芒果苷-磷脂复合物的油制剂在大鼠灌胃后的生物利用度  

Enhanced oral bioavailability of mangiferin phospholipid complexes prepared by its oil-based formulations in rats

作　　者：张杰[1] 孙敏捷[1] 平其能[1] 张灿[2] 

机构地区：[1]中国药科大学药剂学教研室,南京210009 [2]中国药科大学新药研究中心,南京210009

出　　处：《中国新药杂志》2014年第9期1092-1098,共7页Chinese Journal of New Drugs

摘　　要：目的：为了研究芒果苷磷脂复合物的口服吸收，制备了芒果苷磷脂复合物及其与不同油混合的油制剂，比较不同油制剂及复合物水混悬液在大鼠灌胃后的生物利用度。方法：制备芒果苷磷脂复合物，采用甲醇和四氢呋喃（1：1，v／v）溶解芒果苷及磷脂（1：4，w／w），芒果苷浓度为3mg·mL^-1，在温度40℃条件下搅拌1h，减压旋转蒸干溶剂，真空干燥12h。通过紫外全波长扫描，x射线衍射和红外光谱分析确证了磷脂复合物的形成，同时对复合物的溶解性和分配系数等理化性质进行了考察。采取大鼠灌胃，不同时间取点HPLC测定血浆中药物浓度，比较复合物分别混悬在水和中链脂肪酸甘油酯中的生物利用度。继而对油的类型和配比进行了筛选，比较了用油酸和不同链长甘油三酯的混合油对芒果苷磷脂复合物在大鼠灌胃后体内生物利用度的影响。结果：芒果苷与磷脂以非共价键结合形成复合物，复合物明显改善了芒果苷在水中及正辛醇中的溶解性能。复合物的油混悬液的生物利用度高于水混悬液。磷脂复合物在油酸中有更好的溶解性能，溶解在油酸和中链甘油三酯中的复合物的药动学参数Cmax为（2391．43±711．40）ng·mL^-1和AUC0-12h为（466．54±39．41）×10^3ng·mL^-1·min分别是芒果苷复合物水混悬液的5．76和3．17倍。结论：芒果苷复合物与油合用可获得较高的相对生物利用度，这与复合物在油中比在水中有更好的稳定性有关。由于油酸和中链脂肪酸酯增加复合物的溶解并具有促吸收作用，因此复合物在该混合油中有更高的相对生物利用度。Objective： To compare the relative bioavailability of MGN-Phospholipid complex （MGN-PC） in aqueous suspension and in the different oil bases after intragastrical administration to rats. Methods： MGN （3 mg.mL^-1） and phospholipids （1：4, w/w） were placed in a 100 mL round-bottom flask and dissolved in the mixture of methanol and tetrahydrofuran （ 1 ： 1, v/v）. Then solvents were evaporated under vacuum at 40 ℃ , and the dried residues of MGN-PC were collected and placed in a desiccator overnight. The physicochemical properties of the complex were determined by UV, X-ray and IR spectrometry. Lipid-based formulations were prepared by suspending or dissolving the MGN-PC in the different oil media. The plasma concentration of MGN was determined in rats by HPLC method and compared with that of aqueous suspension of MGN-PC. Results： The phospholipids and MGN combined together and a complex with non-covalent-bond was formed. The complex efficiently increased the solubility of MGN in both n-octanol and water. The in vivo experimental result showed that the relative oral bio-availability was enhanced remarkably by suspending the MGN-PC in medium-chain fatty glycerides （MCT） as com- pared with its aqueous suspension. MGN-PC showed greater solubility in oleic acid （OA）. Moreover, the absorp- tion enhancement of oil-based formulation prepared by dissolving the MGN-PC in oil medium composed of OA and MCT （1：4, w/w） was somewhat greater than that prepared by suspending the MGN-PC only in MCT. The Cmax val- ue and AUC0-12h of MGN complex dissolved in OA and MCT was 5.76-fold and 3. 17-fold higher than those of MGN-PC aqueous suspension, respectively. Conclusion： The relative bioavailability of MGN-PC is enhanced by the oil-based formulations, which may relate to its better stability in oil media than in water. This is more pro- nounced for MGN-PC dissolved in oil medium composed of OA and MCT due to the large solubility of the complex in OA and penetration enhancement of OA.

关 键 词：芒果苷磷脂复合物 油制剂 中链甘油三酯 油酸 口服生物利用度 

分 类 号：R945.1[医药卫生—微生物与生化药学]