Nutritional composition and use thereof

Abstract

A nutritional composition, comprising medium- and long-chain triacylglycerols and a milk fat globule membrane in a mass ratio of 2:1-97:1. Further provided are a food product or drug comprising the nutritional composition, and a use of the nutritional composition for promoting bone development and increasing bone mineral density. The described two components exhibit a synergistic effect of promoting bone development, increasing bone mineral density, and preventing or treating osteogenesis imperfecta and osteoporosis.

Description

Nutritional compositions and their applications

[0001] This application claims priority to Chinese patent application filed on March 17, 2025, with application number 202510308178.0 and entitled "Nutritional Composition and Application of Nutritional Composition". Technical Field

[0002] This disclosure relates to the fields of food or pharmaceutical technology, and in particular to nutritional compositions for improving bone development, especially increasing bone density and / or preventing or treating osteogenesis imperfecta and / or osteoporosis, foods and pharmaceuticals containing said nutritional compositions, and the application of said nutritional compositions. Background Technology

[0003] Bone formation is influenced by a variety of factors, including genetics, nutrition, health, and environment. Bone formation begins with embryonic development, and bone mass increases with age during childhood and adolescence, reaching peak mass in youth. An increase in peak bone mass reduces the risk of osteoporosis later in life; a 10% increase in peak bone mass during the growth period can reduce the risk of osteoporotic fractures by 50%. Therefore, improving bone growth through breast milk and dietary nutrition in early life, especially infancy, childhood, and adolescence, can play a significant role in maintaining bone health later in life. Increasing peak bone mass during the growth period is crucial for maintaining bone health in adolescents (Liu et al., Food Science and Technology, 2023; 48(03):253-259).

[0004] Breast milk contains a variety of nutrients and immune factors, making it the best choice for infant nutrition. Breastfeeding is the diet recommended by the World Health Organization for infants in the first 6 months after birth. Studies have shown that breast milk has many beneficial effects on infant growth and development, disease prevention, etc. (HAROON S et al., BMC Public Health, 2013; 13(Suppl3):S20). Among them, medium and long-chain triacylglycerols (MLCT) in breast milk have received widespread attention as a star product among novel structural lipids. The fatty acid composition of MLCT is closer to that of breast milk, which is conducive to fat digestion and absorption, improves the absorption of lipid nutrients, inhibits the accumulation of body fat, and can provide energy quickly and stably (Cheng X et al., Annu Rev Food Sci Technol. 2024; 15(1):381-408). In addition, the main structural feature of MLCT is that medium-chain fatty acids and long-chain fatty acids are connected on the same glycerol backbone. Early studies have shown that MLCT has many health benefits, such as lowering blood lipids, inhibiting obesity, reducing diabetes and cardiovascular disease, and reducing the risk of cancer (Lai Yundong et al., Chinese Journal of Oil Crops, 2024; 46(04):719-727).

[0005] Chinese patent CN118556870B discloses a nutritional composition comprising medium- and long-chain fatty acid triglycerides and casein phosphopeptides in a mass ratio of 8:1 to 25:1. This nutritional composition may be used to improve brain or cognitive development.

[0006] Chinese patent CN118592494B discloses the application of an oil composition in improving the temperament of infants or children, wherein the mass ratio of the UPU structured lipid composition and the medium- and long-chain fatty acid edible oil in the oil composition is 1:1 to 1.5:1.

[0007] Furthermore, the milk fat globule membrane (MFGM) is a complex three-layered phospholipid protein membrane composed of polar lipids, cholesterol, and proteins that surrounds the surface of milk fat droplets. Its safety and tolerability have been confirmed in clinical trials. Early studies have shown that adding "whey protein powder rich in milk fat globule membrane" to infant formula can promote infant cognitive development and improve infant immunity (Chinese Institute of Food Science and Technology, Scientific Consensus on Milk Fat Globule Membrane and its Ingredients, Chinese Journal of Food Science, 2022; 22(04):471-476).

[0008] Chinese patent CN114128757B discloses the application of milk fat globule membrane in reducing the off-odor of dairy products, wherein the dairy products are solid dairy products or liquid dairy products; the solid dairy products are selected from infant formula milk powder, children's formula milk powder or formula milk powder for middle-aged and elderly people.

[0009] However, there are no reports, either domestically or internationally, on the effects of long-chain fatty acid triglycerides and milk fat globule membranes on bone development.

