A traditional Chinese medicine compound preparation for strengthening the spleen, removing dampness, clearing heat and promoting blood circulation and its use

Abstract

The present application relates to the technical field of traditional Chinese medicine, in particular to a traditional Chinese medicine composition for invigorating the spleen, removing dampness, clearing heat and promoting blood circulation, a compound preparation thereof and purposes, wherein the traditional Chinese medicine composition is composed of Rhizoma Coptidis, Cortex Lycii Radicis, Rhizoma Anemarrhenae, Radix Puerariae, Radix Atractylodis Lanceae, Swertia mileensis, Rhizoma Polygonati, Sophora japonica carbon, Herba Lycopi, Rhizoma Alismatis, Lonicera japonica flower, Fructus Crataegi carbon, Fried rice sprout and Fried wheat germ. The traditional Chinese medicine composition can significantly reduce the fasting blood glucose, glycosylated hemoglobin and triglyceride level of patients with type 2 diabetes with damp-heat syndrome, improve the TCM symptom score and insulin resistance, is used for the treatment of type 2 diabetes, has exact curative effect, can significantly improve the clinical symptoms of patients, has remarkable effect, has no toxic side effect and has good safety.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine, in particular to a traditional Chinese medicine composition for invigorating the spleen, removing dampness, clearing heat and promoting blood circulation, and a compound preparation and use thereof. BACKGROUND

[0002] Diabetes mellitus (DM) is a metabolic disease caused by genetic factors, environmental factors and other factors, characterized by insulin secretion and / or utilization defects, and inappropriate increase of glucagon. The main clinical feature is "high blood sugar". Typical cases may present symptoms such as polydipsia, polyuria, polyphagia, and weight loss, i.e. "three more and one less" symptoms. If not properly controlled, diabetes mellitus can cause various complications, such as cardiovascular and cerebrovascular disease, neuropathy, kidney disease, retinopathy, and diabetic foot, which seriously affect the quality of life of patients and increase the risk of death and disability. According to the International Diabetes Federation (IDF) 2019 statistics, there are about 463 million adults worldwide with diabetes. It is estimated that by 2045, the number of diabetes patients may reach 700.02 million. The current international and domestic situation of diabetes is grim and cannot be optimistic. Given the serious impact of diabetes on people's quality of life, the threat to human health, and the shortening of human lifespan, it is urgent to prevent and treat diabetes and its complications.

[0003] The etiology and pathogenesis of type 2 diabetes (T2DM) in modern medicine are not yet fully understood and are still being explored. The current mainstream view is that its onset is the result of the interaction of genetic and environmental factors leading to insulin resistance and beta cell dysfunction. For its treatment, modern medicine mainly adopts a comprehensive treatment measure combining basic treatment and drug therapy. On the basis of diet control and exercise therapy, appropriate oral hypoglycemic drugs or subcutaneous insulin are used according to the patient's blood sugar, islet function and pathogenesis, with clear clinical hypoglycemic effect. In addition, metabolic surgery and other surgical treatments can also be used. These drug hypoglycemic therapies have good effects but have shortcomings in improving patients' symptoms such as gastrointestinal reactions, hypoglycemia risks, liver and kidney function damage and other side effects, affecting patients' compliance and quality of life. Traditional Chinese medicine treats T2DM with the guiding principles of holistic concept and syndrome differentiation and treatment, and effectively improves patients' clinical symptoms and quality of life by regulating the body's internal environment and constitution. Modern research shows that traditional Chinese medicine compound treatment of T2DM mainly works through the synergistic effect of multiple components, multiple targets and multiple pathways, with the characteristics of small side effects and high safety. In addition, traditional Chinese medicine also has certain advantages in preventing and treating diabetic complications. Therefore, traditional Chinese medicine has a good prospect and development and application space in preventing and treating T2DM and its complications.

