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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林文貞(Wen-Jen Lin) | |
| dc.contributor.author | Po-Sheng Huang | en |
| dc.contributor.author | 黃博聖 | zh_TW |
| dc.date.accessioned | 2021-06-08T07:06:59Z | - |
| dc.date.copyright | 2008-09-25 | |
| dc.date.issued | 2008 | |
| dc.date.submitted | 2008-08-25 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/26343 | - |
| dc.description.abstract | 過去十幾年間藥物遞送系統的發展日漸進步。材料來源都是以生物可分解性與生體相容性為前提，希望利用合成的方式製備出具有雙性特質的材料，因此本實驗室利用世界上含量第二豐富的幾丁聚醣與已通過美國食品藥物管理局核可之己內酯與聚乙二醇為材料，用合成方式製備聚乙二醇-g-幾丁寡-g-聚己內酯之接枝共聚合物。
實驗上，首先改變幾丁聚醣的分子量至2000 g/mol，以達到水溶特性，再利用傅立葉轉換紅外光光譜儀與質子核磁共振光譜儀確認與聚己內酯和聚乙二醇接枝合成的每一個產物。另以示差掃描熱分析儀鑑定接枝共聚合物的熱變化性，並測試此材料的臨界微膠粒濃度，同時測試未含藥微膠粒的粒徑分佈，表面電荷與微膠粒的安定性，再分別以indomethacin與theophtlline為模式藥製備微膠粒劑型，探討藥物包覆率(E.E.)和藥物含量(D.L.)，也利用質子核磁共振光譜測試藥物與微膠粒的關係，最後並探討接枝共聚合物與三聚磷酸鈉(TPP)形成錯合物奈米粒的粒徑分佈與表面電荷關係。 所合成的三批聚乙二醇-g-幾丁寡醣-g-聚己內酯共聚合物，其結果如下： 1.粒徑分佈分別為124±9.31nm(#10)、563.57±54.11nm(#11-12)與206.53±9.28nm(#13)。 2.表面電荷3±0.2mV(#10)、2.57±0.32mV(#11-12)與2.80±0.17mV(#13)。 3.吲哚美洒辛的藥物包覆率38.56±2.6%(#10)、38.19±7.37%(#11-12)與23.70±3.04%(#13)。 4.無水茶鹼的包覆率則是10.28±5.65%(#11-12)與2.08±0.09%(#13)。 5.經過數週安定性測試顯示未含藥微膠粒十分穩定。 6.三聚磷酸鈉與接枝共聚合物(#13)混合的表面電荷最負可達到-20~-30mV，粒徑分佈比未添加之前提高約幾十奈米，二者根據共聚合物與三聚磷酸鈉混合的濃度而有所不同。 | zh_TW |
| dc.description.abstract | The development of drug delivery systems were going well, and the releated researches were very numerous in the past few decade. The resources of materials were having two characteristics which were biocompatible and biodegradable. We attempted to synthesize a new amphiphillc graft copolymer, mPEG-g-DADP-CS-g-PCL. The all part of materials were non-toxic. Chitosan is very abundant material in the world, poly(ε-caprolactone) and mPEG are the materials that already approved by FDA.
