Medicinal and edible antihypertensive milk powder and preparation method thereof

The preparation of medicinal and food homologous antihypertensive milk powder through dry and wet mixing method and microcapsule technology has solved the lack of research on the compounding of homologous active ingredients of Chinese medicinal and food in dairy products, and achieved the antihypertensive effect and stability improvement with ACE inhibitory activity.

CN120283838APending Publication Date: 2025-07-11NORTHEAST AGRICULTURAL UNIVERSITY
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Patent Information

Application Number
CN202510513002.9
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-04-23
Publication Date
2025-07-11

AI Technical Summary

Technical Problem

There are few studies on the combination of homologous active ingredients of dairy products and medicine and food in the prior art, and there is a lack of formula milk powder with antihypertensive effects and preparation methods.

Method used

Medicinal and food homologous antihypertensive milk powder is prepared by dry and wet mixing method. Raw milk, skim milk powder, desalted whey protein powder, lactose, galactose and other raw materials are used, combined with microcapsule technology to embed the drug peptide mixture, and the microcapsule preparation of the drug peptide mixture is formed by spray drying, and DHA powder, mixed vitamins and minerals are added to prepare milk powder with ACE inhibitory activity.

Benefits of technology

The uniform wrapping of the microcapsules of the drug peptide mixture and high ACE inhibition rate are achieved, the storage period of milk powder is extended, the stability is improved, and the in vitro ACE inhibitory activity and the effect of lowering blood pressure in vivo, reducing blood vessel damage in organs and improving the antioxidant and anti-inflammatory ability of renal endothelial cells.

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Abstract

The invention discloses medicinal and edible antihypertensive milk powder and a preparation method thereof, and relates to the technical field of functional milk powder. Comprising 150 to 300 parts of raw milk, 12 to 20 parts of dried skim milk, 24 parts of demineralized whey protein powder, 2 to 2.3 parts of lactose, 2 parts of galactooligosaccharide, 0.05 to 0.1 part of DHA powder, 0.5 to 0.7 part of mixed vitamins, 4.5 to 5.5 parts of mixed minerals, 0.006 part of nicotinic acid, 0.0004 part of folic acid, 0.2 part of choline and 0.24 to 0.3 part of a drug peptide mixture microcapsule preparation. The medicinal and edible antihypertensive milk powder provided by the invention reduces Ang II and ACE2 contents of heart, kidney and thoracic aorta vascular endothelial cells so as to alleviate organ vascular injury, improve antioxidation and anti-inflammatory capabilities of the organ endothelial cells and achieve the purpose of reducing blood pressure by virtue of multiple ways, such as reducing Ang II and ACE2 contents of the heart, kidney and thoracic aorta vascular endothelial cells.
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Description

Technical Field

[0001] The present invention relates to the technical field of functional milk powder, and more specifically to a medicated and edible homologous antihypertensive milk powder and a preparation method thereof. Background Art

[0002] Hypertension is a major risk factor for global cardiovascular diseases and premature death, but its awareness rate, treatment rate, and control rate are still at a relatively low level, which poses a severe challenge to the prevention, control, and treatment of hypertension and its complications. Since drugs increase the burden on the kidneys when entering the body, there is now a greater tendency to treat hypertension through diet therapy. Scholars have focused their research on the commonly existing medicated and edible homologous Chinese herbal medicines and their nutritional components in life.

[0003] Medicated and edible homologous materials have increasingly attracted the attention of food researchers due to their high safety and good effects. Among them, ginger, wolfberry, and chrysanthemum, as common medicated and edible homologous materials, have various biological activities such as antioxidant and blood pressure lowering effects, and have great application potential in functional foods. Curcumin is a plant polyphenol extracted from ginger and has antioxidant and blood pressure lowering activities. Wolfberry contains more than 20 kinds of amino acids, and its ethanol extract has a strong blood pressure lowering effect, and the dose-effect relationship is significant. More than 40 active compounds have been isolated and identified from chrysanthemum, including iridoids, flavonoids, organic acid esters, sterols, and pigments, which regulate blood pressure by improving endothelial function. Milk is a commonly used nutritional supplement, which contains rich angiotensin-converting enzyme inhibitors. It can not only improve human immunity but also has significant ACE inhibitory activity. This active ingredient has a synergistic and stable blood pressure effect with medicated and edible homologous materials. However, there are few studies on the compounding of dairy products and medicated and edible homologous active ingredients at present.

[0004] Therefore, how to provide a formula milk powder with antihypertensive efficacy and a preparation method thereof is an urgent problem to be solved by those skilled in the art. Summary of the Invention

[0005] In view of this, the present invention provides a medicated and edible homologous antihypertensive milk powder and a preparation method thereof.