[0004] Traditional Chinese medicine (TCM) has a long history of understanding and researching type 2 diabetes mellitus (T2DM). Based on records from ancient texts, it can be categorized under "Xiao Ke" (wasting and thirsting syndrome) and "Pi Dan" (spleen deficiency). Ancient physicians believed that the basic pathogenesis of Xiao Ke was Yin deficiency and dryness-heat, with "three highs and one low" (excessive thirst, excessive urination, excessive thirst, and insufficient appetite) as its typical symptoms. Treatment was based on the theory of "three wastings" and focused on nourishing Yin and clearing heat. However, with societal development and the widespread availability of health checkups, T2DM is being detected earlier, and more and more patients are experiencing symptoms without typical Xiao Ke symptoms. The pathogenesis of Yin deficiency and dryness-heat can no longer fully encompass the characteristics of T2DM in contemporary society. With deepening theoretical research and clinical practice, it is evident that damp-heat syndrome has become a common basic syndrome in T2DM clinical practice, especially prevalent in the early stages of the disease. Modern lifestyles, including excessive consumption of rich, fatty, and spicy foods, can lead to the accumulation of dampness and heat in the middle jiao (middle burner). Other factors include overeating, excessive consumption of rich and fatty foods, and lack of physical activity, which damage the spleen and stomach in the middle jiao. Excessive thinking and emotional distress can also impair the liver's function of regulating qi, affecting the spleen and stomach. When the spleen and stomach fail to function properly, dampness arises internally, eventually accumulating and turning into damp-heat. This can be compounded by external damp-heat, creating a combined effect. The dampness and heat become intertwined, obstructing and hindering the transformation of nutrients, thus impairing the spleen and stomach. When the middle jiao is trapped, the liver becomes stagnant, leading to spleen disease affecting the liver. The liver and spleen are simultaneously affected, their functions of regulating qi trapped by damp-heat. At this stage, the spleen's inability to transform and transport nutrients prevents the transformation of food essence, and the liver's inability to regulate qi prevents the spleen from ascending clear qi. This stagnation of food essence in the blood becomes a prerequisite for "qi overflowing upwards," a crucial link in the development of hyperglycemia and type 2 diabetes mellitus (T2DM). Based on this, the present invention proposes that strengthening the spleen and resolving dampness, clearing heat and promoting blood circulation can be used as one of the important treatment methods for type 2 diabetes. Summary of the Invention

[0005] The purpose of this invention is to provide a traditional Chinese medicine composition and its compound preparation that invigorates the spleen, eliminates dampness, clears heat and promotes blood circulation, and its use in the preparation of a drug for treating type 2 diabetes.

[0006] In a first aspect, the present invention provides a traditional Chinese medicine composition for invigorating the spleen, resolving dampness, clearing heat, and promoting blood circulation, comprising the following raw materials in parts by weight: 5-10 parts of Coptis chinensis, 10-16 parts of Lycium chinense root bark, 10-16 parts of Anemarrhena asphodeloides rhizome, 10-20 parts of Pueraria lobata root, 10-16 parts of processed Atractylodes lancea rhizome, 10-20 parts of Pyrola rotundifolia herb, 10-20 parts of Smilax china rhizome, 4-8 parts of Sophora japonica flower charcoal, 10-16 parts of Lycopus lucidus rhizome, 8-12 parts of Alisma plantago-aquatica rhizome, 10-20 parts of Campsis grandiflora flower, 8-12 parts of Crataegus pinnatifida flower charcoal, 10-20 parts of roasted rice sprouts, and 10-20 parts of roasted barley sprouts.

[0007] Furthermore, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 6-8 parts Coptis chinensis, 12-14 parts Lycium chinense root bark, 12-14 parts Anemarrhena asphodeloides, 15-20 parts Pueraria lobata, 12-14 parts processed Atractylodes lancea, 15-20 parts Pyrola rotundifolia, 15-20 parts Smilax china, 6-8 parts Sophora japonica flower charcoal, 12-14 parts Lycopus lucidus, 10-12 parts Alisma plantago-aquatica, 15-20 parts Campsis grandiflora, 10-12 parts Crataegus pinnatifida charcoal, 15-20 parts stir-fried Oryza sativa sprouts, and 15-20 parts stir-fried Hordeum vulgare sprouts.

[0008] Further, the traditional Chinese medicine composition is composed of the following raw medicinal materials: Coptis chinensis 6 parts, Cortex Lycii 12 parts, Anemarrhena asphodeloides 12 parts, Pueraria lobata 15 parts, Atractylodes lancea 12 parts, Pyrola rotundifolia 15 parts, Radix Polygonati 15 parts, Sophora japonica charred 6 parts, Lamiophlomis rotata 12 parts, Alisma orientale 10 parts, Honeysuckle flower 15 parts, Crataegus pinnatifida charred 10 parts, Fried rice sprout 15 parts, and Fried wheat germ 15 parts.

