Extraction method and application of qi-tonifying and blood-activating traditional Chinese medicine composition

Abstract

The invention relates to the technical field of traditional Chinese medicine compositions, in particular to an extraction method and application of a qi-tonifying and blood-activating traditional Chinese medicine composition, and the extraction method comprises the following steps: S1, pretreating raw materials, freeze-drying red ginseng, performing supercritical COextraction on salvia miltiorrhiza and the like, stir-frying rhizoma atractylodis with bran, cutting astragalus membranaceus and the like, performing fixation and drying, and stir-frying honey-fried licorice root with honey; s2, composite enzymatic hydrolysis: preparing a composite enzyme liquid containing an enzyme activity protective agent, mixing the composite enzyme liquid with the raw materials and water, adjusting the pH value, performing enzymatic hydrolysis and performing ultrasonic assistance; s3, ultrasonic extraction: heating an enzymolysis system, adding an active synergist and a stabilizer, performing ultrasonic extraction, and supplementing water; s4, purifying and filtering, carrying out microfiltration on the extracting solution, carrying out AB-8 resin pretreatment, loading a sample for elution, and collecting qualified eluent; s5, concentrating and drying, concentrating the eluent under reduced pressure to a set density, performing spray drying, and detecting that an extract reaches the standard to obtain a finished product. The method improves the content and purity of effective components of the extract, shortens the drying time, improves the extraction efficiency, ensures the stable quality of the finished product, is suitable for heart failure treatment, and is superior to the traditional process.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine compositions, in particular to an extraction method and application of a traditional Chinese medicine composition for tonifying qi and activating blood. BACKGROUND

[0002] Traditional Chinese medicine compositions for tonifying qi and activating blood are widely used in the treatment of cardiovascular diseases, especially for heart failure. They can tonify qi to enhance the pumping capacity of the heart, activate blood to improve blood circulation, and relieve symptoms such as fatigue, chest tightness, and palpitations, which is in line with the treatment concept of "harmonizing qi and blood" in traditional Chinese medicine. Heart failure is a common clinical severe disease, and patients often show decreased cardiac function and reduced left ventricular ejection fraction. Current treatments rely on western medicines such as cardiotonic, diuretic, and vasodilator drugs, but long-term use can easily lead to drug resistance and side effects, and it is difficult to fundamentally improve the pathological state of qi deficiency and blood stasis. Therefore, traditional Chinese medicine compositions for tonifying qi and activating blood that have both efficacy and safety have become a research focus.

[0003] Traditional Chinese medicine compositions for tonifying qi and activating blood are widely used in the treatment of cardiovascular diseases, especially for heart failure. They can tonify qi to enhance the pumping capacity of the heart, activate blood to improve blood circulation, and relieve symptoms such as fatigue, chest tightness, and palpitations, which is in line with the treatment concept of "harmonizing qi and blood" in traditional Chinese medicine. Heart failure is a common clinical severe disease, and patients often show decreased cardiac function and reduced left ventricular ejection fraction. Current treatments rely on western medicines such as cardiotonic, diuretic, and vasodilator drugs, but long-term use can easily lead to drug resistance and side effects, and it is difficult to fundamentally improve the pathological state of qi deficiency and blood stasis. Therefore, traditional Chinese medicine compositions for tonifying qi and activating blood that have both efficacy and safety have become a research focus.

[0004] In the effective component extraction stage, the traditional method mainly uses water decoction, which has the problems of high extraction temperature and long extraction time, which can easily damage heat-sensitive active ingredients. Moreover, the impurity content in the extraction liquid is high, and the subsequent purification is difficult. Some processes try single enzyme hydrolysis or ultrasonic extraction, but the single enzyme selection cannot synergistically degrade cellulose, pectin, and other cell wall components, and the enzyme hydrolysis efficiency is limited. The ultrasonic extraction parameters lack precise control, leading to uneven dissolution of active ingredients and poor stability of extraction effect. At the same time, the traditional process does not introduce active synergists and stabilizers, resulting in low active ingredient content and poor stability of the finished product, which is prone to oxidative degradation during storage and affects the efficacy.

[0005] There are also defects in the purification and drying links: traditional purification mostly uses simple filtration or alcohol precipitation, which cannot effectively remove polysaccharides, proteins, and other impurities, resulting in low purity of the extract. Drying mostly uses hot air drying at normal pressure, which has high temperature and long drying time, easily leading to clumping of the extract and further loss of active ingredients. In addition, the existing traditional Chinese medicine composition preparation process lacks standardized quality control means, and the key links such as raw material ratio and extraction parameters fluctuate greatly, resulting in poor consistency of the finished product quality and difficulty in meeting the strict requirements of drug production.

[0006] At the application level, the traditional Yiqi Huoxue traditional Chinese medicine composition is mostly in the form of powder or decoction, the dosage form is single, the patient's convenience is poor, and the application of heart failure disease lacks clear indication definition and clinical data support, and it is difficult to accurately match the treatment needs of specific heart failure population such as NYHA cardiac function classification II-III and left ventricular ejection fraction <45%. In summary, the existing Yiqi Huoxue traditional Chinese medicine composition has short boards in raw material processing, extraction efficiency, purification effect, dosage form optimization and clinical application targeting, and it is urgent to develop an extraction method with precise process, strict quality control, stable efficacy and adaptation to heart failure treatment, so as to promote the high-quality application of Yiqi Huoxue traditional Chinese medicine in the field of cardiovascular disease treatment. SUMMARY

[0007] (I) Technical problems solved In view of the deficiencies of the prior art, the present application provides an extraction method and application of Yiqi Huoxue traditional Chinese medicine composition.

[0008] (II) Technical solutions An extraction method of Yiqi Huoxue traditional Chinese medicine composition, comprising the following steps: S1: raw material pretreatment, selecting 2-2.5 parts of red ginseng, 1-1.2 parts of salvia miltiorrhiza, 1-1.2 parts of chuanxiong, 1-1.2 parts of sanchi, 1-1.2 parts of bran-fried atractylodes, 0.8-1 parts of astragalus, 0.5-0.8 parts of pueraria root, 0.3-0.5 parts of chuanmaiton, and 0.2-0.4 parts of honey-fried licorice; wherein the red ginseng is subjected to freeze-drying treatment; the salvia miltiorrhiza, chuanxiong and sanchi are subjected to supercritical CO2 extraction, and the extract and the remaining dregs are collected; the astragalus, pueraria and ophiopogon are cut into sections, then subjected to steam fixation, and dried in a blast drying oven after fixation; S2: composite enzymolysis, adding composite enzyme solution and deionized water to all the raw materials treated in S1, the composite enzyme solution is composed of cellulase, pectinase and protease; adjusting the pH of the system to 4.5-5.5 with citric acid-sodium citrate buffer, and transferring the mixed system to a constant temperature stirring tank for enzymolysis; during the enzymolysis process, the ultrasonic auxiliary device is started once every 30 minutes, and the enzymolysis system is obtained after the enzymolysis is completed; S3: ultrasonic extraction, transferring the enzymolysis system obtained in S2 to an ultrasonic extraction tank, adding active synergist and stabilizer into the extraction tank, the active synergist is composed of safflower glycoside and paeoniflorin, and the stabilizer is composed of β-cyclodextrin and pectin; starting the ultrasonic extraction device, adding deionized water into the extraction tank every 1 hour during the extraction process, and obtaining the extraction liquid after the extraction is completed; S4: purification filtration, the extract obtained in S3 is transferred to a plate and frame filter device, and the filtrate after filtration is collected; the filtrate is pumped into a chromatography column, and after the whole sample is completed, adsorption is carried out; after adsorption is completed, elution is carried out with ethanol solution, and the eluate is collected; during the elution process, the color of the eluate is observed through the chromatography column sight, and when the color of the eluate changes from dark to light, timing collection is started, and collection is stopped until the color of the eluate is colorless; S5: concentration and drying, the eluate collected in S4 is transferred to a reduced pressure concentration tank, and reduced pressure concentration is started; the relative density of the concentrated solution is determined every 30 minutes with a densitometer, and when the relative density reaches 1.2-1.3, the concentration is stopped, and a concentrated paste is obtained; the concentrated paste is transferred to a spray dryer for spray drying; after drying is completed, the dried product is collected, and a Yiqi Huoxue traditional Chinese medicine composition extract is obtained.

