Pharmaceutical composition for reducing blood fat and blood pressure and preparation method thereof

Abstract

The invention provides a pharmaceutical composition for reducing blood fat and blood pressure and a preparation method thereof, and belongs to the technical field of biological pharmacy, the pharmaceutical composition comprises durian honey seed extract, brassica campestris root-allium wilt composite extract, gastrodin, rhynchophylline, eucommia ulmoides glycoside and puerarin. The durian honey seed extract is prepared by performing enzymolysis on durian honey seeds through cellulase and pectinase, performing enzymolysis step by step through pepsin and ginger protease, adding a DES cosolvent, performing ultrasonic extraction, and performing MCI GEL CHP20P column purification. The red brassica campestris root-allium cervi composite extract is prepared by fermenting red brassica campestris roots and allium cervi herbs through lactobacillus rhamnosus and purifying fermentation liquor through a macroporous adsorption resin HP2MG column. All the components are matched for use, triple optimization of safety-drug effect-mechanism cooperation is achieved, the problems that western medicine is single in target spot and remarkable in side effect after being used for a long time are avoided, and the defects that traditional Chinese medicine is extensive in preparation and unstable in curative effect are overcome.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of biological pharmacy, and particularly relates to a drug composition for reducing blood fat and blood pressure and a preparation method thereof. BACKGROUND

[0002] Blood fat and blood pressure reducing drugs are key means for preventing and controlling cardiovascular diseases (such as coronary heart disease and stroke), and a technical system of western medicine and traditional Chinese medicine has been formed. The two types of technology are based on different medical theories and research and development logic, and each has its own focus in terms of efficacy characteristics and applicable scenarios.

[0003] In the western medicine technical system, the core logic is "precise targeting of pathological links", and by targeting specific targets in lipid metabolism and blood vessel function regulation, rapid control of indicators is achieved. In the field of reducing blood fat, a multi-gradient drug combination has been formed: statins (such as atorvastatin and rosuvastatin) are used as first-line basic drugs, which can reduce low-density lipoprotein cholesterol (LDL-C) by inhibiting HMG-CoA reductase in the liver, while slightly adjusting triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C), but some patients have the risk of muscle damage and abnormal liver function; cholesterol absorption inhibitors (such as ezetimibe) block the absorption of cholesterol in the small intestine, and can reduce LDL-C as a single drug, and are often used in combination with statins to solve the problem of "statin intolerance" or "insufficient efficacy"; PCSK9 inhibitors (such as evolocumab) are used as potent lipid-lowering drugs, which can enhance the clearance capacity of the liver for LDL-C, and are suitable for high-risk groups such as familial hypercholesterolemia, but require subcutaneous injection and are expensive, limiting patient compliance; fibrate drugs (such as fenofibrate) focus on hypertriglyceridemia, and can promote TG metabolism by activating PPARα receptors, filling the treatment gap for specific blood lipid abnormalities.

[0004] Blood pressure reducing western medicine also covers multiple action targets: calcium channel blockers (CCB, such as amlodipine) can expand peripheral blood vessels to reduce blood pressure, and are suitable for elderly patients with hypertension, and long-acting preparations can achieve 24-hour stable pressure control, but can easily cause ankle edema; angiotensin-converting enzyme inhibitors (ACEI, such as enalapril) and angiotensin II receptor antagonists (ARB, such as valsartan) can reduce blood pressure and protect the kidneys and improve ventricular remodeling, and are the preferred choice for patients with diabetic nephropathy, but ACEI can cause dry cough; diuretics (such as small doses of hydrochlorothiazide) can reduce blood volume to reduce blood pressure, and are suitable for patients with heart failure, but long-term use can cause hypokalemia and hyperuricemia; beta blockers (such as metoprolol) can inhibit sympathetic nervous activity, and are suitable for hypertensive patients with coronary heart disease and tachyarrhythmia, and selective preparations can reduce the impact on the bronchus and metabolism. In addition, for people with "high blood fat and high blood pressure", western medicine compound preparations (such as amlodipine / atorvastatin tablets) can achieve dual regulation through a single drug, simplify the drug regimen, and improve patient compliance.

[0005] Traditional Chinese medicine technology system follows the concept of "overall regulation" of traditional Chinese medicine, and aims at the pathogenesis of dyslipidemia (belonging to "phlegm turbidity" and "blood stasis") and hypertension (belonging to "dizziness" and "headache"). It plays a role by regulating the function of viscera and improving the metabolism of the body. Single herb and extract are the technical basis: in terms of lowering blood lipids, hawthorn flavonoids regulate blood lipids by inhibiting cholesterol synthase and promoting lipid excretion, and red yeast rice achieves lipid-lowering by producing natural statins (such as lovastatin), and prepared radix falconiae can reduce liver toxicity, and its stilbene glycoside can regulate lipid metabolism; in terms of lowering blood pressure, gastrodin relieves hypertension by inhibiting sympathetic nerves and dilating blood vessels, and rhynchophylline lowers blood pressure by blocking angiotensin II receptors, and eucommia ulmoides glycoside can promote the release of nitric oxide from vascular endothelium and improve vascular elasticity. Compound preparations are the core form of traditional Chinese medicine application. Xuezhikang capsules use red yeast rice as the core and are supplemented with spleen-strengthening and dampness-eliminating traditional Chinese medicines to achieve multi-component synergistic lipid-lowering; Niuhuang Jiangya tablets are suitable for liver-yang hyperactivity type hypertension through the combination of liver-quieting and blood-activating traditional Chinese medicines; and compound rubus suavissimus pills combine traditional Chinese medicines with western medicines to enhance efficacy and reduce side effects of western medicines.

[0006] However, both types of technology have obvious shortcomings: western medicines have clear targets and fast effects, but single target can easily lead to compensation risk and long-term use has significant side effects; traditional Chinese medicines can regulate the whole body, but the preparation method is rough, the mechanism is unclear, the efficacy is unstable, and the effect is slow. Therefore, the research and development of blood lipid-lowering and blood pressure-lowering drugs needs to find direction in the integration of advantages and breakthroughs of defects of the two types of technology to meet more complex clinical treatment needs. SUMMARY

