A Chinese medicine composition for treating qi deficiency syndrome and its preparation method and use

Abstract

The present invention discloses a syndrome-type Chinese medicine composition, and its raw materials include 3-9 parts of ginseng and 30-90 parts of astragalus by weight. The present invention also discloses a preparation method of the aforementioned composition, comprising the following steps: decoct ginseng and astragalus with water, filter to obtain a medicinal liquid; concentrate the medicinal liquid into a thick paste; dry the thick paste to obtain a powder; mix the powder with a pharmaceutical excipient to prepare a Chinese patent medicine. Ginseng greatly replenishes vital energy, replenishes the spleen and lungs, and is biased towards yin and replenishes the middle; astragalus replenishes qi and raises yang, benefits the defense and consolidates the exterior, and is biased towards yang and solidifies the exterior. The two medicines are mutually dependent, one exterior and one interior, one yin and one yang, and are used for each other, and the function of strengthening the body and replenishing qi is more prominent. Through systematic animal and clinical trial studies, the Chinese medicine composition can treat symptoms of qi deficiency, improve hypoxia tolerance and fatigue resistance, and improve the function of the internal organs of diseases such as chronic heart failure, chronic obstructive pulmonary disease, chronic glomerulonephritis, and chronic atrophic gastritis by improving the overall qi deficiency syndrome of the body, and improve the disease state.

Description

Technical Field

[0001] The invention belongs to the field of traditional Chinese medicine and relates to a Chinese medicine composition, in particular to a Chinese medicine composition for preventing and treating symptoms of qi deficiency syndrome and a preparation method and use thereof. Background Art

[0002] Qi deficiency syndrome is one of the most basic syndromes in TCM theory and clinical syndrome differentiation. In the Yellow Emperor's Classic of Internal Medicine, there is a clear explanation of "Qi deficiency" and "Qi deficiency". Modern TCM has a lot of new cognition and supplements to Qi deficiency syndrome, including diagnostic standards and treatment principles. In the clinical practice of TCM, due to the pathological changes of "Qi", the main pathogenesis of cardiovascular and cerebrovascular diseases, digestive system diseases, respiratory system diseases, urinary system diseases, etc. is "Qi deficiency". For example, cardiovascular diseases such as "true heart pain" and "heart pain due to syncope" are mostly caused by deficiency of the root and excess of the superficial symptoms. "If the heart is blocked, the pulse is blocked" (Huangdi Neijing·Bi Lun), "Yang is weak and Yin is stringy, which means chest pain. The reason for this is that it is extremely weak" (Golden Chamber·Xiongbi, Heart Pain, Shortness of Breath, Pulse Symptoms and Treatments). It can be seen that the deficiency here is mainly Qi deficiency, and replenishing the heart Qi is one of the basic treatment principles. For example, liver diseases such as "accumulation", "bloating" and "liver obstruction" are caused by "the five internal organs, the loss of true qi and the combination of evil qi", which lead to symptoms, masses, accumulation and accumulation. "All of them are caused by the weakness of the spleen and stomach qi, which cannot transport and transform the essence and control the water and grain, and gather without dispersing to form distension." ("Lanshi Mizang·Zhongman Fuzhong Lun"), which shows that qi deficiency is a major pathogenesis. Another example is digestive system diseases such as "stomach distension" and "stomach pain", "diseases are spleen diseases, which are originally caused by spleen qi deficiency and qi stagnation that cannot be circulated, and the heart is blocked and filled, so there is insufficient middle qi and cannot be transported and transformed", which shows that the weakness of the granary body and damage to the middle qi are the main pathogenesis. Another example is respiratory diseases such as "pulmonary distension" and "asthma", "lung obstruction, asthma and fullness of the ribs" (Suwen Daqi Lun), "pulmonary distension is caused by fullness and asthma and cough." (Lingshu Zhanglun), so-called "lungs control the qi of the whole body, and when the lung qi is harmonious, the blood vessels are smooth", because "the cause of pulmonary distension is internal depression, which first damages the lung qi, and then the external evil is affected, and the lung qi cannot be vented, so pulmonary distension occurs" (Zhengyinmaizhi), "the asthma caused by excess is caused by evil, and the evil qi is excess, while the asthma caused by deficiency is caused by no evil, and the original qi is deficient" (Jingyuequanshu Asthma), so it can be seen that weak lung qi is a major pathogenesis of the disease. Another example is urinary diseases such as "lumbar pain", "kidney wind" and "hematuria", because "the kidney is the root of qi and the place of essence", kidney qi deficiency and weakness, and human qi and blood deficiency are the main pathogenesis of edema, lumbago and even hematuria. Qi deficiency is a basic syndrome in TCM clinical practice, mainly manifested by fatigue, lack of energy, laziness to speak, spontaneous sweating, low voice, sallow complexion, pale or dark lips, enlarged tongue, pale or reddish or dull tongue, weak pulse, etc. As mentioned above, the deficiency of vital energy leads to the decline of the functions of Qi in promoting, consolidating, defending, and Qi transformation, or the decline of the functions of the internal organs, thus leading to the decline or decline of the physiological functions of the body, and the decline of disease resistance. Therefore, the treatment should be to strengthen the body and replenish Qi.

[0003] Ginseng and Astragalus are the most widely used classic Qi-tonifying medicines in clinical practice, and are used to treat various Qi-deficiency syndromes. Ginseng is sweet and slightly bitter in taste, slightly warm in nature, and enters the lung, spleen, heart, and kidney meridians. It has the effects of greatly replenishing vital energy, restoring pulse and strengthening collapse, replenishing spleen and lungs, and calming the mind and improving intelligence. Astragalus is slightly warm in nature, sweet in taste, and enters the lung and spleen meridians. It has the effects of replenishing Qi and raising Yang, benefiting the body and strengthening the exterior, supporting poison and promoting muscle growth, and promoting diuresis and reducing swelling. When Astragalus and ginseng are used together, Astragalus is biased towards Yang and strengthens the exterior, while ginseng is biased towards Yin and replenishes the middle. The two medicines complement each other, one exterior and one interior, one Yang and one Yin, and they are used for each other, and their effects are more prominent, playing the role of strengthening the body and replenishing Qi.

[0004] In the clinical practice of traditional Chinese medicine, due to the pathological changes of "qi", the main pathogenesis of cardiovascular and cerebrovascular diseases, digestive system diseases, respiratory system diseases, urinary system diseases, etc. is "qi deficiency". Although the basic clinical treatment of common diseases of multiple systems such as liver, heart, spleen, lung and kidney has become mature, it still fails to achieve satisfactory results, and the patient's body and mind are also troubled by various symptoms. Under the guidance of traditional Chinese medicine theory, the development of effective Chinese medicine combination for clinical application is an important key entry point to highlight the characteristics of Chinese medicine and conduct in-depth research on effective prescriptions / Chinese medicines. Summary of the invention

[0005] In order to solve the problems existing in the prior art, the first aspect of the present invention provides a traditional Chinese medicine composition, wherein the active pharmaceutical ingredients of the traditional Chinese medicine composition are from ginseng and astragalus.

[0006] The invention is a syndrome-type drug, which is simple in medicine but powerful, has a simple production process, contains saponins and polysaccharides and other biologically active ingredients, and has no toxic side effects on the human body after continuous use. The Chinese medicine composition is suitable for the auxiliary treatment of various clinical diseases with qi deficiency syndrome, and has the effect of strengthening the body and replenishing qi.

[0007] In some embodiments, the raw materials of the traditional Chinese medicine composition include, by weight: 3-9 parts of ginseng and 30-90 parts of astragalus.

[0008] In some embodiments, the weight ratio of ginseng to astragalus is 1:5-10 (eg, 1:6, 1:7, 1:8 or 1:9).

[0009] In some embodiments, the Chinese medicine composition further comprises a pharmaceutical excipient. The pharmaceutical excipient of the present invention can be a conventional excipient for making granules, capsules, ointments, etc. Preferably, the excipient comprises a filler and / or a lubricant; more preferably, the filler is starch and / or dextrin.

[0010] In some embodiments, the dosage form of the Chinese medicine composition is oral liquid, granules, capsules, soft capsules, pills or decoctions.

[0011] The second aspect of the present invention provides a method for preparing the Chinese medicine composition according to the first aspect of the present invention, the preparation method comprising the following steps:

[0012] S1: decoct ginseng and astragalus with water and filter to obtain a medicinal solution;

[0013] S2: Concentrating the medicinal solution into a thick paste.

[0014] In some embodiments, the preparation method further comprises the following steps:

[0015] S3: Drying the thick paste to obtain medicine powder.

[0016] In some embodiments, the preparation method further comprises the following steps:

[0017] S4: mixing the medicine powder with the pharmaceutical excipients to prepare a Chinese patent medicine.

[0018] In some embodiments, in step S1, the decoction is performed 2-4 times, and the filtrate from each decoction is combined as the medicinal solution; each decoction takes 60-180 minutes, and the water used for each decoction is 8-15 times the weight of the raw drug or the residue formed by the previous decoction.

[0019] In some embodiments, in step S2, the density of the thick paste is: 1.05-1.10 g / cm 3 .

[0020] In some embodiments, in step S2, the concentration is vacuum concentration.

[0021] In some embodiments, in step S3, the drying is spray drying.

[0022] In some embodiments, in step S3, the thick paste and the filler are mixed in a weight ratio of 5-20:1 and then dried.

[0023] The third party of the present invention provides the Chinese medicine composition described in the first aspect of the present invention or the preparation method described in the second aspect of the present invention, and its use in preparing a preparation for use alone, in combination with other preparations and / or drugs, or as a component of a compound preparation composed of other preparations and / or drugs to treat, prevent, alleviate and / or control a disease or subhealth condition of an animal or improve the body function of an animal, wherein the disease or subhealth condition is selected from: Qi deficiency syndrome; chronic heart failure; chronic obstructive pulmonary disease; chronic glomerulonephritis; chronic atrophic gastritis; the improvement of the body function of an animal is selected from: improving the ability to tolerate hypoxia; improving the ability to resist fatigue.

[0024] In some embodiments, the animal is a mammal.

[0025] In some embodiments, the animal is selected from the group consisting of human, mouse, and rat.

[0026] The fourth aspect of the present invention provides the use of the Chinese medicine composition described in the first aspect of the present invention or the preparation method described in the second aspect of the present invention in preparing a drug for use alone, in combination with other preparations and / or drugs, or as a component of a compound preparation composed of other preparations and / or drugs to treat, prevent, alleviate and / or control diseases or sub-health conditions of animals that can be treated, prevented, alleviated and / or controlled by intervening physiological indicators, wherein the intervention physiological indicators are selected from:

[0027] Improve cardiac ejection fraction; Improve cardiac short-axis shortening rate; Increase cardiac stroke volume; Increase cardiac output; Reduce ventricular end-systolic diameter; Reduce ventricular end-diastolic diameter; Reduce ventricular end-systolic volume; Reduce ventricular end-diastolic volume; Reduce myocardial collagen volume fraction; Inhibit myocardial fibrosis; Reduce angiotensin II content; Reduce serum creatinine content; Enhance lung function FEV1%; Enhance lung function FEV1 / FVC%; Enhance lung function FVC%; Reduce alanine aminotransferase concentration; Reduce AST aspartate aminotransferase concentration; Reduce GGT glutamyl transpeptidase concentration.

[0028] In some embodiments, the animal is a mammal.

[0029] In some embodiments, the animal is selected from the group consisting of human, mouse, and rat.

