Application of traditional Chinese medicine compound preparation in preparation of medicine for treating hyperlipemia

Abstract

The invention relates to the technical field of traditional Chinese medicines, in particular to application of a traditional Chinese medicine compound preparation in preparation of a medicine for treating hyperlipidemia, and the traditional Chinese medicine compound preparation is prepared from the following raw material medicines: polygonum cuspidatum, gardenia, hypericum japonicum, turmeric and oriental wormwood. According to the traditional Chinese medicine compound preparation disclosed by the invention, through clinical test verification of hyperlipemia patients, the result proves that LDL-C and TC levels of the hyperlipemia (damp-heat accumulation syndrome) patients can be obviously reduced, the curative effect is obviously higher than that of a control group in 12 weeks, and no obvious adverse reaction is found; the compound can be used for preparing medicines for preventing and treating hyperlipemia.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, in particular to the use of a traditional Chinese medicine compound preparation in the preparation of a medicine for treating hyperlipidemia. Background Art

[0002] Hyperlipidemia is a common chronic metabolic disease caused by systemic lipid metabolism disorders, characterized by elevated low-density lipoprotein cholesterol (LDL-C) or total cholesterol and decreased high-density lipoprotein cholesterol (HDL-C), also known as dyslipidemia.

[0003] Hyperlipidemia, which can be categorized as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low high-density lipoprotein cholesterol, is a significant risk factor for coronary atherosclerotic cardiovascular disease. Hyperlipidemia, including familial hypercholesterolemia, increases the risk of major cardiovascular events. Levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) are positively correlated with the risk of ischemic cerebrovascular disease. Furthermore, hyperlipidemia is also a contributing factor to fatty liver disease and several metabolic-related diseases.

[0004] Hyperlipidemia is treated by applying lipid-lowering drugs on top of a healthy diet, improved sleep and exercise routine. Currently, lipid-lowering drugs are primarily categorized as cholesterol-lowering and TG-lowering drugs, with statins being the cornerstone of hyperlipidemia treatment. Statins reduce cholesterol synthesis and metabolism in the liver, thereby lowering cholesterol. Clinically, a variety of statins are available, but all have certain self-limiting effects and adverse reactions. For example, when a double dose of statins is used, the increase in efficacy is only approximately 6%. Statins also commonly cause adverse reactions such as abnormal liver function and creatine myalgia. In severe cases, severe symptoms such as rhabdomyolysis and renal failure may occur. Therefore, there remains a significant market demand for safe, effective, and cost-effective lipid-lowering drugs.

[0005] In traditional Chinese medicine (TCM) clinical practice, it is believed that the TCM pathogenesis of hyperlipidemia is the imbalance of zang-fu organs' functions, qi, blood, and body fluids caused by various etiologies, which can result in phlegm turbidity and blood stasis. When phlegm-dampness blocks and obstructs, the vessels become unsmooth, and over time, it turns into heat, leading to the accumulation of damp-heat, which adheres to the vessels, and can form the damp-heat accumulation syndrome of hyperlipidemia. The efficacy of TCM in treating hyperlipidemia has been widely confirmed by clinical practice. Currently, there are many reports on the lipid-lowering effects of traditional Chinese medicines and their active ingredients, but there is a lack of evidence-based verification and transformation from high-quality clinical trials. Therefore, there is a need to develop new TCM compositions with definite efficacy, safety, and reasonable prices for the prevention and treatment of hyperlipidemia.

[0006] The Qushi Huayu Formula has obtained a patent authorization for the treatment of non-alcoholic fatty liver disease (Patent No.: ZL200610009140.0). This application is for a new indication. Hyperlipidemia and non-alcoholic fatty liver disease (NAFLD) are two completely different diseases, and the treatment strategies for the two diseases are completely different. According to the Chinese Guidelines for Lipid Management 2023 and the Chinese Guidelines for Lipid Management for Primary Care 2024, LDL-C is the primary target for lipid intervention, and its purpose is mainly for the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Statins, as the cornerstone drugs for hyperlipidemia, are only recommended for NAFLD patients with combined lipid disorders. So far, there is a lack of histological evidence for statins to improve liver inflammation and fibrosis (2024 Edition of the Guidelines for the Prevention and Treatment of Metabolic (Non-alcoholic) Fatty Liver Disease). In terms of NAFLD, currently only Resmetirom has been approved by the US Food and Drug Administration for the treatment of patients with metabolic-associated fatty hepatitis with significant fibrosis, and this drug has no clinical indication for hyperlipidemia. Therefore, it is of great significance to discover effective treatment compounds for hyperlipidemia. Summary of the Invention

[0007] The purpose of the present invention is to overcome the defects and deficiencies of the prior art and provide the use of a traditional Chinese medicine compound preparation (hereinafter referred to as the Qushi Huayu Formula) composed of Polygonum cuspidatum, Gardenia jasminoides, Hypericum japonicum, Curcuma longa, and Artemisia capillaris in the preparation of a drug for the treatment of hyperlipidemia.

[0008] The Qushi Huayu Formula was previously applied to the clinical prevention and treatment of MAFLD and obtained patent protection (Patent No. ZL200610009140.0). In clinical applications, it was found that it also has good efficacy for patients with damp-heat type hyperlipidemia. Considering the differences between hyperlipidemia and MAFLD diseases, an application for the use in the treatment of hyperlipidemia is filed from the perspective of expanding the indication.

[0009] In the first aspect of the present invention, there is provided an application of a traditional Chinese medicine compound preparation in the preparation of a medicament for treating hyperlipidemia. The raw materials of the traditional Chinese medicine compound preparation are composed of traditional Chinese medicinal materials Herba Artemisiae Scopariae, Polygonum Cuspidatum Sieb. et Zucc., Gardenia jasminoides Ellis, Curcuma longa L., and Hypericum japonicum Thunb. The weight percentages of the components in the raw materials are as follows: Herba Artemisiae Scopariae 26% - 38%, Polygonum Cuspidatum Sieb. et Zucc. 14% - 23%, Hypericum japonicum Thunb. 14% - 23%, Curcuma longa L. 14% - 23%, and Gardenia jasminoides Ellis 14% - 23%. The components in the raw materials are extracted by the following method: Herba Artemisiae Scopariae, Polygonum Cuspidatum Sieb. et Zucc., and Curcuma longa L. are extracted with ethanol three times, each time for 1 - 2 hours; Gardenia jasminoides Ellis and Hypericum japonicum Thunb. are decocted together, that is, Gardenia jasminoides Ellis and Hypericum japonicum Thunb. are soaked in water for 1 hour, added with 8 - 10 times of water, extracted three times, and the water extract is concentrated to a relative density of 1.08 - 1.12, and the temperature for measuring the relative density is 80°C, and purified by ethanol precipitation method, centrifugation method or chitosan clarification method.

[0010] Further, the traditional Chinese medicine compound preparation is an oral preparation such as granules, tablets or capsules. Among them, the granules are prepared by adding dextrin after combining the ethanol extract and the water extract, spray-drying to form a fine powder, and granulating by dry granulation method.

[0011] Further, the hyperlipidemia is hyperlipidemia of the type of accumulation of dampness and heat as judged by the diagnostic criteria of traditional Chinese medicine syndromes.

[0012] Further, the hyperlipidemia is characterized by fasting LDL-C > 3.4 mmol / L and is judged to be the syndrome of accumulation of dampness and heat according to the diagnostic criteria of traditional Chinese medicine syndromes. Main symptoms: obese body, general heaviness and discomfort, heavy head as if wrapped, vomiting and expectorating phlegm, numbness and heaviness of limbs, distension and fullness in the chest and hypochondrium, sticky and unsmooth stools. Secondary symptoms: palpitations, insomnia, restlessness, yellowish urine, sticky feeling in the mouth, dry mouth and bitter taste. Tongue and pulse manifestations: red tongue, yellow and greasy tongue coating, string-like and slippery or soggy and rapid pulse.

[0013] Further, the application of the traditional Chinese medicine compound preparation in the preparation of a medicament for reducing the levels of LDL-C and TC in patients with hyperlipidemia (syndrome of accumulation of dampness and heat).