[0006] In order to achieve the above object, the present invention adopts the following technical scheme:

[0007] A medicated and edible homologous antihypertensive milk powder is made from the following raw material components by weight:

[0008] 150 - 300 parts of raw cow milk, 12 - 20 parts of skim milk powder, 24 parts of demineralized whey protein powder, 2 - 2.3 parts of lactose, 2 parts of galactooligosaccharides, 0.05 - 0.1 part of DHA powder, 0.5 - 0.7 part of mixed vitamins, 4.5 - 5.5 parts of mixed minerals, 0.006 part of niacin, 0.0004 part of folic acid, 0.2 part of choline, 0.24 - 0.3 part of the microencapsulated preparation of the medicinal peptide mixture;

[0009] The core material of the microencapsulated preparation of the medicinal peptide mixture is a homologous complex of medicine and food and an ACE inhibitory peptide, with a mass ratio of 1:2. The wall material is maltodextrin and β - cyclodextrin, with a mass ratio of 2:1, and the core - wall mass ratio is 1:10.

[0010] Furthermore, the dry matter in the raw cow milk is not less than 12%;

[0011] The whey protein powder is WPC35 whey protein powder;

[0012] The demineralized whey powder is D90 demineralized whey powder;

[0013] The skim milk powder is SMP skim milk powder.

[0014] Furthermore, the mixed vitamins are mixed according to the following components and weight percentages: 0.672% vitamin A, 0.01% vitamin D, 5.356% vitamin E, 92.33% vitamin C, 0.04% vitamin K, 1.29% vitamin B1, 0.15% vitamin B2, 0.15% vitamin B6, 0.002% vitamin B12.

[0015] Furthermore, the mixed minerals are mixed according to the following components and weight percentages: 0.64% ferrous sulfate, 0.29% zinc sulfate, 5.83% magnesium sulfate, 46.63% calcium hydrogen phosphate, 17.48% sodium citrate, 29.13% potassium citrate.

[0016] Furthermore, the homologous complex of medicine and food includes wolfberry extract, ginger extract, and chrysanthemum extract, with a mass ratio of 4:1:2.

[0017] Furthermore, the preparation method of the wolfberry extract is as follows: The wolfberry is pretreated, and then extracted with water, centrifuged, filtered, concentrated, and dried; the weight ratio of wolfberry to water is 1:20, the extraction temperature is 30°C, the extraction time is 30 min, and it is filtered through a 0.22 - μm membrane;

[0018] The preparation method of the ginger extract is as follows: The ginger is pretreated, and then extracted with ethanol, centrifuged, filtered, concentrated, and dried; the weight ratio of ginger to ethanol is 1:15, the extraction temperature is 60°C, the extraction time is 30 min, and it is filtered through a 0.22 - μm membrane;

[0019] The preparation method of the chrysanthemum extract is as follows: the chrysanthemum is pretreated, and then extracted with ethanol, centrifuged, filtered, concentrated and dried; the weight ratio of the chrysanthemum to the ethanol is 1:20, the extraction temperature is 40 °C, the extraction time is 30 min, and it is filtered through a 0.22 μm membrane.

[0020] Furthermore, the preparation method of the medicated peptide mixture microcapsule preparation is as follows: the core material and the wall material are mixed according to a mass ratio of 1:10, dissolved in deionized water according to a solid-liquid ratio of 1:15 and mixed, placed in the feed liquid collection tank of a spray dryer, and spray-dried under the conditions of an inlet temperature of 160 °C, an outlet temperature of 80 °C, and a flow rate of 10 mL / min. After drying is completed, the powder is collected to obtain the medicated peptide mixture microcapsule preparation.

[0021] A preparation method of a health-care milk powder with both medicinal and edible properties is characterized in that the milk powder is prepared by a dry-wet mixing method, and comprises the following steps:

[0022] (1) Weighing materials:

[0023] Weigh the raw materials described in claim 1 and set aside;

[0024] (2) Feeding materials:

[0025] Skim milk powder, demineralized whey protein powder, lactose, and galactooligosaccharide are added to the filtered raw milk to obtain mixed milk;

[0026] (3) Homogenization and emulsification:

[0027] The mixed milk is homogenized at a homogenization temperature of 35-40 °C and a homogenization pressure of 15-20 Mpa, and emulsified at 4000 r / min for 15-20 min;

[0028] (4) Sterilization:

[0029] Maintain at 85-90 °C for 18-25 s;

[0030] (5) Concentration:

[0031] Vacuum concentrate to 25-27% of the volume of the mixed milk, and control the mass fraction of solids in the milk at 15%;

[0032] (6) Spray drying:

[0033] The inlet air temperature is 160 °C and the outlet air temperature is 80 °C.

[0034] (7) Cooling the powder:

[0035] Quickly and stably cool the finished milk powder to room temperature to obtain the milk base material.

