青霉素生产课程设计.docx
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青霉素生产课程设计.docx
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青霉素生产课程设计
前言
通过近两个礼拜的尽力,咱们这组终于将课程设计做完,从最初的方向的设定到原始数据及相关文献的搜集乃至写完后的校正,这一路走来,自我感觉仍是很充实的。
可是真正昨晚开始写前言时,却突然不知该如何动笔。
或许是之前从未写过,或许是尽力以后有太多的话想说乃至竟无从下笔。
思前顾后才决定写写咱们关于那个课程设计的观点吧。
1、选择做青霉素的缘故
初识青霉素源于一个小故事。
那个故事是青霉素发觉的进程,那时就感觉很成心思,细菌的产物竟然能拯救生命、消灭病毒。
后来的《微生物》课上,终于明白青霉素是一种真菌。
青霉素是它的次级代谢产物,是通过革兰氏阳性菌的转肽酶来抑制菌体的生长的。
这让咱们对青霉素加倍了解,同时也引发了咱们对其生产进程的爱好。
且最近正好在网上听终南山学者讨论国民的青霉素滥用情形很严峻。
于是在教师发布要做课程设计时,咱们组就决定生产青霉素,从而加倍深切了解青霉素的生产进程。
2、关于文献的查找
起初文献的查找真的很不容易,再加上关于文献检索不是很熟悉,第一个礼拜咱们组仅能在图书馆接一些发酵方面的书看看了解一下发酵知识。
后来看到同窗李峰有一篇关于柠檬酸的发酵方面的文献,很是兴奋。
于是借来看看并询问了如何搜索,原先是在豆丁网上弄的。
于是注册了一个豆丁账号,才发觉原先很多文章是要钱的,比如咱们搜的那片毕业设计需要200元左右。
于是只好截屏并放入word中加以打印,关于文中的一些原始数据网上检索不到只能借鉴两位学长的毕业设计。
在此先拜谢。
在阅读并讨论后发觉两篇毕业设计在运算时均有很多错误且很多方式与所借的较权威的参考书有较大的出入,故仅采纳他们的一些原始数据及相关运算思路。
于是就希望能够真的去一次青霉素生产厂家去实习三个礼拜再花两个礼拜去写这份设计。
希望能够取得自己想要的一手数据。
3、关于设备选择的一些问题
在设备运算进程中有很多辅助设备没有加以衡算,缘故是弄不到很多必需的参数,比如补料流加时它的比例流速文献中仅一句“依PH改变而改变”让人摸不到头脑,因此本设计还有很多不尽如人意的地址,且关于环境治理等一些问题由于缺乏相关方面的知识,且无相应数据文献文中只好仅仅介绍性的加以描述。
这是本设计瑕疵的地方。
另一些设备的运算要设计工程上的一些考虑,沃恩都不清楚。
因此咱们仅是依沃恩所学过所查得的资料文献上的知识去解决,因此不是的地方请教师斧正。
4、关于厂址及一些细节的确信
关于厂址咱们组讨论较多最终决定将厂放在巢湖和县,这是咱们组一同窗家所在。
他介绍了他们本地的一些政策及地理状况。
结合参考文献上选址的标准于是最终决定“落户”和县。
也算是在辛苦劳动的同时一个很小的插曲吧。
5、关于咱们组
提到咱们组,真的很多话要说。
做设计这期间,咱们几乎除最初几天文献查找不在一路,后来几乎成天泡在图书馆,常常到晚上10:
00图书馆关门才归去。
很多时候有时做得晚了食堂没吃的就一路去外面一路吃。
其中D同窗负责录入文字第五章、第六章及相关流程示用意的绘制;TXL同窗负责第一章第二章的书写;S同窗负责第三章第四章相关衡算;TH同窗负责绘制工厂平面图及流程图。
在这期间咱们组都很不遗余力尽责。
对此,咱们感到这将是咱们大学里的一次质的永久珍爱的独家经历!
因此在9月8日晚咱们完成初稿时就一致决定第二天去外面聚一聚庆贺一下!
在此先谢过咱们组的每一个人,谢谢他们给对方的帮忙!
