Nutritional composition and use of the nutritional composition

Abstract

The present invention provides a nutritional composition and the use of the nutritional composition. The nutritional composition comprises medium and long chain triglycerides and milk fat globule membrane in a mass ratio of 2:1 - 97:1, and the two have a synergistic effect in promoting bone development, particularly increasing bone density and / or preventing or treating osteogenesis imperfecta and / or osteoporosis.

Description

Technical Field

[0001] The present disclosure relates to the technical field of food or medicine, and particularly relates to nutritional compositions for improving bone development, particularly increasing bone density and / or preventing or treating osteogenesis imperfecta and / or osteoporosis, foods and drugs containing the nutritional compositions, and the applications of the nutritional compositions. Background Art

[0002] Bone formation is affected by many factors such as genetics, nutrition, health, and environment. Bone formation starts from embryonic development. During childhood and adolescence, bone mass increases with age until young adulthood when bone development is mature and bone mass reaches its peak. An increase in peak bone mass reduces the risk of osteoporosis in later life. A 10% increase in maximum bone mass during the growth period will reduce the risk of osteoporotic fractures by 50%. Therefore, in the early stages of life, especially during infancy, childhood, and adolescence, improving bone growth through breast milk and dietary nutrition may play a huge role in bone health in later life. Increasing peak bone mass during the growth period is of great significance for maintaining bone health in adolescents (Liu Qian et al., Food Science and Technology, 2023; 48(03): 253 - 259).

[0003] Breast milk contains a variety of nutrients and immune factors, so it is the best choice for infant nutrition. Breastfeeding is the dietary method recommended by the World Health Organization for the first 6 months after a baby is born. Research shows 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, as a star product among novel structured lipids, have received extensive attention. The fatty acid composition of MLCT is closer to that of breast milk, which is beneficial for 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., Annual Review of Food Science and Technology. 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 simultaneously linked to the same glycerol backbone. Early studies have shown that MLCT has many health care functions such as reducing blood lipids, inhibiting obesity, reducing the risk of diabetes and cardiovascular diseases, and reducing the risk of cancer (Lai Yundong et al., Chinese Journal of Oil Crop Sciences, 2024; 46(04): 719 - 727).

[0004] 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 - 25:1. This nutritional composition can be applied in improving brain or cognitive development.

[0005] Chinese Patent CN118592494B discloses the application of an oil and fat composition in improving the temperament of infants or children. In the oil and fat composition, the mass ratio of the UPU structured lipid composition to the medium and long-chain fatty acid edible oil is 1:1 - 1.5:1.

[0006] In addition, the milk fat globule membrane (MFGM) is a complex three-layer phospholipoprotein membrane that wraps the surface of milk fat droplets and is composed of polar lipids, cholesterol, proteins, etc. Its safety and tolerance 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 the cognitive development of infants and improve the immunity of infants (China Institute of Food Science and Technology, Scientific Consensus on Milk Fat Globule Membrane and Its Ingredients, Journal of Chinese Institute of Food Science and Technology, 2022;22(04):471 - 476).

[0007] Chinese Patent CN114128757B discloses the application of milk fat globule membrane in reducing the off-flavor of dairy products, where the dairy product is a solid dairy product or a liquid dairy product; the solid dairy product is selected from infant formula milk powder, children's formula milk powder, or middle-aged and elderly formula milk powder.

[0008] However, there have been no corresponding reports at home and abroad on the effects of long-chain fatty acid triglycerides and milk fat globule membrane on bone development.

[0009] There is still a need in the art for methods that can promote bone development and increase bone density. Summary of the Invention

[0010] The present invention is made in view of the above problems in the art.

[0011] In a first aspect of the present invention, there is provided a nutritional composition comprising medium and long-chain fatty acid triglycerides and milk fat globule membrane, wherein the mass ratio of the medium and long-chain fatty acid triglycerides to the milk fat globule membrane is 2:1 - 97:1.

