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
|
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
-
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.
-
References
|
[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. |
-
-
Proportional views
-
DownLoad: