The Secondary Development Of "Zhenyuan Oral Liquid" And Research On The Quality Standards Of The Active Pharmaceutical Ingredient-ginseng Fruit Total Saponins

Objective:Change “Zhenyuan Oral Liquid"”into “Free-sugar ZhenyuanOral Liquid”,including establish new prescription an production technologyof "Zhenyuan Oral Liquid (free-sugar)”,establish the new qualificationstandard of “Zhenyuan Oral Liquid(sugar-free);Also including establish thequalification standard of raw material medicine “ginseng fruit total saponins”in "Zhenyuan Oral Liquid(free-sugar)",at the same time to the research offingerprint on “ginseng fruit total saponins”.Method: According to the requirements that drug supplement registrationclassification(alternation drug prescription has had the pharmaceutic adjuvant)in “drug registration management approach” to conduct relevant experiments,Asfollows:(1)the production technology and the research on the accessories ofprescription in “Zhenyuan Oral Liquid(free-sugar)”.(2)the study on thequalification standard of “Zhenyuan Oral Liquid(free-sugar)”,mainly includethe prescription of the production、the method of producing、properties、identification、 examination、 content determination and so on. and theidentification experiment adopt the method of thin-layer chromatography,thecontent determination adopt the means of Spectrophotometry and high performanceliquid chromatography, under the examine item,according to the relativeregulation of Mixture item in chinese pharmacopoeia(appendix I J of2010).(3)theresearch of qualification standard on raw material medicine “ginseng fruittotal saponins”,including high performance liquid chromatography examines thecontent of ginsenoside Re and ginsenoside Rd in “ginseng fruit totalsaponins”,the research of chromatographic fingerprint of hplc on “ginsengfruit total saponins”,gas chromatographic method to examine the residualquantity of organic pesticide in “ginseng fruit total saponins”,the methodof atomic absorption spectrometry to test the content of heavy metal and harmfulelements(Pb、Cd、As、Hg、Cu).(4)the investigation experiment of stability in Zhenyuan Oral Liquid(sugar-free),adopt two different means-greenhouse placedand accelerated stability to conduct the experiment.Result:(1)The production process of “ZhenyuanOral Liquid(free-sugar)”strictly abide by the preparation procession of“Zhenyuan Oral Liquid”,at the same time more refining and explicit thetechnology parameter for the primary preparation process,and there is no changein extraction preparation itself,as follows:put the ginseng fruit saponinspowder to the ethyl alcohol to dissolve it,and make it into ginseng fruit saponinsethanol solution which is20mg/ml.cold storage for48hours,then filter it andadd water to80%, add20%naoh to adjust PH to9.0,cold storage for24hours,withdilute hydrochloric acid to adjust PH to6.5, and heating boiling to soluble,cold storage for24hours,filtration,and add accessories to it,add water to1000ml,so make it.(2)The accessories of the prescription in “Zhenyuan Oral Liquid(free-surar)”choose newtol instead of honey as sweetening agent,make sure the content ofnewtol is300g/1000ml;the content of potassium sorbate is3g/1000ml;the contentof sodium citrate is6g/1000ml.(3) Establish the new qualification standard of “Zhenyuan OralLiquid(sugar-free),increasing the content datermination of total saponins andmonomer content determination,and define the content limitation of them.Limitthe product per1ml contains ginseng fruit saponins powder with ginseng saponinRe(C48H82O18) calculation, shell not be less than0.31mg;With ginsengsaponin Rd(C48H82O19) calculation, shell not be less than0.18mg.(4)Establish the qualification standard of raw material medicine “ginseng fruittotal saponins” in "Zhenyuan Oral Liquid(free-sugar)", the provisions of thisproduct is calculated on the dried under the content determination, withginseng saponin Re(C48H82O18) calculation, shell not be less than13.0%; Withginseng saponin Rd(C48H82O19) calculation, shell not be less than7.0%.(5)Build the fingerprint of ginseng fruit saponins for the first time,builda total of model mapping, establish13common peak. By the contrast of sample and liquid chromatography-gas chromatography-mass spectrometry,distinguish9of the ingredients: ginsenoside Rg1、ginsenosideRe、ginsenosideRf、ginsenosideRb1、ginsenosideRg2、ginsenosideRc、ginsenosideRb2、ginsenosideRb3、ginsenosideRd. In the meantime,apply Traditional Chinese medicine chromatogramanalysis data management system to analysis the ten batches sample of ginsengfruit saponins,the result shows that the similarity more than0.86.(6)Establish detection method and content limitation of the organochlorinepesticide residues in ginseng fruit saponins,regulate that the DDT in ginsengfruit saponins less than one percent;total BHC less than one in ten millions,PCNB is less than one in ten millions.(7)Establish the examine method and content limitation of heavy metal and harmfulelements(Pb、Cd、As、Hg、Cu) in ginseng fruit saponins,rugulate that the contentof Pb less than two over one thousand; the content of Pb less than two overone million; the content of As less than two over one million; the contentof Cu less than two over one million.(8)The experimental test for long-term stability (18months)and acceleratedstability（6months）、the final result which last18moths’ investigation ofthe stability,their is no significant change in all statics and index comparedwith the start month.Conclusion:This project is based on the original best-selling products "ZhenyuanOral Liquid" for secondary development, not only changing the supplementarymaterials, increasing the product to adapt to the crowd, especially improvingthe quality standard of pharmaceutical preparations and raw material medicinegreatly, increasing the content datermination of total saponins and monomercontent determination, especially establishing the fingerprint of the rawmaterial medicine, determination the method and content limitation oforganochlorine pesticide residues in ginseng fruit total saponins and harmfulelements of heavy metal detection, it is also the first time to conduct asystematized standard research on the typical famous region drug--ginsen fruitin our province,for the development of ginseng fruit related products, making full use of ginseng fruit resources played a good demonstration and leading role.