[0012] In a second aspect of the present invention, there is provided a food comprising the nutritional composition according to the first aspect of the present invention.

[0013] In a third aspect of the present invention, there is provided the application of the nutritional composition according to the first aspect of the present invention in the preparation of a food for promoting bone development, and the food is used for non-therapeutic purposes of promoting bone development.

[0014] 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 a food for increasing bone density.

[0015] The fifth aspect of the present invention provides the use of the nutritional composition described in the first aspect of the present invention for the non-therapeutic purpose of promoting bone development.

[0016] The sixth aspect of the present invention provides the use of the nutritional composition described in the first aspect of the present invention for the non-therapeutic purpose of increasing bone density.

[0017] The seventh aspect of the present invention provides a drug comprising the nutritional composition described in the first aspect of the present invention.

[0018] The eighth 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 drug for preventing or treating osteoporosis and / or osteogenesis imperfecta.

[0019] The present invention discovers that when medium- and long-chain fatty acid triglycerides and milk fat globule membrane are used in combination at the defined mass ratio, there is a synergistic effect between them, which can be used to prepare a food for improving bone development, especially increasing bone density, for non-therapeutic purposes, or to prepare a drug for preventing or treating osteogenesis imperfecta and / or osteoporosis. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 Typical diagrams showing the osteogenic fluorescence intensity of zebrafish after treatment with samples of the normal control group, positive control group, and Formulas 1-6.

[0021] Figure 2 Typical diagrams showing the osteogenic fluorescence intensity of zebrafish after treatment with samples of Comparative Examples 1-6 and Formula 7. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0022] The following definitions are provided to facilitate understanding of the present invention by those skilled in the art. 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 the present invention pertains. Preferred materials and methods are described herein, but any methods and materials similar to or equivalent to those described herein can be used in the practice of testing the present invention. It should also be understood that the terms used herein are for the purpose of describing specific embodiments only and are not intended to be limiting.

[0023] TERM DEFINITIONS

[0024] Unless otherwise indicated or defined, all terms used have their ordinary meaning in the art, which will be understood by those skilled in the art. In addition, unless otherwise stated, all methods, steps, techniques, and operations not specifically detailed can and have been carried out in a manner known per se, which will be understood by those skilled in the art.

[0025] As used herein, the term "medium and long-chain fatty acid triglyceride" or "MLCT" is a special triglyceride in which both medium-chain fatty acids and long-chain fatty acids are present on the triglyceride backbone. MLCT is prepared from edible vegetable oils and medium-chain triglycerides (derived from edible coconut oil and palm kernel oil) through an ester exchange reaction with lipase and processes such as distillation separation, decolorization, and deodorization. Medium and long-chain fatty acid triglycerides can be derived from medium and long-chain fatty acid edible oils.

[0026] As used herein, the term "medium-chain fatty acid" refers to fatty acids having 6 - 12 carbon atoms in the carbon chain, such as caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecanoic acid, lauric acid, etc.; the term "long-chain fatty acid" refers to fatty acids having 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" respectively refer to the esterification reaction products of "medium-chain fatty acid" and "long-chain fatty acid" with glycerol; the term "medium and 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. The present invention has no particular requirements for the medium and long-chain fatty acid triglycerides used, and the medium and long-chain fatty acid triglycerides commonly used in the art can be used. Medium and long-chain fatty acid triglycerides can be used in the form of pure products or in non-pure forms rich in medium and long-chain fatty acid triglycerides. For example, the medium and long-chain fatty acid triglycerides used in the present invention can contain C6 - C 12 fatty acid residues and C 14 -C 30 fatty acid residues. The C6 - C 12 fatty acid residues can be derived from one or more of the following: caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecanoic acid, lauric acid, etc. The C 14 -C 30 fatty acid residues can be derived from one or more of the following: myristic acid, palmitic acid, margaric acid, oleic acid, linoleic acid, stearic acid, nonadecanoic acid, eicosapentaenoic acid, heneicosanoic acid, docosatetraenoic acid, docosahexaenoic acid, tricosanoic acid, tetracosenoic acid, pentacosapentaenoic acid, docosapentaenoic acid, arachidonic acid, etc. In some embodiments, the C6 - C12 fatty acid residues are derived from one or more of the following: caproic acid, caprylic acid, capric acid, and lauric acid; and / or the C14 - C30 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, the C6 - C 12 fatty acid residues to the C14 -C 30 The weight ratio of the fatty acid residue is from 0.124 to 2.000. In some embodiments, C6-C 12 The fatty acid residue to the C 14 -C 30 The weight ratio of the fatty acid residue 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 within the range defined by any two of them. In some embodiments, the "medium and long chain fatty acid triglyceride" can be prepared by referring to the method of patent CN115369132A.