[0030] The Neijing says: "Those who are damaged should be supplemented", and those who are deficient in qi should be supplemented with sweetness. The components of this Chinese medicine composition are simple and powerful. The ginseng in the prescription is sweet, slightly warm, slightly bitter, and enters the spleen and lung meridians, which can rise or fall. It has the function of greatly replenishing the vital energy and has a strong tonic effect. For the symptoms of qi deficiency, ginseng can restore the yang energy to the point of dying, benefit the true qi of the five internal organs, strengthen the body and replenish qi, and is a holy medicine for replenishing qi. The medicine for replenishing qi relies on the product of clearing qi and the qi is doubled. The astragalus in the prescription is sweet and slightly warm, which can replenish qi and raise yang, benefit the defense and consolidate the exterior, and is an essential medicine for replenishing qi. In the human body, the earth is the mother of all things. All internal organs and bones receive qi from the spleen and stomach before they can be strong. Regardless of cold and hot tonic and purgative, first cultivate the middle earth so that the medicinal qi can reach all over the body, so that the mechanism of the whole body can flow and the essence of water and grain can be spread. The lung governs the qi of the whole body. When the lung qi sinks, there is shortness of breath and wheezing. The lung is in charge of all the meridians. When the lung qi is weak, all the meridians are not strong, so the pulse is deep, slow and weak. Ginseng and Astragalus can replenish lung qi and benefit spleen qi. Ginseng "replenishes qi and nourishes yin, guards but does not move", and Astragalus "replenishes qi and supports yang, moves but does not stay". The combination of the two medicines can strengthen the body and replenish qi. The function and indication of the Chinese medicine composition of the present invention: strengthening the body and replenishing qi. It is suitable for the treatment of qi deficiency syndrome. It has an auxiliary therapeutic effect on the common clinical diseases and frequently-occurring diseases of various systems. Symptoms: subjective symptoms such as fatigue, shortness of breath, weakness, spontaneous sweating, lack of breath and laziness, low voice, and clinical manifestations such as pale tongue and weak pulse. For the evaluation of the Chinese medicine composition, the present invention also combines systematic clinical research to observe the clinical efficacy of qi deficiency syndrome of liver cirrhosis, qi deficiency syndrome of chronic atrophic gastritis, qi deficiency syndrome of chronic obstructive pulmonary disease, and qi deficiency syndrome of chronic glomerulonephritis. The TCM syndrome scores were compared using the method of self-control before and after taking the medicine. The results showed that the Chinese medicine composition of the present invention can significantly improve the symptoms of patients and improve the overall evaluation of syndrome manifestations, including subjective symptoms such as fatigue and weakness, as well as the clinical manifestations of tongue and pulse.

[0031] The invention has the beneficial effects that the Chinese medicine composition of the invention has a simple preparation process, is composed of traditional Chinese medicines with significant clinical efficacy, does not add other chemical synthetic products, and has no toxic side effects on the human body after continuous use. The Chinese medicine composition contains saponins and polysaccharides and other biologically active ingredients proven by modern pharmacology, can be effectively used for the clinical treatment of qi deficiency syndrome, and also has a good auxiliary treatment effect on patients with other diseases belonging to qi deficiency syndrome, and has the effect of strengthening the body and replenishing qi. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 Echocardiogram of rats in each group.

[0033] Figure 2 The following are photos of myocardial pathological tissue morphology of rats in each group (Masson staining, 200×), wherein A: sham operation group; B: model group; C: low-dose group of the Chinese medicine composition of the present invention; D: medium-dose group of the Chinese medicine composition of the present invention; E: high-dose group of the Chinese medicine composition of the present invention; and F: valsartan group.

[0034] Figure 3The photographs of the effect of the composition on the myocardial tissue morphology of rats with heart failure after myocardial infarction (HE staining, 200×), wherein A: sham operation group; B: model group; C: low-dose group of the Chinese medicine composition of the present invention; D: medium-dose group of the Chinese medicine composition of the present invention; E: high-dose group of the Chinese medicine composition of the present invention; and F: valsartan group.

[0035] Among them, 1:5, 1:10, and 1:20 represent the dosage ratio of ginseng to astragalus in the composition. DETAILED DESCRIPTION

[0036] In order to make the objectives, technical solutions and advantages of the present invention more clear, the embodiments of the present invention will be further described in detail below with reference to the accompanying drawings.

[0037] The Chinese medicinal raw materials ginseng and astragalus used in the present invention, especially their quality, meet the standards of the 2020 edition of the Chinese Pharmacopoeia, and their effective ingredients, such as ginsenoside Rg1 (C 42 H 72 O 14 ) and ginsenoside Re(C 48 H 82 O 18 ) is not less than 0.27%, ginsenoside Rb1(C 54 H 92 O 23 ) is not less than 0.18%. Astragalus contains calycosin isoflavone glucoside (C 22 H 22 O 10 ) is not less than 0.020%. The raw materials ginseng and astragalus slices used in the following embodiments of the present invention are obtained by the processing method in the 2020 edition of the Chinese Pharmacopoeia.

[0038] Preparation of Compositions 1-5 used in the Test Examples of the Present Invention

[0039] The raw medicinal materials used in the present invention are: 1 part by weight of ginseng, 3-30 parts by weight of astragalus, and the specific parts by weight of the compositions 1-5 are shown in Table 1 below.

[0040] Table 1 Specific weight percentages of raw materials for compositions 1-5

[0041] Composition Ginseng / weight Astragalus root / weight Composition 1 1 3 Composition 2 1 5 Composition 3 1 10 Composition 4 1 20 Composition 5 1 30

[0042] Composition 1-5 is a granule, and the preparation method is as follows: (1) Weigh ginseng and astragalus according to the raw material ratio of composition 1-5, add 10 times the weight of water to decoct 3 times, each time for 2 hours, filter the decoction each time, remove the residue, combine, and stir evenly. (2) Vacuum concentrate the filtrate obtained in step (1) to a relative density of 1.05-1.10 (1.05-1.10 g / cm2) at 60°C with water as the reference density. 3) to form a thick paste. Then add an appropriate amount of dextrin (the weight ratio of crude drug to dextrin is 10:1), stir evenly, pass through a 100-mesh sieve, take the sieve and carry out conventional spray drying to obtain an extract intermediate (or called medicinal powder). (3) Preparation of granules: Add an appropriate amount of dextrin and magnesium stearate to the extract intermediate, mix thoroughly, dry, and granulate by conventional dry method to obtain the granules of the composition of the present invention (composition 1-5). The above preparation examples are only examples of the preparation of the composition of the present invention and do not constitute a limitation on the dosage form of the composition of the present invention. The composition of the present invention can be prepared into any available traditional Chinese medicine dosage form or Chinese patent medicine dosage form by conventional methods in the art.

[0043] Test Example 1: Improvement of hypoxia tolerance and anti-fatigue in mice

[0044] The most important manifestations of clinical qi deficiency syndrome are shortness of breath and fatigue, and the examination of hypoxia tolerance and anti-fatigue effect can indirectly reflect the therapeutic effect of the drug on qi deficiency syndrome. This experiment intends to use the classic normobaric hypoxia tolerance test and weight-bearing exhaustive swimming test to evaluate the effects of the three compatibility ratios of the Chinese medicine composition of the present invention on normobaric hypoxia tolerance and anti-fatigue.

[0045] Test drugs: The Chinese medicine composition of the present invention comprises 1 part of ginseng and 5 parts, 10 parts and 20 parts of astragalus respectively, i.e., ginseng and astragalus 1:5 group (composition 2), ginseng and astragalus 1:10 group (composition 3) and ginseng and astragalus 1:20 group (composition 4).

[0046] Animals: 192 BALB / c mice, SPF grade, half male and half female, weighing 18-20 g, purchased from Sibeifu (Beijing) Biotechnology Co., Ltd., license number: SCXK (Beijing) 2019-0010; raised in the SPF animal room of Xiyuan Hospital, China Academy of Chinese Medical Sciences.

[0047] Effect on hypoxia tolerance at normal pressure in mice Test method: The test was randomly divided into 6 groups, each group had 16 mice, half of them were male and half were female, including blank control group, group using astragalus alone (2.75 g / kg·d), group using ginseng alone (0.34 g / kg·d), group of ginseng and astragalus 1:5 of the Chinese medicine composition of the present invention (4.40 g / kg·d), group of ginseng and astragalus 1:10 of the Chinese medicine composition of the present invention (4.80 g / kg·d), group of ginseng and astragalus 1:20 of the Chinese medicine composition of the present invention (3.93 g / kg·d). The preparation method of the medicine of the group using astragalus alone and the group using ginseng alone is the same as that of composition 1-5. The dosage for mice is calculated according to the effective dosage (raw drug dosage) of the composition for clinical human use, the body surface area of ​​human / mouse, and the rate of ointment, among which 4.40g / kg·d, 4.80g / kg·d, and 3.93g / kg·d are the daily dosages for mice calculated according to the raw drug dosage of the composition of the corresponding groups. The dosage g / kg·d means the number of grams of raw drug used per kilogram of mouse per day. For specific conversion methods, please refer to "Pharmacological Experimental Methodology". For oral administration of the drug to mice, the prepared granules are dissolved in distilled water according to the dosage for mice.

[0048] Dosage method: Oral administration of 0.2 ml / 10 g body weight, once a day, for 14 consecutive days, and the blank control group was given the same volume of distilled water. Body weight was measured before, 7 days after, and 14 days after administration.

[0049] Experimental procedure: After 4 days of adaptive feeding of the mice, the aforementioned gavage administration was performed. One hour after the last administration, each group of mice was placed in a 250 ml wide-mouth bottle containing 5 g of soda lime, with one mouse placed in each bottle. The bottle mouth was sealed with a stopper and vaseline. The time was immediately started until the mouse stopped breathing. The mouse suddenly became paralyzed after struggling and convulsing. The complete cessation of chest cage movement was used as the judgment standard. The survival time of the mouse in the closed wide-mouth glass bottle was recorded and recorded as the survival time of the mouse to withstand hypoxia at normal pressure.

[0050] Mouse weighted swimming test test method: The test was randomly divided into 6 groups, each group had 16 mice, half of them were male and half were female, including blank control group, group using astragalus alone (2.75 g / kg·d), group using ginseng alone (0.34 g / kg·d), group of ginseng and astragalus 1:5 of the present invention's Chinese medicine composition (4.40 g / kg·d), group of ginseng and astragalus 1:10 of the present invention's Chinese medicine composition (4.80 g / kg·d), group of ginseng and astragalus 1:20 of the present invention's Chinese medicine composition (3.93 g / kg·d). The preparation method of the drugs of the group using astragalus alone and the group using ginseng alone was the same as that of composition 1-5.

[0051] Dosage method: Oral administration of 0.2 ml / 10 g body weight, once a day, for 14 consecutive days, and the blank control group was given the same volume of distilled water. Body weight was measured before, 7 days after, and 14 days after administration.

[0052] Experimental process: After 4 days of adaptive feeding, mice were given the above-mentioned oral administration. One hour after the last administration, mice in each group were weighed, and a lead bar weighing 5% of their body weight was tied to the base of their tails. The mice were placed in a swimming box (water temperature 25°C, water depth about 30cm) and forced to swim until exhaustion. The swimming time was recorded from the time when the mouse started to swim until the whole body was submerged in water and could not float to the surface for 8s.

[0053] Statistical methods: Experimental data were The data between the groups were analyzed using t-test, and P < 0.05 was considered statistically significant.

[0054] Test results

[0055] Effect of the Chinese medicine composition of the present invention on the body weight of mice: Compared with the blank control group, the body weight of mice in each administration group increased normally before administration, 7 days after administration and 14 days after administration, with no significant difference. See Table 2.

[0056] Table 2 Effect of the Chinese medicine composition of the present invention on the overall body weight change of mice

[0057]

[0058] Effect of the Chinese medicine composition of the present invention on hypoxia tolerance in mice: Compared with the blank control group, the Chinese medicine composition of the present invention in different proportions was continuously gavaged for 14 days. The Chinese medicine composition 3 of the present invention could prolong the survival time of mice under normobaric hypoxia by 14.13% (P<0.05), the Chinese medicine composition 2 of the present invention could prolong the survival time of mice under normobaric hypoxia by 3.60%, and the Chinese medicine composition 4 could shorten the survival time of mice under normobaric hypoxia by 3.24%, as shown in Table 3 for details.

