Modified milk powder capable of promoting bone health as well as preparation method and application of modified milk powder

Abstract

The invention provides modified milk powder capable of promoting bone health as well as a preparation method and application of the modified milk powder. The total protein content of the modified milk powder is 17-35 g / 100 g, the fat content of the modified milk powder is 1-32 g / 100 g, and the calcium content of the modified milk powder is 0.8-2.1 g / 100 g. Moreover, the modified milk powder contains bovine coloctrum and lactoferrin, the mass ratio of the bovine coloctrum to the lactoferrin is (5-100): 1 on the basis of the dry matter content, and the content of the lactoferrin in the modified milk powder is 2-400 mg / 100 g. The bovine colostrum and the lactoferrin are combined for preparing the milk powder, have a synergistic effect on promoting osteoblasts and inhibiting osteoclast proliferation, and are beneficial to bone health.

Description

Technical Field

[0001] This invention relates to a modified milk powder, its preparation method, and its application. More specifically, it relates to a modified milk powder containing bovine colostrum and lactoferrin that promotes bone health, its preparation method, and its application. Background Technology

[0002] Bones are the most important component of the human body. Bones undergo their own metabolism; this dynamic process keeps bones in a vibrant state—dense, smooth, strong, and resilient. However, with age, the incidence of unhealthy bone conditions increases. Osteoporosis is prevalent among middle-aged and elderly people. Osteoporosis is characterized by decreased bone density and damage to bone microstructure, making bones more prone to fractures and increasing the difficulty of fracture healing.

[0003] Lactoferrin is an iron-binding protein with high bioavailability and bioactivity. Early experimental and clinical studies have shown that lactoferrin intake can affect bone health through multiple pathways. CN108671225A discloses that lactoferrin can activate the VDR signaling pathway, promoting osteoblast proliferation and differentiation, inhibiting osteoclast bone resorption, or inhibiting bone calcium release. However, the dosage of lactoferrin is 100–1000 mg / kg BW, and such high doses are difficult to achieve through daily diet alone.

[0004] Bovine colostrum contains colostrum basic protein (CBP), which studies have reported can improve calcium ion utilization, promote osteoblast proliferation, inhibit osteoclast proliferation, and stimulate growth factor secretion (CN115997937A). However, the extraction process of colostrum basic protein is complex and expensive, making it difficult for the average consumer to accept as a dietary supplement. In addition, there are literature reports on the improving effects of bovine colostrum on bone health, such as: Bovine Colostrum Supplementation Improves Bone Metabolism in an Osteoporosis-Induced Animal Model, Nutrients 2021, 13, 2981. https: / / doi.org / 10.3390 / nu13092981; Pharmacological and Non-Pharmacological Agents versus Bovine Colostrum Supplementation for the Management of Bone Health Using an Osteoporosis-Induced Rat Model, Nutrients 2022, 14, 2837. https: / / doi.org / 10.3390 / nu14142837; Preventive and antioxidant effects of lyophilized bovine colostrum powder and compound preparation on retinoic acid-induced osteoporosis in mice, Anhui Agricultural Sciences, 2021, 49(10): 157-160, 163. However, according to these literature reports, bovine colostrum is used to improve osteoporosis in large doses, has a slow effect, and is difficult to prevent or improve osteoporosis through daily diet.

[0005] Therefore, it is very important to develop and select more effective edible compositions that can promote bone health. Summary of the Invention

[0006] One object of the present invention is to provide a modified milk powder that can promote bone health.

[0007] Another object of the present invention is to provide a method for preparing the modified milk powder.

[0008] Another object of the present invention is to provide the application of the modified milk powder.

[0009] The inventors of this case discovered in their research that when bovine colostrum and lactoferrin are mixed and compounded in a certain proportion, a significant synergistic effect is produced between the two components. The promoting effect on osteoblasts and the inhibiting effect on osteoclast proliferation are both more significant than when lactoferrin or bovine colostrum are used alone. Based on this, this invention provides a modified milk powder that promotes bone health, its preparation method, and related applications.

[0010] Specifically, on the one hand, the present invention provides a modified milk powder, wherein the total protein content of the modified milk powder is 17~35g / 100g, the fat content is 1~32g / 100g, and the calcium content is 0.8~2.1g / 100g; and the modified milk powder contains bovine colostrum and lactoferrin, wherein the mass ratio of bovine colostrum to lactoferrin is (5~100):1 based on dry matter content, and the content of lactoferrin in the modified milk powder is 2~400mg / 100g.

[0011] According to a specific embodiment of the present invention, the bovine colostrum in the modified milk powder of the present invention can be sourced from liquid bovine colostrum or bovine colostrum powder. Unless otherwise specified, the mass ratio or weight parts of bovine colostrum to lactoferrin described in the present invention are based on dry matter.

[0012] The modified milk powder of the present invention has the effect of protecting bones and / or improving bone health. According to a specific embodiment of the present invention, the lactoferrin in the modified milk powder is present in a low dose. The inventors' research has found that the combination of low doses of lactoferrin and bovine colostrum has an unexpectedly significant synergistic effect on promoting osteoblast proliferation and inhibiting osteoclast proliferation.

[0013] According to a specific embodiment of the present invention, the lactoferrin in the modified milk powder of the present invention can be added at an application rate of 2-200 mg / day. Preferably, the application rate of lactoferrin is 2-95 mg / day, and more preferably less than 95 mg / day. According to a further preferred embodiment of the present invention, the dosage of lactoferrin is 2-90 mg / day, more preferably 2-85 mg / day, more preferably 3-90 mg / day, more preferably 3-80 mg / day, more preferably 3-75 mg / day, more preferably 3-70 mg / day, more preferably 3-65 mg / day, more preferably 3-60 mg / day, more preferably 3-55 mg / day, more preferably 3-50 mg / day, more preferably 3-45 mg / day, more preferably 3-40 mg / day, more preferably 3-35 mg / day, more preferably 3-30 mg / day, more preferably 3-25 mg / day, more preferably 3-20 mg / day, more preferably 3-15 mg / day, more preferably 3-10 mg / day. According to a further preferred embodiment of the present invention, the dosage of lactoferrin is at least 4 mg / day, for example, it can be 4~90 mg / day, 4~85 mg / day, 4~80 mg / day, 4~75 mg / day, 4~70 mg / day, 4~65 mg / day, 4~60 mg / day, 4~55 mg / day, 4~50 mg / day, 4~45 mg / day, 4~40 mg / day, 4~35 mg / day, 4~30 mg / day, 4~25 mg / day, 4~20 mg / day, or 4~15 mg / day. According to a further preferred embodiment of the present invention, the dosage of lactoferrin is at least 5 mg / day, for example, it can be 5-90 mg / day, 5-85 mg / day, 5-80 mg / day, 5-75 mg / day, 5-70 mg / day, 5-65 mg / day, 5-60 mg / day, 5-55 mg / day, 5-50 mg / day, 5-45 mg / day, 5-40 mg / day, 5-35 mg / day, 5-30 mg / day, 5-25 mg / day, 5-20 mg / day, or 5-15 mg / day. In some specific embodiments of the present invention, the dosage of lactoferrin is about 4-10 mg / day, for example, about 4 mg / day, about 5 mg / day, about 6 mg / day, about 7 mg / day, about 8 mg / day, about 9 mg / day, or about 10 mg / day.

