A milk-derived exosome-based nutritional composition and uses thereof

Abstract

The present application relates to the field of food technology, and specifically discloses a kind of nutrition composition based on milk source exosome and application thereof.The nutrition composition based on milk source exosome provided by the present application includes milk source exosome, colostrum basic protein and selenium source.It is verified by experiment that the three raw materials in the nutrition composition have significant synergistic effect after compounding, which can not only up-regulate the expression of key marker genes for bone formation, effectively promote osteoblast differentiation and accelerate bone formation, but also can significantly inhibit the expression of pro-inflammatory factors and RANKL, regulate bone metabolism by balancing RANKL / OPG ratio, effectively inhibit abnormal bone resorption and reduce local inflammatory response of bone.The composition relies on the synergistic effect of three mechanisms of promoting bone formation, inhibiting bone resorption and anti-inflammatory, and multi-dimensionally regulates bone metabolism balance, effectively improves bone density and improves bone microstructure, which has important application value for improving bone density and preventing and treating osteoporosis, especially pregnancy and lactation osteoporosis.

Description

Technical Field

[0001] This invention relates to the field of food technology, and specifically discloses a nutritional composition based on milk exosomes and its application. Background Technology

[0002] Osteoporosis is a systemic metabolic bone disease characterized by decreased bone mass, bone microstructure damage, and increased bone fragility. It is clinically prevalent in postmenopausal women and the elderly, and is a common chronic disease that endangers bone health. However, pregnancy and lactation are special physiological stages in which hormonal changes are most significant in non-menopausal women. During these stages, the body's bone metabolism balance is disrupted, making it highly susceptible to bone metabolic disorders. During pregnancy and lactation, to meet the calcium needs of fetal and infant bone growth and development, the mother's body continuously transfers calcium to her offspring. If the intake of calcium supplements, vitamin D, and other nutrients in the daily diet is insufficient, the mother will passively draw on her own bone calcium stores to maintain normal blood calcium levels, leading to rapid bone loss and damage to bone microstructure, significantly increasing the risk of pregnancy- and lactation-related osteoporosis. This type of osteoporosis not only causes a decrease in maternal bone density and an increase in bone fragility, leading to discomfort symptoms such as lower back pain and bone aches, but in severe cases, it can also cause complications such as vertebral compression fractures or osteoporosis, seriously damaging the physical and mental health of women of childbearing age.

[0003] Currently, existing technologies for preventing and treating osteoporosis mainly rely on single-method approaches such as calcium supplementation, vitamin D supplementation, or simple anti-inflammatory and bone resorption inhibition. These approaches have limited mechanisms of action and cannot simultaneously achieve the multiple regulatory effects of promoting bone formation, inhibiting bone resorption, and reducing skeletal inflammation. Furthermore, single nutritional or pharmacological interventions are insufficient to effectively balance the disordered bone metabolism of the mother during specific physiological stages, resulting in limited preventative and therapeutic effects. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention provides a nutritional composition based on milk exosomes and its applications. This invention combines milk exosomes, colostrum basic protein, and a selenium source to prepare a nutritional composition. This composition exhibits a significant synergistic effect in promoting osteoblast differentiation and regulating bone metabolism. Based on these advantages, the milk exosome-based nutritional composition provided by this invention can be widely used in improving bone density and preventing osteoporosis.

[0005] To achieve the above-mentioned objectives, the present invention adopts the following technical solution: In a first aspect, the present invention provides a nutritional composition based on milk exosomes, comprising milk exosomes, colostrum basic protein, and selenium source.

[0006] The nutritional composition based on milk exosomes provided by this invention is a compound of exosomes, colostrum basic protein (CBP), and selenium source. These three ingredients exhibit a significant synergistic effect in promoting osteoblast differentiation and regulating bone metabolism. Within the experimental scope of this invention, this nutritional composition can significantly upregulate the gene expression of key osteogenic markers, while effectively inhibiting the expression of pro-inflammatory factors and receptor activator of nuclear factor kappa (RANKL). Compared to single ingredients or combinations of two ingredients, this nutritional composition not only significantly promotes osteoblast differentiation but also inhibits bone resorption by balancing the RANKL / OPG ratio and significantly reduces inflammatory responses.