[0036] (8) Mixing materials:

[0037] DHA powder, mixed vitamins, mixed minerals, niacin, folic acid, choline, and the microencapsulation preparation of the peptide mixture were added to milk powder and dry-mixed evenly to obtain the mixed milk powder.

[0038] As can be seen from the above technical solutions, compared with the prior art, the beneficial effects of the present invention are as follows:

[0039] In the medicated peptide microcapsule antihypertensive milk powder provided by the present invention, the optimal formulation of the protective agent during the microcapsule spray drying process was determined as maltodextrin 8% (w / w), β-cyclodextrin 4% (w / w), the ratio of the medicated peptide mixture to the protective agent was 1:10, the solid content was 15%, and the inlet air temperature was 160°C. Under these conditions, the ACE inhibition rate of the microcapsules could still be maintained at 76.64%, and the diameter was concentrated in the range of 100 μm, indicating more uniform encapsulation. In terms of bitterness evaluation of the medicated peptide mixture microcapsules, the samples encapsulated by microcapsules were significantly lower than the unencapsulated samples (P<0.05), and the lowest TD value of bitterness was 4.

[0040] The present invention determines the milk powder ingredients according to the requirements of formulated diets, and adopts a production process combining dry and wet methods. Milk, skim milk powder, demineralized whey protein powder, lactose, and galactooligosaccharides are homogenized, emulsified, sterilized and concentrated, and then spray-dried to obtain the milk base powder. Dry materials such as mixed vitamins, mixed calcium, and medicated peptide mixed microcapsules are added to it and dry-mixed to prepare a formulated milk powder with antihypertensive functionality, which can effectively extend the storage period, increase its stability, improve the shelf life, and at the same time has a simple preparation process and low production cost, and has good application prospects.

[0041] The medicated and food homologous antihypertensive milk powder provided by the present invention has strong in vitro ACE inhibitory activity and also strong in vivo antihypertensive activity. It achieves the purpose of lowering blood pressure through multiple pathways such as reducing the content of Ang II and ACE2 in the heart, kidneys, and aortic vascular endothelial cells, thereby reducing organ vascular damage and enhancing the antioxidant and anti-inflammatory abilities of kidney endothelial cells. Description of the Drawings

[0042] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the drawings in the following description are only the embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained according to the provided drawings.

[0043] Figure 1 The drawings are the determination results of the encapsulation rate of the microcapsule antihypertensive milk powder with different wall materials of the present invention;

[0044] Figure 2 The drawings are the protein expression maps of ACE and ACE2 in the kidneys of rats in each group of the present invention;

[0045] Figure 3 The accompanying drawings show the expression levels of ACE and ACE2 proteins in the kidneys of rats in each group of the present invention;

[0046] Figure 4 The accompanying drawings show the expression diagrams of AngII protein in the hearts, kidneys and blood of rats in each group of the present invention;

[0047] Figure 5 The accompanying drawings show the levels of inflammatory factors in the kidney tissues of rats in each group of the present invention. Detailed implementation manners

[0048] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0049] Sources of experimental materials:

[0050] Raw cow milk is commercially available cow milk from Heilongjiang Longdan Dairy Technology Co., Ltd.;

[0051] Whey protein powder is commercially available WPC concentrated whey protein from Qingdao Haiweisen Biotechnology Co., Ltd., product number 160297140;

[0052] Demineralized whey powder is commercially available demineralized whey powder D90 from Davlin International Trade (Shanghai) Co., Ltd., product number 10BLKZ5;

[0053] Skim milk powder is commercially available skim milk powder SMP from Beijing Lanbolide Trading Co., Ltd., product number N7861.

[0054] Example 1

[0055] A medicated and food homologous synergistic angiotensin converting enzyme inhibitor antihypertensive milk powder is prepared from the following raw material components by weight: 200 parts of raw cow milk, 15 parts of skim milk powder, 24 parts of demineralized whey protein powder, 2.1 parts of lactose, 2 parts of galactooligosaccharide, 0.08 part of DHA powder, 0.6 part of mixed vitamins, 5 parts of mixed minerals, 0.006 part of nicotinic acid, 0.0004 part of folic acid, 0.2 part of choline, and 0.28 part of microcapsule preparation of a medicated peptide mixture.

[0056] The mixed vitamins are formulated by mixing the following components in the following weight percentages: 0.672% vitamin A, 0.01% vitamin D, 5.356% vitamin E, 92.33% vitamin C, 0.04% vitamin K, 1.29% vitamin B1, 0.15% vitamin B2, 0.15% vitamin B6, 0.002% vitamin B12.

[0057] The mixed minerals are formulated by mixing the following components in the following weight percentages: ferrous sulfate 0.64%, zinc sulfate 0.29%, magnesium sulfate 5.83%, calcium hydrogen phosphate 46.63%, sodium citrate 17.48%, potassium citrate 29.13%.