[0027] As used herein, the term "milk fat globule membrane" or "MFGM" (Milk Fat Globule Membrane in English) refers to a complex biological membrane structure present in breast milk. The milk fat globule membrane is a complex three-layer phospholipoprotein membrane that envelopes the surface of milk fat droplets and is composed of polar lipids, cholesterol, proteins, etc. Sphingomyelin and gangliosides are characteristic indicators of milk fat globule membrane ingredients, and their safety and tolerance have been confirmed in clinical trials. There are no particular restrictions in principle on the source of the milk fat globule membrane of the present invention. Generally, it can be obtained by extraction from animal milk or its products. In some preferred embodiments, such animal milk or its products can be cow milk, goat milk, camel milk, horse milk, or dairy products based on them (such as cheese), etc. More preferably, it can be extracted from cow milk, including bovine colostrum or normal cow milk. The present invention does not particularly limit the preparation process of MFGM. For example, the method of acidification precipitation - centrifugation - isoelectric point enrichment - drying can be used, or the existing membrane filtration method can also be used to separate MFGM. In addition, MFGM can also be obtained through commercially available products, including milk fat globule membrane whey protein powder and milk fat globule membrane milk protein powder, etc. Milk fat globule membrane whey protein powder refers to a powdery product containing milk fat globule membrane, which is made from raw milk or whey through processes such as separation, concentration, and drying. Milk fat globule membrane milk protein powder refers to a powdery product containing milk fat globule membrane, which is made from raw milk or cream through processes such as separation, concentration, and drying. Commercially available sources of MFGM of the present invention include Lacprodan® MFGM-10, Lacprodan® PL-20, Cor-Powe® SM2, lipid-rich MFGM fraction, or buttermilk powder concentrates BPC50, BPC60, G600, PC700, Hilmar Cor-Power®, or WPC7500 MEGM ENRICHED WPC, etc.

[0028] As used herein, an "osteoblast" is the main functional cell of bone formation and plays a key role in bone growth and development, bone remodeling, and the repair process after fracture. When osteoblasts are activated, they will undergo processes such as cell proliferation, extracellular matrix maturation, and mineralization, thus forming new bone. Osteoblasts play a key role in bone development. Abnormal functions of osteoblasts are closely related to skeletal dysplasia. In this article, skeletal dysplasia can be any type of skeletal dysplasia, including but not limited to skeletal dysplasia caused by abnormal osteoblast functions, such as osteogenesis imperfecta and osteoporosis.

[0029] As used herein, "bone density" refers to the bone mass contained per unit volume (volume density) or per unit area (area density). Osteoblasts are the main functional cells of bone formation and play a crucial role in maintaining and increasing bone density.

[0030] As used herein, "osteoporosis" is a systemic bone disease characterized by reduced bone mass and disrupted bone microstructure, leading to increased bone fragility and thus an increased susceptibility to fractures. A decrease in osteoblast activity results in reduced bone formation, while relatively enhanced osteoclast activity leads to increased bone resorption, ultimately causing bone mass loss and osteoporosis.