[0014] According to some specific embodiments of the present invention, in the modified milk powder of the present invention, the content of lactoferrin in the modified milk powder is 2-190 mg / 100g. According to some specific embodiments of the present invention, in the modified milk powder of the present invention, the content of lactoferrin in the modified milk powder is 2-189 mg / 100g. According to some specific embodiments of the present invention, in the modified milk powder of the present invention, the content of lactoferrin in the modified milk powder is 2-180 mg / 100g. According to some specific embodiments of the present invention, in the modified milk powder of the present invention, the content of lactoferrin in the modified milk powder is 3-160 mg / 100g. According to some specific embodiments of the present invention, in the modified milk powder of the present invention, the content of lactoferrin in the modified milk powder is 3-140 mg / 100g. According to some specific embodiments of the present invention, in the modified milk powder of the present invention, the content of lactoferrin in the modified milk powder is 3-120 mg / 100g. According to some specific embodiments of the present invention, in the modified milk powder of the present invention, the content of lactoferrin in the modified milk powder is 3-100 mg / 100g. According to some specific embodiments of the present invention, in the modified milk powder of the present invention, the content of lactoferrin in the modified milk powder is 3-80 mg / 100g. According to some specific embodiments of the present invention, in the modified milk powder of the present invention, the content of lactoferrin in the modified milk powder is 3-60 mg / 100g. According to some specific embodiments of the present invention, in the modified milk powder of the present invention, the content of lactoferrin in the modified milk powder is 5-40 mg / 100g. According to some specific embodiments of the present invention, in the modified milk powder of the present invention, the content of lactoferrin in the modified milk powder is 8-20 mg / 100g.

[0015] According to some specific embodiments of the present invention, in the modified milk powder of the present invention, the mass ratio of bovine colostrum to lactoferrin is (5~95):1. Preferably, the mass ratio of bovine colostrum to lactoferrin in the modified milk powder is (5~90):1, more preferably (5~85):1, even more preferably (5~80):1, and even more preferably (5~75):1. In some more specific embodiments of the present invention, the mass ratio of bovine colostrum to lactoferrin in the modified milk powder is (5~10):1. In some more specific embodiments of the present invention, the mass ratio of bovine colostrum to lactoferrin in the modified milk powder is (10~15):1. In some more specific embodiments of the present invention, the mass ratio of bovine colostrum to lactoferrin in the modified milk powder is (15~70):1. According to some more specific embodiments of the present invention, in the modified milk powder of the present invention, the mass ratio of bovine colostrum to lactoferrin is about 99:1, about 70:1, about 49:1, about 32:1, about 10:1, or about 5:1.

[0016] According to a specific embodiment of the present invention, the amount of bovine colostrum in the modified milk powder of the present invention can be determined with reference to the aforementioned mass ratio of bovine colostrum to lactoferrin.

[0017] In some specific embodiments of the present invention, the modified milk powder of the present invention contains, based on dry matter content, 0.01g~12g / 100g of bovine colostrum, more preferably 0.02g~11g / 100g, more preferably 0.03g~10g / 100g, more preferably 0.04g~9g / 100g, more preferably 0.05g~8g / 100g, more preferably 0.06g~7g / 100g, more preferably 0.07g~6g / 100g, more preferably 0.08g~5g / 100g, more preferably 0.09g~4g / 100g, more preferably 0.1g~3g / 100g, and more preferably 0.11g~2g / 100g. More preferably, the concentration is 0.12g~1.8g / 100g, more preferably 0.13g~1.6g / 100g, more preferably 0.14g~1.4g / 100g, more preferably 0.15g~1.2g / 100g, more preferably 0.16g~1.0g / 100g, more preferably 0.16g~0.9g / 100g, more preferably 0.16g~0.8g / 100g, more preferably 0.16g~0.7g / 100g, more preferably 0.16g~0.6g / 100g, more preferably 0.16g~0.5g / 100g, and more preferably 0.16g~0.4g / 100g. In some preferred embodiments of the present invention, the amount of bovine colostrum in the aforementioned modified milk powder is at least 0.1g / 100g, at least 0.12g / 100g, at least 0.12g / 100g, at least 0.14g / 100g, at least 0.16g / 100g, at least 0.18g / 100g, at least 0.2g / 100g, at least 0.25g / 100g, at least 0.30g / 100g, or at least 0.32g / 100g, based on dry matter content.

[0018] It should be noted that although the lactoferrin and / or bovine colostrum in the modified milk powder of the present invention can make the modified milk powder have significant effects in protecting bones and promoting bone health with a low application dose (below the dose generally considered to be effective in the prior art), the present invention does not limit the modified milk powder to contain a high amount of lactoferrin and / or bovine colostrum.

[0019] According to some specific embodiments of the present invention, the raw materials providing protein in the modified milk powder of the present invention include one or more of the following: raw cow or sheep milk, whole milk powder, skim milk powder, whey powder, and whey protein powder.

[0020] According to some specific embodiments of the present invention, the raw materials providing fat in the modified milk powder of the present invention include one or more of the following: raw cow or sheep milk, whole milk powder, soybean oil, corn oil, light cream, anhydrous butter, and phospholipids.

[0021] According to some specific embodiments of the present invention, the raw materials (calcium sources) providing calcium in the modified milk powder of the present invention include one or more of the following: calcium carbonate, calcium β-hydroxy-β-methylbutyrate (CaHMB), calcium gluconate, calcium citrate, calcium lactate, calcium hydrogen phosphate, calcium L-threonine, calcium glycine, calcium aspartate, calcium citrate malate, calcium acetate, calcium chloride, tricalcium phosphate, calcium vitamin E succinate, calcium glycerophosphate, calcium oxide, calcium sulfate, calcium dihydrogen phosphate, milk mineral salts, casein calcium, calcium malate, and calcium ascorbate.

[0022] According to a specific embodiment of the present invention, the modified milk powder of the present invention may further include conventional ingredients in the art.