[0010] There is still a need in this field for methods that can promote bone development and increase bone density. Summary of the Invention

[0011] The present invention was made in view of the above-mentioned problems in the art.

[0012] The first aspect of the present invention provides a nutritional composition comprising medium- and long-chain fatty acid triglycerides and milk fat globule membranes, wherein the mass ratio of the medium- and long-chain fatty acid triglycerides to the milk fat globule membranes is 2:1 to 97:1.

[0013] A second aspect of the present invention provides a food comprising the nutritional composition described in the first aspect of the present invention.

[0014] A third aspect of the present invention provides a medicine comprising the nutritional composition described in the first aspect of the present invention.

[0015] The fourth aspect of the present invention provides the use of the nutritional composition described in the first aspect of the present invention in the preparation of food for promoting bone development.

[0016] The fifth aspect of the present invention provides the use of the nutritional composition described in the first aspect of the present invention in the preparation of food for increasing bone density.

[0017] The sixth aspect of the present invention provides the use of the nutritional composition described in the first aspect of the present invention in the preparation of a medicament for the prevention or treatment of osteoporosis and / or osteogenesis imperfecta.

[0018] The seventh aspect of the present invention provides the use of the nutritional composition described in the first aspect of the present invention for non-therapeutic purposes of promoting bone development.

[0019] The eighth aspect of the present invention provides the use of the nutritional composition described in the first aspect of the present invention for non-therapeutic purposes of increasing bone density.

[0020] This invention has discovered that when medium- and long-chain fatty acid triglycerides and milk fat globule membranes are used in combination at a defined mass ratio, there is a synergistic effect between the two, which can synergistically improve bone development, particularly increase bone density and / or prevent or treat osteogenesis imperfecta and / or osteoporosis. Attached Figure Description

[0021] Figure 1 shows typical fluorescence intensity diagrams of zebrafish osteogenic samples after treatment with the normal control group, positive control group, and formulations 1-6.

[0022] Figure 2 shows typical fluorescence intensity diagrams of zebrafish osteogenic samples after treatment for Comparative Examples 1-6 and Formula 7. Detailed Implementation

[0023] The following definitions are provided to enable those skilled in the art to understand the invention. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Preferred materials and methods are described herein, but any methods and materials similar to or equivalent to those described herein may be used in the practice of testing the invention. It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

[0024] Terminology Definition

[0025] Unless otherwise indicated or defined, all terms used have their ordinary meaning in the art as would be understood by those skilled in the art. Furthermore, unless otherwise stated, all methods, steps, techniques, and operations not specifically detailed herein can and have been performed in a manner known per se as would be understood by those skilled in the art.

[0026] As used herein, the term "medium- and long-chain triglycerides" or "MLCT" refers to a special type of triglyceride whose triglyceride backbone contains both medium- and long-chain fatty acids. MLCT is produced from edible vegetable oils and medium-chain triglycerides (derived from edible coconut oil and palm kernel oil) through transesterification with lipase, followed by distillation, decolorization, and deodorization. Medium- and long-chain triglycerides can be derived from medium- and long-chain fatty acid edible oils.

