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Objective:this paper aims to optimizing formulation and preparation technology of Yiqiningshen drop pills by using orthogonal design, studying the effect of sedative,hypnotic,the anti-fatigue and acute toxicity by animal experiment, developing the quality standard by thin layer chromatography and high performance liquid chromatography,meanwhile,the accelerated stability of Yiqiningshen drop pills was tested.To providing the basis for the research and clinical applications of new drugs.Method:1.the study on optimizing formulation technology and preparation technology of drop pillsUsing appearance character ,solution time and weight difference as evaluation parameters, various influencing factors of formulation technology of drop pills (matrix ratio,drugs:matix, mixture temperature, moisture content)were investigated by using orthogonal L9 (3~4).Similarly, various influencing factors of preparation technology of drop pills(inner diameter:outer diameter,coolant liquid temperature,dropping speeding,dropping distance) were investigated. Finally,the optimization formulation technology and preparation technology of drop pills was determined by analysis of direct- viewing, analysis of variance and synthetic evaluation2. the study of pharmacodynamics of Yiqiningshen drop pillsThe sedative and hypnotic effects of Yiqiningshen drop pills were studied by using the mouse spontaneous activity model,pentobarbital sodium (superthreshold dose) body-righting reflex model, pentobarbital sodium ( subthreshold dose) body-righting reflex model and pentobarbital body-righting reflex models about Caffeined mouse. The anti-fatigue effect were studied by using mouse loaded-swimming and rotating-stick models. The determination index of spontaneous activity were number of movement and number of raising up of mouse upper extremities in limited time, The determination index of body-righting were the latent period and duration of mouse sleep.3. the Study on Acute Toxicity Test of Yiqiningshen drop pillsYiqiningshen drop pills is undetected LD50. So we determine the maximum administration doses in mice. Yiqiningshen drop pills was orally given to mice 2 times a day,mice can tolerate a maximum concentration of drug, the largest volume. Acute Toxicity was observed.4. the study on quality standard of Yiqiningshen drop pillsGinseng,Barbary Wolfberry Fruit,Spine Date Seed and Thinleaf Milkwort Root were identified by TLC, The content of Epimedium Herb were determined by HPLC,meanwhile, the accelerated stability of Yiqiningshen drop pills was tested.Results:1. The result of studying on preparation technologythe optimization formulation technology was PEG4000:PEG6000 ( g:g)=1:2,coolant liquid: dimethyl silicone, mixture temperature:85℃,drugs:matix =1:1.5.the optimization preparation technology of drop pills was inner diameter:outer diameter(mm)3.7/4.1, dropping speeding:30d /min,coolant liquid temperature :8～10℃,dropping distance:8cm.2. The result of studying on pharmacodynamicsThe drop pills decreased number of movement and raising up of mouse upper extreety as well as the potentiated effet of Pentobarbital sodium induced sleep.It can shortened sleeping latent phase and prolong time of sleep,in the addition,it had obvious antagonism with excitation which was caused Caffeine.It extended markedly retention time on rotating stick and swimming time in mice.3. The result of studying on Acute Toxicity TestNo one of mice died.Their activities,feeding,drinking water, fur, respiratory,eye,mental state,feces and body weight were normal.The results of examined with naked eye heart about liver,spleen, lung, kidney, adrenal gland, thymus, uterus,ovary or testis, prostate and other organs were normal.It show that the maximum administration doses was 50g/kg/d,it was equivalent to 1142 times the clinical recommended dose of adult.4. The result of studying on quality standardTLC about Ginseng,Barbary Wolfberry Fruit,Spine Date Seed and Thinleaf Milkwort Root had strong specificity without interference in the blank reference,so they were internalized into quality standard of Yiqiningshen dropping pills,TLC about others had strong interference,so they was not internalized into quality standard of Yiqiningshen drop pills.Icariin showed that it had a good linear relationship in the range of 0.01~0.1040mg·mL-1 (r=0.9997), the regression equation was Y = 47850X - 32912, r = 0.9997, the average recover was 100.3% with RSD of 1.34%(n=9). The accelerated stability test indicates that the quality of Yiqiningshen drop pills was stable in 6 months.Conclusion:1. The indexes of solution time and weight difference were consistent with the standards of the Yiqiningshen dropping pills,the technology was simple and controllable,the data were supplied for industrialized production.2. Yiqiningshen drop pills has the obviouse effects of the sedation, hypnotic and anti-fatigue.3. Yiqiningshen drop pills is safe in clinical doses.4. The method is simple and the results are stable with good reproducibility. It can be used for the quality control of Yiqiningshen pills.
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