年产300吨罗红霉素原料药工艺设计

安徽工程科技学院毕业设计

年产300吨罗红霉素原料药工艺设计

（安徽工程科技学院生化系 芜湖 241000）

摘 要

罗红霉素为半合成的大环内酯类抗生素。合成路线基本上都是以硫氰酸红霉素为原料，经肟化成红霉素肟，再和甲氧乙氧氯甲醚反应得罗红霉素。罗红霉素生产过程中，如何提高肟化效率、产品收率、溶剂回收和减少“三废”是医药工业面临的难题?11]。现在国内企业生产罗红霉素所使用的工艺，肟化率在63%－70%范围内，罗红霉素产品质量收率一般在80%左右，但是相比较国外先进工艺，生产成本高，产品纯度低。更为严峻的是很多企业没有对溶剂等原料充分回收利用，选择了直接排放，不但浪费资源，而且污染环境。参考国内外的文献，对罗红霉素工艺路线进行了设计，不但要获得较高的产品收率，而且要对溶剂进行回收，避免污染环境，达到清洁生产。

本文对300吨罗红霉素原料药生产进行工艺设计，主要包括：工艺流程设计及优化、物料衡算、工艺设备的计算和选型、能量计算等。 关键词： 红霉素肟；醚化；罗红霉素；工艺设计。

- 1 -

钟炜：年产300吨罗红霉素原料药工艺设计

The technology design of the erythromycin produced

300 tons per year

zhong wei

（Anhui University of Technology & Science The biochemistry engineering department wuhu 241000）

Abstract

Roxithromyein is a kind of semi-synthetical antibiotic drugs of large ring lactone. Roxithromycin is synthesized from methoxy ethoxy methyl chloride and oximido erythromycin that has been oximated from sulfocyanic acid and erythromycin. In the roxithromycin production line, how to raise efficiency of oximation reaction and the rate of roxithromycin, melting agent recovery are the problems the medicine industry to face. Now the local business enterprise produces roxithromycin, the rate is between 63% and 70%, the quality rate of roxithromycin is generally about 80%, but compare with foreign advanced craft, the production cost is higher, and the product purity is not high. More serious, a lot of business enterprises didn't recover the solvent, and chose direct emissions. Not only resource is wasted, but also environment is polluted. Preparation referred to the literature at home and abroad, The technical course of Roxithromycin was designed, not only want to acquire a higher product rate, but also want to recover the solvent, avoid pollution environment, attain to sweep production.

The scheme to the erythromycin produced 300 tons per year technological design process including technological process design, the balance of calculation，technics calculation and equipment choosing，energy calculation etc.

Keyword： erythromyein oxime； etherifieation； roxithromyein； technological design。

- 2 -

安徽工程科技学院毕业设计

目 录

年产300吨罗红霉素原料药工艺设计 ···································································· 1 插图清单 ···················································································································· 4 表格清单 ···················································································································· 4 引 言 ························································································································· 5 第1章 概述 ·············································································································· 6 1.1 本课题的设计背景及现实意义 ········································································ 6 1.2 国内外研究进展 ································································································ 6 1.3 课题来源 ············································································································ 7 1.4 拟解决的问题 ···································································································· 8 第2章 工艺设计原理 ······························································································ 9 2.1 产品简介 ············································································································ 9 2.2 反应原理 ············································································································ 9 第3章 工艺流程设计 ···························································································· 11 3.1 工艺流程 ·········································································································· 11 3.2 溶剂回收 ·········································································································· 15 3.3 三废处理 ·········································································································· 15 第4章 工艺计算 ···································································································· 18 4.1 物料衡算 ·········································································································· 18 4.2 物料衡算表 ······································································································ 19 4.3 原辅材料消耗表 ······························································································ 20 4.4 排放物综合表 ·································································································· 20 4.5 热量衡算 ·········································································································· 21 第5章 主要设备计算与选型 ················································································ 27 5.1 肟化工段的主设备 ·························································································· 27 5.2 醚化工段的主设备 ·························································································· 28 5.3 精制工段的主设备 ·························································································· 29 第6章 主反应釜设计 ···························································································· 31 6.1 中间体反应釜设计 ·························································································· 31 6.2 醚化反应釜设计 ···························································································· 33 第7章 车间布局设计 ···························································································· 36 7.1 车间主要设备 ·································································································· 36 7.2 车间布置设计 ·································································································· 36 结论与展望 ·············································································································· 37 致 谢 ······················································································································· 38 参考文献 ·················································································································· 38

- 3 -

钟炜：年产300吨罗红霉素原料药工艺设计

插图清单

图1-1 罗红霉素合成图??????????????????????? 6 图2-1 罗红霉素结构图??????????????????????? 9 图2-2 合成罗红霉素肟化反应式简图?????????????????10 图2-3 合成罗红霉素醚化反应式简图?????????????????10 图3-1 罗红霉素生产工艺流程简图??????????????????11 图3-2 肟化工艺流程图及“三废”排放点位??????????????12 图3-3 醚化、精制工艺流程图及“三废”排放点位???????????13 图3-4 三乙胺回收工艺流程图及“三废”排放点位???????????14 图3-5 废气处理工艺流程图 （1）??????????????????15 图3-6 废气处理工艺流程图 （2）??????????????????15

表格清单

表3-1 废渣产生及处置情况表????????????????????16 表4-1 年产300吨罗红霉素生产工艺过程物料衡算表??????????18 表4-2 年产300吨罗红霉素原辅材料消耗表??????????????19 表4-3 年产300吨罗红霉素排放物综合表???????????????19

- 4 -

安徽工程科技学院毕业设计

引 言

20世纪末出现的新型红霉素如罗红霉素、克拉霉素等，它们克服了红霉素容易被酸分解的缺点，拓宽了抗菌谱，已经作为新一代的红霉素药物进入临床应用，并引起了人们对红霉素药物重新评价和研究的高潮。

国内罗红霉素原料生产企业也不下十家，生产工艺和技术主要来源于上海医工院和四川抗生素研究所，并多是从红碱做起，国外企业多是从硫氰酸红霉素做起，硫氰酸红霉素的价格仅为红碱的一半，使罗红霉素的生产成本国内外有一定的差异，最近几年，由于受市场压力的影响，一些厂家都在致力于技术提高和工艺改进，现已接近或达到国际先进水平。但是国内生产企业罗红霉素成品收率平均一般只在80％左右，产品的纯度也不是很高。很难跟国外企业抗衡。

本设计方案把提高产品收率和纯度作为技术难点，优化工艺，设计一套最佳方案。充分参考国内外文献，立足于国内已有原料的实际情况，以硫氰酸红霉素为原料，盐酸羟胺为肟化剂，以甲醇为反应溶剂，在三乙胺的催化作用下进行肟化反应，合成红霉素肟，再以甲氧基乙氧基氯甲醚 (MEMC)为反应原料，以N，N－二甲基甲酰胺 (DMF)为反应溶剂，在甲醇钠的催化作用下与红霉素肟进行醚化反应，得到罗红霉素，收率达到90%(摩尔收率)。

然而光有最佳方案是远远不够的，粗产品生产出来后，精制等后续处理也是至关重要，这直接关系到产品的纯度，当然还有中间产物的处理也要达到最佳。

[1]

[2]

- 5 -

本文来源：https://www.bwwdw.com/article/y22f.html