【作者】 徐巍；

【导师】 邓树海；

【作者基本信息】 山东大学 ， 药剂学， 2006， 硕士

【摘要】 肝癌是最常见的恶性肿瘤之一，在我国，肝癌的死亡率占居民恶性肿瘤死亡率的第二位，严重影响了人们的健康。迄今为止，化学药物疗法仍是治疗肝癌的主要方法之一，抗癌药物肝靶向传输系统为肝癌的药物治疗提供了一种新的思路和给药方法。 大蒜素（allitrid）为百合科植物大蒜（allium sativum L．）鳞茎中所含的一种抗癌活性成分，化学名称为二烯丙基三硫化物（diallyl trisulfide，DATS）。大蒜素有独特的药理活性，其抗癌、防癌作用已被国内外大量实验研究结果证实。它对肝癌、胃癌、结肠癌、肺癌、前列腺癌、乳腺癌、白血病等多种肿瘤均有明显抑制作用。目前临床应用的大蒜素制剂主要有胶囊剂和注射剂，但普遍存在生物半衰期短(t_1／2=2.32h)和一定毒副作用等缺点，而且持续治疗易产生耐药性，理化性质不稳定。 采用现代靶向制剂技术，选择以DATS为模型药物，以生物可降解型高分子材料聚氰基丙烯酸正丁酯为载体材料研制肝靶向性大蒜素聚氰基丙烯酸正丁酯纳米粒，探索肝癌治疗药物肝靶向给药的新思路、新方法和新技术，具有很高的科学技术价值和实践应用价值。主要研究结果如下： 1．利用低温超速离心法对纳米粒与游离药物进行分离，采用HPLC法测定纳米粒中大蒜素的含量和包封率。 2．以大蒜素聚氰基丙烯酸正丁酯纳米粒的形态、包封率等为指标，通过单因素试验考察了表面活性剂和稳定剂的种类、搅拌时间、搅拌速度、制备温度、pH、吸附时间等因素对大蒜素聚氰基丙烯酸正丁酯纳米粒性质的影响，筛选出了影响大蒜素聚氰基丙烯酸正丁酯纳米粒质量指标的主要因素。并在此基础上，以DATS、Dxtran-70、PluronicF-68、α-BCA及NaHSO₃用量、pH值为考察因素，以大蒜素聚氰基丙烯酸正丁酯纳米粒形态、粒径分布、包封率更多还原

【Abstract】 Liver cancer, a most common malignancy, dose great harm to people health. In our country, the death rate of liver cancer ranks the second among those induced by malignancy. Up to now, medication still plays a most important role in the treatment of liver cancer. Due to the development of targeted drug delivery system, Liver-targeted drug delivery system arises and throws a light on a new thought and medication to treat liver cancer.Diallyl trisulfide （DATS） is a major anticancer ingredient from the bulb of garlic of liliaceous plants.It has antitumor activities, and its effects has been tested by many researches both in China and abroad. It can obviously control the liver cancer, stomach cancer, colon cancer, lung cancer, prostate cancer, galactophore cancer and leukaemia. There are capsules and injection in the market,but it has some disadvantages such as short half-life (t_1/2=2.32) , side effect and drug tolerance. Its physic-chemical characteristic was not stable too.In the present study , DATS was taken as the model drug to prepare hepatic targeted polybutylcyanoacrylate nanoparticles of diallyl trisulfide （DATS-PBCA-NP） by modern targeted drug delivery technique. All aspects of DATS-PBCA-NP were investigated in details and systematically to develop a new idea, new method and new technique for hepatic targeted drug delivery system （HTDDS）. The main results were as follows:1. The nanoparticles and free drugs were separated by ultra centrifugation at low temperature, then the content and entrapment efficiency of nanoparticles wasdetermined by HPLC.2. The particle shape and entrapment efficiency were taken as criterions to更多还原