[0059] Table 3. Effects on hypoxia tolerance in mice

[0060]

[0061] Note: Compared with the blank control group, *P<0.05, **P<0.01; compared with the group with a ratio of 1:10 of the Chinese medicinal composition of the present invention, #P<0.05, ##P<0.01. Effect on the weighted swimming time of mice: Compared with the blank control group, the Chinese medicinal composition of the present invention in different ratios was continuously gavaged for 14 days. The Chinese medicinal composition of the present invention in a ratio of 3 can prolong the weighted swimming time of mice by 24.88%, and the Chinese medicinal composition of the present invention in a ratio of 2 can prolong the weighted swimming time of mice by 5.24%. See Table 4 for details.

[0062] Table 4. Effects on weight-bearing swimming time of mice

[0063]

[0064] Note: Compared with the blank control group, *P<0.05, **P<0.01; compared with the group with the ratio of the Chinese medicine composition of the present invention of 1:10, #P<0.05, ##P<0.01

[0065] Conclusion: The experimental results suggest that the ratio of ginseng to astragalus in the Chinese medicine composition of the present invention of 1:10 can significantly improve the body's ability to resist hypoxia, improve hypoxia tolerance, and significantly prolong the weight-bearing swimming survival time of mice. Its effect is significantly better than that of ginseng and astragalus alone and other ratios, indicating that it has a certain improvement effect on the body's sports fatigue. Therefore, from the perspective of hypoxia tolerance and anti-fatigue effect, the ratio of ginseng to astragalus in the Chinese medicine composition of the present invention is best at 1:10.

[0066] Test Example 2: Therapeutic effect of Chinese medicine composition on rats with chronic heart failure

[0067] The occlusion or stenosis of the coronary artery causes myocardial ischemia, decreased myocardial contractility, further expansion of the infarct area of ​​the myocardium and loss of function, which may lead to chronic heart failure after a period of time. In this experiment, the animal model of chronic heart failure was formed by ligating the left anterior descending branch of the coronary artery to cause myocardial infarction in SD rats, and observe the effect of the Chinese medicine composition of the present invention on improving cardiac function.

[0068] Experimental animals: 67 male SD rats, SPF grade, weighing 180-200 g, were purchased from Beijing Weitonglihua Experimental Animal Technology Co., Ltd., license number SCXK (Beijing) 2016-0006. Rats were raised in the SPF Experimental Animal Center of Xiyuan Hospital, China Academy of Chinese Medical Sciences, at a temperature of 23±3℃, humidity of 50±6%, light for 12h, day and night alternation, and free access to food and water.

[0069] Experimental drugs: the Chinese medicine composition of the present invention, 1 part of ginseng, 3 parts of astragalus (ie, composition 1), prepared by the method of Example 1. Valsartan, produced by Novartis Pharmaceuticals.

[0070] Establishment of animal model and experimental grouping: SD rats were subjected to modeling surgery after 3 days of adaptive feeding in the animal room, and fasted from food and water the night before the operation. A 3.5% (w / v, the same below) chloral hydrate solution was prepared with physiological saline, the rats were weighed, and 1 ml solution / 100 g rat body weight was injected intraperitoneally into the rats. After the rats entered the anesthesia state, their limbs were fixed on the mouse board in the supine position, tracheal intubation was performed, and the rats were connected to a small animal ventilator (70 times / minute, respiratory ratio 1:2, tidal volume 9.0). After the rats were breathing stably, thoracotomy was performed. The rat board was placed horizontally, the left chest was depilated, and alcohol was sprayed for disinfection. The skin was cut 1 cm below the left armpit of the rat, and the two layers of muscle tissue were bluntly peeled off to expose the ribs. The 3rd and 4th intercostal spaces on the left side of the rat's chest were bluntly separated and opened with hemostatic forceps. The pericardium was gently peeled off, and cotton was stuffed into the chest cavity to isolate the lungs and thymus tissue to expose the heart completely. The upper part of the left anterior descending branch of the coronary artery was ligated with No. 0 surgical thread. After stabilization for a while, the color of the heart changed from red to pale, indicating that the myocardial infarction model was successfully prepared. The cotton was removed, the chest was closed, the air in the chest cavity was discharged, the double ribs, muscles, and epidermis were immediately sutured, and penicillin was applied to the wound. The tracheal tube was removed after the rats woke up and could turn over independently. After the operation, the rats resumed normal diet and drinking. In order to exclude the influence of surgical factors, sham-operated rats were set up. The sham-operated group only threaded the thread, and the upper part of the left anterior descending branch of the coronary artery was not ligated. The rest of the steps were the same as above. Not ligating the anterior cruciate ligation will only cause surgical trauma and recovery, and will not cause heart failure.

[0071] 50 rats with good surgical effects were selected from 67 rats for follow-up experiments, and the Chinese medicine composition SD rats were randomly divided into 5 groups, namely, sham group (Sham), model group (Model), high-dose group of the Chinese medicine composition of the present invention (raw drug dosage: 4.5g / kg·d), medium-dose group (raw drug dosage: 3.0g / kg·d), low-dose group (raw drug dosage: 1.5g / kg·d) and positive drug valsartan group (valsartan, 30mg / kg), 10 rats in each group. The postoperative drug administration group was continuously gavaged for 28d, once a day, and the sham operation group and the model control group were gavaged with an equal amount of physiological saline. The dosage of each group calculated during the animal test of the present invention is converted according to the effective dosage of the drug used by people in the clinic, including the dosage of the positive drug valsartan group.

[0072] General status observation: After rat modeling, regularly observe the coat color, spirit, and activity status of the rats according to the dosing time points, and record the weekly weight changes of the rats.

[0073] Echocardiography: After 28 days of drug administration, the rats were subjected to echocardiography to determine changes in cardiac structure and function. The rats were weighed and anesthetized by intraperitoneal injection of 3.5% chloral hydrate solution at 1 ml solution / 100 g rat body weight. After anesthesia, the left clavicle to the lower edge of the ribs on the chest of the rats was depilated and skin prepared. The rats were fixed on the platform in a supine position with four limbs, the heart rate was stabilized, and medical ultrasound coupling gel was applied to the skin preparation. Then, the probe was used to perform a two-dimensional scan on the long axis and parasternal short axis sections of the left ventricle. The left ventricular short axis section M-ultrasound was used to measure the left ventricular end-systolic internal diameter (LVIDs), left ventricular end-diastolic internal diameter (LVIDd), left ventricular end-systolic volume (LVEVs), left ventricular end-diastolic volume (LVEVd), ejection fraction (LVEF), short axis shortening rate (LVFS), stroke volume (SV), and cardiac output (CO). The above indicators were measured for five consecutive cycles and the average value was calculated. After the test, the rats woke up and were returned to the animal room.

[0074] Detection of myocardial pathological tissue in rats: After the last administration, rats were anesthetized by intraperitoneal injection of 3.5% chloral hydrate solution, and the thoracotomy was performed to obtain tissue from the edge of myocardial infarction, fixed in 4% tissue fixative, dehydrated, transparent, paraffin-embedded, and sliced ​​for pathological HE and Masson staining analysis.

[0075] Determination of collagen fraction in rat myocardial volume: Masson image acquisition and analysis were performed. Six slices were selected from each group, and three different fields of view were selected from each slice. Image J software was used to calculate the collagen volume fraction (CVF) in each field of view, which was the percentage of the collagen-positive blue area to the total tissue area.

[0076] Plasma AngⅡ detection: After the last administration, rats were anesthetized by intraperitoneal injection of 3.5% chloral hydrate solution, and blood was collected from the abdominal aorta and placed in a citrate anticoagulant tube. The tube was allowed to stand for 15 minutes, centrifuged at 2000g for 10 minutes, and the supernatant was taken as plasma. The AngⅡ level was determined according to the kit instructions.

[0077] Statistical analysis: All measured data were expressed as mean ± standard deviation. SPSS 20.0 software was used for statistical analysis. If the data conformed to the normal distribution, one-way analysis of variance was used, and P < 0.05 was considered statistically significant.

[0078] result

[0079] Effect of the Chinese medicine composition of the present invention on the general state of rats: The sham operation group had a good mental state during the administration period, and the activity was acceptable, the fur color was soft and shiny, and there was less fighting. The model group and the rats in each administration group had a dull fur color, some of the fur was erect and messy, and there were more and more intense fighting activities in the early morning, and biting occurred. As the administration time was prolonged, the fighting situation eased, gradually became docile, and the irritability decreased. The overall state of the model group and other groups of rats was not significantly different. The weight of rats in each group increased to varying degrees during the administration period. After 4 weeks of administration, compared with the sham operation group, the weight of rats in the model group decreased significantly (P<0.01), and the weight of each administration group increased compared with the model control group. The 4.5g / kg·d group of the Chinese medicine composition of the present invention was statistically different from the model group (P<0.05). Overall, the weight changes in the administration groups of each dose did not show dose dependence. See Table 5.

[0080] Table 5 Effect of the Chinese medicine composition of the present invention on the body weight changes of rats

[0081]

[0082] Note: Compared with the sham operation group *P<0.05, **P<0.01; compared with the model group △ P<0.05.

[0083] Effects of the Chinese medicine composition of the present invention on cardiac function and ventricular structure in rats with chronic heart failure

[0084] Effect of the Chinese medicine composition of the present invention on cardiac function of rats with chronic heart failure: After 4 weeks of administration, compared with the sham operation group, the LVEF, LVFS, SV, and CO of the model group rats were significantly reduced (P<0.01). Compared with the model group, the above indicators of the rats in each administration group increased to varying degrees (P<0.01 or P<0.05), among which the indicators of the rats in the high-dose group of the Chinese medicine composition of the present invention were significantly increased compared with the model control group (P<0.01). In general, the dose groups did not show an obvious dose-dependent trend, but the improvement effect of the high-dose group was better. See Table 6.

[0085] Table 6 Effect of the Chinese medicine composition of the present invention on cardiac function in rats with heart failure after myocardial infarction Chinese medicine composition

[0086]

[0087] Note: Compared with sham operation group ## P<0.01, # P<0.05; compared with the model group, **P<0.01, *P<0.05 Chinese medicine composition.

[0088] Effect of the Chinese medicine composition of the present invention on the ventricular structure of rats with chronic heart failure: After 4 weeks of administration, compared with the sham operation group, the LVIDs, LVIDd, LVEVs, and LVEVd of the model group were significantly increased (P<0.01), and compared with the model group, the above indicators of each administration group were significantly decreased, and the difference was statistically significant (P<0.01). See Table 7.

[0089] Table 7 Effects of the Chinese medicine composition of the present invention on ventricular structure in rats with heart failure after myocardial infarction

[0090]

[0091] Note: Compared with the Model group, **P<0.01, *P<0.05

[0092] Effects of the Chinese medicine composition of the present invention on echocardiography of rats with heart failure after myocardial infarction: Cardiac angiography shows that the heart contour of the sham-operated group is normal, the internal structure is normal, and the ventricular wall contraction / diastolic rhythm is normal. In the model group, the whole heart cavity is enlarged, mainly the left heart, and the thickness of the myocardium in the infarcted area is significantly thinned and bulges outward from the heart contour. The systolic thickening rate is reduced, the ventricular wall motion is abnormal, and the compensatory ventricular wall motion amplitude is increased in the non-infarcted area. The M-mode shows that the mitral valve diastolic activity amplitude is reduced and the valve orifice is smaller. Compared with the model group, the ventricular contraction amplitude of each drug-treated group is enhanced, the myocardial contraction speed is accelerated, and there is no obvious thinning of the ventricular septum and left ventricular wall. See Figure 1 The changes of echocardiogram in rats of each group can be found in Figure 1 .

