutritional composition of the first aspect of the present invention are applicable here and will not be repeated here.

[0063] drug

[0064] In a third aspect, the present invention relates to a medicament comprising the nutritional composition according to the first aspect.

[0065] The present invention has no special requirements for the dosage form of the drug, and the commonly used dosage forms of drugs in the art can be used. As an example, the drug of the present invention can be a solid preparation, such as powder, granules, tablets, capsules, drop pills, pills, etc.; a semi-solid preparation, such as an ointment, cream, eye ointment, gel, etc.; a liquid preparation, such as an oral liquid preparation, such as a syrup, mixture, suspension, emulsion, etc.

[0066] It is easy for those skilled in the art to understand that, depending on the dosage form and application scenario of the drug, the drug may also include various excipients permitted in pharmacology. In addition, the drug of the present invention may be prepared by methods commonly used in the art, which is well known to those skilled in the art and will not be described in detail here.

[0067] All the above descriptions about the nutritional composition of the first aspect of the present invention are applicable here and will not be repeated here.

[0068] use

[0069] In a fourth aspect, the present invention relates to use of the nutritional composition according to the first aspect or the food according to the second aspect for the non-therapeutic purpose of promoting bone development, in particular improving bone density.

[0070] The promotion of bone development may, for example, include improving (increasing bone density).

[0071] The promoting bone development may, for example, include, but is not limited to, promoting bone development in infants and / or children and / or adolescents, in particular improving bone density.

[0072] The non-therapeutic purpose may include, for example, nutritional and / or health purposes, such as for preparing food such as ordinary food, functional food, health food or health care products.

[0073] In some embodiments, when the nutritional composition or food is used for oral administration by humans, the dosage is such that the dosage of the medium-chain fatty acid triglyceride is 0.1 to 30 g / day, preferably 1.7 to 30 g / day. As an example, the dosage of the medium-chain fatty acid triglyceride may be 0.1, 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 g / day, or within the range defined by any two of them.

[0074] In some embodiments, when the nutritional composition or food is used for oral administration to humans, the dosage is such that the dosage of the human milk oligosaccharide is 0.05 to 25 g / day, preferably 0.1 to 25 g / day. As an example, the dosage of the human milk oligosaccharide may be 0.05, 0.1, 0.2, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 g / day, or within the range defined by any two of them, the dosage of the medium and long chain fatty acid triglycerides may be converted according to the ratio with human milk oligosaccharides.

[0075] In a fifth aspect, the present invention relates to use of the nutritional composition according to the first aspect in preparing a medicine for promoting bone development, in particular improving bone density.

[0076] All the above descriptions about the nutritional composition of the first aspect, the food of the second aspect and the medicine of the third aspect of the present invention are applicable here and will not be repeated here.

[0077] Example

[0078] 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.

[0079] Experimental Principle

[0080] The embodiment adopts the zebrafish experimental scheme. Compared with traditional animal experiments (piglets, mice and rats) and human experiments, the zebrafish experimental scheme has many advantages in the evaluation of the efficacy of promoting growth (bone) development. (1) Zebrafish is an important model that has been widely used in the establishment of disease models and drug discovery in recent years. The study of its skeleton has a physiological and genetic basis: the skeletal development of zebrafish is extremely similar to that of other vertebrates, and the skeleton is composed of two different tissues, cartilage and bone. (2) At the cellular level, the osteoblasts and osteoclasts of zebrafish have similar functions to those of mammals, and its osteoclasts have bone absorption during the early embryonic development of zebrafish. (3) At the anatomical level, the morphology and development process of the skeleton of zebrafish larvae and adults have been basically clarified, and its skeletal development process is highly consistent with that of mammals, that is, bone formation is through two mechanisms, intramembranous ossification and endochondral ossification. (4) In addition, zebrafish have a high genetic similarity with humans and are suitable for genetic manipulation technologies, such as gene knockout and knock-in. The application of these technologies allows researchers to more precisely study the effects of specific genes on brain development. (5) Zebrafish have strong reproductive capacity, rapid development, and a short sexual maturity period, which makes them very suitable for high-throughput experiments. High-throughput experiments can greatly speed up the research process and improve experimental efficiency. (6) The zebrafish model also has strong translational relevance, that is, its research results are more easily extended to humans. This makes zebrafish have important application value in the evaluation of the efficacy of promoting brain development.