[0009] Preferably, the processing process of honey-fried licorice in S1 is also included; the specific steps are as follows: licorice medicinal materials are taken, impurities are removed, and then the licorice is cut into slices with a thickness of 2-3 mm; honey is weighed at 20-30% of the mass of the licorice slices, deionized water is weighed at 10-15% of the mass of the licorice slices, the honey and the deionized water are mixed, and stirring is carried out until the honey is completely dissolved to obtain honey water; the licorice slices are placed in a stirring tank, the honey water is added, stirring is started, the stirring rate is 40-60 rpm, stirring is stopped after 10-15 minutes, and soaking is carried out for 1-2 hours; after soaking is completed, the licorice slices are transferred to a frying machine, the temperature of the frying machine is set to 110-120℃, the frying time is 8-10 minutes, and the licorice slices are turned over every 2 minutes during the frying; when the surface of the licorice slices is dark yellow and not sticky, the frying is stopped, the licorice slices are taken out and cooled to room temperature, and then the licorice slices are pulverized with a pulverizer, and the pulverized licorice is sieved through a 10-20 mesh sieve to obtain honey-fried licorice, which is ready for use.

[0010] Preferably, the preparation process of the composite enzyme solution in S2 is also included; the specific steps are as follows: cellulase, pectinase, and protease powders are weighed according to the mass ratio of 25-30% cellulase, 15-20% pectinase, and 8-12% protease; deionized water is taken, heated to 35-40℃, and then the weighed enzyme powders are added to the deionized water, stirring is started, the stirring rate is 300-500 rpm, and stirring is carried out for 15-20 minutes until the enzyme powders are completely dissolved; an enzyme activity preservative is added to the enzyme solution, the enzyme activity preservative is added in an amount of 0.01-0.02 parts of the total mass of the enzyme solution, and the enzyme activity preservative is composed of sorbitol and EDTA-2Na, sorbitol accounts for 5-10% of the enzyme activity preservative, and EDTA-2Na accounts for 1-2% of the enzyme activity preservative; stirring is continued for 5-10 minutes to completely mix the enzyme activity preservative, and then the enzyme solution is cooled to room temperature to obtain a composite enzyme solution, which is ready for use.

[0011] Preferably, a temperature sensor is installed in the extraction tank during ultrasonic extraction in S3, and the temperature sensor is connected with a temperature control system to monitor the temperature of the extraction system in real time; when the system temperature is monitored to be lower than 70℃, the temperature control system automatically starts the water bath heating device to pass hot water into the extraction tank jacket, the temperature of the hot water is 85~90℃, until the system temperature rises to the range of 70~80℃, then the water bath heating device is closed; during the whole ultrasonic extraction process, the temperature control method ensures that the system temperature is stable in the range of 70~80℃.

[0012] Preferably, AB-8 macroporous resin is installed in the chromatographic column in S4, and the AB-8 macroporous resin needs to be pretreated before use; the specific steps are as follows: take the AB-8 macroporous resin, soak it in 95% ethanol solution for 24 hours, stir every 6 hours during the soaking period, after the soaking is completed, rinse the resin with deionized water until the rinsing water has no alcohol smell, detect the alcohol content of the rinsing water, and the alcohol content needs to be ≤0.5%; then soak the resin with 5% hydrochloric acid solution for 2 hours, stir every 30 minutes during the soaking process, after the soaking is completed, rinse the resin with deionized water until the rinsing water is neutral, detect the pH value with pH paper, and the pH needs to be 6~7; then soak the resin with 5% sodium hydroxide solution for 2 hours, stir every 30 minutes during the soaking process, after the soaking is completed, rinse the resin with deionized water until the rinsing water is neutral, detect the pH value with pH paper, and the pH needs to be 6~7; finally, drain the pretreated resin, install it in the chromatographic column, and the column height to diameter ratio is 3~5:1, ready for use.

[0013] Preferably, the eluent is collected by a segmented collection method in S4; the specific operation is as follows: prepare multiple collection bottles, each with a volume of 0.5BV; after the elution starts, the first collection bottle collects the first 0.5BV eluent, and the part of the eluent is discarded after the collection is completed; from the second collection bottle, each collection bottle collects 0.5BV eluent, and a total of 3~4 collection bottles are collected; the eluent in each collection bottle is detected by high performance liquid chromatography, and the detection conditions are as follows: C18 column, mobile phase methanol-water, flow rate 1.0mL / min, column temperature 30℃, detection wavelength 280nm; according to the detection results, the eluent with tanshinone IIA content ≥0.2% and notoginseng saponin R1 content ≥0.15% is collected, the eluent meeting the requirements is combined, and used as the raw material for subsequent concentration.

[0014] Preferably, an online density monitor is used in the process of reducing pressure concentration in S5 to monitor the relative density of the concentrated liquid in real time; the online density monitor is connected to the discharge port of the concentration tank, and the relative density data is recorded automatically every 30 minutes; when the monitored relative density reaches 1.2, start recording data every 10 minutes; when the relative density reaches the set value within the interval of 1.2-1.3, immediately turn off the heating device and vacuum system of the concentration tank to stop concentration; after concentration stops, transfer the concentrated paste to a storage tank, keep the temperature of the storage tank at 50-55°C to prevent the concentrated paste from solidifying, and immediately transfer it after the spray drying equipment is ready.

[0015] Preferably, the extract needs to be detected for particle size after spray drying in S5; laser particle size analyzer is used for detection, and the extract sample is mixed with deionized water before detection, ultrasonic dispersion for 5 minutes, and dispersion concentration of 0.1-0.5%; the detection range is set to 0.1-100 μm, each sample is detected for 3 times, and the average value is taken; according to the detection results, if more than 90% of the extract particle size is not within the interval of 10-50 μm, the extract is transferred to a supermicro grinder, the grinding speed is set to 20,000-25,000 rpm, and the grinding time is 1-3 minutes; after grinding, the particle size is detected again until more than 90% of the extract particle size reaches the requirement of 10-50 μm to obtain qualified extract.

[0016] Preferably, the extract needs to be detected for moisture and ash content; vacuum drying method is used for moisture detection, 2-3 g of extract sample is placed in a weighing bottle, placed in a vacuum drying oven, temperature 105°C, vacuum degree 0.09 MPa, dried for 4 hours, weighed after cooling, and the moisture content is calculated, which needs to be ≤3%; muffle furnace calcination method is used for ash content detection, 2-3 g of extract sample is placed in a porcelain crucible, carbonized on an electric stove until smokeless, then transferred to a muffle furnace, temperature 550°C, calcined for 4 hours, weighed after cooling, and the total ash content is calculated, which needs to be ≤5%; if the moisture or ash content does not meet the standard, the extract is returned to the reducing pressure concentration tank in S5 for re-concentration and drying, the concentration time is appropriately extended, the inlet air temperature is appropriately increased by 5-10°C during drying, and the extract is detected again after reprocessing until the moisture and ash content meet the standard.

[0017] Preferably, the Qi-invigorating and blood-activating Chinese medicine composition is used to prepare a medicine for treating heart failure, and the extract is mixed with a pharmaceutical excipient, wherein the pharmaceutical excipient is selected from one or more of microcrystalline cellulose, lactose, and hydroxypropyl methylcellulose, and the mass ratio of the extract to the pharmaceutical excipient is 1~2:1; after mixing, different dosage forms are made as needed. When making capsules, the mixture is filled in hollow capsules, and each capsule has a filling amount of 0.3~0.5g; when making tablets, magnesium stearate is added to the mixture, and tablets with a diameter of 6~8mm are pressed; when making granules, the mixture is made into a soft material with an ethanol solution, granulated through a 16-mesh sieve, dried at 60~70℃, and sieved through a 14-mesh sieve for whole particles; the patient corresponding to the heart failure must meet the NYHA heart function grade II~III and the ventricular ejection fraction is <45%, and the types of heart failure include hypertensive heart disease, cor pulmonale, rheumatic heart disease, and heart failure caused by coronary heart disease.