[0027] As used herein, the term "medium-chain fatty acid" refers to fatty acids with 6-12 carbon atoms in their carbon chain, such as hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, and dodecanoic acid; the term "long-chain fatty acid" refers to fatty acids with 14 or more carbon atoms in their carbon chain, generally 14-30 carbon atoms, such as myristic acid, palmitic acid, oleic acid, linoleic acid, stearic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid. The terms "medium-chain fatty acid triglycerides" and "long-chain fatty acid triglycerides" refer to the esterification products of medium-chain fatty acids and long-chain fatty acids with glycerol, respectively; the term "medium- and long-chain fatty acid triglycerides" refers to triglycerides that contain both medium-chain and long-chain fatty acid residues in their molecular structure. This invention does not have any particular requirements for the medium- and long-chain fatty acid triglycerides used; commonly used medium- and long-chain fatty acid triglycerides in the art can be used. Medium- and long-chain triglycerides can be used in pure form or in a non-pure form rich in medium- and long-chain triglycerides. For example, the medium- and long-chain triglycerides used in this invention may contain C6-C6. 12 fatty acid residues and C 14 -C 30 Fatty acid residues. C6-C 12 Fatty acid residues can originate from one or more of the following: hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, dodecanoic acid, etc. C 14 -C 30 The fatty acid residues may be derived from one or more of the following: myristic acid, palmitic acid, heptadecanic acid, oleic acid, linoleic acid, stearic acid, nonadecanic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapatraenoic acid, docosahexaenoic acid, tricarboxylic acid, docosapentaenoic acid, docosahexaenoic acid, arachidonic acid, etc. In some embodiments, the C6-C... 12 The fatty acid residues are derived from one or more of the following: hexanoic acid, octanoic acid, decanoic acid, and lauric acid; and / or the C... 14 -C 30 The fatty acid residues are derived from one or more of the following: myristic acid, palmitic acid, oleic acid, linoleic acid, stearic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid. In some embodiments, C6-C 12 Fatty acid residues on the C 14 -C 30 The weight ratio of fatty acid residues is from 0.124 to 2.000. In some embodiments, C6-C... 12 Fatty acid residues on the C 14 -C 30The weight ratio of fatty acid residues can 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 any two of these ranges. In some embodiments, the "medium- and long-chain fatty acid triglycerides" can be prepared according to the method of patent CN115369132A.

[0028] As used herein, the term "milk fat globule membrane" or "MFGM" (English: Milk Fat Globule Membrane) is a complex biomembrane structure found in breast milk. The milk fat globule membrane is a complex three-layered phospholipid membrane composed of polar lipids, cholesterol, and proteins, enveloping the surface of milk fat droplets. Sphingomyelin and gangliosides are characteristic indicators of the milk fat globule membrane's composition, and its safety and tolerability have been confirmed in clinical trials. The source of the milk fat globule membrane of this invention is not particularly limited in principle and can generally be obtained by extraction from animal milk or its products. In some preferred embodiments, such animal milk or its products can be cow's milk, sheep's milk, camel's milk, horse's milk, or dairy products based on them (e.g., cheese). More preferably, it can be extracted from cow's milk, including bovine colostrum or regular bovine milk. This invention does not particularly limit the preparation process of MFGM; for example, it can be carried out using an acidification precipitation-centrifugation-isoelectric point enrichment-drying method, or it can be separated using existing membrane filtration methods. Additionally, MFGM can also be obtained from commercially available products, including milk fat globule membrane whey protein powder and milk fat globule membrane milk protein powder. Milk fat globule membrane whey protein powder refers to a powdered product containing milk fat globule membranes, made from raw milk or whey through processes such as separation, concentration, and drying. Milk fat globule membrane milk protein powder refers to a powdered product containing milk fat globule membranes, made from raw milk or cream through processes such as separation, concentration, and drying. The commercial sources of MFGM for this invention include... MFGM-10 PL-20 SM2, lipid-rich MFGM fraction, or buttermilk powder concentrate BPC50, BPC60, G600, PC700, Or WPC7500MEGM ENRICHED WPC, etc.

[0029] As used in this article, "osteoblasts" are the main functional cells in bone formation, playing a crucial role in bone growth and development, bone remodeling, and fracture repair. When osteoblasts are activated, they undergo processes such as cell proliferation, extracellular matrix maturation, and mineralization, thereby forming new bone. Osteoblasts play a key role in skeletal development. Abnormal osteoblast function is closely related to skeletal dysplasia. In this article, skeletal dysplasia can refer to any type of skeletal dysplasia, including but not limited to skeletal dysplasia caused by osteoblast dysfunction, such as osteogenesis imperfecta and osteoporosis.

[0030] As used in this article, "bone mineral density" refers to the amount of bone contained per unit volume (volume density) or per unit area (areal density). Osteoblasts are the main functional cells in bone formation, and they play a crucial role in maintaining and increasing bone mineral density.

[0031] As used in this article, "osteoporosis" is a systemic bone disease characterized by decreased bone mass and destruction of bone microstructure, leading to increased bone fragility and a greater susceptibility to fractures. Decreased osteoblast activity results in reduced bone formation, while relatively increased osteoclast activity leads to increased bone resorption, ultimately causing decreased bone mass and osteoporosis.

[0032] As used in this article, "fracture healing disorder" refers to abnormal conditions that occur during the normal healing process of a fracture, leading to prolonged healing time or complete failure to heal. Osteoblasts are responsible for the synthesis and mineralization of the bone matrix during fracture healing, and impaired function of osteoblasts will delay fracture healing.