[0031] As used herein, "fracture healing disorder" refers to an abnormal condition that occurs during the normal healing process of a fracture, resulting in an extended fracture healing time or a complete inability 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.

[0032] Nutritional composition

[0033] A first aspect of the present invention provides a nutritional composition comprising medium-chain and long-chain triglycerides (MLCT) and milk fat globule membrane (MFGM), wherein the mass ratio of the medium-chain and long-chain triglycerides to the milk fat globule membrane is 2:1 to 97:1.

[0034] The present invention has found that when medium-chain and long-chain triglycerides and milk fat globule membrane are used in combination at the defined mass ratio, there is a synergistic effect between them, which can be used to prepare foods for non-therapeutic purposes to improve bone development, especially to increase bone density, or to prepare drugs for preventing or treating osteogenesis imperfecta and / or osteoporosis.

[0035] In some embodiments, the nutritional composition consists of medium-chain and long-chain triglycerides (MLCT) and milk fat globule membrane (MFGM).

[0036] In an embodiment, the mass ratio of the medium-chain and long-chain triglycerides to the milk fat globule membrane in the nutritional composition is from 2:1 to 97:1, such as 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 within the range defined by any two of them.

[0037] In some embodiments, the mass ratio of the medium-chain and long-chain triglycerides to the milk fat globule membrane in the nutritional composition is from 2.67:1 to -96.03:1, such as 10.67:1, 2.67:1, 32.01:1, 8.01:1, 2.00:1, or 96.03:1.

[0038] Food

[0039] The second aspect of the present invention relates to a food product, which comprises the nutritional composition described in the first aspect of the present invention.

[0040] All of the above descriptions regarding the first aspect of the present invention apply here and will not be repeated herein.

[0041] In some embodiments, the food product may be, for example, a functional food, a health food, or a health supplement.

[0042] In some embodiments, the food product is a general food or a special food. By way of example, the food product may be selected from dairy products, confectionery, beverages, bread, and biscuits, for example, the food product may be selected from milk powder or fermented foods. In some embodiments, the milk powder is an infant formula milk powder.

[0043] In some embodiments, the food product is an infant food such as an infant formula food.

[0044] In some embodiments, the food product may be in the form of a powder, a tablet, or a liquid.

[0045] In some embodiments, based on the dry basis weight of the food product, the content of medium and long-chain fatty acid triglycerides may be from 0.1% to 30.0%, preferably from 0.4% to 30.0%. By way of example, based on the weight of the product, the content of medium and long-chain fatty acid triglycerides may be 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% dry basis weight, or within the range defined by any two of them. The content of milk fat globule membrane can be calculated according to the ratio of the two.

[0046] In some embodiments, based on the dry basis weight of the food product, the content of milk fat globule membrane may be from 0.001% to 15.0%. By way of example, based on the weight of the product, the content of milk fat globule membrane may be 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 basis weight, or within the range defined by any two of them.

[0047] 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 further comprises one or more selected from the following: raw cow milk, demineralized whey powder, concentrated whey protein, lactose, edible vegetable blended oil, fructooligosaccharide, galactooligosaccharide, nucleotide, choline, vitamin, mineral, DHA and taurine.

[0048] 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 further comprise proteins such as α-lactalbumin and milk fat globule membrane protein; saccharides such as lactose; lipids; minerals such as calcium, iron, phosphorus, etc.; vitamins; and other additives such as whey powder, choline bitartrate, docosahexaenoic acid, arachidonic acid, walnut oil, etc.

[0049] The food can be produced by the preparation methods commonly used in the art, which will not be elaborated herein.

[0050] Drug

[0051] The third aspect of the present invention relates to a drug, which comprises the nutritional composition described in the first aspect of the present invention.

[0052] All the above descriptions regarding the first aspect of the present invention are applicable here and will not be elaborated herein.

