Study On The Preparation Technology And Quality Standard Of Qidan Fugan Granules

ObjectiveRecurrent respiratory tract infections(RRTI)in children is a common pediatric disease,ccurred mostly in children under 6 years of age,accounting for pediatric respiratory tract infection in 10 to 30%,the incidence rate increased year by year.The clinical manifestations vary from site of infection varies,generally consistent with a certain part of the corresponding clinical manifestations of infection,repeated episodes,prolonged course,the onset of common symptoms rhinitis,pharyngitis,tonsillitis,bronchitis,pneumonia,etc.The disease causes serious harm to children’s physical health,daily life,learning severely affected,but also severely affected children with relatives living and working,the whole families and society a heavy burden.QidanFugan granules is the recipe of Benifiting Qi,Promoting Blood and Activating Spleen of Clinical experience prescription of Dong zhimen hospital,Significant treatment effect,the prescription consists Astragalus membranaceus,Radix Pseudostellariae,Salvianolic,Szechwan Lovage Rhizome with other Chinese medicine.The prescription focus in benifiting Qi,promoting blood and activating Spleen,stress Persistent illness entering collater of Chinese medicine theory;treatment strengthening body resistance in the same time,through the rule is promoting blood circulation forremoving obstruction in collaterals;Clinical applications effective.On the basis of traditional chinese prescription,this study combined modern science and technology tooptimize the extraction and purification process determine the preparation technology of QidanFugan Granules particles;and undertake preliminary quality standard research.MethodsThis paper includes the three parts:extraction and purification process research,quality standards of QidanFugan Granules particles.The details as follows:The extraction and purification process researchTwo parts of extraction will be undertaken according to medicinal material properties in the prescription and references.First part Astragalus membranaceus,Radix Pseudostellariae,Salvianolic and the other three Chinese medicines use orthogonal experiment and single factor test study on water extraction process,selecting the extraction rate index Astragaloside Ⅳ,Salvianolic acid B,paeoniflorin as index.The second part use steam distillation of ligusticum wallichii,Citri Reticulatae Pericarpium quantity of extracted volatile as indicator to have single-factor inspections of herbs soak or not,extraction duration and solvent times;with orthogonal experiment study of volatile oil from β-cyclodextrin inclusion.The volatile oil extract liquid and Process water extraction solution be combined,choosing the transfer rate of Astragaloside Ⅳ,Salvianolic acid B,paeoniflorin as index,we can have single-factor inspections of relatives density of liquids and concentration of enthanol of alcohol sink fluid,which have influence on alcohol precipitation process.A better purification prcess conditions can be screened after doing these.Optimization of the extraction and purification process:We studied alcohol extraction process of Cornus officinalis Sieb and Coptis chinensis Franch with orthogonal experiment and single factor test,using the extraction rate of loganin and berberine as the assessment index;we studied water extraction and alcohol precipitation process of Rehmannia glutinosa Libosch.Pueraria lobata(Willd.)Ohwi and other herbs with orthogonal experiment and single factor test,using the extraction rate of Puerarin and salvianolic acid B as the assessment index;we studied water vapor distillation process of cortex moutan.With orthogonal experiment,using the extraction rate of paeonol as the assessment index.Forming process research:We investigated the granulation process-related parameters,comparing with dry granulation and wet granulation process feasibility.Based on the granulating process,we determined the amount of excipients using moisture absorption rate of particle,particle forming rate,soft material properties as the assessment index.In addition,we also studied the critical relative humidity of forming particles,providing a reference for the humidity control of preparation process.Establishment of quality standards:To ensure the quality of the particles,we need to obtain pellets for quality control,TLC methods to be used to the qualitative Identification and theHPLC methods to be used to the qualitative determination in the Qidan Fugan Granules particles,in order to develop appropriate quality standards.ResultsExtraction and purification of optimization results:The optimum water extraction:adding 12 times water,extracting 3 times,each time for 1 hour.The optimum volatile oil extraction:adding 8 times water,extracting 10 hours.Using a saturated aqueous solution of volatile oil inclusion,encapsulation average rate of 85.79%.The filtrate was concentrated to a relative density of 1.05-1.10(60℃),the alcohol concentration of 60%.Three Pilotscale experiment showed that the process was stable and feasible.Optimization of the forming process:Dextrin is chosen to be excipient;according to the proportion of 1:1 combined dry,wet granulation,95%ethanol as wetting agent,environmental critical relative humidity at 75%or less.Establishment of quality standards:We have established the TLC method of Astragalus membranaceus,Radix Pseudostellariae,Salvianolic,Szechwan Lovage Rhizome.Etc,as well as set up the HPLC method which is used to measure the content of Astragaloside Ⅳ,Salvianolic acid B,paeoniflorin in Qidan Fugan Granules particles.The chromatographic conditions of Astragaloside Ⅳ:Agilent Eclipse XDB-C18 column(4.6 mm × 250 mm,5μm),mobile phase was acetonitrile-water(32:68),column temperature was 25℃,flow rate was 1.0mL/min,the drift tube temperature 100℃,N2,2.60 mL/min.The chromatographic conditions of salvianolic acid B:Agilent Eclipse XDB-C18 column(4.6 mm × 250 mm,5μm),mobile phase was acetonitrile-1.6%formic acid(21:79),column temperature was 30℃,flow rate was 1.00mL/min,detection wavelength was 286nm.The chromatographic conditions of paeoniflorin:Agilent Eclipse XDB-C18 column(4.6 mm × 250 mm,5μm),mobile phase was methanol-water(65:35),column temperature was 30℃,flow rate was 1.00mL/min,detection wavelength was 320nm.ConclusionThe stable and feasible preparation process was established through the research of extraction,purification and forming process of QidanFugan Granules particles,and prepared qualified shaped particles.By analyzing quality standard,this study set up quality or quantity standards and ensure that the good quality of the granule.In conclusion,the expected experiment was achieved.