[0058] The specific preparation method of the wolfberry extract is as follows:

[0059] The wolfberry is pretreated, extracted with water, centrifuged, filtered, concentrated and dried to obtain the wolfberry extract.

[0060] The weight ratio of wolfberry to water is 1:20; the extraction temperature is 30°C and the time is 30 min; after filtration through a 0.22 μm membrane, centrifugation, concentration and drying, the wolfberry extract is obtained.

[0061] The specific preparation method of the ginger extract is as follows:

[0062] The ginger is pretreated and extracted with 75% (v / v) ethanol; then centrifuged, filtered, concentrated and dried to obtain the ginger extract.

[0063] The weight ratio of ginger to ethanol is 1:15; the extraction temperature is 60°C and the time is 30 min; after filtration through a 0.22 μm membrane, centrifugation, concentration and drying, the ginger extract is obtained.

[0064] The specific preparation method of the chrysanthemum extract is as follows:

[0065] The chrysanthemum is pretreated and extracted with 75% (v / v) ethanol, centrifuged, filtered, concentrated and dried to obtain the chrysanthemum extract.

[0066] The weight ratio of chrysanthemum to ethanol is 1:20; the extraction temperature is 40°C and the time is 30 min; after filtration through a 0.22 μm membrane, centrifugation, concentration and drying, the chrysanthemum extract is obtained.

[0067] The medicated and edible homologous complex includes wolfberry extract, ginger extract, chrysanthemum extract, and the mass ratio is 4:1:2.

[0068] The specific steps for preparing the microcapsules are as follows:

[0069] The extracts of medicated and edible homologous substances and angiotensin-converting enzyme inhibitors are encapsulated using spray drying technology. Take 1 g of the medicated and edible homologous complex and 2 g of angiotensin inhibitor as the core materials, and take 50 g of maltodextrin and 25 g of β-cyclodextrin, 37.5 g of maltodextrin and 37.5 g of β-cyclodextrin, 25 g of maltodextrin and 50 g of β-cyclodextrin as the wall materials respectively, denoted as formula A, formula B, and formula C.

[0070] Dissolve formula A, formula B, and formula C in 750 mL of deionized water respectively, sterilize them using a filter with a membrane pore size of 0.22 μm, place them in the feed liquid collection tank of the spray dryer, and perform spray drying under the conditions of an inlet temperature of 160 °C, an outlet temperature of 80 °C, and a flow rate of 10 mL / min. After drying, collect the powder to obtain the microcapsule preparation of the drug-peptide mixture. Measure the encapsulation rate and ACE inhibition rate of the three microcapsule solids of formula A, formula B, and formula C, and determine the optimal wall material according to the encapsulation rate and ACE inhibition rate.

[0071] The measurement results of the encapsulation rate and ACE inhibition rate of the three formulas are as Figure 1 shown. When using formula A to prepare microcapsules, the encapsulation rate is 81.14 ± 1.05%, and the ACE inhibition rate is 76.64 ± 1.96%. When using formula B to prepare microcapsules, the encapsulation rate is 79.36 ± 2.65%, and the ACE inhibition rate is 72.49 ± 1.25%. When using formula C to prepare microcapsules, the encapsulation rate is 75.21 ± 2.95%, and the ACE inhibition rate is 69.33 ± 1.78%. The order of the encapsulation rate is: formula A > formula B > formula C, and the order of the ACE inhibition rate is: formula A > formula B > formula C. Therefore, maltodextrin:β-cyclodextrin = 2:1 is selected as the optimal wall material.

[0072] The antihypertensive milk powder is prepared by combining the dry method and the wet method, including the following steps:

[0073] (1) Weighing materials:

[0074] Weigh the raw materials described in claim 1 and set aside;

[0075] (2) Feeding materials:

[0076] Add skim milk powder, demineralized whey protein powder, lactose, and galactooligosaccharides to the filtered raw milk to obtain a mixed milk;

[0077] (3) Homogenization and emulsification:

[0078] Homogenize the mixed milk at a homogenization temperature of 38 °C and a homogenization pressure of 18 Mpa, and emulsify it at 4000 r / min for 18 min;

[0079] (4) Sterilization:

[0080] Maintain at 85 - 90 °C for 18 - 25 s;

[0081] (5) Concentration:

[0082] Concentrate under vacuum to 26% of the volume of the mixed milk, controlling the mass fraction of solids in the milk at 15%;

[0083] (6) Spray drying:

[0084] Inlet air temperature 160 °C, outlet air temperature 80 °C.

[0085] (7) Cooling the powder:

[0086] Quickly and stably cool the finished milk powder to room temperature to obtain the milk-based material.

[0087] (8) Mixing:

[0088] Add DHA powder, mixed vitamins, mixed minerals, niacin, folic acid, and the microcapsule preparation of the peptide mixture to the milk powder, and dry mix evenly to obtain the mixed milk powder.

