Traditional Chinese medicine composition for treating atherosclerosis combined with hyperhomocysteinemia, preparation method and use thereof

Abstract

The application discloses a traditional Chinese medicine composition for treating atherosclerosis combined with hyperhomocysteinemia. The traditional Chinese medicine composition is prepared from the following raw medicinal materials: Radix Rehmanniae Preparata 12-15 parts, Cistanche 9-12 parts, Radix Astragali 12-15 parts, Cyperus rotundus 6-9 parts, Salvia miltiorrhiza 15-30 parts and safflower 6-9 parts. In addition, the application also relates to a preparation method of the traditional Chinese medicine composition. The traditional Chinese medicine composition has obvious effects of treating atherosclerosis, reducing homocysteine and blood lipid levels, improving patient symptoms and reducing atherosclerosis-related complications.

Description

TECHNICAL FIELD

[0001] The present application relates to a kind of traditional Chinese medicine composition for treating atherosclerosis combined with hyperhomocysteinemia;The present application also relates to the preparation method and purposes of the traditional Chinese medicine composition. BACKGROUND

[0002] 1. The current situation of atherosclerosis in the field of health in China

[0003] The first cause of death of community residents in China is cardiovascular and cerebrovascular diseases, which accounts for more than 40% of the total death composition, higher than tumors and other diseases, especially in rural areas in recent years, the mortality rate of cardiovascular disease is higher than that in cities. American Heart Association, European Society of Cardiology data also shows that cardiovascular disease is the first cause of death, among which coronary heart disease is the first burden, and stroke is the second. Every year, the economic loss caused by cardiovascular disease is up to 329.7 billion US dollars. Atherosclerosis (AS) is the most common pathological basis of cardiovascular and cerebrovascular diseases, and in the later stage, it often causes acute cardiovascular and cerebrovascular events due to plaque rupture. Therefore, how to effectively limit the progression of atherosclerosis and prevent the occurrence of serious cardiovascular and cerebrovascular events is of great significance.

[0004] 2. Atherosclerosis and hyperhomocysteinemia

[0005] Plasma homocysteine (Hcy) is a sulfur-containing amino acid, which is an important metabolite of methionine and cysteine. When the metabolism of methionine and cysteine is impaired, the level of homocysteine (Hcy) in blood increases. Plasma homocysteine level above 10 μmol / L is called hyperhomocysteinemia (HHcy) or elevated plasma Hcy level. Studies have shown that the increase of plasma Hcy level is an independent risk factor for atherosclerosis. If the plasma Hcy level increases by 5 μmol / L, the risk of coronary heart disease will increase by 20%. On the contrary, if the Hcy level decreases by 3 μmol / L, the risk of coronary heart disease will decrease by 11%. HHcy may cause atherosclerosis by affecting vascular endothelial cells, causing functional damage, promoting the proliferation of vascular smooth muscle cells, platelet adhesion and aggregation, oxidative modification of low-density lipoprotein, and increasing arterial stiffness.

[0006] Elevated homocysteine (Hcy) concentration in blood can promote the degradation of elastic fibers and promote the synthesis of collagen fibers, resulting in a decrease in the ratio of elastin / collagen in the media layer of blood vessels, a decrease in the distensibility of large arteries, and an increase in stiffness. Studies have found that after adjusting age, mean blood pressure, degree of arterial occlusion, glomerular filtration rate and other risk factors, Hcy is positively correlated with carotid and femoral artery pulse rate. In addition, when LP(a) and Hcy increase simultaneously, the risk of atherosclerosis increases greatly.

[0007] 3.Overview of treating atherosclerosis combined with hyperhomocysteinemia with traditional Chinese medicine

[0008] Although great progress has been made in non-drug treatment methods for AS and coronary heart disease, such as percutaneous coronary intervention and coronary artery bypass grafting, patients still have a high risk of cardiovascular events, and are faced with problems such as in-stent restenosis, stent thrombosis and anti-platelet drug resistance. In terms of western medicine treatment, statins are currently mainly used, but they have certain side effects, such as liver and kidney damage or muscle damage, and patients have difficulty in adhering to long-term use. The most safe and effective method known to reduce Hcy is folic acid supplementation, which can be used with or without vitamin B. It is worth noting that some studies suggest that folic acid supplementation therapy can lead to prostate cancer.

[0009] Traditional Chinese medicine has undeniable advantages in treating common cardiovascular and cerebrovascular diseases combined with hyperhomocysteinemia through four diagnostic methods and treatment based on syndrome differentiation. It has clear effects in reducing Hcy, improving hemorheology, stabilizing and resolving atherosclerotic plaques, improving cardiac function and improving the quality of life of patients. Its outstanding features are safety, effectiveness, few side effects, and overall consideration, systemic conditioning, which is especially suitable for chronic patients. Studies have shown that traditional Chinese medicine has certain advantages in the treatment of hyperhomocysteinemia. SUMMARY

[0010] In view of the above shortcomings of the prior art, according to the embodiments of the present application, it is intended to provide a traditional Chinese medicine composition for treating atherosclerosis combined with hyperhomocysteinemia, which can treat atherosclerosis, reduce blood homocysteine and improve the quality of life, and propose a preparation method and use of the traditional Chinese medicine composition.

[0011] To solve the above technical problems, the present application provides a traditional Chinese medicine composition for treating atherosclerosis combined with hyperhomocysteinemia, which is prepared from the following raw materials: Radix Rehmanniae Preparata 12-15 parts, Cistanche 9-12 parts, Radix Astragali 12-15 parts, Rhizoma Cyperi 6-9 parts, Salvia Miltiorrhiza 15-30 parts, and Safflower 6-9 parts.