[0033] Nutritional composition

[0034] The first aspect of the present invention provides a nutritional composition comprising medium- and long-chain triglycerides (MLCT) and milk fat globule membrane (MFGM), wherein the mass ratio of MLCT to MFGM is 2:1 to 97:1.

[0035] This invention has discovered that when medium- and long-chain fatty acid triglycerides and milk fat globule membranes are used in combination at a defined mass ratio, there is a synergistic effect between the two, which can synergistically improve bone development, particularly increase bone density and / or prevent or treat osteogenesis imperfecta and / or osteoporosis.

[0036] In some embodiments, the nutritional composition comprises medium- and long-chain triglycerides (MLCT) and milk fat globule membranes (MFGM).

[0037] In embodiments, the mass ratio of the medium- and long-chain fatty acid triglycerides to the milk fat globule membrane in the nutritional composition is from 2:1 to 97:1, for example, within the range defined by 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 15:1, 20:1, 25:1, 30:1, 35:1, 40:1, 45:1, 50:1, 55:1, 60:1, 65:1, 70:1, 75:1, 80:1, 85:1, 90:1, 95:1, 97:1, or any two of these.

[0038] In some embodiments, the mass ratio of the medium- and long-chain fatty acid triglycerides to the milk fat globule membrane in the nutritional composition is from 2.67:1 to -96.03:1, for example, 10.67:1, 2.67:1, 32.01:1, 8.01:1, 2.00:1, or 96.03:1.

[0039] food

[0040] The second aspect of the present invention relates to food comprising the nutritional composition described in the first aspect of the present invention.

[0041] All descriptions above relating to the first aspect of the present invention are applicable here and will not be repeated here.

[0042] In some embodiments, the food may be, for example, a functional food, a health food, or a health supplement.

[0043] In some embodiments, the food product is a general food or a specialty food. For example, the food product may be selected from dairy products, confectionery, beverages, bread, and biscuits; for instance, the food product may be selected from milk powder or fermented foods. In some embodiments, the milk powder is infant formula.

[0044] In some embodiments, the food is infant food, such as infant formula.

[0045] In some embodiments, the food product may be a powder, tablet, or liquid.

[0046] In some embodiments, the content of medium- and long-chain fatty acid triglycerides may be from 0.1% to 30.0% based on the dry weight of the food product, preferably from 0.4% to 30.0%. As an example, the content of medium- and long-chain fatty acid triglycerides may be within the range defined by any two of the following dry weight percentages: 0.1%, 0.2%, 0.5%, 0.8%, 1.0%, 2.0%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 11.0%, 12.0%, 13.0%, 14.0%, 15.0%, 16.0%, 17.0%, 18.0%, 19.0%, 20.0%, 21.0%, 22.0%, 23.0%, 24.0%, 25.0%, 26.0%, 27.0%, 28.0%, 29.0%, 30.0%. The content of milk fat globule membrane can be calculated based on the ratio of the two.

[0047] In some embodiments, the content of milk fat globule membranes may be from 0.001% to 15.0% based on the dry weight of the food product. As an example, the content of milk fat globule membranes may be within the range defined as 0.001, 0.005, 0.01, 0.05, 0.1, 0.2, 0.5, 0.8, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10.0, 11.0, 12.0, 13.0, 14.0, 15.0% dry weight, or any two of these ranges.

[0048] Furthermore, those skilled in the art will readily understand that, in addition to the nutritional composition of the first aspect of the present invention, the food also includes one or more of the following: raw milk, demineralized whey powder, whey protein concentrate, lactose, blended vegetable oil, fructooligosaccharides, galactooligosaccharides, nucleotides, choline, vitamins, minerals, DHA, and taurine.

[0049] For example, when the food is milk powder, in addition to the nutritional composition described in the first aspect of the present invention, the milk powder may also include proteins such as α-lactalbumin and milk fat globule membrane protein; carbohydrates such as lactose; lipids; minerals such as calcium, iron, and phosphorus; vitamins; and other additives such as whey powder, choline tartrate, docosahexaenoic acid, arachidonic acid, and walnut oil.

[0050] The food product can be produced using preparation methods commonly used in the field, which will not be elaborated here.