[0053] There is no limitation on the dosage form of the drug, and it can be, for example, one or more of tablets, granular powders, capsules and liquid preparations.

[0054] When the drug comprises the nutritional composition, the drug can be used for preventing or treating osteogenesis imperfecta and / or osteoporosis.

[0055] Application in preparing food

[0056] The fourth aspect of the present invention relates to the application of the nutritional composition of the first aspect of the present invention in preparing a food (such as a health food) for promoting bone development, and the use of the food for the non-therapeutic purpose of promoting bone development.

[0057] The promotion of bone development may include, for example, promoting bone formation, growth, remodeling and bone mass accumulation.

[0058] The fifth aspect of the present invention relates to the application of the nutritional composition of the first aspect of the present invention in preparing a food (such as a health food) for increasing bone density.

[0059] The sixth aspect of the present invention relates to the non-therapeutic application of the nutritional composition of the first aspect of the present invention for promoting bone development.

[0060] The seventh aspect of the present invention relates to the non-therapeutic application of the nutritional composition of the first aspect of the present invention for increasing bone density.

[0061] For the nutritional composition, all of the above descriptions regarding the first aspect of the present invention apply thereto and will not be repeated herein.

[0062] For the food, all of the above descriptions regarding the second aspect of the present invention apply thereto and will not be repeated herein.

[0063] All of the above descriptions regarding the first aspect of the present invention apply thereto and will not be repeated herein. In some embodiments, when the nutritional composition or food is orally administered to a 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, such as 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, 16 g / day, 17 g / day, 18 g / day, 19 g / day, 20 g / day, 21 g / day, 22 g / day, 23 g / day, 24 g / day, 25 g / day, 26 g / day, 27 g / day, 28 g / day, 29 g / day, or 30 g / day or a range defined by any two of them. The dosage of the milk fat globule membrane can be converted according to the ratio to the medium and long-chain fatty acid triglycerides.

[0064] In some embodiments, when the nutritional composition or food is orally administered to a human body, the dosage of the milk fat globule membrane is 0.001 g / day - 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, 0.06 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 therebetween. Medium- and long-chain triglycerides and milk fat globule membrane can be formulated into a composition or preparation for easy administration to a subject. Alternatively, medium- and long-chain triglycerides and milk fat globule membrane can be administered separately without being formulated into the same composition, for example, simultaneously or separately. In the case of separate administration, medium- and long-chain triglycerides and milk fat globule membrane can be administered at intervals within a day. Long-chain triglycerides and milk fat globule membrane can also be administered in several doses within a day. The time interval between the administration of the two components or the number of separate administrations can be easily determined by those skilled in the art.

[0065] Use in the preparation of a drug

[0066] The eighth 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 drug for preventing or treating osteogenesis imperfecta and / or osteoporosis.

[0067] For the said nutritional composition, all the descriptions regarding the first aspect of the present invention apply herein and will not be repeated here.

[0068] For the said drug, in some embodiments, its dosage forms include but are not limited to tablets, granular powders, capsules and liquids.

[0069] All of the above descriptions regarding the first aspect of the present invention apply here and will not be repeated. In some embodiments, when the nutritional composition or drug is orally administered to a 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, such as 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, 16 g / day, 17 g / day, 18 g / day, 19 g / day, 20 g / day, 21 g / day, 22 g / day, 23 g / day, 24 g / day, 25 g / day, 26 g / day, 27 g / day, 28 g / day, 29 g / day, or 30 g / day or the range defined by any two of them. The dosage of the milk fat globule membrane can be converted according to the ratio to medium- and long-chain fatty acid triglycerides.