In this research, chitosan was depolymerized until it can dissolve in the water, where the Mn was around 2000 g/mol. Each sample was identified by IR and NMR, and the thermal properties by DSC. The CMC of this new material was measured by using pyrene. Indomethaicn and theophylline were chosen as the model drugs to evaluate the drug loading and loading efficiency in the micelles. The interaction of the drug and micelles were measured by NMR. Finally, the surface charge and size distribution of complex of TPP and graft copolymer were investigated. The properities of three graft copolymers, mPEG-g-DADP-CS-g-PCL, were listed below: 1、 The size distributions were 124±9.31nm(#10), 563.57±54.11nm(#11-12), and 206.53±9.28nm(#13). 2、 The surface charge of this three polymers were 3±0.2mV(#10), 2.57±0.32mV(#11-12), and 2.80±0.17mV(#13). 3、 The entrapment of efficiency(%) of indomethacin were 38.58±2.6%(#10), 38.19±7.37%(#11-12), and 23.70±3.04%(#13). 4、 The entrapment of efficiency(%) of theophylline were 10.28±5.65%(#11-12) and 2.08±0.09%(#13). 5、 The unloaded micelles were very stable during a few weeks. 6、 The surface charge of the complex of the TPP and graft copolymer was reaching -20 to -30mV, and the size was higher than without TPP. Both depended on the concentration of polymer and TPP. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T07:06:59Z (GMT). No. of bitstreams: 1 ntu-97-R94423014-1.pdf: 1788910 bytes, checksum: 0aeb79feefc6b8920598b2c10ea2cc21 (MD5) Previous issue date: 2008 | en |
| dc.description.tableofcontents | 第一章 緒論••••••••••••••••••••••••••••••••••••••••••••••••••••••1
一、 生物醫學材料••••••••••••••••••••••••••••••••••••••••••••••••1 二、 幾丁質與幾丁聚醣之物理化學性質••••••••••••••••••••••••••••••3 三、 聚己內酯物理化學性質••••••••••••••••••••••••••••••••••••••••7 四、 幾丁聚醣與聚己內酯的應用••••••••••••••••••••••••••••••••••••9 五、 聚乙二醇的物化性質•••••••••••••••••••••••••••••••••••••••••10 六、 共聚合物•••••••••••••••••••••••••••••••••••••••••••••••••••10 七、 雙性微膠粒•••••••••••••••••••••••••••••••••••••••••••••••••12 八、 微膠粒的製備方式•••••••••••••••••••••••••••••••••••••••••••13 第二章 試劑與材料介紹•••••••••••••••••••••••••••••••••••••••••••15 一、 幾丁聚醣•••••••••••••••••••••••••••••••••••••••••••••••••••15 二、 己內酯•••••••••••••••••••••••••••••••••••••••••••••••••••••15 三、 甲氧基聚乙二醇•••••••••••••••••••••••••••••••••••••••••••••16 四、 有辛酸亞錫•••••••••••••••••••••••••••••••••••••••••••••••••17 五、 鄰苯二甲酸酐•••••••••••••••••••••••••••••••••••••••••••••••18 六、 水合胼•••••••••••••••••••••••••••••••••••••••••••••••••••••18 七、 吲哚美洒辛•••••••••••••••••••••••••••••••••••••••••••••••••19 八、 無水茶鹼•••••••••••••••••••••••••••••••••••••••••••••••••••20 九、 焦油腦•••••••••••••••••••••••••••••••••••••••••••••••••••••21 一〇、 三聚磷酸鈉•••••••••••••••••••••••••••••••••••••••••••••••••21 第三章 實驗動機與目的•••••••••••••••••••••••••••••••••••••••••••23 第四章 實驗試劑與儀器•••••••••••••••••••••••••••••••••••••••••••25 一、 試劑••••••••••••••••••••••••••••••••••••••••••••••••••••••••25 二、 儀器與耗材••••••••••••••••••••••••••••••••••••••••••••••••••27 三、 藥品溶液及緩衝溶液之配製••••••••••••••••••••••••••••••••••29 第五章 