[0012] Preferably, the weight parts of the above traditional Chinese medicine composition of the present application are as follows: Radix Rehmanniae Preparata 15 parts, Cistanche 12 parts, Radix Astragali 15 parts, Rhizoma Cyperi 6 parts, Salvia Miltiorrhiza 15 parts, and Safflower 6 parts.

[0013] Preferably, the above agent of the present application is a mixture.

[0014] Preferably, the above agent of the present application is a granule.

[0015] The preparation method of the above-mentioned Chinese medicine composition mixture is as follows: the raw medicine is weighed according to the proportion of 6-8 days, and 9-11 times and 7-9 times of water is added respectively, and decocted for two to three times, the filtrate is combined, and the filtrate is concentrated to 5 grams of raw medicine per milliliter; 2-4 times of ethanol is added to the concentrated solution, the alcohol content is 60%, and the concentrated solution is refrigerated and placed for 22-26 hours, then filtered, and the filtrate is recovered to no alcohol taste; the recovered solution is boiled, 2-4 grams of sodium benzoate and 0.23-0.27 grams of nipagin are added, filtered, cooled, added with water to 480-520 ml, and then hot filled to obtain the mixture.

[0016] In addition, the above-mentioned Chinese medicine composition mixture can also be prepared by the following method: the prepared Rehmannia glutinosa, Salvia miltiorrhiza and safflower are ground to 10-40 meshes, and the volatile oil is extracted by steam distillation or supercritical extraction method for standby use; the residues of the prepared Rehmannia glutinosa, Salvia miltiorrhiza and safflower are added with water in an amount of 5-10 times respectively, and decocted for two to three times, the filtrate is combined, and the filtrate is concentrated to 5 grams of raw medicine per milliliter; the flocculation and precipitation method is used, and the mixture is placed for 22-26 hours, then centrifuged and filtered, the centrifugal speed is 4980-5020 rpm / min, the volatile oil of the prepared Rehmannia glutinosa, Salvia miltiorrhiza and safflower is added to the filtrate, mixed, 2-4 grams of sodium benzoate and 0.23-0.27 grams of nipagin are added, filtered, cooled, added with water to 480-520 ml, and then hot filled to obtain the mixture.

[0017] The preparation method of the above-mentioned Chinese medicine composition granules is as follows: the raw medicine is weighed according to the proportion of 6-8 days, and 9-11 times and 7-9 times of water is added respectively, and decocted for two to three times, the filtrate is combined, and the filtrate is concentrated to 5 grams of raw medicine per milliliter; 2-4 times of ethanol is added to the concentrated solution, the alcohol content is 60%, and the concentrated solution is refrigerated and placed for 22-26 hours, then filtered, and the filtrate is recovered to no alcohol taste, the recovered solution is concentrated to a relative density of 1.25-1.30, and a proper amount of dextrin or starch is added, then wet granulation is performed, dried, and 480-520 grams of granules are obtained, which are then packaged.

[0018] In addition, the above-mentioned Chinese medicine composition granules can also be prepared by the following method: the prepared Rehmannia glutinosa, Salvia miltiorrhiza and safflower are ground to 10-40 meshes, and the volatile oil is extracted by steam distillation or supercritical extraction method for standby use; the residues of the prepared Rehmannia glutinosa, Salvia miltiorrhiza and safflower are added with water in an amount of 5-10 times respectively, and decocted for two to three times, the filtrate is combined, and the filtrate is concentrated to 5 grams of raw medicine per milliliter; the flocculation and precipitation method is used, and the mixture is placed for 22-26 hours, then centrifuged and filtered, the centrifugal speed is 4980-5020 rpm / min, the volatile oil of the prepared Rehmannia glutinosa, Salvia miltiorrhiza and safflower is added to the filtrate, mixed, 2-4 grams of sodium benzoate and 0.23-0.27 grams of nipagin are added, filtered, cooled, added with water to 480-520 ml, and then hot filled to obtain the mixture.

[0019] The traditional Chinese medicine composition in the present application is based on the therapeutic principle of tonifying kidney and filling essence, activating blood and dredging collaterals, and is composed of Radix Rehmanniae, Herba Cistanche, Radix Astragali, Rhizoma Cyperi, Radix Salviae Miltiorrhizae and Flos Carthami. Among the drugs, Radix Rehmanniae and Herba Cistanche tonify kidney and fill essence, Radix Astragali invigorates spleen and replenishes qi, Rhizoma Cyperi regulates qi and activates blood, and Radix Salviae Miltiorrhizae and Flos Carthami activate blood, remove blood stasis and dredge collaterals, and the whole prescription takes into account both the root and the branch.

[0020] Modern pharmacological research has confirmed that Radix Rehmanniae and Herba Cistanche have antioxidant effects, improve hemorheology, and have good effects on neurodegenerative diseases, can increase coronary flow after reperfusion, reduce coronary resistance, and promote the recovery of myocardial contractility. Radix Astragali and Radix Salviae Miltiorrhizae have effects of improving myocardial ischemia, dilating blood vessels, resisting thrombus formation, reducing blood viscosity, regulating blood lipids, and reducing homocysteine; Rhizoma Cyperi has the effects of regulating blood lipids and oxidative stress disorder; Flos Carthami has the pharmacological effects of inhibiting inflammatory response, inhibiting vascular smooth muscle cell proliferation, resisting oxidative stress, resisting platelet aggregation, and regulating blood lipids, reducing the level of homocysteine which threatens cardiovascular diseases, etc.