[0007] In view of the problems of single target of western medicines, side effects of long-term use, rough preparation method of traditional Chinese medicines, unstable efficacy, and slow effect of existing blood lipid-lowering and blood pressure-lowering drugs. The present application provides a kind of blood lipid-lowering and blood pressure-lowering drug composition and its preparation method, which uses special method to prepare durian honey seed extract, red cabbage root-koueujie composite extract, and gastrodin, rhynchophylline, eucommia ulmoides glycoside and pueraria radix in scientific proportion to compound the drug composition, realizing the triple optimization of "safety-drug efficacy-mechanism synergy", which not only avoids the problem of single target of western medicines and significant side effects of long-term use, but also solves the defects of rough preparation and unstable efficacy of traditional Chinese medicines. The specific technical scheme is as follows: A pharmaceutical composition for lowering blood lipids and blood pressure comprises durian seed extract, red mustard root-deer ear fungus compound extract, gastrodin, rhizoma lucida, eucommia ulmoides glycoside and puerarin in a mass ratio of (2.0-3.5):(4.5-5.5):(0.8-1.5):(0.5-0.8):(0.3-0.5):(1-1.5). The durian seed extract is prepared by enzymatic hydrolysis of durian seeds by cellulase and pectinase, followed by stepwise enzymatic hydrolysis by pepsin and ginger protease, then ultrasonic extraction with DES co-solvent, and purification by MCI GEL CHP20P column. The red mustard root-deer ear fungus compound extract is prepared by fermentation of red mustard root and deer ear fungus whole herb in a mass ratio of (2-3):(1-1.5) with Lactobacillus rhamnosus, and purification of the fermentation broth by HP2MG macroporous adsorption resin column.

[0008] The preparation method of the durian honey seed extract in the above-mentioned pharmaceutical composition includes: pulverizing dried durian honey seeds to obtain seed powder; adding the seed powder to phosphate buffer at a material-to-liquid mass ratio of 1:(10-15), adding cellulase and pectinase, and enzymatically hydrolyzing at 48℃-53℃ for 2-2.5h; cooling down, adjusting the pH to 2.0-2.5, adding pepsin, and enzymatically hydrolyzing at 37℃-40℃ for 1.5-2h; inactivating the enzyme, cooling down, adjusting the pH to 6.5-7.0, adding ginger protease, and enzymatically hydrolyzing at 50℃-55℃ for 1-1.5h; inactivating the enzyme, cooling down, and obtaining an enzymatic hydrolysate containing polypeptides; adding DES co-solvent to the enzymatic hydrolysate, ultrasonically extracting, filtering, concentrating the filtrate under reduced pressure, centrifuging, taking the supernatant, and loading it onto an MCI gel. The CHP20P column was used to remove impurities by rinsing with 3 BV to 5 BV of deionized water. The eluent was then eluted with 30% to 40% (v / v) ethanol aqueous solution for 2 BV to 3 BV and 50% to 60% (v / v) ethanol aqueous solution for 2 BV to 3 BV. The eluent was collected, concentrated under reduced pressure at 45°C to 50°C, and freeze-dried to obtain durian honey seed extract.

[0009] In the above-mentioned method for preparing durian honey seed extract, the particle size of the seed powder is sieved through a 60-80 mesh sieve; the pH of the phosphate buffer solution is 5.0-5.5; the amount of cellulase added is 0.8%-1.5% of the seed powder mass; the amount of pectinase added is 0.8%-1.5% of the seed powder mass; the amount of pepsin added is 1.0%-1.5% of the seed powder mass; the amount of ginger protease added is 0.5%-1.0% of the seed powder mass; and the enzyme inactivation is performed by heating to 80℃-85℃ for 10-15 minutes.

[0010] In the preparation method of the durian seed extract, the DES cosolvent is added in an amount of 20-25% of the volume of the enzymatic solution; the DES cosolvent contains 30-35 wt% choline chloride and 45-50 wt% lactic acid, and the balance is deionized water; the ultrasonic extraction is performed at 45-55℃ and 300-400W for 40-50min; the filter screen mesh size is 200-250 meshes; the filtrate is concentrated under reduced pressure at 45-50℃ to a volume of 20-30%; the centrifugation is performed at 8000-8500rpm for 10-15min; and the eluent is concentrated under reduced pressure at 45-50℃ to remove ethanol and part of water.

[0011] In the above pharmaceutical composition, the preparation method of the red cabbage root and deer ear chive composite extract comprises: drying and then crushing the red cabbage root and deer ear chive whole grass respectively through a 40-60 mesh screen, mixing the crushed red cabbage root and deer ear chive whole grass at a mass ratio of red cabbage root: deer ear chive whole grass = (2-3): (1-1.5) to obtain a mixed powder; adding the mixed powder into a culture solution at a solid-liquid mass ratio of 1: (10-15), sterilizing, and cooling to obtain a fermentation culture medium, inoculating Lactobacillus rhamnosus activation liquid, and performing anaerobic fermentation at 35-40℃ and pH 5.5-6.5 for 60-72h; after the fermentation is completed, centrifuging, taking the supernatant, filtering to remove bacteria, and concentrating the filtrate under reduced pressure, and then loading onto a macroporous adsorption resin HP2MG column, washing with 2-4BV deionized water to remove impurities, washing with 2-3BV 30-40% volume concentration methanol aqueous solution to remove impurities, eluting with 3-5BV 55-60% volume concentration methanol aqueous solution, collecting the eluent, concentrating the eluent under reduced pressure, and freeze-drying to obtain the red cabbage root and deer ear chive composite extract.

[0012] In the above preparation method of the red cabbage root and deer ear chive composite extract, the culture solution contains 0.5-0.8wt% glucose, 0.3-0.5wt% sucrose, and 0.2-0.4wt% yeast extract, and the solvent is water; the sterilization is performed at 121-125℃ for 15-20min; the inoculation amount of the Lactobacillus rhamnosus activation liquid is 3-5% of the volume of the fermentation culture medium; the bacterial concentration of the Lactobacillus rhamnosus activation liquid is 1×10 8 CFU / mL-1×10 9 CFU / mL.

[0013] In the preparation method of the red cabbage root and deer's ear chives composite extract, the centrifugation is 8000 rpm-10000 rpm for 10 min-15 min; the pore size of the filter sterilization is 0.22 mu m; the filtrate is concentrated under reduced pressure at 45 DEG C-50 DEG C to 20%-30% of the volume; and the eluent is concentrated under reduced pressure at 45 DEG C-50 DEG C to remove methanol and part of water.

[0014] The preparation method of the one kind of blood lipid and blood pressure reducing pharmaceutical composition comprises the following steps: mixing jackfruit seed extract, red cabbage root and deer's ear chives composite extract, gastrodin, uncarine, eucommia glycosides and puerarin according to the prescription mass ratio to obtain the pharmaceutical composition.

[0015] In the preparation method, the pharmaceutical composition is mixed with a pharmaceutically acceptable excipient to prepare any dosage form of the pharmaceutically acceptable excipient, including tablets, capsules, granules, pills, powders and oral liquids.

[0016] The one kind of blood lipid and blood pressure reducing pharmaceutical composition is used for preparing blood lipid and blood pressure reducing drugs.