[0018] (3) Beneficial technical effects Compared with the existing technology, the beneficial effects of the present invention are: 1. Differentiated pretreatment processes are designed based on the characteristics of different medicinal materials. Low-temperature freeze-drying of red ginseng maximizes the retention of heat-sensitive active ingredients such as ginsenosides. Supercritical CO2 extraction pretreatment of salvia miltiorrhiza, Chuanxiong, and Panax notoginseng disrupts the cell wall structure and promotes the subsequent dissolution of active ingredients. Stir-frying Atractylodes macrocephala with bran enhances its dampness-removing effect. Steam fixation and drying of Astragalus membranaceus, Pueraria lobata, and Ophiopogon japonicus reduces the introduction of impurities. These differentiated pretreatments ensure more complete retention of each medicinal material's active ingredients, laying the foundation for subsequent efficient extraction and addressing the issues of rough raw material processing and severe active ingredient loss associated with traditional processes.

[0019] 2. The synergistic effect of combined enzymatic hydrolysis and ultrasonic extraction: multiple enzymes collaborate to degrade cell wall components, while ultrasound assists in improving dissolution efficiency. Precise control of enzymatic hydrolysis temperature, pH, and ultrasonic power and frequency ensures uniform dissolution of active ingredients. The addition of active enhancers enhances the overall biological activity of the extract, while stabilizers improve the stability of the active ingredients and prevent oxidative degradation. The purification stage utilizes a combination of microfiltration membranes and macroporous resin chromatography, precisely controlling sample loading and elution flow rates to effectively remove impurities and enhance extract purity, addressing the issues of low extraction efficiency, poor purification results, and high impurity content in the finished product.

[0020] 3. Combining vacuum concentration with spray drying, by precisely controlling the relative density of the concentrate, the spray drying inlet and outlet air temperatures, and the atomization pressure, we avoid over-concentration or high-temperature damage to the extract. The resulting extract is uniform in particle size and free of agglomerates. Strict quality control of moisture and ash content ensures consistent quality of the finished product. Furthermore, standardized quality control nodes are implemented throughout the process, such as moisture content testing after raw material pretreatment, monitoring the active ingredient content of the extract, and testing the particle size and purity of the extract. This ensures consistent quality of the finished product, meets the stringent requirements of pharmaceutical production, and addresses the significant quality fluctuations associated with traditional processes.

[0021] 4. The resulting extract can be formulated into a variety of dosage forms, including capsules, tablets, and granules, enhancing patient convenience. It is specifically indicated for use in specific heart failure populations, such as those with NYHA class II-III heart function and ventricular ejection fractions <45%, hypertensive heart disease, and cor pulmonale, making clinical applications more targeted. Furthermore, the entire process boasts precise and controllable parameters, reasonable energy consumption, and a balance of efficiency and cost-effectiveness. This not only enhances the efficacy and stability of the Qi-invigorating and blood-activating Chinese medicine composition, but also provides reliable technical support for its industrial production and clinical application, demonstrating significant technological advancement and practical application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is a flow chart of an extraction method of a traditional Chinese medicine composition for invigorating qi and promoting blood circulation disclosed in the present invention; Figure 2 is a line chart comparing the contents of tanshinone IIA and notoginsenoside R1 in the examples and comparative examples; Figure 3 1. It is a bar chart comparing moisture content and total ash content of the embodiment and the comparative example; Figure 4 This is a radar comparison chart made after unifying the dimensions of the comparative data of the active ingredients and purity of the extracts of the examples and comparative examples. DETAILED DESCRIPTION

[0023] according to Figures 1 to 4 , the specific implementation of the present invention is as follows: Raw materials and equipment preparation Raw material specifications Red ginseng: Use 5-year-old forest red ginseng with a thick and mold-free taproot. The slice thickness should be controlled at 2-3 mm. Salvia miltiorrhiza: Henan authentic Salvia miltiorrhiza, the root is thick and reddish brown, after removing the fibrous roots, cut into segments, the length of each segment is 1-2 cm; Chuanxiong: Sichuan authentic Chuanxiong, irregular nodular fist-shaped masses, yellow-white cross section, slice thickness 2 mm; Panax notoginseng: 3-year-old Yunnan Panax notoginseng, the taproot is conical, the surface is gray-brown, and it can be crushed and passed through a 10-mesh sieve; Atractylodes: Choose Atractylodes with a firm texture and yellowish-white cross section. The bran used for bran frying should be medium-fine wheat bran. Astragalus: Mongolian Astragalus, the root is thick, long, hard and powdery, and the length of the cut section is 1~2 cm; Pueraria root: Dried root of Pueraria lobata, peeled and cut into thick slices, 3-4 mm thick; Ophiopogon japonicus: Ophiopogon japonicus from Hubei Province, spindle-shaped with a yellowish-white surface, remove the fibrous roots and set aside; Roasted Licorice: Use licorice produced in Inner Mongolia, use medium honey for honey roasting, and the refining temperature is 116~118℃; Auxiliary materials: cellulase activity 1200 U / g, pectinase activity 900 U / g, protease activity 700 U / g, safflower glycoside purity 98%, paeoniflorin purity 95%, β-cyclodextrin substitution degree 0.7, pectin esterification degree 70%, AB-8 macroporous resin, citric acid, sodium citrate, food-grade ethanol.

[0024] Equipment list Vacuum freeze dryer: temperature control range -50~50℃, vacuum degree 0~0.1MPa; Supercritical CO2 extraction instrument: extraction pressure 0~50MPa, temperature 0~80℃, equipped with CO2 flow control system; Fried medicine machine: temperature control range 50~300℃, stirring rate 0~60rpm, with automatic turning function; Steam fixation machine: steam pressure 0.1~0.3MPa, temperature 100~120℃, can set fixation time; Air drying oven: temperature control range 30~150℃, air speed 0.5~3m / s, with layered tray; Constant temperature stirring tank: temperature control range 20~100℃, stirring rate 0~200rpm, equipped with pH online monitor; Ultrasonic extraction tank: ultrasonic power 0~1000W, frequency 20~40kHz, with jacket temperature control system; Plate and frame filter: equipped with 0.22μm, 0.45μm microfiltration membrane, operating pressure 0~0.5MPa, with pressure gauge; Chromatography column: inner diameter 50mm, column height 300mm, equipped with precise flow rate control pump; Reduced pressure concentration tank: temperature control range 30~100℃, vacuum degree 0~0.1MPa, with online density monitor; Spray dryer: inlet air temperature 100~300℃, outlet air temperature 50~150℃, atomization pressure 0~0.5MPa, with feed rate adjustment function; Laser particle size analyzer: detection range 0.1~1000μm, can automatically record particle size distribution data; High performance liquid chromatograph: equipped with C18 chromatography column, detection wavelength 280nm, with automatic sampling system.

[0025] Example 1

[0026] S1: Raw material pretreatment Red ginseng treatment: take 2 parts of red ginseng with a mass of 100 grams. Put the red ginseng into the vacuum freeze dryer, set the temperature to -35℃, the vacuum degree to 0.02MPa, and the freeze-drying time to 30 hours. After freeze-drying, detect the water content of the red ginseng to ensure that the water content is 4.2%, and then crush the freeze-dried red ginseng and pass it through a 20 mesh sieve for use; Danshen, Chuanxiong, Sanqi processing: Danshen 1 part, Chuanxiong 1 part, Sanqi 1 part, each part with a mass of 50 grams. Put the three kinds of medicinal materials together into the supercritical CO2 extraction instrument, set the extraction pressure to 28 MPa, the extraction temperature to 40℃, the CO2 flow rate to 20 L / h, and the extraction time to 1.8 hours. After the extraction is completed, collect the extract and the remaining dregs, and mix them evenly for later use; Cangzhu processing: Cangzhu 1 part, mass 50 grams. According to the proportion of 10% of the mass of Cangzhu, bran 5 grams is weighed, and Cangzhu and bran are put together into the frying machine, and the frying temperature is set to 125℃, and the frying time is set to 6 minutes. After frying is completed, the water content of Cangzhu is detected to ensure that the water content is 7.5%, and then Cangzhu is crushed and passed through a 20-mesh sieve for later use; Huangqi processing: Huangqi 0.8 parts, mass 40 grams. Cut Huangqi into 1 cm long sections, put it into the steam fixation machine, set the fixation temperature to 102℃, and the fixation time to 4 minutes. After fixation is completed, transfer Huangqi into the air drying oven, set the drying temperature to 65℃, and dry until the water content of Huangqi reaches 11% for later use; Gegen processing: Gegen 0.5 parts, mass 25 grams. Cut Gegen into 1 cm long sections, put it into the steam fixation machine, set the fixation temperature to 102℃, and the fixation time to 4 minutes. After fixation is completed, transfer Gegen into the air drying oven, set the drying temperature to 65℃, and dry until the water content of Gegen reaches 11% for later use; Maidong processing: Maidong 0.3 parts, mass 15 grams. Cut Maidong into 1 cm long sections, put it into the steam fixation machine, set the fixation temperature to 102℃, and the fixation time to 4 minutes. After fixation is completed, transfer Maidong into the air drying oven, set the drying temperature to 65℃, and dry until the water content of Maidong reaches 11% for later use; Zhigancao processing: Gancao 0.2 parts, mass 10 grams. Cut Gancao into 2 mm thick slices, weigh 2 grams of honey according to the proportion of 20% of the mass of Gancao, and weigh 1 gram of deionized water according to the proportion of 10% of the mass of Gancao. Mix the honey and deionized water evenly, pour into the Gancao slices, start the stirring equipment, stir for 15 minutes, then stop stirring, and soak for 1.5 hours. After soaking is completed, put the Gancao slices into the frying machine, set the frying temperature to 115℃, and the frying time to 9 minutes. After frying is completed, take out the Gancao slices and cool them to room temperature, then crush them and pass through a 15-mesh sieve for later use.