6、最后
感激相关文献及资料的编写者,他们给了咱们很多我不曾有的知识。
最后感激教师给了那个能在一路彼此学习彼此尽力的机遇。
再一次真诚感激。
书于四教图书馆
晚
前言·······························································1
目录·······························································3
第一章青霉素的概述················································7
青霉素的相关性质············································7
青霉素的作用机制及相关用途··································8
1.2.1作用机制················································8
1.2.2相关用途···············································8
青霉素目前进展状况··········································8
第二章青霉素的生产工艺············································`9
生产工艺流程简介及生产流程图·······························`9
原料处置工段···············································10
青霉素产生菌的培育工段·····································10
发酵工段···················································10
2.4.1发酵的进程操纵········································10
2.4.1.1培育基··········································10
2.4.1.2培育条件操纵····································11
2.4.2避免染菌的要点········································12
2.4.3空气系统的要求········································12
2.4.4蒸汽系统要求··········································12
发酵液预处置工段···········································12
产品提取工段···············································13
产品精制工段···············································13
2.7.1脱色和去热原质········································13
2.7.2结晶···················································13
2.7.3干燥··················································13
成品鉴定及包装工段·········································14
2.8.1成品鉴定··············································14
2.8.2成品包装···············································14
生产进程中各类相关标准·····································14
2.9.1青霉素原料药质量标准··································14
2.9.2成品包装质量标准······································14
2.9.3标签、说明书、盒的印刷要求····························15
2.9.3.1标签、说明书、盒的装璜设计······················15
2.9.3.2外包装箱的要求··································15
第三章生产工艺计算···············································16
生产进程中的物料衡算·······································16
3.1.1工艺技术指标及基础数据································16
3.1.2原料消耗计算·········································16
3.1.2.1需要产品发酵液·································16
3.1.2.2单个周期所需要的各个成份计算·····················17
3.1.2.3年产1000t/a含水7%的青霉素厂总物料衡算········17
3.1.2.4萃取时萃取剂的用量·······························18
相关热量消耗计算············································18
3.2.1工艺技术指标及相关基础数据······························18
3.2.2相关热量衡算···········································19
3.2.2.1喷射加热器耗热····································19
3.2.2.2蒸汽用量计算······································19
3.2.2.3无菌空气计算······································20
3.2.2.4发酵热量计算······································20
3.2.2.5冷却水量计算······································21
第四章设备选型及计算·············································23
要紧设备选型与计算·········································23
4.1.1发酵罐的选型···········································23
4.1.1.1发酵罐选型········································23
4.1.1.2种子罐选型······································24
4.1.1.3配料罐··········································26
4.1.1.4补料罐···········································27
辅助设备选型··············································27
4.2.1原料预处置工序设备选型·······························27
4.2.1.1磁力除铁器···································28
4.2.1.2挑选设备······································28
4.2.1.3生物质原料的粉碎装置··························28
4.2.2提取工序设备选型·····································29
4.2.2.1过滤··········································29
4.2.2.3萃取··········································30
4.2.2.4结晶··········································30
4.2.2.5干燥··········································30
4.2.3包装·················································31
第五章全厂相关情形概况···········································33
厂址的选择及规模的确信·····································33
5.1.1厂址选择的总原那么·······································33