[0017] The one kind of blood lipid and blood pressure reducing pharmaceutical composition and the preparation method thereof provided by the application have the beneficial effects including: Firstly, the pharmaceutical composition realizes the triple optimization of safety, efficacy and mechanism synergy, avoids the problems of single target of western medicine and significant side effects of long-term use, and solves the defects of traditional Chinese medicine preparation and unstable curative effect. Through accurate regulation of component ratio and preparation process, the cell compatibility (low toxicity and low hemolysis risk) is ensured, and the multiple target point synergistic lipid-lowering and multiple pathway synergistic blood pressure reduction are realized, thereby providing a safer and more efficient treatment option for people with high blood pressure and high blood pressure.

[0018] Secondly, the jackfruit seed extract is subjected to step-by-step enzymolysis of cellulase, pectinase, pepsin and ginger protease, DES ultrasonic extraction and MCI GEL CHP20P purification to generate small molecule active polypeptides, which can repair vascular endothelial cells, reduce red blood cell damage (improve safety), enhance HMG-CoA reductase inhibition efficiency and LDL receptor up-regulation ability (strengthen lipid-lowering), and synergize with the blood pressure lowering effect of the red cabbage root and deer's ear chives composite extract.

[0019] The enzymolysis parameters are as follows: the cellulase and pectinase pretreatment can fully destroy the cell wall of the jackfruit seed and release the internal protein; the step-by-step enzymolysis of pepsin and ginger protease matches the optimal reaction conditions of different enzymes to directionally generate safe and effective small molecule polypeptides.

[0020] Three, Red cabbage root-buckler chives composite extract: Red cabbage root and buckler chives are fermented by Lactobacillus rhamnosus, purified by HP2MG, to generate active ingredients such as organic acids, flavonoids, and buckler chives base, which can inhibit ACE (hypotensive), activate eNOS to promote NO generation (vasodilation), while assisting in reducing the cytotoxicity of durian honey extract (improving safety), and synergizing with the lipid-lowering effect of durian honey extract.

[0021] Four, Gastrodin, Rotalin: auxiliary regulation of lipid metabolism pathway, enhance lipid-lowering synergistic effect; Rotalin can also block angiotensin II receptors, supplement the mechanism of lowering blood pressure.

[0022] Five, Eucommia ulmoides glycosides, puerarin: Eucommia ulmoides glycosides improve vascular elasticity, puerarin assists in regulating lipid metabolism, and both of them together improve the protective effect of the drug on vascular function.

[0023] Six, purification parameters: MCI GEL CHP20P (durian honey extract), HP2MG (composite extract) resin, adsorb active ingredients through specific polarity, remove impurities, and avoid the increase in toxicity caused by harmful residues.

[0024] In summary, the active polypeptide of durian honey seed extract repairs cells and reduces red blood cell rupture, and the organic acids and flavonoids of the red cabbage root-buckler chives composite extract assist in reducing polypeptide stimulation, and the optimal ratio of the two can significantly reduce cytotoxicity and hemolysis risk, achieving safer protection effect. The active polypeptide of durian honey seed extract and the flavonoids of the composite extract synergistically enhance the inhibition of HMG-CoA reductase, blocking the key step of cholesterol synthesis; the active polypeptide upregulates the expression of LDL receptor in hepatocytes, and the flavonoids of the composite extract stabilize the receptor structure, accelerating the uptake and metabolism of LDL-C in blood; gastrodin and rothalin assist in regulating the lipid metabolism pathway, and multiple components jointly construct a lipid-lowering network of "inhibition of synthesis + promotion of clearance". The fermentation components of the composite extract and the durian honey seed extract synergistically inhibit ACE, reducing the vasoconstriction signal; the vasodilating peptide of durian honey seed extract activates eNOS to promote NO generation, and the buckler chives base of the composite extract prolongs the action time of NO; Eucommia ulmoides glycosides improve vascular elasticity, and multiple pathways jointly achieve the synergistic effect of "inhibition of contraction + promotion of dilation + protection of blood vessels" in lowering blood pressure. DETAILED DESCRIPTION

[0025] The present application will be further described below in conjunction with specific implementation examples, but the present application is not limited to these examples.

[0026] Example 1

[0027] A pharmaceutical composition for lowering blood lipids and blood pressure, which is composed of durian honey seed extract, red cabbage root-buckler chives composite extract, gastrodin, rothalin, Eucommia ulmoides glycosides, and puerarin in a mass ratio of 2.8:5:1.2:0.7:0.4:1.3.

[0028] The preparation method of the durian seed extract comprises: crushing dried durian seeds, passing through a 60-mesh sieve to obtain seed powder; adding the seed powder into a pH 5.3 phosphate buffer solution at a material-liquid mass ratio of 1:12, adding cellulase at 1% of the mass of the seed powder and pectinase at 1.2% of the mass of the seed powder, and performing enzymatic hydrolysis at 50°C for 2 hours; reducing the temperature to room temperature, adjusting the pH to 2.3, adding pepsin at 1.2% of the mass of the seed powder, and performing enzymatic hydrolysis at 38°C for 2 hours; increasing the temperature to 82°C to inactivate the enzyme for 12 minutes, reducing the temperature to room temperature, adjusting the pH to 6.8, adding ginger protease at 0.8% of the mass of the seed powder, and performing enzymatic hydrolysis at 52°C for 1 hour; increasing the temperature to 82°C to inactivate the enzyme for 12 minutes, reducing the temperature to room temperature, and obtaining an enzymatic hydrolysate containing polypeptides; adding DES cosolvent (the DES cosolvent contains 32 wt% choline chloride and 48 wt% lactic acid, and the balance is deionized water) at 23% of the volume of the enzymatic hydrolysate into the enzymatic hydrolysate, performing ultrasonic extraction at 50°C and 350W for 45 minutes, filtering through a 250-mesh sieve, concentrating the filtrate to 25% of the volume at 48°C under reduced pressure, centrifuging at 8200 rpm for 12 minutes, taking the supernatant, and loading the supernatant onto an MCI GEL CHP20P column; washing the column with 4 BV of deionized water to remove impurities, eluting the column with 2.5 BV of 35% volume concentration of an ethanol aqueous solution and 2.5 BV of 55% volume concentration of an ethanol aqueous solution, collecting the eluate, removing ethanol and part of water from the eluate at 48°C under reduced pressure, and freeze-drying to obtain the durian seed extract.

