| 雷公藤甲素唱硬脂酸酯的合成及其制剂成药性研究 |
| 投稿时间：2016-12-30 修订日期：2017-02-22 点此下载全文 |
| 引用本文：傅志勤,许幼发,陈炳辰,程丹,马娟娟,陈建明.雷公藤甲素唱硬脂酸酯的合成及其制剂成药性研究[J].药学实践杂志,2017,35(2):141~145 |
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| 中文摘要:目的 合成一种雷公藤甲素脂溶性前药，以期提高其制剂的成药性。方法 以4-二甲氨基吡啶（DMAP）催化的酸与醇的DCC缩合法，合成雷公藤甲素-硬脂酸酯（TP-SA），通过质谱、核磁共振氢谱和碳谱进行结构确认；采用摇瓶法测定化合物油-水分配系数；将TP及TP-SA制备成脂质体及脂肪乳，考察其初步稳定性。结果 实验结果证明：成功合成TP-SA。TP-SA的log P为2.33。相同处方条件下，TP难以制备成脂质体和乳剂；TP-SA制备成脂质体粒径约90 nm，制备成脂肪乳粒径约110 nm，包封率均大于95%；4℃及25℃条件下观察TP-SA脂质体和脂肪乳的放置稳定性，1周内粒径、包封率等制剂参数皆无明显变化。结论 TP-SA显著改善药物制剂成药性，本研究可为TP制剂开发提供参考。 |
| 中文关键词:雷公藤甲素 硬脂酸酯 前药 脂质体 脂肪乳 成药性 |
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| Synthesis and druggability study of triptolide stearate |
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| Abstract:Objective To synthesize a lipophilic prodrug of triptolide (TP) and improve its druggability.Methods Triptolide stearate (TP-SA) was synthesized via the DMAP-catalyzed DCC method and identified by MS, 1H-NMR and 13C-NMR. The shake-flask method was used to study the oil/water partition coefficient. The preparations of TP and TP-SA liposomes and emulsions were compared. Their encapsulation efficiency and stability were investigated.Results TP-SA was synthesized successfully. Its log P in octanol/water system was 2.33. It was difficult to prepare TP liposome or emulsion. By contrast, TP-SA liposome and emulsion can be prepared successfully with the same formulation process. The particle size of TP-SA liposomes were about 90 nm and TP-SA emulsions were about 110 nm. The encapsulation efficiency was above 95%. Their stability were studied at 4℃ and 25℃. The preparation parameters, such as particle size and encapsulation efficiency, had no significant change in a week.Conclusion Triptolide stearate enhanced drug lipophilicity. Its druggability was improved significantly. These data can be used for the TP related drug design and development. |
| keywords:triptolide stearate prodrug liposome emulsion druggability |
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