[0023] According to some specific embodiments of the present invention, the modified milk powder of the present invention, based on 1000 parts by weight, comprises the following raw materials: 1900-4200 parts by weight of raw milk, 0-400 parts by weight of demineralized whey powder, 0-400 parts by weight of skim milk powder, 0-300 parts by weight of whole milk powder, 0-150 parts by weight of white sugar, 0-5 parts by weight of milk mineral salts, 0-5 parts by weight of anhydrous butter, 0-10 parts by weight of phospholipids, 0.5-10 parts by weight of compound vitamins, 0.1-8 parts by weight of compound minerals, 6-21 parts by weight of calcium source (calculated as calcium); 1-31 parts by weight of bovine colostrum (based on dry matter); and 0.05-5 parts by weight of lactoferrin raw material.

[0024] According to some specific embodiments of the present invention, the compound vitamins in the formulated milk powder of the present invention include one or more of vitamin A, vitamin D3, vitamin B1, vitamin B2, vitamin B6, vitamin E, vitamin K, vitamin C, folic acid, and lutein. The specific amount of compound vitamins can be determined with reference to conventional formulations in the relevant field.

[0025] According to some specific embodiments of the present invention, in the formulated milk powder of the present invention, the compound minerals include one or more of ferrous sulfate, zinc sulfate, magnesium sulfate, sodium selenite, and selenium-enriched yeast. The specific amount of compound minerals can be determined with reference to conventional formulations in the relevant field.

[0026] According to some specific embodiments of the present invention, the formulated milk powder of the present invention further comprises one or more of the following raw materials: galactooligosaccharides, fructooligosaccharides, isomaltooligosaccharides, inulin, polydextrose, colostrum basic protein powder, resistant dextrin, solid corn syrup, maltodextrin, probiotics, hydrolyzed egg yolk powder, wolfberry powder, polygonatum powder, eucommia leaf powder, and kudzu root powder. The specific amounts of these substances can be determined with reference to conventional formulations in the relevant art.

[0027] On the other hand, the present invention also provides a method for preparing the aforementioned modified milk powder, the method comprising: Prepare the raw materials for making milk powder, wherein the mass ratio of bovine colostrum to lactoferrin in the raw materials is adjusted to (5~100):1, and the content of lactoferrin in the made milk powder is 2~400mg / 100g; The modified milk powder is prepared by mixing, homogenizing, sterilizing, concentrating, spray drying, and dry mixing of various raw materials. Among them, bovine colostrum and lactoferrin in the raw materials are added during the dry mixing process, and the dry mixing temperature is not higher than 60℃.

[0028] According to some specific embodiments of the present invention, in the preparation method of the modified milk powder of the present invention, the mixing temperature of the ingredient preparation process is 40-60℃, the mixing time is 25-60 min, and the mass concentration of the liquid obtained by ingredient preparation is 10%~30%.

[0029] According to some specific embodiments of the present invention, in the method for preparing the modified milk powder of the present invention, the pressure of the homogenization process is 25-160 MPa, and the homogenization temperature is 50-60℃.

[0030] According to some specific embodiments of the present invention, in the preparation method of the modified milk powder of the present invention, the temperature of the sterilization process is 90-100℃ and the sterilization time is 10-25s.

[0031] According to some specific embodiments of the present invention, in the method for preparing the modified milk powder of the present invention, the temperature of the concentration process is 47-55°C.

[0032] According to some specific embodiments of the present invention, in the preparation method of the modified milk powder of the present invention, during the spray drying process, the inlet air temperature is controlled at 160-230°C and the outlet air temperature is controlled at 75-95°C.

[0033] On the other hand, the present invention also provides the use of the modified milk powder in the preparation of products for protecting bones and / or improving bone health. Specifically, the protection of bones and / or improvement of bone health includes one or more of the following efficacy applications: promoting osteoblast proliferation; increasing osteoblast ALP activity; increasing the expression of osteoblast differentiation genes OCN, OPN, OSX and / or Runx2; inhibiting osteoclast proliferation; inhibiting the expression of osteoclast differentiation genes Atp6v0d2, Cathepsin K, Mmp9 and / or Nfatc1; increasing bone mineral density; increasing the number of trabeculae; enhancing bone biomechanical properties; enhancing bone strength and stiffness; and / or increasing the expression level of serum bone turnover markers. The serum bone turnover marker is preferably type I procollagen carboxy-terminal peptide (PICP).

[0034] The modified milk powder of the present invention can be made to suit people of all ages, especially middle-aged and elderly people.

[0035] On the other hand, the present invention also provides a method for protecting bones and / or improving bone health, the method comprising administering to a subject an effective amount of the modified milk powder of the present invention or a product containing said modified milk powder. Specifically, the protection of bones and / or improvement of bone health includes one or more of the following efficacy applications: promoting osteoblast proliferation; increasing osteoblast ALP activity; increasing the expression of osteoblast differentiation genes OCN, OPN, OSX and / or Runx2; inhibiting osteoclast proliferation; inhibiting the expression of osteoclast differentiation genes Atp6v0d2, Cathepsin K, Mmp9 and / or Nfatc1; increasing bone mineral density (contributing to improved bone density); increasing the number of trabeculae; enhancing bone biomechanical properties; enhancing bone strength and stiffness; and / or increasing the expression level of serum bone turnover markers. The serum bone turnover markers preferably include type I procollagen carboxy-terminal peptide (PICP).

[0036] Overall, this invention prepares a modified milk powder by mixing bovine colostrum and lactoferrin in a certain proportion. This modified milk powder can promote osteoblast proliferation at a relatively low dose, increase osteoblast ALP activity, enhance the expression of osteoblast differentiation genes OCN, OPN, OSX, and / or Runx2, inhibit osteoclast proliferation, and suppress the expression of osteoclast differentiation genes Atp6v0d2, Cathepsin K, Mmp9, and / or Nfatc1. It can increase bone mineral density, increase the number of trabeculae, improve bone biomechanical properties, enhance bone strength and stiffness, and increase the expression levels of serum bone turnover markers. The modified milk powder containing bovine colostrum and lactoferrin of this invention has the effect of protecting bones and / or improving bone health, and helps improve bone mineral density. Attached Figure Description

[0037] Figure 1This is a graph showing the comparison of the effects of each test substance on osteoblast proliferation in Test Example 1.

[0038] Figure 2 This is a graph showing the comparison of the effects of each test substance on osteoblast ALP activity in test example 2.

[0039] Figures 3 to 6 The figures show the comparison of the effects of each test substance on the expression of osteoblast differentiation genes OCN, OPN, OSX, and Runx2 in test example 3.

[0040] Figure 7 This is a graph showing the comparison of the effects of each test substance on osteoclast proliferation in Test Example 4.