[0029] The preparation method of the red cabbage root and deer's ear chive composite extract comprises: drying the red cabbage root and the deer's ear chive whole grass, crushing them separately, passing them through a 40-mesh sieve, mixing them at a mass ratio of red cabbage root: deer's ear chive whole grass = 2.5:1.2 to obtain a mixed powder; adding the mixed powder into a culture solution (the culture solution contains 0.6 wt% glucose, 0.4 wt% sucrose and 0.3 wt% yeast extract, and the solvent is water) at a material-liquid mass ratio of 1:12, sterilizing at 123°C for 18 minutes, cooling to room temperature to obtain a fermentation culture medium, inoculating the fermentation culture medium with a bacterium concentration of 5×10 8 CFU / mL of activated liquid of Lactobacillus rhamnosus, and performing anaerobic fermentation at 38°C and pH 6.0 for 66 hours; after the fermentation is completed, centrifuging at 9000 rpm for 12 minutes, taking the supernatant, filtering the supernatant through a 0.22-μm pore size filter to remove bacteria, concentrating the filtrate to 25% of the volume at 48°C under reduced pressure, and loading the filtrate onto a macroporous adsorption resin HP2MG column; washing the column with 3 BV of deionized water to remove impurities, washing the column with 2.5 BV of 35% volume concentration of a methanol aqueous solution to remove impurities, eluting the column with 4 BV of 58% volume concentration of a methanol aqueous solution, collecting the eluate, removing methanol and part of water from the eluate at 48°C under reduced pressure, and freeze-drying to obtain the red cabbage root and deer's ear chive composite extract.

[0030] Example 2

[0031] The application discloses a pharmaceutical composition for reducing blood pressure and blood fat, which is composed of durian seed extract, red rhizoma and luei allium cyperaceae compound extract, gastrodin, uncarine, eucommia ulmoides oliver and puerarin with a mass ratio of 2.0:5.5:0.8:0.8:0.3:1.5.

[0032] The preparation method of the durian seed extract comprises the following steps: crushing dried durian seeds, and sieving the crushed durian seeds through a 60-mesh sieve to obtain seed powder; adding the seed powder into a pH 5.0 phosphate buffer solution at a material-liquid mass ratio of 1:15, adding cellulase at 1.5% of the mass of the seed powder and pectinase at 0.8% of the mass of the seed powder, and performing enzymolysis at 53 DEG C for 2 hours; reducing the temperature to room temperature, adjusting the pH to 2.5, adding pepsin at 1.0% of the mass of the seed powder, and performing enzymolysis at 40 DEG C for 1.5 hours; increasing the temperature to 85 DEG C to inactivate the enzyme for 10 minutes, reducing the temperature to room temperature, adjusting the pH to 7.0, adding ginger protease at 0.5% of the mass of the seed powder, and performing enzymolysis at 55 DEG C for 1 hour; increasing the temperature to 85 DEG C to inactivate the enzyme for 10 minutes, reducing the temperature to room temperature, and obtaining a polypeptide-containing enzymolysis solution; adding DES cosolvent (the DES cosolvent contains 30 wt% choline chloride and 50 wt% lactic acid, and the rest is deionized water) at 25% of the volume of the enzymolysis solution, and performing ultrasonic extraction at 45 DEG C and 400 W for 40 minutes; filtering through a 250-mesh sieve; concentrating the filtrate to 30% of the volume at 45 DEG C under reduced pressure; centrifuging at 8000 rpm for 15 minutes; taking the supernatant; and loading the supernatant onto an MCI GEL CHP20P column, washing the column with 3 BV of deionized water to remove impurities, eluting the column with 2 BV of 40% volume concentration ethanol aqueous solution and 2 BV of 60% volume concentration ethanol aqueous solution, collecting the eluate, removing ethanol and part of water under reduced pressure at 50 DEG C, and freeze-drying to obtain the durian seed extract.

[0033] The preparation method of the red rhizoma and luei allium cyperaceae compound extract comprises the following steps: drying red rhizoma and luei allium cyperaceae, crushing the dried red rhizoma and luei allium cyperaceae respectively, sieving the crushed red rhizoma and luei allium cyperaceae through a 40-mesh sieve, mixing the crushed red rhizoma and luei allium cyperaceae at a mass ratio of 3:1 to obtain mixed powder, adding the mixed powder into a culture solution (the culture solution contains 0.5 wt% glucose, 0.5 wt% sucrose and 0.4 wt% yeast extract, and the solvent is water) at a material-liquid mass ratio of 1:15, sterilizing the culture solution at 121 DEG C for 20 minutes, cooling the culture solution to room temperature to obtain a fermentation culture medium, inoculating the fermentation culture medium with bacteria at a concentration of 1 x 10 9CFU / mL Lactobacillus rhamnosus activation solution, anaerobic fermentation at 35℃, pH 6.5 for 60h; after fermentation, centrifugation at 10000rpm for 10min, take the supernatant, filter sterilization with 0.22μm pore size, filter the filtrate at 50℃ under reduced pressure to 20% of the volume, load into the macroporous adsorption resin HP2MG column, wash with 4BV deionized water to remove impurities and 2BV 40% volume concentration methanol aqueous solution to remove impurities, elute with 55% volume concentration methanol aqueous solution for 5BV, collect the eluate, reduce pressure and concentrate at 45℃ to remove methanol and part of water, freeze-drying to obtain red cabbage root and deer's onion composite extract.

[0034] Example 3

[0035] A pharmaceutical composition for lowering blood pressure and blood lipids, which is composed of durian seed extract, red cabbage root-deer's onion composite extract, gastrodin, uncarine, eucommioside and puerarin with a mass ratio of 3.5:4.5:1.5:0.5:0.5:1.

[0036] The preparation method of the durian seed extract comprises the following steps: crushing dry durian seed, and passing through an 80-mesh sieve to obtain seed powder; adding the seed powder into a pH 5.5 phosphate buffer solution at a material-liquid mass ratio of 1:10, adding cellulase at 0.8% of the mass of the seed powder and pectinase at 1.5% of the mass of the seed powder, and performing enzymolysis at 48℃ for 2.5h; reducing the temperature to room temperature, adjusting the pH to 2.0, adding pepsin at 1.5% of the mass of the seed powder, and performing enzymolysis at 37℃ for 2h; increasing the temperature to 80℃ to inactivate the enzyme for 15min, reducing the temperature to room temperature, adjusting the pH to 6.5, and adding ginger protease at 1.0% of the mass of the seed powder, and performing enzymolysis at 50℃ for 1.5h; increasing the temperature to 80℃ to inactivate the enzyme for 15min, reducing the temperature to room temperature, and obtaining a polypeptide-containing enzymolysis solution; adding DES cosolvent (the DES cosolvent contains 35wt% choline chloride and 45wt% lactic acid, and the rest is deionized water) at 20% of the volume of the enzymolysis solution, and performing ultrasonic extraction at 55℃ and 300W for 50min; filtering through a 200-mesh screen, concentrating the filtrate at 50℃ under reduced pressure to 20% of the volume, centrifuging at 8500rpm for 10min, taking the supernatant, and loading into an MCI GEL CHP20P column; washing with 5BV deionized water to remove impurities, eluting with 30% volume concentration ethanol aqueous solution for 3BV and 50% volume concentration ethanol aqueous solution for 3BV, collecting the eluate, reducing pressure and concentrating at 45℃ to remove ethanol and part of water, and freeze-drying to obtain the durian seed extract.

