The Processing Research Of Anti-tumor Chinese Compound Zhenyuan Granules

The prescription of Zhenyuan Granules was derived from AnRen Chinesemedicine hospital of Tianjin. With several dependent variables, the appropriate designmethod was adopted to optimize and predict the two extraction processes. We alsomanufactured three batches production of pilot scale which we researched the stability.The main work was as following:1、We established a HPLC method to analysis the assay of Liquiritin andGlycyrrhizic acid by acetonitrile and1%acetic acid aqueous solution as a mobilephase, and velocity of1.0mL/min gradient elution, with Apollo C18(4.6250mm,5μm). The gradient elution process is as following:0-8min，19%A-19%A；8-20min，19%A-33%A；20-25min，33%A-50%A；25-30min，50%A-100%A；30-35min，100%A-19%A；35-40min，19%A-19%A. The samples have a good linearrelationship in2.424×10-3~2.424g/mL and r2is0.9981and0.9993, respectively; Thestability test shows RSD values of Liquiritin and Glycyrrhizic acid by stability test are1.26%and0.94%, respectively; The RSD values of Liquiritin and Glycyrrhizic acidin precision test are1.20%and1.32%, respectively; The RSD value of Liquiritin andGlycyrrhizic acid in reproducibility test are0.86%and1.27%, respectively; Averagerecovery rates of Liquiritin and Glycyrrhizic acid are97.10%and103.41%,respectively. It is proved that this method is accurate and stable.2、With the amount of water and extracting time as independent variables whichrange was0.5-2h,8-12fold,0.5-1.5h,6-10fold, the content of Liquiritin andGlycyrrhizin and dry extraction yield as dependent variable, the Central CompositeDesign(CCD) was adopted to optimize and predict the two extraction processes. Theopitimized extracting process was following: first time extracting1h with12-fold theamount of water; second time extracting1h with10-fold amount of water. Thepredicting deviation of dry extraction yield was2.48%and-1.08%in two extraction,-2.27%and5.00%of Liquiritin,-18.4%and-9.52%of Glycyrrhizic acid.3、We extracted three batches row material according to the reslt of small politproduction. Compared the vacuum microwave drying with vacuum drying, we foundthat the vacuum microwave drying performs much more better than the traditionalvacuum drying. We selected the best excipient, whose type is lactose: dextrin=1:1,from four types of excipients. We researched the Glycyrrhizic acid assay of extractingsolution, extract, dry extract and granules. The Glycyrrhizic acid assay of extracting solution was higher than the others, while the assay of other three was almost thesame. We also studied the extract yield and Glycyrrhizic acid assay for small pilotproduction and pilot production. The pilot production was12.24%and4.234mg/glower than the small pilot production respectively.4、The stability of Zhenyuan Granules was established. The stress test shows thatdry extraction was easy to absorb moisture. The moisture rate was17.75%（RH=755%）in ten days. The content of Glycyrrhizic acid was reduced7.87%by exposed tolight (4500lx500lx) and23.06%by heating (60℃) respectively in ten days. Theaccelerate test also showed that the granules was easy to absorb moisture. Thelong-term test showed all the test items were qualified according to the qualitystandards.