[0027] S2: Compound enzymolysis Compound enzyme solution preparation: cellulase 2.7 g, pectinase 1.8 g, and protease 0.9 g were weighed according to the mass ratio, and the mass ratio of the three enzymes was 27%, 18%, and 9%, respectively. 90 g of deionized water was heated to 35°C, and the weighed three enzyme powders were added to the deionized water. The stirring device was turned on, and the stirring rate was set to 300 rpm. Stirring was performed for 18 minutes until the enzyme powder was completely dissolved. Enzyme activity protective agent 0.01 g was weighed according to 0.01% of the total mass of the enzyme solution, of which sorbitol 0.001 g and EDTA-2Na 0.0002 g. The enzyme activity protective agent was added to the enzyme solution, and stirring was continued for 5 minutes. Then the stirring was stopped, and the enzyme solution was cooled to room temperature to obtain a compound enzyme solution for standby; Enzymatic hydrolysis operation: all the raw materials pretreated in S1 were transferred into a constant temperature stirring tank, and the compound enzyme solution was added into the tank. The addition amount of the compound enzyme solution was 0.1 part of the total mass of the raw materials. Then 800 g of deionized water was added, and the addition amount of the deionized water was 8 times of the total mass of the raw materials. The pH value of the mixed system was adjusted to 5.0 by using a citric acid-sodium citrate buffer solution. The temperature of the constant temperature stirring tank was set to 50°C, and the stirring rate was set to 70 rpm. The enzymatic hydrolysis reaction was started, and the total time of the enzymatic hydrolysis was 3.5 hours. During the enzymatic hydrolysis, the ultrasonic auxiliary device was started every 30 minutes. The ultrasonic power was set to 350 W, and the ultrasonic frequency was set to 28 kHz. Each ultrasonic lasted for 5 minutes. After the enzymatic hydrolysis reaction was completed, the enzymatic hydrolysis system was obtained for standby.

[0028] S3: ultrasonic extraction The enzymatic hydrolysis system obtained in S2 was transferred into an ultrasonic extraction tank, and the heating device was turned on to raise the temperature of the system to 75°C. The active synergist was added at a proportion of 0.1 parts of the total mass of the raw materials, and the active synergist was composed of saffron glycoside 0.01 g and paeoniflorin 0.03 g. The stabilizer was added at a proportion of 0.08 parts of the total mass of the raw materials, and the stabilizer was composed of β-cyclodextrin 0.06 g and pectin 0.02 g. The ultrasonic extraction device was turned on, and the ultrasonic power was set to 550 W and the ultrasonic frequency was set to 32 kHz. The total time of the ultrasonic extraction was 2.5 hours. During the extraction, deionized water was supplemented into the extraction tank every 1 hour, and the supplementing amount was 1% of the total amount of the initially added deionized water, i.e. 8 g. After the extraction was completed, the extraction liquid was obtained for standby.

[0029] S4: purification filtration The extraction liquid obtained in S3 was transferred into a plate and frame filtration device, and a microfiltration membrane with a pore size of 0.3 μm was selected. The operating pressure was set to 0.3 MPa, and the filtration device was started for filtration. The filtered filtrate was collected for standby; AB-8 macroporous resin pretreatment: a certain amount of AB-8 macroporous resin was taken, soaked in 95% ethanol solution for 24 hours, and stirred every 6 hours during the soaking process. After the soaking was completed, the resin was washed with deionized water until there was no alcohol smell in the washing water, the alcohol content of the washing water was detected to ensure that the alcohol content was 0.3%. Then the resin was soaked in 5% hydrochloric acid solution for 2 hours, and stirred every 30 minutes during the soaking process. After the soaking was completed, the resin was washed with deionized water until the pH value of the washing water reached 6.5. Then the resin was soaked in 5% sodium hydroxide solution for 2 hours, and stirred every 30 minutes during the soaking process. After the soaking was completed, the resin was washed with deionized water until the pH value of the washing water reached 6.5. The pretreated resin was loaded into a chromatographic column, and the column height-diameter ratio was controlled to be 4:1 for standby; Loading and elution: the collected filtrate was pumped into the chromatographic column containing AB-8 macroporous resin through the flow rate control pump, and the loading flow rate was set to 1.5 BV / h. After the loading of the filtrate was completed, the flow rate control pump was closed, and the adsorption was carried out for 1 hour. After the adsorption was completed, 7% ethanol solution was used for elution, and the elution flow rate was set to 0.8 BV / h. In the initial stage of elution, the first 0.5 BV of eluate was collected and discarded, and the eluate was collected from 0.5 BV, and a total of 1.8 BV of eluate was collected. The collected eluate was detected by high performance liquid chromatography, and the detection conditions were as follows: C18 column, mobile phase methanol-water (70:30), flow rate 1.0 mL / min, column temperature 30℃, detection wavelength 280 nm, to ensure that the content of tanshinone IIA in the eluate was 0.23%, and the content of notoginseng saponin R1 was 0.17%.

[0030] S5: concentration and drying The eluate collected in S4 was transferred into a vacuum concentration tank, the concentration tank temperature was set to 65℃, the vacuum degree was set to 0.07 MPa, and the vacuum concentration equipment was started to concentrate. The relative density of the concentrated solution was monitored in real time by an online density monitor, and when the relative density reached 1.25, the concentration equipment was closed and the concentration was stopped, to obtain a concentrated paste for standby; The concentrated paste was transferred into a spray dryer, the inlet air temperature was set to 190℃, the outlet air temperature was set to 85℃, the atomization pressure was set to 0.25 MPa, and the feeding rate was set to 12 mL / min, and the spray drying equipment was started to dry. After the drying was completed, the dried product was collected, and a Yiqi Huoxue traditional Chinese medicine composition extract was obtained. The performance of the extract was detected as follows: the particle size was detected by a laser particle size analyzer, to ensure that 90% of the particles had a particle size in the range of 15-45 μm; the moisture content was detected by a vacuum drying method, to ensure that the moisture content was 2.5%; and the total ash content was detected by a muffle furnace calcination method, to ensure that the total ash content was 4.2%.