[0037] The preparation method of the red cabbage root and deer's ear chive composite extract includes: drying and crushing red cabbage roots and deer's ear chives, respectively, passing through a 60-mesh sieve, mixing according to a mass ratio of red cabbage roots to deer's ear chives of 2:1.5 to obtain a mixed powder; adding the mixed powder into a culture solution (the culture solution contains 0.8wt% glucose, 0.3wt% sucrose and 0.2wt% yeast extract, and the solvent is water) according to a solid-liquid mass ratio of 1:10, sterilizing at 125°C for 15min, cooling to room temperature to obtain a fermentation culture medium, inoculating a strain concentration of 1×10 8 CFU / mL Lactobacillus rhamnosus activation solution, anaerobic fermentation at 40°C and pH 5.5 for 72h; after the fermentation is completed, centrifugation is performed at 8000rpm for 15min, the supernatant is taken, bacteria are removed by filtration through a 0.22μm pore size, the filtrate is concentrated to 30% of the volume at 45°C under reduced pressure, and then loaded onto a macroporous adsorption resin HP2MG column, eluted with 2BV deionized water to remove impurities, eluted with 3BV 30% volume concentration methanol aqueous solution to remove impurities, eluted with 60% volume concentration methanol aqueous solution for 3BV, collected eluent, removed methanol and part of water under reduced pressure at 50°C, and freeze-dried to obtain the red cabbage root and deer's ear chive composite extract.

[0038] The preparation method of the drug composition for reducing blood fat and blood pressure in each of the above embodiments includes the following steps: mixing durian seed extract, red cabbage root and deer's ear chive composite extract, gastrodin, uncarine, eucommioside and puerarin according to a prescription mass ratio to obtain a drug composition. The drug composition is mixed with a pharmaceutically acceptable excipient to prepare any pharmaceutically acceptable dosage form, including tablets, capsules, granules, pills, powders and oral liquids. The drug composition is used for preparing a drug for reducing blood fat and blood pressure.

[0039] Comparative Example 1 The difference from Example 1 is that the mass ratio of durian seed extract, red cabbage root and deer's ear chive composite extract, gastrodin, uncarine, eucommioside and puerarin is 5.8:2:1.2:0.7:0.4:1.3.

[0040] Comparative Example 2 The difference from Example 1 is that no durian seed extract is added.

[0041] Comparative Example 3 The difference from Example 1 is that no red cabbage root and deer's ear chive composite extract is added.

[0042] Comparative Example 4 The difference from Example 1 is that no pepsin is used for enzymolysis in the preparation of durian seed extract.

[0043] Comparative Example 5 The difference from Example 1 is that in the preparation of durian seed extract, ginger protease is replaced by papain.

[0044] Comparative Example 6 The difference from Example 1 is that in the preparation of durian seed extract, MCI GEL CHP20P is replaced by macroporous adsorption resin D101.

[0045] Comparative Example 7 The difference from Example 1 is that in the preparation of red cabbage root-kaerf chives composite extract, red cabbage root is not added, and all kaerf chives are used.

[0046] Comparative Example 8 The difference from Example 1 is that in the preparation of red cabbage root-kaerf chives composite extract, kaerf chives are not added, and all red cabbage roots are used.

[0047] Comparative Example 9 The difference from Example 1 is that in the preparation of red cabbage root-kaerf chives composite extract, Lactobacillus rhamnosus is replaced by Lactobacillus plantarum.

[0048] Comparative Example 10 The difference from Example 1 is that in the preparation of red cabbage root-kaerf chives composite extract, macroporous adsorption resin HP2MG is replaced by macroporous adsorption resin D101.

[0049] The raw material sources involved in the above embodiments and comparative examples are as follows: Gastrodin is from Shaanxi Guojian Biotechnology Co., Ltd., with a purity of 98%. Uncarine is from Shanxi Xinnuo Biotechnology Co., Ltd., with a purity of 20%. Eucommioside is from Shanghai Huzeng Biotechnology Co., Ltd., with a purity of 98%. Puerarin is from Shaanxi KeHong Health Industry Co., Ltd., with a purity of 98%. Cellulase is from Shanghai Dinghe Biotechnology Co., Ltd., with an enzyme activity of 100,000 U / g. Pectinase is from Anhui Weimaobiotechnology Co., Ltd., with an enzyme activity of 30,000 U / g. Pepsin is from Xi'an Muguo Biotechnology Co., Ltd., with an enzyme activity of 3,000 U / g. Ginger protease is from Shanghai Yimiao Chemical Technology Co., Ltd., with an enzyme activity of 400 U / mg. Choline chloride is from Hebei Chuangzhiyuan Biotechnology Co., Ltd., with a purity of 98%. Lactic acid is from Shaanxi Mingchong Pharmaceutical Co., Ltd., with a pharmaceutical grade. MCI GEL CHP20P is from Beijing Lvbaicao Technology Development Co., Ltd., with a particle size of 75-150 μm and a manufacturer of Mitsubishi Chemical. Yeast extract is from Jinan Weiduofeng Biotechnology Co., Ltd., for fermentation culture. Lactobacillus rhamnosus (ATCC 53103) is from Shanghai Ruichu Biotechnology Co., Ltd. Macroporous adsorption resin HP2MG is from Beijing Lvbaicao Technology Development Co., Ltd., with a model number of DIAION HP2MGL and a manufacturer of Mitsubishi Chemical. Papain is from Xi'an Changhe Pharmaceutical Co., Ltd., with an enzyme activity of 500,000 U / g. Macroporous adsorption resin D101 is from Shanghai Pukao Biotechnology Co., Ltd., with a particle size range of 0.3-1.2 mm. Lactobacillus plantarum is from Hunan Guangyi Biotechnology Co., Ltd.

[0050] The pharmaceutical composition (without adjuvant) is detected as follows.

[0051] I. Cytotoxicity test Sample preparation: The pharmaceutical composition is dissolved with DMSO to prepare a stock solution of 100 mg / mL. Before use, serial dilution is performed with DMEM culture medium containing 10% fetal bovine serum to obtain working concentrations of 200 μg / mL, 100 μg / mL and 50 μg / mL. The final concentration of DMSO is ensured to be <0.1%. The cell culture medium without the pharmaceutical is set as a blank control, and the culture medium containing 0.1% DMSO is set as a solvent control.

[0052] The detection method comprises the following steps: human umbilical vein endothelial cells (HUVEC) are inoculated in a 96-well plate at a density of 1×10 4 cells / well, and are cultured in a 37°C, 5% CO2 incubator for 24 h to allow the cells to adhere. The old culture medium is discarded, and 200 μL of fresh culture medium containing different concentrations of samples is added to each well. Three replicate wells are set for each concentration. The culture is continued for 24 h. 20 μL of CCK-8 solution is added to each well, which is gently shaken to mix, and the culture is continued for 2 h. The absorbance (OD value) of each well is measured by a microplate reader at a wavelength of 450 nm.