[0007] Selenium sources refer to various raw materials that can provide selenium (Se), and can be divided into two main categories according to their existing form: inorganic selenium and organic selenium.

[0008] As a first limitation of the above-mentioned nutritional composition based on milk exosomes, the mass ratio of the milk exosomes, colostrum basic protein and selenium source is (0.5-15):(80-120):(0.0015-0.05); wherein the mass of the selenium source is expressed as Se.

[0009] Within the experimental scope of this invention, and within the aforementioned ratio of milk-derived exosomes, colostrum basic protein, and selenium source, this nutritional composition can dose-dependently downregulate the expression of nuclear factor kappa receptor activator ligand (RANKL) gene and upregulate the expression of osteoprotegerin (OPG) gene; it inhibits abnormal bone resorption by regulating the RANKL / OPG expression balance. Simultaneously, this nutritional composition can significantly reduce the gene transcription levels of various pro-inflammatory factors in osteoblasts. Through the synergistic effect of promoting bone formation, inhibiting bone resorption, and reducing bone tissue inflammation, it improves the body's bone metabolism, increases bone density, and alleviates osteoporosis-related symptoms, thus achieving the prevention and treatment of osteoporosis.

[0010] As a second limitation on the above-mentioned nutritional composition based on milk exosomes, the selenium source includes at least one of sodium selenite, selenoprotein, selenium-enriched yeast, selenized carrageenan, or L-seleno-methylselenocysteine.

[0011] This invention uses sodium selenite as an example for illustration.

[0012] As a third limitation on the above-mentioned nutritional composition based on milk exosomes, the milk exosomes include at least one of bovine milk exosomes or sheep milk exosomes.

[0013] As a fourth limitation on the above-mentioned nutritional composition based on milk exosomes, the average particle size of the milk exosomes is 100nm-150nm.

[0014] Secondly, the present invention provides the application of the above-mentioned nutritional composition based on milk exosomes in the preparation of products that improve bone density.

[0015] Thirdly, the present invention provides the application of the above-mentioned nutritional composition based on milk exosomes in the preparation of products for the prevention or treatment of osteoporosis.

[0016] Furthermore, the osteoporosis includes osteoporosis during pregnancy and lactation.

[0017] Fourthly, the present invention provides a product for improving bone density, the product comprising the nutritional composition based on milk exosomes described in the first aspect.

[0018] For example, the product includes at least one of functional foods or health foods.

[0019] Fifthly, the present invention provides a product for preventing and treating osteoporosis, the product comprising the nutritional composition based on milk exosomes described in the first aspect.

[0020] For example, the nutritional composition based on milk exosomes can be used to prepare formula milk powder, liquid milk or nutritional supplements suitable for pregnant and postpartum women, to improve bone density and prevent osteoporosis.

[0021] This invention combines milk exosomes, colostrum basic protein, and selenium source to obtain a nutritional composition based on milk exosomes. Experimental verification shows that the three ingredients in this nutritional composition have a significant synergistic effect, dose-dependently upregulating the expression of key osteogenic marker genes, effectively promoting osteoblast differentiation and accelerating bone formation; simultaneously, it significantly inhibits the expression of pro-inflammatory factors and RANKL, regulating bone metabolism by balancing the RANKL / OPG ratio, effectively inhibiting abnormal bone resorption and reducing local inflammatory responses in the bone. This composition, relying on a synergistic triple mechanism of promoting bone formation, inhibiting bone resorption, and anti-inflammation, regulates bone metabolism balance in multiple dimensions, effectively increasing bone density and improving bone microstructure. It has significant application value in improving bone density and preventing osteoporosis, especially during pregnancy and lactation. Attached Figure Description

[0022] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0023] Figure 1 This is a representative scanning electron microscope image of bovine milk exosomes obtained in Example 1 of the present invention; Figure 2 This is a statistical graph showing the cell survival rate in different groups in Example 1 of the present invention; Figure 3 This is a statistical graph showing the relative gene expression levels of osteogenic markers ALP, RANKL, RUNX2, Colla1, OCN, and OPG in different groups in Example 2 of the present invention. Figure 4 This is a statistical graph showing the relative gene expression levels of inflammatory factors IL-6, IL-1β, IL-12, and INOS in different groups in Example 2 of the present invention. Detailed Implementation

[0024] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0025] The colostrum basic protein and sodium selenite used in this invention are both commercially available products. Among them, the colostrum basic protein raw material contains 98% colostrum basic protein; the sodium selenite raw material contains 0.5% selenium.