[0009] In a second aspect of the present application, a traditional Chinese medicine compound preparation is provided, which comprises the traditional Chinese medicine composition as described above as an active ingredient, and is prepared into a common dosage form in pharmacy by using conventional preparation methods in the art.

[0010] Further, the dosage form of the traditional Chinese medicine compound preparation is a decoction, a tablet, a capsule, a granule, a pill, a mixture, an oral liquid, or a syrup.

[0011] Further, the pharmaceutical preparation further comprises a pharmaceutically acceptable excipient.

[0012] Further, the pharmaceutical preparation can be prepared by the following method: (A) weighing each medicinal component, mixing, and obtaining a mixture; (B) adding a pharmaceutically acceptable carrier or excipient to the mixture, and preparing by using conventional preparation methods in the art.

[0013] In a third aspect of the present application, the use of the traditional Chinese medicine composition as described above in the preparation of a medicament for treating type 2 diabetes is provided.

[0014] Further, the type 2 diabetes is type 2 diabetes with internal retention of damp-heat.

[0015] In a fourth aspect of the present application, the use of the traditional Chinese medicine compound preparation as described above in the preparation of a medicament for treating type 2 diabetes is provided.

[0016] Further, the traditional Chinese medicine composition / traditional Chinese medicine compound preparation is used for:

[0017] a) reducing the fasting blood glucose level,

[0018] b) reducing the glycosylated hemoglobin level,

[0019] c) reducing the triglyceride level,

[0020] d) improving the clinical symptoms of patients,

[0021] e) improving insulin resistance.

[0022] The traditional Chinese medicine composition of the present application is formed by carefully selecting medicine and prescription based on many years of clinical practice and traditional Chinese medicine theory. The prescription has the following effects: the atractylodes dry dampness and invigorate the spleen, the radix puerariae ascend yang and assist the spleen to transport, the alisma peltatum discharge heat and penetrate dampness, the radix lamiophlomis eliminate wind and dampness and strengthen the bones and muscles, the smilax dry dampness and remove turbidity, the coptis clear heat and dry dampness, the cortex lycii clear heat and cool blood, the anemarrhena rhizome nourish yin and clear heat, the indigofera carbonize blood and promote water, the campsis flower activate blood and cool blood, the hawthorn carbonize blood, the fried foxtail millet and the fried barley malt promote digestion and invigorate the spleen, and the whole prescription has the effects of invigorating the spleen, removing dampness, clearing heat and activating blood, which is in line with the core pathogenesis of diabetes.

[0023] The weight ratio of the raw materials of the traditional Chinese medicine composition of the present application is obtained by the inventors through long-term clinical practice and prescription based on traditional Chinese medicine theory, and good effects can be achieved within the range of the ratio.

[0024] The present application has the following advantages:

[0025] 1. The present application provides a traditional Chinese medicine composition and a compound preparation with the effects of invigorating the spleen, removing dampness, clearing heat and activating blood based on the understanding of the core pathogenesis of diabetes (spleen dysfunction and dampness-heat). Clinical experiments prove that the present application can significantly reduce the fasting blood glucose, glycosylated hemoglobin and triglyceride levels of patients with type 2 diabetes with dampness-heat syndrome, improve the TCM symptom score and insulin resistance, and is effective for the treatment of type 2 diabetes, can significantly improve the clinical symptoms of patients, and has a significant effect.

[0026] 2. The raw materials of the traditional Chinese medicine composition and the compound preparation of the present application are simple and easy to obtain, low in cost, easy to prepare, suitable for popularization and application, non-toxic, and safe. DETAILED DESCRIPTION

[0027] The specific embodiments provided by the present application will be described in detail below.

[0028] Example 1: The traditional Chinese medicine composition of the present application

[0029] The traditional Chinese medicine composition of the present application is composed of the following raw materials: coptis 5 parts, cortex lycii 10 parts, anemarrhena rhizome 10 parts, radix puerariae 10 parts, prepared atractylodes 10 parts, radix lamiophlomis 10 parts, smilax 10 parts, indigofera carbon 4 parts, indigofera 10 parts, alisma peltatum 8 parts, campsis flower 10 parts, hawthorn carbon 8 parts, fried foxtail millet 10 parts, and fried barley malt 10 parts.

