洛伐他汀生產(chǎn)論文：洛伐他汀生產(chǎn)過程中的溶媒流失控制研究

1、洛伐他汀生產(chǎn)論文：洛伐他汀生產(chǎn)過程中的溶媒流失控制研究【中文摘要】洛伐他汀是臨床上廣泛應(yīng)用的調(diào)節(jié)血脂類藥物，醋酸丁酯作為洛伐他汀提取劑其用量較大。在重慶某藥企的洛伐他汀生產(chǎn)過程中，大量溶媒醋酸丁酯流失。這部分流失的溶媒不僅對相關(guān)從業(yè)人員和附近居民造成健康上的潛在危害，也給周圍環(huán)境帶來極大的壓力，更對企業(yè)是一個(gè)巨大的經(jīng)濟(jì)損失。本論文從重慶某藥企的洛伐他汀實(shí)際生產(chǎn)工藝出發(fā)，分析了溶媒流失各環(huán)節(jié)的流失方式及原因，并對各環(huán)節(jié)分別提出了控制方案。各方案在盡可能保留原有設(shè)備和裝置的基礎(chǔ)上，有效的控制了溶媒流失。實(shí)踐證明，萃取-離心環(huán)節(jié)的降溫及密圭寸,水洗環(huán)節(jié)的逆流洗滌，渣蒸餾環(huán)節(jié)的加水濕蒸，已經(jīng)控制了大部

2、分的氣相溶媒流失，而水相溶媒流失量從190.3t/a降至63.4t/a。針對水相中仍然存在的溶媒流失，本文以液體石蠟作為萃取劑進(jìn)行萃取回收。通過單因素實(shí)驗(yàn)，確定了萃取時(shí)間和萃取比對萃取效果影響較大，萃取溫度的影響較小，而水相中的生物質(zhì)對萃取效果幾乎無影響，在優(yōu)化的條件下（萃取時(shí)間15min,溫度25C,萃取比1:1）,萃取率可達(dá)98%多級萃取實(shí)驗(yàn)證明了液體石蠟?zāi)苡行Ц患嘀械蜐舛鹊拇姿岫□ィ腋骷壍妮腿÷示鼙３州^高水平。富集于液體石蠟中的醋酸丁酯能夠經(jīng)減壓蒸餾得以有效回收。利用先堿洗再水洗的再生方式能夠?qū)κ褂煤蟮囊后w石蠟進(jìn)行再生，再生5次以內(nèi)的液體石蠟?zāi)鼙３州^好的萃取效果。該廠新建生產(chǎn)線將

3、完全采用本研究所提出的溶媒流失控制方案，屆時(shí)將使水相中的溶媒損失量從190.3t/a降至10t/a以下,且能完全解決氣相溶媒的流失問題。該應(yīng)用不僅有效的回收了溶媒，節(jié)約了成本；也大大改善了車間、廠區(qū)及周圍的環(huán)境,消除了溶媒對人員及環(huán)境帶來的威脅，符合了綠色化學(xué)的要求。【英文摘要】Lovastatinisusedforregulatingthebloodlipidextensively,butylacetateasextractantiswidelyusedintheextractionprocess,andlotsofbutylacetatelost.Thelossofbutylacetate

4、isnotonlypotentiallyharmfulforpeople'shealth,butalsoputsgreatstressonenvironment,andcausesseriouseconomiclosses.FromthereallovastatinproductionofChongqingXXcompany,thispaperanalyzedthewaysandthereasonsofthelossofbutylacetate,andproposedsolutionsrespectively.Basedontheoriginalequipmentinstallatio

5、ns,thesolutionscancontrolthesolventlosseffectively.Thetemperaturereductionandsealedoperationwereusedinextractionandcentrifugationprocesses,thecountercurrentwashingwasusedinwashingprocess,andthewetdistillationbyaddingwaterwasusedindistillationprocess,theseappliedsolutionshavecontrolledmostofthesteaml

6、ossofbutylacetate,anddecreasedthesolventlossinwaterfrom190.3t/ato63.4t/a.Therecoveryofbutylacetatefromlovastatinwastewaterwasstudiedbyusingsolventextractionwithliquidparaffinastheextractant.Bysingle-factortests,extractiontimeandphaseratiohavegreateffectsonthesolventextraction,whiletheeffectoftempera

7、tureandbiomasscontentareslight.Inoptimumcondition(15min,25°C,1:1ofphaseratio),theextractionefficiencycanreachto98%.Bymulti-stageextraction,liquidparaffinshowsahighloadingability,andtheextractionefficiencyineachrunremainsefficientwithin10stages.Theloadedbutylacetatecanbeeffectivelyrecoveredbyvac

8、uumevaporation.Moreover,thealkalitreatmentprovidesasuccessfulwaytoregeneratetheusedLP,andtheregeneratedLPcanbereusedasmanyas5timeswithoutnoticeablelossinextractionefficiency.Thecompanywillcompletelyadopttheresearch-proposedlosscontrolsolutionsinitsnew-builtproductionline,bythen,solventlossinwaterwilldropfrom190.3t/atolessthan10t/a,andsteamlossofsolventwillbecontrolledtotally.Theapplicationofthesesolutionsprovidesasuccessfulwaytorecoverbutylacetate,whichcancutthecostssignificantly.Besides