CN113952377A

CN113952377A - Traditional Chinese medicine composition for treating qi deficiency syndrome and preparation method and application thereof

Info

Publication number: CN113952377A
Application number: CN202111467926.8A
Authority: CN
Inventors: 刘建勋; 任钧国; 孟硕; 彭勍; 苗兰; 姚明江
Original assignee: XIYUAN HOSPITAL OF CHINA ACADEMY OF CHINESE MEDICAL SCIENCES
Current assignee: XIYUAN HOSPITAL OF CHINA ACADEMY OF CHINESE MEDICAL SCIENCES
Priority date: 2021-12-03
Filing date: 2021-12-03
Publication date: 2022-01-21

Abstract

The invention discloses a syndrome traditional Chinese medicine composition, which comprises the following raw materials in parts by weight: 3-9 parts of ginseng and 30-90 parts of astragalus. The invention also discloses a preparation method of the composition, which comprises the following steps: decocting Ginseng radix and radix astragali with water, and filtering to obtain medicinal liquid; concentrating the medicinal liquid to obtain soft extract; drying the thick paste to obtain medicinal powder; mixing the medicinal powder with medicinal adjuvants, and making into Chinese patent medicine. Ginseng is effective in invigorating primordial qi, invigorating spleen and lung, and tonifying middle-jiao; astragalus root, radix astragali, invigorating qi and raising yang, benefiting wei-defensive qi and consolidating exterior, prefers to yang and strengthen exterior, the two herbs are reinforced mutually, one is exterior and one is interior, one is yin and one is yang, and the two herbs are mutually combined, so as to strengthen the body resistance and supplement qi. Through systematic animal and clinical trial research, the traditional Chinese medicine composition can treat qi deficiency symptoms, improve the hypoxia tolerance and the fatigue resistance, improve the visceral functions of diseases such as chronic heart failure, chronic obstructive pulmonary disease, chronic glomerulonephritis, chronic atrophic gastritis and the like by improving the whole qi deficiency syndrome of an organism, and improve the disease state.

Description

Traditional Chinese medicine composition for treating qi deficiency syndrome and preparation method and application thereof

Technical Field

The invention belongs to the field of traditional Chinese medicine and pharmacy, relates to a traditional Chinese medicine composition, and particularly relates to a traditional Chinese medicine composition for preventing and treating qi-deficiency syndrome as well as a preparation method and application thereof.

Background

The syndrome of qi deficiency is the most basic syndrome in the theory and clinical differentiation of traditional Chinese medicine, and the "qi deficiency" and "qi deficiency" are clearly explained in "Huangdi's internal classic", and modern traditional Chinese medicine has many new cognitions and supplements for the syndrome of qi deficiency, including diagnostic criteria and therapeutic principles. In the clinical practice of traditional Chinese medicine, the pathological changes of qi include the main pathogenesis of qi deficiency, such as cardiovascular and cerebrovascular diseases, digestive system diseases, respiratory system diseases, urinary system diseases and the like. For instance, the pathogenesis of cardiovascular diseases such as "true heart pain" and "faintness heart pain" is mostly the deficiency of the principal and the excess of the principal, the "heart bi-syndrome with obstructed vessels" ("Huangdi's internal channel Bi-syndrome)", the "yang-yin wiry, i.e. chest bi-syndrome with pain, so the extreme deficiency is also responsible for the treatment of the deficiency syndrome with short-term qi (jin kui-qi deficiency syndrome of heart bi-syndrome with obstruction in the chest), therefore, the deficiency here is mainly qi deficiency, and heart qi tonifying is one of the basic treatment principles. For example, liver diseases such as "accumulation", "tympanites" and "liver stagnation" are marked by symptoms of mass, abdominal mass, accumulation and accumulation due to the deficiency of the vital energy of the five zang-organs and six fu-organs, which are caused by the syndrome of pathogenic qi deficiency of the spleen and stomach, failing to transport and transform essence to produce food, and accumulating and dispersing to form distention. "(" secret book of orchid Chamber. Zhongmang abdominal distention Lun "), it is clear that qi deficiency is a major pathogenesis. In addition, for example, digestive system diseases such as "stomach stuffiness" and "stomachache", the "fullness of disease and spleen disease are also caused by insufficiency of spleen qi and qi stagnation, and the heart-qi deficiency, which results in the failure of transportation and transformation, and thus, the weak of the barn orifices and the damage of the middle-qi are the main pathogenesis. For example, respiratory diseases such as "lung distension" and "dyspnea syndrome" include "32992variant" with congestion of lung and dyspnea syndrome "with fullness" ("Suzhou & Da Qi Lun)", and "lung distension" with fullness and dyspnea syndrome with cough and dyspnea due to deficiency syndrome. ' Lingshu & bloating Lung ' refers to the condition that the lung governs qi and lung qi of the whole body, and the blood vessels are smooth, because of the ' lung bloating, the interior has stagnation, the lung qi is injured first, the exterior is infected with exogenous pathogenic factors, and the lung qi cannot be discharged, the lung bloating is ' as in ' syndrome-induced pulse therapy ', ' excessive asthma has pathogenic factors, excessive pathogenic qi also, deficient asthma has no pathogenic factors, and deficiency of original qi also ' as in ' Jingyue ' quan Shu & dyspnea promotion ', so that the lung qi weakness is the main pathogenesis of the disease. For example, in urinary system diseases such as "lumbago", "kidney wind" and "hematuria", the main pathogenesis of edema, lumbago and hematuria is due to kidney qi deficiency, deficiency of qi and blood, weakness of qi and blood of human body, and the like. The qi-deficiency syndrome is a basic syndrome in the clinical practice of traditional Chinese medicine, and is mainly manifested as lassitude, hypodynamia, spontaneous perspiration, low and slight speech, sallow complexion, pale or dark lip, swollen or enlarged tongue, pale or reddish or dim tongue, weak pulse, etc. As mentioned above, the deficiency of original qi, the hypofunction of qi in promoting, consolidating, defending, and gasifying, or hypofunction of zang-fu organs, results in hypofunction or decline of physiological functions, and decreased disease resistance. Therefore, the treatment is as strengthening body resistance and benefiting qi.

Ginseng and Huang Qi are the most widely used herbs for tonifying qi in clinical tradition and used for treating various syndromes of qi deficiency. Ginseng, sweet in taste, slightly bitter in flavor and slightly warm in nature, enters lung, spleen, heart and kidney meridians, and has the effects of invigorating primordial qi, restoring pulse, relieving depletion, invigorating spleen, benefiting lung, tranquilizing mind and improving intelligence. Astragalus root, radix astragali, with mild nature and sweet taste, enters lung and spleen channels and has the effects of invigorating qi and raising yang, tonifying wei-defensive exterior, relieving toxicity and promoting granulation, inducing diuresis and relieving swelling. The combination of astragalus and ginseng, astragalus being more specific to yang but exterior and ginseng being more specific to yin but middle-energizer, the two herbs are mutually reinforced, one is exterior and interior, and one is yang and one is yin, and the two herbs are mutually combined, so that the functions of the two herbs complement each other and play the roles of strengthening body resistance and invigorating qi together.

In the clinical practice of traditional Chinese medicine, the pathological changes of qi include the main pathogenesis of qi deficiency, such as cardiovascular and cerebrovascular diseases, digestive system diseases, respiratory system diseases, urinary system diseases and the like. Although the clinical basic treatment of many systemic common diseases such as liver, heart, spleen, lung and kidney is mature, the satisfactory effect still cannot be achieved, and the body and mind of the patient are also affected by various symptoms. Under the guidance of the traditional Chinese medicine theory, the development of effective Chinese medicine composition for clinical application is an important key entry point for revealing the characteristics of the traditional Chinese medicine and carrying out the deep research of effective formulas/traditional Chinese medicines.

Disclosure of Invention

In order to solve the problems in the prior art, the invention provides, in a first aspect, a traditional Chinese medicine composition, wherein the pharmaceutically active ingredients of the traditional Chinese medicine composition are from: ginseng radix and radix astragali.

The invention is a syndrome medicine, has simple medicine and simple preparation process, contains biological active ingredients such as saponins and polysaccharides, and has no toxic or side effect on human body after continuous taking. The Chinese medicinal composition is suitable for the clinical adjuvant treatment of various diseases belonging to qi deficiency syndrome, and has the effects of strengthening body resistance and invigorating qi.

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

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

In some embodiments, the Chinese medicinal composition further comprises a pharmaceutical adjuvant. The medicinal auxiliary materials can be conventional auxiliary materials for preparing granules, capsules, paste and the like. Preferably, the adjuvant comprises a filler and/or a lubricant; more preferably, the filler is starch and/or dextrin.

In some embodiments, the dosage form of the Chinese medicinal composition is oral liquid, granules, capsules, soft capsules, dripping pills or soft extracts.

The second aspect of the present invention provides a method for preparing the Chinese medicinal composition of the first aspect of the present invention, wherein the method comprises the following steps:

s1: decocting Ginseng radix and radix astragali with water, and filtering to obtain medicinal liquid;

s2: concentrating the medicinal liquid to obtain soft extract.

In some embodiments, the method of making further comprises the steps of:

s3: drying the thick paste to obtain medicinal powder.

In some embodiments, the method of making further comprises the steps of:

s4: mixing the medicinal powder with the medicinal adjuvants, and making into Chinese patent medicine.

In some embodiments, in step S1, the number of times of decoction is 2-4, and the filtrates from each decoction are combined as the liquid medicine; decocting for 60-180 min each time, wherein the water for each time is 8-15 times of the weight of the crude drug or the residue obtained by the previous decoction.

In some embodiments, in step S2, the thick paste has a density of: 1.05-1.10g/cm³。

In some embodiments, in step S2, the concentrating is vacuum concentrating.

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

In some embodiments, the drying is performed after mixing the thick paste and the filler in a weight ratio of 5-20:1 in step S3.

The third aspect of the present invention provides the use of a composition according to the first aspect of the present invention or a method according to the second aspect of the present invention for the manufacture of a medicament for use alone, in combination with other formulations and/or medicaments, or as a component of a combination formulation with other formulations and/or medicaments for the treatment, prevention, alleviation and/or management of a disease or sub-health condition in an animal selected from: syndrome of qi deficiency; chronic heart failure; chronic obstructive pulmonary disease; chronic glomerulonephritis; chronic atrophic gastritis; the improvement of the body function of the animal is selected from: improving the hypoxia tolerance; improving the anti-fatigue capability.

In some embodiments, the animal is a mammal.

In some embodiments, the animal is selected from a human, a mouse, a rat.

In a fourth aspect, the present invention provides a use of a composition according to the first aspect of the present invention or a process for the preparation according to the second aspect of the present invention for the manufacture of a medicament for use alone, in combination with other formulations and/or medicaments, or as a component of a combination formulation with other formulations and/or medicaments, for the treatment, prevention, alleviation and/or management of a disease or sub-health condition in an animal treatable, preventable, alleviated and/or controllable by intervention in a physiological parameter selected from the group consisting of:

improving the cardiac ejection fraction; the short axis shortening rate of the heart is improved; increasing cardiac stroke volume; improving cardiac output; reducing the end systolic ventricular diameter; reducing the ventricular end-diastolic diameter; reducing ventricular end-systolic volume; reducing ventricular end-diastolic volume; reducing myocardial collagen volume fraction; inhibiting myocardial fibrosis; reducing the angiotensin II content; reducing serum creatinine content; enhancing lung function FEV 1%; enhancing lung function FEV 1/FVC%; enhancing pulmonary function FVC%; reducing the glutamic-pyruvic transaminase concentration; reducing AST aspartate aminotransferase concentration; reducing the concentration of GGT glutamyl transpeptidase.

