紫杉醇口服亚微乳的制备及其肠吸收的初步考察  

Preparation of oral paclitaxel-loaded microemulsion and preliminary study on its intestinal absorption

作　　者：单爽[1] 胥丹 刘冰塞北 孙长山[1] SHAN Shuang;XU Dan;LIU Bingsaibei;SUN Changshan(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China;School of Chinese Materia Medica,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]沈阳药科大学中药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2019年第10期860-868,909,共10页Journal of Shenyang Pharmaceutical University

摘　　要：目的制备优化口服紫杉醇-人参皂苷亚微乳,并对制剂进行评价;考察人参皂苷提取物对紫杉醇亚微乳在大鼠肠道内对紫杉醇吸收情况的影响。方法考察处方中各组分比例及制备工艺因素对亚微乳的影响。比较传统的转相乳匀法及优化的转相-超声乳匀结合法制备亚微乳的形态、粒径及粒度分布的影响。采用透析法考察其包封率的稳定性。采用大鼠在体肠循环法考察亚微乳中紫杉醇吸收情况。结果所制得紫杉醇口服亚微乳粒度分布均匀,优化法较传统法所得载药亚微乳粒径由224.2 nm增至232.0 nm,但多分散系数(polymer dispersity index,PDI)值由0.103 nm降至0.074 nm。药物7 d内包封率达到90%以上。紫杉醇单一亚微乳较泰素肠吸收有显著性提高,吸收百分比分别为4%和2.5%,两者相比有显著性差异(P<0.05);紫杉醇-人参皂苷亚微乳低剂量组、高剂量组(指人参皂苷用量)较紫杉醇单一亚微乳肠吸收有显著性提高,吸收百分比分别为6%、11%和4%,三者相比有显著性差异(P<0.05)。结论人参皂苷提取物可能显著促进口服混合亚微乳中紫杉醇在大鼠肠吸收,以期提高紫杉醇的口服生物利用度。Objective To optimize and evaluate the preparation of a novel paclitaxel/ginsenoside-loaded microemulsion,and investigate the effect of ginsenoside extracts on paclitaxel′s absorption in the intestine of rats.Methods The effects of the proportion of each component in the prescription and the factors of preparation process on the microemulsions were examined.The method of phase inversion homogenizationphase and inversion-ultrasound homogenization was compared by the shape,particle size and PDI of the microelusions.Dialysis method was used to examine the encapsulation efficiency of the microemulsions.Intestinal circulation test in vivo in rats was used to examine the absorption of paclitaxel in paclitaxel-loaded microemulsions.Results The particle size of the paclitaxel/ginsenoside-loaded microemulsions prepared by the optimized method compared by the traditional method increased from 224.2 nm to 232.0 nm,but the PDI value decreased from 0.103 nm to 0.074 nm.The entrapment efficiencies exceed 90%by dialysis method.The intestinal absorption rate of paclitaxel-loaded microemulsions and the control group were above 4%and 2.5%.The absorption rate of paclitaxel-loaded microemulsions(PM),paclitaxel/ginsenoside-loaded microemulsions(PGM)with low dosage,with high dosage(the dosage of ginsenoside extracts)were above 4%,6%,11%,respectively,and there was a significant difference between the three groups(P<0.05).Conclusion The ginsenoside extracts may significantly promote the intestinal absorption of oral paclitaxel-loaded microemulsions in rats,which may increase oral bioavailability of paclitaxel.

关 键 词：紫杉醇 人参皂苷提取物 亚微乳 肠吸收 

分 类 号：R943[医药卫生—药剂学] R96[医药卫生—药学]