[0093] Effect of the Chinese medicine composition of the present invention on myocardial pathological tissue morphology in rats

[0094] Effect of the Chinese medicine composition of the present invention on myocardial fibrosis in rats with chronic heart failure: The results showed that in the sham operation group, myocardial cells had normal morphology and were evenly distributed. There was no obvious collagen deposition in the myocardial interstitial space, and the muscle fibers were densely and regularly arranged with distinct layers. In the model group, the myocardial interstitial space was significantly enlarged, the muscle fibers broke, vacuoles appeared accompanied by a large amount of collagen deposition, and the myocardial fibrosis tissue increased. Compared with the model group, myocardial damage in the group treated with the Chinese medicine composition of the present invention and the valsartan group was improved to a certain extent, the myocardial cell interstitial space was narrowed, a small amount of collagen deposition was observed, the muscle fibers were arranged more completely, the breakage was reduced, and the degree of myocardial fibrosis was alleviated. The recovery degree of the high-dose group was the best according to naked eye observation. This suggests that the Chinese medicine composition of the present invention has an improving effect on myocardial fibrosis damage in rats with heart failure after acute myocardial infarction. See Figure 2 This indicates that the high-dose group of the Chinese medicine composition of the present invention has a significant effect on improving myocardial fibrosis damage in rats with heart failure after acute myocardial infarction.

[0095] Effect of the Chinese medicine composition of the present invention on myocardial collagen volume fraction in rats with chronic heart failure: Compared with the sham operation group, the CVF of rats in the model group increased significantly (P<0.01); compared with the model group, the CVF of rats in each drug administration group decreased significantly (P<0.01), among which the high-dose group of the Chinese medicine composition of the present invention decreased most significantly. Overall, as the dosage increased, the CVF of rats gradually decreased, preliminarily showing dose dependence. It is suggested that the Chinese medicine composition of the present invention can reduce myocardial CVF and inhibit myocardial fibrosis, and the effect is better with medium and high doses. See Table 8.

[0096] Table 8 Comparison of myocardial CVF in rats of each group (n=6, )

[0097]

[0098] Note: Compared with the Model group, **P<0.01, *P<0.05

[0099] Effect of the Chinese medicine composition of the present invention on the myocardial tissue morphology of rats with chronic heart failure: The results showed that the myocardial tissue of rats in the sham operation group was tightly and regularly arranged, the myocardial cell morphology was intact, the peripheral blood vessels were clear and there was no connective hyperplasia. The myocardial tissue of the model group was irregularly distributed, the structure was relatively disordered, the myocardial cell morphology was changed, the myocardial gap was enlarged, the interstitial collagen fibers increased, some muscle fibers were broken, and a large amount of inflammatory factors were seen infiltrating. Compared with the model group, the myocardial tissue damage in the group treated with the Chinese medicine composition of the present invention was improved to a certain extent, the myocardial tissue was densely arranged, the cell morphology was relatively intact, the congestion and swelling of the interstitial tissue, the breakage and dissolution of muscle fibers were alleviated, and the inflammatory infiltration was not obvious. The results suggest that the Chinese medicine composition of the present invention can improve ischemic myocardial damage in rats with heart failure after acute myocardial infarction. See Figure 3 This indicates that the high-dose group of the Chinese medicine composition of the present invention has a significant effect on improving ischemic myocardial damage in rats with heart failure after acute myocardial infarction.

[0100] Effect of the Chinese medicine composition of the present invention on the level of angiotensin II in rats with chronic heart failure: Ang II is a characteristic marker of the pathological process of heart failure. The results showed that compared with the sham operation group, the plasma Ang II content of the model group rats was significantly increased (P<0.01). After high-dose treatment with the Chinese medicine composition of the present invention, its content in plasma was significantly decreased, and the effect was similar to that of the positive drug valsartan (P<0.01). See Table 9.

[0101] Table 9 Effect of the Chinese medicine composition of the present invention on angiotensin II levels in rats with heart failure after myocardial infarction

[0102]

[0103] Note: Compared with the Model group, **P<0.01, *P<0.05

[0104] in conclusion

[0105] Effect of the Chinese medicine composition of the present invention on body state: The Chinese medicine composition of the present invention and valsartan can significantly improve the body weight of rats in myocardial infarction model, indicating that it has a good regulating effect on the overall state of rats after illness.

[0106] The effect of the Chinese medicine composition of the present invention on cardiac function and ventricular structure: The Chinese medicine composition of the present invention has a good protective effect on cardiac function damage caused by heart failure after myocardial infarction. Echocardiography is a non-invasive imaging examination method for judging cardiac structure and function. It can quantitatively and visually evaluate the systolic and diastolic function of the local myocardium and the whole heart and myocardial dyskinesia, and is a reliable diagnostic method for cardiovascular disease. The results of this experiment showed that the ejection fraction, contraction fraction, stroke volume and cardiac output of the model rats decreased significantly, indicating that the heart function was seriously damaged. After the intervention of the Chinese medicine composition of the present invention, the above indicators all rebounded and were different. In heart failure, persistent hemodynamic changes and disordered body fluid compensation mechanisms increase myocardial wall pressure, increase the heart load, and produce a series of structural and phenotypic functional changes in the myocardium, including ventricular dilatation, ventricular structural remodeling, etc. The experimental results show that each dose group of the Chinese medicine composition of the present invention can significantly reduce the left ventricular end-diastolic and end-systolic inner diameters and left ventricular end-diastolic and end-systolic volumes of rats with heart failure, indicating that it has a good improvement effect on ventricular remodeling in rats with heart failure.

[0107] Effect of the Chinese medicine composition of the present invention on myocardial pathological tissue structure: Myocardial fibrosis refers to excessive aggregation of collagen fibers in the normal tissue structure of the myocardium, a significant increase in collagen concentration in heart tissue, or changes in collagen composition. This pathological change is an inevitable result of the late development of various cardiovascular diseases and an important form of ventricular remodeling. Based on the results of HE and Masson staining and myocardial CVF determination, we found that the Chinese medicine composition of the present invention can reduce the degree of myocardial fibrosis in rats with heart failure, inhibit collagen deposition, and improve ventricular remodeling, suggesting that inhibiting myocardial fibrosis may be an important mechanism for the Chinese medicine composition of the present invention to protect ischemic myocardium. And its effect shows dose dependence, with the best therapeutic effect in the high-dose group.

[0108] Effect of the Chinese medicine composition of the present invention on plasma angiotensin: Angiotensin (ANG) is a characteristic marker of the pathological process of heart failure, and plays an important role in vasoconstriction, increased blood pressure, and the promotion of adrenal hormone release. In the process of heart failure, persistent ischemia and hypoxia aggravate myocardial damage and deteriorate cardiac function, resulting in increased plasma AngⅡ levels, which bind to angiotensin receptors (AT1) to promote collagen deposition, and ultimately cause ventricular remodeling and myocardial fibrosis. The results of this experiment showed that the high-dose group of the Chinese medicine composition of the present invention can down-regulate the plasma AngⅡ content of rats with heart failure, and its effect is similar to that of the valsartan group. Combined with the staining results, it is suggested that the mechanism by which the Chinese medicine composition of the present invention exerts its therapeutic effect on heart failure may be related to the inhibition of myocardial fibrosis and ventricular remodeling.

[0109] Test Example 3: Acute toxicity test of oral administration in mice

[0110] The Chinese medicine composition of the present invention adopts the maximum dosage experimental method to observe the nature, degree, time-effect relationship and reversibility of the acute toxic reaction induced by the prescription in ICR mice.

[0111] Drug: The Chinese medicine composition of the present invention comprises 1 part of ginseng and 10 parts of astragalus. The preparation method is the same as that of composition 3 in Example 1, and the powder is prepared after step (2).

[0112] Animals and groups: SPF ICR mice, weighing 20±2 g, half male and half female, were purchased from Beijing Weitonglihua Experimental Animal Technology Co., Ltd., license number: SCXK (Beijing) 2010-0010. They were randomly divided into 2 groups according to body weight, including 20 in the control group and 20 in the Chinese medicine composition group of the present invention.

[0113] Administration method: After adaptive feeding, mice were fasted (free drinking water) for 16 hours before the test. The mice were randomly divided into a control group and a Chinese medicine composition group of the present invention according to their body weight, with 20 mice in each group, half male and half female. Water was used as the solvent, with the maximum concentration (1.9g crude drug / ml) and the maximum volume (40ml / kg body weight), and a No. 12 gavage needle was used for gavage twice within 24 hours. The cumulative dosage was 152g crude drug / kg body weight. The control group was gavaged with an equal volume of purified water. After administration, the state of the animals was closely observed and recorded. After administration, the mice were observed continuously for 14 days. After the observation period, all mice were dissected, and the conditions of each tissue and organ were observed and recorded with the naked eye.

[0114] Dosage design reason: Clinical usage and dosage: The Chinese medicine composition of the present invention is equivalent to 66g of crude drug / day, calculated at 70kg / human body weight, and the clinical dose is 0.9g of crude drug / kg. Because this experiment is a maximum dosage experiment, the dosage regimen of maximum dosage concentration and maximum dosage volume is adopted. The maximum concentration of the aqueous extract of this medicine can be prepared is 1.9g of crude drug / ml. The mice adopt the maximum dosage volume (40ml / kg), and the dosage is twice within 24h. The dosage is: 1.9g crude drug / ml×2×40ml / kg=152g crude drug / kg, 152g crude drug / kg÷0.9g crude drug / kg=168 times. That is: the maximum dosage for mice is 168 times the highest dosage to be used clinically.

[0115] Observation of animal status before and after administration (drug administration day)

[0116] Number of observations: All animals. Observation method: Observation in cages. Observation content: Observe the appearance, activity, respiration, excretion, etc. of the animals on the day of administration, and record the symptoms of animal poisoning after administration (the starting time, duration, and disappearance time of the symptoms) and animal deaths. Number of observations: Animals in each group were observed once before administration and continuously observed for 5 hours after administration.

[0117] Observation of general condition of animals (non-drug administration day)

[0118] Number of observations: All animals. Observation method: Observation in cages. Observation content: Observe the toxic reactions of animals 1h, 3h and 1-14 days after administration: observe whether there is dyspnea, apnea, cyanosis, tachypnea, abnormal nasal secretions; observe whether spontaneous activities, probing, combing hair, and movement are normal, whether there are abnormal conditions such as drowsiness, loss of normal reflexes, anesthesia, catalepsy, ataxia, abnormal movement, proneness, tremor, fasciculations, etc.; whether there are convulsions such as clonic, tonic, and syncope; observe whether the corneal eyelid closure, righting reflex, stretch reflex, startle reflex, etc. are normal; whether there is tearing, ptosis, etc.; observe whether there are vasodilation symptoms such as skin, tail, tongue, ears, foot pads, conjunctiva and body temperature, whether there is edema or erythema on the skin; observe whether there is excessive salivation; whether there is contraction of the arrector pili muscles of the hair follicles; observe muscle tone; observe dry or watery stools; observe whether there is red urine or urinary incontinence, etc. Observation times: 14 consecutive days after administration, once a day.

[0119] Body weight measurement:

[0120] Number of measurements: 7 times. Number of measurements: All animals before and after administration. Measurement method: Body weight before administration; body weight on days 1, 2, 3, 4, 7 and 14 after administration.

[0121] Autopsy and observation Number of autopsy cases: All animals. Autopsy method: ① Before autopsy, the experimenter shall fill in the autopsy record form according to the observation records of the state of the autopsied mice before and after administration and the observation records of the general state of the animals. ② Perform an appearance inspection on the animals, kill the mice by dislocating the neck, and perform autopsy on the main organs. Observe with the naked eye for obvious abnormalities of tissues and organs, and fill in the autopsy record form.

[0122] Organs examined: brain, heart, liver, spleen, lungs, kidneys, adrenal glands, stomach, pancreas, small intestine, large intestine, testicles, ovaries, uterus, thymus, lymph nodes, etc.

