五胺基酮戊酸之劑型及分析方法研究

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。

關鍵字

光動力治療；五胺基酮戊酸；原紫質環IX ；安定性；劑型

並列摘要

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.