莪術(shù)油口服吸收機理及制劑前研究-3

1、TABLE OF CONTENTSLIST OF FIGURES.viLIST OF TABLES .viiiLIST OF ABBREVIATIONS.xPREFACE.xiACKNOWLEDGEMENTS.xiiiCHAPTER 1: Introduction .11.1. Zedoary Turmeric Oil.11.1.1. Introduction.11.1.2. Chemical constituents.11.1.2.1. Volatile components .11.1.2.2. Non-volatile and other components.31.1.2.3. Str

2、uctures elucidation.31.1.3. Pharmacological activities of Zedoary Turmeric Oil.51.1.4. Pharmacological activities of active components in Zedoary Turmeric Oil.71.1.4.1. Curcumol.71.1.4.2. Beta-elemene.81.1.5. Pharmacokinetics of Zedoary Turmeric Oil .91.1.6. Formulation development of Zedoary Turmer

3、ic Oil .101.1.6.1. Nanocapsule freeze-dried powder injection.101.1.6.2. Hydroxypropyl-beta-cyclodextrin inclusion complex.111.1.6.3. Soft-gel capsule.111.1.6.4. Dripping-pill .111.2. The Caco-2 cell culture model.121.2.1. Introduction.121.2.2. Transport pathways of intestinal absorption.131.2.3. Adv

4、antages and disadvantages of Caco-2 cell model.151.2.4. Applications of Caco-2 model in drug absorption and metabolism.151.2.4.1. Absorption screening.151.2.4.2. Absorption mechanism .161.2.4.3. Drug metabolism.161.2.5. In vitro-in vivo comparisons.171.3. Self-emulsifying drug delivery systems (SEDD

5、S).181.3.1. Introduction.181.3.2. Mechanism of self-emulsification.191.3.3. Excipients of SEDDS.201.3.3.1. Oil .201.3.3.2. Surfactants.211.3.3.3. Co-sulvents .211.3.4. Conclusions.22CHAPTER 2: Analytical methods of Zedoary Turmeric Oil .232.1. Materials .232.1.1. Chemicals.232.1.2. Instruments.232.2

6、. Methods.242.2.1. Analytical methods of Zedoary Turmeric Oil and its pure compounds.242.2.1.1. HPLC analysis of Zedoary Turmeric Oil.242.2.1.2. HPLC analysis of individual pure component of Zedoary Turmeric Oil.262.2.2. Preformulation study of Zedoary Turmeric Oil.302.2.2.1. Determination of propor

7、tion of each constituents .302.2.2.2. Sample prepration for aqueous solubility determination.312.2.2.3. Determination of solubility.312.2.2.4. Determination of stability.312.2.3. Validation of HPLC methods.322.3. Results.332.3.1. Preformulation studies and sample treatment of Zedoary Turmeric Oil.33

8、2.3.1.1. Proportion of each constituents in Zedoary Turmeric Oil.332.3.1.2. Solubility of constituents of Zedoary Turmeric Oil.332.3.1.3. Stability of constituents of Zedoary Turmeric Oil.352.3.2. Validation of HPLC methods.402.3.2.1. Calibration curve.402.3.2.2. Precision.422.3.2.3. Accuracy.432.4.

9、 Discussion.442.4.1. Solubility of Zedoary Turmeric Oil and pure compounds.442.4.2. Stability of Zedoary Turmeric Oil and pure compounds.442.5. Conclusion.45CHAPTER 3: Transport mechanism of Zedoary Turmeric Oil.463.1. Materials .463.1.1. Chemicals.463.1.2. Materials for cell culture.463.1.3. Instru

10、ments.463.2. Methods.483.2.1. Analytical methods for validation of Caco-2 model.483.2.1.1. Fluorescence analysis of lucifer yellow.483.2.1.2. HPLC analysis of propranolol .483.2.2. Cell culture.483.2.3. Validation of Caco-2 cell monolayer model.493.2.3.1. Integrity of Caco-2 cell monolayer.493.2.3.2

11、. Permeability of paracellular and transcellular markers .493.2.4. Transport study of Zedoary Turmeric Oil using Caco-2 cell monolayer model .493.2.4.1. Preparation of dosing formulations of Zedoary Turmeric Oil .493.2.4.2. Cytotoxicity test.503.2.4.3. Protocols of permeability study.513.2.4.4. Tran

12、sport experiment of pure compounds in Zedoary Turmeric Oil.513.2.4.5. Infection of other components in Zedoary Turmeric Oil to the permeability of active compounds.523.2.4.6. Uptake experiment.523.2.4.7. Sample treatment .533.2.5. Calculation.533.2.6. Statistical analysis.533.3. Results.543.3.1. Val

13、idation of Caco-2 cell model.543.3.1.1. Integrity of Caco-2 cell monolayer.543.3.1.2. Permeability of paracellular and trancellular markers.543.3.2. Transport study of Zedoary Turmeric Oil.553.3.2.1. Cytotoxicity test.553.3.2.2. Transport experiment of pure compounds in Zedoary Turmeric Oil.573.3.2.

14、3. Absorption of curdione and germacrone at different concentrations.593.3.2.4. Infection of other components in Zedoary Turmeric Oil to the permeability of active compounds.603.3.2.5. Uptake experiment of furanodiene.643.4. Discussion.683.4.1. Validation of Caco-2 cell model.683.4.2. Transport mechnism of Zedoary Turmeric Oil.683.4.2.1. Bi-directional transport of constituents in Zedoary Turmeric Oil.683.4.2.2. Concentration dependency of curdione and germacrone.683.4.2.3. Infection of other components in Zedoary Turmeric Oil to the transport of active compounds.693.4.2.4. Uptake of furanodi