[0053] Evaluation index: cell survival rate (%) = (OD value of sample group - blank background OD value) / (OD value of solvent control group - blank background OD value) x 100%.

[0054] Table 1 Cell survival rate

[0055] The above results are average values.

[0056] II. Hemolysis test: Sample preparation: Take the pharmaceutical composition, dissolve and dilute to 1 mg / mL, 0.5 mg / mL, 0.1 mg / mL working concentration with normal saline. Positive control: distilled water; negative control: normal saline.

[0057] The detection method includes: taking fresh human anticoagulant blood (heparin anticoagulant), washing the red blood cells 3 times with normal saline (1500xg, 10min), and finally preparing a 2% (v / v) red blood cell suspension. Take the test tube, add 0.5 mL of red blood cell suspension and 0.5 mL of each concentration of sample solution, positive control, negative control, respectively. Gently vortex to mix, incubate in a 37°C water bath for 1 h. After incubation, centrifuge the test tube at 1500xg for 10 min. Carefully pipette the supernatant and move it to a 96-well plate, and measure the absorbance at 540 nm wavelength with a microplate reader. Each group has 3 parallel samples.

[0058] Evaluation index: hemolysis rate (%) = (OD value of sample - OD value of negative control) / (OD value of positive control - OD value of negative control) x 100%.

[0059] Table 2 Hemolysis rate

[0060] The above results are average values.

[0061] III. HMG-CoA reductase inhibitory activity detection: Sample preparation: Take the pharmaceutical composition, dissolve and dilute to 200 μg / mL, 100 μg / mL, 50 μg / mL working concentration with enzyme reaction buffer (50 mM Tris-HCl, 5 mM MgCl2, pH 7.4). Set up a blank control group without drug.

[0062] The detection method comprises: constructing a 200 μL reaction system in a 96-well plate: containing 50 μL of a sample, 10 μL of HMG-CoA reductase (0.2 U / mL), 50 μL of a substrate mixture (containing 0.2 mM HMG-CoA and 0.1 mM NADPH), and the balance is enzyme reaction buffer. Incubate the reaction plate at 37°C for 50 min. Using a microplate reader, monitor the rate of decrease of NADPH absorbance (ΔOD / min) at 340 nm wavelength. Three parallel samples per group.

[0063] Evaluation index: inhibition rate (%) = [1- (sample group ΔOD / min) / (blank control group ΔOD / min)] x 100%.

[0064] Table 3 HMG-CoA reductase activity inhibition rate

[0065] The above results are average values.

[0066] Four, angiotensin converting enzyme (ACE) inhibition activity detection: Sample preparation: Take the pharmaceutical composition, dissolve and dilute to 200 μg / mL, 100 μg / mL, 50 μg / mL working concentration with buffer (100 mM borate buffer containing 300 mM NaCl, pH 8.3). Set up a blank control group without drugs.

[0067] The detection method comprises: in a test tube, sequentially add: 50 μL of a sample, 50 μL of an ACE solution (0.1 U / mL), mix well, and pre-incubate at 37°C for 10 min. Add 150 μL of substrate (Hippuryl-His-Leu hippuryl-histidyl-leucine, 5 mM in the same buffer) to start the reaction, and continue to incubate at 37°C for 30 min. Add 250 μL of 1M HCl to terminate the reaction. Add 1.0 mL of ethyl acetate, vortex to extract, and after the layers are separated, take 0.8 mL of the upper organic phase to a new tube. Evaporate the organic solvent in a 60°C water bath. Redissolve the residue with 1.0 mL of distilled water, and measure the absorbance at 228 nm wavelength using a microplate reader. Three parallel samples per group.

[0068] Evaluation index: inhibition rate (%) = [1- (sample group OD value) / (blank control group OD value)] x 100%.

[0069] Table 4 ACE activity inhibition rate

[0070] The above results are average values.

[0071] Five, LDL receptor protein expression detection (Western Blot): Sample preparation: The pharmaceutical composition was dissolved and diluted with serum-free cell culture medium to a working concentration of 100 μg / mL, 50 μg / mL, and 10 μg / mL.

[0072] The detection method comprises: human liver cancer cells (HepG2) are inoculated in a 6-well plate at a density of 5×10 5 cells / well, and are cultured for 24 h. The culture medium is replaced with serum-free culture medium containing different concentrations of the sample, and the cells are cultured for another 24 h. The cells are lysed, total protein is extracted, and the protein is quantified by the BCA method. An equal amount of protein is subjected to SDS-PAGE electrophoresis and transferred to a PVDF membrane. After blocking with 5% skim milk for 1 h, the primary antibody (rabbit anti-human LDL receptor monoclonal antibody, dilution ratio 1:1000) is incubated, the HRP-labeled secondary antibody (goat anti-rabbit IgG, dilution ratio 1:5000) is incubated at 4°C overnight, and the HRP-labeled secondary antibody is incubated at room temperature for 1 h. The ECL chemiluminescence kit is used for development, and the chemiluminescence imaging system is used to collect images. The gray value of the target band is analyzed by using software such as Image J. Each group has three parallel samples.

[0073] Evaluation index: Relative expression amount of LDL receptor protein (GAPDH as internal reference). Compared with the solvent control group, the up-regulation fold of the LDL receptor protein expression of each concentration of the sample is calculated.

[0074] Table 5 LDL receptor protein expression up-regulation fold

[0075] The above results are average values.

[0076] Six, nitric oxide release amount detection (Griess method): Sample preparation: The pharmaceutical composition was dissolved and diluted with serum-free cell culture medium to a working concentration of 100 μg / mL, 50 μg / mL, and 10 μg / mL.

[0077] The detection method comprises: HUVEC cells are inoculated in a 6-well plate at a density of 5×10 4Cells were seeded at a density of 1 x 105cells / well in 24-well plates and incubated for 24 h to reach 80% confluence. The medium was replaced with 500 μL of low serum (1% FBS) medium containing different concentrations of the sample and incubated for another 24 h. The cell supernatant was collected and centrifuged at 12,000 x g for 5 min to remove cell debris. 100 μL of the supernatant was mixed with an equal volume of Griess reagent (containing 1% sulfanilamide, 0.1% NEDD in 2.5% H3PO4) in a 96-well plate and incubated at room temperature for 15 min in the dark. The absorbance was measured at 540 nm using a microplate reader. Three replicates were performed for each group. The concentration of nitrite (NO2 - ) in the supernatant was calculated using a sodium nitrite (NaNO2) standard curve (0 μM-100 μM) to represent the amount of NO released.

[0078] Evaluation index: NO release concentration (μM).