[0030] Example 2: The traditional Chinese medicine composition of the present application

[0031] The traditional Chinese medicine composition of the present application is composed of the following raw materials: coptis 6 parts, cortex lycii 12 parts, anemarrhena rhizome 12 parts, radix puerariae 15 parts, prepared atractylodes 12 parts, radix lamiophlomis 15 parts, smilax 15 parts, indigofera carbon 6 parts, indigofera 12 parts, alisma peltatum 10 parts, campsis flower 15 parts, hawthorn carbon 10 parts, fried foxtail millet 15 parts, and fried barley malt 15 parts.

[0032] Example 3: Traditional Chinese medicine composition of the present application

[0033] consists of the following raw medicinal materials by weight: Coptis 8 parts, Cortex Lycii 14 parts, Anemarrhena 14 parts, Pueraria 18 parts, Atractylodes 14 parts, Swertia 18 parts, Smilax 18 parts, Sophora 8 parts, Lamiophlomis 14 parts, Alisma 10 parts, Honeysuckle 18 parts, Crataegus 12 parts, Fried rice sprout 18 parts, Fried wheat germ 18 parts.

[0034] Example 4: Traditional Chinese medicine composition of the present application

[0035] consists of the following raw medicinal materials by weight: Coptis 10 parts, Cortex Lycii 16 parts, Anemarrhena 16 parts, Pueraria 20 parts, Atractylodes 16 parts, Swertia 20 parts, Smilax 20 parts, Sophora 6 parts, Lamiophlomis 16 parts, Alisma 12 parts, Honeysuckle 20 parts, Crataegus 12 parts, Fried rice sprout 20 parts, Fried wheat germ 20 parts.

[0036] Example 5: Preparation of decoction

[0037] The traditional preparation method of traditional Chinese medicine decoction is used, that is, the traditional Chinese medicine composition of any one of examples 1-4 is weighed and decocted with water to obtain a decoction.

[0038] Example 6: Preparation of tablets / capsules

[0039] The traditional Chinese medicine composition of any one of examples 1-4 is weighed, finely ground, decocted, and concentrated under reduced pressure to obtain an extract. The extract is dried and crushed to prepare granules. Pharmaceutical excipients are added, and tablets or capsules are prepared by compression or filling.

[0040] Example 7: Preparation of granules

[0041] The traditional Chinese medicine composition of any one of examples 1-4 is weighed and decocted twice, each time for 1 hour. The decoction is filtered, and the filtrate is concentrated to a thick extract. The extract is vacuum dried, powdered, and packaged as granules.

[0042] Example 8: Preparation of pills, mixtures, oral solutions, and syrup

[0043] The traditional Chinese medicine composition of any one of examples 1-4 is weighed, finely ground, decocted, and the supernatant is concentrated to a thick extract. Appropriate pharmaceutical excipients (such as white sugar, honey, benzylpropionic acid, or hydroxyphenyl ethyl ester) are added to prepare pills, mixtures, oral solutions, or syrup.

[0044] Example 9: Clinical experiment of the traditional Chinese medicine composition of the present application

[0045] 1. Case source: 66 clinical cases were all from 2021-05 / 2023-05 Dawn Hospital patients diagnosed with type 2 diabetes and TCM syndrome of damp-heat accumulation.

[0046] Inclusion criteria: (1) meet the T2DM Western medicine diagnostic criteria and TCM syndrome differentiation for damp-heat accumulation syndrome;

[0047] (2) not using hypoglycemic drugs for the treatment of initial treatment patients;

[0048] (3) after the screening period (diet control and exercise therapy for 2 weeks), the patients with FPG≤9mmol / L, 2hPG≤15mmol / L were measured;

[0049] (4) age 20-70 years old, male and female;

[0050] (5) voluntarily participate in this project, and sign the informed consent form.

[0051] 2. Grouping and treatment: this project adopts a randomized, controlled clinical research method, and 66 patients meeting the inclusion criteria are randomly divided into two groups according to the random number table, 33 cases in each group. Control group: basic treatment, that is, diabetes knowledge education, reasonable diet, appropriate exercise, self-blood glucose monitoring, at the same time of basic treatment; placebo granules; treatment group: at the same time of basic treatment, the traditional Chinese medicine composition granules prepared by example 2 and example 7 of the application are given, 2 packs per day, 1 time in the morning and 1 time in the evening, 200ml water, warm and take.

[0052] 3. Observation index and method:

[0053] (1) efficacy evaluation: TCM symptom score, FPG, 2hPG, HbAlc, insulin resistance index (HOMA-IR), TC, TG, HDL-C, LDL-C, etc.