[0026] Example 1 This invention provides a nutritional composition based on milk exosomes, comprising the following raw materials in parts by weight: 1 part bovine milk exosomes, 100 parts colostrum basic protein raw material, and 0.01 parts sodium selenite raw material (calculated as Se).

[0027] The preparation method of bovine milk exosomes is as follows: exosomes are extracted from fresh bovine milk using an exosome extraction kit-milk milk (BioBio Corporation, catalog number BB-39015) to obtain bovine milk exosomes.

[0028] The specific procedure is as follows: Take 2 mL of fresh milk, centrifuge at 3000×g for 15 minutes at 4℃, discard the precipitate, and collect the supernatant; centrifuge the supernatant at 10000×g for 20 minutes at 4℃, collect the supernatant again, add 2 mL of extraction solution A, tighten the centrifuge tube cap, and mix well; add 1 mL of extraction solution B, tighten the centrifuge tube cap, mix well again, centrifuge at 10000×g for 60 minutes at 4℃, and collect the precipitate. Add 50-100 μL of exosome preservation solution to the precipitate to resuspend it, thus obtaining milk exosomes; store at -80℃ or use directly.

[0029] The concentration of the extracted protein was determined using a BCA protein concentration kit. The protein concentration of the bovine milk exosomes obtained in this example was determined to be 2 mg / mL.

[0030] The morphology and size of bovine milk exosomes were observed using scanning electron microscopy. Representative scanning electron micrographs of bovine milk exosomes obtained in this embodiment of the invention are shown below. Figure 1 As shown. By Figure 1 It can be seen that the bovine milk exosomes exhibit a typical cup-shaped or saucer-shaped structure, and the average particle size of the bovine milk exosomes is calculated to be 145 nm.

[0031] According to the above mass ratio, the colostrum basic protein raw material and sodium selenite raw material are mixed evenly, and the bovine milk exosomes are stored separately in a -80℃ refrigerator. They are prepared as needed to obtain nutritional composition I based on milk exosomes.

[0032] Example 2 This invention provides a nutritional composition based on milk exosomes and its preparation method, comprising the following raw materials in parts by weight: 5 parts bovine milk exosomes, 100 parts colostrum basic protein raw material, and 0.01 parts sodium selenite raw material (calculated as Se).

[0033] The raw materials and preparation method of bovine milk exosomes used in this embodiment are the same as those in Example 1.

[0034] According to the above mass ratio, the colostrum basic protein raw material and sodium selenite raw material are mixed, and the bovine milk exosomes are stored separately in a -80℃ refrigerator. They are prepared and used immediately to obtain nutritional composition II based on milk exosomes.

[0035] Example 3 This invention provides a nutritional composition based on milk exosomes and its preparation method, comprising the following raw materials in parts by weight: 10 parts of bovine milk exosomes, 100 parts of colostrum basic protein raw material, and 0.01 parts of sodium selenite raw material (calculated as Se).

[0036] The raw materials and preparation method of bovine milk exosomes used in this embodiment are the same as those in Example 1.

[0037] According to the above mass ratio, the colostrum basic protein raw material and sodium selenite raw material are mixed evenly, and the bovine milk exosomes are stored separately in a -80℃ refrigerator. They are prepared as needed to obtain nutritional composition III based on milk exosomes.

[0038] Example 4 This invention provides a nutritional composition based on milk exosomes and its preparation method, comprising the following raw materials in parts by weight: 0.5 parts bovine milk exosomes, 80 parts colostrum basic protein raw material, and 0.008 parts sodium selenite raw material (calculated as Se).

[0039] The preparation method of bovine milk exosomes in this embodiment is basically the same as that in Example 1, except that the fresh bovine milk in this embodiment is from a different batch than that in Example 1, and the protein concentration of the obtained bovine milk exosomes is 1.8 mg / mL.

[0040] According to the above mass ratio, the colostrum basic protein raw material and sodium selenite raw material are mixed evenly, and the bovine milk exosomes are stored separately in a -80℃ refrigerator. They are prepared as needed to obtain nutritional composition IV based on milk exosomes.

[0041] Example 5 This invention provides a nutritional composition based on milk exosomes and its preparation method, comprising the following raw materials in parts by weight: 12 parts bovine milk exosomes, 120 parts colostrum basic protein raw material, and 0.05 parts sodium selenite raw material (calculated as Se).

[0042] The preparation method of bovine milk exosomes in this embodiment is basically the same as that in Example 1, except that the fresh bovine milk in this embodiment is from a different batch than that in Example 1, and the protein concentration of the obtained bovine milk exosomes is 2.2 mg / mL.

[0043] According to the above mass ratio, the colostrum basic protein raw material and sodium selenite raw material are mixed evenly, and the bovine milk exosomes are stored separately in a -80℃ refrigerator. They are prepared as needed to obtain nutritional composition V based on milk exosomes.

[0044] Example of effect 1 This invention uses the nutritional compositions based on milk exosomes prepared in Examples 1-3 as examples to investigate the effects of single components or combinations of bovine milk exosomes, colostrum basic protein, and sodium selenite on the survival rate of MC3T3-E1 osteoblasts. The specific details are as follows: MC-3T3E1 osteoblasts were seeded in DMEM basal medium containing 10% fetal bovine serum and passaged in a 37°C, 5% CO2 incubator until the logarithmic growth phase. The logarithmic-phase osteoblasts were then added to 96-well plates and randomly divided into 12 groups. After overnight culture, different final concentrations of bovine milk exosomes, colostrum basic protein, sodium selenite or combinations thereof, and / or dexamethasone were added to each well according to the group, and the plates were incubated at 37°C, 5% CO2 for 24 hours. Then, 10 μL of CCK-8 reaction solution was added, and incubation continued for 1-2 hours. The absorbance (A) value at 450 nm was measured using a microplate reader. Cell viability was calculated based on the A value. It should be noted that negative control group 1 and negative control group 2 did not contain osteoblasts. Unless otherwise specified, "DMEM basal medium containing 10% fetal bovine serum" in the following groups is abbreviated as "medium"; the experimental group containing osteoblasts contains 100 μL of DMEM basal medium with a cell concentration of 3 × 10⁻⁶ cells / mL. 4Osteoblast culture medium (obtained from the above culture medium) with cells / mL; the bovine milk exosomes used in this effect example were prepared in Example 1.

[0045] The specific grouping arrangements are as follows: Normal group: osteoblasts; Negative control group 1: Contains only culture medium; Negative control group 2: The types and concentrations of raw materials in the culture medium and the corresponding composition to the experimental group; Negative control group 3: osteoblasts and the types and concentrations of raw materials in the composition corresponding to the experimental group; Model group: osteoblasts were treated with a final concentration of 10... -5 mol / L dexamethasone; Low-dose nutritional composition group: Added to osteoblasts at a final concentration of 10... -5 Dexamethasone at mol / L was added along with the following raw materials at final concentrations: 10 μg / mL bovine milk exosomes, 1 mg / mL CBP, and 20 μg / mL sodium selenite (as Se). Dosage group in the nutritional composition: Added to osteoblasts at a final concentration of 10 -5 Dexamethasone at mol / L, with the following raw materials added to the final concentration: bovine milk exosomes 50 μg / mL, CBP 1 mg / mL and sodium selenite (calculated as Se) 20 μg / mL; High-dose nutritional composition group: Added to osteoblasts at a final concentration of 10... -5 Dexamethasone at mol / L, with the following raw materials added to the final concentration: 100 μg / mL bovine milk exosomes, 1 mg / mL CBP and 20 μg / mL sodium selenite (as Se); Exosomes + CBP group: osteoblasts were treated with a final concentration of 10 -5 Dexamethasone at mol / L was added along with the following raw materials at the final concentrations: 100 μg / mL bovine milk exosomes and 1 mg / mL CBP; Exosomes + Selenium group: Added to osteoblasts at a final concentration of 10... -5 Dexamethasone at mol / L, with the following raw materials added to the final concentration: 100 μg / mL bovine milk exosomes and 20 μg / mL sodium selenite (as Se); CBP+Selenium group: Added to osteoblasts at a final concentration of 10 -5 Dexamethasone at mol / L, with the following raw materials added to the final concentration: CBP 1 mg / mL and sodium selenite (calculated as Se) 20 μg / mL; Exosome group: osteoblasts were added to a final concentration of 10 -5 Dexamethasone at mol / L and bovine milk exosomes at a final concentration of 100 μg / mL; CBP group: osteoblasts were added with a final concentration of 10 -5 Dexamethasone at mol / L and CBP at a final concentration of 1 mg / mL; Selenium group: Added to osteoblasts at a final concentration of 10 -5 Dexamethasone at mol / L and sodium selenite (calculated as Se) at a final concentration of 20 μg / mL.

