| Gualou Xiebai baijiu decoction is a very valuable ancient prescription,derived from the Golden Chamber which was written by great physician Zhang Zhongjing in Han Dynasty,it is one of the basic herbal prescriptions applied in the treatment of cardiovascular disease in recent years.Gualou Xiebai drop pills were prepared by improving dosage form based on Gualou Xiebai baijiu decoction.The main research contents includes below four parts:Part one: Extraction,refinement and verifyication of medical components in Gualou XiebaiIndicated by contents of total flavonoids in Gualou Xiebai,three extraction methods such as ultrasound,microwave and refluxing were studied by orthogonall design and combined with the actual situation of laboratory production,the final extraction condition of crude extract was determined as follows: ethanol concertation 60%,ratio of material to liquid 1:10,extraction time 1.5h and total 3 times by alcohol reflux extraction method.To ensure the preparation and application of drop pills,the Gualou Xiebai crude extract(analogous to crude herb 2g/ml)was refined by alcohol precipitation method.Through the study of influence of antioxidant activity of refined solution in different concentrate alcohol deposit,contents of NO and SOD in mouse blood plasma and the difference of chemical compositions before and after alcohol precipitation,75% ethanol was confirmed as optimum purification condition.Part two: Preparation and process investigation of Gualou Xiebai drop pillsWith the hardness,spherical degree,tailing and adhesion of the drop pills as the optimizing indexes,and using the four-factor Box-Behnken design-response surface method to study the preparation technology for Gualou Xiebai drop pills,and the effects on the preparation process of base,the proportion of extract and bases,the diameter of the dropping tip,and dropping speed were studied.The binomial fitting equations was established,and equations fitted well.The optimum preparation conditions of Gualou Xiebai drop pills were as follows: PEG6000 was base,the mass ratio of extract and base was 1:2,the caliber size of dripping faucet was 2.0 mm,and the speed of droping was 30d/min.Part three: Determination on concentration of 3,29-dibenzoyl-karounitriol in Gualou Xiebai drop pills and fingerprint of ethyl acetate extraction in Gualou Xiebai drop pills3,29-dibenzoyl-karounitriol in Gualou Xiebai drop pills was identified by HPLC,the chromatographic conditions included: Lichrospher C18 column(4.6mm×250mm,5?m),methanol-water(93:7)as mobile phase with the flow rate of 1.0mlˇmin-1;The temperature of column was at 30?,DAD detector,the detection wavelength was 231 nm.The characteristic spectrum for ethyl acetate extraction in GualouXiebai drop pills was established by HPLC,there were 22 common peaks in different spectrum,the average similarity degree was calculated by the correlation coefficient method: as the value of mean was 0.9038,and the value of the median was 0.9047,and the average similarity degree was calculated by the included angle cosine method: as the value of mean was0.9217,and the value of the median was 0.9131.Part four: Pharmacodynamic study on Gualou Xiebai drop pillsIn order to study the pharmacodynamics of Gualou Xiebai drop pills on acute myocardial ischemia of rat,screened rats of SPF species were divided randomly into eleven groups with ten rats in each group and half male and half female,the rats were respectively given the physiological saline,Gualou single medicine 22.5g/kg(equivalent to the crude herb),Xiebai single medicine 22.5g/kg(equivalent to the crude herb),Gualou Xiebai baijiu decoction 22.5g/kg(equivalent to the crude herb),Gualou Xiebai drop pills in the doses of 3.75g/kg,11.25g/kg,22.5g/kg,33.75g/kg,45g/kg(equivalent to the crude herb)and Compound Danshen Drop Pills 0.126g/kg by gavage one time a day for seven days,except the blank group,other rats were given by intraperitoneal injection of isoprenaline to establish myocardial ischemia models,changes of S-T sigments in ECG were observed in all groups,and the level of SOD,NO,HDL-C,MDA,CAT,LDH and CK in blood plasma were detected;and the pathological changes of myocardial tissues were observed by HE staining.The results showed that Gualou Xiebai drop pills group could effectively restrain the acute myocardial ischemia induced by Isoproterenol in rats,compared with the Gualou single medicine,Xiebai single medicine and Gualou Xiebai baijiu decoction,Gualou Xiebai drop pills obtained a favourable effect,and in certain dose range,Its inhibition effect on the acute myocardial ischemia was dose depended strongly. |
PDF Full Text Request