In some embodiments, the animal is a mammal.

In some embodiments, the animal is selected from a human, a mouse, a rat.

The "Nei Jing" has cloud: for those with impairment of the body's vitality and qi deficiency, the tonifying herbs are sweet. The traditional Chinese medicine composition has simple and powerful components. In the formula, ginseng is sweet, slightly warm and slightly bitter, enters spleen and lung meridians, and can ascend and descend. Has the effects of invigorating primordial qi and tonifying, and is a holy medicine for invigorating qi, because ginseng can return yang qi to cause prolapse, thereby benefiting vital qi of five internal organs, strengthening body resistance and benefiting qi. Qi-tonifying herbs depend on the qi-clearing herbs and tonify qi. In the recipe, Huangqi, sweet in flavor and slightly warm in flavor, is the essential herb for invigorating qi and invigorating yang, and reinforcing defensive qi and consolidating superficial resistance. Covering the whole body, the soil is the mother of all things, all viscera and bones can be strengthened after receiving qi in spleen and stomach, no matter cold or heat reinforcing and reducing, the soil is cultivated first, so that the medicine qi reaches four places, the whole body is transported and circulated, and the food essence is spread slightly. The lung governs qi of the whole body, and lung qi sinks, so it is short in breath and dyspnea, lung qi goes to all pulses, and lung qi deficiency makes all pulses unable to go, so it is deep, slow and weak. Ginseng and Huang Qi can tonify lung qi and nourish spleen qi. Ginseng, radix astragali, radix Ginseng and radix astragali are used for invigorating qi, nourishing yin, and strengthening body resistance and invigorating qi. The traditional Chinese medicine composition has the main functions: strengthen body resistance and replenish qi. It is suitable for treating qi deficiency syndrome. Has adjuvant therapeutic effect on qi deficiency syndrome of common diseases and frequently encountered diseases in various systems. The symptoms are as follows: mental fatigue, shortness of breath, fatigue, spontaneous perspiration, shortness of breath, no speaking desire, low and slight speech and other subjective symptoms, and pale tongue, weak pulse and other clinical manifestations. For the evaluation of the traditional Chinese medicine composition, the invention also combines the systematic clinical research to carry out clinical curative effect observation on the liver cirrhosis gas deficiency syndrome, the chronic atrophic gastritis gas deficiency syndrome, the chronic obstructive pulmonary disease gas deficiency syndrome and the chronic glomerulonephritis gas deficiency syndrome. The traditional Chinese medicine composition can obviously improve the symptoms of patients and improve the overall evaluation of syndrome manifestations, including subjective symptoms such as listlessness and the like and clinical manifestations of tongue and pulse.

The invention has the beneficial effects that: the traditional Chinese medicine composition has simple preparation process, is prepared from traditional Chinese medicines with remarkable clinical efficacy, does not add other chemical synthetics, and has no toxic or side effect on human bodies after being continuously taken. The traditional Chinese medicine composition contains saponin, polysaccharide and other bioactive components proved by modern pharmacology, can be effectively used for clinical treatment of qi deficiency syndrome, has a better auxiliary treatment effect on other diseases belonging to qi deficiency syndrome, and has the effects of strengthening body resistance and tonifying qi.

Drawings

FIG. 1 is an echocardiogram of rats in each group.

FIG. 2 is a photograph showing the pathological tissue morphology of the myocardium of rats in each group (Masson staining, 200X), wherein A is a sham-operated group; b: a model group; c: the traditional Chinese medicine composition of the invention is used in a low-dose group; d: the dosage group of the traditional Chinese medicine composition is prepared; e: the high dose group of the traditional Chinese medicine composition of the invention F: and (4) valsartan group.

FIG. 3 is a photograph (HE staining, 200X) of the composition on the morphology of myocardial tissue of rats with heart failure after myocardial infarction, wherein A is in the sham operation group; b: a model group; c: the traditional Chinese medicine composition of the invention is used in a low-dose group; d: the dosage group of the traditional Chinese medicine composition is prepared; e: the high dose group of the traditional Chinese medicine composition of the invention F: and (4) valsartan group.

Wherein, 1:5, 1:10 and 1:20 represent the dosage ratio of the human and the astragalus root in the composition.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, embodiments of the present invention will be described in detail with reference to the accompanying drawings.

The Chinese medicinal raw materials of the invention, namely ginseng and astragalus, particularly the quality of the ginseng and the astragalus meet the standard of 2020 edition Chinese pharmacopoeia, and the effective components of the ginseng, such as ginsenoside Rg1 (C) in the ginseng₄₂H₇₂O₁₄) And ginsenoside Re (C)₄₈H₈₂O₁₈) The total content of ginsenoside Rb1 (C) is not less than 0.27%₅₄H₉₂O₂₃) Not less than 0.18 percent. Radix astragali contains calycosin glucoside (C)₂₂H₂₂O₁₀) Not less than 0.020%. The raw material medicines of ginseng and astragalus root decoction pieces used in the following embodiments of the invention are obtained by a processing method in 2020 edition Chinese pharmacopoeia.

Preparation of compositions 1 to 5 used in test examples of the present invention

The raw material medicaments used by the invention are as follows: 1 part by weight of ginseng, 3-30 parts by weight of astragalus and 1-5 parts by weight of composition are shown in the following table 1.

TABLE 1 specific parts by weight of compositions 1-5

Composition comprising a metal oxide and a metal oxide	Ginseng/part by weight	Astragalus root/weight part
			Composition 1	1	3
Composition 2	1	5
			Composition 3	1	10
Composition 4	1	20
			Composition 5	1	30

The compositions 1 to 5 are granules, and the preparation method is as follows: (1) weighing Ginseng radix and radix astragali according to the raw materials of composition 1-5, decocting with 10 times of water for 3 times (2 hr each time), filtering the decoction, mixing, and stirring. (2) Vacuum concentrating the filtrate obtained in step (1) to relative density of 1.05-1.10(1.05-1.10 g/cm) at 60 deg.C with water as reference density³) Is thick paste. Adding appropriate amount of dextrin (the weight ratio of crude drug to dextrin is 10: 1), stirring, sieving with 100 mesh sieve, and spray drying the undersize product to obtain extract intermediate (or called powder). (3) Preparation of granules: and adding a proper amount of dextrin and magnesium stearate into the extract intermediate, fully and uniformly mixing, drying, and performing conventional dry granulation to obtain granules (compositions 1-5) of the composition. The above preparation examples are merely examples of the preparation of the composition of the present invention, and do not limit the dosage form of the composition of the present invention, and the composition of the present invention can be prepared into any useful Chinese medicinal dosage form or Chinese medicinal dosage form by using the conventional methods in the art.

Test example 1: improving effect on hypoxia tolerance and fatigue resistance of mice

The most important clinical manifestations of qi deficiency syndrome are shortness of breath and hypodynamia, and the examination of anoxia resistance and fatigue resistance can reflect the treatment effect of the medicine on qi deficiency syndrome. The experiment aims to adopt a classical normal-pressure hypoxia-resistant experiment and a load-bearing exhaustive swimming experiment to evaluate the effects of three compatibility proportions of the traditional Chinese medicine composition on normal-pressure hypoxia resistance and fatigue resistance.

The tested drugs are: the traditional Chinese medicine composition comprises 1 part of ginseng and 20 parts of astragalus, wherein the astragalus is 5 parts, 10 parts and 20 parts, namely the ginseng and astragalus are 1: group 5 (composition 2), ginseng astragalus 1: group 10 (composition 3), ginseng, astragalus 1: group 20 (composition 4).

Animals: 192 BALB/c mice, SPF grade, half male and female, weight 18-20 g, purchased from Sibefu (Beijing) Biotechnology Limited, license number: SCXK (Jing) 2019-; SPF animal room feeding in western aster hospital of Chinese academy of science and technology.

The method for testing the influence of the normal-pressure hypoxia tolerance of the mice comprises the following steps: the test was randomly divided into 6 groups of 16 mice each, each half of male and female, a blank control group, a radix astragali group (2.75 g/kg. d) alone, a ginseng group (0.34 g/kg. d) alone, a traditional Chinese medicine composition of the present invention of radix ginseng and radix astragali 1:5 (4.40 g/kg. d), a traditional Chinese medicine composition of the present invention of radix ginseng and radix astragali 1:10 (4.80 g/kg. d), and a traditional Chinese medicine composition of the present invention of radix ginseng and radix astragali 1:20 (3.93 g/kg. d). The preparation method of the medicine using radix astragali group and radix Ginseng group is the same as that of composition 1-5. The mouse administration dose is calculated according to the effective drug consumption (crude drug quantity) of the composition for clinical human according to the body surface area, the cream yield and the like of a human/mouse, wherein 4.40 g/kg-d, 4.80 g/kg-d and 3.93 g/kg-d are the mouse daily administration doses obtained by calculating the crude drug quantity of the composition of the corresponding group, and the administration dose g/kg-d means the gram of the crude drug quantity used per kilogram of mouse per day. The specific conversion method can be referred to pharmacological experimental methodology. The drug for gastric administration to mice is prepared by dissolving the prepared granules in distilled water according to the administration dosage of the mice.

The administration method comprises the following steps: gavage was performed with 0.2ml/10g body weight 1 time per day for 14 consecutive days, and the blank control group was given the same volume of distilled water. The body weight was weighed before administration, 7 days after administration, and 14 days after administration, respectively.

The experimental process comprises the following steps: after mice are adaptively fed for 4 days, the mice are subjected to intragastric administration, 1 hour after the last administration, each group of mice are respectively placed into a 250ml wide-mouth bottle filled with 5g of soda lime, 1 mouse is placed into each bottle, the bottle mouth is sealed by a bottle plug and vaseline, the time is immediately counted until the mice stop breathing, the mice are suddenly paralyzed after struggling and twitching, the complete stop of the fluctuation motion of the thorax is taken as a judgment standard, and the survival time of the mice in a closed wide-mouth glass bottle is recorded and recorded as the survival time of the mice with oxygen deficiency resistance under normal pressure.

The experimental method for the mouse weight-bearing swimming comprises the following steps: the test was randomly divided into 6 groups of 16 mice each, each half of male and female, a blank control group, a radix astragali group (2.75 g/kg. d) alone, a ginseng group (0.34 g/kg. d) alone, a traditional Chinese medicine composition of the present invention of radix ginseng and radix astragali 1:5 (4.40 g/kg. d), a traditional Chinese medicine composition of the present invention of radix ginseng and radix astragali 1:10 (4.80 g/kg. d), and a traditional Chinese medicine composition of the present invention of radix ginseng and radix astragali 1:20 (3.93 g/kg. d). The preparation method of the medicine using radix astragali group and radix Ginseng group is the same as that of composition 1-5.

The experimental process comprises the following steps: after the mice are adaptively fed for 4 days, the intragastric administration is carried out, 1h after the last administration, each group of mice is respectively weighed, lead strips with the weight of 5 percent of the weight of the mice are bound at the root of the tail, the mice are placed in a swimming box (the water temperature is 25 ℃, the water depth is about 30cm) for swimming, and the swimming is forced to be exhausted. The swimming time is recorded from the beginning of swimming of the mouse to the time when the whole body is not submerged for 8s and can not float out of the water surface.

The statistical method comprises the following steps: experimental data on

Showing that the data among the groups are subjected to t test, P<A difference of 0.05 is statistically significant.

Test results

The traditional Chinese medicine composition has the following effects on the weight of a mouse: compared with a blank control group, the body weight of mice in each administration group is normally increased without significant difference before, 7 days and 14 days of administration. See table 2.