[0014] The advantages of the present invention are as follows:

[0015] 1. The traditional Chinese medicine compound preparation of the present invention is composed of 5 traditional Chinese medicines, namely Polygonum Cuspidatum Sieb. et Zucc., Hypericum japonicum Thunb., Curcuma longa L., Herba Artemisiae Scopariae, and Gardenia jasminoides Ellis, and has the effects of clearing heat, promoting diuresis, detoxifying, activating blood circulation and removing stasis. In the formula, both Polygonum Cuspidatum Sieb. et Zucc. and Hypericum japonicum Thunb. have the effects of clearing heat, promoting diuresis, activating blood circulation and removing stasis, and are used as the main drugs together. Curcuma longa L. is used as an adjuvant to promote qi circulation and strengthen the effect of removing stasis; Herba Artemisiae Scopariae and Gardenia jasminoides Ellis are used to assist in clearing heat and resolving dampness and detoxifying.

[0016] 2. The traditional Chinese medicine compound preparation of the present invention has been proven in a prospective randomized, double-blind, placebo-controlled clinical trial participated by patients with hyperlipidemia to significantly reduce the LDL-C and TC levels in patients with hyperlipidemia, and the curative effect at 12 weeks is significantly higher than that of the control group. Moreover, no obvious adverse reactions have been found compared with the control group, and it can be used to prepare drugs for preventing and treating hyperlipidemia. Detailed implementation manners

[0017] The following further elaborates on the specific implementation manners provided by the present invention in conjunction with the embodiments.

[0018] Example 1: Preparation of the traditional Chinese medicine compound preparation of the present invention

[0019] The weight parts of each component are as follows: 16 parts of Artemisia capillaris Thunb., 12 parts of Hypericum japonicum Thunb., 12 parts of Polygonum cuspidatum Sieb. et Zucc., 8 parts of Curcuma longa L., and 8 parts of Gardenia jasminoides Ellis.

[0020] For Artemisia capillaris Thunb., Polygonum cuspidatum Sieb. et Zucc., and Curcuma longa L., they are extracted with ethanol three times, each extraction lasting for 1 to 2 hours. For Gardenia jasminoides Ellis and Hypericum japonicum Thunb., a combined decoction extraction process is adopted, that is, Gardenia jasminoides Ellis and Hypericum japonicum Thunb. are soaked in water for 1 hour, added with 8 to 10 times the amount of water, and extracted three times. After the water extract is concentrated to a relative density of 1.08 - 1.12 (80 °C), purification treatment is carried out. The purification method can be ethanol precipitation method, centrifugation method, or chitosan clarification method. The ethanol extracts of the above Artemisia capillaris Thunb., Polygonum cuspidatum Sieb. et Zucc., and Curcuma longa L. are combined and mixed evenly with the purified extracts of other medicinal flavors obtained by water extraction, dried, added with dextrin, and spray-dried to form fine powder, and then made into granules by dry granulation.

[0021] Example 2: Randomized, double-blind, placebo-controlled trial of using the traditional Chinese medicine compound preparation (Qushi Huayu Prescription) of the present invention to treat hyperlipidemia (syndrome of damp-heat accumulation)

[0022] 1. Materials and methods

[0023] 1.1 Source of cases

[0024] The cases were collected from January 2020 to June 2021 at the outpatient department and wards of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, and a total of 210 cases were included.

[0025] 1.2 Diagnostic criteria

[0026] 1.2.1 Western medicine diagnostic criteria

[0027] Refer to the "Guidelines for the Prevention and Treatment of Dyslipidemia in Chinese Adults". The diagnostic criterion for hyperlipidemia is set as fasting LDL-C > 3.4 mmol / L.

