摘要
目的制备鸦胆子油(BFO)交联环糊精(CDP)包合物(BFO-CDP-IC),并通过急性毒性实验比较BFO-CDP-IC与市售BFO乳剂的安全性。方法提取BFO及合成CDP;采用均质法制备BFO-CDP-IC,通过单因素试验及正交试验设计优化BFO-CDP-IC处方及制备工艺;通过扫描电镜(SEM)法、红外光谱(FTIR)法、核磁共振(1H-NMR)法验证CDP及BFO-CDP-IC的形成;HPLC法测定BFO-CDP-IC中BFO的包封率;通过小鼠急性毒性实验并与市售BFO乳剂进行比较,考察其安全性。结果 BFO得率为17.3%;CDP产率49.26%,交联度8.47;BFO-CDP-IC最佳包合工艺为BFO与CDP投料比1∶10,包合温度20℃,均质时间6 min,稀释BFO的乙醚用量0.5 g;经SEM、FTIR和1H-NMR表明了CDP及BFO-CDPIC形成;HPLC法测得BFO包封率达80%,载药量为7.1%。BFO-CDP-IC的半数致死量(LD_(50))未测出,安全性显著高于市售BFO乳剂(LD_(50)为9.780 g/kg)。结论制备的BFO-CDP-IC包封率高,且与市售BFO乳剂相比毒性降低,安全性高。
Objective To prepare Bruceae Fructus oil （BFO） β-cyclodextrin polymer （CDP）inclusion complexes （BFO-CDP-IC）, andinvestigate its safety by acute toxicity test. Methods BFO was extracted and CDP was prepared according to the literature, the IC of BFO with CDP （BFO-CDP） was prepared by homogenizing method and characterized by SEM,1H-NMR, and FT-IR. The optimum preparation process was determined by single factor test and L9（3^4） orthogonal test. Entrapment efficiency （EE） was determined by HPLC. Acute toxicity of BFO-CDP-IC was assessed by determining the number of deaths of ICR mice over gavage treatment for 2 weeks. The commercial emulsion ofBFO （BFOE） was used as a reference. Results The extraction rate of BFO was 17.3%, the yield of CDP was 49.26%, and the degree of crosslinking was 8.47. The optimal conditions for preparation were as follows, ratio of BFO and CDP was 1：10, preparation temperature and time was 20 ℃ and 6 min, the amount of ether was 0.5 g. Additionally, the HPLC data showed that drug loading of complexes was 7.1%, and EE was 80%. In the acute toxicity test, the median lethal dose （LDs0） of BFOE was 9.78 g/kg. In contrast, all mice treated with IC survived even at the highest dosage （15.36 g/kg）： Conclusion The prepared BFO-IC has high EE compared with commercially available BFOE, BFO-CDP polymer significantly decreased toxicity of BFO.
出处
《中草药》
CAS
CSCD
北大核心
2016年第16期2843-2849,共7页
Chinese Traditional and Herbal Drugs
基金
研究生创新工程项目(CXLX_1441)
关键词
鸦胆子油
交联环糊精
包合物
核磁共振
红外光谱
急性毒性试验
Bruceae Fructus oil
β-cyclodextrin polymers
inclusion complexes
1H-NMR
FT-IR
acute toxicity test