[0051] drug

[0052] A third aspect of the present invention relates to a medicine comprising the nutritional composition described in the first aspect of the present invention.

[0053] All descriptions above relating to the first aspect of the present invention are applicable here and will not be repeated here.

[0054] The dosage form of the drug is not limited and may be, for example, one or more of tablets, granules, powders, capsules, and liquids.

[0055] When the drug contains the nutritional composition, the drug can be used to prevent or treat osteogenesis imperfecta and / or osteoporosis.

[0056] application

[0057] The fourth aspect of the present invention relates to the use of the nutritional composition of the first aspect of the present invention in the preparation of food (e.g., health food) that promotes bone development.

[0058] Promoting bone development may include, for example, promoting bone formation, growth, remodeling, and bone mass accumulation.

[0059] The fifth aspect of the present invention relates to the use of the nutritional composition of the first aspect of the present invention in the preparation of foods (e.g., health foods) that increase bone density.

[0060] The sixth aspect of the present invention relates to the use of the nutritional composition of the first aspect of the present invention in the preparation of a medicament for the prevention or treatment of osteogenesis imperfecta and / or osteoporosis.

[0061] The seventh aspect of the present invention relates to the use of the nutritional composition of the first aspect of the present invention for non-therapeutic purposes of promoting bone development.

[0062] The eighth aspect of the present invention relates to the use of the nutritional composition of the first aspect of the present invention for non-therapeutic purposes of increasing bone density.

[0063] All the above descriptions of the first aspect of the invention apply to the nutritional composition described herein, and will not be repeated here.

[0064] The above description of the second aspect of the present invention applies to the food product, and will not be repeated here.

[0065] In some embodiments, the dosage form of the drug includes, but is not limited to, tablets, granules, powders, capsules, and liquids.

[0066] All descriptions of the first aspect of the present invention above are applicable here and will not be repeated here. In some embodiments, when the composition, food, or pharmaceutical is taken orally in the human body, the dosage of medium- and long-chain fatty acid triglycerides is 0.1 to 30 g / day, preferably 0.4 to 30 g / day, for example, 0.1 g / day, 0.2 g / day, 0.3 g / day, 0.4 g / day, 0.5 g / day, 0.6 g / day, 0.7 g / day, 0.8 g / day, 0.9 g / day, 1 g / day, 2 g / day, 3 g / day, 4 g / day, 5 g / day, 6 g / day, etc. The dosage of the milk fat globule membrane can be calculated based on its ratio to medium- and long-chain triglycerides. The dosage ranges are 7g / day, 8g / day, 9g / day, 10g / day, 11g / day, 12g / day, 13g / day, 14g / day, 15g / day, 16g / day, 17g / day, 18g / day, 19g / day, 20g / day, 21g / day, 22g / day, 23g / day, 24g / day, 25g / day, 26g / day, 27g / day, 28g / day, 29g / day, or 30g / day, or any two of these ranges.

[0067] In some embodiments, when the composition, food, or pharmaceutical is taken orally in humans, the dosage of milk fat globule membrane is 0.001 g / day to 15 g / day, for example, 0.001 g / day, 0.002 g / day, 0.003 g / day, 0.004 g / day, 0.005 g / day, 0.006 g / day, 0.007 g / day, 0.008 g / day, 0.009 g / day, 0.01 g / day, 0.02 g / day, 0.03 g / day, 0.04 g / day, 0.05 g / day, 0.0 The recommended daily dose is 6 g / day, 0.07 g / day, 0.08 g / day, 0.09 g / day, 0.1 g / day, 0.2 g / day, 0.3 g / day, 0.4 g / day, 0.5 g / day, 0.6 g / day, 0.7 g / day, 0.8 g / day, 0.9 g / day, 1 g / day, 2 g / day, 3 g / day, 4 g / day, 5 g / day, 6 g / day, 7 g / day, 8 g / day, 9 g / day, 10 g / day, 11 g / day, 12 g / day, 13 g / day, 14 g / day, 15 g / day, or any range between these values. Medium- and long-chain fatty acid triglycerides and milk fat globule membranes can be formulated into a composition or preparation for administration to the subject. Alternatively, medium- and long-chain fatty acid triglycerides and milk fat globule membranes can be taken separately, for example, either concurrently or separately, without being formulated into the same composition. When taken separately, medium- and long-chain triglycerides and milk fat globule membranes can be administered at intervals throughout the day. Long-chain triglycerides and milk fat globule membranes can also be administered several times a day. The interval between the two components or the number of separate administrations is readily determined by those skilled in the art.