[0123] Pathological histological examination: After the experiment, all animals were dissected for gross observation. If any organ showed changes in volume, color, texture, etc., it should be recorded and histopathological examination should be performed. Since no pathological tissues or organs were observed with the naked eye during the autopsy, no histopathological examination was performed.

[0124] Test data statistics: Test data is used The differences among the groups were compared using t-test, and P < 0.05 was considered statistically significant.

[0125] Test results

[0126] General status: The weight and food intake of mice in the Chinese medicine composition group of the present invention were normal after administration; there were no phenomena such as hair erection, salivation, breathing difficulties, nasal secretion obstruction, convulsion, etc., and spontaneous activities, food and water intake, various reflexes, eyelids, cardiovascular system appearance, muscle tension, defecation, skin, etc. were normal, and there was no significant difference compared with the control group, and there was no obvious adverse reaction or death. Results: There were 20 animals in each of the control group and the Chinese medicine composition group of the present invention. Each animal was observed for respiration, movement, reflexes, cardiovascular, salivation, muscle tension, defecation, and hair before administration and 1h, 3h, 1d, 2d, 3d, 4d, 5d, 6d, 7d, 8d, 9d, 10d, 11d, 12d, 3d, and 14d after administration, and no abnormalities were found.

[0127] Body weight changes: The body weight of the Chinese medicine composition group was normal after administration, and the weight gain of male mice 1 to 14 days after administration was not significantly different from that of the control group. The statistical results of body weight are shown in Tables 10 and 11.

[0128] Table 10. Effects of the Chinese medicine composition of the present invention on the body weight of male mice (g, n=10, )

[0129]

[0130]

[0131] Table 11. Effects of the Chinese medicine composition of the present invention on the body weight of female mice (g, n=10, )

[0132] Group Control group (female) The Chinese medicine composition of the present invention (female) Before administration 21.07±1.10 20.72±1.12 1 day medication 22.34±0.98 21.58±1.19 Administer for 2 days 23.08±0.98 22.21±1.28 Administer for 3 days 23.96±1.35 22.74±1.45 4 days of medication 25.76±1.48 24.08±1.71 7 days of medication 26.23±1.91 24.84±2.00 14 days of medication 28.76±2.13 27.99±1.79

[0133] Death: No animals died in the control group and the Chinese medicine composition group during the 14 days of observation after administration.

[0134] Anatomical observation: After the experiment, a comprehensive and detailed naked eye observation was conducted on the brain, heart, liver, spleen, lungs, kidneys, adrenal glands, stomach, pancreas, small intestine, large intestine, testicles, ovaries, uterus, thymus, lymph, etc. No abnormalities were found in the volume, color, and texture of each organ.

[0135] Conclusion: After administration of the Chinese medicine composition group of the present invention, mice did not show hair erection, salivation, dyspnea, nasal secretion obstruction, convulsion and other phenomena. Spontaneous activity, drinking water, various reflexes, eyelids, cardiovascular system appearance, muscle tension, defecation, skin, weight gain, etc. were all normal, and there was no significant difference compared with the control group. There was no obvious adverse reaction or death. After the experiment, a comprehensive and detailed autopsy was performed, and no abnormalities were found in the volume, color and texture of each organ. It is suggested that with the maximum concentration (1.9g crude drug / ml) and the maximum volume (40ml / kg), the cumulative administration dose is 152g crude drug / kg, which is approximately equivalent to 168 times the clinical dose (the clinical dosage is 66g crude drug / person / day, calculated at 70kg / person, then the clinical dose is 0.9g crude drug / kg), the animal is in good condition, and there is no acute toxic reaction or death.

[0136] Experimental Example 4: Study on the intervention effect of the Chinese medicine composition of the present invention on the lung function of patients with COPD (chronic obstructive pulmonary disease)

[0137] The Chinese medicine composition of the present invention has a significant intervention effect on model animals during the research process of basic medical experiments, and can significantly improve the cardiac function and other indicators of experimental rats. The most direct and critical role of drugs for treating syndromes should be reflected in the clinical efficacy, especially in terms of improvement of patient symptoms and improvement of viscera function. The following clinical cases are used to illustrate the therapeutic effect of the composition of the present invention on chronic obstructive pulmonary disease.

[0138] Diagnostic criteria

[0139] Clinical diagnostic criteria for Qi deficiency syndrome

[0140] Qi deficiency syndrome (Eight-category differentiation) is caused by insufficient vital energy, which results in the decline of the functions of Qi such as pushing, consolidating, defending, and qi transformation, or the decline of the functions of the internal organs. Syndrome diagnosis refers to the "Terms of Clinical Diagnosis and Treatment of Traditional Chinese Medicine·Syndrome Part" (GB / T 16751.2-1997) and "Terms of Traditional Chinese Medicine and Pharmacy" (2004, Science Press). Main symptoms: fatigue, shortness of breath, weakness, spontaneous sweating. Secondary symptoms: laziness to speak, low voice. Tongue and pulse: pale tongue, weak pulse. Diagnostic basis: 2 main symptoms plus 1 or more concurrent symptoms, combined with tongue and pulse for diagnosis.

[0141] Disease diagnostic criteria

[0142] Refer to the diagnostic criteria of the 2018 "Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD)" and the "Guidelines for the Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease" formulated by the Respiratory Disease Branch of the Chinese Medical Association in 2013: ① Clinical symptoms of cough, sputum, shortness of breath or dyspnea; ② History of exposure to risk factors (family history, tobacco, occupation, indoor and outdoor pollution); ③ Persistent airflow limitation (essential condition): Pulmonary function tests show that FEV1 / FVC <70% after inhalation of short-acting bronchodilators, which can be determined as incomplete reversible airflow limitation; ④ Stable period: The patient's symptoms such as cough, sputum and shortness of breath are stable or mild.

[0143] Selection of subjects

[0144] Inclusion criteria: (1) aged 35-70 years, regardless of gender; (2) diagnosed with qi deficiency according to TCM syndrome; (3) GOLD lung function level 2-3, and patients with stable chronic obstructive pulmonary disease in group B or group C according to comprehensive assessment (according to the comprehensive assessment ABCD grouping model updated in GOLD 2017); (4) voluntary participation and signing of the informed consent form.

[0145] Exclusion criteria

[0146] (1) Patients with bronchiectasis, bronchial asthma, active pulmonary tuberculosis, pulmonary embolism, pneumothorax, and pleural effusion; (2) Patients with major systemic diseases such as the cardiovascular system, nervous system, and immune system, or poorly controlled chronic diseases such as hypertension and diabetes; (3) Patients with more complex syndromes, including solid syndromes such as phlegm, blood stasis, cold, and heat toxicity, as well as patients with obvious yin deficiency and yang deficiency; (4) Patients with allergic constitution or allergies to known components of the trial drug; (5) Women of childbearing age who are pregnant or lactating, have had pregnancy intentions in the past six months, or have a positive pregnancy test (urine or blood HCG test), and cannot take effective contraceptive measures during the study (effective contraceptive measures include sterilization, intrauterine devices, oral contraceptives, or diaphragm method as required by local laws); (6) Patients who have participated in other drug clinical trials in the past month; (7) Patients with mental or neurological disorders, inability to express their wishes correctly, and communication disorders; (8) Alcoholics and drug abusers and addicts.

[0147] Dosage regimen of the Chinese medicine composition of the present invention

[0148] Test drug: 1 part of the Chinese medicine composition of the present invention, 10 parts of Radix Astragali (Composition 3). Usage and Dosage: Oral, one dose per day, the amount of raw medicine is 66g / day, dissolved in hot water and taken twice a day, morning and evening.

[0149] Basic treatment

[0150] According to the COPD Global Initiative, standardized treatment is given during the stable period, including inhaled and oral bronchodilators, inhaled hormones, anti-inflammatory drugs, etc. The purpose of treatment is to relieve symptoms, improve pathological conditions, prevent further development of lesions, and improve quality of life. During the trial, it is prohibited to use other Chinese herbal medicines, compound prescriptions or Chinese patent medicines. Concomitant medication: All concomitant medications must be recorded in detail in the original records and CRF, including the generic name of the drug, dosage and method of administration, start time of medication and reason for use.

[0151] Evaluation criteria: An improvement of ≥50% in the quantitative score of Qi deficiency syndrome is considered effective, and an improvement of <50% is considered ineffective.

[0152] The treatment cycle of the Chinese medicine composition of the present invention is: every 2 weeks is a node, and those who meet the evaluation criteria can be discharged from the group, and the longest cycle is 12 weeks. After the treatment period, conventional medical treatment is carried out.

[0153] Observation indicators. Main indicators: TCM Qi deficiency syndrome quantitative scoring table (main symptoms: fatigue, shortness of breath, weakness, spontaneous sweating; secondary symptoms: laziness, low voice). Secondary indicators: 6-minute walk test, lung function (FEV1%, FEV1 / FVC%, TLC%), Borgscale classification, mMRC questionnaire, CAT score, PRO scale, ESQ scale, SF-36 scale.

[0154] result

[0155] General information: A total of 55 patients with chronic obstructive pulmonary disease were included in the study, with 1 patient dropping out. Among them, 41 were males and 14 were females; the average age was 54.2±8.53 years old, the oldest was 69 years old, and the youngest was only 29 years old; a total of 41 patients had comorbidities and 36 patients took concomitant medications.

[0156] Effect of the Chinese medicine composition of the present invention on the symptom score of patients with qi deficiency syndrome of COPD: The total symptom score and the single TCM symptom score of the two groups of data before and after treatment roughly conform to the normal distribution, and the paired sample t test was used for comparison. The total symptom score and the single symptom score after treatment were significantly reduced compared with those before treatment, with statistical difference (P < 0.05), indicating that the Chinese medicine composition of the present invention can significantly improve the symptoms of fatigue, weakness, shortness of breath, spontaneous sweating, laziness, low voice, etc. in patients with chronic obstructive pulmonary disease, see Table 12 for details.

[0157] Table 12. Comparison of Qi deficiency syndrome symptom scores before and after treatment

[0158]

[0159] Note: Compared with before treatment, *P<0.05.

[0160] The effect of the Chinese medicine composition of the present invention on the evaluation indicators related to lung function of patients with qi deficiency syndrome of COPD is shown in Table 13: the lung function, 6-minute walk test, CAT score, and PRO score of the two groups of data before and after treatment conform to the normal distribution, while the ESQ score, mMRC score, Borg score, and SF36 score data do not conform to the normal distribution, and the paired sample t test and non-parametric test are used respectively. The results show that after treatment, the patient's lung function, 6-minute walk test, CAT score, PRO score, ESQ score, mMRC score, and Borg score are significantly improved compared with before treatment, and the difference before and after treatment is statistically significant (P < 0.05), indicating that the Chinese medicine composition of the present invention can significantly improve the lung function of patients with chronic obstructive pulmonary disease, alleviate the clinical symptoms of patients, improve the exercise endurance of patients, and improve the quality of life of patients.

[0161] Table 13. Changes of lung function related indicators before and after treatment

[0162]

[0163]

[0164] Note: Compared with before treatment, *P<0.05.

[0165] The effect of the Chinese medicine composition of the present invention on the immune indexes of COPD patients with qi deficiency syndrome is shown in Table 14: The immune index data of the disease group and the healthy control group roughly conform to the normal distribution, and the independent sample t test is used. The results show that compared with the healthy control group, the Th2 content of the disease group decreased, the Th17 content increased, and the difference was statistically significant (P < 0.05), and the difference between Th1 and Treg was not statistically significant. The immune index data of the disease group before and after treatment roughly conform to the normal distribution, and the paired sample t test is used. The results show that compared with before treatment, the Th17 content after treatment decreased, and the difference was statistically significant (P < 0.05), the Th2 content decreased, and the Th1 and Treg contents increased, but the difference was not statistically significant.

[0166] Table 14. Changes of immune indicators before and after treatment

[0167]

[0168] Note: Compared with the healthy control group, #P<0.05; compared with before treatment, *P<0.05.