[0028] 1.2.2 Traditional Chinese medicine syndrome diagnostic criteria

[0029] According to the traditional Chinese medicine (TCM) syndrome diagnostic criteria in "Guiding Principles for Clinical Research of New TCM Drugs (Trial Version) in 2002" and "Draft Criteria for TCM Diagnosis and Treatment of Dyslipidemia", it was determined as the syndrome of damp-heat accumulation. Based on the main symptoms: obesity, general heaviness and discomfort, head feeling heavy as if wrapped, nausea and expectoration of phlegm, numbness and heaviness of limbs, chest and hypochondrium distension and fullness, sticky and unsmooth stools. Secondary symptoms: palpitations, insomnia, restlessness, yellowish urine, sticky feeling in the mouth, dry mouth and bitter taste. Tongue and pulse manifestations: red tongue, yellow and greasy tongue coating, string-taut, slippery or soggy and rapid pulse.

[0030] 1.3 Inclusion criteria

[0031] (1) Those who meet the above-mentioned Chinese and Western medicine diagnostic criteria;

[0032] (2) Adults aged over 18 years old;

[0033] (3) 3.4 mmol / L < fasting LDL-C < 4.9 mmol / L;

[0034] (4) Fasting TG < 5.7 mmol / L;

[0035] (5) BMI < 35 kg / m2;

[0036] (6) Agree and be able to execute the scheduled visit plan, including improving diet, strengthening exercise, and completing laboratory tests and other experimental procedures within the follow-up time window;

[0037] (7) Sign the patient informed consent form.

[0038] 1.4 Exclusion criteria

[0039] (1) Those who have used other lipid-lowering drugs within 4 weeks before screening and affect the efficacy evaluation;

[0040] (2) Those with uncontrolled endocrine or metabolic diseases that may interfere with blood lipid levels;

[0041] (3) Patients who are using corticosteroid drugs;

[0042] (4) Those with a history of alcohol or anesthetic drug abuse within 1 year before screening;

[0043] (5) Those at high or very high risk of coronary atherosclerotic heart disease;

[0044] (6) Those with a history of congestive heart failure, unstable angina pectoris, myocardial infarction, stroke, coronary artery bypass surgery or angioplasty, or unstable or severe peripheral arterial disease within 6 months before screening;

[0045] (7) Those who have undergone gastrointestinal weight loss surgery within the past year or those who have taken weight loss drugs and had a weight loss of > 10% within the past 3 months;

[0046] Pregnant women and lactating women

[0047] (9) Suffering from other major diseases such as severe organic diseases or malignant tumors.

[0048] 1.5 Withdrawal criteria

[0049] According to the patient management and protection rules, patients have the right to withdraw from the study at any time for any reason, and it is guaranteed that it will not affect future treatment. In addition, the following events may lead to the termination of treatment for the subjects:

[0050] (1) Any unexpected adverse reaction event;

[0051] (2) Liver function decompensation occurred during the enrollment period;

[0052] (3) Compliance < 80% or > 120%, non-compliance with treatment;

[0053] (4) Pregnancy during the study;

[0054] (5) Intolerable adverse events;

[0055] (6) The occurrence of diseases or factors unrelated to the treatment;

[0056] (7) Loss to follow-up;

[0057] (8) Unblinded cases.

[0058] 1.6 Criteria for terminating cases

[0059] (1) After being evaluated by the principal investigator, it is determined to be a serious adverse reaction event;

[0060] (2) Unstable or severe peripheral arterial diseases, myocardial infarction, coronary artery bypass surgery or angioplasty occurred within 3 months after the start of the study;

[0061] (3) Newly diagnosed diabetes within 1 month after enrollment in the study;

[0062] (4) The occurrence of other serious co-morbidities;

[0063] (5) Violation of the research protocol;

[0064] (6) Death.

[0065] 2 Trial design

[0066] This study is a prospective clinical trial with a randomized, double-blind, placebo-controlled design. The experimental drugs are packaged and coded according to the double-blind requirements, and the drug randomization assignment table is provided by a third-party professional statistician.

[0067] 2.1 Sample size estimation

[0068] Based on the previous clinical observation results of the Qushi Huayu formula in a single center, after treatment with the Qushi Huayu formula group, the fasting TC level decreased by an average of 23.84% compared with the baseline, and the fasting TC level in the control group decreased by an average of 12.71% compared with the baseline. It is predicted that after treatment with the Qushi Huayu formula granules, the decrease level of fasting LDL-C compared with the baseline can be increased by 15% compared with the control group. Assuming α = 0.05, β = 0.2, nT:nC = 1:1, and δ = 0.3, according to the superiority sample size calculation formula, the sample size for each group is 94 cases. Considering a 10% dropout rate, at least 105 cases are required for each group.