TABLE 2 Effect of the Chinese medicinal composition of the present invention on the overall body weight change of mice

The traditional Chinese medicine composition has the following effects on the hypoxia tolerance of mice: compared with a blank control group, the traditional Chinese medicine composition disclosed by the invention is compatible in different proportions and is continuously administered for 14 days by intragastric administration, the survival time of a mouse under the condition of normal pressure and oxygen deficiency can be prolonged by 14.13% by the proportion of the traditional Chinese medicine composition 3 (P is less than 0.05), the survival time of the mouse under the condition of normal pressure and oxygen deficiency can be prolonged by 3.60% by the traditional Chinese medicine composition 2, and the survival time of the mouse under the condition of normal pressure and oxygen deficiency can be shortened by 3.24% by the proportion of the traditional Chinese medicine composition 4, which is specifically shown in Table 3.

TABLE 3 Effect on hypoxia tolerance in mice

Note P <0.05, P <0.01, compared to the blank control group; compared with the traditional Chinese medicine composition in the ratio of 1:10, the influence of # P <0.05 and # P <0.01 on the weight swimming time of mice is as follows: compared with a blank control group, the traditional Chinese medicine composition disclosed by the invention is compatible in different proportions and is continuously infused for 14 days, the weight swimming time of a mouse can be prolonged by 24.88% according to the proportion of the traditional Chinese medicine composition 3, and the weight swimming time of the mouse can be prolonged by 5.24% according to the proportion of the traditional Chinese medicine composition 2, which is specifically shown in a table 4.

TABLE 4 Effect on weight bearing swimming time of mice

Note: p <0.05, P <0.01, compared to the blank control group; compared with the traditional Chinese medicine composition with the ratio of 1:10, # P <0.05, # P <0.01

And (4) conclusion: the experimental result indicates that the traditional Chinese medicine composition of the invention, namely the ginseng and the astragalus root with the ratio of 1:10, can obviously improve the anti-hypoxia capability of an organism, has the function of improving hypoxia tolerance, can obviously prolong the survival time of mice in load swimming, and has the effect obviously superior to that of independent administration of the ginseng and the astragalus root and other ratios, thereby showing that the traditional Chinese medicine composition has a certain effect of improving the exercise fatigue of the organism. Therefore, the proportion of the ginseng and the astragalus root of the traditional Chinese medicine composition is optimally 1:10 from the aspects of anoxia tolerance and anti-fatigue effect.

Test example 2: therapeutic effect of traditional Chinese medicine composition on chronic heart failure rats

The occlusion or stenosis of the coronary arteries causes myocardial ischemia, myocardial contractility decreases, infarcted area of the myocardium further expands and loses function, and chronic heart failure can form after a period of time. In the experiment, the effect of the traditional Chinese medicine composition on improving the heart function is observed by ligating the left anterior descending branch of the coronary artery to cause myocardial infarction of SD rats and then forming an animal model of chronic heart failure.

Experimental animals: 67 male SD rats, SPF grade, weighing 180-200 g, were purchased from the animal technology of experiments, Inc. of Wei Tony Hua, Beijing under license number SCXK (Beijing) 2016-. The rats are raised in the center of SPF-level experimental animals in western milk vetch hospital of Chinese academy of science, the temperature is 23 +/-3 ℃, the humidity is 50 +/-6%, the illumination is 12h, the rats are alternately eaten and drunk day and night freely.

Experimental drugs: the traditional Chinese medicine composition comprises 1 part of ginseng and 3 parts of astragalus (namely the composition 1), and the preparation method adopts the embodiment 1. And (4) valsartan and nova are produced in pharmacy.

Establishing and experimental grouping of animal models: SD rats are subjected to model building operation after being adaptively raised in an animal house for 3 days, and are fasted and water is forbidden one night before operation. Preparing 3.5% (w/v, the same below) chloral hydrate solution by using normal saline, weighing a rat, performing intraperitoneal injection on the rat according to 1ml of the solution per 100g of the weight of the rat, fixing the rat in a rat plate with four limbs facing upward after the rat enters an anesthetic state, inserting a trachea, and accessing a small animal respirator (70 times/minute, the respiratory ratio of 1:2 and the tidal volume of 9.0). After a rat is subjected to thoracotomy after stable respiration, a rat board is transversely placed, the left chest is unhaired, alcohol is sprayed for disinfection, the outer skin is cut at a position 1cm below the left armpit of the rat, two layers of muscle tissues are passively stripped, ribs are exposed, the left side 3 and the left side 4 of the chest of the rat are passively separated and are spread by hemostatic forceps, the pericardium is lightly stripped, cotton is inserted into the chest to isolate the lung and thymus tissues, the heart is completely exposed, the upper part of the left anterior descending branch of the coronary artery is ligated by using a No. 0 surgical thread, the color of the heart is observed to be changed from red to pale after a stabilization period, and the successful preparation of the myocardial infarction model is prompted. Taking out cotton, closing chest, exhausting air from chest cavity, sewing ribs, muscle and epidermis, and smearing penicillin on wound. The trachea cannula can be taken out after the rat is awake and can turn over automatically. After the operation, the rats recover normal diet and drinking water. To exclude the effect of surgical factors, sham-operated rats were set up. The sham operation group only threaded, not ligated the upper left anterior descending branch of coronary artery, and the rest steps were as above. If not, only the operation trauma and recovery are caused, and the heart failure can not be caused.

After 50 rats with good operation effect were selected from 67 rats and the following experiments were carried out, the rats with the Chinese medicinal composition SD were randomly divided into 5 groups of 10 groups, namely, a Sham operation group (Sham), a Model group (Model), a high dose group (crude drug dosage: 4.5 g/kg. d) of the Chinese medicinal composition of the present invention, a medium dose group (crude drug dosage: 3.0 g/kg. d), a low dose group (crude drug dosage: 1.5 g/kg. d) and a valsartan group (valsartan, 30mg/kg) as a positive drug. The postoperative administration group is continuously administered for 28 days by intragastric administration, 1 time per day, and the sham operation group and the model control group are administered with the same amount of physiological saline for intragastric administration. The dosage calculated in the animal test of the invention is converted according to the effective dosage of the medicine for human in clinic, and comprises the dosage of the positive medicine valsartan group.

General state observation: after the model of the rat is built, the hair color, spirit and activity state of the rat are regularly observed according to the administration time node, and the change of the weight of the rat per week is recorded.

Echocardiography detection: after 28 days of administration to rats, echocardiography was performed to determine changes in cardiac structure and function. Rats were weighed, anesthetized by intraperitoneal injection using a 3.5% chloral hydrate solution at a concentration of 1ml per 100g of rat weight, and after the anesthetized state, the rat was subjected to depilatory skin preparation treatment from the left clavicle of the chest to the lower edge of the rib. The rat is fixed on a platform in a supine position, the heart rate is stabilized, medical ultrasonic coupling gel is smeared on the skin preparation, then a probe is used for two-dimensional scanning on a left ventricular long axis and a short axis section beside a sternum, a left ventricular short axis section M is selected for carrying out ultrasonic measurement on left ventricular systolic end inner diameter (LVIDs), left ventricular diastolic end inner diameter (LVIDd), left ventricular systolic end volume (LVEVs), left ventricular diastolic end volume (LVEVd), ejection fraction (LVEF), short axis shortening rate (LVFS), stroke output (SV) and Cardiac Output (CO), the indexes are continuously measured for five cycles, and an average value is obtained for calculation. After the detection is finished, the rat is recovered and put back into the animal room.

Detecting myocardial pathological tissues of rats: after the last administration of the rats, 3.5 percent chloral hydrate solution is injected into the abdominal cavity for anesthesia, the chest is opened to take materials, myocardial infarction marginal area tissues are reserved and fixed in 4 percent tissue fixing solution, and the rats are dehydrated, transparent, embedded by paraffin and sliced. Ready for pathological HE and Masson staining analysis.

Rat myocardial volume collagen fraction determination: masson Image acquisition and analysis, 6 slices are selected in each group, 3 different fields are selected in each slice, and the Collagen Volume Fraction (CVF) of each field, namely the percentage of the positive blue area of collagen to the total area of tissues, is measured by using Image J software.

Plasma Ang ii assay: after the rat is administered for the last time, 3.5% chloral hydrate solution is injected into the abdominal cavity for anesthesia, the abdominal aorta is used for taking blood, the blood is put into a citric acid anticoagulation tube and is kept stand for 15min, 2000g is centrifuged for 10min, and the supernatant is taken as plasma. Ang ii levels were determined according to kit instructions.

Statistical treatment: all measurements are taken as mean. + -. standard deviation

It shows that SPSS 20.0 software is adopted for statistical treatment, if the SPSS is in accordance with normal distribution, single-factor variance analysis is adopted, and P is less than 0.05, which means that the difference has statistical significance.

Results

The influence of the traditional Chinese medicine composition on the general state of rats: the sham operation group had good mental status, smooth and bright hair color and less struggle during the administration period. The rats in the model group and the administration groups have dark hair, part of skin and hair are upright and messy, fighting activities are more and violent in early morning, and the phenomenon of biting appears. With the prolonged administration time, the fighting condition is mild, the temperature tends to be smooth, the irritability is reduced, and the general state difference of the model group and other rats in each group is not obvious. The weight of rats in each group is increased in different degrees during the administration period, after 4 weeks of administration, the weight of rats in the model group is obviously reduced (P <0.01), the weight of rats in each administration group is increased compared with that in the model control group, and the weight of rats in the administration group is statistically different from that in the model group (P <0.05) in the 4.5 g/kg.d group of the traditional Chinese medicine composition. As a whole, the body weight change of each dose-administered group showed no dose dependence. See table 5.

TABLE 5 Effect of the Chinese medicinal composition of the present invention on the change of body weight of rats

Note: p <0.05, P <0.01 compared to sham group; comparison with model group^△P＜0.05。

The influence of the traditional Chinese medicine composition on the heart function and the ventricular structure of a rat with chronic heart failure

The traditional Chinese medicine composition has the following effects on the heart function of rats with chronic heart failure: after 4 weeks of administration, model rats all had significant decreases in LVEF, LVFS, SV, CO (P <0.01) compared to sham operated groups. Compared with the model group, the indexes of rats in each administration group are increased to different degrees (P <0.01 or P <0.05), wherein the indexes of rats in the high-dose group of the traditional Chinese medicine composition are obviously increased (P <0.01) compared with the model control group. Overall, the dose groups showed no significant dose-dependent trend, but the improvement was better in the high dose group. See table 6.

TABLE 6 Chinese medicinal composition for treating heart failure after myocardial infarction

Note: comparison with sham group^##P<0.01，^#P<0.05; comparison with model group<0.01，*P<0.05 Chinese medicinal composition.

The traditional Chinese medicine composition has the following effects on the ventricular structure of a rat with chronic heart failure: after 4 weeks of administration, the LVIDs, LVIDd, LVEVs and LVEVd in the model group were all significantly up-regulated (P <0.01) compared with those in the sham operation group, and the indexes in each administration group were all significantly reduced compared with those in the model group, and the differences had statistical significance (P < 0.01). See table 7.