[0068] Example

[0069] The invention will be more readily understood by referring to the following examples, which are only used to illustrate certain aspects and embodiments of the invention and are not intended to limit the invention.

[0070] Unless otherwise stated, all reagents used in this embodiment are commercially available or conventional materials. In all the following embodiments, the medium- and long-chain triglycerides (MLCT) were derived from medium- and long-chain fatty acid edible oil (purity 69±10%), produced by Qingdao Haizhiyuan Life Science Technology Co., Ltd., batch number Y1505-22120101; milk fat globule membrane (MFGM) was purchased from Arla, product name [product name missing]. MFGM-10, batch number P510216, contains 8±2% phospholipids, 71.5±5% protein by weight, and 25±10g sphingomyelin / 100g phospholipids.

[0071] Vancomycin is derived from Shanghai Maclean Biochemical Technology Co., Ltd., and is a white powder with batch number C12976208.

[0072] AB strain zebrafish: provided by the fish breeding center of Hangzhou Huante Biotechnology Co., Ltd.

[0073] Example 1: Determination of Maximum Tolerated Concentration (MTC) for a Single Sample

[0074] Wild-type AB strain zebrafish, 3 days post-fertilization (3 dpf), were randomly selected and placed in beakers, with 30 zebrafish treated in each beaker (experimental group). The samples were administered in water (concentrations shown in Table 1), and a normal control group was also included. Each beaker had a volume of 20 mL. The medium was changed every 5 dpf. After 3 days of treatment at 28℃, the MTC of the samples relative to normal zebrafish was measured.

[0075] Table 1. Results of the concentration exploration experiment for the efficacy of single samples in promoting bone development (n=30)

[0076] As shown in Table 1, the MTC of medium- and long-chain fatty acid triglycerides was 750 μg / mL; the MTC of milk fat globule membrane (MFGM) was 125 μg / mL. Subsequent dosing experiments were designed based on the above MTC values.

[0077] Example 2: Evaluation Experiment of the Sample's Efficacy in Promoting Bone Development

[0078] Osteoblast fluorescence intensity is closely related to bone development and disease. Studies have shown that changes in osteoblast fluorescence intensity can reflect their biological function and state. For example, osteoblast-like cells undergo changes in the cytoskeletal microfilament structure after stress, resulting in a decrease in fluorescence intensity. However, the fluorescence intensity gradually recovers and increases after the stimulus is removed, indicating that changes in the cytoskeletal structure are reversible and remodelable. Furthermore, changes in fluorescence intensity are also related to osteoblast differentiation and activity; for instance, the fluorescence intensity of osteoblast cytoskeletal proteins increases after treatment with a static magnetic field. These changes may be related to bone development, repair, and disease states (such as osteoporosis). Osteoblast fluorescence intensity is an important indicator for studying bone health and disease.

[0079] 3-day-first-flush (3dpf) transgenic bony green fluorescent zebrafish were randomly selected and placed in beakers, with 30 zebrafish treated in each beaker (experimental group). Samples were administered via water-soluble administration (concentrations shown in Table 2), with a positive control of Swisse "Calcium & Vitamin D" at a concentration of 500 μg / mL. A normal control group was also included. Each beaker contained 20 mL. The medium was changed once every 5dpf. After 3 days of treatment at 28℃, 10 zebrafish from each experimental group were randomly selected and photographed under a fluorescence microscope. Data were analyzed and collected using NIS-ElementsD 3.20 advanced image processing software. The osteogenic fluorescence intensity of the zebrafish was analyzed, and the statistical analysis results of this index were used to evaluate the efficacy of the samples in promoting bone development. Statistical results are expressed as mean ± SE. Statistical analysis was performed using SPSS 26.0 software; p < 0.05 indicated statistical significance.

[0080] Following the above method, zebrafish were administered medium- and long-chain fatty acid triglycerides, MFGM alone, and in different ratios and dosages of their combinations. The dosages are shown in Table 2. The results are shown in Table 2 and Figures 1-2.

[0081] Table 2. Evaluation results of the samples' efficacy in improving bone development (osteogenic fluorescence intensity). Note: Compared with the normal control group, *P<0.05, ***P<0.001.