[0021] The traditional Chinese medicine composition in the present application has been proved by clinical trials to have obvious effects of treating atherosclerosis, reducing the levels of homocysteine and blood lipids, improving the symptoms of patients, and reducing the occurrence of atherosclerosis-related complications. DETAILED DESCRIPTION

[0022] The present application will be further described below in conjunction with specific examples. These examples should be understood as merely illustrative of the present application and not used to limit the protection scope of the present application. After reading the content described in the present application, those skilled in the art can make various changes or modifications to the present application, and these equivalent changes and modifications also fall within the scope defined by the claims of the present application.

[0023] The Radix Rehmanniae used in the following examples of the present application is determined to be produced in Shanghai, and is the tuberous root of Rehmannia glutinosa of the family Scrophulariaceae.

[0024] The Herba Cistanche used in the following examples of the present application is determined to be produced in Inner Mongolia, and is the succulent stem of Cistanche deserticola Y.C.Ma of the family Orobanchaceae with scale leaves.

[0025] The Radix Astragali used in the following examples of the present application is determined to be produced in Inner Mongolia, and is the root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao of the family Leguminosae.

[0026] The Rhizoma Cyperi used in the following examples of the present application is determined to be produced in Shandong, and is the dried rhizome of Cyperus rotundus L. of the family Cyperaceae.

[0027] The determined producing area of the Danshen used in the following examples of the present application is Jiangsu, and is the root and rhizome of Salvia miltiorrhiza Bge., a perennial herbaceous plant of Labiatae.

[0028] The determined producing area of the Honghua used in the following examples of the present application is Yunnan, and is the dried flower of Carthamus tinctorius L., a plant of Asteraceae.

[0029] Example 1 (preparation of the combined preparation)

[0030] The above-mentioned medicinal materials are weighed according to the proportion, and then 9 times and 7 times of water are added respectively, and decocted for two to three times. The filtrates are combined and concentrated to 5g of crude drug per ml. 2 times of ethanol is added to the concentrated solution, and the alcohol content is about 60%. The solution is refrigerated and placed for 22 hours, filtered, and the filtrate is recovered to be alcohol-free. The recovered solution is boiled, 2g of sodium benzoate and 0.23g of nipagin (which has been dissolved in water) are added, filtered, and cooled. Water is added to 480ml, and then hot filling is performed to obtain the product.

[0031] Example 2 (preparation of the combined preparation)

[0032] The above-mentioned medicinal materials are weighed according to the proportion, and then 10 times and 8 times of water are added respectively, and decocted for two to three times. The filtrates are combined and concentrated to 5g of crude drug per ml. 3 times of ethanol is added to the concentrated solution, and the alcohol content is about 60%. The solution is refrigerated and placed for 24 hours, filtered, and the filtrate is recovered to be alcohol-free. The recovered solution is boiled, 3g of sodium benzoate and 0.25g of nipagin (which has been dissolved in water) are added, filtered, and cooled. Water is added to 500ml, and then hot filling is performed to obtain the product.

[0033] Example 3 (preparation of the combined preparation)

[0034] The above-mentioned medicinal materials are weighed according to the proportion, and then 11 times and 9 times of water are added respectively, and decocted for two to three times. The filtrates are combined and concentrated to 5g of crude drug per ml. 4 times of ethanol is added to the concentrated solution, and the alcohol content is about 60%. The solution is refrigerated and placed for 26 hours, filtered, and the filtrate is recovered to be alcohol-free. The recovered solution is boiled, 4g of sodium benzoate and 0.27g of nipagin (which has been dissolved in water) are added, filtered, and cooled. Water is added to 520ml, and then hot filling is performed to obtain the product.

[0035] Example 4 (preparation of the combined preparation)

[0036] Take Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos 6 days' quantity by proportion, crush to 10-40 meshes, extract volatile oil by water vapor distillation method or supercritical extraction method for standby; add water 5-10 times to the residue of Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos and the rest of crude drugs by proportion, decoct for two to three times, combine the filtrate, concentrate the filtrate to equivalent to 5g of crude drug per milliliter; adopt flocculation and sedimentation method, stand for 22 hours, centrifugal filter, centrifugal speed is 4980r / min, add volatile oil of Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos to the filtrate, mix, add sodium benzoate 2g and nipagin ethyl 0.23g, filter and cool, add water to 480ml, fill in hot and get.

[0037] Example 5 (preparation of mixture)

[0038] Take Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos 7 days' quantity by proportion, crush to 10-40 meshes, extract volatile oil by water vapor distillation method or supercritical extraction method for standby; add water 5-10 times to the residue of Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos and the rest of crude drugs by proportion, decoct for two to three times, combine the filtrate, concentrate the filtrate to equivalent to 5g of crude drug per milliliter; adopt flocculation and sedimentation method, stand for 24 hours, centrifugal filter, centrifugal speed is 5000r / min, add volatile oil of Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos to the filtrate, mix, add sodium benzoate 3g and nipagin ethyl 0.25g (which has been dissolved in water), filter and cool, add water to 500ml, fill in hot and get.

[0039] Example 6 (preparation of mixture)

[0040] Take Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos 8 days' quantity by proportion, crush to 10-40 meshes, extract volatile oil by water vapor distillation method or supercritical extraction method for standby; add water 5-10 times to the residue of Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos and the rest of crude drugs by proportion, decoct for two to three times, combine the filtrate, concentrate the filtrate to equivalent to 5g of crude drug per milliliter; adopt flocculation and sedimentation method, stand for 26 hours, centrifugal filter, centrifugal speed is 5020r / min, add volatile oil of Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos to the filtrate, mix, add sodium benzoate 4g and nipagin ethyl 0.27g, filter and cool, add water to 520ml, fill in hot and get.

