水飞蓟宾磷脂复合物的制备与大鼠生物利用度的研究  

Preparation of silybin-phospholipid complex and its bioavailability in rats

作　　者：肖衍宇[1] 宋赟梅[1] 陈志鹏[1] 平其能[1] 

机构地区：[1]中国药科大学药剂教研室,江苏南京210009

出　　处：《药学学报》2005年第7期611-617,共7页Acta Pharmaceutica Sinica

摘　　要：目的制备水飞蓟宾磷脂复合物并对其理化性质进行考察,比较水飞蓟宾磷脂复合物与水飞蓟宾原料在大鼠体内的生物利用度.方法以丙酮为溶剂,加入水飞蓟宾和大豆磷脂,充分搅拌至澄清,真空干燥即得黄白色固体;用 DSC,UV,IR 等方法测定水飞蓟宾磷脂复合物的理化性质;两组大鼠分别灌胃给予水飞蓟宾磷脂复合物和水飞蓟宾原料后,用 RP-HPLC 法测定不同时间血浆中总的和游离的水飞蓟宾的浓度,通过3P97程序计算药代动力学参数。结果研究表明水飞蓟宾磷脂复合物是以非共价键结合,而不是新的化合物;水飞蓟宾磷脂复合物明显改善了水飞蓟宾在水中及正辛醇中的溶解性能;大鼠灌胃给予水飞蓟宾磷脂复合物,体内吸收符合一级吸收一室模型,血浆中游离药物和总的药物浓度的 T_(max)分别为10min 和2h;C_(max)分别为0.11和1.08μg·mL^(-1);T_(1/2)2分别为2.18和3.84h;AUC_(0-∞)。分别为1.71和12.94μg·mL^(-1)·h,而给予水飞蓟宾原料,大鼠体内吸收的浓度在检测限以下,不能测定。结论水飞蓟宾磷脂复合物与水飞蓟宾原料相比亲脂性显著增加,从而增强了水飞蓟宾在胃肠道中的吸收,提高了水飞蓟宾的口服生物利用度.Aim To prepare silybin-phospholipid complex and study its physicochemical properties. To compare the pharmacokinetic characteristics and bioavailability after oral administration of silybin- phospholipid complex and silybin material in rats.Methods Using acetone as a reaction medium,silybin and phospholipid were resolved into the medium,when the organic solvent was clear,then removed under vacuum evaporation,silybin-phospholipid complex was obtained.The new complex's physicochemical properties including DSC,UV,IR were determined.The concentrations of non-conjugated and total silybin after oral administration of silybin-phospholipid complex and silybin material at different time in rats were determined by RP-HPLC.The pharmacokinetic parameters were computed by software program 31797. Results Experiment results showed that silybin and phospholipid in the silybin-phospholipid complex were combined by non-covalent-bond,not forming a new compound and the solubility of silybin- phospholipid complex in water and n-octanol was effectively enhanced.It was found that mean plasma concentration-time curve of silybin after oral administration of silybin-phospholipid complex in rats was in accordance with one-compartment model with first-order absorption.Pharmacokinetic parameters of non- conjugated and total silybin in rats were respectively T_(max)10 min and 2 h;C_(max)0.11 and 1.08μg·mL^(-1); T_(1/2)2.18 and 3.84 h; AUC_(0—∞)1.71 and 12.94μg·mL^(-1)·h.However,after oral administration of silybin material,plasma levels of both non-conjugated and total silybin were within the analytical detection limit.Conclusion It was concluded that after oral administration of silybin-phospholipid complex in rats the bioavailability of silybin increased greatly.This was mainly due to an obvious improvement of the lipophilic property of silybin-phospholipid complex compared with silybin material and an increase in gastrointestinal absorption.

关 键 词：水飞蓟宾磷脂复合物 理化性质 口服生物利用度 药代动力学 

分 类 号：R943.4[医药卫生—药剂学] R945.1[医药卫生—药学]