[0082] As shown in Table 2 and Figures 1-2, compared with the normal control group, the groups treated with MLCT (83.3 μg / mL, 250 μg / mL, 750 μg / mL) and MFGM (125 μg / mL) showed significantly enhanced osteogenic fluorescence intensity (P < 0.05), indicating that each sample has the effect of improving bone development. Furthermore, compared with the normal control, the combination of MLCT and MFGM (formulas 1-7) significantly improved bone development, specifically manifested as a significant increase in osteogenic fluorescence intensity (P < 0.05). Additionally, as shown in Table 2, formulas 1-2 and 4-7 with MLCT to MFGM ratios of 2:1-96.03:1 exhibited higher osteogenic fluorescence than formula 3 with an MLCT to MFGM ratio of 0.67, indicating a better effect in improving bone development, particularly increasing bone mineral density and / or improving osteoporosis. Furthermore, Table 2 shows that, in terms of composition, Formula 1 is equivalent to a combination of Comparative Example 1 and Comparative Example 4. Formula 1, Comparative Example 1, and Comparative Example 4 increased the osteogenic fluorescence intensity by 521,979 pixels, 346,080 pixels, and 12,893 pixels, respectively, compared to the normal control. The increase in osteogenic fluorescence intensity of Formula 1 (521,979 pixels) is greater than the sum of the increases of Comparative Example 1 and Comparative Example 4 (358,973 pixels), indicating that MLCT and MFGM in Formula 1 have a synergistic effect in improving bone development, especially increasing bone mineral density and / or improving osteoporosis. Similarly, for Formula 2, 4-7, it can also be concluded that MLCT and MFGM have a synergistic effect in improving bone development, especially increasing bone mineral density and / or improving osteoporosis. That is, Formulas 1-2 and 4-7 with an MLCT to MFGM ratio of 2.00-96.03 have a synergistic effect in improving bone development, especially increasing bone mineral density and / or improving osteoporosis.

[0083] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A nutritional composition, characterized in that, It comprises medium- and long-chain fatty acid triglycerides and milk fat globule membranes, wherein the mass ratio of medium- and long-chain fatty acid triglycerides to milk fat globule membranes is 2:1 to 97:

1.

2. Food products, characterized in that, Includes the nutritional composition according to claim 1.

3. The food product according to claim 2, characterized in that, The food is selected from one or more of dairy products, confectionery, beverages, bread, and biscuits.

4. The food product according to claim 2 or 3, characterized in that, The food product is milk powder or fermented food.

5. The food product according to any one of claims 2-4, characterized in that, The food in question is infant food.

6. The food product according to claim 4, characterized in that, The milk powder in question is infant formula.

7. The application of the nutritional composition according to claim 1 in the preparation of food, characterized in that, The food is intended to promote bone development.

8. The application of the nutritional composition according to claim 1 in the preparation of food, characterized in that, The food is intended to increase bone density.

9. The application according to claim 7, characterized in that, The promotion of bone development includes bone formation, growth, remodeling, and bone mass accumulation.

10. The application according to any one of claims 7-9, characterized in that, The food in question is a health food.

11. A drug, characterized in that, Includes the nutritional composition according to claim 1.

12. The use of the nutritional composition according to claim 1 in the preparation of a medicine, characterized in that, The drug is used to prevent or treat osteogenesis imperfecta and / or osteoporosis.

13. The application according to claim 12, characterized in that, The dosage form of the drug is one or more of tablets, granules, powders, capsules, and liquids.

14. The use of the nutritional composition according to claim 1 for non-therapeutic purposes of promoting bone development.

15. The use of the nutritional composition according to claim 1 for non-therapeutic purposes of increasing bone density.

16. A method for promoting bone development in a subject, comprising administering to the subject the nutritional composition according to claim 1.

17. The method according to claim 16, characterized in that, The promotion of bone development includes bone formation, growth, remodeling, and bone mass accumulation.

18. A method for increasing bone density in a subject, comprising administering to the subject the nutritional composition according to claim 1.

19. The nutritional composition according to claim 1, for the prevention or treatment of osteogenesis imperfecta and / or osteoporosis.

20. The nutritional composition according to claim 1, used to promote bone development.

21. The nutritional composition according to claim 1, used to increase bone density.

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