TABLE 7 Effect of the Chinese medicinal composition of the present invention on ventricular structure of rats with heart failure after myocardial infarction

Note: p <0.01, P <0.05, compared to Model group

The traditional Chinese medicine composition has the following effects on echocardiography of rats with heart failure after myocardial infarction: as can be seen from the cardiography, the heart contour of the sham operation group is normal, the internal structure is not abnormal, and the contraction/relaxation rhythm of the chamber wall is normal. The model group can show the enlargement of the whole heart chamber, mainly the enlargement of the left heart, the thickness of the myocardium at the infarct part is obviously reduced and the myocardium bulges outwards to the outline of the heart. The contraction thickening rate is reduced, the wall motion is abnormal, and the compensatory wall motion amplitude of the non-infarcted part is enhanced. The M type shows that the diastolic activity amplitude of the mitral valve is reduced and the valve orifice is reduced. Compared with the model group, the administration groups have the advantages of increased ventricular contraction amplitude, accelerated myocardial contraction speed and no obvious thinning of ventricular septum and left ventricular wall. See fig. 1. The echocardiography changes of the rats in each group are shown in FIG. 1.

The traditional Chinese medicine composition of the invention has the influence on the pathological tissue morphology of rat myocardium

The traditional Chinese medicine composition has the following effects on myocardial fibrosis of rats with chronic heart failure: the results show that the myocardial cells of the sham operation group have normal forms, uniform distribution, no obvious collagen deposition in the myocardial gaps, compact and regular arrangement of the muscle fibers and clear layers. The myocardial gap of the model group is obviously increased, the muscle fiber is broken, vacuole is generated and is accompanied with a great deal of collagen deposition, and the myocardial fibrosis tissue is increased. Compared with the model group, the treatment group of the traditional Chinese medicine composition and the valsartan group have certain improvement on myocardial damage, the myocardial cell gap is reduced, a small amount of collagen deposition can be seen, the arrangement of muscle fibers is complete, the breakage is reduced, the myocardial fibrosis degree is reduced, and the best recovery degree is observed by naked eyes in a high-dose group. The Chinese medicinal composition has the function of improving myocardial fibrosis injury of rats with acute myocardial infarction after heart failure. Fig. 2 shows that the high-dosage group of the traditional Chinese medicine composition has very obvious effect on improving myocardial fibrosis injury of rats with acute myocardial infarction heart failure.

The traditional Chinese medicine composition has the following effects on the myocardial collagen volume fraction of rats with chronic heart failure: compared with the sham operation group, the CVF of the rats in the model group is remarkably increased (P < 0.01); compared with the model group, the CVF of rats in each administration group is remarkably reduced (P is less than 0.01), wherein the reduction degree of the high-dose group of the traditional Chinese medicine composition is most obvious, and the CVF of rats gradually shows a reduction trend along with the increase of the administration dose in a comprehensive view, and the dose dependence is preliminarily shown. The Chinese medicinal composition can reduce myocardial CVF and inhibit myocardial fibrosis, and has better effect at medium and high doses. See table 8.

Table 8 comparison of myocardial CVF in rats (n-6,

)

note: p <0.01, P <0.05, compared to Model group

The traditional Chinese medicine composition has the following effects on the myocardial tissue morphology of rats with chronic heart failure: the results show that the myocardial tissues of the rats in the sham operation group are closely and regularly arranged, the myocardial cells are complete in shape, the peripheral blood vessels are clear, and no connective hyperplasia exists. The myocardial tissues of the model group are distributed irregularly, the structure is relatively disordered, the shapes of myocardial cells are changed, the myocardial gaps are increased, interstitial collagen fibers are increased, part of the muscle fibers are broken, and a large amount of inflammatory factors are infiltrated. Compared with a model group, the traditional Chinese medicine composition for treating myocardial tissue injury has the advantages of certain improvement, compact arrangement of myocardial tissue, complete cell morphology, relief of congestion and swelling of interstitial tissues and rupture and dissolution of muscle fibers, and unobvious inflammatory infiltration. The result indicates that the traditional Chinese medicine composition can improve the ischemic myocardial injury of rats with acute myocardial infarction and heart failure. Fig. 3 shows that the high-dose group of the traditional Chinese medicine composition has very obvious effect on improving ischemic myocardial damage of rats with acute myocardial infarction and heart failure.

The traditional Chinese medicine composition has the following effects on the level of angiotensin II of rats with chronic heart failure: ang ii is a characteristic marker of the pathological process of heart failure. The result shows that the content of Ang II in the plasma of rats in the model group is obviously increased (P <0.01) compared with that in the sham operation group, the content of Ang II in the plasma of rats is obviously reduced after the rats are treated by the traditional Chinese medicine composition with high dose, and the action effect is similar to that of the positive medicine valsartan (P < 0.01). See table 9.

TABLE 9 Effect of the Chinese medicinal composition of the present invention on the level of angiotensin II in rats with heart failure after myocardial infarction

Note: p <0.01, P <0.05, compared to Model group

Conclusion

The traditional Chinese medicine composition of the invention has the following influence on the body state: the traditional Chinese medicine composition and the valsartan can obviously improve the weight of a rat of a myocardial infarction model. Shows that the compound has better regulation effect on the overall state of the sick rat.

The traditional Chinese medicine composition of the invention has the following effects on cardiac function and ventricular structure: the traditional Chinese medicine composition has good protection effect on heart function damage caused by heart failure after myocardial infarction. The echocardiogram is a non-invasive imaging examination means for judging the structure and the function of the heart, can quantitatively and visually evaluate the local myocardium, the whole systolic and diastolic function and the myocardial dyskinesia, and is a reliable diagnosis method for cardiovascular diseases. The experimental result shows that the heart ejection fraction, the contraction fraction, the stroke volume and the cardiac output of the model rat are obviously reduced, which indicates that the cardiac function is seriously damaged, and after the traditional Chinese medicine composition is dried, the indexes are all raised, and the traditional Chinese medicine composition has difference. In heart failure, the persistent hemodynamic changes and the fluid compensatory mechanism disorder increase the pressure of the myocardial wall, which aggravates the cardiac load, and the myocardium undergoes a series of structural and phenotypic changes, including ventricular dilatation, ventricular structural remodeling, etc. Experimental results show that all dosage groups of the traditional Chinese medicine composition can obviously reduce left ventricular end diastole and end systole internal diameters and left ventricular end diastole and end systole volumes of heart failure rats, and the traditional Chinese medicine composition has a good improvement effect on ventricular remodeling of the heart failure rats.

The traditional Chinese medicine composition has the following effects on the myocardial pathological tissue structure: myocardial fibrosis refers to excessive accumulation of collagen fibers in the normal tissue structure of the myocardium, a significant increase in collagen concentration in cardiac tissue, or a change in collagen composition, which is a necessary consequence of the late stages of development of various cardiovascular diseases, and is an important form of ventricular remodeling. Based on HE and Masson dyeing results and myocardial CVF determination, the Chinese medicinal composition can relieve the myocardial fibrosis degree of heart failure rats, inhibit collagen deposition, improve ventricular remodeling and prompt that the inhibition of the myocardial fibrosis is probably an important mechanism for protecting ischemic myocardium by the Chinese medicinal composition. And the effect showed dose dependence, with the best treatment effect in the high dose group.

The influence of the traditional Chinese medicine composition on the blood plasma angiotensin: angiotensin (ANG) is a characteristic marker of the pathological process of heart failure, playing an important role in vasoconstriction, blood pressure elevation and promotion of adrenal hormone release. In the process of heart failure, continuous ischemia and hypoxia aggravate myocardial damage and cardiac function deterioration, so that the blood plasma Ang II level is increased, and the Ang II level is combined with angiotensin receptor (AT1) to promote collagen deposition, and finally ventricular remodeling and myocardial fibrosis are caused. The experimental result shows that the high-dose group of the traditional Chinese medicine composition can reduce the content of Ang II in the blood plasma of rats with heart failure, the effect of the high-dose group is similar to that of the valsartan group, and the dyeing result is combined to prompt that the mechanism of the traditional Chinese medicine composition for playing the treatment effect of the heart failure is probably related to the inhibition of myocardial fibrosis and ventricular remodeling.

Test example 3: acute toxicity test of oral administration to mice

The Chinese medicinal composition adopts a maximum dosage experimental method, and the nature, degree, time-effect relationship, reversibility and the like of the acute toxicity reaction of ICR mice caused by the prescription are observed.

Medicine preparation: the traditional Chinese medicine composition comprises 1 part of ginseng and 10 parts of astragalus membranaceus, and the preparation method adopts the medicinal powder prepared by the step (2) and the composition 3 in the embodiment 1.

Animals and groups: SPF grade ICR mice, weight 20 + -2 g, sex half each, purchased from Beijing Wittingle laboratory animal technology Limited company, license number: SCXK (Kyoto) 2010-0010. The weight of the Chinese medicinal composition is randomly divided into 2 groups, wherein 20 control groups and 20 Chinese medicinal composition groups are selected.

The administration method comprises the following steps: after adaptive feeding, the mice were fasted (freely drinking) for 16 hours before the test, and the mice were randomly divided into a control group and a Chinese medicinal composition group according to the weight, wherein each group contains 20 mice, and the number of the mice is half of that of the mice. Taking water as solvent, performing intragastric administration for 2 times in 24h by using a No. 12 intragastric administration needle with maximum concentration (1.9g crude drug/ml) and maximum volume (40ml/kg body weight), wherein the cumulative administration dose is 152g crude drug/kg body weight, and the control group is administered with purified water with equal volume, and closely observing and recording the state of animals after administration. After administration, observation was continued for 14 days, and all mice were subjected to a dissection after the end of the observation period, and the conditions of each tissue and organ were visually observed and recorded.

Reason for designing administration dose: clinical application and dosage: the traditional Chinese medicine composition is equivalent to 66g of crude drugs per day, and the clinical dose is 0.9g of crude drugs per kg of human body weight calculated according to 70kg of crude drugs per day. Since this test is a maximum dose test, a dosing regimen of maximum dose concentration and maximum dose volume is used. The maximum preparation concentration of the liquid medicine extract is 1.9g crude drug/ml, the maximum administration volume (40ml/kg) of a mouse is adopted, and the administration dosage is as follows for 2 times within 24 h: 1.9g crude drug/ml × 2 × 40 ml/kg-152 g crude drug/kg, 152g crude drug/kg ÷ 0.9g crude drug/kg-168 times. Namely: the maximum dose of the mice was determined to be 168 times the highest dose clinically planned.

Observation of animal before and after administration (day of administration)

The number of observation examples: all animals were used. The observation method comprises the following steps: and (4) observing in the cage. And (4) observing the content: the animals were observed for physical signs, activity, respiration, excretion, etc. on the day of administration, and the symptoms of the toxic reaction (onset time, duration, disappearance time of symptoms) and death of the animals were recorded after administration. The observation times are as follows: each group of animals was observed once before dosing and continuously for 5h after dosing.

General State Observation of animals (non-dosing days)

The number of observation examples: all animals were used. The observation method comprises the following steps: and (4) observing in the cage. And (4) observing the content: the toxic reaction condition of the animals is observed every day for 1h, 3h and 1-14 days after the administration: observing whether dyspnea, apnea, cyanosis, tachypnea and abnormal nasal secretion exist; observing whether spontaneous activity, probing, hair combing and movement are normal or not, and whether abnormal conditions such as drowsiness, normal reflex loss, anesthesia, catatonic syncope, movement disorder, abnormal movement, prostration, tremor, fasciculation and the like exist; clonic, tonic, syncope and other convulsions; observing whether the corneal eyelid closure, orthostatic reflection, stretch reflection, fright reflection and the like are normal; whether there is lacrimation, ptosis, etc.; observing whether the skin has vasodilatation symptoms such as skin, tail, tongue, ear, foot pad, conjunctiva, body temperature rise and the like, and whether the skin has edema or erythema; observing whether the saliva is hypersecretion or not; with or without hair follicle to erect hair muscle contraction; observing muscle tone; observing dry excrement or water-like excrement; whether or not there is red urine or urinary incontinence is observed. The observation times are as follows: the observation was continued for 14 days after the administration, 1 time per day.

