Study On Preparation Technology And Quality Control Method Of Sugar - Free Depression Granules

Sugarless-Migan granules,as a traditional Chinese medicine proportion（TCMP）,comprise extracts of nine medicinal herbs,including Bupleurum chinense DC.,Schisandra chinensis（Turcz.）Baill.,Polygonum aviculare L.,Phellodendron chinense Schneid.,Angelica dahurica（Fisch,ex Hoffm.）Benth.et Hook.f.,Dispsacus asperoides C.Y.Cheng et T.M.Ai, Taxillus chinensis（DC.）Danser.,Glycyrrhiza uralensis Fisch.and Malva verticillata L..In recent clinical application,these medicinal materials are widely used in traditional Chinese medicine（TCM）.The Migan granules were used for the acute and chronic urinary system infection,and applied to treating cystitis,urethritis,acute and chronic nephritis,limbs edemata, pelvic inflammation,precipitant urination,urodynia and reproductive system infections,such as vaginitis,annexitis,prostatitis.The procedure of production of Sugarless-Migan granules has been systematically studied. The results indicated that the preparation procedure of the production is reasonable and feasible. Based on the quality study of the product,quality control standard was set up,and the preliminary study on the stability of this product indicated that the preparation was stable and the quality was controllable.A high-performance liquid chromatography method was described for the determination of akebia saponin D in rat plasma with ultraviolet（UV）absorbance detection. It should be helpful for acquiring a deep development and application in the future drug design.1.Preparation process researchThe effective components of Schisandra chinensis（Turcz.）Baill and Angelica dahurica（Fisch,ex Hoffm.）Benth.et Hook.f.are essential oils.In order to reduce the loss of the essential oils in the decoction process and enhance efficacy of the preparation,a new preparation technology was introduced.The essential oils of Schisandra chinensis（Turcz.）Baill and Angelica dahurica（Fisch,ex Hoffm.）Benth.et Hook.f.were extracted by supercritical carbon dioxide, respectively.These essential oils were enclosed withβ-cyclodextrin,then the inclusions and the water decocted extracts（dry）of the other seven medicinal herbs[except Schisandra chinensis（Turcz.）Balll and Angelica dahurica（Fisch,ex Hoffm.）Benth.et Hook.f.]were added excipients and made into granules.2.Ouality standard researchThe TLC methods were set up for examination of Phellodendron chinense Schneid.and Glycyrrhiza uralensis Fisch.in Sugarless-Migan granules.A HPLC method for testing the contents of berberine and quercetin in this preparation as produced,and the lower limit contents of the two components were developed.A Diamonsil C18（250mm×4.6mm,5μm）column was used with a mobile phase of acetonitrile-0.05 mol·L^-1potassium dihydrogen phosphate（27:73）, and a flow rate of 1.0 mL·min^-1;The detection wavelength was set at 360 nm and the column emperature was room temperature.And then,a reliable and accurate gas chromatography（GC） method coupled with flame ionization detector（FID）was developed for the simultaneous quantitative determination of four bioactive components,i.e.,deoxyschizandrin,Schizandrin B, schisandrol A and imperatorin,in the preparation.The essential oils that containing these analytes,were extracted with steam distillation.The Separation was achieved on an HP-5 Phenyl Methyl Siloxane capillary column（30.0m×0.32mm,×0.50μm）with temperature programmed. The developed GC method was successfully utilized to analyze four bioactive components in Sugarless-Migan granules,and the results demonstrate that this GC analytical method is suitable for the quality control of this commonly used TCMP.3.Investigation on stabilityof Sugarless-Migan granulesThe accelerated stability and long-term stability test of the preparation has been carried on. During the inspection time,the physics and chemistry characters of Sugarless-Migan granules were inspected and the content of active ingredient confined to the draft quality control standard. These indicated that Sugarless-Migan granules was stable,the preparation procedure and the draft quality control standard was reasonable and feasible.4.Determination of akebia saponin D in rat plasma.A validated high-performance liquid chromatography method was described for the determination of akebia saponin D in rat plasma with ultraviolet（UV）absorbance detection.The separation was performed ona Diamonsil ODS column（250mm×4.6mm,5μm）with an isocratic mobile phase consisting of methanol-acetonitrile-water（32:17:51,v/v/v）.The ultraviolet detector was operated at 205 nm.Plasma samples were precipitated with methanol after acidification.The extraction recovery ofakebia saponin D ranged from 83.6 to 86.6%.High selectivity and a low quantitation limit（5.0μg/mL）were achieved.The linear range was 5.0-500.0μg/mL,correlation coefficient r was 0.9946.The method had a good reproducibility, RSD values were below 10%for intra-day and inter-day precision.It is simple,rapid,and applicable to preliminary pharrnacokinetic studies of akebia saponin D in rats.