實驗方法•••••••••••••••••••••••••••••••••••••••••••••••••31 一、 接枝共聚合物mPEG-g-DADP-CS-g-PCL的合成••••••••••••••••••33 二、 傅立葉轉換紅外光光譜(FT-IR) •••••••••••••••••••••••••••••••45 三、 核磁共振光譜(NMR) •••••••••••••••••••••••••••••••••••••••45 四、 示差掃瞄熱分析(DSC) ••••••••••••••••••••••••••••••••••••••45 五、 膠體滲透層析(GPC) ••••••••••••••••••••••••••••••••••••••••46 六、 幾丁聚醣分子量與穿透度分析••••••••••••••••••••••••••••••••47 七、 臨界微膠粒濃度測試(CMC) •••••••••••••••••••••••••••••••••47 八、 製備微膠粒••••••••••••••••••••••••••••••••••••••••••••••••48 九、 醣類定量分析(測量mPEG-g-DADP-CS-g-PCL中DADP-CS的含量) 49 一〇、 微膠粒安定性試驗•••••••••••••••••••••••••••••••••••••••••••49 一一、 含藥微膠粒劑型之製備•••••••••••••••••••••••••••••••••••••••50 一二、 吲哚美洒辛(Indomethacin)HPLC定量方法•••••••••••••••••••••••51 一三、 吲哚美洒辛包覆率測定•••••••••••••••••••••••••••••••••••••••51 一四、 無水茶鹼(theophylline) HPLC定量方法••••••••••••••••••••••••••52 一五、 無水茶鹼包覆率測定•••••••••••••••••••••••••••••••••••••••••52 一六、 共聚合物之奈米粒製備•••••••••••••••••••••••••••••••••••••52 第六章 結果與討論•••••••••••••••••••••••••••••••••••••••••••••••••55 一、 DA-CS分子量的探討•••••••••••••••••••••••••••••••••••••••55 二、 DADP-CS水溶性的探討••••••••••••••••••••••••••••••••••••58 三、 mPEG-g-DADP-CS-g-PCL合成之測定•••••••••••••••••••••••••61 四、 產物(mPEG-g-DADP-CS-g-PCL)結構上的討論•••••••••••••••••••87 五、 外觀型態•••••••••••••••••••••••••••••••••••••••••••••••••88 六、 GPC測量mPEG-g-DADP-CS-g-PCL分子量與元素分析••••••••••••88 七、 共聚合物示差掃描熱分析儀的測試•••••••••••••••••••••••••••90 八、 共聚合物之臨界微焦粒濃度(CMC)測量•••••••••••••••••••••••92 九、 微膠粒粒徑分析•••••••••••••••••••••••••••••••••••••••••••93 一〇、 微膠粒表面電位的測試•••••••••••••••••••••••••••••••••••••94 一一、 接枝共聚合物－醣類的定量•••••••••••••••••••••••••••••••••95 一二、 HPLC藥物檢量線•••••••••••••••••••••••••••••••••••••••••97 一三、 微膠粒藥物包覆率測試•••••••••••••••••••••••••••••••••••••98 一四、 利用NMR觀察藥物與微膠粒的關係••••••••••••••••••••••••••100 一五、 接枝共聚合物與TPP混合成錯合物奈米粒之粒徑與電荷的探討•••102 一六、 微膠粒安定性測試•••••••••••••••••••••••••••••••••••••••••105 一七、 含藥微膠粒與示差掃描熱分析儀•••••••••••••••••••••••••••••106 第七章 結論••••••••••••••••••••••••••••••••••••••••••••••••••••109 第八章 參考文獻••••••••••••••••••••••••••••••••••••••••••••••••111 | |
| dc.language.iso | zh-TW | |
| dc.subject | 聚乙二醇 | zh_TW |
| dc.subject | 微膠粒 | zh_TW |
| dc.subject | 甲殼素 | zh_TW |
| dc.subject | 聚己內酯 | zh_TW |
| dc.subject | micelles | en |
| dc.subject | polyethylene glycol | en |
| dc.subject | polycaprolactone | en |
| dc.subject | chitosan | en |
| dc.title | 甲殼素/聚己內酯共聚合物之合成與性質研究 | zh_TW |
| dc.title | The Synthesis and Characterization of Chitosan/Poly(caprolactone) Copolymer | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 96-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 王麗芳,黃義侑,陳錦龍 | |
| dc.subject.keyword | 微膠粒,甲殼素,聚己內酯,聚乙二醇, | zh_TW |
| dc.subject.keyword | micelles,chitosan,polycaprolactone,polyethylene glycol, | en |
| dc.relation.page | 118 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2008-08-25 | |
| 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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| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-97-1.pdf 未授權公開取用 | 1.75 MB | Adobe PDF |
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