[0041] Figure 8 Fluorescence microscopy images showing the effects of each test substance on osteoclast differentiation in Test Example 5.

[0042] Figures 9 to 12 The figures show the comparison of the effects of each test substance on the expression of osteoclast differentiation genes Atp6v0d2, CathepsinK, Mmp9, and Nfatc1 in Test Example 6.

[0043] Figure 13 This is a comparison of the effects of each test substance on bone density in OVX mice in Test Example 7.

[0044] Figure 14 and Figure 15 This is a comparison of the microstructure of the trabecular bone of OVX mice by each test substance in Test Example 7.

[0045] Figure 16 and Figure 17 Figure 8 shows the comparison of the effects of each test substance on the biomechanical properties of OVX mice.

[0046] Figure 18 This is a graph showing the comparison of the effects of each test substance on bone turnover markers in OVX mice in Test Example 9. Detailed Implementation

[0047] To better understand the above-mentioned objectives, features, and advantages of the present invention, the solutions of the present invention will be further described below. It should be noted that, unless otherwise specified, the embodiments of the present invention and the features thereof can be combined with each other.

[0048] Before further describing specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terminology used in the embodiments of the present invention is for describing specific embodiments and not for limiting the scope of protection of the present invention.

[0049] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the present invention, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art. In addition to the specific methods, apparatus, and materials used in the embodiments, based on the knowledge of the prior art possessed by one of ordinary skill in the art and the description of this invention, any prior art methods, apparatus, and materials similar to or equivalent to those described, apparatus, and materials in the embodiments of this invention may be used to implement the present invention.

[0050] Unless otherwise stated, the experimental methods, detection methods and preparation methods disclosed in this invention all adopt conventional techniques in this technical field.

[0051] In this embodiment, the bovine colostrum raw material used is commercially available pure bovine colostrum powder, and the lactoferrin raw material used is commercially available pure lactoferrin powder.

[0052] The materials and reagents used in the examples include: α-MEM medium (HyClone), DMEM medium (gibco), trypsin (feimobio), fetal bovine serum (Sijiqing), penicillin-streptomycin mixture (feimobio), MTT thiazolyl blue (solarbio), DMSO (Macklin), alkaline phosphatase assay kit (Beyotime), reverse transcription kit (abm), qPCR mix SYBR (Thermo), tartrate-resistant acid phosphatase kit (Amizona Scientific), Cathepsin K antibody (abcam), Nfatc1 antibody (abcam), and β-actin antibody (proteintech).

[0053] Example 1: Preparation of milk powder

[0054] The raw materials for the modified milk powder in this embodiment include: 1900 kg of raw milk, 500 kg of skim milk powder, 150 kg of demineralized whey powder D90, 71 kg of polydextrose, 37 kg of galactooligosaccharides, 1.55 kg of colostrum basic protein powder, 16 kg of calcium carbonate, 3 kg of milk mineral salts, 2 kg of phospholipids, 2.5 kg of compound vitamins (including vitamin D3, vitamin A, vitamin E, vitamin C, vitamin B6, and vitamin C), 6 kg of compound minerals (including ferrous sulfate, zinc sulfate, and magnesium sulfate), 0.5 kg of lactoferrin, and 5 kg of bovine colostrum powder.

[0055] The main nutritional components of the modified milk powder in this embodiment are as follows: protein content 23.5%, fat content 9.0%, calcium 1.5%, and the mass ratio of bovine colostrum (on a dry matter basis) to lactoferrin is 10:1.

[0056] The production method of the modified milk powder in this embodiment is as follows: 1) Add raw milk, skim milk powder, demineralized whey powder D90, polydextrose, galactooligosaccharides, colostrum basic protein powder, calcium carbonate, milk mineral salts, phospholipids, compound vitamins, and compound minerals into the mixing system, add water, and mix at high speed. The mixing temperature is 50℃, the mixing time is 40 minutes, and the mass concentration of the liquid is 19.6%.

[0057] 2) After the mixed liquid is preheated to 60°C, it is homogenized at a homogenization pressure of 150 MPa.

[0058] 3) Quickly cool the homogenized liquid to below 6°C and pump it into a temporary storage tank.

[0059] 4) Pasteurize the liquid at a temperature of 91℃ for 15 seconds.

[0060] 5) The sterilized liquid is concentrated at a concentration temperature of 47-55℃, and the dry matter content of the concentrated liquid is 49%.

[0061] 6) The concentrated liquid is spray-dried at an inlet air temperature of 190℃ and an outlet air temperature of 88℃. Then it is cooled to below 35℃ through a fluidized bed to obtain the base powder.

[0062] 7) Dry mix the base powder with lactoferrin and bovine colostrum powder for 2 minutes to obtain a uniform and consistent modified milk powder.

[0063] Example 2: Preparation of milk powder

[0064] The raw materials for the modified milk powder in this embodiment include: 3700 kg of raw milk, 280 kg of skim milk powder, 260 kg of solid corn syrup, 0.5 kg of milk mineral salts, 2 kg of phospholipids, 1.2 kg of wolfberry powder, 0.22 kg of bifidobacteria, 0.4 kg of lactoferrin, 10 kg of bovine colostrum powder, 2.5 kg of compound vitamins (including vitamin A, vitamin D, vitamin E, vitamin C, and vitamin B6), 1 kg of compound minerals (including ferrous sulfate and zinc sulfate), and 16 kg of calcium carbonate.

[0065] The main nutritional components of the modified milk powder in this embodiment are as follows: protein content 20.5%, fat content 14.0%, calcium content 1.36%, and the mass ratio of bovine colostrum (on a dry matter basis) to lactoferrin is 25:1.

[0066] The production method of the modified milk powder in this embodiment is as follows: 1) Add raw milk, skim milk powder, solid corn syrup, milk mineral salts, phospholipids, calcium carbonate, compound vitamins, and compound minerals into the mixing system, add water, and mix at high speed. The mixing temperature is 55℃, the mixing time is 50 minutes, and the mass concentration of the liquid is 17.6%.

[0067] 2) After the mixed liquid is preheated to 55°C, it is homogenized at a homogenization pressure of 140 MPa.

[0068] 3) Quickly cool the homogenized liquid to below 6°C and pump it into a temporary storage tank.

[0069] 4) Pasteurize the liquid at a temperature of 95°C for 20 seconds.

[0070] 5) The sterilized liquid is concentrated at a concentration temperature of 47-55℃, and the dry matter content of the concentrated liquid is 48%.

[0071] 6) The concentrated liquid is spray-dried at an inlet air temperature of 192°C and an outlet air temperature of 76°C. Then it is cooled to below 35°C through a fluidized bed to obtain the base powder.