[0031] Example 2 S1: raw material pretreatment Red ginseng processing: take 2.2 parts of red ginseng with a mass of 110 grams. Put the red ginseng into a vacuum freeze-drying machine, set the temperature to -32°C, the vacuum degree to 0.015 MPa, and the freeze-drying time to 28 hours. After freeze-drying, detect the water content of the red ginseng to ensure that the water content is 4.5%, and then crush the freeze-dried red ginseng and pass it through a 20-mesh sieve for use; Salvia miltiorrhiza, chuanxiong, and sanqi processing: take 1.1 parts of salvia miltiorrhiza, 1.1 parts of chuanxiong, and 1.1 parts of sanqi, each with a mass of 55 grams. Put the three kinds of medicinal materials together into a supercritical CO2 extraction instrument, set the extraction pressure to 26 MPa, the extraction temperature to 38°C, the CO2 flow rate to 20 L / h, and the extraction time to 1.6 hours. After extraction, collect the extract and the remaining dregs, and mix them evenly for use; Atractylodes processing: take 1.1 parts of atractylodes with a mass of 55 grams. Take 8.25 grams of bran at a proportion of 15% of the mass of atractylodes, and put the atractylodes and the bran together into a frying machine, set the frying temperature to 128°C, and the frying time to 7 minutes. After frying, detect the water content of the atractylodes to ensure that the water content is 7.8%, and then crush the atractylodes and pass it through a 20-mesh sieve for use; Radix astragali processing: take 0.9 parts of radix astragali with a mass of 45 grams. Cut the radix astragali into 1-centimeter-long segments, put them into a steam fixation machine, set the fixation temperature to 103°C, and the fixation time to 3.5 minutes. After fixation, transfer the radix astragali into a hot air drying oven, set the drying temperature to 68°C, and dry it until the water content of the radix astragali reaches 11.5% for use; Radix puerariae processing: take 0.6 parts of radix puerariae with a mass of 30 grams. Cut the radix puerariae into 1-centimeter-long segments, put them into a steam fixation machine, set the fixation temperature to 103°C, and the fixation time to 3.5 minutes. After fixation, transfer the radix puerariae into a hot air drying oven, set the drying temperature to 68°C, and dry it until the water content of the radix puerariae reaches 11.5% for use; Radix ophiopogonis processing: take 0.4 parts of radix ophiopogonis with a mass of 20 grams. Cut the radix ophiopogonis into 1-centimeter-long segments, put them into a steam fixation machine, set the fixation temperature to 103°C, and the fixation time to 3.5 minutes. After fixation, transfer the radix ophiopogonis into a hot air drying oven, set the drying temperature to 68°C, and dry it until the water content of the radix ophiopogonis reaches 11.5% for use; Roasted licorice processing: take 0.3 parts of licorice with a mass of 15 grams. Cut the licorice into 2-millimeter-thick slices, take 4.5 grams of honey at a proportion of 30% of the mass of the licorice, and take 2.25 grams of deionized water at a proportion of 15% of the mass of the licorice. Mix the honey and the deionized water evenly, pour them into the licorice slices, start the stirring equipment, stop stirring after 15 minutes, and soak for 1.8 hours. After soaking, put the licorice slices into a frying machine, set the frying temperature to 118°C, and the frying time to 8 minutes. After frying, take out the licorice slices, cool them to room temperature, then crush them, and pass them through a 15-mesh sieve for use.

[0032] S2: complex enzymatic hydrolysis Compound enzyme solution preparation: according to the mass ratio, 3 grams of cellulase, 1.5 grams of pectinase and 1 gram of protease were weighed, and the mass ratio of the three enzymes was 30%, 15% and 10% respectively. 100 grams of deionized water was taken and heated to 38℃, the three enzyme powders were added to the deionized water, the stirring equipment was started, the stirring speed was set to 400 rpm, and the stirring was continued for 16 minutes until the enzyme powder was completely dissolved. According to the proportion of 0.012% of the total mass of the enzyme solution, 0.012 grams of enzyme activity protective agent was weighed, of which 0.0012 grams of sorbitol and 0.00024 grams of EDTA-2Na, the enzyme activity protective agent was added to the enzyme solution, and the stirring was continued for 5 minutes, then the stirring was stopped, and the enzyme solution was cooled to room temperature to obtain the compound enzyme solution for standby; Enzymatic hydrolysis operation: all the raw materials pretreated in S1 step were transferred into a constant temperature stirring tank, and the compound enzyme solution was added into the tank, the addition amount of the compound enzyme solution was 0.11 parts of the total mass of the raw materials. 990 grams of deionized water was added, and the addition amount of the deionized water was 9 times of the total mass of the raw materials. The pH value of the mixed system was adjusted to 4.8 by using citric acid-sodium citrate buffer solution, the temperature of the constant temperature stirring tank was set to 48℃, the stirring speed was set to 65 rpm, the enzymatic hydrolysis reaction was started, and the total time of the enzymatic hydrolysis was 3.8 hours. During the enzymatic hydrolysis process, the ultrasonic auxiliary device was started once every 30 minutes, the ultrasonic power was set to 320 W, the ultrasonic frequency was set to 26 kHz, and each ultrasonic lasted for 5 minutes. After the enzymatic hydrolysis reaction was completed, the enzymatic hydrolysis system was obtained for standby.

[0033] S3: ultrasonic extraction The enzymatic hydrolysis system obtained in S2 step was transferred into an ultrasonic extraction tank, and the heating device was started to raise the temperature of the system to 72℃. According to the proportion of 0.15 parts of the total mass of the raw materials, the activity synergist was added, and the activity synergist was composed of 0.015 grams of saffron glycoside and 0.045 grams of paeoniflorin; according to the proportion of 0.07 parts of the total mass of the raw materials, the stabilizer was added, and the stabilizer was composed of 0.05 grams of β-cyclodextrin and 0.02 grams of pectin. The ultrasonic extraction device was started, the ultrasonic power was set to 520 W, the ultrasonic frequency was set to 30 kHz, and the total time of the ultrasonic extraction was 2.8 hours. During the extraction process, deionized water was supplemented into the extraction tank once every 1 hour, and the supplementing amount was 1.5% of the total amount of the initially added deionized water, i.e. 14.85 grams. After the extraction was completed, the extraction liquid was obtained for standby.

[0034] S4: purification and filtration The extraction liquid obtained in S3 step was transferred into a plate and frame filtration equipment, a microfiltration membrane with a pore size of 0.25 μm was selected, the operating pressure was set to 0.3 MPa, and the filtration equipment was started for filtration, and the filtered filtrate was collected for standby; AB-8 macroporous resin pretreatment: the operation steps were consistent with those of example 1, the pretreated resin was loaded into the chromatography column with a column height to diameter ratio of 4:1 for standby; Loading and elution: the collected filtrate was pumped into a chromatographic column filled with AB-8 macroporous resin through a flow rate control pump, and the loading flow rate was set to 1.2 BV / h. After the completion of the loading of the filtrate, the adsorption was allowed to stand for 1 hour. After the adsorption was completed, elution was performed with 6% ethanol solution, and the elution flow rate was set to 0.6 BV / h. In the initial stage of elution, the first 0.5 BV of the eluate was collected and discarded, and the eluate was collected from 0.5 BV onwards, and a total of 1.6 BV of the eluate was collected. The collected eluate was subjected to high performance liquid chromatography detection to ensure that the content of tanshinone IIA in the eluate was 0.21% and the content of notoginseng saponin R1 was 0.16%.

[0035] S5: Concentration and drying The eluate collected in the S4 step was transferred into a reduced pressure concentration tank, the temperature of the concentration tank was set to 62°C, the vacuum degree was 0.065 MPa, and the reduced pressure concentration equipment was started. The online density monitor was turned on, and the relative density change of the concentrated liquid was recorded in real time. When the relative density reached 1.22, the heating device and the vacuum system were immediately turned off, and the concentration was stopped, obtaining a concentrated paste for standby; The concentrated paste was delivered to the feed inlet of the spray dryer through a feed pump, the air inlet temperature of the spray dryer was set to 185°C, the air outlet temperature was 82°C, the atomization pressure was 0.22 MPa, and the feed rate was 11 mL / min. The spray dryer was started, and after the equipment was running stably, the concentrated paste was continuously delivered for drying. During the drying process, the material state in the drying tower was observed in real time through the observation window to ensure that there was no wall sticking phenomenon. After the drying was completed, the equipment was turned off, and the extract at the bottom of the drying tower was collected.