[0169] Conclusion: The effect of the Chinese medicine composition of the present invention on the symptom score of Qi deficiency syndrome: The patient's symptoms were significantly improved before and after taking the medicine, and the single symptom and the overall symptom score were significantly reduced, indicating that the Chinese medicine composition of the present invention has a significant effect on the improvement of Qi deficiency syndrome. The effect of the Chinese medicine composition of the present invention on lung function: The lung governs qi and controls breathing. This functional description is similar in Chinese and Western medicine. FEV1 (forced expiratory volume in 1 second) represents the volume of gas exhaled in the first second after deep inhalation, that is, the forced expiratory volume in 1 second. It is a common indicator for diagnosing asthma and COPD. The obstruction of the lungs leads to a decrease in the FEV1% value. The Chinese medicine composition of the present invention can significantly increase the effect of FEV1%. Obstructive airway dysfunction is mainly characterized by a decrease in FEV1 / FVC. The Chinese medicine composition of the present invention can increase the ratio of FEV1 / FVC, which may be related to the simultaneous increase in the value of FVC (forced vital capacity) of COPD patients. The core significance of the CAT (Chronic Obstructive Pulmonary Disease Assessment Test) scale lies in the evaluation of the six subjective indicators of cough, sputum, chest tightness, sleep, energy, and mood, as well as exercise tolerance, and the impact of daily exercise on these two tolerances. The score will gradually increase with the increase of the grade of COPD. The results show that the Chinese medicine composition of the present invention significantly reduces the CAT score, prevents further deterioration of lung function, and has the effect of protecting lung function. The effect of the Chinese medicine composition of the present invention on the immune system of patients with qi deficiency syndrome of COPD: the body's immune system is similar to the function of "positive energy" in traditional Chinese medicine theory, "positive energy is stored inside, and evil cannot be interfered with", that is, if there is positive energy in the body, evil energy cannot invade, and the body can be free from illness. The immune system also embodies such an effect on the human body, so abnormal immune system is also a manifestation of qi deficiency. The Th2 and Th17 of the subjects with qi deficiency syndrome of chronic obstructive pulmonary disease were significantly higher than those of the healthy control group, and the Chinese medicine composition of the present invention can significantly improve the abnormal state of the immune system.

[0170] Experimental Example 5: Study on the intervention effect of the Chinese medicine composition of the present invention on patients with chronic glomerulonephritis with qi deficiency syndrome

[0171] Diagnostic criteria

[0172] Clinical diagnostic criteria for Qi deficiency syndrome

[0173] Qi deficiency syndrome (Eight-Principle Syndrome Differentiation) is caused by insufficient vital energy, which results in the decline of the functions of Qi such as pushing, consolidating, defending, and qi transformation, or the decline of the functions of the internal organs. Syndrome diagnosis refers to the "Terms of Clinical Diagnosis and Treatment of Traditional Chinese Medicine·Syndrome Part" (GB / T 16751.2--1997) and "Terms of Traditional Chinese Medicine and Pharmacy" (2004, Science Press). Main symptoms: fatigue, shortness of breath, weakness, spontaneous sweating. Secondary symptoms: laziness to speak, low voice. Tongue and pulse: pale tongue, weak pulse. Diagnostic basis: 2 main symptoms plus 1 or more concurrent symptoms, combined with tongue and pulse for diagnosis.

[0174] Disease diagnostic criteria

[0175] Diagnostic criteria for chronic glomerulonephritis: refer to the "Proceedings of the Symposium on Classification, Treatment and Diagnostic Criteria of Primary Glomerular Diseases" published in the 1993 Chinese Journal of Internal Medicine.

[0176] Selection of subjects

[0177] Inclusion criteria

[0178] (1) Aged 18-70 years, regardless of gender; (2) Meet the diagnostic criteria for Qi deficiency in Traditional Chinese Medicine; (3) Primary chronic glomerulonephritis, more than 50% with a renal biopsy pathology report; (4) Urine protein quantification of 0.5-6.0 g / 24 h; (5) eGFR ≥ 30 ml / min; plasma albumin ≥ 30 g / L; (6) Blood pressure stabilized below 140 / 90 mmHg after antihypertensive treatment; (7) Able to understand the procedures and methods of this clinical study, voluntarily participate and sign the informed consent form.

[0179] Exclusion criteria

[0180] (1) Secondary glomerular diseases, such as diabetic nephropathy, purpuric nephritis, lupus nephritis, and renal damage caused by hypertension; (2) Patients with more complex combined syndromes, including phlegm, blood stasis, cold, heat toxicity and other solid syndromes, as well as patients with obvious yin deficiency and yang deficiency; (3) Patients with major systemic diseases such as cardiovascular and cerebrovascular systems, nervous systems, and immune systems; (4) Patients who have used glucocorticoids, immunosuppressants, and antibiotics in the past month. (5) Patients with allergic constitution or allergies to known components of the test drug; (6) Women of childbearing age who are pregnant or lactating, have had pregnancy intentions in the past six months, or have positive pregnancy tests (urine or blood HCG), and cannot take effective contraceptive measures during the study (effective contraceptive measures include sterilization, intrauterine devices, oral contraceptives, or diaphragm methods as required by local laws); (7) Patients who have participated in other drug clinical trials in the past month; (8) Patients with mental or neurological disorders, inability to express their wishes correctly, and communication disorders; (9) Alcoholics and drug abusers and addicts

[0181] Normal control subjects

[0182] (1) Age ≥ 18 years, body mass index (BMI: weight / height) 2 ) is 19-26kg / m 2 , regardless of gender. (2) Those who have no symptoms of Qi deficiency according to TCM diagnosis. (3) Routine physical examination, vital signs (temperature, blood pressure, heart rate, respiration), electrocardiogram and laboratory tests (including blood, urine, stool routine, liver, kidney function and other biochemical indicators) are normal. (4) Have not participated in other drug clinical trials in the past month. (5) Able to understand the procedures and methods of this clinical study, voluntarily and sign the informed consent.

[0183] Exclusion criteria:

[0184] (1) Patients with other major systemic diseases such as the nervous system and immune system, or patients with malignant tumors, allergic constitutions, or patients with severe trauma or infection; (2) Patients with poorly controlled chronic diseases such as hypertension and diabetes; (3) Women of childbearing age who are pregnant, lactating, or menstruating; (4) People with mental or neurological disorders who cannot express their wishes correctly; (5) Alcoholics and drug abusers and addicts.

[0185] Dosage regimen of the Chinese medicine composition of the present invention

[0186] Test drug: 1 part of the Chinese medicine composition of the present invention, 30 parts of Radix Astragali (ie, Composition 5). Usage and Dosage: Oral, one dose per day, the amount of raw medicine is 93g / day, dissolved in hot water and taken twice a day, morning and evening.

[0187] Basic treatment

[0188] According to the diagnosis and treatment guidelines of chronic glomerulonephritis, standardized treatment is given, including blood pressure control, ACEI or ARB drugs are used to reduce urine protein, blood pressure is controlled below 140 / 90 mmHg; statins are used as lipid-lowering treatment to prevent further development of the disease and improve the quality of life. During the trial, it is prohibited to use other Chinese herbal medicines, compound prescriptions or Chinese patent medicines with effects other than invigorating qi. Concomitant medication: All combined medications must be recorded in detail in the original records and CRF, including the generic name of the drug, dosage and method of administration, start time of medication and reason for use.

[0189] Evaluation criteria: An improvement of ≥50% in the quantitative score of Qi deficiency syndrome is considered effective, and an improvement of <50% is considered ineffective.

[0190] The treatment cycle of the Chinese medicine combination is 4 weeks as a node. Patients who meet the evaluation criteria can leave the group. The longest cycle is 8 weeks. After the treatment period, patients will be transferred to conventional medical treatment.

[0191] Observation indicators

[0192] Main Outcome Measures: Quantitative Scoring Table for Qi Deficiency Syndrome in Traditional Chinese Medicine (main symptoms: fatigue, shortness of breath, weakness, spontaneous sweating; secondary symptoms: laziness to speak, low voice).

[0193] Secondary indicators: 24-hour urine protein quantification, creatinine, eGFR, SCr, BUN.

[0194] Results: A total of 40 patients with chronic glomerulonephritis were included in the study, 1 of whom was missing. There were 11 males and 29 females. The average age was 45.79±11.81 years old, the oldest was 67 years old, and the youngest was only 22 years old. There were 3 patients with comorbidities, 11 patients with combined medications, and 1 patient was missing.

[0195] The effect of the Chinese medicine composition of the present invention on the symptom score of patients with chronic glomerulonephritis with qi deficiency syndrome is shown in Table 15: the total symptom score and the single TCM symptom score of the two groups of data before and after treatment are roughly in line with the normal distribution, and the paired sample t test is used for comparison. The total symptom score and the single symptom score after treatment are significantly reduced compared with those before treatment, with a statistically significant difference (P<0.05), indicating that the Chinese medicine composition of the present invention can significantly improve the symptoms of fatigue, weakness, shortness of breath, spontaneous sweating, laziness, low voice, etc. in patients with chronic glomerulonephritis.

[0196] Table 15. Comparison of Qi deficiency syndrome symptom scores before and after treatment

[0197]

[0198] Note: *P<0.05 compared with before treatment.

[0199] The effect of the Chinese medicine composition of the present invention on the renal function of patients with chronic glomerulonephritis and qi deficiency syndrome is shown in Table 16: the 24h urine protein quantification and Scr of the two groups of data before and after treatment did not conform to the normal distribution, while eGFR and BUN conformed to the normal distribution, and non-parametric test and paired sample t test were used respectively. The results showed that after treatment, the expression levels of various indicators of renal function of patients were improved compared with those before treatment, and Scr (creatinine) was statistically significant (P < 0.05), while the other indicators had no statistically significant differences before and after treatment.

[0200] Table 16. Changes of renal function indicators before and after treatment

[0201]

[0202]

[0203] Note: Compared with the normal control group, *P<0.05.

[0204] The effect of the Chinese medicine composition of the present invention on the immune indexes of patients with chronic glomerulonephritis with qi deficiency syndrome is shown in Table 17: The immune index data of the disease group and the healthy control group roughly conform to the normal distribution, and the independent sample t test is used. The results show that compared with the healthy control group, the Th1 content of the disease group increased, the Th2 content decreased, and the difference was statistically significant (P < 0.05), and the difference between Th17 and Treg was not statistically significant. The immune index data of the disease group before and after treatment roughly conform to the normal distribution, and the paired sample t test is used. The results show that compared with before treatment, the Th1 content decreased, the Th2 content increased, and the difference was statistically significant (P < 0.05), and the difference between Th17 and Treg was not statistically significant.

[0205] Table 17. Changes of immune indicators before and after treatment

[0206]

[0207] Note: Compared with the healthy control group, #P<0.05; compared with before treatment, *P<0.05.

[0208] in conclusion

[0209] The effect of the Chinese medicine composition of the present invention on the symptom score of Qi deficiency syndrome: the symptom score of the diseased subjects is significantly higher, and the symptoms of the patients are significantly improved after taking the medicine, and the symptom score is significantly reduced, indicating that the improvement of Qi deficiency syndrome by the Chinese medicine composition of the present invention has a significant effect. The effect of the Chinese medicine composition of the present invention on renal function: the kidney is the root of Qi, and the kidney is responsible for receiving Qi. The renal function of modern medicine and the role of "kidney" in traditional Chinese medicine have some similar meanings. Scr (serum creatinine) mainly reflects the glomerular filtration function and is an important indicator for evaluating kidney damage. The Chinese medicine composition of the present invention can significantly reduce the Scr level, indicating that it has a significant protective effect on renal function. The Chinese medicine composition of the present invention also has an effect on the BUN (urea nitrogen) 24h urine protein quantification and eGFR levels, but there is no significant difference. The effect of the Chinese medicine composition of the present invention on the immune system of patients with chronic glomerulonephritis with Qi deficiency syndrome: Th1 and Th2 of chronic glomerulonephritis with Qi deficiency syndrome subjects are abnormal compared with the healthy control group, and the Chinese medicine composition of the present invention can significantly improve the abnormal state of the immune system.