[0089] Example 2

[0090] A health food and medicine homologous synergistic angiotensin-converting enzyme inhibitor antihypertensive milk powder is made from the following raw material components by weight: 150 parts of raw milk, 12 parts of skim milk powder, 24 parts of demineralized whey protein powder, 2 parts of lactose, 2 parts of galactooligosaccharide, 0.05 part of DHA powder, 0.5 part of mixed vitamins, 4.5 parts of mixed minerals, 0.006 part of niacin, 0.0004 part of folic acid, 0.2 part of choline, and 0.24 part of the microcapsule preparation of the peptide mixture.

[0091] The preparation method of the microcapsule preparation of the peptide mixture uses Formula A;

[0092] The rest is the same as in Example 1;

[0093] Prepare the antihypertensive milk powder by combining dry and wet methods, including the following steps:

[0094] (1) Weighing the materials:

[0095] Weigh the raw materials described in Claim 1 and set aside;

[0096] (2) Feeding the materials:

[0097] Add skim milk powder, demineralized whey protein powder, lactose, and galactooligosaccharide to the filtered raw milk to obtain the mixed milk;

[0098] (3) Homogenization and emulsification:

[0099] Homogenize the mixed milk at a homogenization temperature of 35 °C and a homogenization pressure of 15 Mpa, and emulsify at 4000 r / min for 20 min;

[0100] (4) Sterilization:

[0101] Maintain at 85 - 90 °C for 18 - 25 s;

[0102] (5) Concentration:

[0103] Vacuum concentrate to 25% of the volume of the mixed milk, and control the mass fraction of solids in the milk at 15%;

[0104] (6) Spray drying:

[0105] Inlet air temperature is 160 °C, outlet air temperature is 80 °C.

[0106] (7) Cooling the powder:

[0107] Quickly and stably cool the finished milk powder to room temperature to obtain the milk base material.

[0108] (8) Mixing:

[0109] Add DHA powder, mixed vitamins, mixed minerals, niacin, folic acid, and the microcapsule preparation of the peptide mixture to the milk powder, and dry mix evenly to obtain the mixed milk powder.

[0110] Example 3

[0111] A health food homologous and synergistic angiotensin - converting enzyme inhibitor antihypertensive milk powder is made from the following raw material components by weight: 300 parts of raw cow milk, 20 parts of skim milk powder, 24 parts of demineralized whey protein powder, 2.3 parts of lactose, 2 parts of galactooligosaccharide, 0.1 part of DHA powder, 0.7 part of mixed vitamins, 5.5 parts of mixed minerals, 0.006 part of niacin, 0.0004 part of folic acid, 0.2 part of choline, and 0.3 part of the microcapsule preparation of the peptide mixture.

[0112] The preparation method of the microcapsule preparation of the peptide mixture uses Formula A;

[0113] The rest is the same as in Example 1;

[0114] The antihypertensive milk powder is prepared by combining the dry method and the wet method, and includes the following steps:

[0115] (1) Weighing the materials:

[0116] Weigh the raw materials described in Claim 1 and set aside;

[0117] (2) Feeding the materials:

[0118] Add skim milk powder, demineralized whey protein powder, lactose, and galactooligosaccharide to the filtered raw cow milk to obtain the mixed milk;

[0119] (3) Homogenization and emulsification:

[0120] Homogenize the mixed milk at a temperature of 40°C and a pressure of 20 Mpa, and emulsify it at 4000 r / min for 15 min;

[0121] (4) Sterilization:

[0122] Maintain at 85 - 90°C for 18 - 25 s;

[0123] (5) Concentration:

[0124] Vacuum concentrate to 27% of the volume of the mixed milk, and control the mass fraction of solids in the milk at 15%;

[0125] (6) Spray drying:

[0126] The inlet air temperature is 160°C and the outlet air temperature is 80°C.

[0127] (7) Cooling the powder:

[0128] Quickly and stably cool the finished milk powder to room temperature to obtain the milk base material.

[0129] (8) Blending:

[0130] Add DHA powder, mixed vitamins, mixed minerals, niacin, folic acid, and the microcapsule preparation of the drug peptide mixture to the milk powder, and dry blend evenly to obtain the mixed milk powder.

[0131] Currently, two methods, in vitro and in vivo, are mainly used to measure the blood pressure-lowering effect of functional products. In vitro measurement is mainly the angiotensin-converting enzyme (ACE) inhibitory activity experiment; in vivo measurement is mainly the hypertensive rat model. The biological effect of the product on blood pressure regulation and its possible mechanism of action are comprehensively evaluated through the detection of renin-angiotensin system (RAS) - related indicators and histopathological examinations to observe the protective effect on target organs.

