论文总字数：17843字

摘 要

溴芬酸钠是2 -氨基 -3 -苯甲酰基苯乙酸类衍生物之一,是一类非甾体类抗炎药( non-steroidal anti-inflammatory drugs，NSAIDS) ，构造与酮洛芬和双氯芬酸相类似，是最为有效的环氧合( cyclooxy-genase，COX) 抑制剂之一，可以抑制环氧合酶的合成，从而使环氧合酶介导的前列腺素类炎症炎症介质的合成得到抑制；溴芬酸钠拥有比较强的镇痛、消炎功效，是其他非甾体抗炎药(NSAIDS)作用强度的10 倍^［1－2］；现今眼部炎症性疾病的治疗多普遍使用溴芬酸钠。研究表明，环氧合酶-2的高度表达性与眼部新生血管有相当密切的关系^［3］；而作为环氧合酶-2的选择性抑制剂，溴芬酸钠能够通过抑制 环氧合酶-2从而抑制新生角膜血管的产生。溴芬酸钠最先由日本 Senju公司开发 ,在 2000年于日本上市, 多用于治疗外眼部及前眼部炎症性疾病, 主要有结膜炎、眼睑炎、强膜炎 (包括上强膜炎 )、术后炎症等炎症的对症治疗。它在美国已完成关于治疗白内障术后眼部发炎 、疼痛及畏光症状^[4]的Ⅲ期临床研究, 并且在 2004年第二季度向 FDA提出新药申请, 以商品名 Xibrom在 2005年 3月初于美国市场上市。目前，溴芬酸钠用于眼部疾病治疗的主要问题是药物的效用时间短、需要经常给药、患者的依从性差，且在眼深部构造不能得到治疗需要的药物浓度。

溴芬酸钠在治疗眼部疾病方面具有广阔的应用前景,本文对其工艺制备的合成路线进行了研究。

关键词： 溴芬酸钠 中间体 NSAIDs 合成

The Study on Preparation of bromfenac Sodium Eye Drops

Abstract

Bromfenac sodium (bromfenac sodium, BF) is 2 - amino - 3 - One of benzoyl acid derivative, is a non-steroidal anti-inflammatory drugs (non-steroidal anti-inflammatory drugs, NSAIDS), is similar to ketoprofen and diclofenac,and it can inhibit the synthesis of cyclooxygenase-mediated prostanoid mediators of inflammation.It is the most effective cyclooxygenase (cyclooxy-genase, COX) inhibitor, has a strong anti-inflammatory, town pain effect, potency of other nonsteroidal anti-inflammatory drugs (NSAIDS) 10 times [1-2]. Now it is widely used in the treatment of ocular inflammatory disease. The study was found, high expression of COX2 is closely related toocular angiogenesis [3], as a COX2 selective inhibitors .Bromfenac sodium can suppress the generation of corneal neovascularization by inhibiting COX2. Bromfenac sodium was first developed by the Japanese company Senju, launched in Japan in 2000, for the outer eye and anterior segment inflammatory diseases, such as blepharitis, conjunctivitis, uveitis strong (strong including meningitis), surgery inflammation and other symptomatic treatment. In the United States it has completed treatment of ocular inflammation after cataract surgery, pain and photophobia [4] Ⅲ clinical studies. And in the second quarter of 2004,they put forward new drug application to the FDA, use the trade name Xibrom in early March 2005 in the United States market. Currently, the main problem of bromfenac sodium for the treatment of eye diseases is the effect of the drug in a short time, frequent administration needs, poor compliance of patients, and in the eye deep tissue is difficult to obtain effective drug concentration.

   Bromfenac sodium has broad application in the treatment of eye diseases, the article is studied to its preparation of synthetic route in technology.

Key words：Bromfenac sodium ；Midbody ；NSAIDs；Synthesis

目 录

摘 要 Ⅰ

Abstract Ⅱ

第一章 文献综述 3

1.1溴芬酸钠 3

1.1.1 溴芬酸钠简介 3

1.1.2非甾体抗炎药在眼科中的应用 3

1.1.3 NSAIDs的作用机制 4

1.1.4 溴芬酸钠眼局部应用的抗炎作用 5

1.1.5 应用溴芬酸钠滴眼液的不良反应 6

1.1.6 应用溴芬酸钠滴眼液的注意事项 6

第二章 溴芬酸钠中间体的合成路线 7

2.1溴芬酸钠中间体的合成路线 7

第三章 实验部分 10

3.1实验试剂及仪器 10

3.1.1实验试剂 10

3.1.2实验仪器 11

3.2 详细实验步骤 12

3.2.1 中间体c的合成 12

3.2.2 中间体d的合成 12

3.2.3 中间体e的合成 13

3.2.4 中间体f的合成 13

3.2.5 中间体g的合成及终产物h的合成 13

3.2.6 讨论 14

3.3反应监控 15

3.4三废处理方案 15

第四章 总结与展望 16

4.1 结论 16

4.2 展望 16

参考文献 17

致 谢 21

第一章 文献综述

1.1溴芬酸钠

1.1.1 溴芬酸钠简介

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