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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

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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: 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
shu
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
shu

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。
    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.
  • [1] Liu Q. Triptolide and its expanding multiple pharmacological functions[J]. Int Immunopharmacol,2011,11(3):377-383.
    [2] Wang CY,Bai XY,Wang CH. Traditional Chinese medicine:a treasured natural resource of anticancer drug research and development[J]. Am J Chin Med,2014,42(3):543-559.
    [3] Li XJ,Jiang ZZ,Zhang LY. Triptolide:Progress on research in pharmacodynamics and toxicology[J]. J Ethnopharmacol,2014,155(1):67-79.
    [4] Himes R,Lee S,Mcmenigall K,et al. Reduction in inflammation in the footpad of carrageenan treated mice following the topical administration of anti-TNF molecules formulated in a micro-emulsion[J]. J Control Release,2010,145(3):210-223.
    [5] Slingerland M,Guchelaar HJ,Gelderblom H. Liposomal drug formulations in cancer therapy:15 years along the road[J]. Drug Discov Today,2012,17(3-4):160-166.
    [6] 姚媛,廖琼峰,曾丽英,等. 穿心莲内酯和脱水穿心莲内酯表观油水分配系数的测定及pH值对其的影响[J]. 中药材,2009,32(10):1610-1612.
    [7] 宋桂军,柳菡,冯芳,等. 替米沙坦油水分配系数的测定及其意义[J]. 药物分析杂志,2007,27(11):1704-1706.
    [8] 吕文莉,郭健新,平其能. 灯盏花素脂质体的制备及其理化性质的测定[J]. 中国天然药物,2004,2(5):289-292.
    [9] 何海冰,殷春阳,徐丽双,等. 丁酸氯维地平亚微乳注射液的制备与理化性质考察[J]. 沈阳药科大学学报,2015,32(10):760-766.
    [10] 陶小妹,张强,顾红燕,等. 共轭亚油酸-吉西他滨脂质体的制备、表征及体外抗肿瘤活性[J]. 中国新药杂志,2016,25(10):1177-1185.
    [11] 庄莹,宋敏,杭太俊,等. 雷公藤多苷片中雷公藤总内酯及雷公藤内酯醇的测定[J]. 药物分析杂志,2008,28(1):36-40.
    [12] Zhou ZL,Yang YX,Ding J,et al. Triptolide:structural modifications,structure-activity relationships,bioactivities,clinical development and mechanisms[J]. Nat Prod Rep,2012,29(4):457-475.
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出版历程
  • 收稿日期:  2016-12-30
  • 修回日期:  2017-02-22

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

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

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: 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
shu
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
shu

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