[0132] The main steps of in vitro detection are as follows:

[0133] Weigh 1 g of the blood pressure-lowering milk powder and dissolve it thoroughly in 5 mL of distilled water. Pipette 100 μL of the blood pressure-lowering milk powder sample solution, add 100 μL of the FAPGG solution (1.0 mmol / L, prepared with 1.0 mol / L HEPES buffer), add 20 μL of the ACE enzyme solution (0.1 U / mL) to initiate the reaction. After mixing, measure the absorbance at 340 nm using a microplate reader, react at 37°C for 30 min, and then measure the absorbance at 340 nm at the end. Use distilled water instead of the sample solution as a control, calculate the ACE inhibition rate according to formula (1), measure 3 parallel groups, and take the average value.

[0134]

[0135] Where: A0: Absorbance difference before and after 30 min in the blank group; A1: Absorbance difference before and after 30 min in the sample group;

[0136] The ACE inhibition rate of the microcapsule antihypertensive milk powder measured by the above experiments is still 76.64%, indicating that after processing, the in vitro ACE inhibitory activity and synergy of the compound components have hardly decreased, and still have a good antihypertensive effect.

[0137] To further verify the antihypertensive effect of the antihypertensive milk powder in Example 1 of this application on spontaneously hypertensive rats, it will be described below in combination with animal experiments.

[0138] The rats used in the experiment were male spontaneously hypertensive (SHR) rats and male Wistar rats (WKY), with a body weight of about 260 g, provided by Beijing Vital River Laboratory Animal Technology Co., Ltd., and the certificate number: SCXK (Jing) 2021-0011.

[0139] Weigh 100 mg of the antihypertensive milk powder in Example 1 and 1 mg of captopril and dissolve them in 0.75% physiological saline as the test drugs.

[0140] 8 male Wistar rats were used as the control group; 24 SHR rats were randomly divided into three groups, with 8 rats in each group, namely the model group (0.5% CMC-Na 10 mL / kg), the antihypertensive milk powder group (100 mg / kg), and the captopril group (1 mg / kg), and the drugs were administered continuously for 4 weeks. The blood pressure was measured once a week.

[0141] Rat blood pressure detection

[0142] Use an RBP-1 type rat sphygmomanometer to measure the systolic blood pressure of the caudal artery of rats in each group in a conscious and quiet state. Heat the rats for 10 min to 37 °C before measurement to make the artery full for measurement. The blood pressure values of rats in each group were measured by a dedicated person every afternoon, and the average value of multiple measurements was taken as the blood pressure value of the rat in that week.

[0143] Blood pressure detection results

[0144] Table 1 Changes in systolic blood pressure of rats in each group ( mmHg)

[0145]

[0146] Table 2 Changes in diastolic blood pressure of rats in each group ( mmHg)

[0147] Group Before administration The 1st week The 2nd week The 3rd week The 4th week Control group 82±7.89 79±5.37 80±7.42 85±7.19 84±7.94 Model group 144±7.96** 142±5.82** 137±7.44** 141±3.89** 142±5.82** Captopril group 141±7.89** 89±11.09##* 91±7.48##* 73±9.24##* 72±7.94##* Hypotensive milk powder group 140±6.85** 110±5.69#** 98±6.54##* 93±8.81##* 84±5.47##

[0148] Note: Compared with the control group, *P < 0.05; compared with the model group, #P < 0.05.

[0149] As shown in Table 1 and Table 2, after 4 weeks of intragastric administration, the systolic and diastolic blood pressures of the rats in the antihypertensive milk powder group were significantly lower than those in the model group (P<0.05) compared with the captopril group. In contrast, the effect of captopril was more obvious and the antihypertensive process was rapid, while the process of reducing the diastolic blood pressure of the antihypertensive milk powder in SHR rats was relatively mild, showing a slow downward trend.

[0150] Protein expression of ACE and ACE2 in rat kidneys

[0151] It was measured by Western Blot experiment. Calculation: The image was collected by a gel imaging system, and the gray value analysis was performed by Image J analysis software. The ratio of the gray value of the target protein band to the internal reference band was used as the relative protein expression level.

[0152] Results of protein expression of ACE and ACE2 in rat kidneys

[0153] The results of the Western Blot experiment were as Figure 2-3 shown. It was analyzed that compared with the control group, the protein expression of ACE in the rat kidneys in the model group was significantly increased, and the protein expression level of ACE2 was significantly decreased (P<0.01). The expression levels of ACE protein in the rat kidney tissues of the captopril group and the milk powder group could be significantly decreased, and the protein expression level of ACE2 was significantly increased (P<0.05).

[0154] AngⅡ protein expression in rat heart, kidney and thoracic aorta

[0155] The tissue samples of the heart, kidney and thoracic aorta were prepared into paraffin sections, and the expression of AngⅡ protein was observed using an optical microscope.

