紫杉醇自乳化给药体系的构建研究.docVIP

紫杉醇自乳化给药体系的构建研究 摘 要 紫杉醇是一种天然的抗癌原料药，(Taxus brevifolia)的树皮中分离得到的单体双萜类化合物0.006mg/ml）导致其口服生物利用度很低，且存在急性过敏反应等问题。为此，我们尝试采用自乳化药物传递系统（SEDDS），使紫杉醇与油相、水相、表面活性剂、助表面活性剂形成O/W型微乳，解决其水溶性差的问题，同时降低毒性，提高药物的生物利用度。 本研究通过对油相、水、表面活性剂、助表面活性剂的选择和配比优化，成功地将紫杉醇包埋在乳液中，由伪三元相图得到相应的微乳区域，并结合自乳化速率及对紫杉醇的溶解性能来筛选处方。最终确立微乳的最优配方为：油酸正丁酯+聚氧乙烯蓖麻油+1，2丙二醇（3:7(2:1)），经去离子水稀释迅速形成稳定的微乳，粒径在30nm。实验条件为在37℃水浴中，温和搅拌。并在229nm,以甲醇：乙腈：水＝14：36：50为流动相，流速为1ml/min的条件下，用高效液相色谱法（HPLC）准确分析紫杉醇含量，为构建紫杉醇自乳化给药体系作了初步探索。 关键词：紫杉醇 自乳化 微乳 拟三元相图 高效液相色谱 Studies on the SEDDS of paclitaxel ABSTRACT Paclitaxel is a kind of natural anti-cancer drugs separated from the cortices of Taxus brevifolia. It is a monomer of di-terpene. It is active to many human cancer cell systems such as ovary cancer, breast cancer and so on. Because of its special anti-cancer mechanism and its obvious effect, Paclitaxel may become the preferred drug in curing the ovary and breast cancer in recent years. To solve all kinds of troubles caused by the clinical using of paclitaxel, such as the hypersensitivity reactions and the poor bioavailability, we try to prepare a Self-emulsifying Drug Delivery System (SEDDS) of Paclitaxel . The oil, water, surfactant and co-surfactant were chosen to establish a system which can dissolve the paclitaxel. SEDDS can improve the bio-absorbption of paclitaxel meanwhile reduce its toxicity. We choose prescription by portraying the pseudo-ternary phase diagram and testing the selfemulsifying rate. We successefully embed paclitaxel in the SEDDS microemulsion, and find the best prescription : normal-butyl oleate + Cremophor-EL + propane-1，2-diol（3:7(2:1)）.The HPLC method was established to determine the concentration of paclitaxel in Self-emulsifying Drug Delivery System. Keywords: paclitaxel SEDDS microemulsions HPLC 一．前 言 癌症是当今威胁人类健康的最凶顽疾之一，是疾病导致死亡的头号杀手。据世界卫生组织统计，全世界平均每年死于癌症的患者达690多万人，每年新增患者约为870万例，而且该数字呈逐年上升的趋势。对于这种全身性、全程性的疾病，紫杉醇是一种单体双萜类天然抗癌原料药，(Taxus brevifolia)的树皮中分离得到，taxane）衍生的生物碱。 其分子式为C47H51NO14， 分子