对乙酰氨基酚包合物的制备与研究.doc

对乙酰氨基酚包合物的制备与研究

摘    要
对乙酰氨基酚为苯胺类解热镇痛药，简称APAP，又称扑热息痛，化学名为N－(4－羟基苯基)乙酰胺，是一种常用的解热镇痛药物。用于普通感冒或流行性感冒引起的发热，也用于缓解轻中度终痛如关节痛、偏头痛、头痛、肌肉痛、牙痛、神经痛。其解热作用缓慢而持久，与其它解热镇痛药相比，具有刺激性小，极少有过敏反应等优点。
β－环糊精作为一种常用的药用包合材料应用广泛，药物与β－环糊精或其衍生物制成包合物后，可显著增加难溶性药物的溶解度，提高药物的稳定性，减少药物的刺激性，降低毒副作用，掩盖不良气味。
本文对对乙酰氨基酚β－环糊精包合物的制备工艺及最佳处方条件进行了研究，用饱和水溶液法进行制备，用紫外分光光度法测定包合率、溶解度来验证包合效果，比较包合物与原药的核磁共振谱图差别来验证包合物的生成，用正交试验来分析各种因素的对包合率的影响，分析各种因素对包合率影响的轻重，从而确定最佳制备工艺条件。

关键词  对乙酰氨基酚；包合物；制备工艺；方法学考察

Acetaminophen inclusion compound and Research
Abstract
Acetaminophen for aniline antipyretic analgesics, referred to as APAP, acetaminophen, chemical, N－(4－hydroxyl phenyl ethyl amide). This product can inhibit prostaglandins by the synthesis, is a kind of common chp.2000 drugs. For pediatric common cold or flu causes fever, also to alleviate pain mild－to－moderate end joint pain, migraine headache, muscle pain, and toothache, neuralgia. Its slow and lasting antipyretic actions, compared with aspirin has excitant small, rarely have allergic reaction, etc
    β－cyclodextrins is a kind of common medicinal materials with wide application, drugs and beta cyclodextrins and its derivatives is made with, can significantly increase the undissolved chiral drugs, improve the stability of the drug solubility, reduce medicine excitant, reduce toxicity, cover the advantages of bad smell.
In this APAP，paracetamol β－cyclodextrin inclusion complexes and the bestprescription process conditions were studied, prepared by different methods, using UV spectrophotometric determination of inclusion rate of charge, to verify the package and the effect of solubility, NMR determination of indicators to observe the original package and material differences in the drug spectrum, measured to compare the in vitro dissolution of ibuprofen dissolution inclusion on the impact of the orthogonal analysis of various factors on the package and rate, analysis of various factors on the package and rate the severity of impact to determine the best preparation conditions.
Key words：Paracetamol; Inclusion; Preparation; Methodology.

 
目录
摘    要 I
Abstract II
第1章  绪   论 1
1.1课题背景 1
1.2对乙酰氨基酚的概述 1
1.2.1.对乙酰氨基酚的理化性质 1
1.2.2对乙酰氨基酚的药代动力学研究 2
1.2.3对乙酰氨基酚药理作用 2
1.2.4对乙酰氨基酚的不良反应 2
1.3包合物的研究进展 3
1.3.1包合物概述 3
1.3.2 β－环糊精包合物的概述 5
1.3.3包合物应用展望 7
1.4对乙酰氨基酚包合物的研究目的和内容 7
1.4.1研究目的 7
1.4.2研究内容 7
第２章 对乙酰氨基酚包合物的制备 8
2.1试剂与仪器 8
2.1.1试剂 8
2.1.2仪器 8
2.2实验方法 8
2.2.1饱和水溶液法制备包合物 8
2.2.2单因素考察 9
2.2.3正交试验 11
2.2.4包合率的测定 12
2.2.5包合物中对乙酰氨基酚含量的测定 12
2.2.6包合物性能考察 12
2.3实验结果 15
2.4讨论 15
2.5本章小结 16
第3章   方法学考察 17
3.1仪器与药品 17
3.1.1仪器 17
3.1.2药品 17
3.2实验前准备 17
3.2.1对照品溶液的制备 17
3.2.2供试品溶液的制备 17
3.2.3测定方法 17
3.3方法学考察试验 17
3.3.1标准曲线的绘制 18
3.3.2精密度实验 18
3.3.3重复性实验 19
3.3.4稳定性实验 19
3.3.5加样回收率实验 20
3.4讨论 20
3.5 本章小结 20
结论 21
参考文献 22
致谢 23
附录A 24
附录B 28