[0156] Results of AngⅡ protein expression in rat heart, kidney and blood

[0157] As Figure 4 shown, the positive expression of AngⅡ enzyme in the tissue sections of the arteries, heart and kidneys of the rats in the model group increased, while in the rats of the captopril group and the milk powder group, the expression of AngⅡ in the thoracic aorta, heart and kidneys decreased significantly, indicating that the milk powder could inhibit the synthesis of AngⅡ and reduce the expression of AngⅡ in target organs, and the effect was similar to that of the drug.

[0158] Determination of IFN-γ, TNF-α, IL-1 and IL-6 levels in rat kidney tissues

[0159] Use the double-antibody one-step sandwich enzyme-linked immunosorbent assay (ELISA). Add the specimen, standard, and HRP-labeled detection antibody to the pre-coated microplate wells in sequence. Incubate and wash thoroughly. Color the substrate TMB. TMB is converted into blue under the catalysis of peroxidase and into the final yellow under the action of acid. The color intensity is positively correlated with the detected substance in the sample. Measure the absorbance (OD value) with an enzyme-labeled instrument at a wavelength of 450 nm and calculate the sample concentration.

[0160] Measurement results of IFN-γ, TNF-α, IL-1, and IL-6 levels in rat kidney tissues

[0161] From Figure 5 it can be seen that the expression of TNF-α, IFN-γ, IL-1, and IL-6 in each group is as follows: model group > antihypertensive milk powder group > captopril group > control group. Compared with the control group, the inflammatory factors in the model group increased significantly (P < 0.01). Compared with the model group, the antihypertensive milk powder group and captopril group decreased (P < 0.01). This shows that the antihypertensive milk powder has a good effect on reducing inflammatory factors.

[0162] Through animal experiments, it was found that the antihypertensive milk powder containing homologous substances of medicine and food and synergistic angiotensin-converting enzyme inhibitors can slowly reduce the systolic and diastolic blood pressures of spontaneously hypertensive rats, effectively improve the health status of the hearts, kidneys, and thoracic aortas of hypertensive rats, and play a significant intervention role in the inflammatory response.

[0163] An accelerated shelf-life experiment was conducted on the adjuvant antihypertensive milk powder in Example 1. Set up two constant temperature and humidity incubators, maintaining the temperature at 40 ± 0.5 °C and 50 ± 0.5 °C respectively, and the relative humidity constant at 75 ± 2% RH. Conduct an accelerated aging experiment on the vacuum-packed samples to simulate long-term storage conditions and deeply analyze the evolution law of the quality stability of the milk powder. A evaluation group consisting of 10 systematically trained sensory evaluators was formed, and the samples were evaluated in multiple dimensions using the five-point scale method, specifically including color and luster (whiteness value, uniformity), solubility (dissolution time, dispersion degree, precipitation amount), flavor characteristics (intensity of milk flavor, degree of off-flavor), tissue state (fineness, fluidity), and overall acceptability and other indicators to ensure the scientificity and reliability of the experimental data.

[0164] Table 3 Sensory evaluation standard table of milk powder

[0165]

[0166] Table 4 Sensory evaluation table of the results of the accelerated experiment of milk powder

[0167]

[0168]

[0169] As can be seen from the acceleration results in Table 4, the shelf life of the milk powder in Example 1 is stable. At 40 °C in the accelerated experiment for 30 days, the reconstitution property, color, taste and overall acceptability of the milk powder show no obvious change and still remain at the level of "good" or above. This indicates that the milk powder in Example 1 has strong stability. Calculated by the Arrhenius equation, the storage period ratio Q10 = shelf life at 40 °C / shelf life at 50 °C = 65 days / 20 days = 3.25. Therefore, the theoretical shelf life of the milk powder prepared by the compound microcapsule technology is about 687 days under the environment of 20 °C and 75% relative humidity. In terms of bitterness evaluation, the milk powder prepared from the samples encapsulated by microcapsules is significantly lower than that prepared from the unencapsulated samples (P<0.05), and its lowest bitterness TD value is 4%. It meets the requirements of the national standard GB 19644-2010 "National Food Safety Standard Milk Powder" and can meet the needs of daily storage.

[0170] Usage method:

[0171] The usage method of the medicated and edible homologous substances synergistic angiotensin-converting enzyme inhibitor antihypertensive formula milk powder prepared in the present invention:

[0172] Packaging form: 900 g / can;

[0173] Shelf life: half a year;

[0174] Instructions for use: Drink 2 cups every day. Take 4 spoons (about 40 g) and add them to 200 ml of warm water at 50 °C for modulation. You can do it in small amounts multiple times and stir evenly before drinking.

