Pharmacy Study On Yizhixingnao Granules

Objective:The main purpose of this study is to develop a safe,effective,convenient Chinese medicine preparation on the basis of the clinical experience of the treatment of Alzheimer’s disease,using modern pharmaceutical technology and optimizing the preparation method.Methods:(1)Comparing the safety of process A and process B and screening safer extraction process through the acute toxicity test.(2)The ginsenoside Rg1,Re,Rb1 were determined by HPLC,optimizing the extraction process of Panax quinque folium,the ethanol concentration of single factor was studied firstly,and then the orthogonal design method was applied,the amount of alcohol,alcohol concentration,extraction time was taken as independent variables,ginsenoside Rg1,Re,Rb1 extraction rate,extract yield was taken as dependent variables;The stilbene glucoside were determined by HPLC,taking extraction rate of stilbene glucoside and extract yield as index,water addition,extraction time and extraction times were researched through the reasonable allocation of water addition and extraction time and response surface methodology;Taking the extraction rate of volatile oil as the index,the extraction time was taken as the single factor firstly,and then the orthogonal design method was used to optimize the extraction process of volatile oil and the adding water,extraction time and soaking time were taken as the independent variables;Based on the composite index of volatile oil:β-cyclodextrin,inclusion temperature and inclusion time as the independent variables,the volatile oil inclusion rate and the inclusion rate were taken as the index,the orthogonal design method was used to optimize the β-Saturated solution method of the best inclusion process;Based on the retention rate of active ingredients and the impurity removal rate,the optimum alcohol precipitation conditions were optimized by orthogonal design.(3)Based on the grain yield,the moisture absorption rate and the angle of repose,the Box-Behnken response surface method was used to optimize the forming process of the yizhixingnao granule with the excipients:powder,lactose dosage,the amount of wetting agent.(4)The model of Alzheimer’s disease was established by bilateral common carotid artery ligation,model rats were divided into sham operation group,model group,piracetam group(378mg/kg),compound extract high,medium and low dose(1260,630,315mg/kg)group,once a day,1ml/100g,continuous gavage for 4 weeks,after the last administration,the water maze test was used to detect the behavior of rats,The levels of Ach,AchE,GSH-Px,SOD,MDA and MAO-B were determined.(5)TLC method was used to qualitatively identify the Panax quinque folium,Polygonum multiflorum and Polygala tenuifolia in the intermediates and finished products of yizhixingnao granule,The content of ginsenoside and stilbene glucoside in intermediates and finished products was determined by HPLC,On this basis,establishing the product quality standards of the intermediates and finished products of yizhixingnao granule.Results:(1)The results of acute toxicity test show that the safety of process B is greater than that of process A,and finally the extraction scheme process B is determined.(2)Combined with single factor experiments and orthogonal experimental results,the final determination of the ginseng alcohol extraction process was as follows:adding 12 times of 70%ethanol to extract 2h;Based on the experimental results and the actual situation,the water extraction process of the yizhixingnao granule was as follows:adding 18(8+5+5)times of water to extract 3 times for 3.5 h(1.5+1+1);Combined with single factor experiment and orthogonal experiment,the extraction process of volatile oil from Shichangpu was as follows:adding 12 times of water for 7 h;The optimum process of volatile oil inclusion by saturated aqueous solution was as follows:volatile oil:β-cyclodextrin=1:8,30℃ inclusion 1.5h;Combined with single factor experiments and orthogonal experimental results,the final determination of the best alcohol precipitation process was as follows:Concentrating the liquid to the crude drug containing 1.0g/ml,adding 95%ethanol to ethanol content of 70%,standing 6h.(3)According to the single factor experiment results,the wetting agent selected in the forming process is anhydrous ethanol,the selected excipients are corn dextrin and lactose according to a certain proportion of mixing,Based on the experimental results and the actual situation,the final determination of the molding process:Accessories:powder=1.7,which accounted for 10%of the proportion of lactose excrement,wetting agent dosage of 0.5ml/g.(4)Pharmacodynamics results showed that compared with the sham group,the escape latency of the model group was prolonged,SOD activity decreased,MDA content increased,MAO-B activity increased,Ach content decreased,AchE content increased,GSH-Px activity decreased,piracetam group and high and middle dose group compared with the model group,the results are opposite and significant differences,in the low-dose group,although the results of the same trend with the piracetam group but compared with the model group did not Significant differences.(5)The TLC identification conditions of Panax quinque folium,Polygonum multiflorum and Polygala tenuifolia in the intermediates and finished products of yizhixingnao granule were determined,the contents of ginsenoside and stilbene glucoside were detected and the quality standards initial of the two was established.Conclusion:the preparation process of yizhixingnao granule is stable and reliable,the finished product is safe and stable and has a certain effect for patients with Alzheimer’s disease.