對乙酰氨基酚包合物的制備與研究

摘    要
對乙酰氨基酚為苯胺類解熱鎮(zhèn)痛藥，簡稱APAP，又稱撲熱息痛，化學(xué)名為N－(4－羥基苯基)乙酰胺，是一種常用的解熱鎮(zhèn)痛藥物。用于普通感冒或流行性感冒引起的發(fā)熱，也用于緩解輕中度終痛如關(guān)節(jié)痛、偏頭痛、頭痛、肌肉痛、牙痛、神經(jīng)痛。其解熱作用緩慢而持久，與其它解熱鎮(zhèn)痛藥相比，具有刺激性小，極少有過敏反應(yīng)等優(yōu)點(diǎn)。
β－環(huán)糊精作為一種常用的藥用包合材料應(yīng)用廣泛，藥物與β－環(huán)糊精或其衍生物制成包合物后，可顯著增加難溶性藥物的溶解度，提高藥物的穩(wěn)定性，減少藥物的刺激性，降低毒副作用，掩蓋不良?xì)馕丁?br /> 本文對對乙酰氨基酚β－環(huán)糊精包合物的制備工藝及最佳處方條件進(jìn)行了研究，用飽和水溶液法進(jìn)行制備，用紫外分光光度法測定包合率、溶解度來驗(yàn)證包合效果，比較包合物與原藥的核磁共振譜圖差別來驗(yàn)證包合物的生成，用正交試驗(yàn)來分析各種因素的對包合率的影響，分析各種因素對包合率影響的輕重，從而確定最佳制備工藝條件。

關(guān)鍵詞  對乙酰氨基酚；包合物；制備工藝；方法學(xué)考察

Acetaminophen inclusion compound and Research
Abstract
Acetaminophen for aniline antipyretic analgesics, referred to as APAP, acetaminophen, chemical, N－(4－h(huán)ydroxyl 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.

 
目錄
摘    要 I
Abstract II
第1章  緒   論 1
1.1課題背景 1
1.2對乙酰氨基酚的概述 1
1.2.1.對乙酰氨基酚的理化性質(zhì) 1
1.2.2對乙酰氨基酚的藥代動(dòng)力學(xué)研究 2
1.2.3對乙酰氨基酚藥理作用 2
1.2.4對乙酰氨基酚的不良反應(yīng) 2
1.3包合物的研究進(jìn)展 3
1.3.1包合物概述 3
1.3.2 β－環(huán)糊精包合物的概述 5
1.3.3包合物應(yīng)用展望 7
1.4對乙酰氨基酚包合物的研究目的和內(nèi)容 7
1.4.1研究目的 7
1.4.2研究內(nèi)容 7
第２章 對乙酰氨基酚包合物的制備 8
2.1試劑與儀器 8
2.1.1試劑 8
2.1.2儀器 8
2.2實(shí)驗(yàn)方法 8
2.2.1飽和水溶液法制備包合物 8
2.2.2單因素考察 9
2.2.3正交試驗(yàn) 11
2.2.4包合率的測定 12
2.2.5包合物中對乙酰氨基酚含量的測定 12
2.2.6包合物性能考察 12
2.3實(shí)驗(yàn)結(jié)果 15
2.4討論 15
2.5本章小結(jié) 16
第3章   方法學(xué)考察 17
3.1儀器與藥品 17
3.1.1儀器 17
3.1.2藥品 17
3.2實(shí)驗(yàn)前準(zhǔn)備 17
3.2.1對照品溶液的制備 17
3.2.2供試品溶液的制備 17
3.2.3測定方法 17
3.3方法學(xué)考察試驗(yàn) 17
3.3.1標(biāo)準(zhǔn)曲線的繪制 18
3.3.2精密度實(shí)驗(yàn) 18
3.3.3重復(fù)性實(shí)驗(yàn) 19
3.3.4穩(wěn)定性實(shí)驗(yàn) 19
3.3.5加樣回收率實(shí)驗(yàn) 20
3.4討論 20
3.5 本章小結(jié) 20
結(jié)論 21
參考文獻(xiàn) 22
致謝 23
附錄A 24
附錄B 28