[0054] (2) safety evaluation: liver and kidney function of patients in both groups before and after treatment are checked to observe whether the drug has an impact on liver and kidney function.

[0055] (3) TCM symptom score standard: according to the "Guidelines for Clinical Research of New Drugs of Traditional Chinese Medicine" published by China Science and Technology Press in 2002, the main symptoms are divided into 4 grades of no, mild, moderate and severe, and scored with 0, 2, 4 and 6 points; the secondary symptoms are divided into 4 grades of no, mild, moderate and severe, and scored with 0, 1, 2 and 3 points. Score before and after treatment is recorded respectively, and the changes of each single score and total score are observed. The scoring table is shown in Table 1.

[0056] Table 1 TCM syndrome questionnaire

[0057]

[0058] 4. Statistical method:

[0059] SPSS25.0 statistical software is used to input data for data analysis. Count data is expressed by frequency and percentage, χ 2Inspection; measurement data conform to normal distribution and variance Indicated, using t-test; non-normal distribution of measurement data using median and interquartile range, using non-parametric rank test. Differences are represented by probability value P, P <0.05 for statistically significant differences.

[0060] 5. Results:

[0061] (1) Sugar metabolism index: all cases of the main efficacy of sugar metabolism index (FPG, 2HPG, HbA1c) using two independent sample T test, INS and HOMA-IR using two independent sample rank test, according to the test level of α> 0.05, fasting blood glucose and glycosylated hemoglobin difference was statistically significant, showing that the difference between the two groups of patients with sugar metabolism index was statistically significant, with comparability. See Table 2.

[0062] Table 2 Comparison of two groups of sugar metabolism index observation

[0063]

[0064] Compared with the control group, ☆P<0.05.

[0065] (2) Lipid metabolism index: all cases of lipid metabolism related indicators (TC, TG, LDL, HDL) using two independent sample T test, according to the test level of α> 0.05, triglyceride difference was statistically significant, showing that the difference between the two groups of patients with triglyceride was statistically significant, with comparability. See Table 3.

[0066] Table 3 Comparison of two groups of lipid metabolism related indicators observation

[0067]

[0068] Compared with the control group, ☆P<0.05.

[0069] (3) Comparison of TCM symptom score

[0070] The total symptom score and each single symptom score of the two groups of patients before treatment were not in accordance with the normal distribution after normality test, so the data results were represented by median (interquartile range). The difference was statistically significant (P<0.05) by non-parametric rank test. See Table 4:

[0071] Table 4 Comparison of TCM symptom score before and after treatment [median (interquartile range)]

[0072]

[0073] Compared with the control group, ☆P<0.05.

[0074] (4) Observation and comparison of safety-related indicators (AST, ALT, AST / ALT, GGT, TBIL, Cr, eGFR, UA, BUN, HSCRP) in the intervention group before and after intervention. Paired sample T test was used, and it was found that eGFR decreased in the intervention group before and after intervention, and the difference was statistically significant (P<0.05). The rest of the safety indicators had no statistically significant difference before and after intervention (P>0.05), as shown in Tables 5, 6, 7 and 8.

[0075] Table 5 Comparison of liver function-related indicators in the intervention group before and after intervention

[0076]

[0077] Table 6 Comparison of kidney function-related indicators in the intervention group before and after intervention

[0078]

[0079]

[0080] Compared with the control group, ★P<0.05.

[0081] Table 7 Comparison of liver function-related indicators in the control group before and after intervention

[0082]

[0083] Table 8 Comparison of kidney function-related indicators in the control group before and after intervention

[0084]

[0085] Note: ★ represents comparison with before intervention, P<0.05.

[0086] The above test shows that: compared with the control group, the total symptom score of the intervention group decreases (P<0.05), the fasting blood glucose, glycosylated hemoglobin and HOMA-IR of the patients in the intervention group improve, and the triglyceride level decreases, and the differences are statistically significant (P<0.05). The liver and kidney functions of the two groups before and after intervention are not significantly damaged, which shows that the traditional Chinese medicine composition of the present application can significantly improve the fasting blood glucose, glycosylated hemoglobin and HOMA-IR of patients with type 2 diabetes with internal retention of damp-heat, and can improve the clinical symptoms of patients, and has good safety.

[0087] Example 10: Toxicological study of the traditional Chinese medicine compound preparation of the present application

[0088] 1. Acute toxicity experiment

[0089] (1) Experimental animals

[0090] Healthy SPF level KM mice 40, 4 weeks old, body weight (20±2) g, half male and half female. Raising in Shanghai University of Traditional Chinese Medicine Experimental Animal Center, given 12h light, 45% humidity environment, free drinking water, eating standard ordinary feed, adaptive feeding for 1 week. Experimental animal license number: SYXK (Shanghai) 2020-0009.

[0091] (2) Drug preparation

[0092] The experimental drug is the traditional Chinese medicine composition prepared in Example 2 of the application. The 12 kg mixture is divided into low, medium and high dose groups, each group of 4 kg, respectively add water 10 L, soak for 1 hour, heat to boiling. The low dose group is concentrated to 2 L to obtain an extract liquid with a concentration of 1.8 g / kg (crude drug amount / body weight); the medium dose group is concentrated to 2 L to obtain an extract liquid with a concentration of 3.6 g / kg (crude drug amount / body weight); the high dose group is concentrated to 0.5 L to obtain an extract liquid with a concentration of 7.2 g g / kg (crude drug amount / body weight).

[0093] (3) Animal grouping

[0094] Take 40 healthy KM mice, according to the random number table method, divide them into 4 groups, 10 in each group: ① low dose group: give traditional Chinese medicine liquid with a concentration of 1.8 g / kg (crude drug amount / body weight) by gavage (equivalent to 25 times of the clinical equivalent dose); ② medium dose group: give traditional Chinese medicine liquid with a concentration of 3.6 g / kg (crude drug amount / body weight) by gavage (equivalent to 50 times of the clinical equivalent dose); ③ high dose group: give traditional Chinese medicine liquid with a concentration of 7.2 g / kg (crude drug amount / body weight) by gavage (equivalent to 100 times of the clinical equivalent dose); ④ solvent control group: give the same volume of solvent by gavage.

[0095] (4) Intervention method

[0096] Each group of mice is given by gavage according to 1 ml / 10 g body weight, twice a day, for 7 consecutive days.

[0097] (5) Observation index

[0098] Through various acute toxicity experiments, the appearance, behavior, diet, and shape of the feces of the mice were observed. Continuous observation was carried out within 4 hours after administration, and observation was carried out once in the morning and once in the afternoon every day from 2 to 14 days. Body weight was measured before administration, 7 days after administration, and at the end of the observation period. The animals were anesthetized and euthanized, and the main organs of the mice were observed macroscopically.

[0099] (6) Experimental results

[0100] The appearance, behavior, diet, and fecal shape of each group of mice during administration were normal; no decrease in activity, curling, loose hair, and other phenomena were observed; no secretions were observed in the nose, eyes, or mouth; and no deaths occurred. The results showed that when the maximum dose of the mice was 7.2 g / kg (crude drug amount / body weight), i.e., 100 times the clinical equivalent dose, no acute toxicity reaction of the traditional Chinese medicine compound preparation occurred.

[0101] 2. Long-term toxicity experiment

[0102] After 180 days of continuous administration, the long-term toxicity of the traditional Chinese medicine composition prepared in Example 2 of the present application on rats was observed, blood routine and blood biochemical indexes were determined, organ coefficients were calculated, and histopathological changes of organ tissues were observed.

[0103] (1) Experimental animals

[0104] Healthy SPF level SD rats 120, 6 weeks old, body weight (200 ± 30) g, half male and half female. Raising in Shanghai University of Traditional Chinese Medicine Experimental Animal Center, giving 12h light, 45% humidity environment, free drinking water, eating standard ordinary feed, adaptive feeding for 1 week. Experimental animal license number: SYXK (Shanghai) 2020-0009.

[0105] (2) Drug preparation

[0106] The preparation method is the same as before. The drug solution concentration of the low-dose group is concentrated to 0.6 g (crude drug) / ml; the drug solution concentration of the medium-dose group is 1.2 g (crude drug) / ml; and the drug solution concentration of the high-dose group is 2.4 g (crude drug) / ml.

[0107] (3) Animal grouping

[0108] Take 120 healthy SD rats, according to the random number table method, divide them into 4 groups, 30 in each group: ① blank control group: give the same amount of normal saline by gavage; ② low-dose group: give the traditional Chinese medicine liquid with a concentration of 0.6 g / ml by gavage (equivalent to 10 times the clinical equivalent dose); ③ medium-dose group: give the traditional Chinese medicine liquid with a concentration of 1.2 g / ml by gavage (equivalent to 20 times the clinical equivalent dose); ④ high-dose group: give the traditional Chinese medicine liquid with a concentration of 2.4 g / ml by gavage (equivalent to 40 times the clinical equivalent dose).

