| Objective:The preparation technology of ZhuYang KaiYu granule was optimized,the corresponding quality standards were established,and the pharmacodynamic effect and acute toxicity of its antidepressant were studied,so as to provide experimental research basis for the application of this preparation in hospitals and its wider clinical application.Method s 1.Preparation process:orthogonal experiment was used to optimize the extraction process of volatile oil with the extraction amount of volatile oil as the evaluation index.Taking the inclusion rate of volatile oil as the index,the inclusion process of volatile oil was optimized.The extraction process of decocting water was optimized with the total alkaloid content as the index.The technological conditions of spray drying and dry granulation were optimized by taking the forming rate,solubility and hygroscopicity as the indexes.2.Quality standards:TLC was used to qualitatively identify radix glycyrrhizae,cortex phellodendron,cassia twig and fructus amomum.According to the general principles of the four related preparations in the Chinese pharmacopoeia 2015 edition,the water content,particle size and solubility of the preparation were examined.A HPLC method was developed for the determination of aconitoid alkaloids in the preparation.3.Antidepressant effect:chronic unpredictable mild stimulation was used to replicate the depression model in rats,and the open-field test and forced swimming test were conducted,and the contents of Cort,ACTH and 5-ht in the serum of rats were determined.4.Primary exploration of acute toxicity:the drug was administered by gavage at the maximum concentration of 4.74g/mL and the maximum volume of 40mL/kg in the administration group,while the same volume of normal saline was administered in the control group.For 14 days,the body mass,food intake,poisoning,death and organ variation of the animals were observed.Results:1.Preparation process:(1)The extraction condition of volatile oil was 10 times of added water,soaked for 0.5 h and extracted for 6 h.(2)The inclusion condition of volatile oil was 1:5,4 times of added water,and the inclusion time was 3h.(3)The decoction condition is 10 times the amount of water added,the decoction times are 3 times,and the decoction time is 90min.(4)The spray drying conditions for inlet air temperature of 180 ℃,feeding rate of 50%,the outlet air temperature 130 ℃.(5)The dosage of adjuvant was 0.333 times of maltodextrin,0.05 times of microcrystalline cellulose,and 0.011 times of soluble starch.(6)The dry granulation conditions were:feeding speed 51.23r·min-1,roller speed 11.99r·min-1,roller pressure 69.35MPa.2.Quality standards.(1)A TLC method was established to identify radix glycyrrhizae,cortex phellodendron,cassia twig and fructus amomum.(2)The content determination methods were preliminarily investigated,and the indexes were benzoyl aconitine,benzoyl aconitine and benzoyl aconitine.The three components presented good linearity in the range of 0.0820～4.1000g,0.0420～2.1000 g,0.0840～4.2000 g,and the correlation coefficients were 0.9998,0.9999 and 0.9999,respectively.The RSD values of precision,stability and repeatability were all less than 3%,the recoveries were 106.3%,101.1%,94.5%,1.45%,2.77%and 1.46%,respectively.3.Anti-depression experiment.In terms of Cort and ACTH,the content of model group was significantly higher than that of blank group,and the modeling was successful(p<0.01).Compared with the model group,the content in the drug administration group was significantly lower,indicating that the depression symptoms in the rats in the drug administration group were alleviated(p<0.01).In terms of 5-ht,the content of the drug delivery group was decreased compared with the model group,and the modeling was successful(p<0.01).Compared with the model group,the content in the drug administration group increased,indicating that the depression symptoms of the rats in the drug administration group were alleviated(p<0.01).4.Preliminary study on acute toxicity.No deaths occurred in either the administration group or the control group.Compared with the control group,there was no significant difference in body mass and food intake of the mice in the administration group,and there was no abnormal behavior and activity.No abnormalities were found in the viscera of the mice in the administration group after dissection.Conclusion:The physical properties of the zhuyang kaiyu granules prepared under the selected technological conditions were in accordance with the pharmacopoeia.The TLC identification method and the content determination method were both specific and reproducible,which could meet the quality control requirements of zhuyang kaiyu granules.The inspection items of the general principles of preparation all conform to the provisions of the pharmacopoeia,indicating that the quality of zhuyang kaiyu granules is controllable.The experimental results showed that zhuyang kaiyu granule had better anti-depression effect and no obvious toxicity,which provided experimental basis for clinical application of zhuyang kaiyu granule. |
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