[0041] Example 7 (preparation of granules)

[0042] Take Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos 8 days' quantity by proportion, crush to 10-40 meshes, extract volatile oil by water vapor distillation method or supercritical extraction method for standby; add water 5-10 times to the residue of Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos and the rest of crude drugs by proportion, decoct for two to three times, combine the filtrate, concentrate the filtrate to equivalent to 5g of crude drug per milliliter; adopt flocculation and sedimentation method, stand for 26 hours, centrifugal filter, centrifugal speed is 5020r / min, add volatile oil of Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos to the filtrate, mix, add sodium benzoate 4g and nipagin ethyl 0.27g, filter and cool, add water to 520ml, fill in hot and get.

[0043] Example 8 (preparation of granules)

[0044] The raw medicine is weighed according to the proportion, and then boiled in water for 2-3 times with 10 times and 8 times of water respectively. The filtrate is combined and concentrated to 5g / ml. Then 3 times of alcohol is added to the concentrated solution to reach 60% of alcohol content. The solution is cooled and stored for 24 hours, filtered, and then the alcohol is recovered to remove the alcohol smell. The recovered solution is concentrated to 1.25-1.30 (room temperature), and then dextrin or starch is added to make granules of 500g, which are packed.

[0045] Example 9 (preparation of granules)

[0046] The raw medicine is weighed according to the proportion, and then boiled in water for 2-3 times with 11 times and 9 times of water respectively. The filtrate is combined and concentrated to 5g / ml. Then 4 times of alcohol is added to the concentrated solution to reach 60% of alcohol content. The solution is cooled and stored for 26 hours, filtered, and then the alcohol is recovered to remove the alcohol smell. The recovered solution is concentrated to 1.25-1.30 (room temperature), and then dextrin or starch is added to make granules of 520g, which are packed.

[0047] Example 10 (preparation of granules)

[0048] The rehmannia, salvia miltiorrhiza and safflower are weighed according to the proportion, and then powdered to 10-40 mesh. The volatile oil is extracted by steam distillation or supercritical extraction method. The residues of the rehmannia, salvia miltiorrhiza and safflower are boiled in water for 2-3 times with 5-10 times of water respectively. The filtrate is combined and concentrated to 5g / ml. The solution is stored for 22 hours by flocculation and precipitation method, centrifuged and filtered, mixed, concentrated to 1.25-1.30 (room temperature), and then dextrin or starch is added to make granules of 480g, which are packed.

[0049] Example 11 (preparation of granules)

[0050] The rehmannia, salvia miltiorrhiza and safflower are weighed according to the proportion, and then powdered to 10-40 mesh. The volatile oil is extracted by steam distillation or supercritical extraction method. The residues of the rehmannia, salvia miltiorrhiza and safflower are boiled in water for 2-3 times with 5-10 times of water respectively. The filtrate is combined and concentrated to 5g / ml. The solution is stored for 24 hours by flocculation and precipitation method, centrifuged and filtered, mixed, concentrated to 1.25-1.30 (room temperature), and then dextrin or starch is added to make granules of 500g, which are packed.

[0051] Example 12 (preparation of granules)

[0052] The Rehmannia glutinosa, Salvia miltiorrhiza and Crocus sativus were weighed according to the proportion, crushed to 10-40 meshes, and the volatile oil was extracted by steam distillation or supercritical extraction method for standby; the residues of Rehmannia glutinosa, Salvia miltiorrhiza and Crocus sativus were added with water in an amount of 5-10 times, decocted for two to three times, the filtrates were combined, concentrated to 5 grams of crude drug per milliliter; the flocculation and precipitation method of chitosan was used, and the mixture was left to stand for 26 hours, centrifuged and filtered, mixed, the mixture was concentrated to a relative density of 1.25-1.30 (room temperature), and then a proper amount of dextrin or starch and volatile oil β-cyclodextrin inclusion compound of Rehmannia glutinosa, Salvia miltiorrhiza and Crocus sativus were added, and the granules were prepared by wet granulation or one-step granulation method, and then dried at low temperature or vacuum, to obtain 520 grams of granules.

[0053] The beneficial effects of the medicine according to the present application are further illustrated by the following test examples, which use the traditional Chinese medicine composition (hereinafter also referred to as the kidney-tonifying and blood-activating formula) according to the present application:

[0054] Test Example (Clinical Study on the Intervention of Kidney-tonifying and Blood-activating Formula on Atherosclerosis Combined with Hyperhomocysteinemia)

[0055] 1. Test subjects

[0056] The cases treated in the outpatient department, ward and atherosclerosis specialist clinic of Geriatrics Department of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, and the ward of Shanghai Jinshan District Zhongren Geriatric Care Hospital from January 1, 2022 to January 1, 2024 were selected for this study. The test cases must meet the Western medical diagnostic criteria for carotid atherosclerosis and hyperhomocysteinemia, and the diagnostic criteria for kidney deficiency and blood stasis type in traditional Chinese medicine. According to the random number table method, the cases were randomly divided into the integrated traditional Chinese and Western medicine group and the Western medicine group, and then followed up for 3 months.

[0057] 2. Test design

[0058] According to the random number table method, the patients with kidney deficiency and blood stasis type carotid atherosclerosis combined with hyperhomocysteinemia were randomly divided into the integrated traditional Chinese and Western medicine group and the Western medicine group.

[0059] (1) Integrated traditional Chinese and Western medicine group: among the kidney deficiency and blood stasis type CAS combined with Hhcy patients included, the kidney-tonifying and blood-activating formula and moderate-intensity statin (atorvastatin 10 mg, see treatment regimen) were used for treatment, which was defined as the integrated traditional Chinese and Western medicine group. The original treatment regimen was maintained, including drug treatment of hypertension, diabetes, hyperuricemia, coronary heart disease, etc.

[0060] (2) Western medicine group: among the included patients with kidney deficiency and blood stasis type CAS combined with Hhcy, moderate intensity statin therapy [19-20] (atorvastatin 10 mg) was used, which was defined as the western medicine group. The original treatment plan was maintained, including drug treatment of hypertension, diabetes, hyperuricemia, coronary heart disease, etc.

[0061] 3. Treatment plan

[0062] (1) Control group: according to the recommendations of the China Lipid Management Guidelines (2023)

[19] , it is recommended to use moderate intensity statins (atorvastatin 10-20 mg, rosuvastatin 5-10 mg, pitavastatin 1-4 mg, pravastatin 40 mg, simvastatin 20-40 mg, Xuezhi Kang 1.2 g) as the initial drug treatment on the basis of lifestyle intervention, so this topic uses atorvastatin 10 mg QN lipid-lowering treatment on the basis of western anti-coagulation and anti-platelet.

[0063] (2) Treatment group: on the basis of western anti-coagulation and anti-platelet, moderate intensity statins (atorvastatin 10 mg QN) and traditional Chinese medicine compound Shenshu Huoxue Decoction (prescription composition: Radix Rehmanniae Preparata 15g, Herba Cistanche 12g, Radix Astragali 15g, Rhizoma Cyperi 6g, Radix Salviae Miltiorrhizae 15g, Flos Carthami 6g, this preparation is a traditional Chinese medicine decoction, which is provided by Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, and the method of taking is: 1 bag each time, 1 time in the morning and 1 time in the evening, taken after meals) are used for treatment.

[0064] (3) The treatment course of both groups is 12 weeks, and the treatment group and the control group are prohibited from using other traditional Chinese medicine preparations related to the treatment of this disease.

[0065] 4. Observation index:

[0066] (1) General information: name, age, gender, combined medication, history of allergy, etc.

[0067] (2) Physical examination: heart rate, blood pressure, respiration, body weight, recorded before treatment, 4 weeks and 12 weeks after treatment.

[0068] (3) Compliance observation: whether the patient can take the medicine on time and in the right amount; whether the patient takes other drugs by himself / herself. Observation and recording are performed every 4 weeks.

[0069] (4) Safety observation: ① blood, urine, and stool routine, liver and kidney function, blood glucose, creatine kinase, electrocardiogram, etc., recorded before treatment, 4 weeks and 12 weeks after treatment. ② Adverse reactions occurring after drug administration are observed and recorded in real time.

[0070] (5) Efficacy observation: detected and recorded before treatment and 12 weeks after treatment.

[0071] Main efficacy index:

[0072] ① Carotid artery structure detection Carotid artery ultrasound examination of cIMT and plaque area. Detection instrument: Bensheng magic 90 expert version of ultrasonic diagnostic instrument, pulse probe for 10-13 MHZ, by the same skilled operator using the same instrument hidden random grouping is completed.

[0073] ② Serum homocysteine (Homocysteine, Hcy) detection instrument: automatic biochemical detector (model: 7170, HITACHI company). Completed by the inspection department of Shanghai University of Chinese Medicine Affiliated Longhua Hospital.

[0074] Secondary efficacy index:

[0075] ① Blood lipid metabolism detection detection instrument: biochemical detector, model 7170, Hitachi company. Completed by the inspection department of Shanghai University of Chinese Medicine Affiliated Longhua Hospital.

[0076] ② TCM syndrome score According to the TCM syndrome score table, the score is recorded. The main symptoms are divided into four levels: no, light, medium and heavy, respectively, 0, 2, 4 and 6 points, and the secondary symptoms are divided into four levels: no, light, medium and heavy, respectively, 0, 1, 2 and 3 points.

[0077] ③ After completing 12 weeks of clinical observation, continue to take medicine for 12 weeks to observe the hard endpoint, and finally compare the average medication time, acute coronary syndrome, acute cerebrovascular accident and the incidence of endpoint events of the two groups.

[0078] 5. Results

[0079] 5.1 General information

[0080] This study a total of 72 cases, including 36 cases of integrated traditional Chinese and Western medicine group, 36 cases of Western medicine group. During the treatment, 1 case of each group dropped out, the loss rate was 2.7%. Finally, 70 cases of subjects completed 3 months of observation and follow-up and were included in statistical analysis, 35 cases in each group. The reason for 1 case of subjects dropping out in the integrated traditional Chinese and Western medicine group was that no adverse reactions occurred after taking medicine on time for 1 month, but still refused to follow-up and follow-up. The reason for 1 case of subjects dropping out in the Western medicine group was that he took Chinese medicine with the effect of promoting blood circulation and unblocking collaterals after 1 month of entering the group, and refused to follow-up and review.

[0081] The youngest patient was 64 years old and the oldest was 106 years old. There were 29 males (41.4%) and 41 females (58.6%). The average BMI was 23.38±0.99. Three patients (4.3%) had a history of smoking and three patients (4.3%) had a history of drinking. In terms of dietary habits, 16 patients (22.9%) chose light diet, 26 patients (37.1%) chose regular diet, 24 patients (34.3%) chose fatty diet, and 4 patients (5.7%) chose salty diet. In terms of underlying diseases, 36 patients (51.4%) had hypertension, 20 patients (28.6%) had diabetes, 21 patients (30.0%) had hyperlipidemia, 8 patients (11.4%) had hyperuricemia, 48 patients (68.6%) had cerebrovascular disease, and 54 patients (77.1%) had coronary heart disease.

[0082] 5.2 Main efficacy index evaluation

[0083] 5.2.1 Comparison of maximum plaque area before and after treatment

[0084] Intracompartmental comparison: The maximum plaque area of the integrated Chinese and Western medicine group before and after treatment had significant difference (Z=-5.159, P<0.01), indicating that integrated Chinese and Western medicine treatment could effectively reduce plaque area; the maximum plaque area of the Western medicine group before and after treatment showed no significant difference (Z=-1.163, P=0.245>0.05), indicating that simple Western medicine treatment had no obvious effect on reducing plaque area, as shown in Table 1.

[0085] Inter-group comparison: The median difference of the maximum plaque area of the integrated Chinese and Western medicine group before and after treatment was -6.92mm 2 , and the median difference of the maximum plaque area of the Western medicine group before and after treatment was 4.85mm 2 . Independent sample Mann-Whitney U test showed Z=-3.641, P<0.01. This suggests that integrated Chinese and Western medicine treatment is more effective in reducing the maximum plaque area of patients with carotid artery.

[0086] Table 1. Comparison of maximum plaque area before and after treatment [M(P25, P75), mm 2 ]

[0087]

[0088] Note: *Intracompartmental comparison P<0.05, **Intracompartmental comparison P<0.01, ▲Inter-group comparison P<0.05, ▲▲Inter-group comparison P<0.01. The following charts are the same.

[0089] 5.2.2 Maximum plaque area regression efficiency after treatment

[0090] The total number of subjects followed up for 3 months was 70, including 35 cases in the combined group, of which 2 cases were cured, 4 cases were markedly effective, 9 cases were effective, and 20 cases were ineffective, with a total effective rate of 42.9%; 35 cases in the western medicine group, of which there was no cure, only 1 case was markedly effective, 3 cases were effective, and 31 cases were ineffective, with a total effective rate of 11.4%. Chi-square test results showed that the combined group and the western medicine group had significant differences in the effective rate of maximum plaque area regression (χ 2 = 8.741, P = 0.003 < 0.01), as shown in Table 2. The combined treatment of traditional Chinese and western medicine can more effectively regress the carotid plaque area of patients.

[0091] Table 2. Comparison of total effective rate of maximum plaque area regression between groups after treatment (cases)

[0092]

[0093] 5.2.3 Comparison of CIMT values before and after treatment

[0094] Intra-group comparison: Z = -4.492, P < 0.01 in the combined group, and Z = -4.399, P < 0.01 in the western medicine group. Combined with the specific values, it can be found that the CIMT value in the combined group was significantly reduced, while the CIMT value in the western medicine group was increased, as shown in Table 3.

[0095] Inter-group comparison: the median difference of CIMT before and after treatment was -0.10 in the combined group, and 0.10 in the western medicine group. Independent sample Mann-Whitney U test showed Z = -6.599, P < 0.01, as shown in Table 3. It is suggested that the difference in CIMT change value between the two groups is significant, indicating that the combined group is superior to the western medicine group in reducing CIMT value.

[0096] Table 3. Comparison of CIMT values before and after treatment [M(P25, P75)]

[0097]

[0098] 5.2.4 Soft plaque effective conversion rate after treatment

[0099] The total number of patients followed up for 3 months was 70, including 35 cases in the combined group and 35 cases in the western medicine group. Before treatment, there were 21 cases of soft plaque in the combined group, and after treatment, 2 cases of plaque disappeared and 9 cases converted to mixed plaque or hard plaque; before treatment, there were 14 cases of soft plaque in the western medicine group, and after treatment, 2 cases converted to mixed plaque or hard plaque. Chi-square test results showed that there was a statistical difference between the combined group and the western medicine group in the conversion of soft plaque (χ 2=5.221, P=0.022<0.05). It suggested that the combination of traditional Chinese and western medicine treatment was better in soft plaque transformation, and could better play a role in stabilizing the plaque. See Table 4.

[0100] Table 4. Comparison of effective rate of soft plaque transformation after treatment (cases, %)

[0101]

[0102] 5.2.5 Comparison of homocysteine index values before and after treatment

[0103] Intra-group comparison: Z=-5.161, P<0.01 in the combination of traditional Chinese and western medicine group, and Z=-5.160, P<0.01 in the western medicine group. According to the specific numerical value, it was found that the homocysteine index value in the combination of traditional Chinese and western medicine group was significantly lower than before, and the homocysteine index value in the western medicine group was increased instead. See Table 5.

[0104] Inter-group comparison: The median of the difference in homocysteine index value before and after treatment was-1.70 in the combination of traditional Chinese and western medicine group, and 2.20 in the western medicine group. By independent sample Mann-Whitney U test, Z=-7.196, P<0.01. See Table 5. It suggested that the difference in the change value of homocysteine index before and after treatment was significant in the two groups, indicating that the combination of traditional Chinese and western medicine group was superior to the western medicine group in reducing homocysteine.

[0105] Table 5. Comparison of homocysteine index values before and after treatment [M(P25, P75), umol / L]

[0106]

[0107] 5.3 Evaluation of secondary efficacy indicators

[0108] 5.3.1 Comparison of blood lipid indicators before and after treatment

[0109] 5.3.1.1 Comparison of blood lipid TG indicators before and after treatment

[0110] Intra-group comparison: T=6.677, P<0.01 in the combination of traditional Chinese and western medicine group, and T=4.780, P<0.01 in the western medicine group. It was indicated that the blood lipid TG indicators in the two groups were lower than before treatment. See Table 6.

[0111] Inter-group comparison: The median of the difference in blood lipid TG before and after treatment was-0.09 mmol / L in the combination of traditional Chinese and western medicine group, and-0.09 mmol / L in the western medicine group. By independent sample Mann-Whitney U test, Z=-0.600, P=0.549>0.05. See Table 6. It suggested that after 3 months of intervention, simple western medicine treatment and the combination of traditional Chinese and western medicine treatment could effectively reduce the blood lipid TG indicators, and there was no significant difference in the efficacy of the two.

[0112] Table 6. Comparison of blood lipid TG index before and after treatment [M(P25, P75), mmol / L]

[0113]

[0114] 5.3.1.2 Comparison of blood lipid TC index before and after treatment

[0115] Intra-group comparison: T = 5.154, P < 0.01 in the combination group, T = 4.544, P < 0.01 in the western medicine group, indicating that the blood lipid TC index in both groups was lower than before treatment, as shown in Table 7.

[0116] Inter-group comparison: The median difference of blood lipid TC before and after treatment was -0.27 mmol / L in the combination group, and -0.21 mmol / L in the western medicine group. Independent sample Mann-Whitney U test showed Z = -0.159, P = 0.874 > 0.05, as shown in Table 7. It was suggested that after 3 months of intervention, simple western medicine treatment and combination treatment could effectively reduce the blood lipid TC index, and there was no significant difference between the two.

[0117] Table 7. Comparison of blood lipid TC index before and after treatment [M(P25, P75), mmol / L]

[0118]

[0119] 5.3.1.3 Comparison of blood lipid HDL-C index before and after treatment

[0120] Intra-group comparison: Paired sample T test before and after treatment showed T = -4.740, P < 0.01 in the combination group, and T = -7.973, P < 0.01 in the western medicine group, indicating that the blood lipid HDL-C in both groups was higher than before treatment, as shown in Table 8.

[0121] Inter-group comparison: The median difference of blood lipid HDL-C before and after treatment was 0.11 mmol / L in the combination group, and 0.10 mmol / L in the western medicine group. Independent sample Mann-Whitney U test showed Z = -0.523, P = 0.601 > 0.05, as shown in Table 8. It was suggested that after 3 months of intervention, simple western medicine treatment and combination treatment could effectively improve the blood lipid HDL-C index, and there was no significant difference between the two.

[0122] Table 8. Comparison of blood lipid HDL-C index before and after treatment [M(P25, P75), mmol / L]

[0123]

[0124] 5.3.1.4 Comparison of blood lipid LDL-C index before and after treatment

[0125] Intra-group comparison: T=5.475, P<0.01 in the combination group, T=4.993, P<0.01 in the western medicine group, indicating that the LDL-C index of both groups was reduced compared with before treatment, as shown in Table 9.

[0126] Inter-group comparison: The median difference of LDL-C before and after treatment was -0.18 mmol / L in the combination group, and -0.13 mmol / L in the western medicine group. The independent sample Mann-Whitney U test showed Z=-2.069, P=0.039<0.05, as shown in Table 9. It was suggested that after 3 months of intervention, compared with simple western medicine treatment, the combination of traditional Chinese medicine and western medicine treatment had more benefits in reducing LDL-C.

[0127] Table 9. Comparison of LDL-C index before and after treatment (mmol / L) [M(P25, P75), mmol / L]

[0128]

[0129] 5.3.2 Reduction in TCM syndrome score

[0130] Intra-group comparison: T=9.852, P<0.01 in the combination group, T=5.770, P<0.01 in the western medicine group, indicating that the TCM syndrome score of both groups was reduced compared with before treatment, as shown in Table 10.

[0131] Inter-group comparison: The median difference of TCM syndrome score before and after treatment was -9.00 in the combination group, and -6.00 in the western medicine group. The independent sample Mann-Whitney U test showed Z=-3.001, P=0.003<0.01, as shown in Table 10. It was suggested that simple western medicine treatment and combination of traditional Chinese medicine and western medicine treatment could both reduce the TCM syndrome score, but the combination of traditional Chinese medicine and western medicine treatment could more effectively improve the TCM syndrome score on the basis of western medicine treatment.

[0132] Table 10. TCM syndrome score before and after treatment

[0133]

[0134] There were 35 cases in each group who were followed up for 3 months. In the combination group, there were 0 cases of cure, 3 cases of marked effectiveness, 21 cases of effectiveness, and 11 cases of invalid, with a total effective rate of 68.6%; in the western medicine group, there were 0 cases of cure, 1 case of marked effectiveness, 10 cases of effectiveness, and 24 cases of invalid, with a total effective rate of 31.4%. The chi-square test result showed that there was a significant difference in the reduction of TCM syndrome score between the combination group and the western medicine group (χ2=4.000, P=0.045<0.05). 2= 9.657, P = 0.002 < 0.01), see Table 11. It is shown that the TCM syndrome score can be improved more effectively by taking the TCM compound recipe of Bushen Huoxue recipe on the basis of western medicine treatment.

[0135] Table 11. Comparison of effective rate of TCM syndrome score reduction between groups (cases)

[0136]

[0137] 5.4 Endpoint events

[0138] After 12 weeks of follow-up, there were no major endpoint events in 35 patients in the integrated TCM and Western medicine group, and one case of secondary endpoint event occurred; there were 35 patients in the Western medicine group, one case of major endpoint event occurred, and 11 cases of secondary endpoint event occurred.

