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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳進庭 | |
| dc.contributor.author | Jun-Yan Chen | en |
| dc.contributor.author | 陳俊諺 | zh_TW |
| dc.date.accessioned | 2021-06-07T18:06:59Z | - |
| dc.date.copyright | 2012-07-26 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-07-24 | |
| dc.identifier.citation | 1. Dougherty, T. J. et al. Photodynamic therapy. J Natl Cancer Inst 90, 889-905 (1998).
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Microneedle pre-treatment of human skin improves 5-aminolevulininc acid (ALA)- and 5-aminolevulinic acid methyl ester (MAL)-induced PpIX production for topical photodynamic therapy without increase in pain or erythema. Pharmaceutical Research 27, 2213-2220 (2010). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16256 | - |
| dc.description.abstract | 光動力治療(photodynamic therapy, PDT)是具潛力的腫瘤治療方法，五胺基酮戊酸(5-aminolevulinic acid, ALA)為目前臨床上常使用於光動力治療的光感物質前驅藥物。ALA可經血紅素合成路徑而轉化為光感物質原紫質環IX(protoporphyrin IX, PpIX)。但ALA安定性並不佳，目前市面上常見之ALA製劑需使用前預混或開封一週後拋棄。因此開發安定且便利的ALA劑型有其需要性。另一方面，分析ALA含量常需將ALA衍生為螢光產物，再以高效液相層析儀(high-performance liquid chromatography, HPLC)進行分析，在分析上除需費時費工製作螢光衍生物，分析上也易受雜訊干擾。所以找尋新的ALA分析方法以增加分析之便利性，亦有其必要性。本研究建立新的ALA含量及降解產物的分析方法，與常用之ALA衍生搭配HPLC分析方法比較，兩者線性相關(R2)>0.9。此外本研究亦篩選適合於藥物使用之賦形劑，藉由細胞試驗來探討這些賦形劑是否適合做為ALA製劑之材料，並就做成之成品進行物化性質探討及動物試驗。 | zh_TW |
| dc.description.abstract | Photodynamic therapy is a therapeutic modality for cancer treatment. 5-Aminolevulinic acid (ALA) is currently used as a photosensitizer precursor in clinical application. ALA is not a photosensitizer and converted into the photosensitizer, protoporphyrin IX (PpIX), via heme biosynthetic pathway. Due to the poor stability, current products of ALA either has to be used prior to mix with the solvent vehicle or has to be discarded one week after opening. For these reasons, it is necessary to develop a stable and convenient ALA dosage form. Meanwhile, due to the weak absorbance and high noise, the fluorescent derivatives of ALA is prepared and further analyzed in HPLC. However, such analysis method is time and labor comsuming, and easily interfered by noise. In this study, a new method for analyzing ALA content and its degradation was developed, and the linear regression correlation (R2) to the HPLC method is greater than 0.9. In addition, excipient screening and cell culture tests were carried out to select suitable excipients for ALA dosage form. The final preparation was examined for its physiochemical properties and in an animal model. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-07T18:06:59Z (GMT). No. of bitstreams: 1 ntu-101-R99b22053-1.pdf: 1975705 bytes, checksum: 83e60cbf07a7fd8cbe5efca07cbad83d (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | 摘要 I
Abstract II 圖目錄 VI 表目錄 VII 第一章 緒論 1 1.1光動力治療(Photodynamic therapy, PDT) 1 1.1.1發展起源 1 1.1.2光動力治療的作用機制 2 1.1.3光感物質 3 1.1.4五胺基酮戊酸(5-aminolevulinic acid, ALA)在體內扮演的角色 4 1.1.5 ALA-PDT在臨床的使用 5 1.2 5-Aminolevulinic acid的安定性與分析 6 1.2.1 ALA的降解機制 7 1.2.2影響ALA降解路徑的因子 7 1.2.3 ALA分析 9 1.3研究動機與目的 12 第二章 材料與方法 13 2.1藥品與儀器 13 2.1.1藥品 13 2.1.2細胞培養試劑 14 2.1.3儀器 14 2.2細胞株 15 2.2.1細胞繼代培養 15 2.2.3細胞計數 16 2.3 5-Aminolevulinic acid分析 16 2.3.1 HPLC管柱前衍生(ALA衍生) 16 2.3.2 HPLC樣本測定 16 2.3.3毛細管電泳 17 2.4劑型開發 17 2.4.1賦形劑篩選 17 2.4.2賦形劑對細胞累積PpIX之影響 18 2.4.3薄膜製程 18 2.4.4薄膜保存 18 2.5薄膜特性分析 19 2.5.1藥物滲透測定 19 2.5.2樣本pH之測定 19 2.5.3薄膜含水率之測定 19 2.5.4薄膜厚度測定 20 2.5.5 5-Aminolevulinic acid安定性 20 2.6動物試驗 20 2.6.1動物與腫瘤模式 20 2.6.2給藥流程 20 2.6.3 Protoporphyrin IX之測定 21 2.6.4樣本包埋、冷凍切片及共軛焦顯微鏡之方法 21 2.7 統計分析 21 第三章 結果 22 3.1劑型開發 22 3.1.1薄膜賦形劑篩選 22 3.1.2塑化劑賦形劑篩選 22 3.1.3賦形劑對細胞累積Protoporphyrin IX的影響 23 3.1.4最佳化具潛力配方 23 3.2薄膜特性分析 24 3.2.1薄膜藥物滲透 24 3.2.2各薄膜之pH、含水量及厚度 25 3.2.3 HPMC薄膜藥物析出 26 3.2.4 ALA在劑型中之安定性分析 26 3.3動物試驗 27 3.3.1評估各薄膜在動物模式上累積PpIX之差異 27 3.3.2不同濃度ALA的PCM薄膜在動物模式累積PpIX圖譜 27 3.3.3評估不同薄膜使用時間及劑量在動物模式上累積PpIX之差異 28 3.3.5以冷凍切片觀察PpIX在組織的分佈 28 第四章 討論 29 4.1劑型開發 29 4.1.1賦形劑篩選 29 4.1.2賦形劑增進細胞累積PpIX 29 4.2薄膜特性分析 30 4.2.1薄膜的物理性質 30 4.2.2 ALA分析及在薄膜之安定性 32 4.3動物試驗 33 4.3.1薄膜不同配方、ALA濃度及用藥時間在動物模式的PpIX累積 33 4.3.2 PpIX使用薄膜後在動物組織的分佈 34 第五章 結論與未來工作 36 圖 37 表格 55 附錄 58 參考文獻 61 | |
| dc.language.iso | zh-TW | |
| dc.title | 五胺基酮戊酸之劑型及分析方法研究 | zh_TW |
| dc.title | 5-Aminolevulinic acid analysis and dosage form development | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 蔡翠敏,黃慶璨,許瑞祥 | |
| dc.subject.keyword | 光動力治療,五胺基酮戊酸,原紫質環IX,安定性,劑型, | zh_TW |
| dc.subject.keyword | Photodynamic therapy,5-ALA,Protoporphyrin IX,Stability,Dosage form, | en |
| dc.relation.page | 72 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2012-07-24 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科技學系 | zh_TW |
| 顯示於系所單位： | 生化科技學系 | |
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