[0069] 2.2 Random allocation method

[0070] A third-party data manager uses the SAS Ver 9.1 statistical software to generate a random sequence according to the ratio of 1:1 for each group and seals it as a confidential document in the blind envelope. The random allocation concealment is not lifted until all the data of each subject have been uploaded and locked.

[0071] 2.3 Blinding method

[0072] The double-blind method is adopted to blind the researchers (i.e., medical staff, data managers, and statistical analysts who come into contact with patients during the trial implementation process) and the research subjects (i.e., the subjects). According to the random sequence, the first-level blind envelope and the second-level blind envelope are made in duplicate and properly stored in the sponsor and the clinical responsible unit, and neither party shall damage or unseal them at will. This study adopts the double-blind method. All the blinding processes are recorded. In case of emergency, when breaking the blind for analysis, record the reasons, time, and location of breaking the blind, and the cases of breaking the blind are treated as dropout cases.

[0073] 2.4 Intervention plan

[0074] 2.4.1 Basic treatment

[0075] After the subjects are enrolled, the researchers will conduct health education for them and, during each follow-up, urge them to improve their lifestyle, such as controlling diet, increasing physical exercise, quitting smoking and alcohol, and regular sleep, as the basic treatment.

[0076] (1) Adjust the diet, recommend a low-sugar, low-fat, and high-vitamin diet, in which the fat content is less than 30% of the total daily energy, the protein content accounts for 15%-18% of the total daily energy, and the carbohydrate accounts for 52%-55% of the total daily energy;

[0077] (2) Strengthen physical exercise (exercise for at least 30 minutes each time and exercise 4 times a week);

[0078] (3) Maintain an optimistic and positive attitude;

[0079] (4) During the trial period, Chinese patent medicines and western medicines with lipid-lowering effects are prohibited.

[0080] 2.4.2 Drug Therapy

[0081] (1)Treatment group: Qushi Huayu Fang granule, with a treatment course of 24 weeks;

[0082] (2)Control group: Simulated Qushi Huayu Fang granule, with a treatment course of 24 weeks.

[0083] 2.4.3 Drug Dosage and Administration Method

[0084] The Qushi Huayu Fang granule and its simulated agent are taken 1 packet each time, 2 times a day, and taken with warm water half an hour after meals.

[0085] 2.4.4 Drug Preparation and Simulation

[0086] (1)Qushi Huayu Fang granule: The daily crude drug dosage for adults: 16 grams of Artemisia capillaris, 12 grams of Hypericum japonicum Thunb., 12 grams of Polygonum cuspidatum Sieb. et Zucc., 8 grams of Curcuma longa L., 8 grams of Gardenia jasminoides Ellis. The ready-to-drink granule is prepared by the preparation method of Example 1;

[0087] (2)Simulated Qushi Huayu Fang granule: 10% Qushi Huayu Fang granule and 90% maltodextrin.

[0088] 2.5 Drug Inventory and Storage

[0089] The drugs are stored in the clinical trial base certified by the Good Clinical Practice for drugs, and the drug management and distribution are carried out by designated personnel. At each follow-up, the researchers need to record the patients' medication information in detail and calculate the compliance.

[0090] 3 Clinical Observation Contents

[0091] (1)General information: Age, gender, past medical history, medication history, etc.;

[0092] (2)Adverse event records;

[0093] (3)Observation time window: ±5 days.