And (3) measuring the body weight:

the number of times of measurement: and 7 times. Determination of example number: all animals were dosed before and after administration. The determination method comprises the following steps: measuring the weight before administration; body weights were measured on days 1, 2, 3, 4, 7 and 14 after dosing.

And (4) performing autopsy and observing the number of autopsy examples: all animals were used. The dissection method comprises the following steps: firstly, a test person before the autopsy fills in an autopsy record table according to observation records of the state of the mice to be autopsy before and after administration and observation records of the general state of animals. Secondly, performing appearance inspection on the animals, killing the mice by cervical dislocation, performing autopsy on main organs, observing whether obvious tissue and organ abnormality exists or not by naked eyes, and filling an autopsy record table.

Performing autopsy on organs: brain, heart, liver, spleen, lung, kidney, adrenal gland, stomach, pancreas, small intestine, large intestine, testis, ovary, uterus, thymus, lymph, etc.

Pathological histological examination: after the experiment, all animals were dissected and observed for gross observation, and if any organ was found to have changed in volume, color, texture, etc., histopathological examination should be recorded and performed. Since no diseased tissue organs were visible during the dissection, no histopathological examination was performed.

And (3) test data statistics: for test data

Showing that the difference between groups is compared by t test, P<0.05 is statistically significant.

Test results

General state: the weight of the mice taking the traditional Chinese medicine composition is normal, and the food intake is normal; the phenomena of hair erection, salivation, dyspnea, nostril secretion blockage, convulsion and the like are not seen, spontaneous activity, ingestion and drinking of water, various reflexes, eyelid, cardiovascular system appearance, muscle tension, defecation, skin and the like are normal, and compared with a control group, the traditional Chinese medicine composition has no obvious difference, no obvious adverse reaction and no death. As a result: the control group and the traditional Chinese medicine composition group respectively comprise 20 animals, and the abnormal conditions of respiration, movement, reflex, cardiovascular, salivation, muscle tension, defecation and hair are observed in each animal before administration and 1h, 3h, 1d, 2d, 3d, 4d, 5d, 6d, 7d, 8d, 9d, 10d, 11d, 12d, 3d and 14d after administration.

Weight change: the weight of the traditional Chinese medicine composition is normal after administration, and the weight increase of the male mouse in 1-14 days has no obvious difference compared with that of a control group. The results of the body weight statistics are shown in tables 10 and 11.

Table 10. effect of the traditional Chinese medicine composition of the present invention on body weight of male mice (g, n-10,

)

table 11. effect of the traditional Chinese medicine composition of the present invention on the body weight of female mice (g, n-10,

)

group of	Control group (female)	The Chinese medicinal composition of the invention (female)
			Before administration	21.07±1.10	20.72±1.12
Administration for 1 day	22.34±0.98	21.58±1.19
			The administration is carried out for 2 days	23.08±0.98	22.21±1.28
The administration is carried out for 3 days	23.96±1.35	22.74±1.45
			The administration is carried out for 4 days	25.76±1.48	24.08±1.71
The administration is carried out for 7 days	26.23±1.91	24.84±2.00
			The administration is carried out for 14 days	28.76±2.13	27.99±1.79

Death status: no animal death occurred in the control group and the Chinese medicinal composition group of the invention within 14 days after administration.

And (3) anatomical observation: after the experiment, the brain, heart, liver, spleen, lung, kidney, adrenal gland, stomach, pancreas, small intestine, large intestine, testis, ovary, uterus, thymus, lymph, etc. were visually observed in a comprehensive and fine manner, and the volume, color, texture, etc. of each organ were not abnormal.

And (4) conclusion: after the traditional Chinese medicine composition is administrated to mice, the phenomena of hair erection, salivation, dyspnea, nostril secretion blockage, convulsion and the like are not seen, spontaneous activity, drinking water, various reflexes, eyelid, cardiovascular system appearance, muscle tension, defecation, skin, weight increase and the like are normal, and compared with a control group, the traditional Chinese medicine composition has no obvious difference, and has no obvious adverse reaction and death. After the experiment, a comprehensive and detailed gross autopsy was performed, and the volume, color, texture, and the like of each organ were not abnormal. It was suggested that the cumulative dose of 152g crude drug/kg at the maximum concentration (1.9g crude drug/ml) and the maximum volume (40ml/kg) was about 168 times the clinical dose (the clinical dose was 66g crude drug/human/day, and the clinical dose was 0.9g crude drug/kg in 70 kg/human), and that the animal condition was good and there was no acute toxic reaction and death.

Test example 4: research on intervention effect of traditional Chinese medicine composition on lung function of COPD (chronic obstructive pulmonary disease) patient

The traditional Chinese medicine composition has obvious intervention effect on model animals in the research process of basic medical experiments, can obviously improve indexes such as cardiac function and the like of experimental rats, and the most direct and most key effect of the medicine for treating symptoms is reflected in clinical curative effect, particularly on the aspects of improving symptoms of patients, improving functions of internal organs and the like, and the treatment effect of the composition on chronic obstructive pulmonary disease is illustrated by clinical cases.

Diagnostic criteria

Clinical diagnosis standard for qi deficiency syndrome

Qi deficiency syndrome (syndrome differentiation in eight principles) is caused by deficiency of original qi, hypofunction of qi in promoting, consolidating, defending, and gasifying, or hypofunction of zang-fu organs. The syndrome diagnosis refers to "Chinese medicine clinical diagnosis and treatment terms & syndrome parts" (GB/T16751.2-1997) and "Chinese medicine and pharmacy noun" (2004, science publishers). The main symptoms are: mental fatigue, shortness of breath, fatigue, spontaneous perspiration. The secondary symptoms are as follows: lazy speaking, low voice. Tongue pulse: pale tongue and weak pulse. The basis of diagnosis is as follows: the diagnosis is performed by combining tongue pulse, with the principal symptoms 2 and the accompanying symptoms 1 or more.

Criteria for disease diagnosis

Referring to 2018, the global initiative for chronic obstructive pulmonary disease (GOLD) and 2013, the diagnosis standard of 'guidance for diagnosis and treatment of chronic obstructive pulmonary disease' formulated by respiratory disease academic conference of zhonghua medical society: there are clinical symptoms of cough, expectoration, shortness of breath or dyspnea; secondly, there is a medical history of exposure to risk factors (family history, tobacco, occupation, indoor and outdoor pollution); ③ continuous air flow limitation (indispensable conditions): the pulmonary function examination indicates that FEV1/FVC is less than 70% after the short-acting bronchodilator is inhaled, and the incomplete reversible airflow limitation can be determined; fourthly, in a stable period: the patient has stable symptoms such as cough, expectoration, short breath and the like or slight symptoms.

Selection of the subject

Inclusion case criteria: (1) the age is 35-70 years old, and the nature is not limited; (2) the traditional Chinese medicine distinguishes the syndrome of qi deficiency; (3) grade GOLD2-3 lung function, combined assessment of chronic obstructive pulmonary disease patients in stable phase in group B or group C (updated combined assessment ABCD cohort pattern according to GOLD 2017); (4) voluntarily attend and sign an informed consent.

Exclusion criteria

(1) Patients with bronchiectasis, bronchial asthma, active pulmonary tuberculosis, pulmonary embolism, pneumothorax, and pleural effusion; (2) complicated with major systemic diseases such as cardiovascular and cerebrovascular diseases, nervous system, and immune system, or chronic diseases such as hypertension and diabetes; (3) complicated syndrome type including excess syndrome such as phlegm, blood stasis, cold, heat-toxin, etc., and obvious deficiency of yin and yang; (4) those with allergic constitution or those allergic to known ingredients of the test drugs; (5) those with pregnancy, lactation, pregnancy in the last half of the year or positive pregnancy tests (urine or blood HCG), and who are unable to take effective contraceptive measures during the study (effective contraceptive measures include sterilization, intrauterine devices, oral contraceptives or local diaphragm methods as prescribed by law); (6) patients who participated in other drug clinical trials within the last 1 month; (7) mental and neurological disorders, those who fail to express their will and communication disorders correctly; (8) alcoholics and drug abuse and addiction.

Dosage regimen of the Chinese medicinal composition of the invention

The tested drugs are: the traditional Chinese medicine composition comprises 1 part of ginseng and 10 parts of astragalus (composition 3). The usage and dosage are as follows: the oral preparation is taken orally, one dose is taken every day, the crude drug amount is 66 g/day, and the oral preparation is taken twice in the morning and at night after being dissolved in hot boiled water.

Basic therapy

According to the global initiative of COPD, the stable-phase standard treatment is given, including inhalation and oral administration of bronchodilators, inhalation of hormones, anti-inflammation and the like, and the treatment aims at relieving symptoms, improving pathological states, preventing further development of lesions and improving the quality of life. During the test period, other traditional Chinese medicine decoction pieces, compound medicines or Chinese patent medicines are forbidden to be applied together. Combining the medicines: all combinations must be documented in the original record and CRF, including the common name of the drug, the dosage and method of administration, the time of initiation of administration, and the reason for use.

Evaluation criteria: an improvement of > 50% in the quantitative score of qi-deficiency syndrome is considered to be effective, and an improvement of < 50% is considered to be ineffective.

The treatment period of the traditional Chinese medicine composition is as follows: every 2 weeks is 1 node, and the group can be obtained when the evaluation standard is met, and the longest period is 12 weeks. After the treatment period is finished, the conventional medical treatment is carried out.

And (5) observing indexes. The main indexes are as follows: the Chinese medicine qi deficiency syndrome quantitative score table (the main symptoms-mental fatigue, short breath, hypodynamia, spontaneous perspiration; the accompanying symptoms-laziness in speaking and low voice). Secondary indexes are as follows: 6 min walk test, lung function (FEV 1%, FEV 1/FVC%, TLC%), Borg scale grading, mMRC questionnaire, CAT score, PRO scale, ESQ scale, SF-36 scale.

Results

General data: the study included 55 patients with chronic obstructive pulmonary disease, with 1 shedding, 41 males and 14 females; the average age is 54.2 +/-8.53 years, the highest age can reach 69 years, and the youngest people are only 29 years old; in total, 41 cases have combined diseases, and 36 cases have combined medication.

The traditional Chinese medicine composition has the following effects on the syndrome integral of COPD patients with qi deficiency syndrome: the total symptom integral and the single traditional Chinese medicine symptom integral of the two groups of data before and after treatment approximately accord with normal distribution, and a matched sample t test is adopted for comparison. The total score and the single score of the symptoms after treatment are obviously reduced compared with those before treatment, and have statistical difference (P is less than 0.05), which prompts that the Chinese medicinal composition can obviously improve symptoms of mental fatigue, hypodynamia, shortness of breath, spontaneous perspiration, no speaking, low voice and the like of patients with chronic obstructive pulmonary disease, and the specific reference is made in Table 12.

TABLE 12 comparison of the integral of the symptoms of qi deficiency syndrome before and after treatment

Note: p <0.05 compared to pre-treatment.

