| Objective: Compound Ling Xian cough oral liquid is a valid prescription derived from clinic,according to Chinese medicine,natural medicine registration data classification and reporting requirements issued by State Food and Drug Administration,and on the basis of long-term clinical practice,the topic propose to develop 6 groups of new drugs of traditional Chinese medicine for the effective prescription.Methods:With the content,extract rate,transfer rate of hederagenin in the monarch drug radix clematidis as the index,optimized the extraction and refining process of radix clematidis in compound Ling Xian cough formula by orthogonal experiment,chose a preferred molding process of oral liquid through multi-factor,multi-index control method,and observed the stability of compound Ling Xian cough oral liquid by means of combining accelerated test and room temperature retention sample observation method.Produced 3 batches of middle test production volumes according to the lab production parameters.To control product quality of compound Ling Xian cough oral liquid,researched on the quality draft standard,identified each active ingredients in the formula via TLC,and measured the content of 2 active ingredients in the finished product based on high performance liquid chromatography.In addition,investigation of the lowest loaded amount of the production,heavy metals,arsenic salt and microbial limit were also involved in the study.Results: Following is the optimal preparation process of Ling Xian cough oral liquid compound: Prepared radix clematidis,mint and acorus gramineus,then added 12 times water of the total amount of the medicine,next extracted volatile oil by steam distillation for 7 hours and collect it,put tween-80 in it to solubilize,spared.Filtered the mother liquor,then added 10 times water in the filter residue and boiling 3 times,merged decoction fluid and oil extraction mother liquor,centrifuged 20 min to remove the precipitation by the speed of 3500r/min,concentrated the supernatant to a density of1.05 g / cm3,and added 95% ethanol until the containing alcohol amount got to 65%,removed it after refrigerator standing,filtrated,then reclaimed ethanol in filter liquor through depressurizing until no alcohol taste.Mixed the solubilized volatile oil,simple syrup,stevia and sodium benzoate and drug liquid evenly,and set the volume to liquid concentration of 1g · m L-1.Through 3 batches of middle test production,production parameters established by laboratory determined to be basically stable,suitable for large-scale production.Experiments showed that under TLC method employed by quality draft standard,the spot color were clear,negative drug liquor had no interference;Measured the content of 4 effective components in the finished product by high performance liquid chromatography,negative drug liquor had no interference,the linear relationship investigation showed: Plotted on the x-axis the reference substance concentration of hederagenin and plotted peak area on the y-axis,the regression equation were y = 6077.8x-573.93.The linear range of hederagenin were between22.16 to 554.00?g·m L-1(r = 1),the average recovery rate were 101.99%(RSD2.28%).For oleanolic acid,with reference substance concentration as the abscissa,peak area as the ordinate,the regression equation were y = 5785.6x + 617.74.The linear range of oeanolic acid were between 16.24 to 406.00?g·m L-1(r=1),the average recovery rate were 101.99% 96.42%(RSD1.31%).Conclusion: The thesis mainly carried out the following aspects of the new drug development study of compound Ling Xian cough oral liquid: Firstly,detected the quality of each ingredient in the prescription comprehensively by utilizing the method in<Chinese Pharmacopoeia> of 2010 edition;secondly,designed extraction process routes of each prescription drug,through the combination of evaluation process,chemical evaluation and efficacy evaluation,screened the appropriate extracted route initially;thirdly,optimized the preparation method of compound Ling Xian cough oral liquid using content of multiple effective ingredients as evaluation indicator,including obtained the preferable prescription technology by Single factor investigation,and determined the extraction process,the refining process and molding process of compound Ling Xian cough oral liquid finally by way of orthogonal experiment;fourthly,the topic researched the quality draft standard of compound Ling Xian cough oral liquid,mainly covered character identification,TLC,minimum loading capacity examination,microorganism,arsenic salt and heavy metals examination and content determination. |
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