[0210] Test Example 6: Study on the intervention effect of the Chinese medicine composition of the present invention on chronic atrophic gastritis with spleen qi deficiency syndrome

[0211] Diagnostic criteria

[0212] Clinical diagnostic criteria for Qi deficiency syndrome

[0213] Refer to "Chinese Medicine Clinical Diagnosis and Treatment Terminology·Syndrome Part" (GB / T 16751.2--1997) and "Chinese Medicine and Pharmacy Terminology" (2004, Science Press). Syndrome diagnosis: Qi deficiency syndrome (Eight-Principle Syndrome Differentiation) due to: insufficient vital energy, decreased functions of Qi in promoting, consolidating, defending, and Qi transformation, or decreased function of internal organs. Main symptoms: fatigue, shortness of breath, weakness, spontaneous sweating. Secondary symptoms: lazy speech, low voice. Tongue and pulse: pale tongue, weak pulse. Diagnostic basis: 2 main symptoms plus 1 or more concurrent symptoms, combined with tongue and pulse for diagnosis.

[0214] Disease diagnostic criteria

[0215] Diagnostic criteria for chronic atrophic gastritis: formulated with reference to the "Chinese Consensus on Chronic Gastritis (2017)" and the "Consensus on the Diagnosis and Treatment of Chronic Atrophic Gastritis with Integrated Traditional Chinese and Western Medicine (2017)".

[0216] Selection of subjects

[0217] Inclusion criteria

[0218] (1) Aged 35-70 years, regardless of gender; (2) TCM syndrome differentiation meets the criteria for Qi deficiency and spleen qi deficiency, and the "Qi deficiency syndrome quantitative score of TCM" is ≥10 points; (3) Western medicine diagnosis meets the diagnostic criteria for chronic atrophic gastritis (supported by gastroscopy and pathological diagnosis within 3 months); (4) Patients with chronic atrophic gastritis of moderate or above pathological grade; (5) Voluntary participation and signing of informed consent.

[0219] Exclusion criteria

[0220] (1) Patients with dysplasia and gastric precancerous lesions; (2) Patients with major systemic diseases such as cardiovascular and cerebrovascular systems, nervous systems, and immune systems, or poorly controlled chronic diseases such as hypertension and diabetes; (3) Patients with more complex combined syndromes, including phlegm, blood stasis, cold, heat toxicity, and obvious yin deficiency and yang deficiency; (4) Patients with allergic constitution or allergy to known components of the trial drug; (5) Women of childbearing age who are pregnant, lactating, have pregnancy intentions, or have a positive pregnancy test (urine or blood HCG test), and cannot take effective contraceptive measures during the study (effective contraceptive measures include sterilization, intrauterine devices, oral contraceptives, or diaphragm method as required by local laws); (6) Patients who have participated in clinical trials of other drugs or medical devices in the past 3 months; (7) Patients with mental or neurological disorders who cannot express their wishes correctly; (8) Alcoholics and drug abusers and addicts.

[0221] Normal control subjects

[0222] (1) Age ≥ 18 years, body mass index (BMI: weight / height) 2 ) is 19-26kg / m 2 , regardless of gender. (2) Those who have no symptoms of Qi deficiency according to TCM diagnosis. (3) Routine physical examination, vital signs (temperature, blood pressure, heart rate, respiration), electrocardiogram and laboratory tests (including blood, urine, stool routine, liver, kidney function and other biochemical indicators) are normal. (4) Have not participated in other drug clinical trials in the past month. (5) Able to understand the procedures and methods of this clinical study, voluntarily and sign the informed consent.

[0223] Exclusion criteria:

[0224] (1) Patients with other major systemic diseases such as the nervous system and immune system, or patients with malignant tumors, allergic constitutions, or patients with severe trauma or infection; (2) Patients with poorly controlled chronic diseases such as hypertension and diabetes; (3) Women of childbearing age who are pregnant, lactating, or menstruating; (4) Patients with mental or neurological disorders who cannot express their wishes correctly; (5) Alcoholics and drug abusers and addicts.

[0225] Dosage regimen of the Chinese medicine composition of the present invention

[0226] Test drug: 1 part of the Chinese medicine composition of the present invention, 1 part of ginseng, 3 parts of astragalus (ie, composition 1). Usage and dosage: Oral, one dose per day, the amount of raw medicine is 39g / day, dissolved in hot water and taken twice a day, morning and evening.

[0227] Basic treatment

[0228] Choose the corresponding western medicine or Chinese patent medicine according to the symptom type. For those with stomach pain, heartburn and acid reflux, add PPIs, such as pantoprazole, rabeprazole, etc.; for those with obvious gastric bloating, add gastrointestinal motility drugs such as Weisu Granules, Xiangsha Pingwei Granules or Metoclopramide. During the trial, it is prohibited to use other Chinese herbal medicines, compound prescriptions or Chinese patent medicines with functions other than invigorating qi. Concomitant medication: All concomitant medications must be recorded in detail in the original records and CRF, including the generic name of the drug, dosage and method of administration, starting time of medication and reason for use or Chinese patent medicine

[0229] Evaluation criteria: An improvement of ≥50% in the quantitative score of Qi deficiency syndrome is considered effective, and an improvement of <50% is considered ineffective.

[0230] The treatment cycle of the Chinese medicine combination is 2 weeks per node. Patients who meet the evaluation criteria can leave the group. The longest cycle is 8 weeks. After the treatment period, patients will be transferred to conventional medical treatment.

[0231] Observation indicators

[0232] Main indicators: TCM Qi deficiency syndrome quantitative scoring table (main symptoms: fatigue, shortness of breath, weakness, spontaneous sweating; secondary symptoms: laziness, low voice). Secondary indicators: spleen deficiency syndrome score, chronic atrophic gastritis disease symptom score.

[0233] Results: A total of 51 patients with chronic atrophic gastritis were included in the study, 1 of whom was missing. There were 19 males and 32 females; the average age was 54.2±8.53 years old, the oldest was 69 years old, and the youngest was only 29 years old; a total of 19 patients had comorbidities, of which 13.7% had hypertension, 5.9% had diabetes, 12 cases were taking concomitant medications, and 7 cases were missing.

[0234] The effect of the Chinese medicine composition of the present invention on the symptom score of patients with chronic atrophic gastritis with spleen qi deficiency syndrome is shown in Table 18: the total symptom score and the single TCM symptom score of the two groups of data before and after treatment roughly conform to the normal distribution, and the paired sample t test is used for comparison. The total symptom score and the single symptom score after treatment are significantly reduced compared with those before treatment, with statistical difference (P<0.05), indicating that the Chinese medicine composition of the present invention can significantly improve the symptoms of fatigue, weakness, shortness of breath, spontaneous sweating, laziness, low voice, etc. in patients with chronic atrophic gastritis.

[0235] Table 18. Comparison of Qi deficiency syndrome symptom scores before and after treatment

[0236]

[0237] Note: Compared with before treatment, *P<0.05.

[0238] The effect of the Chinese medicine composition of the present invention on the spleen deficiency scale and disease symptom scale of patients with chronic atrophic gastritis with spleen deficiency syndrome is shown in Table 19: The spleen deficiency syndrome scores and chronic atrophic gastritis disease symptom scores of the two groups of data before and after treatment do not conform to the normal distribution, and non-parametric tests are used. The results show that after treatment, the spleen deficiency syndrome and disease symptom scores of patients decreased compared with those before treatment, and the difference before and after treatment was statistically significant (P < 0.01), indicating that the Chinese medicine composition of the present invention can significantly improve the clinical symptoms of patients with chronic atrophic gastritis, such as bloating, stomach pain, poor appetite, loose stools, etc.

[0239] Table 19. Changes in the scores of the spleen qi deficiency scale and disease scale before and after treatment

[0240]

[0241] Note: Compared with before treatment, *P<0.05, **P<0.01.

[0242] The effect of the Chinese medicine composition of the present invention on the immune indexes of patients with chronic atrophic gastritis with spleen qi deficiency syndrome is shown in Table 20: The immune index data of the disease group and the healthy control group roughly conform to the normal distribution, and the independent sample t test is used. The results showed that compared with the healthy control group, the Th1 and Th17 levels in the disease group increased, the Th2 level decreased, and the difference was statistically significant (P < 0.05), and the Treg difference was not statistically significant. The immune index data of the disease group before and after treatment roughly conform to the normal distribution, and the paired sample t test is used. The results showed that compared with before treatment, the Th1 and Th17 levels after treatment decreased, the Th2 level increased, and the difference was statistically significant (P < 0.05), and the Treg difference was not statistically significant.

[0243] Table 20. Changes of immune indicators before and after treatment

[0244]

[0245] Note: Compared with the healthy control group, #P<0.05; compared with before treatment, *P<0.05.

[0246] Conclusion: The effect of the Chinese medicine composition of the present invention on the symptom score of Qi deficiency syndrome: The symptom score of the patients was significantly higher, and the single symptom and overall symptom score of the patients after taking the medicine were significantly improved, and the symptom score was significantly reduced, indicating that the Chinese medicine composition of the present invention has a significant improvement effect on the symptoms of Qi deficiency syndrome such as fatigue, weakness, shortness of breath, spontaneous sweating, laziness, and low voice in patients with chronic atrophic gastritis. The effect of the Chinese medicine composition of the present invention on the spleen deficiency scale and disease symptom scale: After treatment with the Chinese medicine composition of the present invention, the spleen deficiency syndrome and disease symptom scores of patients with chronic atrophic gastritis decreased compared with those before treatment, indicating that the Chinese medicine composition of the present invention can significantly improve the clinical symptoms of patients with chronic atrophic gastritis such as bloating, stomach pain, poor appetite, and loose stools. The effect of the Chinese medicine composition of the present invention on the immune system of patients with chronic atrophic gastritis with Qi deficiency syndrome: The Th1, Th2, and Th17 of the patients with chronic atrophic gastritis with Qi deficiency syndrome showed abnormalities compared with the healthy control group, and the Chinese medicine composition of the present invention can significantly improve the abnormal state of the immune system.

[0247] Test Example 7: Study on the intervention effect of the Chinese medicine composition of the present invention on liver cirrhosis with Qi deficiency syndrome

[0248] Diagnostic criteria

[0249] Clinical diagnostic criteria for Qi deficiency syndrome

[0250] Refer to "Chinese Medicine Clinical Diagnosis and Treatment Terminology·Syndrome Part" (GB / T 16751.2--1997) and "Chinese Medicine and Pharmacy Terminology" (2004, Science Press). Syndrome diagnosis: Qi deficiency syndrome (Eight-Principle Syndrome Differentiation) due to: insufficient vital energy, decreased functions of Qi in promoting, consolidating, defending, and Qi transformation, or decreased function of internal organs. Main symptoms: fatigue, shortness of breath, weakness, spontaneous sweating. Secondary symptoms: lazy speech, low voice. Tongue and pulse: pale tongue, weak pulse. Diagnostic basis: 2 main symptoms plus 1 or more concurrent symptoms, combined with tongue and pulse for diagnosis.

[0251] Disease diagnostic criteria

[0252] Diagnostic criteria for liver cirrhosis: refer to the "Clinical Diagnosis and Treatment Guidelines - Digestive System Diseases" (edited by the Chinese Medical Association, People's Medical Publishing House); "Practical Internal Medicine (13th Edition)" (edited by Shanghai Medical College of Fudan University, People's Medical Publishing House); "2009 American Association for the Study of Liver Diseases Guidelines for the Treatment of Ascites in Cirrhosis"; "2010 European Association for the Study of the Liver Diseases Clinical Practice Guidelines: Management of Cirrhosis Ascites, Spontaneous Peritonitis, and Hepatorenal Syndrome", etc.