The traditional Chinese medicine composition has the influence on the lung function related evaluation indexes of patients with COPD (chronic obstructive pulmonary disease) qi deficiency, and is shown in a table 13: before and after treatment, lung function, 6-minute walk test, CAT score and PRO score of the two groups of data conform to normal distribution, ESQ score, mMRC score, Borg score and SF36 score data do not conform to normal distribution, and matched sample t test and non-parametric test are respectively adopted. The results show that after treatment, the lung function, the 6-minute walk test, the CAT score, the PRO score, the ESQ score, the mMRC score and the Borg score of a patient are all obviously improved compared with those before treatment, and the comparison difference before and after treatment has obvious statistical significance (P is less than 0.05), so that the traditional Chinese medicine composition disclosed by the invention can obviously improve the lung function of patients with chronic obstructive pulmonary diseases, relieve the clinical symptoms of the patients, improve the exercise endurance of the patients and improve the life quality of the patients.

TABLE 13 pulmonary function-related index changes before and after treatment

Note: p <0.05 compared to pre-treatment.

The influence of the traditional Chinese medicine composition on the immunity indexes of patients with COPD qi deficiency syndrome is shown in Table 14: the immunity index data of the disease group and the healthy control group approximately accord with normal distribution, and independent sample t test is adopted. The results show that compared with the healthy control group, the content of Th2 in the disease group is reduced, the content of Th17 is increased, the difference is statistically significant (P is less than 0.05), and the difference of Th1 and Treg is not statistically significant. Immune index data before and after treatment of the disease groups approximately accord with normal distribution, and a matched sample t test is adopted. The results show that the content of Th17 is reduced after treatment compared with that before treatment, the difference is statistically significant (P <0.05), the content of Th2 is reduced, the content of Th1 and Treg is increased, but the difference is not statistically significant.

TABLE 14 immunological index changes before and after treatment

Note: compared with a healthy control group, # P < 0.05; p <0.05 compared to pre-treatment.

And (4) conclusion: the traditional Chinese medicine composition has the following effects on the syndrome integral of qi deficiency syndrome: the symptoms of patients before and after taking the medicine are obviously improved, and the integral of the single syndrome and the whole syndrome is obviously reduced, which shows that the traditional Chinese medicine composition has obvious effect on improving qi deficiency syndrome. The influence of the traditional Chinese medicine composition on the lung function is as follows: the lung governs qi and controls respiration. This functional description is similar in traditional Chinese and western medicine. FEV1(1 second forced expiratory volume) represents the volume of gas exhaled in the first second of forced expiration after deep inspiration, namely the 1 second forced expiratory volume, which is a common index for diagnosing asthma and COPD, the obstruction of the pulmonary tract causes the decrease of FEV 1%, and the traditional Chinese medicine composition can obviously increase the FEV 1%. Obstructive airway dysfunction is dominated by a decrease in FEV1/FVC, and the traditional Chinese medicine composition of the invention can increase the FEV1/FVC ratio, possibly related to a simultaneous increase in the amount of FVC (forced vital capacity) in COPD patients. The core significance of the CAT (chronic obstructive pulmonary disease assessment test) scale is that the 6 subjective indexes of cough, expectoration, chest distress, sleep, energy and emotion and exercise endurance are evaluated, and daily exercise influences the two endurance. The score will gradually increase as the COPD progression increases. The result shows that the traditional Chinese medicine composition obviously reduces CAT score, prevents further deterioration of lung function and has the function of protecting lung function. The traditional Chinese medicine composition has the following effects on the immune system of patients with COPD (chronic obstructive pulmonary disease) qi deficiency syndrome: the immune system of the organism is similar to the function of the vital qi in the theory of traditional Chinese medicine, the vital qi exists in the body, the pathogenic factors cannot dry, namely the body is protected by the vital qi, the pathogenic factors cannot invade, and the organism can be prevented from getting ill. The immune system also has the effect on the human body, so that the abnormal immune system is also the expression of qi deficiency. Th2 and Th17 of the sufferers with chronic obstructive pulmonary disease and qi deficiency are obviously higher than those of healthy control groups, and the traditional Chinese medicine composition can obviously improve the abnormal state of the immune system.

Test example 5: the traditional Chinese medicine composition of the invention is used for researching the intervention effect of chronic glomerulonephritis patients with qi deficiency syndrome

Diagnostic criteria

Clinical diagnosis standard for qi deficiency syndrome

Criteria for disease diagnosis

Diagnosis standard of chronic glomerulonephritis: refer to the chapter of the monograph seating conference for the classification and treatment and diagnosis standard of primary glomerular disease in the journal of China medical department in 1993.

Selection of the subject

Inclusion case criteria

(1) The age is 18-70 years, with unlimited nature; (2) the diagnosis standard of the traditional Chinese medicine qi deficiency syndrome is met; (3) primary chronic glomerulonephritis, more than 50% with pathological reports of kidney perforation; (4) the quantitative amount of urine protein is 0.5-6.0g/24 h; (5) the eGFR is more than or equal to 30 ml/min; the plasma albumin is more than or equal to 30 g/L; (6) the blood pressure is stabilized below 140/90mmHg by the treatment of lowering blood pressure; (7) the procedure and method of the clinical study can be understood to voluntarily attend and sign informed consent.

Exclusion criteria

(1) Secondary glomerular diseases such as diabetic nephropathy, purpuric nephritis, lupus nephritis, hypertensive renal injury, etc.; (2) complicated syndrome type including excess syndrome such as phlegm, blood stasis, cold, heat-toxin, etc., and obvious deficiency of yin and yang; (3) serious systemic diseases such as cardiovascular and cerebrovascular diseases, nervous system and immune system are combined; (4) the patients who have used glucocorticoid, immunosuppressant and antibiotic within about 1 month. (5) Those with allergic constitution or those allergic to known ingredients of the test drugs; (6) those with pregnancy, lactation, pregnancy in the last half of the year or positive pregnancy tests (urine or blood HCG), and who are unable to take effective contraceptive measures during the study (effective contraceptive measures include sterilization, intrauterine devices, oral contraceptives or local diaphragm methods as prescribed by law); (7) patients who participated in other drug clinical trials within the last 1 month; (8) mental and neurological disorders, those who fail to express their will and communication disorders correctly; (9) alcoholics and drug abuse and addiction

Normal control subjects

(1) Age greater than or equal to 18 years and body weightIndex (BMI: weight/height)²) Is 19-26kg/m²The nature is not limited. (2) The syndrome differentiation of TCM is for the patients with syndrome of qi deficiency. (3) The routine physical examination, vital signs (body temperature, blood pressure, heart rate and respiration), electrocardiogram and laboratory examination (including blood, urine, routine defecation, various biochemical indexes of liver and kidney functions and the like) are not abnormal. (4) No other drug clinical trials were performed in the last 1 month. (5) The procedure and method of the clinical study can be understood, voluntarily and with informed consent.

Exclusion criteria:

(1) combined with other major systemic diseases such as nervous system, immune system, etc., or patients with malignant tumor, allergic constitution, or patients with severe wound and infection, etc.; (2) patients with chronic diseases such as hypertension and diabetes; (3) those in pregnancy, lactation or menstrual period; (4) mental, neurological disorders, those who do not express their will correctly; (5) alcoholics and drug abuse and addiction.

Dosage regimen of the Chinese medicinal composition of the invention

The tested drugs are: the traditional Chinese medicine composition comprises 1 part of ginseng and 30 parts of astragalus (namely composition 5). The usage and dosage are as follows: the oral preparation is taken orally, one dose is taken every day, the crude drug amount is 93 g/day, and the oral preparation is taken twice in the morning and at night after being dissolved in hot boiled water.

Basic therapy

According to the diagnosis and treatment guidance of chronic glomerulonephritis, standard treatment is given, including blood pressure control, wherein ACEI or ARB medicines are mainly used for reducing urine protein, and the blood pressure is controlled below 140/90 mmHg; the lipid-lowering treatment mainly comprises statins, and the like, prevents further development of pathological changes, and improves the quality of life. During the experiment, the combined application of other traditional Chinese medicine decoction pieces, compound medicines or Chinese patent medicines with the effect of tonifying qi is forbidden. Combining the medicines: all combinations must be documented in the original record and CRF, including the common name of the drug, the dosage and method of administration, the time of initiation of administration, and the reason for use.

The treatment period of the traditional Chinese medicine composition is as follows: every 4 weeks is 1 node, and the group can be obtained when the evaluation standard is reached, and the longest period is 8 weeks. After the treatment period is finished, the conventional medical treatment is carried out.

Observation index

The main indexes are as follows: the Chinese medicine qi deficiency syndrome quantitative score table (the main symptoms-mental fatigue, short breath, hypodynamia, spontaneous perspiration; the accompanying symptoms-laziness in speaking and low voice).

Secondary indexes are as follows: urinary protein quantification at 24 hours, creatinine, eGFR, SCr, BUN.

As a result: the study included 40 patients with chronic glomerulonephritis, with 1 shedding, 11 men and 29 women; the average age is 45.79 + -11.81 years, the highest age can reach 67 years, and the youngest people are only 22 years old; in total, 3 cases have combined diseases, 11 cases have combined medicines and 1 case has no medicines.

The influence of the traditional Chinese medicine composition on the syndrome integration of the chronic glomerulonephritis qi-deficiency syndrome patient is shown in the table 15: the total symptom integral and the single traditional Chinese medicine symptom integral of the two groups of data before and after treatment approximately accord with normal distribution, and a matched sample t test is adopted for comparison. The total score and the single score of the symptoms after treatment are obviously reduced compared with those before treatment, and the traditional Chinese medicine composition has statistical difference (P <0.05), and prompts that the traditional Chinese medicine composition can obviously improve symptoms of mental fatigue, hypodynamia, shortness of breath, spontaneous perspiration, no speaking, low voice and the like of patients with chronic glomerulonephritis.

TABLE 15 comparison of the integral of the symptoms of qi deficiency syndrome before and after treatment

Note: p <0.05 compared to pre-treatment.

The influence of the traditional Chinese medicine composition on the kidney function of the chronic glomerulonephritis qi deficiency patient is shown in the table 16: the 24h urine protein quantification and Scr of the two groups of data before and after treatment do not accord with normal distribution, eGFR and BUN accord with normal distribution, and nonparametric detection and paired sample t detection are respectively adopted. The results show that after treatment, the expression level of each index of renal function of a patient is improved compared with that before treatment, Scr (creatinine) has statistical significance (P is less than 0.05), and comparison differences of other indexes before and after treatment have no statistical significance.

TABLE 16 renal function index changes before and after treatment

Note: p <0.05 compared to normal control.

The influence of the traditional Chinese medicine composition on the immunity indexes of the chronic glomerulonephritis qi deficiency patients is shown in the table 17: the immunity index data of the disease group and the healthy control group approximately accord with normal distribution, and independent sample t test is adopted. The results show that compared with the healthy control group, the content of Th1 in the disease group is increased, the content of Th2 is reduced, the difference is statistically significant (P is less than 0.05), and the difference of Th17 and Treg is not statistically significant. Immune index data before and after treatment of the disease groups approximately accord with normal distribution, and a matched sample t test is adopted. The results show that the content of Th1 is reduced and the content of Th2 is increased after treatment compared with the content before treatment, the difference is statistically significant (P is less than 0.05), and the difference of Th17 and Treg is not statistically significant.

