用于鼻腔给药的载酮咯酸氨丁三醇温敏即型凝胶的制备与评价

发布时间：2018-04-24 15:09

  本文选题：酮咯酸氨丁三醇 + 即型凝胶　； 参考：《黑龙江中医药大学》2014年硕士论文

【摘要】：近年来,鼻腔给药以其吸收迅速、给药方便和避免首过效应等优点引起了广泛的关注,研究日益深入,应用不断拓展。即型凝胶其兼具溶液剂给药方便与凝胶剂长久滞留的优点,在缓控释递药领域有着广阔的应用前景,在鼻腔给药中的重要性和实用性尤其凸显。 非甾体抗炎药酮咯酸氨丁三醇(Ketorolac Tromethamine,简称Ket)在手术后中重度疼痛控制方面疗效确切,但临床上目前以注射给药为主,虽亦有鼻腔用溶液制剂上市,但在鼻腔内流失快,滞留短,吸收不充分,给药频繁,给患者带来不便。为了改善酮咯酸氨丁三醇鼻腔给药的药代动力学特征,本论文制备了基于卡拉胶-泊洛沙姆407复合温敏凝胶体系(carrageenan-poloxamer407hydrogel, CPH)的酮咯酸氨丁三醇鼻腔温敏即型凝胶,对其进行了较为系统的体内外表征。 在体外表征部分,本文考察了载酮咯酸氨丁三醇的卡拉胶-泊洛沙姆407复合温敏凝胶(简称Ket-CPH)的溶蚀特征、释药行为以及流变学性质,着重考察了Ket载药浓度对CPH溶蚀速度、释药速度以及凝胶化温度的影响。结果表明,Ket-CPH具有一定的药物缓释能力。Ket浓度越高,凝胶溶蚀越快,药物释放速度越快。Ket-CPH凝胶化温度亦随Ket浓度的增大而升高,其温度敏感性相转变行为符合给药的实际需要,当Ket含量为15%(w/w)时,CPH的凝胶化温度约为33℃,可在鼻腔内温度刺激下顺利发生凝胶化,在室温下粘度低,便于给药,且该载药浓度与市售鼻腔制剂相同,因此选其进行进一步体内评价。 Ket-CPH的体内评价包括药代动力学研究和安全性考察两大方面。大鼠鼻腔给予Ket-CPH后的药代动力学数据表明,Ket-CPH鼻腔给药后的药时曲线曲线下面积(AUC)显著高于溶液组,平均滞留时间(MRT)显著延长(p0.05),而血药浓度达峰时间相似,提示CPH这一给药系统形式有利于提高Ket在鼻腔的吸收程度,具有一定的体内缓释效果,而对吸收速度影响不大。在蟾蜍上腭模型上进行的鼻纤毛毒性研究结果表明,CPH凝胶基质本身以及Ket-CPH对纤毛形态均无明显影响,无明显鼻腔刺激性。 综上所述,Ket-CPH是一种方便、安全的鼻腔缓释给药系统,有利于迅速、充分、持久的药物吸收。本文工作为用于鼻腔给药的Ket-CPH研究的进一步开展奠定了良好基础。
[Abstract]:In recent years, nasal administration has attracted wide attention due to its advantages of rapid absorption, ease of administration and avoidance of first-pass effect. The gel has the advantages of convenient administration of solution agent and long retention of gel. It has a broad application prospect in the field of slow and controlled delivery of drugs, especially in nasal administration of the importance and practicability. Ketorolac Tromethamine (Ketorolac Tromethamine), a non-steroidal anti-inflammatory drug, is effective in the treatment of moderate and severe pain after surgery. The absorption is not sufficient, the drug is given frequently, bring inconvenience to the patient. In order to improve the pharmacokinetic characteristics of ketorolac aminobutanol in nasal administration, a temperature-sensitive ketobutanol nasal thermo-sensitive gel based on carrageenan-poloxamer407hydrogel (CPHH) was prepared in this paper, which was composed of carrageenan-poloxamer 407hydrogelatin (CPHG), carrageenan-poloxamer 407hydrogelatin (CPHG). The internal and external signs were systematically carried out. In the part of in vitro characterization, the dissolution characteristics, drug release behavior and rheological properties of carrageenan-Poloxamer 407 complex thermosensitive gel (Ket-CPH) were investigated, with emphasis on the dissolution rate of CPH by the concentration of Ket. The effect of release rate and gelation temperature. The results showed that the higher the concentration of Ket-CPH, the faster the gel dissolution and the faster the release rate. The gelation temperature of Ket-CPH also increased with the increase of Ket concentration, and the temperature sensitive phase transition behavior was in line with the actual need of drug administration. When the content of Ket is 15% / w, the gelation temperature of Ket is about 33 鈩，

本文编号：1797150