紫杉醇-天然冰片复合物亚微乳的制备与质量标准及初步活性研究  

Preparation,Quality Standard and Preliminary Activity of Paclitaxel/Natural Borneol Compound Submicroemulsion

作　　者：叶小玲[1] 聂华[1] 古炳明 刘小敏 吴慧敏 杨晓如 谭家伟 许俊雅 YE Xiaoling;NIE Hua;GU Bingming;LIU Xiaomin;WU Huimin;YANG Xiaoru;TAN Jiawei;XU Junya(College of Medical,Jiaying University,Meizhou 514015,China;Meizhou Istitute for Food and Drug Control,Guangdong Province,Meizhou 514011,China)

机构地区：[1]嘉应学院医学院,梅州514015 [2]广东省梅州市食品药品监督检验所,梅州514011

出　　处：《医药导报》2024年第6期949-956,共8页Herald of Medicine

基　　金：广东省医学科研基金资助项目(A2020215);广东省自然科学基金-面上项目(2022A1515011529);嘉应学院一般项目(2022KJY10)。

摘　　要：目的制备紫杉醇-天然冰片复合物,同时探究紫杉醇-天然冰片复合物亚微乳的处方和制备工艺及体外抗肿瘤效果。方法采用研磨法制备紫杉醇-天然冰片复合物并经红外光谱(FT-IR)和差式扫描量热(DSC)分析鉴定所得固体复合物;采用两步高压乳匀法制备复合物亚微乳,应用单因素考察和正交实验优化处方及制备工艺,通过噻唑蓝(MTT)比色法实验、细胞克隆形成实验、细胞划痕实验,考察该制剂对HCT-116细胞的作用效果。结果复合物中紫杉醇3312.76 cm^(-1)和3513.92 cm^(-1)的红外光谱吸收峰消失,且DSC分析显示在154.56℃处出现一个明显的新的吸收峰,表明紫杉醇可能与天然冰片偶联,形成新的复合物。复合亚微乳最佳处方为10%脂肪酸甘油酯,原料药0.44%[紫杉醇-天然冰片(1∶3)],3%混合乳化剂[蛋黄卵磷脂-泊洛沙姆188(1∶2)],2.0%甘油,0.3%油酸;最佳工艺为80℃乳化,60 MPa高压均质10次,再于100℃水浴灭菌45 min。细胞MTT实验中其半数抑制浓度(IC 50)为0.75μg·mL^(-1),细胞克隆实验结果中,空白对照组、紫杉醇原料药及紫杉醇-天然冰片亚微乳的划痕愈合面积分别为(36.44±3.35)%、(13.59±9.28)%、(8.30±4.09)%(P<0.05);平板克隆实验中,空白对照组,紫杉醇原料药组,亚微乳组细胞克隆率分别为(37.92±0.729)%、(9.16±1.335)%、(3.36±1.065)%(P<0.05)。结论紫杉醇-天然冰片亚微乳注射液处方及工艺合理,质量稳定。细胞实验表明,该亚微乳注射剂能明显抑制HCT-116细胞的增殖和迁移。Objective To prepare paclitaxel-natural borneol complex,and to explore the prescription and preparation process of paclitaxel-natural borneol complex drug-loaded submicroemulsion,and its in vitro anti-tumor effect.Methods The Paclitaxel-natural borneol complex was prepared by grinding method and identified by Fourier Transform infrared spectroscopy(FT-IR)and differential scanning calorimetry(DSC).The compound drug-loaded submicroemulsion was prepared using a two-step high-pressure emulsification method.The single-factor investigation and the orthogonal experimental design were applied to optimize the formulation and preparation process.MTT assay,cell cloning assay,and cell scratch assay were used to evaluate the effect of this preparation on HCT-116 cells.Results The infrared spectral absorption peaks of taxol-natural borneol complex at 3312.76 cm^(-1) and 3513.92 cm^(-1) disappeared,and DSC analysis showed that a new absorption peak of taxol-natural borneol complex appeared at 154.56℃,indicating that taxol be coupled with natural borneol to form a new complex.The optimal prescription was 0.44%active pharmaceutical ingredient[paclitaxel-natural borneol(1∶3)],10%medium chain triglyceride,3%emulsifier[egg yolk lecithin-Poloxam 188(1∶2)],2%glycerol,0.3%oleate.The optimal process was emulsification at 80℃,60 MPa high pressure homogenization 10 times.The half inhibitory concentration(IC 50)was 0.75μg·mL^(-1) by MTT asssy in cell.In the cell cloning assay,the scratch healing area of blank control group,paclitaxel raw material and paclitaxel/natural borneol submicroemulsion were(36.44±3.35)%,(13.59±9.28)%,(8.30±4.09)%,respectively.The results were statistically significant(P<0.05).In the plate cloning experiment,the cell cloning rates of blank control group,paclitaxel bulk drug group and submicroemulsion group were(37.92±0.729)%,(9.16±1.335)%and(3.36±1.065)%,respectively,the differents were statistically significant(P<0.05).Conclusion This submicroemulsion has reasonable prescription,feasible process and

关 键 词：紫杉醇-天然冰片复合物 亚微乳 HCT-116细胞 

分 类 号：R979[医药卫生—药品] R943[医药卫生—药学]