Clinical Trial Of Jiang Zhuo Decoction On Treating Hyperlipidemia (Phlegm And Turbid Repression Syndrome)

Recently, the incidence of hyperlipidemia in China is increasing. Hyperlipidemia is an risky factor of atherosclerosis, moreover, hyperlipidemia is closely related to coronary heart disease, cerebrovascular disease, diabetes, and metabolic syndrome, etc. Traditional Chinese medicine (TCM) has its unique and abundant understanding of treating hyperlipidemia, and Chinese herbal medicine perform good effects on the prevention of hyperlipidemia. Modern pharmacological studies indicate that a large number of single herbs and classic formulas possess definite lipid-lowering efficacy and effective mechanism of action. Professor Tong propose the theory of "Gao Zhuo disease" according to clinical experience and classical description of Huang Di Nei Jing, which guide for the prevention and treatment of hyperlipidemia and metabolic syndrome. The pathological center of "Guo Zhuo disease" exist stomach and intestine, which generally use modified Dahuang Huanglian Xiexin Decoction for the treatment. Jiang Zhuo Formula is composed by Dahuang Huanglian Xiexin Decoction and some anti-hyperlipidemic herbs, and Jiang Zhuo Formula has effects on clearing the heat, dissolving the phlegm, decreasing the turbid and losing the weight.The dissertation is composed of four sections:No.1:Summary of the understanding of TCM on hyperlipemia and the application of Chinese herbal medicine in the treatment of hyperlipemia within nearly eight years. No.2:Clinical case observation of Dahuang Huanglian Xiexin Decoction in the treatment of dyslipidemia combined with type 2 diabetes. No.3:A randomized control clinical trial of Jiang Zhuo Decoction on treating hyperlipidemia (phlegm and turbid repression syndrome). No.4:Summary of clinical experience of Professor Tong on treating hyperlipemia and analysis of research results.Objective:The clinical trial was designed to observe the effect and safety of Jiang Zhuo Decoction on hyperlipidemia (phlegm and turbid repression syndrome).Method:1. Clinical case observation of Dahuang Huanglian Xiexin Decoction used the method of retrospective analysis.The patients who use Dahuang Huanglian Xiexin Decoction to treat dyslipidemia combined with type 2 diabetes in Professor Tong’s clinic from April 2013 to December 2013were adopted as research object. The inclusion criteria and exclusion criteria were drawn up. The patients must be treated by Dahuang Huanglian Xiexin Decoction, when saw doctor in the first time, and must take medicine more than three months. The patients" diagnosis records of 0 month, 1 month,2month,3month and 6 month were collected, then entered with epidata software. The efficacy assessment adopted indicators of lipid series (TQ CHO, LDL-C, and HDL-C), FBG,HbA1C, weight, and BMI, the regular pattern of Professor’s prescription was analysed.2.The clinical trial is a randomized, parallel, placebo-controlled trial.One hundred and fifty-nine patients with hyperlipidemia from multi-centers (including Guang "anmen Hospital,Dongzhimen Hospital,and Civil Aviation General Hospital)were selected for clinical trial after two-week washout period,and randomly divided into 80 cases of Jiang Zhuo Decoction group(treatment group,JZD)and 79 cases of placebo group(control group).The duration period lasted 12 weeks, patients in the JZD group were given JZD(1 decoction po bid,300ml per day);patients in the placebo group were given placebo(1 capsule po qd,200mg per day).One,four,eight,and twelve weeks later, blood lipids,blood glucose,body weight,waist,BMI, and clinical symptoms and signs were assessed; One and twelve weeks later,insulin,liver ultrasound,blood uric acid,liver and kidney function,creatine kinase,blood routine,urine routine,and ECG were assessed.Results:1. The clinical case observation of Dahuang Huanglian Xiexin Decoction included 63 cases (217 frequency), of which,30 cases combined with overweight,23 cases combined with obesity,56 cases combined with fatty liver,30 cases combined with hypertension,5 cases combined with hyperuricemia. Results indicated that the level of TG, CHO, LDL-C, FBG, HbAIC, BMI and weight were effectively decreased after 3 month’s treatment and 6 month’s treatment, which showed significant difference compared with before treatment (P<0.05 or P<0.01). After 6 month’s treatment, the level of HDL-C increased, and showed significant difference compared with before treatment(P<0.05), while after 3 month’s treatment, the level of HDL-C increased, but showed no significant difference compared with before treatment(P>0. 05).During the intervention, there was no patient that transaminase increased markedly. The commonly used herbs, their doses, and the regular pattern of Professor’s prescription were analysed. Result indicated that the most ten frequency drugs were Huang Lian (Rhizoma Coptidis), Da Huang (Radix et Rhizoma Rhei), Zhi Mu (Rhizoma Anemarrhenae), Hong Qu (red yeast rice), Sheng Jiang (Rhizoma Zingiberis Recens), Gan Jiang (Rhizoma Zingiberis), Qing Ban Xia (Rhizoma Pinelliae Concisum),Xi Yang Shen (Radix Panacis Quinquefolii), Tian Hua Fen (Radix Trichosanthis),Yin Chen (Herba Artemisiae Scopariae). The average doses of Huang Lian (Rhizoma Coptidis) were 20g, the average doses of Da Huang (Radix et Rhizoma Rhei) were 6g, the average doses of Zhi Mu (Rhizoma Anemarrhenae) were 34g, the average doses of Hong Qu (red yeast rice) were 8g, the average doses of Qing Ban Xia (Rhizoma Pinelliae Concisum) were 23g, and the average doses of Yin Chen (Herba Artemisiae Scopariae) were 24g. The relationship between herbs and* indicators (blood glucose and lipids) was analysed, general speaking, with the increase of TG、CHO、LDL-C and BMI, the doses of herbs also