TABLE 17 immunological index changes before and after treatment

Conclusion

The traditional Chinese medicine composition has the following effects on the syndrome integral of qi deficiency syndrome: the syndrome score of the sick testee is obviously higher, the symptoms of the patient are obviously improved after the medicine is taken, and the syndrome score is obviously reduced, which shows that the Chinese medicinal composition has obvious effect of improving the qi deficiency syndrome. The traditional Chinese medicine composition has the following effects on the kidney function: kidneys are the root of qi and they govern qi reception. The kidney function of modern medicine and the kidney function of traditional Chinese medicine have partially similar meanings. Scr (serum creatinine) mainly reflects the glomerular filtration function and is an important index for evaluating kidney injury. The traditional Chinese medicine composition can obviously reduce the level of Scr, which shows that the traditional Chinese medicine composition has obvious protective effect on renal function. The traditional Chinese medicine composition also has an effect on the quantification of BUN (urea nitrogen) 24h urine protein and the level of eGFR, but has no significant difference. The traditional Chinese medicine composition has the following effects on the immune system of a patient with chronic glomerulonephritis qi deficiency syndrome: compared with a healthy control group, the Th1 and the Th2 of the subject suffering from the chronic glomerulonephritis qi deficiency syndrome are abnormal, and the traditional Chinese medicine composition can obviously improve the abnormal state of an immune system.

Test example 6: research on intervention effect of traditional Chinese medicine composition on spleen-qi deficiency syndrome of chronic atrophic gastritis

Diagnostic criteria

Clinical diagnosis standard for qi deficiency syndrome

Refer to the Chinese medicine clinical diagnosis and treatment terms, syndrome part (GB/T16751.2-1997) and the Chinese medicine noun (2004, science publishers). Syndrome diagnosis: the syndrome of qi deficiency (syndrome differentiation in eight classes) is due to: the failure of original qi, the hypofunction of qi in promoting, consolidating, defending and transforming qi, or the hypofunction of zang-fu organs. The main symptoms are: mental fatigue, shortness of breath, fatigue, spontaneous perspiration. The secondary symptoms are as follows: lazy speaking, low voice. Tongue pulse: pale tongue and weak pulse. The basis of diagnosis is as follows: the diagnosis is performed by combining tongue pulse, with the principal symptoms 2 and the accompanying symptoms 1 or more.

Criteria for disease diagnosis

Diagnostic criteria for chronic atrophic gastritis: reference is made to the Chinese consensus on chronic gastritis (2017) and the Chinese-western medical diagnosis and treatment consensus on chronic atrophic gastritis (2017).

Selection of the subject

Inclusion case criteria

(1) The age is 35-70 years old, and the nature is not limited; (2) the traditional Chinese medicine syndrome differentiation meets the standards of qi deficiency and spleen qi deficiency, and the quantitative score of the traditional Chinese medicine qi deficiency is more than or equal to 10 points; (3) the western medicine diagnosis meets the diagnosis standard of the chronic atrophic gastritis (gastroscope within 3 months and pathological diagnosis support); (4) the pathological classification is that the chronic atrophic gastritis patients are moderate or above; (5) voluntarily attend and sign an informed consent.

Exclusion criteria

(1) Patients with gastric precancerous lesions accompanied by dysplasia; (2) complicated with major systemic diseases such as cardiovascular and cerebrovascular diseases, nervous system, and immune system, or chronic diseases such as hypertension and diabetes; (3) complicated syndrome type including excess syndrome such as phlegm, blood stasis, cold, heat-toxin, etc., and obvious deficiency of yin and yang; (4) those with allergic constitution or those allergic to known ingredients of the test drugs; (5) those with women of childbearing age who are pregnant, lactating, pregnant, or pregnant positive (urine or blood HCG), and who are unable to take effective contraceptive measures during the study (effective contraceptive measures include sterilization, intrauterine devices, oral contraceptives, or local legal diaphragm methods); (6) patients who have participated in clinical trials with other drugs or medical devices within the last 3 months; (7) mental, neurological disorders, those who do not express their will correctly; (8) alcoholics and drug abuse and addiction.

Normal control subjects

(1) Age greater than or equal to 18 years, body mass index (BMI: weight/height)²) Is 19-26kg/m²The nature is not limited. (2) The syndrome differentiation of TCM is for the patients with syndrome of qi deficiency. (3) The routine physical examination, vital signs (body temperature, blood pressure, heart rate and respiration), electrocardiogram and laboratory examination (including blood, urine, routine defecation, various biochemical indexes of liver and kidney functions and the like) are not abnormal. (4) No other drug clinical trials were performed in the last 1 month. (5) The procedure and method of the clinical study can be understood, voluntarily and with informed consent.

Exclusion criteria:

(1) or other major systemic diseases such as nervous system and immune system, or patients with malignant tumor, allergic constitution, severe wound, and infection; (2) patients with chronic diseases such as hypertension and diabetes; (3) those in pregnancy, lactation or menstrual period; (4) mental, neurological disorders, those who do not express their will correctly; (5) alcoholics and drug abuse and addiction.

Dosage regimen of the Chinese medicinal composition of the invention

The tested drugs are: the traditional Chinese medicine composition comprises 1 part of ginseng and 3 parts of astragalus (namely the composition 1). The usage and dosage are as follows: the oral preparation is taken orally, one dose is taken every day, the crude drug amount is 39 g/day, and the oral preparation is taken twice in the morning and at night after being dissolved in hot boiled water.

Basic therapy

Selecting corresponding western medicine or Chinese patent medicine according to symptom type, and adding PPIs (PPIs) such as pantoprazole and rabeprazole for patients with stomachache and heartburn and acid regurgitation; for patients with marked gastrectasia, gastrointestinal motility drugs such as WEISHU granule, XIANGSHAPINGWEI granule or MOTILIN can be added. During the experiment, the combined application of other traditional Chinese medicine decoction pieces, compound medicines or Chinese patent medicines with the effect of tonifying qi is forbidden. Combining the medicines: all combinations must be documented in the original record and CRF, including the common name of the drug, the dosage and method of administration, the time of initiation of administration and the reason for use or the Chinese patent drug

The treatment period of the traditional Chinese medicine composition is as follows: every 2 weeks is 1 node, and the group can be obtained when the evaluation standard is reached, and the longest period is 8 weeks. After the treatment period is finished, the conventional medical treatment is carried out.

Observation index

The main indexes are as follows: the Chinese medicine qi deficiency syndrome quantitative score table (the main symptoms-mental fatigue, short breath, hypodynamia, spontaneous perspiration; the accompanying symptoms-laziness in speaking and low voice). Secondary indexes are as follows: spleen deficiency syndrome score, chronic atrophic gastritis disease symptom score.

As a result: the study included 51 patients with chronic atrophic gastritis with 1 shedding, 19 in men and 32 in women; the average age is 54.2 +/-8.53 years, the highest age can reach 69 years, and the youngest people are only 29 years old; in 19 cases, combined hypertension accounted for 13.7%, combined diabetes accounted for 5.9%, 12 cases combined medication, 7 cases of absence.

The influence of the traditional Chinese medicine composition on the syndrome integral of patients with chronic atrophic gastritis and spleen-qi deficiency is shown in the table 18: the total symptom integral and the single traditional Chinese medicine symptom integral of the two groups of data before and after treatment approximately accord with normal distribution, and a matched sample t test is adopted for comparison. The total score and the single score of the symptoms after treatment are obviously reduced compared with those before treatment, and the traditional Chinese medicine composition has statistical difference (P <0.05), and prompts that the traditional Chinese medicine composition can obviously improve symptoms of mental fatigue, hypodynamia, shortness of breath, spontaneous perspiration, no speaking, low voice and the like of patients with chronic atrophic gastritis.

TABLE 18 comparison of the integral of the symptoms of qi deficiency syndrome before and after treatment

Note: p <0.05 compared to pre-treatment.

The traditional Chinese medicine composition has the effects on the spleen-qi deficiency scale and the disease symptom scale of patients with chronic atrophic gastritis and spleen-qi deficiency, which are shown in the table 19: the spleen deficiency syndrome score and the chronic atrophic gastritis symptom score of the two groups of data before and after treatment do not accord with normal distribution, and non-parameter detection is adopted. The results show that the scores of the spleen deficiency syndrome and the disease symptoms of the patients are reduced compared with the scores before treatment, and the comparison difference before and after treatment has obvious statistical significance (P is less than 0.01), which indicates that the traditional Chinese medicine composition can obviously improve the clinical symptoms of gastrectasia, stomachache, anorexia, loose stool and the like of the patients with chronic atrophic gastritis.

TABLE 19 spleen Qi deficiency before and after treatment and disease Scale score changes

Note: p <0.05, P <0.01 compared to pre-treatment.

The influence of the traditional Chinese medicine composition on the immunity index of the patient with the chronic atrophic gastritis and the spleen-qi deficiency syndrome is shown in a table 20: the immunity index data of the disease group and the healthy control group approximately accord with normal distribution, and independent sample t test is adopted. The results show that compared with the healthy control group, the content of Th1 and Th17 in the disease group is increased, the content of Th2 is reduced, the difference is statistically significant (P is less than 0.05), and the Treg difference is not statistically significant. Immune index data before and after treatment of the disease groups approximately accord with normal distribution, and a matched sample t test is adopted. The results show that the content of Th1 and Th17 is reduced and the content of Th2 is increased after treatment compared with before treatment, the difference is statistically significant (P <0.05), and the Treg difference is not statistically significant.

TABLE 20 immunological index changes before and after treatment

And (4) conclusion: the traditional Chinese medicine composition has the following effects on the syndrome integral of qi deficiency syndrome: the syndrome score of a patient with the disease is obviously higher, the single syndrome and the whole syndrome score of a patient after taking the medicine are obviously improved, and the syndrome score is obviously reduced, which shows that the traditional Chinese medicine composition has obvious improvement effect on qi deficiency syndrome symptoms of chronic atrophic gastritis patients, such as listlessness, hypodynamia, short breath, spontaneous perspiration, talk reluctance, low voice and the like. The traditional Chinese medicine composition has the following effects on the spleen-qi deficiency scale and the disease symptom scale: after the traditional Chinese medicine composition is used for treating, the spleen deficiency syndrome and disease symptom scores of patients with chronic atrophic gastritis are reduced compared with those before treatment, and the traditional Chinese medicine composition provided by the invention is prompted to be capable of remarkably improving clinical symptoms of patients with chronic atrophic gastritis, such as gastrectasia, stomachache, anorexia, loose stool and the like. The traditional Chinese medicine composition has the following effects on the immune system of a patient with chronic atrophic gastritis and qi deficiency syndrome: compared with healthy control groups, Th1, Th2 and Th17 of the sufferers with chronic atrophic gastritis and qi deficiency syndrome show abnormality, and the Chinese medicinal composition can obviously improve the abnormal state of the immune system.

Test example 7: research on intervention effect of traditional Chinese medicine composition on liver cirrhosis qi deficiency syndrome

Diagnostic criteria

Clinical diagnosis standard for qi deficiency syndrome

Criteria for disease diagnosis

Diagnosis criteria for liver cirrhosis: refer to "clinical practice guide-digestive system disease booklet" (edited by the Chinese medical society, public health Press); "practical medicine (13 th edition) (written by Shanghai medical college of Compound Dan university, people's health Press); treatment guidelines for ascites due to cirrhosis, American society for liver disease, 2009; 2010 clinical practice guidelines of European liver disease institute, ascites due to cirrhosis, idiopathic peritonitis, hepatorenal syndrome treatment, etc.

Selection of the subject

Inclusion case criteria

(1) The age is 35-70 years old, and the nature is not limited; (2) the traditional Chinese medicine distinguishes the syndrome of qi deficiency or the syndrome of concurrent yang deficiency; (3) meets the diagnosis standard of liver cirrhosis. Patients with or without grade 1-2 ascites due to cirrhosis; (4) blood pressure is stabilized below 160/100mmHg by blood pressure lowering treatment, blood sugar is basically controlled, and glycosylated hemoglobin is controlled below 6.5%; (5) the procedure and method of the clinical study can be understood to voluntarily attend and sign informed consent.

