白杨素磷脂复合物的制备及其药动学行为  

Preparation of chrysin-phospholipid complex and its pharmacokinetic behaviors

作　　者：崔晓鸽 曹伶俐 侯佳威 王姣姣[2] 郝海军[2,3] 王建新[3] 

机构地区：[1]郑州澍青医学高等专科学校药学系,河南郑州450064 [2]中国医药工业研究总院上海医药工业研究院,上海201203 [3]复旦大学药学院,上海201203

出　　处：《中成药》2017年第5期934-939,共6页Chinese Traditional Patent Medicine

摘　　要：目的制备白杨素磷脂复合物,并考察其药动学行为。方法溶剂挥发法制备复合物。以制备温度、制备时间、白杨素质量浓度、药脂比(白杨素-磷脂)为影响因素,复合率为评价指标,正交试验优化制备工艺。对所得复合物进行X射线衍射、差示扫描量热、~1H-NMR、^(31)P-NMR分析,并考察其溶解性。SD大鼠分别灌胃给予白杨素及其磷脂复合物,HPLC法测定白杨素血药浓度,计算药动学参数。结果最佳条件为制备温度40℃、制备时间2 h,白杨素质量浓度20 mg/m L,药脂比1∶2,复合率接近100%。白杨素以无定型状态存在于复合物中,是一种新物相,而非物理混合物(白杨素-磷脂酰胆碱),并未形成新化学键。磷脂复合物可显著增加白杨素在水和正辛醇中的表观溶解度,其C_(max)、AUC_(0-t)、AUC_(0-∞)与原料药相比也均明显提高。结论磷脂复合物可改善白杨素溶解性,并提高其口服生物利用度。AIM To prepare the chrysin-phospholipid complex and to investigate its pharmacokinetic behaviors. METHODS Solvent evaporation method was used for preparing the complex. With preparation temperature, preparation time, chrysin concentration and drug-lipid ratio （chrysin-phospholipid） as influencing factors, together with recombination rate as an evaluation index, the preparation was optimized by orthogonal test. The obtained complex was analyzed by X-ray diffraction, differential scanning calorimetry, ^1H-NMR and n P-NMR, whose solubility was examined as well. SD rats were intragastrically administered with chrysin and its phospholipid complex, respectively. The blood concentration of chrysin was detected by HPLC, after which the pharmacokinetic parameters were calculated. RESULTS The optimal conditions were determined to be 40 ℃for preparation temperature, 2 h for preparation time, 20 mg/mL for chrysin concentration, and 1 ： 2 for drug-lipid ratio, the recombination rate was close to 100%. Chrysin existed in an amorphous state in the phospholipid complex, which was a new phase rather than physical mixture （ chrysin-phosphatidylcholine ）, and no new chemical bond was generated. Phospholipid complex could significantly increase chrysin＇ s apparent solubility in water and n-octanol, the C AUC0_t and AUC0_∞ were also obviously increased as compared with raw medicine. CONCLUSION Phospholip- id complex can improve both the solubility of chrysin and its oral bioavailability.

关 键 词：白杨素 磷脂复合物 制备 药动学行为 

分 类 号：R944[医药卫生—药剂学]