[0072] 7) Dry mix the base powder with lactoferrin, bovine colostrum powder, wolfberry powder, and bifidobacteria for 2 minutes to obtain a uniform and consistent modified milk powder.

[0073] Example 3: Preparation of milk powder

[0074] The raw materials for the modified milk powder in this embodiment include: 3500 kg of raw goat milk, 350 kg of skim milk powder, 200 kg of demineralized whey powder D90, 2 kg of phospholipids, 0.45 kg of Eucommia ulmoides leaf powder, 0.25 kg of Bifidobacterium, 0.3 kg of lactoferrin, 21 kg of bovine colostrum powder, 1.5 kg of compound vitamins (including vitamin A, vitamin D, vitamin E, and vitamin C), 1 kg of compound minerals (including ferrous sulfate and zinc sulfate), 6 kg of calcium carbonate, and 20 kg of calcium β-hydroxy-β-methylbutyrate (CaHMB).

[0075] The main nutritional components of the modified milk powder in this embodiment are as follows: protein content 21.5%, fat content 13.5%, calcium content 1.6%, and the mass ratio of bovine colostrum (on a dry matter basis) to lactoferrin is 70:1.

[0076] The production method of the modified milk powder in this embodiment is as follows: 1) Add raw sheep milk, skimmed milk powder, demineralized whey powder, phospholipids, calcium carbonate, compound vitamins, compound minerals, and calcium β-hydroxy-β-methylbutyrate (CaHMB) into the mixing system, add water, and mix at high speed. The mixing temperature is 52℃, the mixing time is 30 minutes, and the mass concentration of the liquid is 18%.

[0077] 2) After the mixed liquid is preheated to 50°C, it is homogenized at a homogenization pressure of 75 MPa.

[0078] 3) Quickly cool the homogenized liquid to below 6°C and pump it into a temporary storage tank.

[0079] 4) Pasteurize the liquid at a temperature of 90℃ for 25 seconds.

[0080] 5) The sterilized liquid is concentrated at a concentration temperature of 47-55℃, and the dry matter content of the concentrated liquid is 48%.

[0081] 6) The concentrated liquid is spray-dried at an inlet air temperature of 210℃ and an outlet air temperature of 90℃. Then it is cooled to below 35℃ in a fluidized bed to obtain the base powder.

[0082] 7) Dry mix the base powder with lactoferrin, bovine colostrum powder, bifidobacteria, and eucommia leaf powder for 2 minutes to obtain a uniform and consistent modified milk powder.

[0083] Example 4: Experiment on the bone-strengthening effects of bovine colostrum and lactoferrin in modified milk powder

[0084] This embodiment provides three compound compositions of bovine colostrum and lactoferrin in different proportions: BL1, BL2, and BL3, each composed of bovine colostrum powder and lactoferrin powder in different proportions. Specifically, based on the total mass of the compositions (100%), composition BL1 contains 1% lactoferrin (BC:LF = 99:1), composition BL2 contains 2% lactoferrin (BC:LF = 49:1), and composition BL3 contains 3% lactoferrin (BC:LF = 32.3:1).

[0085] This embodiment demonstrates the bone-strengthening effects of the bovine colostrum and lactoferrin composition of the present invention through test examples.

[0086] The details of the test substances in each test case are shown in Table 1.

[0087] Table 1. Test Substances in Each Group

[0088] Test Example 1: MTT assay to detect the effect of the compound composition on osteoblast proliferation

[0089] Thiazol blue, abbreviated as MTT, is a chemical compound. Succinate dehydrogenase in cellular mitochondria can reduce exogenous MTT to water-insoluble blue-violet formazan crystals, which then deposit within the cell. Dead cells lack this ability. Dimethyl sulfoxide (DMSO) can dissolve the formazan in cells, and its absorbance at 570 nm using an enzyme-linked immunosorbent assay (ELISA) can indirectly reflect the number of viable cells. Within a certain cell count range, the amount of MTT crystals formed is directly proportional to the cell count. In this test example, to compare the effects of different ratios of bovine colostrum and lactoferrin compound combinations on osteoblast proliferation, an MTT assay was used to detect cell proliferation rate.

[0090] The specific method is as follows: Adjust the MC3T3-E1 cell concentration to 10 per well. 3 -10 4 Cells were seeded into 96-well plates at a volume of 200 μL per well. Bovine colostrum (BC), lactoferrin (LF), and different proportions of compound preparations (BL1, BL2, and BL3) were then added. The concentrations of each test substance in the culture system are shown in Table 1. The plates were placed in a CO2 incubator at 37°C. After 44 hours of incubation, the culture medium was aspirated, a certain amount of MTT buffer was added, and the plates were returned to the incubator. After 4 hours of incubation, the MTT buffer was aspirated, and DMSO was added to dissolve the generated methyltetrazole salt. The absorbance values ​​were measured and recorded to detect osteoblast proliferation.

[0091] like Figure 1 As shown, by measuring the osteoblast proliferation capacity, it was found that the combination of bovine colostrum and lactoferrin promotes osteoblast proliferation. As the proportion of LF in the composition increases, the cell proliferation rate increases, reaching a maximum at an LF concentration of 3%.

[0092] Test Example 2: Effect of ALP Detection on Osteoblast Differentiation of Compound Composition

[0093] Osteoblasts synthesize and secrete organic matrix to form osteoid, primarily composed of type I collagen. A key characteristic is alkaline phosphatase (ALP), an early marker of osteoblast differentiation and maturation. ALP activity reflects the bone-forming capacity of osteoblasts. To investigate the effect of different ratios of bovine colostrum and lactoferrin blends on osteoblast differentiation capacity, ALP-stained cells were used to assess osteoblast differentiation levels.

[0094] The specific method is as follows: MC3T3-E1 cells were used at a rate of 2×10⁻⁶. 4 cell / cm 2Cells were seeded at a density of 90% in 24-well cell culture plates and cultured normally for 2 days until 90% confluence. The differentiation medium was then changed, and the medium was changed every other day for 4 consecutive days (i.e., day 7 after inoculation). The culture was then changed to serum-free medium and incubated overnight. Bovine colostrum (BC), lactoferrin (LF), and different proportions of compound combinations (BL1, BL2, BL3) were then added and cultured for 24 hours. A blank control group was included, receiving no treatment. The original medium was removed, and the cells were washed three times with 4% pre-chilled PBS. Cell lysis buffer was added on ice, and cells were scraped off using a cell scraper. Cells were dispersed by repeated pipetting, sonicated for 1 min, and centrifuged at 12000 rpm at 4℃ for 10 min. The supernatant was collected, and protein concentration was measured. The activity of ALP in the pre-test samples was measured using the Roche alkaline phosphatase diagnostic kit, and the results were corrected for protein concentration to obtain the relative ALP activity. Using the blank control as a reference, the fold increase of each group relative to the blank control was calculated to obtain the alkaline phosphatase activity.