[0253] Selection of subjects

[0254] Inclusion criteria

[0255] (1) Aged 35-70 years, regardless of gender; (2) TCM diagnosis of Qi deficiency or Yang deficiency; (3) Meet the diagnostic criteria for liver cirrhosis, with or without grade 1-2 liver cirrhosis ascites; (4) Blood pressure stabilized below 160 / 100 mmHg after antihypertensive treatment, blood sugar basically controlled, and glycosylated hemoglobin controlled below 6.5%; (5) Able to understand the procedures and methods of this clinical study, voluntarily participate and sign the informed consent form.

[0256] Exclusion criteria

[0257] (1) Patients with active gastrointestinal bleeding or spontaneous peritonitis; (2) Patients with more complex syndromes, including phlegm, blood stasis, cold, heat and toxicity, as well as patients with obvious yin deficiency; (3) Patients with severe liver failure; (4) Patients with other major systemic diseases such as respiratory system, nervous system, immune system, malignant tumors or patients with severe trauma or infection; (5) Patients with allergic constitution or allergy to known components of the trial drug; (6) Women of childbearing age who are pregnant, lactating, have pregnancy intention or have a positive pregnancy test (urine or blood HCG test), and cannot take effective contraceptive measures during the study (effective contraceptive measures include sterilization, intrauterine device, oral contraceptive pills or diaphragm method as required by local laws); (7) Patients who have participated in clinical trials of other drugs or medical devices in the past month; (8) Patients with mental or neurological disorders who cannot express their wishes correctly; (9) Alcoholics and drug abusers and addicts.

[0258] Normal control subjects

[0259] Inclusion criteria:

[0260] (1) Age ≥ 18 years, body mass index (BMI: weight / height) 2 ) is 19-26kg / m 2 , regardless of gender. (2) Those who have no symptoms of Qi deficiency according to TCM diagnosis. (3) Routine physical examination, vital signs (temperature, blood pressure, heart rate, respiration), electrocardiogram and laboratory tests (including blood, urine, stool routine, liver, kidney function and other biochemical indicators) are normal. (4) Have not participated in other drug clinical trials in the past month. (5) Able to understand the procedures and methods of this clinical study, voluntarily and sign the informed consent.

[0261] Exclusion criteria:

[0262] (1) Patients with other major systemic diseases such as the nervous system and immune system, or patients with malignant tumors, allergic constitutions, or patients with severe trauma or infection; (2) Patients with poorly controlled chronic diseases such as hypertension and diabetes; (3) Women of childbearing age who are pregnant, lactating, or menstruating; (4) Patients with mental or neurological disorders who cannot express their wishes correctly; (5) Alcoholics and drug abusers and addicts.

[0263] Dosage regimen of the Chinese medicine composition of the present invention

[0264] Test drug: 1 part of the Chinese medicine composition of the present invention, 1 part of ginseng, 3 parts of astragalus (ie, composition 1). Usage and dosage: Oral, one dose per day, the amount of raw medicine is 39g / day, dissolved in hot water and taken twice a day, morning and evening.

[0265] Basic treatment

[0266] According to the diagnosis and treatment guidelines related to liver cirrhosis, standardized treatment is given, including liver protection and etiological treatment. The purpose of treatment is to alleviate symptoms, improve pathological conditions, prevent further development of lesions, and improve quality of life. For liver cirrhosis caused by hepatitis B or C, antiviral treatment is required; for non-alcoholic fatty cirrhosis, basic therapies such as diet and exercise are very critical; alcoholic cirrhosis must be absolutely abstinent; drug-induced cirrhosis is to stop using drugs suspected of liver damage; autoimmune cirrhosis is treated with hormones as the basis; primary biliary cirrhosis requires long-term use of ursodeoxycholic acid to slow down bile stasis. At the same time, liver protection drugs are given, such as cell membrane protectants, antioxidants, anti-inflammatory liver protection drugs, liver-soothing and choleretic drugs. For patients with ascites, diuresis and liver protection are the main treatments, and those with hypoproteinemia are transfused with human albumin when necessary. During the trial, it is prohibited to combine the use of other Chinese herbal medicines, compound prescriptions or Chinese patent medicines with effects other than invigorating qi. Concomitant medication: All concomitant medications must be recorded in detail in the original records and CRF, including the generic name of the drug, dosage and administration method, starting time of medication and reason for use.

[0267] Evaluation criteria: An improvement of ≥50% in the quantitative score of Qi deficiency syndrome is considered effective, and an improvement of <50% is considered ineffective.

[0268] The treatment cycle of the Chinese medicine combination is 2 weeks per node. Patients who meet the evaluation criteria can leave the group. The longest cycle is 4 weeks. After the treatment period, patients will be transferred to conventional medical treatment.

[0269] Observation indicators

[0270] Main indicators: TCM Qi deficiency syndrome quantitative scoring table (main symptoms - fatigue, shortness of breath, weakness, spontaneous sweating; secondary symptoms - laziness, low voice). Secondary indicators: ascites disappearance rate, human serum albumin; changes in body weight and waist circumference; improvement of biochemical indicators (liver function, prealbumin, cholinesterase).

[0271] Results: A total of 49 patients with liver cirrhosis were included in the study, 3 of whom dropped out, including 26 males and 23 females; the average age was 55.35±8.51 years old, the oldest was 71 years old, and the youngest was only 38 years old; a total of 38 patients had comorbidities, of which 57.1% had chronic hepatitis B, 20.4% had hypertension, and 14.3% had diabetes. 37 patients were taking concomitant medications. One case was missing.

[0272] The effect of the Chinese medicine composition of the present invention on the symptom score of patients with liver cirrhosis and qi deficiency syndrome is shown in Table 21: the total symptom score and the single TCM symptom score of the two groups of data before and after treatment are in accordance with normal distribution, and the paired sample t test is used for comparison. The total symptom score and the single symptom score after treatment are significantly reduced compared with those before treatment, with statistical difference (P<0.05), indicating that the Chinese medicine composition of the present invention can significantly improve the symptoms of fatigue, weakness, shortness of breath, spontaneous sweating, laziness, low voice, etc. in patients with liver cirrhosis.

[0273] Table 21. Comparison of Qi deficiency syndrome symptom scores before and after treatment

[0274]

[0275] Note: *P<0.05 compared with before treatment.

[0276] The effect of the Chinese medicine composition of the present invention on the liver function of patients with liver cirrhosis and qi deficiency syndrome is shown in Table 22: ALT, AST, GGT, and ALB of the two groups of data before and after treatment did not conform to the normal distribution, and the comparison was made by non-parametric test. The results showed that after treatment, the expression levels of ALT, AST, and GGT of the patients decreased compared with those before treatment, and ALB did not change significantly. Among them, the difference of GGT before and after treatment was statistically significant, with a P value of 0.013, and the difference of the expression levels of other indicators before and after treatment was not statistically significant (P>0.05).

[0277] Table 22. Changes of liver function indicators before and after treatment

[0278]

[0279] Note: *P<0.05 compared with before treatment.

[0280] The effect of the Chinese medicine composition of the present invention on the immune indexes of patients with liver cirrhosis and qi deficiency syndrome is shown in Table 23: The immune index data of the disease group and the healthy control group roughly conform to the normal distribution, and the independent sample t test is used. The results show that compared with the healthy control group, the Th2 content of the disease group decreased, the Th17 and Treg contents increased, and the difference was statistically significant (P < 0.05), and the Th1 difference was not statistically significant. The immune index data of the disease group before and after treatment roughly conform to the normal distribution, and the paired sample t test is used. The results show that compared with before treatment, the Th1 and Treg contents after treatment decreased, and the difference was statistically significant (P < 0.05), and the Th2 content increased, and the difference was statistically significant (P < 0.05).

[0281] Table 23. Changes of immune indicators before and after treatment

[0282]

[0283] Note: Compared with the healthy control group, #P<0.05; compared with before treatment, *P<0.05

[0284] Conclusion: The effect of the Chinese medicine composition of the present invention on the symptom score of Qi deficiency syndrome: The symptom score of the patients was significantly higher, and the single symptom and overall symptom score of the patients after taking the medicine were significantly improved, and the symptom score was significantly reduced, indicating that the Chinese medicine composition of the present invention has a significant improvement effect on the symptoms of Qi deficiency syndrome such as fatigue, weakness, shortness of breath, spontaneous sweating, laziness, and low voice. The effect of the Chinese medicine composition of the present invention on liver function: Liver function test is an examination item reflecting the physiological function of the liver. Abnormal liver function is also a manifestation of abnormal physiological function of the liver. From the manifestation of Qi deficiency, abnormal liver function is also an external manifestation of liver Qi deficiency. ALT, AST, GGT, and ALB are important indicators reflecting liver function. The Chinese medicine composition of the present invention can significantly reduce the GGT level of patients, and ALT and AST also have a trend of improvement, indicating that it has a significant protective effect on liver function. The effect of the Chinese medicine composition of the present invention on the immune system of patients with cirrhosis: Th2, Th17, and Treg of subjects with cirrhosis showed abnormalities compared with the healthy control group, and the Chinese medicine composition of the present invention can significantly improve the abnormal state of the immune system.

[0285] "Qi deficiency syndrome" is a basic syndrome in clinical Chinese medicine, and is also a common pathogenesis in common and frequently occurring diseases in clinical practice. According to the knowledge of Chinese medicine, due to insufficient vital energy, the functions of Qi such as promotion, consolidation, defense, and gasification are reduced, or the functions of organs and tissues are reduced, which manifests as a series of weakness symptoms such as mental fatigue, weakness, shortness of breath, and weak pulse. Strengthening the body and replenishing Qi is its basic treatment principle. The Chinese medicine composition of the present invention is simple in medicine and powerful in strength, can strengthen the body and replenish Qi, and has significant and reliable clinical efficacy in treating common diseases with Qi deficiency syndrome in clinical practice.

[0286] It is known from common technical knowledge that the present invention can be implemented by other embodiments that do not deviate from its spirit or essential features. Therefore, the above disclosed embodiments are only illustrative in all respects and are not exclusive. All changes within the scope of the present invention or within the scope equivalent to the present invention are included in the present invention.

Claims

1. Use of a Chinese medicine composition in the preparation of a preparation for use alone to treat, prevent, alleviate and / or control a disease in an animal, The disease is chronic heart failure; The raw materials of the traditional Chinese medicine composition are composed of ginseng and astragalus by weight, wherein: The weight ratio of ginseng to astragalus is 1:3; The preparation method of the Chinese medicine composition comprises the following steps: S1: decoct ginseng and astragalus with water and filter to obtain a medicinal solution; S2: Concentrating the medicinal solution into a thick paste.

2. The use according to claim 1, characterized in that The traditional Chinese medicine composition also includes pharmaceutical excipients, which include fillers and / or lubricants.

3. The use according to claim 2, characterized in that The filler is starch and / or dextrin.

4. The use according to claim 1, characterized in that The dosage form of the Chinese medicine composition is oral liquid, granules, capsules, soft capsules, dropping pills or decoction.

5. The use according to claim 1, characterized in that The animal is a mammal.

6. The use according to claim 5, characterized in that The mammal is selected from humans, mice and rats.

7. The use according to claim 1, wherein the Chinese medicine composition can treat, prevent, alleviate and / or control chronic heart failure of animals by intervening physiological indicators, and the intervening physiological indicators include: Improve cardiac ejection fraction; Increase the rate of shortening of the heart's minor axis; Increase cardiac output per stroke; Increase cardiac output; Decreases ventricular end-systolic diameter; Decreased ventricular end-diastolic diameter; Decreased ventricular end-systolic volume; Decreased ventricular end-diastolic volume; Reduce myocardial collagen volume fraction; Inhibit myocardial fibrosis; and Reduce angiotensin II levels.

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