The Preparation Technology Of Reduqing Granule

Speciality:Pharmaceutical analysisAuthor:Huang Bao-MingTutor:Professor Zhang JunObjective:Reduqing granule have been used as a hospital preparation in Zhujiang hospital for many years, it has good public praise because of the good cure for influenza.The new drug developement of Reduqing granule bases on the clinical experience,including the extraction route with water and the dosage.Methods and Results:The dosage of Reduqing granule as a hospital preparation is equivalent to45g crude drug,using water to extract, the coefficient of unguent was about20%. It is used in three time in a day, equivalent to3g extractum, the drug loading is too large to make it the tablet and capsule, the granule is suitable because of the large drug loading.According to the pre-experiment, in the extraction route that crude drugs decocts all at once(decoct three times with water,12、8、8times amount,1.5、1、1hours),the retention rate of chlorogenic acid and forsythiaside A were36.1%and36.9%,it suggested that this extraction route was not reasonable.In the father research,we found that the retention rate of chlorogenic acid would be low when Lonicera japonica Thunb. decocted with the Uncaria rhynchophylla (Miq.) Miq.ex Havil;and it could be a50%degradation of forsythiaside A when it herted at100℃in one hour.It suggested that the Lonicera japonica Thunb.should not decoct with the Uncaria rhynchophylla (Miq.) Miq.ex Havil);and the Forsythia Sllspensa(Thunb.)Vahl should not decoct for a long time.So we tried to soak and decoct the Lonicera japonica Thunb. and Forsythia Sllspensa(Thunb.)Vahl (grinding) along(soaked at80℃for1hour,then decocted for20minutes), separated from the other13crude drugs.The pilot test showed that the retention rate of chlorogenic acid and forsythiaside A were both beyond70%.Based on the pre-experiment,used the One-factor experimental design and orthogonal test with five index components(chlorogenic acid、forsythiaside A、phillyrin、harpagoside and pulegone) to optimize the extraction route.The optimized extraction route was:the Lonicera japonica Thunb. and Forsythia Sllspensa(Thunb.)Vahl (grinding) soak with10times amount of water at80℃for1hour,then decoct with10times amount of water for20minutes,the herb residue of the the Lonicera japonica Thunb. and Forsythia Sllspensa(Thunb.)Vahl decoct with the other13crude drugs with10times amount of water for twice,1.5hours and1hour, and collect the volatile oil during the decoction(the volatile oil showed up about15minutes after the water boiled, reached the peak in35minutes,and ended in70minutes).In this extraction route, the retention rate of chlorogenic acid、forsythiaside A、phillyrin and harpagoside were75.11%、74.97%、73.10%、90.63%、80.71%, the weighted average was77.19%.Used the orthogonal test with the index component of pulegone(containing in the volatile oil) to optimize the inclusion route of volatile oil,the optimized inclusion route was:volatile oil:β-cyclodextrin:water=1:6:12, stirring for1hour.The inclusion rate was beyond90%,and it had good repetitiveness.The inclusion complex dried with the spray dryer, the retention rate of pulegone was beyond90%.It suggested that the inclusion complex and the concentrated solution can be mixed,and dried with the spray dryer.The extraction liquid of Honeysuckle (Lonicera japonica Thunb.) and forsythia reduced-pressure concentrated to the relative density of1.05(50℃).The extraction liquid of the herb residue[the Honeysuckle (Lonicera japonica Thunb.) and forsythia] decocted with the other13crude drugs reduced-pressure concentrated to the relative density of1.10(50℃).This two groups of concentrated solution mixed and dried. This concentration route is in favour of the thermo-labile constituents.To study on the influence of different drying mode (atmospheric-drying hypobaric-drying、spray-drying) to the index components.It showed that:using the atmospheric-drying,the retention rates of chlorogenic acid、forsythiaside A、phillyrin and harpagoside were88.70%、93.59%、79.48%、98.84%;using the hypobaric drying, the retention rates were89.34%、99.70%、85.66%、96.18%; using the spray-drying,the retention rates were89.62%、100.21%、85.99%,94.39%. The retention rate of harpagoside in atmospheric-drying is lower than that in hypobaric-drying and spray-drying.It suggested that the hypobaric-drying and spray-drying were better.The pharmaceutic adjuvant used in this granule were:β-yclodextrin that0.5times amount of the dry extract and sucrose that3times amount of the dry extract.These two pharmaceutic adjuvants mixed to the spray dried powder for dry-granulation.The index of dry-granulation:feeding rate was18rpm, rate of the roller was lOrpm, main pressure was4.5Mpa.The critical relative humidity of Reduqing granule was68.43%.Carried out the pilot test to investigate the feasibility of the extraction, inclusion concentration、drying and granulation route that based on the lab experiment.It showed that the the retention rates of chlorogenic acid, forsythiaside A、harpagoside. phillyrin and pulegone were78.46%.68.88%.52.39%,82.60%.58.06%.The product of the pilot test was qualified.It suggested that the preparing technology of Reduqing granule was suitable for industrialized production. Conclusion:The preparing technology of Reduqing granule can increase the retention rates of chlorogenic acid and forsythiaside A remarkablely,this preparing technology simple and convenient.This new preparing technology can be a reference to the preparation that includes the the Lonicera japonica Thunb. and Forsythia Sllspensa(Thunb.)Vahl.