[0175] The above description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be obvious to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but will be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A homologous medicine and food antihypertensive milk powder, characterized in that, It is made from the following raw material components by weight: 150 - 300 parts of raw cow milk, 12 - 20 parts of skim milk powder, 24 parts of demineralized whey protein powder, 2 - 2.3 parts of lactose, 2 parts of galactooligosaccharide, 0.05 - 0.1 part of DHA powder, 0.5 - 0.7 part of mixed vitamins, 4.5 - 5.5 parts of mixed minerals, 0.006 part of niacin, 0.0004 part of folic acid, 0.2 part of choline, 0.24 - 0.3 part of the microcapsule preparation of the medicine - peptide mixture; The core material of the microcapsule preparation of the medicine - peptide mixture is a medicine - food homologous complex and an ACE - inhibiting peptide, with a mass ratio of 1:

2. The wall material is maltodextrin and β - cyclodextrin, with a mass ratio of 2:1, and the core - wall mass ratio is 1:

10.

2. The anti-hypertensive milk powder according to claim 1, characterized in that The dry matter in the raw cow milk is not less than 12%; The whey protein powder is WPC35 whey protein powder; The demineralized whey powder is D90 demineralized whey powder; The skim milk powder is SMP skim milk powder; 3. The hypotensive milk powder according to claim 1, wherein, The mixed vitamins are mixed and prepared according to the following components and weight percentages: 0.672% vitamin A, 0.01% vitamin D, 5.356% vitamin E, 92.33% vitamin C, 0.04% vitamin K, 1.29% vitamin B1, 0.15% vitamin B2, 0.15% vitamin B6, 0.002% vitamin B12; 4. The hypotensive milk powder according to claim 1, characterized in that, The mixed minerals are mixed and prepared according to the following components and weight percentages: 0.64% ferrous sulfate, 0.29% zinc sulfate, 5.83% magnesium sulfate, 46.63% calcium hydrogen phosphate, 17.48% sodium citrate, 29.13% potassium citrate; 5. The antihypertensive milk powder according to claim 1, wherein The medicine - food homologous complex includes wolfberry extract, ginger extract, and chrysanthemum extract, with a mass ratio of 4:1:2; 6. The hypotensive milk powder according to claim 5, characterized in that, The preparation method of the wolfberry extract is: wolfberry is pretreated, extracted with water, centrifuged, filtered, concentrated, and dried; the weight ratio of wolfberry to water is 1:20, the extraction temperature is 30°C, the time is 30 min, and it is filtered through a 0.22 - μm membrane; The preparation method of the ginger extract is: ginger is pretreated, extracted with ethanol, centrifuged, filtered, concentrated, and dried; the weight ratio of ginger to ethanol is 1:15, the extraction temperature is 60°C, the time is 30 min, and it is filtered through a 0.22 - μm membrane; The preparation method of the chrysanthemum extract is: chrysanthemum is pretreated, extracted with ethanol, centrifuged, filtered, concentrated, and dried; the weight ratio of chrysanthemum to ethanol is 1:20, the extraction temperature is 40°C, the time is 30 min, and it is filtered through a 0.22 - μm membrane; 7. The antihypertensive milk powder according to claim 1, wherein The preparation method of the microcapsule preparation of the medicine - peptide mixture is: the core material and the wall material are mixed according to a mass ratio of 1:10, dissolved in deionized water according to a solid - liquid ratio of 1:15 and mixed, placed in the feed liquid collection tank of a spray dryer, and spray - dried under the conditions of an inlet temperature of 160°C, an outlet temperature of 80°C, and a flow rate of 10 mL / min. After drying is completed, the powder is collected to obtain the microcapsule preparation of the medicine - peptide mixture.

8. The preparation method of the antihypertensive milk powder according to any one of claims 1 - 7, characterized in that The milk powder is prepared by the dry - wet mixing method, including the following steps: (1) Weighing materials: Weigh the raw materials described in claim 1 and set aside for later use; (2) Feeding: Add skim milk powder, demineralized whey protein powder, lactose, and galactooligosaccharide to the filtered raw milk to obtain a mixed milk; (3) Homogenization and emulsification: Homogenize the mixed milk at a temperature of 35 - 40°C and a pressure of 15 - 20 Mpa, and emulsify it at 4000 r / min for 15 - 20 minutes; (4) Sterilization: Maintain at 85 - 90°C for 18 - 25 seconds; (5) Concentration: Vacuum concentrate to 25 - 27% of the volume of the mixed milk, and control the mass fraction of solids in the milk at 15%; (6) Spray drying: The inlet air temperature is 160°C and the outlet air temperature is 80°C; (7) Cooling the powder: Quickly and stably cool the finished milk powder to room temperature to obtain a milk base material; (8) Mixing: Add DHA powder, mixed vitamins, mixed minerals, niacin, folic acid, choline, and a microcapsule preparation of a peptide mixture to the milk powder, and dry mix evenly to obtain a mixed milk powder.