請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19115完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 梁碧惠 | |
| dc.contributor.author | Tsung-Yun Wong | en |
| dc.contributor.author | 翁琮昀 | zh_TW |
| dc.date.accessioned | 2021-06-08T01:45:32Z | - |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-12 | |
| dc.identifier.citation | References
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19115 | - |
| dc.description.abstract | 類黃酮化合物具有廣效的活性，如抗氧化、抗凝血、抗發炎。但類黃酮之水溶性限制其動物實驗的活性探討。本研究將針對類黃酮A進行結構相同性研究(cluster study)，以細胞模型探討構效關係；為了提升其水溶解度將其製成微脂體劑型，並合成類黃酮A之葡萄糖苷9、硫酸鉀鹽12、磷酸鈉鹽13，及為了增加其穿透血腦屏障能力與甘胺酸甲酯及甘胺酸形成之氨基甲酸酯15b與16。除了進行這些衍生物的細胞活性試，同時也開發HPLC分析方法測試其溶解度及logP值。綜合以上之結果，可提供類黃酮A結構優化方向，以提供其解決腦神經相關疾病之研究。 | zh_TW |
| dc.description.abstract | Flavonoids comprise multiple biological activities, e.g., anti-oxidative, antithrombotic, and anti-inflammatory activities. Some of flavonoids are of low water solubility which limits their development in animal study. In this thesis, the structure-activity relationship (SAR) of flavonoid A would be discussed via a cluster study. To improve its water solubility, liposome suspension of various formulations have been designed and prepared. For its structural modification, the corresponding glucoside 9, potassium sulfate salt 12, and phosphate sodium salt 13 have also been designed and synthesized. Additionally, to promote its BBB permeation, glycine methyl ester and glycine were coupled with it to form the corresponding carbamates 15b and 16. These derivatives were subsequently measured for their log P values and solubility by the HPLC method. Overall, this study provides the direction of future optimization for the studies of CNS diseases. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T01:45:32Z (GMT). No. of bitstreams: 1 ntu-105-R03423001-1.pdf: 2729973 bytes, checksum: e3dd54841bb8713f38a1a42e939036ef (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | Table of Contents
中文摘要............................................................................................................................i Abstract.............................................................................................................................ii Table of Contents..............................................................................................................iv List of Figures.................................................................................................................vii List of Schemes…………………………………………………………………..…….vii List of Tables……………………………………………………………………..…….vii List of Abbreviations………...…………………………………………………...……viii Chapter 1 – Introduction 1.1 Flavonoids……………………….………………………………………………….1 1.1.1 Major Backbones ………………………………….…………………..…….1 1.1.2 Configurations……………………………………………………………..…2 1.1.3 Natural Sources…………………………………………………………..….3 1.1.4 Bioactivities …………………………………….…………………...…..….4 1.1.4.1 Antioxidant Activity…………………………….………...……….…4 1.1.4.2 Antithrombotic Activity……………………………………..………5 1.1.4.3 Anti-inflammatory Activity…………………….…………..…...…….5 1.1.5 Pharmacokinetics……………………………...………………………..…….6 1.2 Blood-Brain Barrier…………………………………….………………………...….7 1.2.1 The Fundamental of BBB……………………………………………...……..7 1.2.2 Mechanisms Affecting BBB Permeation…………………………………......8 1.2.2.1 Facilitative Transportation of Glucose……………….………………9 1.2.2.2 Facilitative Transportation of Monocarboxylic Acids………….……..9 1.2.2.3 Facilitative Transportation of Amino Acids………………...….……...9 1.2.2.3.1 System L – Large Essential Neutral Amino Acids…..……….10 1.2.2.3.2 System y+ – Cationic Amino Acids……………………..…....10 1.2.2.3.3 System x- – Anionic Amino Acids………………...………….10 1.2.2.3.4 System n – Nitrogen-Rich Amino Acids………..………..…..11 1.2.2.4 Na+-dependent Transportation of Amino Acids……..………………11 1.2.2.4.1 System A – Small Nonessential Neutral Amino Acids…..…11 1.2.2.4.2 System ASC – Some Large and Small Neutral Amino Acids...11 1.2.2.4.3 System N – Nitrogen-Rich Amino Acids………..……..…….12 1.2.2.4.4 System EAAT – Acidic Amino Acids………………………12 1.2.2.4.5 System Na+-LNAA – Large Neutral Amino Acids………..….12 1.2.3 Structure-BBB Penetration Relationships…………………………………..…..12 1.2.4 Structure Modification Strategies for Brain Penetration Improvement………...13 Chapter 2 – Results, Discussion and Conclusion 2.1 Objective……………………………………………………………………..…..14 2.2 Strategy…………………………………………………………………….…….14 2.3 Apigenin Liposome Suspension……………………………………………..….15 2.4 Apigenin and Its Derivatives………………………………………………........17 2.4.1 Synthesis of Apigenin…………………………………………….……….20 2.4.2 Apigenin Derivatives……………………………………………………....20 2.4.2.1 Apigenin Glucosides………………………………………….....…20 2.4.2.2 Apigenin, Sulfate and Phosphate salts……………………………..21 2.4.2.3 Apigenin–Amino Acid Carbamates………………………………..22 2.5 Physical/Chemical Properties of Apigenin and Its Derivatives…………….....23 2.6 Biological Results—The Stracture-Activity Relationship of Flavonoids…..…..24 2.7 Conclusion…………………………………………………………………………29 Chapter 3 – Experimental Section 3.1 General Information…………………………………………………………….30 3.2 General Procedures for Compounds Preparation.…………...…………………32 3.3 Preparation and Physicochemical Characterization of Apigenin Liposome…45 3.3.1 Preparation of Apigenin Liposome…………………………………..……45 3.3.2 Determination of Particle Size………………………………………………45 3.3.3 Determination of Entrapment Efficiency…………………………………45 3.4 Measurement of Log P …………………………………………………………46 3.5 Measurement of Solubility………………………………………………………47 3.6 Luciferase Assay…………………………………………………………………47 References………………………………………………………………………..……48 Appendix………………………………………………………………………..……57 | |
| dc.language.iso | en | |
| dc.subject | 類黃酮 | zh_TW |
| dc.subject | flavonoids | en |
| dc.title | 設計與合成類黃酮衍生物及劑型優化 | zh_TW |
| dc.title | Design and Synthesis of Flavonoid Derivatives and Formulation Optimization | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林淑華,許麗卿 | |
| dc.subject.keyword | 類黃酮, | zh_TW |
| dc.subject.keyword | flavonoids, | en |
| dc.relation.page | 90 | |
| dc.identifier.doi | 10.6342/NTU201602488 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2016-08-12 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥學研究所 | zh_TW |
| 顯示於系所單位： | 藥學系 | |
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