[0095] like Figure 2 As shown, the determination of ALP activity revealed that bovine colostrum and lactoferrin promote osteoblast differentiation, and ALP activity increased with increasing LF content in the composition. The composition contained 1% lactoferrin, resulting in the lowest ALP activity. The composition contained 3% lactoferrin, achieving the maximum ALP activity.

[0096] Test Example 3: RT-qPCR detection of the effect of the compound composition on osteoblast differentiation

[0097] OCN is a late-stage marker gene for osteoblast differentiation, primarily expressed in the bone matrix. It plays a crucial role in bone mineralization and calcium homeostasis, promoting bone matrix mineralization and bone mechanical strength. OCN is also considered an important indicator of bone formation. OPN is a mid-to-late-stage marker gene for osteoblast differentiation. It plays a role in bone matrix synthesis and bone mineralization, contributing to the deposition and crystallization of mineralized substances, thereby enhancing bone hardness and stability. Furthermore, OPN plays an important role in signal transduction and regulation between osteocytes. OSX is a mid-stage marker gene for osteoblast differentiation. Following Runx2, it further promotes the differentiation of pre-osteoblasts into osteoblasts. OSX plays a vital role in bone matrix synthesis and trabecular bone formation, helping to maintain the structure and mechanical function of bone tissue. Runx2 is an early-stage marker gene for osteoblast differentiation, playing a crucial role in osteoblast precursor cells. Runx2 promotes the differentiation of stem cells into pre-osteoblasts and is a key regulator of bone matrix synthesis and bone mineralization. It participates in regulating the expression of other differentiation marker genes, driving osteoblast differentiation.

[0098] This study used osteoblast precursor cells for culture and differentiation experiments. To compare the cell differentiation levels of osteoblasts after treatment with different proportions of compound compositions, the expression levels of four genes, OCN, OPN, OSX, and Runx2, were analyzed using qPCR technology.

[0099] Cells from each group were collected, RNA was extracted using the Trizol method, and cDNA was synthesized using a reverse transcription kit. Amplification was performed using the SYBR PremixEx Taq™ kit, following the kit instructions. Ct values ​​were obtained after the reaction, with GADPH as an internal control. A 2... -ΔΔCt The relative expression levels of osteoblast differentiation genes were analyzed using a method. Primer sequences are shown in Table 2.

[0100] Table 2. Primer sequences used in quantitative real-time PCR

[0101] like Figures 3-6 As shown, the expression levels of osteoblast differentiation genes OCN, OPN, OSX, and Runx2 mRNA were measured. The results showed that the compound composition shown in Example 1 promoted osteoblast differentiation. In the experimental group containing 3% lactoferrin, the transcriptional levels of differentiation genes were significantly upregulated compared to the control group.

[0102] Test Example 4: MTT assay to detect the effect of the compound composition on osteoclast proliferation

[0103] To detect and compare the cell proliferation rate of osteoclasts after treatment with different proportions of compound combinations, this test case used the MTT cell proliferation assay to assess the impact on cell survival and proliferation.

[0104] The specific method is as follows: Stably grown RAW264.7 cells are introduced into each well at a density of 5 × 10⁶ cells / well. 3 Cells were seeded at a density in 96-well plates and incubated overnight at 37 °C with 5% CO2. Bovine colostrum (BC), lactoferrin (LF), and different ratios of compound preparations (BL1, BL2, BL3) were added separately and incubated for 44 hours in DMEM medium containing 50 ng / mL RANKL. The culture medium was then aspirated, and a certain amount of MTT buffer was added. The plates were then returned to the incubator. After 4 hours of incubation, the MTT buffer was aspirated, and DMSO was added to dissolve the generated methyltetrazole salt. Absorbance values ​​were measured and recorded to detect osteoclast proliferation.

[0105] like Figure 7As shown, the effects of each protein group on osteoclast proliferation were detected using the MTT assay. The results showed that the composition had an inhibitory effect on osteoclast proliferation, with the experimental group containing 3% lactoferrin showing the most significant inhibitory effect, but there was no significant difference compared with the control group.

[0106] Test Example 5: TRAP assay to detect the effect of the compound composition on osteoclast differentiation

[0107] TRAP staining is based on the acid phosphatase contained in osteoclasts, an enzyme that is highly active in acidic environments. TRAP staining is a staining technique commonly used to study the presence and activity of osteoclasts in bone tissue. The number and distribution of osteoclasts are determined by observing purple-red or brown TRAP-positive cells.

[0108] The specific method was as follows: Bovine colostrum (BC), lactoferrin (LF), and different proportions of compound compositions (BL1, BL2, BL3) were used to treat RAW264.7 cells that were about to stabilize after induced differentiation. The cells were grown at a density of 10 cells per well. 4 Cells were seeded at a density in 24-well plates and incubated overnight. 50 ng / mL RANKL was added to each well of both the experimental and positive control groups to induce osteoclast differentiation. The experimental groups were cultured in the same medium containing bovine colostrum (BC), lactoferrin (LF), and different proportions of compound preparations (BL1, BL2, BL3), with the medium changed every 2 days. Around day 5, osteoclasts in the positive control group matured. Cells in each group were fixed with paraformaldehyde for 20 min, and then incubated at 37°C for 45 min with 50 μL of tartrate-resistant acid phosphatase staining solution in each well. Images were then taken using an inverted fluorescence microscope. The following experimental results were obtained.

[0109] like Figure 8 As shown, TRAP staining of osteoclasts reduced the number of multinucleated osteoclasts in the experimental group, indicating that the combination of bovine colostrum and lactoferrin inhibits osteoclast formation.

[0110] Test Example 6: RT-qPCR Detection of the Effect of the Compound on Osteoclast Differentiation

[0111] Atp6v0d2: The protein encoded by Atp6v0d2 is a subunit of the H+ transporter complex, involved in maintaining an acidic environment, which plays an important role in the early stages of osteoclast differentiation. An acidic environment facilitates the release of acidic proteases and acid phosphatases by osteoclasts, thereby enabling the absorption and degradation of the bone matrix.

[0112] Cathepsin K: Cathepsin K encodes an enzyme that is primarily found in osteoclasts and has the ability to degrade bone matrix proteins. It is highly expressed during the mid-to-late stages of osteoclast differentiation and plays a crucial role in bone matrix degradation and remodeling.

[0113] Mmp9: The protein encoded by Mmp9 is a matrix metalloproteinase involved in the degradation of bone matrix and osteoclast activity. It is upregulated in the mid-to-late stages of osteoclast differentiation and is associated with bone matrix remodeling and mineralization regulation.

