鸦胆子油乳剂的处方优化及其药代动力学研究

发布时间：2018-05-10 16:09

  本文选题：鸦胆子油 + 乳剂　； 参考：《广东药学院》2014年硕士论文

【摘要】：当今，恶性肿瘤依然是人类的头号杀手，化疗则是目前主要的治疗手段之一，但化疗的严重副作用却给患者带来了很大的痛苦。近年来，由于中药在肿瘤治疗方面具有副作用少、疗效较好的优势，已经得到了大家的肯定。鸦胆子油乳剂是临床上治疗肿瘤的常用的中药制剂之一，主要包括口服乳剂和注射剂两种剂型。由于乳剂为动力学和热力学不稳定体系，若处方欠佳或保存不当，往往会出现乳滴变大，进而破乳分层等现象，极大影响了产品的质量。本文主要从鸦胆子油乳剂的处方优化、制剂的生物等效性进行研究，主要包括以下四部分： 1.鸦胆子油乳剂处方优化研究 本文对鸦胆子油乳剂的制备工艺进行了优化，并以外观、离心稳定性参数Ke、平均粒径和d90为稳定性指标，对单独使用大豆卵磷脂为乳化剂制备鸦胆子油乳剂进行乳化剂用量考察，最终确定单一乳化剂的合适用量为1.4%。通过处方优选得到最佳的复合乳化剂配比为大豆卵磷脂-泊洛沙姆188（2.75:1），在乳化剂用量相同的条件下，于一定条件下（30℃和4℃下各12小时交替）放置4周后对比发现，用该复合乳化剂所制备的鸦胆子油乳剂稳定性优于单独使用卵磷脂所制备的乳剂；另外对复合乳化剂的用量进行优选发现，与单独使用大豆卵磷脂作为乳化剂相比，使用该配比的乳化剂，还可以减少乳化剂的总用量且获得更好的乳剂稳定性。 2.气相色谱法测定血样中油酸和亚油酸浓度方法学的建立 本文建立了用气相色谱法测定全血中油酸和亚油酸含量的分析方法，其色谱条件为色谱柱：Aglient DB-FFAP（30m×0.25mm×0.25μm）；检测器：300℃；进样口：250℃；柱温：205℃；进样量：2μl；分流比：10:1；载气流速：1mL·min-1。本方法具有专属性强、稳定性好、准确度高等特点，可满足样品测定的需要。 3.处方优化后的鸦胆子油乳剂与市售鸦胆子油乳剂的生物等效性研究 把SD大鼠随机分成两组，并分别灌胃给予油酸等量的市售鸦胆子油乳剂和处方优化后的鸦胆子油乳剂，以AUC0-t、Cmax、Tmax为指标，评价处方优化后的鸦胆子油乳剂的生物等效性。实验结果显示，处方优化后的鸦胆子油乳剂具有生物等效性。 4.平均粒径大小不同的两种鸦胆子油乳剂的药代动力学研究 本文采用相同的鸦胆子油乳剂处方，通过不同的制备工艺得到两种平均粒径大小不同的鸦胆子油乳剂，并分别给予两组大鼠相同剂量的两种乳剂，实验结果显示，大粒径的鸦胆子油乳剂吸收慢且差，，Cmax和AUC0-t明显低于小粒径的乳剂。
[Abstract]:Nowadays, malignant tumor is still the leading killer of human beings, chemotherapy is one of the main treatment methods, but the serious side effects of chemotherapy bring great pain to patients. In recent years, traditional Chinese medicine has been affirmed because of its advantages of less side effects and better curative effect. Brucea javanica oil emulsion is one of the commonly used traditional Chinese medicine preparations in the treatment of tumor, mainly including oral emulsion and injection. Because the emulsion is an unstable system of dynamics and thermodynamics, if the prescription is not good or the storage is not proper, the emulsion droplets will become larger and demulsifying and delamination will occur, which will greatly affect the quality of the product. In this paper, the optimization of the formulation of Brucea javanica oil emulsion and the bioequivalence of the preparation were studied, including the following four parts: 1. Optimization study on the formulation of Brucea javanica Oil Emulsion In this paper, the preparation process of Brucea javanica oil emulsion was optimized. The appearance, centrifugal stability parameter Ke, average particle size and d90 were taken as the stability index. The amount of emulsifier used in the preparation of Brucea javanica oil emulsion by soybean lecithin alone was investigated, and the suitable amount of single emulsifier was determined to be 1.4%. The optimum compound emulsifier ratio of soybean lecithin to Poloxamer 2.75: 1 was obtained by optimum selection of the formula. Under the same emulsifier dosage, the emulsifier was alternately stored at 30 鈩

本文编号：1869976