莪术油口服吸收机理及制剂前研究-6

1、LIST OF ABBREVIATIONSAPApicalBLBasolateralDMEMDulbeccos Modified Eagles mediumDMSODimethyl sulfoxideFBSFetal bovine serumHPLCHigh performance liquid chromatographyMTT3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromideNMRNuclear magnetic resonancePappApparent permeability coefficientPBS+Ph

2、osphate buffered saline plusP-gpP-glycoproteinTEERTransepithelial electrical resistanceUVUltravioletSEDDSSelf-emulsifying drug delivery systemsHLBHydrophilic-lipophilic balancePREFACEZedoary Turmeric (Ezhu), which is the rhizomes of three species of Curcuma including Curcuma phaeocaulis, Curcuma kwa

3、ngsiensis and Curcuma wenyujin, has been used over a long periods as a traditional Chinese medicine for removing blood stasis and alleviating pain. The essential oil extracted from the herb medicine which consisted most of the bioactive components in Zedoary Turmeric is also named Zedoary Turmeric O

4、il (Ezhu oil). The essential oil in Zedoary Turmeric is at the percentage at about 1%2.5%. The main compositions of Zedoary Turmeric Oil are uniterpenoids, sesquiterpenoids and derivative of oxo-compoinds. It has been reported that over twenty components had been extracted from the essential oil and

5、 the structures of above compounds had been identified. The characteristic components are mainly curdione, curcumenol, neocurdione, germacrone, furanodiene, isocurcumenol, curcumol, furanodienone, -elemene, -elemene, curzerene, germacrzene B, germacrzene D, and camphor. It is reported that Zedoary T

6、urmeric Oil has some definitely biological activities including anti-tumor, anti-inflammatory, anti-viral, anti-thrombosis and liver protection activities etc. There are already several kinds of formulations containing Zedoary Turmeric Oil have been invented due to its preferable treatment effects.

7、The glucose injection of Zedoary Turmeric Oil is one of the formulations which plentiful used in clinical therapy. But some allergic side effects and toxicity reactions have also been reported along with its increased usage. In the consideration of the therapy effects of Zedoary Turmeric Oil, it is

8、worthy of researches to develop other formulations, especially oral formulation. However, the studies concerning the oral absorption mechanism and bioavailability of Zedoary Turmeric Oil are incompletely. Although a few studies are focus on one or two main components of Zedoary Turmeric Oil such as

9、germacrone and -elemene and provide a metabolism profile of these compounds, the overall study of the absorption mechanism of Zedoary Turmeric Oil was not investigated. The lack of objective information on the subject has driven our interest towards setting up the Caco-2 cell model for a study of th

10、e intestinal permeation of Zedoary Turmeric Oil. This model is extensively used as an in vitro model in studying small intestinal absorption concerning active transport, efflux mechanisms, paracellular and transcellular diffusion and metabolic activity during absorption. It is described as good corr

11、elation between oral drug absorption in humans and drug permeability coefficients in Caco-2 cells. Caco-2 cell model has some advantages as compared to intestine in vivo or in vitro, such as simple epithelial monolayer structure, free of mucus or underlying sub-mucosal and muscle tissues, ease of ma

12、intenance of tissues viability, as well as its human origin. Hence, the Caco-2 cell line is a well accepted model of intestinal absorption and was broadly used as a tool for evaluating human intestinal permeability and interaction with transporters.The current study will use Caco-2 cell model to inv

13、estigate the absorption mechanism of Zedoary Turmeric Oil. The permeability of the main components in Zedoary Turmeric Oil will be calculated and the study of the active compounds including curdione and germacrone about the influence of transport directions, drug concentrations and other composition

14、s to the permeability of active compounds in the essential oil will also be investigated.ACKNOWLEDGMENTSDuring the master degree education in Institute of Chinese Medical Sciences at University of Macau, I have made great progress whatever at learning knowledge or living way. I would like to sincere

15、ly thank the people who have ever helped me in the 2 years study.Especially thank my supervisors Dr. Zheng Ying and Prof. Wang Yi-Tao who have given me kindly and self-giving guidance and helping during my experiment work and thesis accomplishment. Thank Dr. Li Shao-Ping, Dr. Lee Ming-Yuen and Dr. Z

16、hang Qing-Wen for their heartily help of my study and work.Thank all PhD students, Wan Jian-Bo, Li Peng, Yang Feng-Qing, Gao Jian-Li and Yu hua, who have ever earnest help me at the difficulty in research work and give me correct direction. Also genuinely thank the lab technicians Leon Lai and Sandy Lao who have give the great support during my research experiment.Thank my graduate students, who have given me much sustain and care at my study life. Thank Zhang Yi, Hong Si-Jia, Li Su-Ying, Xie Jing-Jing, Yu Yue, Liang Qing-You, Dong Xiao-Bing, Zhang Jin, Jin Si-Che