[0139] The number of cases of major endpoint events, secondary endpoint events, and cumulative endpoint events in the two groups were compared by chi-square test. The results showed that the number of cases of major endpoint events: χ 2 = 1.014, P = 0.314 > 0.05, indicating that there was no significant statistical difference in the number of major endpoint events between the two groups; the number of cases of secondary endpoint events: χ 2 = 10.057, P = 0.002 < 0.01, indicating that the number of secondary endpoint events in the integrated TCM and Western medicine group was significantly lower than that in the Western medicine group; the number of cases of cumulative endpoint events: χ 2 = 11.430, P < 0.01, indicating that the number of cumulative endpoint events in the integrated TCM and Western medicine group was significantly lower than that in the Western medicine group; it is shown that the TCM compound recipe of Bushen Huoxue recipe on the basis of western medicine treatment can significantly reduce the incidence of secondary endpoint events and cumulative endpoint events, see Table 12.

[0140] Table 12. Comparison of the number of endpoint events between the two groups (cases, %)

[0141]

[0142] 5.5 Safety indicators

[0143] In this study, none of the patients had allergic symptoms during treatment, and the results of liver function, kidney function, and creatine kinase tests of all patients were also within the normal range. Due to the low frequency of adverse events, there was no significant difference in statistics.

Claims

1. A traditional Chinese medicine composition for treating atherosclerosis combined with hyperhomocysteinemia, characterized in that, The traditional Chinese medicine composition is a medicine prepared from the following raw materials: Radix Rehmanniae Preparata 12-15 parts, Herba Cistanche 9-12 parts, Radix Astragali 12-15 parts, Rhizoma Cyperi 6-9 parts, Salvia miltiorrhiza 15-30 parts, and Flos Carthami 6-9 parts.

2. The Chinese medicine composition for treating atherosclerosis combined with hyperhomocysteinemia according to claim 1, characterized in that, The weight parts of each raw material are as follows: Radix Rehmanniae Preparata 15 parts, Herba Cistanche 12 parts, Radix Astragali 15 parts, Rhizoma Cyperi 6 parts, Salvia miltiorrhiza 15 parts, and Flos Carthami 6 parts.

3. The traditional Chinese medicine composition for treating atherosclerosis combined with hyperhomocysteinemia according to claim 1 or 2, characterized in that, The medicine is a mixture.

4. The Chinese medicine composition for treating atherosclerosis combined with hyperhomocysteinemia according to claim 1 or 2, characterized in that, The medicine is a granule.

5. The preparation method of the Chinese medicine composition mixture of claim 3, characterized in that, The method comprises the following steps: The raw materials are weighed according to the proportion, and then boiled with 9-11 times and 7-9 times of water respectively for two to three times. The filtrates are combined and concentrated to 5g / ml. The concentrated solution is added with 2-4 times of ethanol, and then stored in cold storage for 22-26 hours. The filtrate is recovered to remove the ethanol. The recovered solution is boiled, added with sodium benzoate and nipagin, and then filtered and cooled. Water is added to 480-520ml, and then the mixture is filled into bottles while hot to obtain the granule.

6. The preparation method of the Chinese medicine composition mixture of claim 3, characterized in that, The method comprises the following steps: The Radix Rehmanniae Preparata, Salvia miltiorrhiza, and Flos Carthami are ground to 10-40 meshes, and then the volatile oil is extracted by steam distillation or supercritical extraction method. The residues of the Radix Rehmanniae Preparata, Salvia miltiorrhiza, and Flos Carthami are boiled with 5-10 times of water respectively with the rest of the raw materials, and then the filtrates are combined and concentrated to 5g / ml. The mixture is stored in cold storage for 22-26 hours, and then centrifuged and filtered. The mixture is concentrated to 1.25-1.30, and then added with the volatile oil of the Radix Rehmanniae Preparata, Salvia miltiorrhiza, and Flos Carthami, and the β-cyclodextrin inclusion compound. The mixture is granulated by wet granulation or one-step granulation method, and then dried at low temperature or in vacuum to obtain the granule.

7. The preparation method of the granules of the traditional Chinese medicine composition of claim 4, characterized in that, The method comprises the following steps: The raw materials are weighed according to the proportion, and then boiled with 9-11 times and 7-9 times of water respectively for two to three times. The filtrates are combined and concentrated to 5g / ml. The concentrated solution is added with 2-4 times of ethanol, and then stored in cold storage for 22-26 hours. The filtrate is recovered to remove the ethanol, and then concentrated to 1.25-1.

30. The mixture is added with dextrin or starch, and then granulated by wet granulation to obtain the granule.

8. The preparation method of the granules of the traditional Chinese medicine composition of claim 4, characterized in that, The method comprises the following steps: The Radix Rehmanniae Preparata, Salvia miltiorrhiza, and Flos Carthami are ground to 10-40 meshes, and then the volatile oil is extracted by steam distillation or supercritical extraction method. The residues of the Radix Rehmanniae Preparata, Salvia miltiorrhiza, and Flos Carthami are boiled with 5-10 times of water respectively with the rest of the raw materials, and then the filtrates are combined and concentrated to 5g / ml. The mixture is stored in cold storage for 22-26 hours, and then centrifuged and filtered. The mixture is concentrated to 1.25-1.30, and then added with the volatile oil of the Radix Rehmanniae Preparata, Salvia miltiorrhiza, and Flos Carthami, and the β-cyclodextrin inclusion compound. The mixture is granulated by wet granulation or one-step granulation method, and then dried at low temperature or in vacuum to obtain the granule.

9. The use of the traditional Chinese medicine composition of any one of claims 1-4 in the preparation of a medicine for treating atherosclerosis combined with hyperhomocysteinemia.

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