[0081] raw materials

[0082] The sources and specifications of the raw materials used in the following examples are as follows:

[0083] Medium-chain fatty acid triglycerides: derived from medium-chain fatty acid edible oil (provided by Qingdao Haizhiyuan Life Science Technology Co., Ltd., batch number Y1501-23070101), purity 69.8%;

[0084] 2'-fucosyllactose: provided by DSM Vitamins Trading (Shanghai) Co. Ltd. SHANGHAI, purity 99.2%, batch number: 21107002;

[0085] 3'-Sialyl lactose: provided by DSM Vitamins Trading (Shanghai) Co. Ltd. SHANGHAI, purity 95.2%, batch number: DK21294101;

[0086] Lactose-N-neotetraose: provided by DSM Vitamins Trading (Shanghai) Co. Ltd. DTL DutyPaid. Shanghai, purity 100.5%, batch number: 20454001;

[0087] Swisse "Calcium & Vitamin D": Swisse "Calcium & Vitamin D", batch number 33152A, provided by Swisse, specification: each tablet contains 333.33 mg calcium;

[0088] Wild-type AB strain zebrafish: bred and provided by the fish breeding center of Hangzhou Huante Biotechnology Co., Ltd., with the experimental animal use license number: SYXK (Zhejiang) 2022-0004.

[0089] Positive Control

[0090] Swisse "Calcium & Vitamin D"

[0091] In the following examples, AB strain zebrafish were used for animal experiments.

[0092] 1. Test materials

[0093] 1.1. Sample preparation information

[0094] For MLCT, 2'-FL, LNnT, and 3'-SL, the solvent was standard dilution water.

[0095] Positive control: Swisse "Calcium & Vitamin D", milky white tablets, batch number 33152A, Swisse, solvent is standard dilution water.

[0096] 1.2. Experimental animals

[0097] Zebrafish were raised in fish farming water at 28°C (water quality: 200 mg of instant sea salt was added to every 1 L of reverse osmosis water, conductivity was 450-550 μS / cm; pH was 6.5-8.5; hardness was 50-100 mg / L CaCO3), bred and provided by our company's fish farming center, with the experimental animal use license number: SYXK (Zhejiang) 2022-0004, and the breeding management complies with the requirements of the international AAALAC certification (certification number: 001458), and the IACUC ethics review number: IACUC-2024-9219-01.

[0098] 1.3. Instruments, consumables and reagents

[0099] Dissecting microscope (SZX7, OLYMPUS, Japan); CCD camera (VertA1, Shanghai Tusen Vision Technology Co., Ltd., China); motorized focus continuous zoom fluorescence microscope (AZ100, Nikon, Japan); precision electronic balance (CP214, OHAUS, USA); 6-well plate (Zhejiang Bellambo Biotechnology Co., Ltd., China); fully automatic sample rapid grinding machine (JXFSTPRP-24L, Shanghai Jingxin Experimental Equipment Technology Department, China); ultrasonic cleaning machine (JP-010T, Shenzhen Jiemeng Cleaning Equipment Co., Ltd., China).

[0100] Methylcellulose (Batch No. B2006074, Shanghai Aladdin Biochemical Technology Co., Ltd., China); Alizarin Red (Batch No. C12071107, Shanghai MacLean Biochemical Technology Co., Ltd., China); Anhydrous Magnesium Chloride (Batch No. E2322159, Shanghai Aladdin Biochemical Technology Co., Ltd., China); Potassium Hydroxide (Batch No. E2361048, Shanghai Aladdin Biochemical Technology Co., Ltd., China); Glycerol (Batch No. H2220221, Shanghai MacLean Biochemical Technology Co., Ltd., China); Anhydrous Ethanol (Batch No. 20240426, Shanghai Aladdin Biochemical Technology Co., Ltd., China); Hydrogen Peroxide Solution (Batch No. G2023089, Shanghai Aladdin Biochemical Technology Co., Ltd., China); 4% Tissue Cell Fixative (Batch No. 240005013, Beijing Solebold Technology Co., Ltd., China); PBS Phosphate Buffer (Dry Powder) (Batch No. 18624437V, Biosharp, China).

