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표제지=0,1,3

List of Contents=i,4,5

List of Schemes=vi,9,1

List of Figures=vii,10,11

List of Tables=xviii,21,2

List of Abbreviations=xx,23,2

Abstract=xxii,25,2

Chapter I. General Introduction=1,27,1

1. Ginseng pharmacology=2,28,2

1.1 Adeptogenic effect=3,29,1

1.2 Effects on CNS=3,29,2

1.3 Anticancer effect=4,30,2

1.4 Antidiabetic effect=5,31,1

1.5 Antioxidant effect=5,31,2

1.6 Antiplatelet effect=6,32,1

2. IH-901=7,33,1

2.1 Anticancer effect=7,33,2

2.2 Antiallergic effect=8,34,1

3. The liver=9,35,1

4. Hepatic uptake=10,36,1

4.1 Na+-taurocholate cotransporting polypeptide(Ntcp)(이미지참조)=10,36,1

4.2 Organic anion transporting polypeptiedes(Oatps)=11,37,1

4.3 Organic cation transporters(Octs)=12,38,1

5. Biliary excretion=13,39,1

5.1 Multidrug resistance proteins(Mdrs)=13,39,1

5.2 Bile salt export pump(BSEP)=14,40,1

5.3 Multidrug resistance-associated proteins(Mrps)=14,40,1

6. Methods to study hepatobiliary transport=15,41,1

6.1 Intact liver in vivo=15,41,1

6.2 Isolated perfused liver=15,41,2

6.3 Precision-cut liver slice=16,42,1

6.4 Isolated hepatocyte suspension=16,42,2

6.5 Cultured hepatocyte=17,43,2

6.6 Sandwich configuration of cultured hepatocyte=18,44,1

6.7 Membrane vesicle[원본불량;p.21]=19,45,8

References=27,53,14

Chapter II. Pharmacokinetic Characteristics and Bioavailability of IH-901=41,67,1

1. Introduction=42,68,2

2. Materials and Methods=44,70,1

2.1 Chemicals=44,70,1

2.2 Animals=44,70,1

2.3 Preparation of β-cyclodextrin:IH-901 inclusion complex=44,70,1

2.3.1 Solubility study=44,70,2

2.3.2 Preparation of β-cyclodextrin:IH-901 inclusion complex=45,71,1

2.3.3 Characterization Infrared spectroscopy=45,71,2

2.3.4 Dissolution studies=46,72,1

2.4 Pharmacokinetic studies=46,72,1

2.5 Determination of IH-901=47,73,1

2.5.1 HPLC condition=47,73,1

2.5.2 LC/MS/MS condition=47,73,2

2.6 Data analysis=48,74,2

3. Results and Discussions=50,76,1

3.1 Preparation of β-cyclodextrin:IH-901 inclusion complex=50,76,1

3.1.1 Solubility study=50,76,1

3.1.2 Preparation of β-cyclodextrin:IH-901 inclusion complex=50,76,1

3.1.3 Characterization Infrared spectroscopy=51,77,2

3.1.4 Release studies=52,78,1

3.2 Pharmacokinetic studies[원본불량;p.57]=52,78,25

References=77,103,4

Chapter III. Kinetic Analysis of the Hepatic Uptake and Biliary Excretion of IH-901 in Rats=81,107,1

1. Introduction=82,108,2

2. Materials and Methods=84,110,1

2.1 Chemicals=84,110,1

2.2 Animals=84,110,1

2.3 In vivo uptake studies(Integration plot analysis)=84,110,2

2.4 In vivo infusion studies=86,112,1

2.5 Determination of IH-901=86,112,2

3. Results and Discussions=88,114,1

3.1 In vivo uptake studies(Integration plot analysis)=88,114,1

3.2 In vivo infusion studies=88,114,12

References=100,126,2

Chapter IV. Kinetic Analysis of the Hepatic Uptake IH-901 in Isolated Rat Hepatocytes=102,128,1

1. Introduction=103,129,2

2. Materials and Methods=105,131,1

2.1 Chemicals=105,131,1

2.2 Animals=105,131,1

2.3 Isolation of rat hepatocytes=105,131,2

2.4 Uptake studies=106,132,2

2.4.1 Concentration dependence=107,133,1

2.4.2 Effects of temperature=107,133,1

2.4.3/2.4.2 Effects of various inhibitors, substrates, and ion substitution=107,133,1

2.4.4/2.4.2 Effects of other ginsenosides=107,133,2

2.5 Determination of IH-901=108,134,1

26 Date analysis=108,134,2

3. Results and Discussions=110,136,1

3.1 Concentration dependence uptake=110,136,1

3.2 Effects of temperature=110,136,1

3.3 Effects of various inhibitors, substrates, and ion substitution=110,136,2

3.4 Effects of other ginsenosides=111,137,16

References=127,153,5

Chapter V. Kinetic Analysis of the Hepatic Uptake and Biliary Excretion of IH-901 in Cultured Rat Hepatocytes=132,158,1

1. Introduction=133,159,2

2. Materials and Methods=135,161,1

2.1 Chemlcals=135,161,1

2.2 Animals=135,161,1

2.3 Preparation of culture dishes=136,162,1

2.4 Isolation and culture of rat hepatocytes=136,162,2

2.5 Western blot analysis=137,163,2

2.6 Fluorescence microscopy=138,164,1

2.7 Uptake studies in sandwich-cultured hepatocytes=138,164,1

2.8 Data analysis=138,164,2

3. Results and Discussions=140,166,1

3.1 Effect of an upper layer of collagen gel on morphology of cultured hepatocyte=140,166,1

3.2 Western blot analysis=140,166,1

3.3 Fluorescence microscopy=140,166,2

3.4 Uptake studies in sandwich-cultured hepatocytes=141,167,11

References=152,178,3

Chapter VI. Conclusions=155,181,3

[Summary]=158,184,2

[Acknowledge]=160,186,1

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