二氢杨梅素磷脂复合物及其滴丸的制备及其体内药动学比较  

Preparation of dihydromyricetin phospholipids complex and its dropping pills and comparison of their in vivo pharmacokinetics

作　　者：魏永鸽[1] 黄贺梅[1] 徐凯[2] 孙永武[1] 李姝颖 范明松 WEI Yong-ge;HUANG He-mei;XU Kai;SUN Yong-wu;LI Shu-ying;FAN Ming-song(Zhengzhou Railway Vocational&Technical College,Zhengzhou 450052,China;Huanghe Science and Technology College,Zhengzhou 450005,China;Technique Center,Shanghai Leiyunshang Pharmaceutical Co.,Ltd.,Shanghai 201401,China)

机构地区：[1]郑州铁路职业技术学院,河南郑州450052 [2]黄河科技学院,河南郑州450005 [3]上海雷允上药业有限公司技术中心,上海201401

出　　处：《中成药》2021年第12期3270-3274,共5页Chinese Traditional Patent Medicine

摘　　要：目的制备二氢杨梅素磷脂复合物及其滴丸,并比较其体内药动学。方法溶剂挥发法制备磷脂复合物,测定其紫外吸收光谱、晶型、表观溶解度。以PEG 6000为基质,将磷脂复合物进一步制成滴丸,测定其累积溶出度。大鼠分别灌胃给予二氢杨梅素、磷脂复合物、滴丸的0.5%CMC-Na溶液(100 mg/kg),于0.25、0.5、1、1.5、2、2.5、3、4、6、8、10 h采血,HPLC法测定二氢杨梅素血药浓度,计算主要药动学参数。结果二氢杨梅素在磷脂复合物中以无定型状态存在,磷脂复合物在水、正辛醇中的表观溶解度高于原料药(P<0.01)。磷脂复合物240 min内累积溶出度为63.74%,而滴丸30 min内累积溶出度达95.43%。与原料药比较,磷脂复合物、滴丸C_(max)、AUC_(0~t)、AUC_(0~∞)升高(P<0.05,P<0.01),以滴丸更明显(P<0.01),并且滴丸t_(max)缩短(P<0.01),相对生物利用度分别提高至1.68、3.72倍。结论滴丸可改善二氢杨梅素磷脂复合物的累积溶出度及口服生物利用度。AIM To prepare dihydromyricetin phospholipids complex and its dropping pills,and to compare their in vivo pharmacokinetics.METHODS Solvent volatilization method was used to prepare phospholipids complex,after which the ultraviolet absorption spectrum,crystalline and apparent solubility were determined.With PEG 6000 as a matrix,the phospholipids complex was further prepared to dropping pills,after which the accumulative dissolution rate was determined.Rats were given intragastric administration(100 mg/kg)of the 0.5%CMC-Na suspensions of dihydromyricetin,phospholipids complex and dropping pills,respectively,after which blood collection was made at 0.25,0.5,1,1.5,2,2.5,3,4,6,8,10 h,HPLC was adopted in the plasma concentration determination of dihydromyricetin,and main pharmacokinetic parameters were calculated.RESULTS Dihydromyricetin existed in an amorphous state in the phospholipids complex.The phospholipids complex demonstrated higher apparent solubilities in water and n-octanol than the raw medicine(P<0.01).The phospholipids complex displayed the accumulative dissolution rate of 63.74%within 240 min,while that of the dropping pills within 30 min reached 95.43%.Compared with the raw medicine,the phospholipids complex and dropping pills exhibited increased C_(max),AUC_(0-t)and AUC_(0-∞)(P<0.05,P<0.01),especially for the dropping pills(P<0.01),along with shortened t_(max) for the dropping pills(P<0.01),the relative bioavailabilities was enhanced to 1.68 times and 3.72 times,respectively.CONCLUSION Dropping pills can improve the accumulative dissolution rate and oral bioavailability of dihydromyricetin phospholipids complex.

关 键 词：二氢杨梅素 磷脂复合物 滴丸 制备 体内药动学 溶剂挥发法 HPLC 

分 类 号：R944[医药卫生—药剂学]