[0036] Performance detection of the extract: the particle size was detected by a laser particle size analyzer, 0.5 grams of the extract sample was mixed with 10 milliliters of deionized water, and the detection was performed after ultrasonic dispersion for 5 minutes. The results showed that 90% of the particles had a particle size in the range of 12-48 μm. The moisture content was detected by a vacuum drying method, 2 grams of the extract sample was laid in a weighed bottle with a constant weight, and was placed in a vacuum drying oven, the temperature was set to 105°C, the vacuum degree was 0.09 MPa, and the sample was dried for 4 hours. After cooling and weighing, the moisture content was calculated to be 2.8%. The total ash content was detected by a muffle furnace calcination method, 2 grams of the extract sample was placed in a porcelain crucible with a constant weight, was carbonized on an electric stove until there was no smoke, and was then transferred into a muffle furnace, the temperature was set to 550°C, and the sample was calcined for 4 hours. After cooling and weighing, the total ash content was calculated to be 4.5%, and finally a qualified Yiqi Huoxue traditional Chinese medicine composition extract was obtained.

[0037] Example 3 S1: Raw material pretreatment Red ginseng processing: Weigh 2.5 parts of red ginseng (125 grams). Place the red ginseng in a vacuum freeze dryer at -38°C, 0.025 MPa vacuum, and freeze-dry for 32 hours. After freeze-drying, test the red ginseng for a moisture content of 4.0%. Then, crush the freeze-dried red ginseng and pass it through a 20-mesh sieve for later use. Treatment of Salvia miltiorrhiza, Chuanxiong, and Panax notoginseng: Weigh 1.2 parts of Salvia miltiorrhiza, 1.2 parts of Chuanxiong, and 1.2 parts of Panax notoginseng, each weighing 60 grams. Place all three herbs in a supercritical CO2 extractor, set the extraction pressure to 30 MPa, the extraction temperature to 42°C, the CO2 flow rate to 20 L / h, and the extraction time to 2 hours. After the extraction is completed, collect the extract and the remaining medicinal residue, mix them evenly, and set aside. Atractylodes lancea preparation: Weigh 1.2 parts of Atractylodes lancea (60 g). Weigh 7.2 g of bran (12% of the Atractylodes lancea's mass). Place the Atractylodes lancea and bran in a stir-fry machine and set the stir-fry temperature to 122°C for 5.5 minutes. After stir-frying, test the Atractylodes lancea to ensure it is 7.2% water. Then, crush the Atractylodes lancea and pass it through a 20-mesh sieve for later use. Astragalus root processing: Weigh 1 portion of Astragalus root, weighing 50 grams. Cut the Astragalus root into 1 cm long segments and place it in a steam-curing machine at 105°C for 3 minutes. After curing, transfer the Astragalus root to a forced-air drying oven at 70°C and dry until the moisture content reaches 10.5%. Pueraria root treatment: Weigh 0.8 parts of 40 grams of kudzu root. Cut the kudzu root into 1 cm long segments and place them in a steam-curing machine at 105°C for 3 minutes. After the curing is complete, transfer the kudzu root to a forced air drying oven at 70°C and dry until the moisture content reaches 10.5%. Ophiopogon japonicus treatment: Weigh 0.5 parts of Ophiopogon japonicus, with a mass of 25 grams. Cut the Ophiopogon japonicus into 1 cm long segments and place them in a steam fixing machine, set the fixing temperature to 105°C, and fix the fixing time for 3 minutes. After fixing, transfer the Ophiopogon japonicus to a blast drying oven, set the drying temperature to 70°C, and dry until the moisture content reaches 10.5% for later use; Licorice root processing: Weigh 0.4 parts of licorice root, with a mass of 20 grams. Cut the licorice root into 2 mm thick slices, weigh 5 grams of honey at a ratio of 25% of the mass of the licorice, and weigh 2.5 grams of deionized water at a ratio of 12.5% ​​of the mass of the licorice. Mix the honey and deionized water evenly, pour it into the licorice slices, turn on the stirring equipment, stir for 15 minutes, then stop stirring, and let it soak for 1.2 hours. After the soaking is completed, put the licorice slices into the medicine stir-frying machine, set the stir-frying temperature to 112°C, and stir-fry for 10 minutes. After the stir-frying is completed, take out the licorice slices and cool them to room temperature, then crush them and pass them through a 15-mesh sieve for later use.

[0038] S2: complex enzymatic hydrolysis Compound enzyme solution preparation: cellulase 2.5 g, pectinase 2 g, protease 1.2 g were weighed according to the mass ratio, and the mass ratio of the three enzymes was 25%, 20%, and 12% respectively. Take 110 g of deionized water and heat it to 36℃, then add the weighed three enzyme powders to the deionized water, start the stirring equipment, set the stirring speed to 350 rpm, and stir for 20 minutes until the enzyme powder is completely dissolved. According to the proportion of 0.015% of the total mass of the enzyme solution, weigh 0.015 g of enzyme activity protective agent, of which sorbitol is 0.0015 g and EDTA-2Na is 0.0003 g, and add the enzyme activity protective agent to the enzyme solution. Continue stirring for 5 minutes, then stop stirring, and cool the enzyme solution to room temperature to obtain a compound enzyme solution for standby; Enzymatic hydrolysis operation: all the raw materials pretreated in step S1 were transferred into a constant temperature stirring tank, and compound enzyme solution was added to the tank. The addition amount of compound enzyme solution was 0.12 parts of the total mass of raw materials. Then 1200 g of deionized water was added, and the addition amount of deionized water was 10 times the total mass of raw materials. The pH value of the mixed system was adjusted to 5.2 with citric acid-sodium citrate buffer solution, the temperature of the constant temperature stirring tank was set to 52℃, and the stirring speed was set to 75 rpm. The enzyme hydrolysis reaction was started, and the total hydrolysis time was 3 hours. During the hydrolysis process, the ultrasonic auxiliary device was started once every 30 minutes, the ultrasonic power was set to 380 W, the ultrasonic frequency was set to 29 kHz, and each ultrasonic lasted for 5 minutes. After the enzyme hydrolysis reaction was completed, the enzyme hydrolysis system was obtained for standby.

[0039] S3: ultrasonic extraction The enzyme hydrolysis system obtained in step S2 was transferred into an ultrasonic extraction tank, and the heating device was started to raise the temperature of the system to 78℃. According to the proportion of 0.2 parts of the total mass of raw materials, active synergist was added, which was composed of saffron glycoside 0.02 g and paeonol 0.06 g; according to the proportion of 0.1 parts of the total mass of raw materials, stabilizer was added, which was composed of β-cyclodextrin 0.07 g and pectin 0.03 g. The ultrasonic extraction device was started, the ultrasonic power was set to 580 W, the ultrasonic frequency was set to 34 kHz, and the total ultrasonic extraction time was 2.2 hours. During the extraction process, deionized water was supplemented to the extraction tank every 1 hour, and the supplementing amount was 2% of the total amount of initially added deionized water, i.e. 24 g. After the extraction was completed, the extract was obtained for standby.

[0040] S4: purification filtration The extract obtained in step S3 was transferred into a plate and frame filtration equipment, a microfiltration membrane with a pore size of 0.4 μm was selected, the operating pressure was set to 0.3 MPa, and the filtration equipment was started for filtration. The filtered filtrate was collected for standby; AB-8 macroporous resin pretreatment: the operation steps were consistent with example 1, the pretreated resin was loaded into the chromatography column with a column height-diameter ratio of 4:1 for standby; Loading and elution: the collected filtrate was pumped into a chromatographic column filled with AB-8 macroporous resin through a flow rate control pump, and the loading flow rate was set to 1.8 BV / h. After the completion of the loading of the filtrate, the adsorption was allowed to stand for 1 hour. After the adsorption was completed, elution was performed with 8% ethanol solution, and the elution flow rate was set to 0.9 BV / h. In the initial stage of elution, the first 0.5 BV of the eluate was collected and discarded, and the eluate was collected from 0.5 BV onwards, and a total of 1.9 BV of the eluate was collected. The collected eluate was subjected to high performance liquid chromatography detection to ensure that the content of tanshinone IIA in the eluate was 0.25% and the content of notoginseng saponin R1 was 0.18%.