[0079] Table 6. Nitric oxide release amount

[0080] The above results are the average values.

[0081] As can be seen from the above results, the active drugs of Examples 1 to 3 have better efficacy and safety. The active polypeptide of durian seed extract can repair cells and reduce red blood cell rupture. The fermentation components (organic acids, flavones) of the composite extract of rhizoma pyrrosiae and tulipa gesneriana assist in reducing polypeptide stimulation. The two are matched in an optimized ratio to reduce cytotoxicity and hemolysis risk. The durian seed extract is enzymatically digested by pepsin and ginger protease to generate safe small molecule polypeptides, avoiding harmful protein residues. The durian seed extract is further purified by MCI GEL CHP20P column to remove impurities. The composite extract of rhizoma pyrrosiae and tulipa gesneriana is fermented by lactobacillus rhamnosus and purified by HP2MG column to double-ensure biocompatibility. The active polypeptide of durian seed extract and the fermentation components of the composite extract of rhizoma pyrrosiae and tulipa gesneriana synergistically enhance the inhibition of HMG-CoA reductase to block the key step of cholesterol synthesis. The active polypeptide upregulates the expression of LDL receptor in hepatocytes, and the flavones in the composite extract stabilize the receptor structure to accelerate the uptake and metabolism of LDL-C in the blood. Gastrodin and uncarine assist in regulating the lipid metabolism pathway, and multiple targets synergistically reduce lipids. The fermentation components of the composite extract of rhizoma pyrrosiae and tulipa gesneriana and the durian seed extract synergistically inhibit ACE to weaken the contraction signal. The diastolic peptide of the durian seed extract activates eNOS to promote NO generation, and the tulipa gesneriana alkaloid in the composite extract prolongs the action time of NO. Eucommia ulmoides syrup improves vascular elasticity.

[0082] Example 1: The ratio of durian seed extract and red vegetable root-bulrush complex extract is changed. The core problem is that the balance of the synergistic effect between the components is destroyed. The lipid-lowering (inhibition of HMG-CoA reductase, up-regulation of LDL receptors), blood pressure-lowering (inhibition of ACE, promotion of NO release), and cell protection functions of the pharmaceutical composition depend on the optimal ratio of durian seed extract (active polypeptide) and red vegetable root-bulrush complex extract (fermented active ingredients). After the ratio is reversed, the low-dose complex extract cannot provide enough organic acids and flavonoid components, which cannot assist polypeptides in reducing cell toxicity and cannot synergistically enhance enzyme inhibition and receptor regulation ability, ultimately leading to a comprehensive weakening of drug efficacy indicators and a decrease in safety.

[0083] Example 2: No durian seed extract is added. Durian seed extract is the core of cell protection and lipid-lowering synergy. The small molecule active polypeptide (generated by stepwise enzymolysis by pepsin and ginger protease) contained in it can repair vascular endothelial cells, reduce red blood cell membrane damage, and at the same time enhance the efficiency of HMG-CoA reductase inhibition and the ability to up-regulate LDL receptors. Without this extract, the cells lose their protective barrier, the risk of toxicity and hemolysis increases, and the lipid-lowering pathway loses a key synergistic factor, and the ability to release NO (vasodilation) is weakened due to the absence of polypeptides, leading to all indicators being inferior to the example.

[0084] Example 3: No red vegetable root-bulrush complex extract is added. This complex extract has a synergistic effect with durian seed extract. After fermentation by Lactobacillus rhamnosus, the product can strongly inhibit ACE and activate endothelial NO synthase. After the absence of the complex extract, ACE inhibition rate and NO release amount significantly decrease, and the blood pressure-lowering effect is weakened; in addition, the synergistic effect of the complex extract on the durian seed extract disappears, leading to a simultaneous deterioration of lipid-lowering indicators and cell safety.

[0085] In Example 4, pepsin is not used in the preparation of durian seed extract; in Example 5, papain is used instead of ginger protease in the preparation of durian seed extract. The use of pepsin and ginger protease in combination provides complementary enzymolysis, which can generate specific efficacy polypeptides. The absence of pepsin or the replacement of ginger protease with papain results in mismatched enzymolysis, different polypeptide structures, and a direct impact on the efficacy of the product. Some products bind to cell surface receptors, increasing toxicity and hemolysis risk; at the same time, specific active polypeptides are insufficient to synergistically enhance enzyme inhibition, receptor up-regulation, and NO release.

[0086] Example 6: D101 resin is used instead of MCI GEL CHP20P in the preparation of durian seed extract. MCI GEL CHP20P and D101 have different polarities, resulting in different purified products. The replacement of D101 leads to the loss of effective active ingredients, the retention of harmful impurities, cell damage, increased toxicity, and hemolysis rate; insufficient active ingredients weaken enzyme inhibition, receptor up-regulation, and NO release.

[0087] In Comparative Example 7, the roots of Rhizoma Coptidis were not added in the preparation of the Rhizoma Coptidis-Flueggea Ipecacuanha complex extract; in Comparative Example 8, the whole grass of Flueggea Ipecacuanha was not added. The synergistic components of the roots of Rhizoma Coptidis or Flueggea Ipecacuanha were missing, and the types of effective components were insufficient when only the whole grass of Flueggea Ipecacuanha or the roots of Rhizoma Coptidis was used. The single raw material substrate led to an increase in some harmful substances after fermentation, the synergistic effect of the two was missing, and the indicators decreased.

[0088] Comparative Example 9: Lactobacillus plantarum was used to replace Lactobacillus rhamnosus in the preparation of the Rhizoma Coptidis-Flueggea Ipecacuanha complex extract. Lactobacillus plantarum cannot fully release the active components of the roots of Rhizoma Coptidis and the whole grass of Flueggea Ipecacuanha; its metabolic products contain more propionic acid, inhibit the conversion of active components, and some metabolic byproducts will damage cells. The final complex extract is insufficient in active components, and all the pharmacodynamic and safety indicators are significantly inferior to those of the embodiment.

[0089] Comparative Example 10: D101 resin was used to replace HP2MG in the preparation of the Rhizoma Coptidis-Flueggea Ipecacuanha complex extract. The adsorption and purification products of D101 and HP2MG are different, and the replacement of D101 leads to the loss of some effective active components, and the retention of some harmful impurities, damage to cells, and an increase in toxicity and hemolysis rate; the insufficient active components weaken the enzyme inhibition, receptor up-regulation, and NO release abilities.