[0109] (4) Intervention method

[0110] The rats in each dose group of traditional Chinese medicine were given gavage at 10 ml / 100 g body weight, twice a day.

[0111] (5) Observation index

[0112] The changes of the rats in each group in appearance, behavior, diet, and fecal shape were observed by long-term toxicity experiment; the secretion of the rats' nose, eyes, and oral cavity was observed; the body weight change and death of the rats were observed and recorded. Recovery observation was conducted for 2 weeks after drug administration (recovery period). The body weight of the rats was measured once a week. After continuous administration for 1 month, 3 months, and 2 weeks after drug withdrawal, 10 rats (half male and half female) in each dose group were randomly selected, and blood routine and blood biochemical indexes were detected, and the heart, liver, spleen, lung, kidney, brain, and other tissues and organs of the rats were taken, the weights of the organs were weighed, the organ coefficients were calculated, and histopathological examination was conducted.

[0113] (6) Experimental results

[0114] During the administration period, the rats in each group were normal in appearance, behavior, diet, and fecal shape; no phenomena such as reduced activity, curling, and loose fur were observed; no abnormal secretions were observed in the nose, eyes, and oral cavity; and no death was observed. After 180 days of administration, the blood samples of the rats in each group were collected for testing and analysis, and the results showed that the blood routine (red blood cell count, hemoglobin, platelet count, and white blood cell count) and coagulation time of the rats in each group were normal; the liver function (glutamic-pyruvic transaminase, glutamic-oxalacetic transaminase, alkaline phosphatase, serum total protein, albumin, etc.), kidney function (urea nitrogen, creatinine, etc.), blood lipids, blood sugar, etc. had no statistically significant difference compared with the blank control group. The rats were sacrificed by cervical dislocation, and no obvious abnormal changes were observed in the appearance observation and histological section examination of each tissue and organ (heart, liver, kidney, spleen, lung, testis, uterus and ovary, brain, stomach, pancreas, adrenal gland, thymus, thyroid, etc.). The above results show that when the administration amount of the rats is 6g (crude drug) / kg, 12g (crude drug) / kg, and 24g (crude drug) / kg of body weight, and the rats are continuously administered for 6 months, the traditional Chinese medicine compound preparation of the application does not show obvious toxic reaction.

[0115] The preferred embodiments of the application have been specifically described above, but the application is not limited to the described embodiments, and those skilled in the art can make various equivalent modifications or replacements without departing from the spirit of the application. These equivalent modifications or replacements are all included in the scope defined by the claims of the present application.

Claims

1. A traditional Chinese medicine composition for strengthening the spleen, removing dampness, clearing heat and activating blood, characterized in that, The traditional Chinese medicine composition is prepared from the following raw materials: Coptis chinensis 5-10 parts, Cortex Lycii 10-16 parts, Anemarrhena asphodeloides 10-16 parts, Pueraria lobata 10-20 parts, Atractylodes lancea 10-16 parts, Pyrola rotundifolia 10-20 parts, Sophora japonica 4-8 parts, Lonicera japonica 10-16 parts, Alisma orientale 8-12 parts, Campsis grandiflora 10-20 parts, Crataegus pinnatifida 8-12 parts, Fried Oryza sativa 10-20 parts, and Fried Hordeum vulgare 10-20 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition is prepared from the following raw materials: Coptis chinensis 6-8 parts, Cortex Lycii 12-14 parts, Anemarrhena asphodeloides 12-14 parts, Pueraria lobata 15-20 parts, Atractylodes lancea 12-14 parts, Pyrola rotundifolia 15-20 parts, Sophora japonica 6-8 parts, Lonicera japonica 12-14 parts, Alisma orientale 10-12 parts, Campsis grandiflora 15-20 parts, Crataegus pinnatifida 10-12 parts, Fried Oryza sativa 15-20 parts, and Fried Hordeum vulgare 15-20 parts.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition is prepared from the following raw materials: Coptis chinensis 6 parts, Cortex Lycii 12 parts, Anemarrhena asphodeloides 12 parts, Pueraria lobata 15 parts, Atractylodes lancea 12 parts, Pyrola rotundifolia 15 parts, Sophora japonica 6 parts, Lonicera japonica 12 parts, Alisma orientale 10 parts, Campsis grandiflora 15 parts, Crataegus pinnatifida 10 parts, Fried Oryza sativa 15 parts, and Fried Hordeum vulgare 15 parts.