[0101] 2. Detection Method

[0102] 2.1. Maximum tested concentration (MTC)

[0103] Wild-type AB zebrafish at 3 days post-fertilization (3 dpf) were randomly selected and placed in beakers, with 30 zebrafish treated in each beaker. The samples were dissolved in water (concentrations shown in Table 1), and the capacity of each beaker was 20 mL. A total of 4 samples (2'-FL, 3'-SL, LNnT, and medium-chain fatty acid triglycerides (MLCT)) were tested at 5 concentrations for each sample, and a normal control group was set up at the same time. There were 30 zebrafish in each group. After treatment at 28℃ for 3 days, the MTC of the samples on normal zebrafish was measured.

[0104] 2.2. Evaluation of the efficacy of single sample in promoting bone development

[0105] 3 dpf wild-type AB strain zebrafish were randomly selected and placed in beakers, with 30 zebrafish treated in each beaker. The samples were dissolved in water (concentrations are shown in Table 2), the positive control group was Swisse "Calcium & Vitamin D" 500 μg / mL, and a normal control group was set up at the same time, with a capacity of 20 mL per beaker. After treatment at 28℃ for 3 days, the fish were fixed and stained with alizarin red. Ten zebrafish were randomly selected from each experimental group and photographed under a fluorescence microscope. The data were analyzed and collected using NIS-ElementsD3.20 advanced image processing software. The fluorescence intensity of the zebrafish skull was analyzed, and the statistical analysis results of this indicator were used to evaluate the efficacy of the samples in promoting bone development. The statistical analysis results were expressed as mean ± SE. SPSS26.0 software was used for statistical analysis, and p < 0.05 indicated that the difference was statistically significant.

[0106] 2.3. Evaluation of the efficacy of the composition in promoting bone development

[0107] 3 dpf wild-type AB strain zebrafish were randomly selected in beakers, and 30 zebrafish were treated in each beaker. The samples were dissolved in water (concentrations are shown in Table 3), for a total of 25 groups. There were 21 combinations and 4 single samples. At the same time, a positive control group of Swisse "Calcium & Vitamin D" 500 μg / mL concentration was set, and a normal control group was set. The capacity of each beaker was 20 mL. After treatment at 28℃ for 3 days, they were fixed and stained with alizarin red. Ten zebrafish were randomly selected from each experimental group and photographed under a fluorescence microscope. NIS-ElementsD3.20 advanced image processing software was used to analyze and collect data, and the fluorescence intensity of the zebrafish skull was analyzed. The statistical analysis results of this indicator were used to evaluate the efficacy of the samples in promoting bone development. The statistical analysis results are expressed as mean ± SE. SPSS26.0 software was used for statistical analysis, and p < 0.05 indicated that the difference was statistically significant.

[0108] 3. Test results

[0109] 3.1.MTC

[0110] Under the experimental conditions, the maximum detection concentration (MTC) of 2FL and LNnT in promoting growth (bone) development is 2000 μg / mL; the MTC of MLCT in promoting growth (bone) development is 1500 μg / mL; the MTC of 3SL in promoting growth (bone) development is 1000 μg / mL. The zebrafish is in poor condition, so the maximum concentration of 3SL in subsequent experiments is 500 μg / mL. See Table 1 for details.

[0111] Table 1. Results of the experimental study on the concentration of samples to promote growth (bone) development (n = 30)

[0112]

[0113] 3.2. Evaluation of single sample efficacy in promoting bone development

[0114] Under the experimental conditions, 2'-FL, LNnT, MLCT and 3'-SL all have the effect of promoting bone development, which is specifically manifested by increasing the fluorescence intensity of the skull. See Table 2 for details. Figure 1 and Figure 2 .

