用于炎症性肠病结肠特异性给药的5-氨基水杨酸相互偶氮前药的合成、动力学研究及药理学评价
Synthesis, kinetic studies and pharmacological evaluation of mutual azo prodrug of 5-aminosalicylic acid for colon-specific drug delivery in inflammatory bowel disease.
作者信息
Dhaneshwar Suneela S, Kandpal Mini, Vadnerkar Gaurav, Rathi Badal, Kadam S S
机构信息
Department of Pharmaceutical Chemistry, Bharati Vidyapeeth Deemed University, Poona College of Pharmacy, Pune-411038, Maharashtra, India.
出版信息
Eur J Med Chem. 2007 Jun;42(6):885-90. doi: 10.1016/j.ejmech.2006.11.017. Epub 2006 Dec 15.
Mutual azo prodrug of 5-aminosalicylic acid with l-tyrosine was synthesized by coupling l-tyrosine with salicylic acid, for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. The structure was confirmed by elemental analysis, IR and NMR spectroscopy. In vitro kinetic studies in rat fecal matter showed 87.18% release of 5-aminosalicylic acid with a half-life of 140.28min, following first order kinetics. Therapeutic efficacy of the carrier system and the mitigating effect of the azo conjugate were evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model. Myeloperoxidase activity was determined by the method of Krawisz et al. The synthesized prodrug was found to produce comparable mitigating effect as that of sulfasalazine on colitis in rats.
通过将L-酪氨酸与水杨酸偶联，合成了5-氨基水杨酸与L-酪氨酸的相互偶氮前药，用于在炎症性肠病中靶向药物递送至炎症肠道组织。通过元素分析、红外光谱和核磁共振光谱对结构进行了确证。在大鼠粪便中的体外动力学研究表明，5-氨基水杨酸的释放率为87.18%，半衰期为140.28分钟，遵循一级动力学。在三硝基苯磺酸诱导的实验性结肠炎模型中评估了载体系统的治疗效果和偶氮缀合物的缓解作用。采用Krawisz等人的方法测定髓过氧化物酶活性。发现合成的前药对大鼠结肠炎产生的缓解作用与柳氮磺胺吡啶相当。
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