[0070] In some embodiments, when the nutritional composition or drug is orally administered to a human body, the dosage of milk fat globule membrane is 0.001 g / day - 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, 0.06 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 therebetween. Medium- and long-chain triglycerides and milk fat globule membrane can be formulated into a composition or preparation for easy administration by a subject. Alternatively, medium- and long-chain triglycerides and milk fat globule membrane can be administered separately without being formulated into the same composition, for example, simultaneously or separately. In the case of separate administration, medium- and long-chain triglycerides and milk fat globule membrane can be administered at intervals within a day. Long-chain triglycerides and milk fat globule membrane can also be administered in several doses within a day. The time interval between the administration of the two components or the number of separate administrations can be easily determined by those skilled in the art.

[0071] Examples

[0072] The present invention will be more easily understood with reference to the following examples, which are only used to illustrate certain aspects and embodiments of the present invention and are not intended to limit the present invention.

[0073] Unless otherwise specified, the reagents used in this example are all commercially available materials or conventional materials. The medium- and long-chain triglycerides (MLCT) in all the following examples are derived from medium- and long-chain fatty acid edible oil (purity 69 ± 10 %), produced by Qingdao Haizhiyuan Life Science Co., Ltd., production batch number Y1505 - 22120101; milk fat globule membrane (MFGM), purchased from Arla, product name Lacprodan® MFGM-10, batch number P510216, the phospholipid content in this raw material is 8 ± 2 %, the protein content is 71.5 ± 5 wt%, and the sphingomyelin per 100 g of phospholipid is 25 ± 10 g.

[0074] Vancomycin is sourced from Shanghai Macklin Biochemical Co., Ltd., in the form of white powder, with batch number C12976208.

[0075] AB strain zebrafish: Provided by the fish breeding center of Hangzhou Huante Biotechnology Co., Ltd.

[0076] Example 1 Determination of the single-sample maximum tolerated concentration (MTC, Maximum tolerated concentration)

[0077] Randomly select wild-type AB strain zebrafish at 3 days post-fertilization (3 dpf) and place them in beakers, with 30 zebrafish in each beaker (experimental group). Administer the sample in water solution (concentrations are shown in Table 1), and simultaneously set up a normal control group. The capacity of each beaker is 20 mL. Change the solution at 5 dpf. After treatment at 28°C for 3 days, determine the MTC of the sample for normal zebrafish.

[0078] Table 1. Results of the experiment for exploring the concentration for promoting bone development efficacy of a single sample (n = 30)

[0079]

[0080] As can be seen from Table 1, the MTC of medium- and long-chain fatty acid triglycerides is 750 μg / mL; the MTC of milk fat globule membrane MFGM is 125 μg / mL. The subsequent dosing experiment design refers to the above MTC.

[0081] Example 2 Experiment for evaluating the efficacy of the sample in promoting bone development

[0082] The fluorescence intensity of osteoblasts is closely related to bone development and diseases. Research shows that the change in the fluorescence intensity of osteoblasts can reflect their biological functions and states. For example, when osteoblast-like cells are stressed, the microfilament structure of the cytoskeleton will change, and the fluorescence intensity will decrease accordingly. However, after removing the stimulus, the fluorescence intensity gradually recovers and increases, indicating that the change in the cytoskeleton is recoverable and remodelable. In addition, the change in fluorescence intensity is also related to the differentiation and activity of osteoblasts. For example, after treatment with static magnetic fields, the fluorescence intensity of the cytoskeletal proteins of osteoblasts increases. These changes may be related to bone development, repair, and disease states (such as osteoporosis). The fluorescence intensity of osteoblasts is an important indicator for studying bone health and diseases.

[0083] Randomly select 3-dpf transgenic teleost green fluorescent zebrafish into a beaker, with 30 zebrafish in each beaker (experimental group). Administer the samples (concentrations are shown in Table 2) in aqueous solution, with the positive control being Swisse "Calcium & Vitamin D" at a concentration of 500 μg / mL. At the same time, set up a normal control group, and the capacity of each beaker is 20 mL. Change the solution once at 5 dpf. After treatment at 28 °C for 3 days, randomly select 10 zebrafish from each experimental group and place them under a fluorescence microscope for photographing. Use the NIS-Elements D3.20 advanced image processing software to analyze and collect data, and analyze the osteogenic fluorescence intensity of zebrafish. Evaluate the efficacy of the samples in promoting bone development based on the statistical analysis results of this index. The statistical processing results are expressed as mean ± S.E. Use SPSS 26.0 software for statistical analysis, and p < 0.05 indicates that the difference is statistically significant.

