雷公藤甲素唱硬脂酸酯的合成及其制剂成药性研究

傅志勤; 许幼发; 陈炳辰; 程丹; 马娟娟; 陈建明

doi:10.3969/j.issn.1006-0111.2017.02.011

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雷公藤甲素唱硬脂酸酯的合成及其制剂成药性研究

傅志勤, 许幼发, 陈炳辰, 程丹, 马娟娟, 陈建明

文章导航 > 药学实践与服务 > 2017 > 35(2): 141-145

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]. 药学实践与服务, 2017, 35(2): 141-145. doi: 10.3969/j.issn.1006-0111.2017.02.011

引用本文:

FU Zhiqin, XU Youfa, CHEN Bingchen, CHENG Dan, MA Juanjuan, CHEN Jianming. Synthesis and druggability study of triptolide stearate[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(2): 141-145. doi: 10.3969/j.issn.1006-0111.2017.02.011

Citation:

FU Zhiqin, XU Youfa, CHEN Bingchen, CHENG Dan, MA Juanjuan, CHEN Jianming. Synthesis and druggability study of triptolide stearate[J]. Journal of Pharmaceutical Practice and Service, 2017, 35(2): 141-145. doi: 10.3969/j.issn.1006-0111.2017.02.011

雷公藤甲素唱硬脂酸酯的合成及其制剂成药性研究

doi: 10.3969/j.issn.1006-0111.2017.02.011

1.
福建中医药大学药学院, 福建福州 350122;第二军医大学药学院, 上海 200433
2.
第二军医大学学员旅学员6队, 上海 200433
3.
第二军医大学药学院, 上海 200433

Synthesis and druggability study of triptolide stearate

1.
School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China;School of Pharmacy, Second Military Medical University, Shanghai 200433, China
2.
The sixth Team of Student Brigade, Second Military Medical University, Shanghai 200433, China
3.
School of Pharmacy, Second Military Medical University, Shanghai 200433, China

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。
- 雷公藤甲素 /
- 硬脂酸酯 /
- 前药 /
- 脂质体 /
- 脂肪乳 /
- 成药性
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.
- triptolide stearate /
- prodrug /
- liposome /
- emulsion /
- druggability /

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雷公藤甲素唱硬脂酸酯的合成及其制剂成药性研究

doi: 10.3969/j.issn.1006-0111.2017.02.011

1. 福建中医药大学药学院, 福建福州 350122;第二军医大学药学院, 上海 200433

2. 第二军医大学学员旅学员6队, 上海 200433

3. 第二军医大学药学院, 上海 200433

收稿日期: 2016-12-30
修回日期: 2017-02-22

关键词:

雷公藤甲素 /

硬脂酸酯 /

前药 /

脂质体 /

脂肪乳 /

成药性

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。

English Abstract

Synthesis and druggability study of triptolide stearate

1. School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China;School of Pharmacy, Second Military Medical University, Shanghai 200433, China

2. The sixth Team of Student Brigade, Second Military Medical University, Shanghai 200433, China

3. School of Pharmacy, Second Military Medical University, Shanghai 200433, China

Received Date: 2016-12-30
Rev Recd Date: 2017-02-22

Keywords:

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.