Study On Preparation And Physico-chemical Property And Anti-hepatoma Activity Of Tirptolide Succinate

Triptolide is a diterpenoid,which was isolated from tripterygiumwilfordii,Tripterygium hypoglaucum Hutch and Tripterygium regeliiSpraque et Tak..It’s one of the main active ingredients of tripterygium wilfordii.Triptolide’s anti-tumor activity was strong and its also h-as good effect on anti-hepatoma activity.However,because of its lowsolubility in water,its intake and body treatment effectiveness wasvery poor,coupled with its strong toxicity,therapeutic window was na-rrow and its application in clinic has been limited greatly.In thispaper,we used triptolide for lead compounds,to study the preparationof its derivatives,aimed at maintaining its anti liver cancer activity,improving its solubility in water and reducing toxicity,for expandingclinical application of triptolide and provide theoretical basis for theresearch and development of anti-hepatoma drugs.To investigate the best synthesis process of triptolide derivative,systematic study have been carried out on this part.Target product wasprepared by triptolide with succinic anhydride under the action ofcatalyst.Pre test was studied under the reference of literature,the singlefactor experiment focuses on reaction temperature, reaction time,reactantmole ratio and catalyst dosage.Based on the above research,we used the yield of target product as a evaluation indexes,used L9(34) orthogonalexperiment design method to screen the best preparation process.Resultwas:molar ratio(triptolide:succinic anhydride=1:12),reaction temperaturewas35℃,reaction timewas48h,catalyst dosage was45mg.The optimalprocess was stable and reliable,its also has a mild reaction conditions andhigh product yield,suitable for industrial production.To investigate the main physico-chemical property of triptolidederivative,physical and chemical properties of the triptolide derivativ-e have been studied.Triptolide succinate content determination meth-od has been established firstly.Triptolide succinate solubility in thedifferent pH medium and oil-water partition coefficient were determi-ned by the shaker-HPLC method at37℃.The results showed that t-riptolide succinate’s water solubility was102.69g/mL,oil-water partit-ion coefficient was16.61(logP=1.22),suggested that triptolide succin-ate has good solubility in water and suitable oil-water partition coe-fficient,compared with triptolide.It was better on the development o-f new dosage forms and clinical medicine,compared with triptolide.To investigate the preliminary evaluation of anti-hepatoma activityabout triptolide derivative,we used thiazole blue colorimetry(determinedby MTT)to study triptolide succinate’s anti-hepatoma activity onhepatocellular carcinoma HepG2cells proliferation.Test results showedthat triptolide succinate’s four doses(5,20,40,80nmol/L) in hepatocellularcarcinoma cell proliferation both have inhibitory effect,dose-effect andtime-effct relation with the inhibitory activity.Under the same dose andduration of the test’s data showed that its activity was better thanCisplatin,indicated that triptolide succinate in regard to the development of liver cancer chemotherapy drug has good application prospect.