[0084] According to the above method, administer medium- and long-chain fatty acid triglycerides, MFGM alone, and the composition with different ratio doses to zebrafish, and the administration doses are shown in Table 2. The administration results are shown in Table 2 and Figure 1 - Figure 2 as follows.

[0085] Table 2 Evaluation experimental results of the efficacy of samples in improving bone development (osteogenic fluorescence intensity)

[0086] Note: Compared with the normal control group, *P < 0.05, ***P < 0.001.

[0087] From Table 2, Figure 1 - Figure 2The results showed that, compared with the normal control group, the osteogenic fluorescence intensity in the groups treated with MLCT (83.3 µg / mL, 250 µg / mL, 750 µg / mL) and MFGM (125 µg / mL) was significantly enhanced (P < 0.05), indicating that the single sample had the effect of improving bone development. In addition, compared with the normal control, the combined use of MLCT and MFGM (Formulas 1-7) could significantly improve bone development, as manifested by a significant increase in osteogenic fluorescence intensity (P < 0.05). In addition, as can be seen from Table 2, Formulas 1-2 and 4-7 with a ratio of MLCT to MFGM of 2:1 - 96.03:1 had higher osteogenic fluorescence compared to Formula 3 with a ratio of MLCT to MFGM of 0.67, indicating better effects in improving bone development, especially increasing bone density and / or improving osteoporosis. In addition, it can also be seen from Table 2 that in terms of composition, Formula 1 was equivalent to the 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 the osteogenic fluorescence intensity of Formula 1 (521,979 pixels) was greater than the sum of the increases of Comparative Example 1 and Comparative Example 4 (358,973 pixels) respectively, indicating a synergistic effect between MLCT and MFGM in Formula 1 in improving bone development, especially increasing bone density and / or improving osteoporosis; similarly, for Formula 2, 4-7, it can also be concluded that there was a synergistic effect between MLCT and MFGM in them in improving bone development, especially increasing bone density and / or improving osteoporosis; that is, Formulas 1-2 and 4-7 with a MLCT to MFGM ratio of 2.00 - 96.03 had a synergistic effect in improving bone development, especially increasing bone density and / or improving osteoporosis.

[0088] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements for some of the technical features; and these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the various embodiments of the present invention.

Claims

1. A nutritional composition, characterized in that, It contains medium and long-chain fatty acid triglycerides and milk fat globule membrane, and the medium and long-chain fatty acid triglycerides and milk fat globule membrane have a mass ratio of 2:1 to 97:

1.

2. A food product, characterized in that, It includes the nutritional composition described in claim 1.

3. The food according to claim 2, wherein The food is selected from one or more of dairy products, candies, beverages, breads, and biscuits.

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

5. The food according to claim 2, characterized in that, The food is infant food.

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

7. Use of the nutritional composition according to claim 1 in the preparation of a food, characterized in that, Use of the food for non-therapeutic purposes of promoting bone development.

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

9. The application according to claim 7, wherein 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 is a health food.

11. A drug, characterized in that, It includes the nutritional composition described in claim 1.

12. Use of the nutritional composition according to claim 1 in the preparation of a medicament, characterized in that, The drug is used for preventing or treating osteogenesis imperfecta and / or osteoporosis.

13. The application according to claim 12, wherein The dosage form of the drug is one or more of tablets, granular powders, capsules, and liquids.

14. Use of the nutritional composition described in claim 1 for non-therapeutic purposes of promoting bone development.

15. Use of the nutritional composition described in claim 1 for non-therapeutic purposes of increasing bone density.

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