[0114] Nfatc1: Nfatc1 is a key transcription factor in osteoclast differentiation, and it is regulated in the early stages of stem cell differentiation into osteoclasts. Nfatc1 promotes osteoclast differentiation and regulates the expression of osteoclast-related genes, including acid phosphatase.

[0115] The specific method used in this test case was as follows: cells from each group were collected, RNA was extracted using the Trizol method, and cDNA was synthesized using a reverse transcription kit. The cDNA was then expanded using the SYBR Premix Ex Taq™ kit according to the kit instructions. After the reaction, Ct values ​​were obtained, and the relative expression levels of osteoblast differentiation genes were analyzed using the 2-ΔΔCt method, with GADPH as an internal control. Primer sequences are shown in Table 3.

[0116] Table 3. Primer sequences used in quantitative real-time PCR

[0117] like Figures 9-12 As shown, the expression levels of osteoclast differentiation genes Cathepsin, Mmp9, Atp6v0d2, and Nfatc1 mRNA were measured. The results indicated that the combination of bovine colostrum and lactoferrin inhibited osteoclast differentiation. In the experimental group containing the 2% lactoferrin composition, the transcriptional level of differentiation genes was most significantly downregulated compared to the control group.

[0118] Test Example 7: Animal Experiment on the Bone-Promoting Effect of a Combination of Bovine Colostrum and Lactoferrin

[0119] 1. Experimental Design and Methods

[0120] 1.1 Construction and Sample Preparation of Osteoporosis (OVX) Mouse Model

[0121] Female C57BL / 6J mice (8 weeks old, weighing approximately 20g) were selected. All animals were randomly divided into four groups: model group, bovine colostrum powder (BC) group, lactoferrin (LF) group, and combined group (BLL). Mice were housed in a standard environment for one week, with a constant temperature of 20℃, humidity of 48%, and a 12-hour light-dark cycle, and their condition was closely monitored. After weighing, the mice were anesthetized by intraperitoneal injection of 4% chloral hydrate. After skin preparation, the mice were fixed in a lateral recumbent position, exposing the skin above the thigh on the back. After disinfection with iodine and alcohol, a longitudinal incision of approximately 0.5cm was made one finger-width below the ribs and one finger-width lateral to the midline of the back. After separating the subcutaneous tissue and muscle, a milky white fat mass was visible. The ovary was located along the fat mass, gently lifted with forceps, the fallopian tube was ligated, and the ovary was removed. The muscle and skin were sutured separately. The other ovary was removed using the same method. The ovary was not removed in the sham surgery group. Postoperatively, antibiotics were administered for 3 days, along with routine nursing care. All animals were administered the drug by gavage according to the experimental grouping and test sample protocol in Table 4 (the test drug dosage in Table 4 has been converted to the adult daily dose), once a day, for a period of 12 weeks, with mouse weight being measured weekly.

[0122] Table 4. Experimental Groups and Subject Samples

[0123] Specimen Acquisition: After 12 weeks, some mice were euthanized under anesthesia, and fresh tibias and femurs were isolated from them. In another group, after normal anesthesia, blood was collected from the heart, which was then perfused with 4% paraformaldehyde for fixation. The rat tibias and femurs were then isolated and immersed in 4% paraformaldehyde solution for another 24 hours, followed by immersion in PBS, and stored at 4°C.

[0124] 1.2 Micro-CT Scanning and Reconstruction

[0125] Micro-CT scanning was performed at a resolution of 14.8 μm, a voltage of 70 kVp, and a current of 200 mA. The scanning area was the distal femoral metaphysis, and the three-dimensional image was reconstructed by the Micro-CT analysis system, while longitudinal and transverse tomographic images were acquired simultaneously.

[0126] Bone mineral density (BMD) is an important indicator for quantifying bone mass in bone mineral metabolism. BMD is significant for predicting fracture risk, early diagnosis of osteoporosis, and evaluation of intervention measures. Figure 13 Bone mineral density (BMD) measurements showed that BC had no significant effect on bone mineral density, but LF and BLL significantly increased bone mineral density compared to the Model group, especially BLL, which significantly increased bone mineral density compared to BC and LF.

[0127] The number of trabecular bone (Tb.N) is the number of intersections between bone and non-bone tissues within a given length. When the skeleton is unhealthy, the value of Tb.N decreases. Figure 14 The results of trabecular bone number determination showed that BC, LF and BLL could significantly increase the BVTV bone volume fraction compared with the Model group, especially BLL, which had a more significant effect than BC and LF.

[0128] When bones are unhealthy, trabeculae are lost, and the BV / TV value decreases. Figure 15 Bone volume fraction results showed that BC, LF, and BLL all significantly increased BV / TV bone volume fraction compared to the Model group, especially BLL, which showed a more significant increase compared to BC and LF.

[0129] 1.3 Measurement of bone biomechanical properties

[0130] Bone biomechanical properties mainly reflect the functional status of the skeleton from multiple perspectives, including load-bearing capacity, degeneration capacity, and strain. To evaluate the macroscopic mechanical properties of bone from a macroscopic perspective, this experiment obtained macroscopic mechanical parameters such as maximum load, stiffness, ultimate load energy, elastic modulus, and fracture energy of bone through a three-point bending test. These parameters are used to quantitatively assess the strength and stiffness of bone, reflecting its ability to resist damage and deformation.

[0131] The maximum load test data for bones in each group are shown in Table 5.

[0132] Table 5. Maximum load on bone (N)

[0133] See the fracture energy and stiffness test results. Figures 16-17 .

[0134] After the onset of osteoporosis, the dynamics of bone formation and resorption are disrupted, leading to a disordered bone metabolism. Abnormal levels of bone metabolism impair bone mineralization, consequently damaging various properties of the bone, including load-bearing capacity and strain resistance, ultimately resulting in a higher risk of fractures. The results of this test case demonstrate that intervention using the bovine colostrum and lactoferrin composition of this invention can reverse the aforementioned damage to bone load-bearing capacity and strain resistance following osteoporosis.

[0135] 1.4 Detection of Bone Turnover Markers

[0136] Osteoblasts and osteoclasts release specific proteins and peptides during bone formation and resorption, known as bone turnover markers (BTMs). By detecting serum BTM levels, we can understand bone tissue metabolism, assess bone metabolic status, predict fracture risk, and evaluate treatment effectiveness.

