【作者】 杨艳；

【导师】 倪京满；

【作者基本信息】 兰州大学 ， 药学·药剂学， 2014， 硕士

【摘要】 纳米纤维素(NCC)是微晶纤维素通过酸水解而成的。它是具有生物相容性,生物降解性,环境友好等优点的可再生生物大分子材料。随着NCC优越的性能被人们发现以来,它在医学领域中的应用备受关注,从NCC作为金属纳米粒子的赋形剂到它在载体领域中的应用,NCC显示了它作为纳米载体材料的优良性能。但是NCC由于比表面积比较大,氢键作用比较强,容易产生聚集使得它的使用受到限制。所以本论文为了改善NCC的聚集现象分别进行了化学修饰制备衍生成羧甲基纳米纤维素(N-CMC)和季铵化纳米纤维素(N-QC)。并且对NCC、N-CMC和N-QC作为缓控释纳米载体材料进行了初步的研究和探讨。本论文的负载药物是我们研究组研究的多肽EN-9(Tyr-Pro-Phe-Phe-Gln-Pro-Gln-Arg-Phe-NH2),EN-9是一种具有高镇痛活性和低成瘾性、低耐受性的嵌合肽。本论文确定EN-9-NCC、EN-9-N-CMC和EN-9-N-QC纳米粒子的制备工艺,初步制备了 EN-9-NCC、EN-9-N-CMC、EN-9-N-QC纳米粒子,测其包埋率分别为84.7%,72.37%和97.10%;对EN-9-NCC、EN-9-N-CMC和EN-9-N-QC纳米粒子进行了体外释放试验,分别在模拟的胃液、小肠液、生理体液和去离子水中进行,释放在前1.5 h为爆发式释放,后随着时间的延长而缓慢的释放,到4h以后接近平衡,释放率都在75%以上。动物的甩尾镇痛实验结果显示,EN-9-NCC、EN-9-N-CMC和EN-9-N-QC纳米粒子具有控制缓慢释放的能力,EN-9-NCC、EN-9-N-CMC和EN-9-N-QC纳米粒子的镇痛能力比原料药EN-9的要弱,但是镇痛效果要比原料药持久。EN-9-N-QC纳米粒子的镇痛持续时间和强度都要优于EN-9-NCC和EN-9-N-CMC纳米粒子。本论文的研究为NCC及其衍生物作为缓控释制剂的载体材料的研发和临床应用提供了基础,也为EN-9这种多肽类药物新剂型的研发和临床应用提供了研究基础。更多还原

【Abstract】 Nanocrystalline cellulose(NCC)is obtained by hydrolysis of microcrystalline cellulose with acid.NCC is biocompatibility,biodegradability,environmental friendly and friendly renewable biological macromolecular materials.Because of its superior performance,NCC has been paid to its application in the medical field.From excipient of metal nanoparticles to its application as carriers,NCC shows its good performance as nano-materials carriers.Due to the specific surface area of NCC is larger,stronger hydrogen bonding interaction of surface of NCC caused gather between molecules.In order to break NCC aggregate phenomenon respectively,chemical modification was conducted for NCC.The hydroxyl of NCC surface was derived into carboxymethyl and amino to get carboxymethyl nanocrystalline cellulose(N-CMC)and quaternary ammoniation nanocrystalline cellulose(N-QC)to abate aggregate phenomenon of NCC.The purpose of this paper is to the preliminary research and discussion for NCC,N-CMC and N-QC as slow release drug delivery material.The model drug is EN-9(Tyr-Pro-Phe-Phe-Gln-Pro-Gln-Arg-Phe-NH2)which was synthesized by our term.EN-9 has high analgesic activity,low addiction and low tolerance of chimeric peptide.This paper preliminary studies EN-9-NCC,EN-9-N-CMC and EN-9-N-QC nanoparticles preparation to determine the EN-9-NCC,EN-9N-CMC and EN-9N-QC nanoparticles prepare conditions that is:at room temperature,200 r min-1 of stirring speed,EN-9 and NCC(CMC,QC)in deionized water and were incubated for 48 h and encapsulation efficiency were 84.7%,72.37%and 95.12%.Release test of EN-9-NCC,EN-9-N-CMC and EN-9-N-QC nanoparticles in vitro respectively were detected in simulated gastric juice,intestinal juice,physiological fluids and deionized water.Explosive release was before 1.5 h and after 1.5 h time it is slow release to 4 h after close to balance,release rate is over 75%.Analgesic activity experiment showed that EN-9-NCC,EN-9-N-CMC and EN-9-N-QC nanoparticles have analgesic activity in vivo.Analgesia activities of EN-9-NCC,EN-9-N-CMC and EN-9-N-QC nanoparticles were weaker than that of EN-9,but the analgesic times of EN-9-NCC,EN-9-N-CMC and EN-9-N-QC nanoparticles were much longer than that of EN-9.The analgesic time and strength of EN-9-N-QC nanoparticles was better than that of EN-9-NCC and EN-9-N-CMC nanoparticles.This research provided referential basis for the new preparation formulation of EN-9 and the application of NCC and its derivatives as long-time release carrier.更多还原