[0046] The formula for calculating cell viability is as follows: Cell viability (%) = (A 实验组 -A 空白组 ) / (A 对照组 -A 空白组 ) × 100%.

[0047] When calculating the cell viability of the remaining nine groups (excluding the model group and negative control groups 1-3), the blank group in the formula refers to negative control group 2, and the control group refers to negative control group 3. When calculating the cell viability of the model group, the blank group in the formula refers to negative control group 1, and the control group refers to the normal group.

[0048] The statistical results of cell viability in different groups are shown in Table 1. The statistical graph of cell viability in different groups is shown below. Figure 2 As shown.

[0049] Table 1

[0050] Depend on Figure 1 As shown in Table 1, intervention with MC-3T3E1 osteoblasts using single, two-ingredient, or three-ingredient combinations of bovine milk exosomes, colostrum basic protein, and sodium selenite all improved osteoblast survival rates (P < 0.05). The high-dose group of the nutritional composition with the highest exosome content showed the best effect on improving osteoblast survival rates, and was significantly higher than the medium-dose group, low-dose group, two-ingredient combination group, and single-ingredient group.

[0051] Example 2 This invention investigated the effects of a nutritional composition based on milk exosomes on osteogenic markers and inflammatory factors in osteoblast MC3T3-E1 cells. The specific details are as follows: Logarithmic-phase osteoblasts MC3T3-E1 were cultured in 6-well plates with a final concentration of 10... -5Osteoporosis cell models were constructed by treating cells with mol / L dexamethasone solution for 15 h and randomly dividing them into 10 groups. Following the classification method and treatment dosage described in Example 1, the groups were: model group, low-dose nutritional composition group, medium-dose nutritional composition group, high-dose nutritional composition group, exosome + CBP group, exosome + selenium group, CBP + selenium group, exosome group, CBP group, and selenium group. Osteoblasts were treated with the corresponding components and dosages for 24 h. RNA was then extracted according to the kit requirements, and the gene expression levels of osteogenic specific markers and inflammatory factors were detected by qPCR. Osteogenic markers included alkaline phosphatase (ALP), receptor activator of nuclear factor-κB ligand (RANKL), osteogenic-associated transcription factor-2 (RUNX2), type I collagen (Colla1), osteocalcin (OCN), and osteoprotegerin (OPG), with the gene encoding β-actin used as an internal reference gene. Inflammatory factors included IL-6, IL-1β, IL-12, and INOS.

[0052] The specific primer sequences for osteogenic markers and inflammatory factors are shown in Table 2.

[0053] Table 2

[0054] The qPCR reaction conditions were as follows: pre-denaturation at 95℃ for 10 min; followed by 40 cycles, each cycle consisting of: denaturation at 95℃ for 15 s, annealing at 60℃ for 30 s, extension at 72℃ for 10 s; and final extension at 72℃ for 10 min.

[0055] The statistical results of gene expression levels of osteogenic markers ALP, RANKL, RUNX2, Colla1, OCN, and OPG in different groups are shown in Table 3. The statistical graph of the relative gene expression levels of osteogenic markers ALP, RANKL, RUNX2, Colla1, OCN, and OPG in different groups is shown below. Figure 3 As shown.