Claims

1. A pharmaceutical composition for lowering blood pressure and blood lipid, characterized in that, The pharmaceutical composition is composed of durian seed extract, red cabbage root and deer's ear chive composite extract, gastrodin, uncarine, eucommioside and puerarin in a mass ratio of (2.0-3.5):(4.5-5.5):(0.8-1.5):(0.5-0.8):(0.3-0.5):(1-1.5); The durian seed extract is prepared by the following steps: after cellulase and pectinase are used for co-enzymolysis, the durian seed is subjected to step-by-step enzymolysis by pepsin and ginger protease, then DES cosolvent is added for ultrasonic extraction, and the extract is purified by an MCI GEL CHP20P column. The red cabbage root and deer's ear chive composite extract is prepared by the following steps: red cabbage root and deer's ear chive are fermented by Lactobacillus rhamnosus, and the fermentation liquor is purified by a macroporous adsorption resin HP2MG column.

2. The pharmaceutical composition for reducing blood pressure and blood lipid according to claim 1, wherein The preparation method of the durian seed extract comprises the following steps: dried durian seed is crushed to obtain seed powder; the seed powder is added into a phosphate buffer solution in a solid-liquid mass ratio of 1:(10-15), cellulase and pectinase are added, and enzymolysis is carried out at 48-53 ℃ for 2-2.5 h; the temperature is lowered, the pH is adjusted to 2.0-2.5, pepsin is added, and enzymolysis is carried out at 37-40 ℃ for 1.5-2 h; the enzyme is inactivated, the temperature is lowered, the pH is adjusted to 6.5-7.0, ginger protease is added, and enzymolysis is carried out at 50-55 ℃ for 1-1.5 h; the enzyme is inactivated, the temperature is lowered, and a polypeptide-containing enzymolysis liquor is obtained; DES cosolvent is added to the enzymolysis liquor, ultrasonic extraction is carried out, filtration is carried out, the filtrate is concentrated under reduced pressure, centrifugation is carried out, the supernatant is taken, and the supernatant is loaded onto an MCI GEL CHP20P column; 3-5 BV of deionized water is used for elution and impurities removal, 2-3 BV of 30%-40% volume concentration ethanol aqueous solution is used for elution, 2-3 BV of 50%-60% volume concentration ethanol aqueous solution is used for elution, the eluate is collected, the eluate is concentrated under reduced pressure at 45-50 ℃, and freeze-drying is carried out to obtain the durian seed extract.

3. The pharmaceutical composition for reducing blood pressure and blood lipid according to claim 2, characterized in that, The particle size of the seed powder is 60-80 mesh; the pH of the phosphate buffer solution is 5.0-5.5; the cellulase is added in an amount of 0.8%-1.5% of the mass of the seed powder; the pectinase is added in an amount of 0.8%-1.5% of the mass of the seed powder; the pepsin is added in an amount of 1.0%-1.5% of the mass of the seed powder; the ginger protease is added in an amount of 0.5%-1.0% of the mass of the seed powder; and the inactivation of the enzymes is carried out by raising the temperature to 80-85 ℃ for 10-15 min.

4. The pharmaceutical composition for reducing blood pressure and blood lipid according to claim 2, wherein the composition is a tablet. The adding amount of the DES cosolvent is 20% to 25% of the volume of the enzymatic hydrolysis liquid; the DES cosolvent contains 30wt% to 35wt% choline chloride and 45wt% to 50wt% lactic acid, and the balance is deionized water; the ultrasonic extraction is carried out at 45°C to 55°C and 300W to 400W for 40min to 50min; the mesh size of the filter screen is 200 meshes to 250 meshes; the filtration liquid is concentrated under reduced pressure at 45°C to 50°C to a volume of 20% to 30%; the centrifugation is carried out at 8000rpm to 8500rpm for 10min to 15min; and the eluent is concentrated under reduced pressure at 45°C to 50°C to remove ethanol and part of water.

5. The pharmaceutical composition for reducing blood pressure and blood lipid according to claim 1, wherein The preparation method of the red cabbage root and deer ear chive composite extract includes: drying and then crushing the red cabbage root and deer ear chive whole grass respectively, passing through 40 meshes to 60 meshes screen, mixing according to the mass ratio of red cabbage root: deer ear chive whole grass = (2 to 3): (1 to 1.5) to obtain mixed powder; adding the mixed powder into culture solution according to the solid-liquid mass ratio of 1: (10 to 15), sterilizing, and cooling to obtain fermentation culture medium, inoculating Lactobacillus rhamnosus activation liquid, and carrying out anaerobic fermentation at 35°C to 40°C and pH 5.5 to 6.5 for 60h to 72h; after the fermentation is completed, centrifuging, taking the supernatant, filtering to remove bacteria, and concentrating the filtrate under reduced pressure, and then loading onto a macroporous adsorption resin HP2MG column, washing with 2BV to 4BV deionized water to remove impurities, and then washing with 2BV to 3BV 30% to 40% volume concentration methanol aqueous solution to remove impurities, and then eluting with 55% to 60% volume concentration methanol aqueous solution for 3BV to 5BV, collecting the eluent, concentrating the eluent under reduced pressure, and then freeze-drying to obtain the red cabbage root and deer ear chive composite extract.

6. The pharmaceutical composition for reducing blood pressure and blood lipid according to claim 5, wherein, The culture solution contains 0.5wt%-0.8wt% glucose, 0.3wt%-0.5wt% sucrose and 0.2wt%-0.4wt% yeast extract, and the solvent is water; the sterilization is 121°C-125°C sterilization for 15min-20min; the inoculation amount of the Lactobacillus rhamnosus activation solution is 3%-5% of the volume of the fermentation medium; and the bacterial concentration of the Lactobacillus rhamnosus activation solution is 1×10 8 CFU / mL-1×10 9 CFU / mL.

7. The pharmaceutical composition for reducing blood pressure and blood lipid according to claim 5, wherein the composition is in the form of tablet, capsule, granule, powder, injection, suppository, or the like. The centrifugation is carried out at 8000rpm to 10000rpm for 10min to 15min; the pore size of the filter for removing bacteria is 0.22μm; the concentration of the filtrate under reduced pressure is carried out at 45°C to 50°C to a volume of 20% to 30%; and the concentration of the eluent under reduced pressure is carried out at 45°C to 50°C to remove methanol and part of water.

8. A process for the preparation of a pharmaceutical composition for lowering blood pressure and blood lipids according to any one of claims 1 to 7, characterized in that, The method comprises the following steps: mixing the durian seed extract, the red cabbage root and deer ear chive composite extract, the gastrodin, the uncarine, the eucommioside and the puerarin according to the prescription mass ratio to obtain a pharmaceutical composition.

9. The method of claim 8, wherein the pharmaceutical composition is prepared by mixing the active ingredients in a suitable solvent. The pharmaceutical composition is mixed with a pharmaceutically acceptable excipient to prepare any pharmaceutically acceptable dosage form, including tablets, capsules, granules, pills, powders and oral liquids.

10. Use of the pharmaceutical composition for lowering blood fat and blood pressure according to any one of claims 1 to 7 in the preparation of a medicine for lowering blood fat and blood pressure.

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