[0137] In this test case, after completing the 12-week experimental process, blood collection began. Mice were anesthetized, and blood was collected from the heart using a vacuum sputum collection needle. The blood was centrifuged at 3000 rpm for 20 min at room temperature, and the supernatant serum was collected. The serum was aliquoted into 1.5 ml EP tubes and labeled. Serum levels of bone turnover markers in OVX mice were detected by ELISA. The markers detected included the bone formation marker: type I procollagen carboxy-terminal peptide (P1CP). P1CP is a fragment released during the processing of type I procollagen molecules, representing the synthesis of type I collagen. Since type I collagen is a major component of the bone matrix, P1CP levels can reflect bone formation activity.

[0138] See test results Figure 18 This indicates that the bovine colostrum and lactoferrin composition of the present invention can significantly increase the serum level of PICP, a bone formation marker, in individuals with osteoporosis.

[0139] The above description of the embodiments is provided to enable those skilled in the art to understand and use the invention. It will be apparent to those skilled in the art that various modifications can be made to these embodiments, and the general principles described herein can be applied to other embodiments without inventive effort. Therefore, the present invention is not limited to the above embodiments, and any improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the invention should be within the protection scope of the present invention.

Claims

1. A modified milk powder, wherein the modified milk powder has a total protein content of 17-35g / 100g, a fat content of 1-32g / 100g, and a calcium content of 0.8-2.1g / 100g; and wherein the modified milk powder contains bovine colostrum and lactoferrin, wherein the mass ratio of bovine colostrum to lactoferrin is (5-100):1 based on dry matter content, and the content of lactoferrin in the modified milk powder is 2-400mg / 100g.

2. The modified milk powder according to claim 1, wherein, The lactoferrin content in the modified milk powder is 2~190mg / 100g; Preferably, the lactoferrin content in the modified milk powder is 2~189 mg / 100g; Further preferably, the content of lactoferrin in the modified milk powder is 2~180mg / 100g; Further preferably, the content of lactoferrin in the modified milk powder is 3~160mg / 100g; The lactoferrin content in the modified milk powder is further preferably 3~140mg / 100g; Further preferably, the content of lactoferrin in the modified milk powder is 3~120mg / 100g; Further preferably, the content of lactoferrin in the modified milk powder is 3~100mg / 100g; The lactoferrin content in the modified milk powder is further preferably 3~80mg / 100g; The lactoferrin content in the modified milk powder is further preferably 3~60mg / 100g; The lactoferrin content in the modified milk powder is further preferably 5~40mg / 100g; Further preferred is that the content of lactoferrin in the modified milk powder is 8~20mg / 100g.

3. The modified milk powder according to claim 1 or 2, wherein, The mass ratio of bovine colostrum to lactoferrin is (5~95):1; Preferably, the mass ratio of bovine colostrum to lactoferrin in the formulated milk powder is (5~90):1, more preferably (5~85):1, and even more preferably (5~80):

1.

4. The modified milk powder according to any one of claims 1-3, wherein: The raw materials that provide protein include one or more of the following: raw cow's milk, sheep's milk, whole milk powder, skim milk powder, whey powder, and whey protein powder; The raw materials that provide fat include one or more of the following: raw cow's milk, sheep's milk powder, whole milk powder, soybean oil, corn oil, light cream, anhydrous butter, and phospholipids; The raw materials that provide calcium include one or more of the following: calcium carbonate, calcium β-hydroxy-β-methylbutyrate (CaHMB), calcium gluconate, calcium citrate, calcium lactate, calcium hydrogen phosphate, calcium L-threonine, calcium glycine, calcium aspartate, calcium citrate malate, calcium acetate, calcium chloride, tricalcium phosphate, calcium vitamin E succinate, calcium glycerophosphate, calcium oxide, calcium sulfate, calcium dihydrogen phosphate, milk mineral salts, casein calcium, calcium malate, and calcium ascorbate.

5. The modified milk powder according to any one of claims 1-4, based on 1000 parts by weight of the product, comprises the following raw material composition: Raw milk 1900~4200 parts by weight, demineralized whey powder 0~400 parts by weight, skim milk powder 0~400 parts by weight, whole milk powder 0~300 parts by weight, white sugar 0~150 parts by weight, milk mineral salts 0~5 parts by weight, anhydrous butter 0~5 parts by weight, phospholipids 0~10 parts by weight, compound vitamins 0.5~10 parts by weight, compound minerals 0.1~8 parts by weight, calcium source (calculated as calcium) 6~21 parts by weight; bovine colostrum (calculated as dry matter) 1~31 parts by weight; lactoferrin raw material 0.05~5 parts by weight.

6. The modified milk powder according to claim 5, wherein the raw material composition further includes one or more of the following: galactooligosaccharides, fructooligosaccharides, isomaltooligosaccharides, inulin, polydextrose, colostrum basic protein powder, resistant dextrin, solid corn syrup, maltodextrin, probiotics, hydrolyzed egg yolk powder, wolfberry powder, polygonatum powder, eucommia leaf powder, and kudzu root powder.

7. A method for preparing the modified milk powder according to any one of claims 1-6, the method comprising: Prepare the raw materials for making milk powder, wherein the mass ratio of bovine colostrum to lactoferrin in the raw materials is adjusted to (5~100):1, and the content of lactoferrin in the made milk powder is 2~400mg / 100g; The modified milk powder is prepared by mixing, homogenizing, sterilizing, concentrating, spray drying, and dry mixing of various raw materials. Among them, bovine colostrum and lactoferrin in the raw materials are added during the dry mixing process, and the dry mixing temperature is not higher than 60℃.

8. The preparation method according to claim 7, wherein: The mixing temperature during the batching process is 40-60℃, the mixing time is 25-60 min, and the mass concentration of the resulting liquid is 10%~30%. The homogenization process is carried out at a pressure of 25-160 MPa and a homogenization temperature of 50-60℃. The sterilization process takes place at a temperature of 90-100℃ for 10-25 seconds. The concentration process takes place at a temperature of 47-55℃. During the spray drying process, the inlet air temperature is controlled at 160-230℃ and the exhaust air temperature is controlled at 75-95℃.

9. The use of the modified milk powder according to any one of claims 1-6 in the preparation of products for protecting bones and / or improving bone health.

10. The application according to claim 9, wherein, The protection of bones and / or improvement of bone health includes: Promotes osteoblast proliferation; Enhance osteoblast ALP activity; Increase the expression of osteoblast differentiation genes OCN, OPN, OSX and / or Runx2; Inhibit osteoclast proliferation; Inhibit the expression of osteoclast differentiation genes Atp6v0d2, Cathepsin K, Mmp9 and / or Nfatc1; Increase bone density; Increase the number of trabeculae; Enhance bone biomechanical properties; To enhance bone strength and stiffness; and / or Increase the expression level of serum bone turnover markers; preferably, the serum bone turnover marker is type I procollagen carboxyl-terminal peptide (PICP).

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