[0041] S5: Concentration and drying The eluate collected in step S4 was transferred into a reduced pressure concentration tank, the temperature of the concentration tank was set to 68°C, the vacuum degree was 0.075 MPa, and the reduced pressure concentration equipment was started. The online density monitor was turned on, and the relative density change of the concentrated liquid was recorded in real time. When the relative density reached 1.28, the heating device and the vacuum system were turned off, and the concentration was stopped, obtaining a concentrated paste for standby use. The concentrated paste was delivered to the feed inlet of the spray dryer through a feed pump, the air inlet temperature of the spray dryer was set to 195°C, the air outlet temperature was 88°C, the atomization pressure was 0.28 MPa, and the feed rate was 14 mL / min. The spray dryer was started, and after the equipment was stable, the concentrated paste was continuously delivered for drying. After the drying was completed, the extract at the bottom of the drying tower was collected.

[0042] Performance detection of the extract: the particle size was detected by a laser particle size analyzer, and the results showed that 90% of the particles had a particle size in the range of 18-42 μm; the moisture content was detected by a vacuum drying method, and the moisture content was 2.3%; the total ash content was detected by a muffle furnace calcination method, and the total ash content was 4.0%, and finally a qualified Yiqi Huoxue traditional Chinese medicine composition extract was obtained.

[0043] Comparative example S1: Raw material treatment 100 grams of red ginseng, 50 grams of salvia miltiorrhiza, 50 grams of ligusticum wallichii, 50 grams of panax notoginseng, 50 grams of atractylodes lancea (not subjected to bran-fried treatment), 40 grams of astragalus membranaceus, 25 grams of pueraria lobata, 15 grams of ophiopogon japonicus, and 10 grams of fried licorice were weighed. All the medicinal materials were simply washed to remove surface impurities, the red ginseng, salvia miltiorrhiza, ligusticum wallichii, and atractylodes lancea were cut into 2-3 mm thick slices, the astragalus membranaceus, pueraria lobata, and ophiopogon japonicus were cut into 1-2 cm long segments, and the panax notoginseng was directly pulverized through a 10 mesh sieve without the need for pretreatment steps such as freeze-drying, supercritical CO2 extraction, and steam fixation. After the treatment, they were ready for use.

[0044] S2: Water decoction extraction All the raw materials after step S1 were transferred to a casserole together, and 800 grams of deionized water were added, with the addition amount of deionized water being 8 times the total mass of the raw materials. The casserole was placed on an electric stove, heated to a boil over high heat, and then decocted over low heat for 2 hours. During the decocting process, due to water evaporation, 40 grams of deionized water were added when decocting for 1 hour, and the additional amount was 5% of the total amount of deionized water initially added. After the decocting was completed, the extract was filtered through gauze and the first extract was collected; 600 grams of deionized water were added again to the remaining medicinal residue in the casserole, the above-mentioned decocting step was repeated, and the extract was filtered after decocting for 1.5 hours to collect the second extract. The two extracts were merged to obtain a mixed extract for standby use.

[0045] S3: Purification and drying The mixed extract was transferred to a normal pressure concentration pot and heated on an electric stove, maintaining a slight boil for normal pressure concentration. Stirring was continued to prevent sticking. Concentration was stopped when the relative density of the concentrate reached 1.2, resulting in a concentrated paste. The concentrated paste was transferred to a tray and placed in a forced air drying oven set at 80°C and a wind speed of 1.0 m / s. Dry for 8 hours before removal. After cooling to room temperature, the dried product was pulverized to obtain the traditional process extract.

[0046] The performance of the extract was tested: the particle size was tested using a laser particle size analyzer, and the results showed that 90% of the particles were within the range of 50-100 μm; the moisture content was tested using a vacuum drying method, and the moisture content was 5.8%; the total ash content was tested using a muffle furnace combustion method, and the total ash content was 7.3%; and the tanshinone IIA content and notoginseng saponin R1 content were 0.12% and 0.08% respectively using high performance liquid chromatography.

[0047] The comparison of the active ingredients and purity of the extracts of the embodiment and the comparative example is shown in the following table: Table 1 Index Example 1 Example 2 Example 3 Comparative Example Tanshinone IIA (%) 0.23 0.21 0.25 0.12 Panax notoginseng saponin R1 (%) 0.17 0.16 0.18 0.08 Moisture content (%) 2.5 2.8 2.3 5.8 Total ash (%) 4.2 4.5 4.0 7.3 90% extract particle size (μm) 15~45 12~48 18~42 50~100 The key process parameters and efficiency comparisons of the embodiment and the comparative example are shown in the following table: Table 2 Index Example 1 Example 2 Example 3 Comparative Example Red ginseng freeze-drying time (h) 30 28 32 None Supercritical extraction time (h) 1.8 1.6 2.0 None Enzymatic hydrolysis time (h) 3.5 3.8 3.0 None Ultrasonic extraction time (h) 2.5 2.8 2.2 None Drying time (h) 1.2 1.1 1.3 8.0 Total yield of effective components (%) 1.8 1.7 1.9 0.9 The extracts of Examples 1-3 were significantly superior to the comparative examples in terms of active ingredient content, purity, and physical properties. The comparative examples used a traditional water decoction process, lacking differentiated pretreatment, efficient extraction, and precise purification steps, resulting in severe loss of active ingredients, high impurity content, and poor physical properties. This further demonstrates that the process of the present invention, through multi-step technological innovation, can effectively improve the quality of the extracts of the traditional Chinese medicine composition for invigorating qi and promoting blood circulation.

[0048] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A method for extracting a traditional Chinese medicine composition for invigorating qi and promoting blood circulation, characterized in that: The following steps are involved: S1: Pretreatment of raw materials: 2-2.5 parts of red ginseng, 1-1.2 parts of salvia miltiorrhiza, 1-1.2 parts of chuanxiong, 1-1.2 parts of panax notoginseng, 1-1.2 parts of bran-fried atractylodes, 0.8-1 parts of astragalus, 0.5-0.8 parts of kudzu root, 0.3-0.5 parts of ophiopogon, and 0.2-0.4 parts of honey-roasted licorice; wherein the red ginseng is freeze-dried; salvia miltiorrhiza, chuanxiong, and panax notoginseng are extracted with supercritical CO2, and the extract and the remaining medicinal residue are collected; astragalus, kudzu root, and ophiopogon are first cut into sections, then steam-fixed, and then sent to a forced air drying oven for drying; S2: Composite enzymatic hydrolysis: Add composite enzyme solution composed of cellulase, pectinase, and protease and deionized water to all raw materials treated in S1; adjust the pH of the system to 4.5-5.5 with citric acid-sodium citrate buffer, and transfer the mixed system to a constant temperature stirring tank for enzymatic hydrolysis; during the enzymatic hydrolysis process, turn on the ultrasonic auxiliary device every 30 minutes, and obtain the enzymatic hydrolysis system after the enzymatic hydrolysis is completed; S3: Ultrasonic extraction: transfer the enzymatic hydrolysis system obtained in S2 to an ultrasonic extraction tank, add an activity enhancer and a stabilizer to the extraction tank, wherein the activity enhancer is composed of safflower glycoside and paeoniflorin, and the stabilizer is composed of β-cyclodextrin and pectin; turn on the ultrasonic extraction device, and during the extraction process, add deionized water to the extraction tank once every hour to obtain an extract after the extraction is completed; S4: Purification and filtration: transfer the extract obtained in S3 to a plate and frame filtration device and collect the filtered filtrate; pump the filtrate into the chromatography column, and after all the filtrate is loaded, let it stand for adsorption; after adsorption is complete, elute with ethanol solution and collect the eluate; during the elution process, observe the color of the eluate through the chromatography column sight glass, start collecting the time when the color of the eluate changes from dark to light, and stop collecting when the eluate is colorless; S5: Concentration and drying: the eluate collected in S4 is transferred to a vacuum concentration tank and vacuum concentration is started; the relative density of the concentrate is measured with a density meter every 30 minutes, and when the relative density reaches 1.2-1.3, the concentration is stopped to obtain a concentrated paste; the concentrated paste is transferred to a spray dryer for spray drying; after drying, the dry product is collected to obtain an extract of the traditional Chinese medicine composition for invigorating qi and activating blood circulation.

