吳茱萸之市售科學中藥品質分析及其奈米粒子之製備與抗癌活性評估

Quality assessment of traditional Chinese medicine in Euodiae Fructus, preparation of nanoparticles and evaluation of anti-cancer effects

蘇沛云(Pei-Yun Su)

指導教授 ： 吳育澤

高雄醫學大學/藥學院/藥學系碩士班/碩士(2019年)

摘要

吳茱萸具有諸多的藥理活性，然而其生物鹼中最主要的成分為去氫吳茱萸鹼(dehydroevodiamine)、吳茱萸鹼(evodiamine)和吳茱萸次鹼(rutaecarpine)，但因為其水溶性低、生體可用率差等問題，限制在臨床上的應用，又因市售科學中藥眾多品質含量不均，因此本研究之目的為開發HPLC分析方法以分析市售吳茱萸中藥之三種活性成分的含量。本研究亦利用聚乳酸甘醇酸(poly-lactide-co-glycolide, PLGA)，經由介面沉積(Interfacial deposition)以及高速均質法，製備含有吳茱萸鹼、吳茱萸次鹼和吳茱萸乙醇萃取物之奈米粒子。處方經由粒徑大小、外觀型態、藥品載藥量、藥品包埋率、體外溶離試驗、細胞存活率及安定性等進行評估。實驗開發之HPLC分析方法成功地同時分析吳茱萸的三種生物鹼，同日與異日間之精密度介於0.3至4.7%之間，而準確度介於93.6至108.7%之間，由此得知此方法具有良好的再現性與準確度。在PLGA奈米劑型中，載藥之奈米劑型組粒徑大小介於250至400 nm。在pH 7.4溶離試驗中，吳茱萸次鹼PLGA奈米劑型可以將吳茱萸次鹼溶離率從8.87提升至30.12%。細胞存活率試驗中，可以發現吳茱萸鹼在乳癌細胞和膀胱癌細胞濃度10 M時，皆有明顯降低癌細胞的增生效果。

關鍵字

吳茱萸 ； 去氫吳茱萸鹼 ； 吳茱萸鹼 ； 吳茱萸次鹼 ； 抗癌活性 ； PLGA奈米粒子

並列摘要

Euodiae Fructus (Wu-Zhu-Yu) has many pharmacological activities, however the major components are dehydroevodiamine, evodiamine and rutaecarpine. According to its poor water solubility and poor bioavailability, leading to the problems on clinical applications. The traditional Chinese medicine content is different; therefore, the aim of study is to analyze and compare the content of three active ingredients in the commercial products of Euodiae Fructus. In this study, poly-lactide-co-glycolide (PLGA) was used to prepare nanoparticle containing evodiamine, rutaecarpine and Euodiae Fructus with ethanol extract via interfacial deposition and high-speed homogenization. The formulation was characterized by its particle size, morphology, drug-loading content, drug encapsulation, in vitro release, cell survival ratio and stability. The HPLC method for analyzing Euodiae Fructus was successfully development. Moreover, the precision was between intra-day and inter-day ranged from 0.3 to 4.7%, and the accuracy was between 93.6 and 108.7%. In PLGA nanoparticles formulations, the particle sizes of evodiamine, rutaecarpine and Euodiae Fructus with ethanol extract loaded PLGA nanoparticels formulations of range were 250 nm to 400 nm. In the pH 7.4 dissolution test, the rutaecarpine PLGA nanoparticles formulation could enhance the dissolution efficiency of rutaecarpine from 8.87 to 30.12%. In the MTT assay, it was found that evodiamine significantly reduced the proliferation of breast cancer cells and bladder cancer cells when the concentration was 10 M.

並列關鍵字

Euodiae Fructus (Wu-Zhu-Yu) ； dehydroevodiamine ； evodiamine ； rutaecarpine ； anti-cancer effect ； PLGA nanaoparticles

參考文獻

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