Synthesis Of Rhein Ester Derivatives And Study On Its Nanosuspension

Rhein,a kind of anthraquinone compounds.Which is extracted from Chinese medicine rhubarb,has anti-tumor,anti-inflammatory,antibacterial activity and so on.But because of its poor solubility in water and organic solvent,it is not suitable for formulation,In this paper,rhein ester derivatives was synthesized,By introducing ester bond and long carbon chains,the lipid solublility of rhein has been improved and because of the slow-releasing,the rhein role of time in vivo was extended.Then rhein ester derivative was prepared into a nanosuspension,so as to improve its solubility in water and the same time improving the bioavailability.The purity of rhein ester derivatives were determined through DAD,the structural identification of the product was testing by IR,MS,1HMR.The result indicates that the structure and functional groups are confirmed,and the purity was all above 97%.To study the physicochemical properties,the solubility,melting point,oil/water partition were tested.the result of solubility was RH-BE>RH-PE>RH-EE>RH>RH-DE>RH-TE,The result of melting point was RH>RH-PE>RH-EE>RH-DE>RH-BE>RH-TE.To prepared RH-NS and RHBE-NS,we choose the simple factor investigation,at last we achieved the optimal formulations of RH-BE-NS and RH-NS as follows.RH-NS:200 mg B,20 mg F68 and 20 mg lecthin respectively.RH-BE-NS:100 mg E,25 mg F68 and 25 mg lecthin respectively.The preparations properties evaluation of RH-NS and RH-BE-NS were determined through DSC,TEM,SEM.The mean particle size,Zeta potention and PDI of RH-NS are 210 nm,22.6 mv,0.156 respectively.The mean particle size,Zeta potention and PDI of RH-BE-NS are 230 nm,21.6 mv,0.215 respectively.In this paper,HPLC method was used to determine the content of rhein in plasma samples,and we calculated the pharmacokinetic parameters of RH-NS,RH,RH-EE,RH-PE,RH-BE,RH-DE,RH-TE,RH-BE-NS by DAS.The AUC of RH-BE-NS is 84.096,Compared with rhein,Which increased 2.47-fold,And the AUC of RH-TE is 74.285,Compared with rhein,Which increased about 2.18-fold.It indicated that RH-BE-NS effectively increased the bioavailability of RH.Our study is the first report on the preparation of RH-NS and RH-BE-NS.The results of our study were helpful for the development of poorly soluble drug.And our study had a very important significance for the clinical application of rhein.