2. The extraction method of the Qi-invigorating and blood-activating Chinese medicine composition according to claim 1, characterized in that: It also includes the preparation process of honey-roasted licorice in S1; the specific steps are: taking licorice herbs, removing impurities and cutting into licorice slices with a thickness of 2-3 mm; weighing honey according to 20-30% of the mass of the licorice slices, weighing deionized water according to 10-15% of the mass of the licorice slices, mixing the honey and deionized water, and stirring until the honey is completely dissolved to obtain honey water; putting the licorice slices into a mixing tank, adding the honey water, turning on the stirring at a stirring rate of 40-60 rpm, stirring for 10-15 minutes, then turning off the stirring, and stewing for 1-2 hours; after the stewing is completed, transferring the licorice slices into a medicine stirrer, setting the temperature of the medicine stirrer to 110-120°C, and the stirrer time to 8-10 minutes, during which the licorice slices are turned over every 2 minutes; when the surface of the licorice slices is dark yellow and no longer sticky, stopping the stirrer, taking out and cooling to room temperature, and then crushing with a grinder, passing through a 10-20 mesh sieve after crushing to obtain honey-roasted licorice, which is set for later use.

3. The extraction method of the Qi-invigorating and blood-activating Chinese medicine composition according to claim 1, characterized in that: It also includes a preparation process of the composite enzyme solution in S2; the specific steps are: weighing cellulase, pectinase, and protease powders according to the mass ratio of 25-30% cellulase, 15-20% pectinase, and 8-12% protease respectively; taking deionized water, heating it to 35-40°C, adding the weighed enzyme powders to the deionized water, starting stirring, stirring at a stirring rate of 300-500 rpm, and stirring for 15-20 minutes until the enzyme powders are completely dissolved; adding an enzyme activity protectant to the enzyme solution, the amount of the enzyme activity protectant added is 0.01-0.02 parts of the total mass of the enzyme solution, the enzyme activity protectant is composed of sorbitol and EDTA-2Na, sorbitol accounts for 5-10% of the enzyme activity protectant, and EDTA-2Na accounts for 1-2% of the enzyme activity protectant; continuing stirring for 5-10 minutes to completely mix the enzyme activity protectant, and then cooling the enzyme solution to room temperature to obtain a composite enzyme solution for standby use.

4. The extraction method of the Qi-invigorating and blood-activating Chinese medicine composition according to claim 1, characterized in that: During ultrasonic extraction in S3, a temperature sensor needs to be installed in the extraction tank. The temperature sensor is connected to the temperature control system to monitor the temperature of the extraction system in real time. When the system temperature is detected to be lower than 70°C, the temperature control system automatically starts the water bath heating device and passes hot water at a temperature of 85-90°C into the jacket of the extraction tank until the system temperature returns to the range of 70-80°C. The water bath heating device is then turned off. During the entire ultrasonic extraction process, this temperature control method ensures that the system temperature is stable in the range of 70-80°C.

5. The extraction method of the Qi-invigorating and blood-activating Chinese medicine composition according to claim 1, characterized in that: The chromatography column in S4 is filled with AB-8 macroporous resin, which needs to be pretreated before use; the specific steps are as follows: take AB-8 macroporous resin, soak it in 95% ethanol solution for 24 hours, stir it every 6 hours, rinse the resin with deionized water until the rinsed water has no alcohol taste, and test the alcohol content of the rinse water, which must be ≤0.5%; then soak the resin in 5% hydrochloric acid solution for 2 hours, stir it every 30 minutes during the soaking process, and rinse the resin with deionized water until the pH of the rinse water is neutral, and test the pH value with pH paper, which must be 6~7; then soak the resin in 5% sodium hydroxide solution for 2 hours, stir it every 30 minutes during the soaking process, and rinse the resin with deionized water until the pH of the rinse water is neutral, and test the pH value with pH paper, which must be 6~7; finally, drain the pretreated resin and load it into the chromatography column with a column height-to-diameter ratio of 3~5:1 for standby use.

6. The extraction method of the Qi-invigorating and blood-activating Chinese medicine composition according to claim 1, characterized in that: The eluate in S4 is collected in a segmented collection method; the specific operation is as follows: prepare multiple collection bottles, each with a volume of 0.5BV; after the elution starts, the first collection bottle collects the first 0.5BV of eluate, and this part of the eluate is discarded after the collection is completed; starting from the second collection bottle, each collection bottle collects 0.5BV of eluate, and a total of 3 to 4 collection bottles are collected; the eluate in each collection bottle is subjected to high performance liquid chromatography detection, and the detection conditions are: chromatographic column C18 column, mobile phase methanol-water, flow rate 1.0mL / min, column temperature 30℃, detection wavelength 280nm; according to the test results, the eluate with tanshinone IIA content ≥0.2% and notoginseng saponin R1 content ≥0.15% is collected, and the eluate that meets the requirements is combined as the raw material for subsequent concentration.

7. The extraction method of the Qi-invigorating and blood-activating Chinese medicine composition according to claim 1, characterized in that: During the vacuum concentration process in S5, an online density monitor is required to monitor the relative density of the concentrate in real time; The online density monitor is connected to the discharge port of the concentration tank and automatically records the relative density data every 30 minutes. When the relative density reaches 1.2, the data will be recorded every 10 minutes. When the relative density reaches the set value in the range of 1.2 to 1.3, the heating device and vacuum system of the concentration tank will be immediately turned off to stop the concentration. After the concentration stops, the concentrated paste will be transferred to the storage tank. The storage tank temperature is maintained at 50 to 55 ° C to prevent the concentrated paste from solidifying. The transfer will be made immediately after the spray drying equipment is ready.

8. The extraction method of the Qi-invigorating and blood-activating Chinese medicine composition according to claim 1, characterized in that: After spray drying in S5, the extract needs to be tested for particle size; the test uses a laser particle size analyzer, and before testing, the extract sample is mixed with deionized water and ultrasonically dispersed for 5 minutes, with a dispersion concentration of 0.1~0.5%; the detection range is set to 0.1~100μm, each sample is tested 3 times, and the average value is taken; based on the test results, if the particle size of more than 90% of the extract is not within the range of 10~50μm, the extract is transferred to an ultrafine grinder, and the grinding speed is set to 20000~25000rpm and the grinding time is 1~3 minutes; after grinding, the particle size test is performed again until the particle size of more than 90% of the extract reaches the requirement of 10~50μm, and a qualified extract is obtained.

9. The extraction method of the Qi-invigorating and blood-activating Chinese medicine composition according to claim 1, characterized in that: The extract needs to be tested for moisture and ash content; the moisture content is tested by the vacuum drying method, 2~3g of the extract sample is taken, spread flat in a weighing bottle, placed in a vacuum drying oven, temperature 105℃, vacuum degree 0.09MPa, dried for 4 hours, weighed after cooling, and the moisture content is calculated. The moisture content must be ≤3%; the ash content is tested by the muffle furnace burning method, 2~3g of the extract sample is taken, placed in a porcelain crucible, first carbonized on an electric furnace until smokeless, then transferred to a muffle furnace, temperature 550℃, burned for 4 hours, weighed after cooling, and the total ash content is calculated. The total ash content must be ≤5%; if the moisture or ash content does not meet the standard, the extract will be returned to the S5 vacuum concentration tank and re-concentrated and dried. The concentration time should be appropriately extended during concentration, and the inlet air temperature should be appropriately increased by 5~10℃ during drying. After reprocessing, it will be tested again until the moisture and ash contents meet the standards.

10. Use of a traditional Chinese medicine composition prepared by the extraction method according to any one of claims 1 to 9 in preparing a medicine for treating heart failure, characterized in that: The extract is mixed with pharmaceutical excipients, and the pharmaceutical excipients are selected from one or more of microcrystalline cellulose, lactose, and hypromellose, and the mass ratio of the extract to the pharmaceutical excipient is 1~2:1; after mixing, different dosage forms are made according to needs. When making capsules, the mixture is filled in hollow capsules, and each capsule is filled with 0.3~0.5g; when making tablets, magnesium stearate is added to the mixture, and tablets with a diameter of 6~8mm are made; when making granules, the mixture is made into a soft material with ethanol solution, granulated through a 16-mesh sieve, dried at 60~70℃, and then granulated through a 14-mesh sieve; the patients corresponding to the heart failure disease must meet the NYHA heart function grade II~III and the ventricular ejection fraction is <45%, and the types of heart failure disease include hypertensive heart disease, cor pulmonale, rheumatic heart disease, and heart failure caused by coronary heart disease.

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