A lipophilic prodrug of Danshensu:preparation,characterization,and in vitro and in vivo evaluation  

作　　者：GUO Xue-Jiao FAN Xue-Jiao QIAO Bin GE Zhi-Qiang 

机构地区：[1]Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Education Ministry Key Laboratory of Systems Bioengineering, Tianjin 300072, China

出　　处：《Chinese Journal of Natural Medicines》2017年第5期355-362,共8页中国天然药物（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.31371014)

摘　　要：Danshensu [3-(3, 4-dihydroxyphenyl) lactic acid, DSS], one of the significant cardioprotective components, is extracted from the root of Salvia miltiorrhiza. In the present study, an ester prodrug of Danshensu(DSS), palmitoyl Danshensu(PDSS), was synthesized with the aim to improve its oral bioavailability and prolong its half-life. The in vitro experiments were carried out to evaluate the physicochemical properties and stability of PDSS. Although the solubility of PDSS in water was only 0.055 mg·mL^(-1), its solubility in Fa SSIF and Fe SSIF reached 4.68 and 9.08 mg·mL^(-1), respectively. Octanol-water partition coefficient(log P) was increased from-2.48 of DSS to 1.90 of PDSS. PDSS was relatively stable in the aqueous solution in pH range from 5.6 to 7.4. Furthermore, the pharmacokinetics in rats was evaluated after oral administration of PDSS and DSS. AUC and t1/2 of PDSS were enhanced up to 9.8-fold and 2.2-fold, respectively, compared to that of DSS. Cmax was 1.67 ± 0.11 μg·mL^(-1) for PDSS and 0.81 ± 0.06 μg·m L-1 for DSS. Thus, these results demonstrated that PDSS had much higher oral bioavailability and longer circulation time than its parent drug.Danshensu [3-（3, 4-dihydroxyphenyl） lactic acid, DSS], one of the significant cardioprotective components, is extracted from the root of Salvia miltiorrhiza. In the present study, an ester prodrug of Danshensu（DSS）, palmitoyl Danshensu（PDSS）, was synthesized with the aim to improve its oral bioavailability and prolong its half-life. The in vitro experiments were carried out to evaluate the physicochemical properties and stability of PDSS. Although the solubility of PDSS in water was only 0.055 mg·mL^（-1）, its solubility in Fa SSIF and Fe SSIF reached 4.68 and 9.08 mg·mL^（-1）, respectively. Octanol-water partition coefficient（log P） was increased from-2.48 of DSS to 1.90 of PDSS. PDSS was relatively stable in the aqueous solution in pH range from 5.6 to 7.4. Furthermore, the pharmacokinetics in rats was evaluated after oral administration of PDSS and DSS. AUC and t1/2 of PDSS were enhanced up to 9.8-fold and 2.2-fold, respectively, compared to that of DSS. Cmax was 1.67 ± 0.11 μg·mL^（-1） for PDSS and 0.81 ± 0.06 μg·m L-1 for DSS. Thus, these results demonstrated that PDSS had much higher oral bioavailability and longer circulation time than its parent drug.

关 键 词：DANSHENSU PRODRUG Oral bioavailability Circulation time 

分 类 号：R965[医药卫生—药理学]