[0094] 4 Efficacy Evaluation

[0095] 4.1 Main Efficacy Index

[0096] Percentage change in fasting LDL-C compared with the baseline at 12 weeks of intervention

[0097] 4.2 Secondary Efficacy Index

[0098] (1)Percentage change in fasting LDL-C compared with the baseline at 12 weeks

[0099] (2)Percentage change in fasting TC compared with the baseline at 12 weeks and 24 weeks;

[0100] (3) Percentage change in fasting TG at 12 weeks and 24 weeks compared to baseline;

[0101] (4) Percentage change in fasting HDL-C at 12 weeks and 24 weeks compared to baseline;

[0102] (5) Percentage change in fasting non-HDL-C at 12 weeks and 24 weeks compared to baseline;

[0103] (6) Percentage change in fasting TC / HDL-C at 12 weeks and 24 weeks compared to baseline;

[0104] (7) Percentage change in fasting ApoA-I at 12 weeks and 24 weeks compared to baseline;

[0105] (8) Percentage change in fasting ApoA-II at 12 weeks and 24 weeks compared to baseline;

[0106] (9) Percentage change in fasting ApoB at 12 weeks and 24 weeks compared to baseline;

[0107] 4.5 Observation of adverse events

[0108] (1) The researcher will record in detail the adverse reactions reported by the subjects during each follow-up after enrollment, including the severity of the adverse reactions (none, mild, moderate, severe), as well as the symptoms, onset time, occurrence pattern, factors for exacerbation or alleviation, duration, and resolution time of the adverse reactions;

[0109] (2) The correlation between the occurrence of adverse reactions and the drug;

[0110] (3) Calculate the incidence of adverse reactions = number of cases occurred / total number of cases × 100%;

[0111] (4) Comprehensively evaluate the tolerance of the patients to the drug after treatment;

[0112] (5) Serious adverse events should be reported to the drug regulatory department in a timely manner;

[0113] (6) If moderate or severe adverse reactions judged to be related to the clinical trial occur in more than 25% of the subjects, this clinical trial may be terminated prematurely.

[0114] 4.6 Statistical analysis

[0115] 4.6.1 Statistical software

[0116] The data management and statistical analysis of this trial will be carried out using SPSS Ver 25.0 statistical software.

[0117] 4.6.2 Selection of statistical analysis data

[0118] Full Analysis Set (FAS): Subjects who meet the inclusion and exclusion criteria of the trial, have not been excluded, and have used the trial drug at least once will be included in the FAS. The efficacy of this group of patients will be statistically analyzed. For cases that drop out midway, the last observation will be carried forward to the final trial result (last observation carried forward, LOCF). Safety Analysis Set (SS): Subjects who meet the inclusion and exclusion criteria of the trial, have not been excluded, have used the trial drug at least once, and have at least one post-treatment safety evaluation data record will be included in the SS.

[0119] 4.6.3 Statistical Analysis Plan

[0120] (1) This trial will conduct efficacy analysis on the FAS.

[0121] (2) Consider P < 0.05 as the standard for statistical significance of differences.

[0122] (3) Measurement data will be described by mean ± standard deviation or median (quartiles). When comparing with the baseline values, paired t-tests / Wilcoxon rank sum tests will be used to compare the differences before and after within the group. For within-group comparison of multiple measurement data, repeated measures analysis of variance / generalized estimating equations will be used.

[0123] (4) Count data and rank data will be described by frequency (constituent ratio). Chi-square tests / Fisher's exact probability method will be used for within-group comparison before and after, and Wilcoxon rank sum tests will be used for within-group comparison of multiple measurement data.

[0124] 5 Ethical Review

[0125] This clinical trial protocol was jointly determined by the principal investigator and the sponsor and implemented after being approved by the Ethics Committee of our hospital (Ethical Approval Number: 2019 - 780 - 135 - 01). This trial is funded and supervised by the Shanghai Municipal Science and Technology Commission.

