Study On Preparation Technology,Stability And Safety Evaluation Of Fangjiewan

Objective:This paper was to study the preparation process,stability,acute toxicity and long-term toxicity of Fangjiewan.Methods:(1)Orthogonal method was applied to determine the extraction processes of wintercreeper and astragalus membranaceus and screen the dosage form and preparation methods of Fangjiewan and finally determine its preparation technology.(2)Three batches of samples were drawn respectively and received preliminary stability test under the relative humidity of 75±2%at 38±2? for 1,2,3 and 6 months and stability test for 0,1,2,3,6,9,12,18 months according to Fangjiewan quality standard(draft).(3)Kunming mice taken as study system were gavaged with Fangjiewan and the maximum tolerance dose was observed.(4)Wistar rats taken as experimental objects were gavaged with low,medium and high doses(1.5,3.0 and 6.0g/kg/time)of Fangjiewan for 3 months(calculated by raw medicinal materials),three times a day,which were equivalent to 15,30 and 60 times of human clinical dose of 102.6mg/kg/time respectively.Blood,biochemistry,body-mass indexes of the experimental objects were observed and non-toxic dose was determined.Results:(1)The preparation technology of Fangjiewan was determined by screening its dosage form and preparation methods,radices trichosanthis and dragon's blood were smashed into fine powder,wintercreeper and astragalus membranaceus were decocted with water for 12 h twice,12 times of water each time,and then filtered together with water decoction.The filter liquor concentrated to 1.10?1.15 of relative density(70 ?)was cooled to room temperature and then added with 3 times of ethyl alcohol and mixed and placed for 48 h.The supernatant liquor was taken and ethyl alcohol was recycled and concentrated into thick paste and then baked into dry extract and smashed into fine powder.It was then mixed with radices trichosanthis and dragon's blood and floated with water and dried.(2)Preliminary stability and drug stability tests indicated that the evaluation indexes of Fangjiewan conformed to "Fangjiewan" drug quality standard(draft)for 18 months of storage at room temperature;microbial limit was inspected and found to be in line with the provision of Chinese Pharmacopoeia(2015)appendix microbial limit standard and drug quality was stable.(3)20.5g/kg of Fangjiewan(by raw medicinal materials)was dissolved with distilled water and gavaged to mice,three times a day,with daily dose of 61.6g/kg(by raw medicinal materials).After 7-day continuous observation,the mice were found without death and abnormality in spirit,activity,urination and defecation and appetite.(4)Compared with the blank control group,the above observation indexes of Fangjiewan in low,medium and high dose groups had no obvious abnormal changes.Research results showed that non-toxic dose of Fangjiewan was more than 6.0g/kg(by raw medicinal materials)in long-term toxicity test.Conclusions:The preparation process is feasible,the product is of even quality and high safefy.The term of validity may be limited to 24 months.