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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78292完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林峯輝(Feng-Huei Lin) | |
| dc.contributor.author | I-En Lin | en |
| dc.contributor.author | 林逸恩 | zh_TW |
| dc.date.accessioned | 2021-07-11T14:49:44Z | - |
| dc.date.available | 2025-08-11 | |
| dc.date.copyright | 2020-08-26 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-08-11 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78292 | - |
| dc.description.abstract | 停經後的女性會因為體內雌激素的濃度劇烈下降，而有像熱潮紅、盜汗、失眠的全身性的症狀，以及陰道萎縮、乾燥搔癢等局部不適的問題，除身體不舒服外還會嚴重降低生活素質，也可能因為情緒不定影響周遭親友。 目前臨床上最普遍使用於治療陰道乾燥萎縮的方式為塗抹陰道軟膏，但由於軟膏的黏膜貼附效果不佳，需要頻繁的塗抹給藥才能維持陰道的雌激素濃度，造成使用者的不便。再來是目前市面上所使用的有效成分皆為雌二醇及其衍生物，屬於處方藥物，須經醫師看診才能取得，無法在藥局臨櫃購買，會造成部分不願意上醫院看病的更年期女性無法受益。 本研究使用幾丁聚醣做為水膠主成分，以BDDE交聯、接上含硫醇乙酸增加黏膜貼覆性，動物黏膜表面的musin含有半胱胺酸未鍵結的 -SH基，可與實驗製備的含硫醇基水膠形成較穩固的雙硫鍵鍵結，並利用黏膜表面對硫的氧化還原特性達到將水膠緩慢代謝排出體外的目的。水膠內會加入雌激素類似物Di (2-ethylhexyl) phthalate (DEHP) 或Genistein以取代現有雌激素軟膏中的作用成分。 本實驗實驗材料合成後以Ellman's assay、FTIR及NMR檢測官能基及含硫量，能成功的將Chitosan接上硫基，加入DEHP、Genistein後利用HPLC測量兩者的釋放曲線。In vitro 則根據ISO 10993，以L929進行WST-1及Live Dead，確認材料沒有細胞毒性，以Caco2細胞進行微流道實驗，確認修飾後材料對黏膜的貼附能力提升。In vivo以去除雙側卵巢的SD大鼠模擬停經女性，於陰道給予含有DEHP或Genistein的水膠一個月後犧牲，透過量測體重、量測陰道子宮濕重量、製作陰道抹片、計算陰道成熟指數，及觀察組織切片HE染色後之表皮厚度，確認材料能部分緩解陰道萎縮的症狀。 | zh_TW |
| dc.description.abstract | Vagina atrophy is a common symptom in women after menopause due to lowering of estrogen level. Discomforts such as itch, dryness, irritation and soreness can bother for years. The most general treatment is estrogen cream, which is cheap and flexible in dosing. However, the cream contains the prescription drug, estrogen, which is not available at over-the-counter pharmacy. The other disadvantage is the weak adhesion to the vagina mucus, which means that frequent application is needed daily. In this study, we used BDDE to crosslink and conjugate chitosan and thiol glycolic acid to improve the mucoadhesive property of chitosan. The results of Ellman’s assay, FTIR and NMR confirm the functional groups and chemical structure of thiolated chitosan, and the release profile of DEHP/ genistein was checked by HPLC. WST-1 assay and Live Dead assay both showed that our material had low cytotoxicity. The mucoadhesive property was checked by microfluidic channel cultured with Caco2 cells and FITC-labeled material, and showed that thiolated chitosan is about two fold stronger against the constant flow compared with the unmodified one. The animal model was built up one month after bilateral ovariectomy of SD rats and divided into five groups, control group (C), ovariectomy group (OVX), estradiol group (E), thiolated chitosan with genistein (CT-G), and thiolated chitosan with DEHP (CT-D). By checking body weight, vagina smear, blood tests and histology, the results showed that our material can reverse about 50% of the epithelium thickness of atrophic vagina and had no toxicity to liver nor kidney. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T14:49:44Z (GMT). No. of bitstreams: 1 U0001-0908202012194100.pdf: 4144361 bytes, checksum: af9f2435a4d7d3ed0db5f01a47cff71b (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 摘要 ii Abstract iii 目錄 iv 圖目錄 vii 表目錄 ix 縮寫目錄 x 第一章 簡介 1 1.1 流行統計 1 1.2 症狀 2 1.3 陰道截面與黏膜性質 3 1.4 評估方式 3 1.4.1 陰道上皮厚度 3 1.4.2 陰道黏膜之pH值 4 1.4.3 陰道成熟指數 4 1.5 治療方式 6 1.5.1 荷爾蒙療法 6 1.5.2 非荷爾蒙療法 8 1.6 研究目的 11 第二章 基礎理論 12 2.1 陰道吸收途徑 12 2.2 黏膜貼附理論 12 2.3 氧化還原環境 13 2.4 材料選擇 14 2.4.1 Chitosan 14 2.4.2 BDDE 15 2.4.3 TGA 15 2.4.4 DEHP 16 2.4.5 Genistein 17 2.4.6 FITC 17 第三章 實驗步驟與方法 18 3.1 實驗藥品 18 3.2 實驗儀器 20 3.3 實驗架構 21 3.4 材料合成 22 3.4.1 Crosslinked chitosan-TGA (CT) 22 3.4.2 Crosslinked chitosan-TGA-FITC (CTF) 22 3.4.3 DEHP/ Genistein釋放曲線 23 3.5 材料分析 23 3.5.1 EDS 23 3.5.2 Ellman’s assay 23 3.5.3 FTIR 24 3.5.4 NMR 25 3.5.5 HPLC-MS/MS 25 3.6 In vitro study 26 3.6.1 細胞培養 26 3.6.2 WST-1 26 3.6.3 Live Dead 27 3.6.4 Cell adhesion test 27 3.7 In vivo study 28 3.7.1 動物實驗設計及組別 28 3.7.2 體重與子宮陰道濕重量 29 3.7.3 陰道抹片 29 3.7.4 血球計數及血清生化檢查 30 3.7.5 組織切片 30 3.8 統計方法 30 第四章 結果與討論 31 4.1 材料分析 31 4.1.1 EDS 31 4.1.2 Ellman’s assay 32 4.1.3 FTIR 33 4.1.4 NMR 34 4.1.5 HPLC-MS/MS 35 4.2 In vitro study 36 4.2.1 WST-1 36 4.2.2 Live Dead 37 4.2.3 Cell adhesion test 38 4.3 In vivo study 40 4.3.1 體重與子宮及陰道濕重量 40 4.3.2 陰道抹片 41 4.3.3 血球計數及血清生化檢查 42 4.3.4 組織切片 43 第五章 結論 44 第六章 參考文獻 45 | |
| dc.language.iso | zh-TW | |
| dc.subject | 幾丁聚醣 | zh_TW |
| dc.subject | 陰道萎縮 | zh_TW |
| dc.subject | 硫醇 | zh_TW |
| dc.subject | 金雀異黃酮 | zh_TW |
| dc.subject | 鄰苯二甲酸二(2-乙基己基) 酯 | zh_TW |
| dc.subject | DEHP | en |
| dc.subject | thiolglycolic acid | en |
| dc.subject | vagina atrophy | en |
| dc.subject | chitosan | en |
| dc.subject | genistein | en |
| dc.title | 開發含有雌激素類似物之硫醇乙酸修飾幾丁聚醣用於舒緩陰道萎縮 | zh_TW |
| dc.title | The Development of Thioglycolic Acid Immobilized Chitosan Hydrogel as Carrier of Estrogen Analog for Vaginal Atrophy | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 吳鴻明(Hung- Ming Wu),郭士民(Shi-Min Kuo) | |
| dc.subject.keyword | 陰道萎縮,幾丁聚醣,硫醇,金雀異黃酮,鄰苯二甲酸二(2-乙基己基) 酯, | zh_TW |
| dc.subject.keyword | vagina atrophy,chitosan,thiolglycolic acid,genistein,DEHP, | en |
| dc.relation.page | 49 | |
| dc.identifier.doi | 10.6342/NTU202002704 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2020-08-12 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 醫學工程學研究所 | zh_TW |
| dc.date.embargo-lift | 2025-08-11 | - |
| 顯示於系所單位： | 醫學工程學研究所 | |
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