[0126] 6 Results

[0127] 6.1 Distribution of Enrolled Cases

[0128] A total of 210 patients were enrolled, with 105 patients in each of the control group and the experimental group. During the treatment process, 13 patients dropped out, including 9 patients (8.57%) in the control group and 4 patients (3.81%) in the experimental group, and there was no significant statistical difference between the two groups (P = 0.152); 8 patients were excluded, including 5 patients (4.76%) in the control group and 3 patients (2.86%) in the experimental group, and there was no significant statistical difference between the two groups (P = 0.718); finally, 190 cases were completed, including 91 cases (86.67%) in the control group and 98 cases (93.33%) in the experimental group, and there was no significant difference between the two groups (P = 0.107) (see Table 1). In the FAS, there were 100 cases in the control group and 102 cases in the experimental group, a total of 202 cases, accounting for 96.19% of the enrolled cases; in the SS, there were 96 cases in the control group and 102 cases in the experimental group, a total of 198 cases, accounting for 94.29% of the enrolled cases (see Table 2). A total of 13 cases dropped out during the experiment in the two groups of cases, including 9 cases in the control group and 4 cases in the experimental group; a total of 8 cases were excluded in the two groups of cases, including 5 cases in the control group and 3 cases in the experimental group.

[0129] Table 1 Distribution of enrolled cases

[0130]

[0131] Table 2 Distribution of the number of cases in each dataset (cases)

[0132]

[0133] 6.2 Comparison of baseline information

[0134] Among the baselines of the two groups of subjects, there were no significant statistical differences in gender, age, smoking, alcohol consumption, etc. between the groups; there were no significant statistical differences in BMI, heart rate, systolic blood pressure, and diastolic blood pressure at baseline between the two groups of subjects; there were no significant statistical differences in the course of disease, treatment history, comorbid diseases, and family history in the past medical history between the groups (see Table 3). There were no significant statistical differences in the blood lipid indexes at baseline between the two groups of subjects (see Table 4).

[0135] Table 3 Comparison of baseline information of two groups of patients ; M(Q1,Q3); n(%)]

[0136]

[0137] Table 4 Comparison of baseline levels of blood lipid indexes of two groups of patients [M(Q1,Q3)]

[0138]

[0139] 6.3 Efficacy evaluation

[0140] 6.3.1 Percentage change in fasting LDL-C, the main efficacy index, compared with the baseline at 12 weeks

[0141] At baseline (0W), there was no significant difference in LDL-C between the two groups (P > 0.05). After 12W of intervention, compared with the control group, the percentage difference in LDL-C in the experimental group was significantly lower, and the difference was statistically significant (P < 0.05) (see Table 5).

[0142] 6.3.2 Comparison of the levels of other blood lipid indices among the secondary efficacy indices

[0143] At baseline (0W), there were no significant differences in LDL-C, TC, TG, HDL-C, non-HDL-C, TC / HDL, ApoA-I, ApoA-II, and ApoB between the two groups (P > 0.05).

[0144] After 12W of intervention, LDL-C, TC, TG, HDL-C, non-HDL-C, TC / HDL-C, ApoA-I, and ApoB decreased in the experimental group, while ApoA-II increased. Among them, the differences in LDL-C, TC, non-HDL-C, ApoA-I, ApoA-II, and ApoB were statistically significant (P < 0.05); in the control group, LDL-C, TC, TG, non-HDL-C, TC / HDL-C, ApoA-I, and ApoB decreased, while HDL-C and ApoA-II increased. Among them, the differences in LDL-C, ApoA-II, and ApoB were statistically significant (P < 0.05) (see Table 5). Compared with the control group, the percentage differences in TC and HDL-C in the experimental group were significantly lower, and the differences were statistically significant (P < 0.05), while the differences in the remaining blood lipid indices were not statistically significant (P > 0.05) (see Table 6).

[0145] After 24W of intervention, the levels of LDL-C, TC, TG, non-HDL-C, TC / HDL-C, ApoA-I, and ApoB in the experimental group were all lower than those at baseline (0W), while the levels of HDL-C and ApoA-II were higher than those at baseline (0W). Among them, the differences in LDL-C, TC, HDL-C, non-HDL-C, TC / HDL-C, ApoA-I, and ApoA-II were statistically significant (P < 0.05); in the control group, the levels of LDL-C, TC, TG, non-HDL-C, TC / HDL-C, and ApoB were all lower than those at baseline (0W), while the levels of HDL-C, ApoA-I, and ApoA-II were higher than those at baseline (0W). Among them, the differences in LDL-C, HDL-C, non-HDL-C, TC / HDL-C, ApoA-II, and ApoB were statistically significant (P < 0.05) (see Table 5). The differences in the percentage differences of each blood lipid index between the two groups were not statistically significant (P > 0.05) (see Table 6).