[0115] Table 2. Results of single sample evaluation experiment on promoting bone development (n = 10)

[0116]

[0117] Note: Compared with the normal control group, *p < 0.05, **p < 0.01, ***p < 0.001

[0118] Figure 1 A typical graph of zebrafish skull fluorescence intensity after sample treatment is shown. As can be seen from the figure, in the area marked with dotted lines, compared with the normal control group, samples treated with 2'-FL, LNnT, MLCT and 3'-SL all showed an increase in skull fluorescence intensity, confirming the efficacy of promoting bone development.

[0119] Figure 2 A bar graph showing the fluorescence intensity of zebrafish skulls after sample processing is shown. This graph is based on the data in Table 2.

[0120] 3.3. Evaluation of the efficacy of the combination (MLCT + human milk oligosaccharides) in promoting bone development

[0121] The results of measuring the fluorescence intensity (bone density) of zebrafish skull using the experimental composition are shown in Table 3 below.

[0122]

[0123]

[0124]

[0125]

[0126]

[0127] 3.3.1. Experimental results analysis

[0128] (1) MLCT + a type of human milk oligosaccharide

[0129] By analyzing the data in Table 3, the effects of MLCT and one type of human milk oligosaccharide on the fluorescence intensity (bone density) of zebrafish skull are shown in the following Tables 4 to 6.

[0130] Table 4. Effects of MLCT + 2'-FL on the fluorescence intensity (bone density) of zebrafish skull

[0131]

[0132] According to the results in Table 4, it can be seen that compared with MLCT alone (Formula 1), 2'-FL alone (Formula 2), and a combination of MLCT and 2'-FL with a ratio of 0.1:1 (Formula 14), the combination of MLCT and 2'-FL with a ratio of MLCT to 2'-FL ranging from 2:1 to 9:1 (Formula 20, Formulation 21, and Formulation 7) achieved a significant increase in the fluorescence intensity of the skull. This indicates that the combination of MLCT and 2'-FL has a synergistic effect in promoting bone development within this weight ratio range.

[0133] Table 5. Effects of MLCT + LNnT on the fluorescence intensity (bone density) of zebrafish skull

[0134]

[0135] According to the results in Table 5, it can be seen that the combination of MLCT and LNnT (Formula 6, Formulation 23 and Formulation 22) with a ratio of MLCT to LNnT ranging from 2:1 to 9:1 achieved a significant increase in the fluorescence intensity of the skull compared to MLCT alone (Formula 1) and LNnT alone (Formula 16). This indicates that the combination of MLCT and LNnT has a synergistic effect in promoting bone development within this weight ratio range.

[0136] Table 6. Effects of MLCT + 3'-SL on the fluorescence intensity (bone density) of zebrafish skull

[0137]

[0138] According to the results in Table 6, it can be seen that the combination of MLCT and 3'-SL (Formula 25, Formulation 5 and Formulation 24) with a ratio of MLCT to 3'-SL ranging from 2:1 to 9:1 achieved a significant increase in the fluorescence intensity of the skull compared to MLCT alone (Formula 1) and 3'-SL alone (Formula 17). This indicates that the combination of MLCT and 3'-SL has a synergistic effect in promoting bone development within this weight ratio range.

[0139] (2) MLCT + two types of human milk oligosaccharides

[0140] By analyzing the data in Table 3, the effects of MLCT and two types of human milk oligosaccharides on the fluorescence intensity (bone density) of zebrafish skull are shown in the following Tables 7 to 9.

[0141] Table 7. Effects of MLCT + (2'-FL+LNnT) on the fluorescence intensity (bone density) of zebrafish skull

[0142]

[0143] According to the results of Table 7, it can be seen that compared with Formula 1 using MLCT alone, Formula 2 using 2'-FL alone, Formula 16 using LNnT alone, and Formula 3 using (2'-FL+LNnT) alone, Formula 8 using MLCT in combination with (2'-FL+LNnT) achieved a significant increase in the fluorescence intensity of the skull. This indicates that the combination of MLCT and (2'-FL+LNnT) in Formula 8 has a synergistic effect in promoting bone development.

[0144] Table 8. Effects of MLCT + (LNnT+3'-SL) on the fluorescence intensity (bone density) of zebrafish skull

[0145]

[0146] According to the results of Table 8, it can be seen that compared with Formula 1 using MLCT alone, Formula 16 using LNnT alone, and Formula 17 using 3'-SL alone, Formula 9 combining MLCT with (LNnT+3'-SL) achieved a significant increase in skull fluorescence intensity. This indicates that the combination of MLCT and (LNnT+3'-SL) in Formula 9 has a synergistic effect in promoting bone development.

[0147] Table 9. Effects of MLCT + (2'-FL+3'-SL) on the fluorescence intensity (bone density) of zebrafish skull

[0148]

[0149] According to the results of Table 9, it can be seen that compared with Formula 1 using MLCT alone, Formula 2 using 2'-FL alone, and Formula 17 using 3'-SL alone, Formula 10 using MLCT in combination with (2'-FL+3'-SL) achieved a significant increase in skull fluorescence intensity. This indicates that the combination of MLCT and (2'-FL+3'-SL) in Formula 10 has a synergistic effect in promoting bone development.

[0150] (3) MLCT + three types of human milk oligosaccharides

[0151] By analyzing the data in Table 3, the effects of MLCT and three types of human milk oligosaccharides on the fluorescence intensity (bone density) of zebrafish skull are shown in the following Table 10.

[0152] Table 10. Effects of MLCT + (2'-FL+LNnT+3'-SL) on the fluorescence intensity (bone density) of zebrafish skull

[0153]

[0154] According to the results in Table 10, it can be seen that compared with Formula 1 using MLCT alone, Formula 2 using 2'-FL alone, Formula 16 using LNnT alone, Formula 17 using 3'-SL alone, and Formula 13 and Formula 15 with ratios of MLCT to (2'-FL+LNnT+3'-SL) of 10:1 and 20:1, Formulas 11 and 12 with ratios of MLCT to (2'-FL+LNnT+3'-SL) of 1:1 and 3:1 achieved significant improvements in skull fluorescence intensity, indicating that the combination of MLCT and (2'-FL+LNnT+3'-SL) in Formulas 11-12 has a synergistic effect in promoting bone development.

[0155] 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, characterized in that It includes: Medium and long chain fatty acid triglycerides; and Human milk oligosaccharides, The weight ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides is 1:1 to 9:

1.

2. The nutritional composition according to claim 1, characterized in that The weight ratio of the medium-chain fatty acid triglycerides to the human milk oligosaccharides is 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1 or 9:

1.

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

1.

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

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

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

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

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

9. The nutritional composition 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.

10. The nutritional composition according to any one of claims 1 to 9, characterized in that The human milk oligosaccharide is a combination of 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 9:

1.

11. The nutritional composition according to any one of claims 1 to 9, 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.

12. The nutritional composition according to any one of claims 1 to 9, characterized in that The human milk oligosaccharide is 2'-fucosyllactose, and the weight ratio of the medium- and long-chain fatty acid triglycerides to the human milk oligosaccharide is 5:1 to 9:

1.

13. Food, characterized in that It comprises the nutritional composition according to any one of claims 1-12.

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

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

16. The food according to claim 13, characterized in that The food is milk powder or fermented food.

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

18. The food according to any one of claims 13 to 17, characterized in that The content of the medium-chain fatty acid triglycerides is 0.1% to 30%, and the content of the human milk oligosaccharides is 0.01% to 20%, based on the total dry weight of the food.

19. The food according to any one of claims 13 to 17, further comprising one or more selected from the group consisting of raw cow's milk, desalted whey powder, concentrated whey protein, lactose, edible vegetable blending oil, oligofructose, oligogalactose, nucleotides, choline, vitamins, minerals, DHA and taurine.

20. A medicament comprising the nutritional composition according to any one of claims 1 to 12.

21. Use of the nutritional composition according to any one of claims 1 to 12 or the food according to any one of claims 13 to 19 for the non-therapeutic purpose of promoting bone development.

22. The use according to claim 21, characterized in that The promoting bone development includes improving bone density.

23. The use according to any one of claims 21-22, characterized in that The promoting bone development includes promoting bone development in infants and / or children.

24. Use of the nutritional composition according to any one of claims 1 to 12 in the preparation of a medicine for promoting bone development.

25. The use according to claim 24, characterized in that The promoting bone development includes improving bone density.

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