increased.2. The clinical trial of Jiang Zhuo Decoction on treating hyperlipidemia (phlegm and turbid repression syndrome):With the exclusion of dropped patients,a total of 154 patients were included in the statistics, including 77 cases of JZD group and 77 cases of placebo group. All the patients completed the trial with good compliance,and no significant difference was showed between two groups, when general data(sex, age, course of disease, height, weight, BMI, waistline,blood pressure,complications),related metabolic indicators, and clinical sympotoms compared.After a 12-week treatment, the level of triglyceride decreased by 0.48± 1.34 mmo/1 in the JZD group,which showed significantly statistical difference compared with pre-treatment(P<0.05),but showed no significant difference statistically compared with placebo group(P>0.05).The method of stratified analysis was applied to analyse the effect of JZD on triglyceride, indicating that the primary-treated patients,the overweight and obese patients, hypertriglyceridemia (normal level of CHO) and patients with the moderate level of triglyceride(O week between 1 and 4mmol/l), performed better efficacy and showed significantly statistical difference after a 12-week treatment, when compared with placebo group(P <0.05 or P<0.01). After a 12-week treatment,the level of cholesterol decreased by 0.41±0.99 mmo/1 in the JZD group,which showed significantly statistical difference compared with pre-treatment(P<0.01),and significantly statistical difference compared with placebo group(P<0.05). After a 12-week treatment,the level of cholesterol decreased by 0.41±0.99mmo/l in the JZD group,which showed significantly statistical difference compared with pre-treatment(P<0.01),and significantly statistical difference compared with placebo group(P<0.05). After a 12-week treatment,the level of low density lipoprotein decreased by 0.33±0.71mmo/1 in the JZD group,which showed significantly statistical difference compared with pre-treatment(P<0.01),and significantly statistical difference compared with placebo group(P<0.05).After a 12-week treatment,the level of high density lipoprotein slightly increased in the JZD group,but there was no significant difference compared with pre-treatment and placebo group(P>0.05). After a 12-week treatment,the body weight decreased by 1.73±2.12 kg, BMI decreased by 0.62±1.25 kg/m2,and waistline decreased by4.21±4.66 cm,all of which showed significantly statistical difference compared with pre-treatment(P<0.01),and significantly statistical difference compared with placebo group(P<0.05). After a 12-week treatment,fasting blood-glucose, postprandial blood glucose,and fasting insulin moderately decreased in the JZD group,but there was no significant difference statistically compared with pre-treatment and placebo group(P>0.05). After a 12-week treatment,there was a marked improvement of fatty liver,which showed significantly statistical difference when compared with placebo group(P<0.01). After a 12-week treatment,the level of systolic pressure decreased by 9.86±9.11mmHQ and the level of diastolic pressure decreased by 3.12±9.42 mmHG in the JZD group,both of which showed significantly statistical difference compared with pre-treatment(P<0.01),and significantly statistical difference compared with placebo group(P<0.05). After a 12-week treatment, the level of blood uric acid markedly decreased in the JZD group,but there was no significant difference statistically compared with pre-treatment and placebo group(P>0.05). After a 12-week treatment,the total scores of TCM syndrome decreased by 4.82±4.99 in the JZD group,which showed significantly statistical difference compared with pre-treatment(P<0.01),and significantly statistical difference compared with placebo group(P<0.01).The effective rate of treating TCM syndrome in the JZD was 75.32%,which showed significantly statistical difference compared with placebo group(P<0.01).Each single symptom scores significantly decreased.especially fatigue,a heavy body,gastric and abdominal stuffiness, phlegm-drool coagulation, sticky sensation in the mouth,sticky stool,which showed significantly statistical difference compared with placebo group(P<0.05).Compared with placebo group, there was no marked difference in body obesity, bitter taste in the mouth,and the sign of palse(P>0.05).The trials showed no abnormal safety indicators related with the drugs.Conclusion:The trials demonstrated that JZD, a modified Dahuang Huanglian Xiexin Decoction, is an effective and safe decoction for treating hyperlipidemia with TCM syndrome of phlegm and turbid repression syndrome, JZD has effects on clearing heat, dissolving phlegm and removing turbidity. After a 12-week intervention and treatment, JZD have good efficacies in lowering the level of triglyceride and show significant difference compared with before treatment. Through stratified analysis, we found the party crowd that most applicable to JZD:after a 12-week treatment, the primary-treated patients, the overweight and obese patients, hypertriglyceridemia (normal level of CHO) and patients with the moderate level of triglyceride (0 week between 1 and 4mmol/l) performed better efficacy and showed significantly statistical difference when compared with placebo group. Moreover, JZD have better efficacies in lowering the level of cholesterol, low density lipoprotein and blood pressure, losing the body weight, waistline, and BMI, treating the fatty liver, and improving TCM syndrome when compared with placebo group. There was no abnormal safety indicator. The clinical trial have demonstrated that JZD possess the efficacies on regulating the blood lipids, losing weight, lowering blood pressure, blood glucose and blood uric acid, which indicate the comprehensive regulation of TCM.