[0146] Table 5 Comparison of intra-group before and after blood lipid levels in two groups of patients with hyperlipidemia [M(Q1,Q3)]

[0147]

[0148] Table 6 Inter-group comparison of percentage changes in blood lipid levels of two groups of patients with hyperlipidemia compared to baseline (%) [M(Q1,Q3)]

[0149]

[0150] 6.4 Adverse event situation

[0151] After some patients took the test drug, mild diarrhea occurred, mostly within one week of initial medication, and then relieved, mostly with self-limiting nature. No serious adverse events occurred in the 198 patients in the SS set during the trial. There was no significant difference in the incidence of adverse events between the two groups of patients (P = 0.242) (see Table 7).

[0152] Table 7 Comparison of the incidence of adverse events between two groups (SS)

[0153]

[0154] 7 Conclusion

[0155] (1) The traditional Chinese medicine compound preparation (Qushi Huayu Formula) of the present invention can significantly reduce the LDL-C and TC levels in patients with hyperlipidemia (syndrome of accumulation of dampness and stasis of heat), and the curative effect at 12 weeks is significantly higher than that of the control group.

[0156] (2) No obvious adverse reactions were found in the treatment of patients with hyperlipidemia (syndrome of accumulation of dampness and stasis of heat) with the traditional Chinese medicine compound preparation (Qushi Huayu Formula) of the present invention compared with the control group.

[0157] The preferred embodiments of the present invention have been specifically described above, but the present invention is not limited to the described embodiments. Those skilled in the art can also make various equivalent variations or substitutions without departing from the spirit of the present invention, and these equivalent variations or substitutions are all included within the scope defined by the claims of this application.

Claims

1. Use of a traditional Chinese medicine compound preparation in the preparation of a medicament for treating hyperlipidemia, characterized in that, The raw materials of the traditional Chinese medicine compound preparation are composed of Chinese medicinal materials Herba Artemisiae Scopariae, Polygonum Cuspidatum, Gardenia Jasminoides, Curcuma Longa, and Hypericum Japonicum Thunb.; the weight percentages of each component in the raw materials are as follows: Herba Artemisiae Scopariae 26% - 38%, Polygonum Cuspidatum 14% - 23%, Hypericum Japonicum Thunb 14% - 23%, Curcuma Longa 14% - 23%, Gardenia Jasminoides 14% - 23%; each component in the raw materials is extracted by the following method: Herba Artemisiae Scopariae, Polygonum Cuspidatum, and Curcuma Longa are extracted with ethanol three times, each time for 1 - 2 hours; Gardenia Jasminoides and Hypericum Japonicum Thunb are decocted together, that is, Gardenia Jasminoides and Hypericum Japonicum Thunb are soaked in water for 1 hour, added with 8 - 10 times of water, extracted three times, and the water extract is concentrated to a relative density of 1.08 - 1.12, and the temperature for measuring the relative density is 80°C, and purified by ethanol precipitation method, centrifugation method or chitosan clarification method.

2. Use of the traditional Chinese medicine compound preparation according to claim 1 in the preparation of a medicament for treating hyperlipidemia, characterized in that, The traditional Chinese medicine compound preparation is a granule, tablet or capsule.

3. Use of the traditional Chinese medicine compound preparation according to claim 3 in the preparation of a medicament for treating hyperlipidemia, characterized in that, The granule is prepared by adding dextrin after the ethanol extract and the water extract are combined, spray-drying to form fine powder, and granulating by dry granulation method.

4. Use of the traditional Chinese medicine compound preparation according to claim 1 in the preparation of a medicament for treating hyperlipidemia, characterized in that, The hyperlipidemia is hyperlipidemia of damp-heat accumulation type.

5. Use of the traditional Chinese medicine compound preparation according to claim 1 in the preparation of a medicament for treating hyperlipidemia, characterized in that, The application of the traditional Chinese medicine compound preparation in the preparation of a drug for reducing the levels of low-density lipoprotein cholesterol and total cholesterol in patients with hyperlipidemia.

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