[0056] Table 3

[0057] Depend on Figure 3As shown in Table 3, compared with the model group induced by dexamethasone alone and the single-component experimental group, the combination of bovine milk exosomes, colostrum basic protein, and sodium selenite in pairs or in all three combinations significantly increased the levels of key osteogenic markers in MC-3T3E1 osteoblasts, indicating a positive synergistic enhancement effect. Furthermore, this enhancement effect exhibited a clear dose-dependent characteristic, with the expression levels of each osteogenic marker in the high-dose nutritional composition group being significantly better than in other groups. Our results demonstrate that intervention with a nutritional composition based on milk exosomes downregulated RANKL gene expression and upregulated OPG gene expression in osteoblasts. This composition can regulate the RANKL / OPG balance and inhibit bone resorption. This dual synergistic mechanism of promoting bone formation and inhibiting resorption has a significant promoting effect on increasing bone mineral density and alleviating osteoporosis.

[0058] The statistical results of the relative gene expression levels of inflammatory factors IL-6, IL-1β, IL-12, and INOS in different groups are shown in Table 4. The statistical graph of the relative gene expression levels of inflammatory factors IL-6, IL-1β, IL-12, and INOS in different groups is shown below. Figure 4 As shown.

[0059] Table 4

[0060] Depend on Figure 4 As shown in Table 4, compared with the model group induced by dexamethasone alone, the high, medium, and low dose groups of the nutritional composition, the combination groups, and the single ingredient groups all significantly reduced the expression of pro-inflammatory gene genes in osteoblasts. The nutritional composition based on milk exosomes inhibited inflammation better than the combination groups and the single ingredient groups. Furthermore, the high dose group of the nutritional composition had a significantly better effect on reducing inflammation than the low dose group. This indicates that the nutritional composition based on milk exosomes provided by this invention can improve bone metabolism by reducing inflammation.

[0061] In summary, this invention combines milk exosomes, colostrum basic protein, and selenium source to obtain a nutritional composition based on milk exosomes. Verification has shown that this nutritional composition not only upregulates the expression of key osteogenic marker genes, effectively promoting osteoblast differentiation and accelerating bone formation, but also significantly inhibits the expression of pro-inflammatory factors and RANKL. By balancing the RANKL / OPG ratio to regulate bone metabolism, it effectively inhibits abnormal bone resorption and reduces local inflammatory responses in the bones. This composition, relying on a synergistic triple mechanism of promoting bone formation, inhibiting bone resorption, and reducing inflammation, regulates bone metabolism balance in multiple dimensions, effectively increasing bone density and improving bone microstructure. It has significant application value in improving bone density and preventing osteoporosis, especially during pregnancy and lactation. Therefore, the nutritional composition based on milk exosomes can be used to prepare products that improve bone density and / or prevent osteoporosis, especially for the prevention of osteoporosis during pregnancy and lactation.

[0062] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions or improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A nutritional composition based on milk exosomes, characterized in that, This includes milk exosomes, colostrum basic proteins, and selenium sources.

2. The nutritional composition based on milk exosomes as described in claim 1, characterized in that, The mass ratio of the milk exosomes, colostrum basic protein and selenium source is (0.5-15):(80-120):(0.0015-0.05); wherein the mass of the selenium source is expressed as Se.

3. The nutritional composition based on milk exosomes as described in claim 1 or 2, characterized in that, The selenium source includes at least one of sodium selenite, selenoprotein, selenium-enriched yeast, selenized carrageenan, or L-seleno-methylselenocysteine.

4. The nutritional composition based on milk exosomes as described in claim 1 or 2, characterized in that, The milk-derived exosomes include at least one of bovine milk exosomes or sheep milk exosomes; and / or The average particle size of the milk-derived exosomes is 100nm-150nm.

5. The use of the nutritional composition based on milk exosomes according to any one of claims 1-4 in the preparation of products that improve bone density.

6. The use of the nutritional composition based on milk exosomes according to any one of claims 1-4 in the preparation of products for the prevention or treatment of osteoporosis.

7. The application as described in claim 6, characterized in that, The osteoporosis mentioned includes osteoporosis during pregnancy and lactation.

8. A product for improving bone density, characterized in that: The product comprises the nutritional composition based on milk exosomes as described in any one of claims 1-4.

9. A product for preventing and treating osteoporosis, characterized in that: The product comprises the nutritional composition based on milk exosomes as described in any one of claims 1-4.

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