Exclusion criteria

(1) Patients with combined active gastrointestinal bleeding or idiopathic peritonitis; (2) complicated syndrome type including excess syndrome such as phlegm, blood stasis, cold, heat-toxin, etc., and obvious yin deficiency; (3) patients with severe liver failure; (4) combined with other major systemic diseases of respiratory system, nervous system, immune system, etc., patients with malignant tumor or patients with severe wound and infection, etc.; (5) those with allergic constitution or those allergic to known ingredients of the test drugs; (6) those with women of childbearing age who are pregnant, lactating, pregnant, or pregnant positive (urine or blood HCG), and who are unable to take effective contraceptive measures during the study (effective contraceptive measures include sterilization, intrauterine devices, oral contraceptives, or local legal diaphragm methods); (7) patients who have participated in clinical trials with other drugs or medical devices within the last 1 month; (8) mental, neurological disorders, those who do not express their will correctly; (9) alcoholics and drug abuse and addiction.

Normal control subjects

Inclusion criteria were:

Exclusion criteria:

Dosage regimen of the Chinese medicinal composition of the invention

Basic therapy

According to diagnosis and treatment guidelines related to liver cirrhosis, standard treatment is given, including liver protection, etiological treatment and the like, and the treatment aims at relieving symptoms, improving pathological states, preventing further development of pathological changes and improving life quality. For cirrhosis caused by hepatitis b or hepatitis c, antiviral therapy is required; the basic therapy such as non-alcoholic fatty liver cirrhosis, diet exercise and the like is very critical; absolute abstinence from alcoholic cirrhosis; drug induced cirrhosis is a drug that disables suspected liver injury; autoimmune liver cirrhosis is hormone-based treatment; primary biliary cirrhosis requires chronic administration of ursodeoxycholic acid to slow cholestasis. Meanwhile, the liver-protecting medicine is used for treatment, such as cell membrane protective agent, antioxidant, anti-inflammatory liver-protecting medicine, liver-soothing and gallbladder-benefiting medicine and the like. For ascites patients, diuresis and liver protection are mainly performed, and patients with hypoproteinemia are infused with human serum albumin when necessary. During the experiment, the combined application of other traditional Chinese medicine decoction pieces, compound medicines or Chinese patent medicines with the effect of tonifying qi is forbidden. Combining the medicines: all combinations must be documented in the original record and CRF, including the common name of the drug, the dosage and method of administration, the time of initiation of administration, and the reason for use.

The treatment period of the traditional Chinese medicine composition is as follows: every 2 weeks is 1 node, and the group can be obtained when the evaluation standard is reached, and the longest period is 4 weeks. After the treatment period is finished, the conventional medical treatment is carried out.

Observation index

The main indexes are as follows: the Chinese medicine qi deficiency syndrome quantitative score table (the main symptoms-mental fatigue, short breath, hypodynamia, spontaneous perspiration; the accompanying symptoms-laziness in speaking and low voice). Secondary indexes are as follows: ascites regression rate, human serum albumin; body weight, waist circumference variation; improvement in biochemical indices (liver function, prealbumin, cholinesterase).

As a result: the study included 49 patients with cirrhosis, 3 patients with shedding, 26 in men and 23 in women; the average age is 55.35 + -8.51 years, the highest age can reach 71 years, and the youngest people are only 38 years old; in 38 cases, the combined disease exists, wherein the combined chronic hepatitis B accounts for 57.1%, the combined hypertension accounts for 20.4%, and the combined diabetes accounts for 14.3%. 37 cases are combined for administration. 1 case is missing.

The influence of the traditional Chinese medicine composition on the syndrome integration of patients with liver cirrhosis and qi deficiency is shown in table 21: the total symptom products of two groups of data before and after treatment and the symptom products of single traditional Chinese medicine are in accordance with normal distribution, and a matched sample t test is adopted for comparison. The total score and the single score of the symptoms after treatment are obviously reduced compared with those before treatment, and the traditional Chinese medicine composition has statistical difference (P <0.05), and prompts that the traditional Chinese medicine composition can obviously improve symptoms of mental fatigue, hypodynamia, shortness of breath, spontaneous perspiration, no speaking, low voice and the like of patients with liver cirrhosis.

TABLE 21 comparison of the integral of the symptoms of qi deficiency syndrome before and after treatment

Note: p <0.05 compared to pre-treatment.

The influence of the traditional Chinese medicine composition on the liver function of patients with liver cirrhosis and qi deficiency is shown in table 22: ALT, AST, GGT and ALB of the two groups of data before and after treatment do not accord with normal distribution, and non-parameter test is adopted for comparison. The results show that after treatment, the ALT, AST and GGT expression levels of patients are reduced compared with the expression levels before treatment, ALB has no significant change, wherein the comparison difference before and after the GGT treatment has statistical significance, the P value is 0.013, and the comparison difference before and after the other index expression levels has no statistical significance (P is more than 0.05).

TABLE 22 hepatic function index changes before and after treatment

Note: p <0.05 compared to pre-treatment.

The influence of the traditional Chinese medicine composition on the immunity index of patients with liver cirrhosis and qi deficiency is shown in table 23: the immunity index data of the disease group and the healthy control group approximately accord with normal distribution, and independent sample t test is adopted. The results show that compared with a healthy control group, the content of Th2 in the disease group is reduced, the content of Th17 and Treg is increased, the difference is statistically significant (P is less than 0.05), and the difference of Th1 is not statistically significant. Immune index data before and after treatment of the disease groups approximately accord with normal distribution, and a matched sample t test is adopted. The results show that the content of Th1 and Treg is reduced after treatment compared with that before treatment, the difference is statistically significant (P <0.05), and the content of Th2 is increased, and the difference is statistically significant (P < 0.05).

TABLE 23 immunological index changes before and after treatment

Note: compared with a healthy control group, # P < 0.05; p <0.05 compared to before treatment

And (4) conclusion: the traditional Chinese medicine composition has the following effects on the syndrome integral of qi deficiency syndrome: the syndrome score of the sick testee is obviously higher, the single syndrome and the whole syndrome score of the patient after the medicine is taken are obviously improved, and the syndrome score is obviously reduced, which shows that the traditional Chinese medicine composition has obvious improvement effect on qi deficiency syndrome symptoms such as mental fatigue, hypodynamia, short breath, spontaneous perspiration, talk reluctance, low voice and the like. The traditional Chinese medicine composition of the invention has the following effects on liver function: liver function examination is an examination item reflecting liver physiological functions, liver dysfunction is an expression of liver physiological dysfunction, and liver dysfunction is an external expression of liver qi deficiency in terms of the expression form of qi deficiency. ALT, AST, GGT, ALB are important indicators reflecting liver function. The traditional Chinese medicine composition can obviously reduce the GGT level of a patient, and has the tendency of improving ALT and AST, which shows that the traditional Chinese medicine composition has obvious protective effect on liver function. The traditional Chinese medicine composition has the following effects on the immune system of a liver cirrhosis patient: compared with healthy control groups, Th2, Th17 and Treg of the patients with liver cirrhosis show abnormality, and the traditional Chinese medicine composition can obviously improve the abnormal state of the immune system.

The qi-deficiency syndrome is a basic syndrome in the clinical practice of traditional Chinese medicine, and is also a common pathogenesis in common diseases and frequently encountered diseases in the clinical practice. According to the understanding of traditional Chinese medicine, the basic treatment principle is that the body resistance and qi tonifying are caused by the deficiency of original qi, the hypofunction of qi promotion, consolidation, defense, qi transformation and the like, or the hypofunction of visceral organs and tissues, which are manifested as a series of weak symptoms such as mental fatigue, short breath, weak pulse and the like. The traditional Chinese medicine composition is simple and powerful, can strengthen body resistance and tonify qi, is used for clinically treating the common diseases of qi deficiency, and has obvious and reliable clinical curative effect.

It will be appreciated by those skilled in the art that the invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The embodiments disclosed above are therefore to be considered in all respects as illustrative and not restrictive. All changes which come within the scope of or equivalence to the invention are intended to be embraced therein.

Claims

1. A traditional Chinese medicine composition comprises the following medicinal active ingredients: ginseng radix and radix astragali.

2. The traditional Chinese medicine composition of claim 1, wherein the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 3-9 parts of ginseng and 30-90 parts of astragalus membranaceus, wherein the preferable weight ratio of the ginseng to the astragalus membranaceus is as follows: 1: 5-10;

preferably, the traditional Chinese medicine composition further comprises a pharmaceutical adjuvant, and preferably, the adjuvant comprises a filler and/or a lubricant; more preferably, the filler is starch and/or dextrin;

preferably, the dosage form of the traditional Chinese medicine composition is oral liquid, granules, capsules, soft capsules, dripping pills or soft extracts.

3. A process for the preparation of a Chinese medicinal composition as claimed in claim 1 or 2, which comprises the steps of:

s2: concentrating the medicinal liquid to obtain soft extract.

4. The method of claim 3, further comprising the steps of:

s3: drying the thick paste to obtain medicinal powder;

preferably, the preparation method further comprises the following steps:

5. The preparation method according to claim 3, wherein in step S1, the number of times of decoction is 2-4, and filtrates from each decoction are combined as the liquid medicine; decocting for 60-180 min each time, wherein the water for each time is 8-15 times of the weight of the crude drug or the residue obtained by the previous decoction;

preferably, inIn step S2, the density of the thick paste is: 1.05-1.10g/cm³；

Preferably, in step S2, the concentration is vacuum concentration.

6. The method according to claim 4, wherein in step S3, the drying is spray drying;

preferably, in step S3, the drying is performed after mixing the thick paste and the filler in a weight ratio of 5-20: 1.

7. Use of a traditional Chinese medicine composition according to claim 1 or 2 or a method of manufacture according to any one of claims 3 to 6, for the manufacture of a formulation for use alone, in combination with other formulations and/or medicaments, or as a component of a combination formulation with other formulations and/or medicaments, for the treatment, prevention, alleviation and/or control of a disease or sub-health condition in an animal selected from:

syndrome of qi deficiency;

chronic heart failure;

chronic obstructive pulmonary disease;

chronic glomerulonephritis;

chronic atrophic gastritis;

the improvement of the body function of the animal is selected from:

improving the hypoxia tolerance;

improving the anti-fatigue capability.

8. The use of claim 7, wherein the animal is a mammal;

preferably, the animal is selected from the group consisting of human, mouse, rat.

9. Use of a traditional Chinese medicine composition of claim 1 or 2 or a method of manufacture of any one of claims 3-6 in the manufacture of a medicament for use alone, in combination with other formulations and/or medicaments, or as a component of a co-formulation with other formulations and/or medicaments, for the treatment, prevention, alleviation and/or management of a disease or sub-health condition of an animal that can be treated, prevented, alleviated and/or controlled by intervention in a physiological metric selected from the group consisting of:

improving the cardiac ejection fraction;

the short axis shortening rate of the heart is improved;

increasing cardiac stroke volume;

improving cardiac output;

reducing the end systolic ventricular diameter;

reducing the ventricular end-diastolic diameter;

reducing ventricular end-systolic volume;

reducing ventricular end-diastolic volume;

reducing myocardial collagen volume fraction;

inhibiting myocardial fibrosis;

reducing the angiotensin II content;

reducing serum creatinine content;

enhancing lung function FEV 1%;

enhancing lung function FEV 1/FVC%;

enhancing pulmonary function FVC%;

reducing the glutamic-pyruvic transaminase concentration;

reducing AST aspartate aminotransferase concentration;

reducing the concentration of GGT glutamyl transpeptidase.

10. The use of claim 9, wherein the animal is a mammal;