4. A Chinese medicine compound preparation using the Chinese medicine composition for strengthening the spleen, removing dampness, clearing heat and promoting blood circulation according to any one of claims 1-3 as the active ingredient, characterized in that, The traditional Chinese medicine composition is prepared from the following raw materials: Coptis chinensis 5-10 parts, Cortex Lycii 10-16 parts, Anemarrhena asphodeloides 10-16 parts, Pueraria lobata 10-20 parts, Atractylodes lancea 10-16 parts, Pyrola rotundifolia 10-20 parts, Sophora japonica 4-8 parts, Lonicera japonica 10-16 parts, Alisma orientale 8-12 parts, Campsis grandiflora 10-20 parts, Crataegus pinnatifida 8-12 parts, Fried Oryza sativa 10-20 parts, and Fried Hordeum vulgare 10-20 parts.

5. The traditional Chinese medicine compound preparation according to claim 4, characterized in that, The traditional Chinese medicine composition is prepared from the following raw materials: Coptis chinensis 6-8 parts, Cortex Lycii 12-14 parts, Anemarrhena asphodeloides 12-14 parts, Pueraria lobata 15-20 parts, Atractylodes lancea 12-14 parts, Pyrola rotundifolia 15-20 parts, Sophora japonica 6-8 parts, Lonicera japonica 12-14 parts, Alisma orientale 10-12 parts, Campsis grandiflora 15-20 parts, Crataegus pinnatifida 10-12 parts, Fried Oryza sativa 15-20 parts, and Fried Hordeum vulgare 15-20 parts.

6. The traditional Chinese medicine compound preparation according to claim 5, characterized in that, The traditional Chinese medicine composition is prepared from the following raw materials: Coptis chinensis 6 parts, Cortex Lycii 12 parts, Anemarrhena asphodeloides 12 parts, Pueraria lobata 15 parts, Atractylodes lancea 12 parts, Pyrola rotundifolia 15 parts, Sophora japonica 6 parts, Lonicera japonica 12 parts, Alisma orientale 10 parts, Campsis grandiflora 15 parts, Crataegus pinnatifida 10 parts, Fried Oryza sativa 15 parts, and Fried Hordeum vulgare 15 parts. The traditional Chinese medicine composition is prepared from the following raw materials: Coptis chinensis 5-10 parts, Cortex Lycii 10-16 parts, Anemarrhena asphodeloides 10-16 parts, Pueraria lobata 10-20 parts, Atractylodes lancea 10-16 parts, Pyrola rotundifolia 10-20 parts, Sophora japonica 4-8 parts, Lonicera japonica 10-16 parts, Alisma orientale 8-12 parts, Campsis grandiflora 10-20 parts, Crataegus pinnatifida 8-12 parts, Fried Oryza sativa 10-20 parts, and Fried Hordeum vulgare 10-20 parts. The traditional Chinese medicine composition is prepared from the following raw materials: Coptis chinensis 6-8 parts, Cortex Lycii 12-14 parts, Anemarrhena asphodeloides 12-14 parts, Pueraria lobata 15-20 parts, Atractylodes lancea 12-14 parts, Pyrola rotundifolia 15-20 parts, Sophora japonica 6-8 parts, Lonicera japonica 12-14 parts, Alisma orientale 10-12 parts, Campsis grandiflora 15-20 parts, Crataegus pinnatifida 10-12 parts, Fried Oryza sativa 15-20 parts, and Fried Hordeum vulgare 15-20 parts.

9. Use according to claim 7 or 8, characterized in that, The traditional Chinese medicine composition is prepared from the following raw materials: Coptis chinensis 6 parts, Cortex Lycii 12 parts, Anemarrhena asphodeloides 12 parts, Pueraria lobata 15 parts, Atractylodes lancea 12 parts, Pyrola rotundifolia 15 parts, Sophora japonica 6 parts, Lonicera japonica 12 parts, Alisma orientale 10 parts, Campsis grandiflora 15 parts, Crataegus pinnatifida 10 parts, Fried Oryza sativa 15 parts, and Fried Hordeum vulgare 15 parts.

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