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  • 學位論文

第一部分:結合五氨基酮戊酸之光動力效應與Carbopol應用於CL1系列細胞之研究 第二部分:建置化學性防曬產品成分的安全性評估及流程管理體系與品質規範之架構

Part 1:The Effect of Carbopol on ALA-induced PDT in CL1 cells Part 2:Establish the Skeleton of Safety Evaluation and Standard Regulation in Chemical Sunscreen Products

指導教授 : 蔡翠敏

摘要


第一部分: 光動力治療(Photodynamic Therapy;PDT)為近三十年新興發展的癌症治療技術,藉由在腫瘤組織累積的光感物質(Photosensitizer)受到特定波長光的刺激產生光化學作用繼而對細胞產生毒殺效果。五氨基酮戊酸(aminolevulinic acid;ALA)在原血紅素合成路徑(Heme Biosynthetic Pathway)中能代謝成內生性的光感物質—吡喀紫質(Protoporphyrin IX;PpIX);五氨基酮戊酸現已在臨床診斷及治療中廣泛使用,光動力治療是目前用於癌症治療以及診斷的嶄新方法,當其運用於腸胃癌、食道癌及肺癌的治療過程中,相較於其他外科手術具有較低侵略性,而光動力治療的另一向特質為對腫瘤細胞有特殊選擇性,因此在臨床上使用時,此方法具有相當的安全性且能有效率的針對癌細胞做治療,使其接受度更為廣泛。 在本研究中將使用ALA-PDT來處理肺腺癌細胞,以及確認賦形劑—Carbopol 971P (CP971P)在此當中所扮演的角色,研究中所使用的肺腺癌細胞CL1-0以及CL1-2是由一位64歲的台灣男性患部取得,而在研究結果中發現CL1-0的PpIX累積量高於CL1-2,而且對於光照後產生的毒性也高於CL1-2,這結果顯示,較高侵入能力的細胞—CL1-2對於ALA-PDT的敏感度較低,而在賦形劑的運用方面,CP971P在與ALA培養後也確實能增加CL1-0的光毒性且能增加PpIX的累積量,但在CL1-2卻無觀察到此現象。 第二部分: 化妝保養品產業是低污染、高附加價值的產業,結合生物科技、美學與市場行銷的新興產業,亦被政府列為2008國家發展計畫重點之一。目前世界各國均致力於國際間化妝品管理調和以擬定相關法規,使標準趨於一致性,我國也順應國際潮流,期望建立符合國際趨勢之化妝品管理辦法。 防曬用品日前已成為民眾之民生必需品,化學性防曬成分的安全性一直是近年來的討論議題,而目前各國已投入相當多經費在防曬化妝品中,但卻未有一定的管理方式及法規,各國政策對於管理心態大多劃地自限,制訂適合該國的管理模式,且過於保護本國企業,但國際間對於化妝品均傾向於寬鬆管理的方式,望各國政府鬆綁法令;全球化的市場競爭激烈,為求得最佳生存空間,制訂管理化妝產品已勢在必行。 本研究特別就「化學性防曬成分的化妝品」擬定其安全性評估之模式及檢驗方法,提供化學性成分用於化妝品其間交互作用之參考依據;首先蒐集彙整歐盟、美國、日本及澳洲等各先進國家對於化學性防曬成分化妝品之管理法規、檢驗方法進行比較,並擬定化學性防曬化妝品管理之相關規範及管理流程,加以建立化學性防曬化妝品之安全性資料庫,接著擬定其管理流程,為日後化學性防曬化妝品安全性評估之依據,期望建立其安全性評估模式及試驗方法,以提供未來行政管理之參考。

並列摘要


Part 1: Photodynamic therapy (PDT) is a novel methodology used in the treatment of neoplastic lesion. Due to its safety, efficiency, and minimal invasion, PDT has become more popular in the treatment of gastrointestinal cancers, esophageal cancer, and lung cancer. Aminolevulinic acid (ALA) was applied in this study. PDT employing ALA as a precursor of the photosensitizer Protoporphyrin IX (PpIX) has become a promising approach to treat superficial cancers. ALA has been successfully used to diagnose and treat neoplastic tissue. In this study, we tried to investigate the potential of using ALA-PDT to treat the lung adenocarcinoma, and the role of the excipient Carbopol 971P (CP971P) on the formation of PpIX. Human lung adenocarcinoma cell lines, CL1-0 and CL1-2 cell lines (obtained from a 64-year-old male in Taiwan) with various in vitro invasive abilities were used in this study. Compared to CL1-2 cells, PpIX formation was more in the CL1-0 cells. Significant phototoxicity was observed in CL1-0 while CL1-2 cells were less sensitive to ALA-PDT. These results indicate that, higher invasive ability of CL1-2 cells express less sensitive to ALA-PDT induced phototoxicity. The presence of CP971P during the ALA incubation seemed to enhance the phototoxicity in CL1-0 cells but not in CL1-2 cells. Part 2: The sunscreen products had already become the people's livelihood necessities in recent years. However, the safety of chemical sunscreen ingredients had been questioned and world-wide discussed for the past. Large numbers of countries have already invested lots of finance in sunscreen products. Global cosmetic harmonization of the regulations that control these products is a priority for all over the world. The competition of marketing is fierce in the whole world. In order to get the best existence space, it is already imperative to make and manage to cosmetic products. In this study, we aimed to compile the safety and assessment methods to inspect the chemical sunscreens products. We tried to establish the data base of the interactions between sunscreen ingredients and other cosmetic compositions. We searched the regulation rules of sunscreens in U.S., European Union, Australia and Japan, and compared the management and inspection of the chemical sunscreens. We proposed a regulation scheme of chemical sunscreens to fit the folkway in Taiwan under global harmonization.

參考文獻


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