| Objective:to optimize the extraction and refining process of Guizhi jieYu Fangreasonable,establish quality standard of the capsule,observe and study the stability ofthe preparation,lay on the basis of the development of new drugs of traditionalChinese medicine for the treatment of depression.Methods: In this study, the national new drug registration technical requirementsare used for guidance.First screening pharmacodynamic method the Guizhi stagnationand side extraction process, and then the orthogonal design the optimized extractionprocess;Paeoniflorin in the extraction rate and total solids in the extraction process asindex, the orthogonal experiments to optimize the water extraction process conditions;for the reduction in dose of paeoniflorin in the loss rate indicators, to examine itswater extractand alcohol precipitation conditions;Nystose, licorice glycoside,glycyrrhizic acid extraction rate and total solids yield of indicators, the orthogonalexperiments to optimize the alcohol extraction process conditions; the same time,theproposed Pharmacopoeia method and optimization of the extraction method,indicating that Morinda, licorice extraction method is reasonable; As an indicator ofthe amount of volatile oil extraction, the use of single factor experiments andorthogonal design to examine the essential oil extraction conditions to ensure that thevolatile oil extraction completely; the same time, the grinding method, theencapsulation efficiency of the volatile oil, inclusion rate as the index using theorthogonal experimental study of process parameters of the Guizhi volatile oil of thebest inclusion, HPLC determination of cinnamic aldehyde content in the inclusioncompound;During the molding process, to extract concentration conditions, the drying process, the choice of excipients, capsule filling are investigated.In order to control its quality, using the thin-layer chromatography whichCinnamomum cassia Presl, Paeonia lactiflora Pall., Morinda officinalis How,Glycgrrhiza identified, and the establishment of cinnamic aldehyde in the HPLCmethod in which the main drug Guizhi, Paeonia lactiflora Pall of paeoniflorinquantitative.Experimental Study on Stability, to carry out accelerated tests and long-termtrials.Preparation of the preliminary stability test, simulation of commerciallyavailable packaged three batches of samples, at a temperature of40℃±1℃, relativehumidity75%±10%condition place, in the time of sampling, in accordance withthe inspection items for testing. Long term experiment used in close proximity to theactual drug storage conditions, sample3batch, commercial packaging, at atemperature of25℃±2℃, relative humidity60%±10%under the conditionsplaced12months, in the time of sampling, according to stability key inspection iteminspection.Results: Pharmacodynamic screening method with Guizhi solution Yu Fangextraction experiments,Process4,Morinda officinalis How, Glycgrrhiza by ethanolextraction, and the remaining herbs extracted with water, the system extract the"behavioral despair animal models of the antidepressant effect is significant, in the tailsuspension and mouse forced swimming,the experiment could significantly reduce themouse does not move.Experimental studies show that experiment for extractingtechnology research foundation,using an appropriate extraction process, the effect ismaintain the original prescription pharmacodynamic;This experimental study todetermine the extraction and purification process: Weigh the medicine as prescribedproportion, add water,10times the amount of extracted2times, each time1.5h,merge extract, filtration, the filtrate was concentrated to1.10(26℃)for60%concentrations of ethanol and alcohol precipitation of impurities removal;Todetermine the Morinda licorice extraction conditions for A1B3C2D3,30%ethanol, and12times the volume, extracted three times, each time1.5h; with Nystose, licorice glycoside, glycyrrhizic acid extraction rate As index,experimental determination ofextracting technical conditions comparaed with that of《Chinese Pharmacopoeia》extraction methods, extraction rate of the extraction process of Optimization is highthan that of the Pharmacopoeia method.Optimized by orthogonal experimental design,the extraction process of Guizhi volatile oil optimum extraction A1B3D3, liquid tosolid ratio is6:1, the extraction time was5h, and the soaking time of2h to optimizethe extraction process is stable and reliable; in the volatile oil packagebonding processto determine the inputs to10times the amount of β-CD, plus water for four times,theamount of beta-CD inclusion time was0.5hours for the best package bonding processconditions;The enrichment process parameter control in this experiment asfollows:temperature55℃~65℃,vacuum-0.09Mpaand-0.10Mpa. Process parametersis moderate.The transfer rate of the active ingredients is high, heat a little damage;Bythe basis of existing experimental conditions, the vacuum dryingprocessparameters:temperature65℃~70℃, acuum-0.08Mpa~-0.09Mpa,determinationof the dry samples before and after the loss of every active ingredient is little (lessthan12%are lost);Experiment is estimated by adding1%magnesium stearate, selectNo.0capsule to meet capsule filling and clinical needs.Quality standards, all identification methods are negative control samples and thecorresponding active ingredients or the reference drug, controlled trials,the results ofthe specific separation of clear spots,strong specificity, many experiments show goodreproducibility,can be used for the qualitative identification.Method for thedetermination of cinnamic aldehyde in the range of0.04319μg~0.8639μg, theinjection volume and peak area showed good linearity(r=1.0000), the sample averagerecovery of99.05%, RSD2.79%; paeoniflorin0.0566μg~1.7μg within the scope of theinjection volume and peak area showed good linearity (r=0.9998), the sample averagerecovery of97.75%, RSD2.39%.Accelerated stability test shows that, this product measured indicators in thequality standard of range, indicating that the sample properties of stability, forecastthe preserving period corresponds to the room temperature for two years. Conclusion: the Guizhi Antidepression Capsules extraction and purificationprocess of rigorous design, system, reasonable, forming process parameters reliability;in the research on the quality standard established by the detection method, simple,strong specificity, good reproducibility, and can effectively control the quality of theproduct; quality of the preparation was stable. |
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