5.1.2工厂规模确信···········································33
工厂概况一览···············································33
5.2.1总平面设计的原那么和要求································33
5.2.2本设计中工厂总平面设计································34
5.2.3厂房建设标准··········································35
车间设计···················································35
5.3.1车间布置设计的依据····································35
5.3.2车间布置设计的原那么····································36
5.3.3药厂干净室············································36
5.3.3.1干净室生产设备的一样要求·······················36
5.3.3.2干净室的平面布置·······························37
5.3.3.3干净室的消毒···································37
5.4厂间人员配置·············································37
第六章环保及废物处置·············································39
生物工程工厂污染情形······································39
6.1.1生物工程工厂污染的特点·······························39
6.1.2生物工程工厂污染的现状·······························39
6.1.3污染防治方法·········································39
三废处置··················································41
6.2.1废气处置·············································41
6.2.1.1二氧化碳的处置································41
6.2.1.2好气发酵系统排放废气的利用和防范··············41
6.2.2废水处置·············································41
6.2.2.1废水检测的项目与含义··························41
6.2.2.2青霉素废水处置································42
6.2.3废渣处置·············································42
可行性评估························································43
参考资料···························································44
附录1·····························································45
附录2·····························································46
第一章青霉素的概述
青霉素的相关性质
青霉素是(6-aminopenicillanicacid,6-APA)苯乙酰衍生物。
侧链基团不同,形成不同的青霉素。
青霉素的结构通式可表示为:
青霉素为白色结晶状粉末,无臭或微有特异性臭;有吸湿性;遇酸、碱、氧化剂、青霉素酶等均能使其β-内酰胺环打开而失效;极易溶于水,溶于乙醇,不溶于脂肪油和液体石蜡。
结晶青霉素钠盐性质稳固,其水溶液在室温放置易失效,不能煮沸。
(一)稳固性:
干燥纯净的青霉素盐很稳固,有效期都在三年以上,而且对热稳固,如结晶青霉素钾盐在150OC加热小时效价不降低。
青霉素水溶液PH=5-7较稳固。
最稳固的PH为。
(二)溶解度:
青霉素本身是一种游离酸,能与碱金属或碱土金属及有机氨类结合成盐类。
青霉素游离酸易溶液于醇类、酮类、醚类和酯类,但在水溶液中溶解度很小;青霉素钾、钠盐那么易溶于水和甲醇、微溶于乙醇、丙醇、丙酮、乙醚、氯仿,在醋酸丁酯或戊酯中难溶或不溶。
若是有机溶剂中含有少量水分时,那么青霉素G碱金属盐在溶剂中的溶解度就大大增加。
目前国际上青霉素活性单位表示方式有两种:
一是指定单位(unit);二是活性质量(μg),最先为青霉素规定的指定单位是:
50mL肉汤培育基中恰能抑制标准金葡萄菌生长的青霉素量为一个青霉素单位。
在以后,证明了一个青霉素单位相当于μg青霉素钠。
因此青霉素的质量单位为:
μg青霉素钠等于1个青霉素单位。
由此,1mg青霉素钠等于1670个青霉素单位(unit)。
青霉素的作用机制及相关用途
1.2.1作用机制
已有的研究以为,青霉素的抗菌作用与抑制细胞壁的合成有关。
细菌的细胞壁是一层坚韧的厚膜,用以抗击外界的压力,维持细胞的形状。
细胞壁的里面是细胞膜,膜内裹着细胞质。
细菌的细胞壁要紧有多糖组成,也含有蛋白质和脂质。
革兰氏阳性菌细胞壁的组成是肽聚糖占细胞壁干重的50%~80%(革兰氏阴性菌为1%~10%)、磷壁酸质、脂蛋白、多糖和蛋白质。
其中肽聚糖是一种含有乙酰基葡萄糖胺和短肽单元的网状生物大分子,在它的生物合成中需要一种关键的酶即转肽酶。
青霉素作用的部位确实是那个转肽酶。
现已证明青霉素内酞胺环上的高反映性肽键受到转肽酶活性部位上丝氨酸残基的羟基的亲核进攻形成了共价键,生成青霉噻唑酰基-酶复合物,从而不可逆的抑制了该酶的催化活性。
通过抑制转肽酶,青霉素使细胞壁的合成受到抑制,细菌的抗渗透压能力下降,引发菌体变形,破裂而死亡。
1.2.2相关用途
临床应用:
40连年,要紧操纵灵敏金黄色葡萄球菌、链球菌、肺炎双球菌、淋球菌、脑膜炎双球菌、螺旋体等引发感染,对大多数革兰氏阳性菌(如金黄色葡萄球菌)和某些格兰氏阴性细菌及螺旋体有抗菌作用。
优势:
抗菌作用强、疗效高及毒性小,但由于难以分离除去青酶噻唑酸蛋白(微量可能引发过敏反映),需要皮试。
各类半合成抗生素的原料:
青霉素的缺点是对酸不稳固,不能口服,排泄快,对阴性菌无效。
氨苄青霉素耐酸广谱;对抗绿脓杆菌的磺苄青霉素,耐酸、耐酶、口服的乙氧萘青霉素等。
提供头孢菌素母核。
青霉素目前进展状况
抗生素在目前的制药工业中仍占有举足轻重的地位,尤其是下游半合成抗生素的进展。
进一步刺激了上有的工业发酵。
一些抗生素的工厂生产规模超级大,如β-内酰胺类的青霉素、头孢菌素C,大环内酯类的红霉素、利福霉素,氨基环醇类的链霉素、庆大霉素。
在我国,青霉素是医药工业的重量级产品,是抗生素原料药产量最大的品种,目前年产量已达2万多吨,总产量占世界的80%左右。
其生产技术已和国际接轨,生产本钱具有很强的竞争力,年出口量达到万吨左右。
青霉素是世界上第一个应用于临床的抗感染类药物。
长期以来,青霉素在抗生素市场上长盛不衰,已成为全世界普遍应用的一线抗菌药物。
国内较大规模的生产企业有华药、哈医药、石药、鲁抗,单个发酵罐规模均在100m³以上,发酵单位在70000U/mL左右,而世界青霉素工业发酵水平达100000U/mL以上。
第二章青霉素的生产工艺
生产工艺流程简介及生产流程图
本次生产工艺的大体进程是:
将砂土保藏的孢子进行斜面培育,得单菌落,再传斜面培育得斜面孢子,斜面孢子移植到优质小米或大米固体培育基上制得小米孢子;
将配成的一级发酵原料进行分批灭菌并冷却后,送入一级种子发酵罐,接入小米孢子,通入无菌空气好哦哦呢进行发酵;
将配成的二级发酵原料进行分批灭菌并冷却后,送入二级发酵罐,并加入一级种子发酵罐的发酵液和无菌空气后进行发酵;
将配成的三级发酵原料进行分批灭菌并冷却后,送入三级发酵罐,并加入二级发酵罐的发酵液和无菌空气后进行发酵;
发酵液经酸化、过滤处置后,进入混合罐,用醋酸丁酯萃取两次;
萃取液再通过加入活性炭脱色,然后通过过滤器过滤除去废炭;在滤液中加醋酸钠和乙醇反映,取得青霉素湿晶体;
结晶后,用真空抽滤机进行固液分离,取得的晶体加入丁醇洗涤后送入真空干燥机进行干燥,最后取得青霉素成品送入包装车间包装。
原料处置工段
依照发酵的要求,对玉米原料,采纳直接粉碎、磨粉、调浆、分批灭菌的处置方式:
以玉米原料生产时,依照我国玉米粗料的特点,发酵工艺要求将玉米从原料仓库运至备料车间,通过磁选装置除去原料中含铁杂质,以爱惜设备。
然后进入粗粉碎机,将玉米先轧成2~4mm大小的小块,以提高磨粉机的效率,便于物料的输送。
粗碎后,由斗式提升机送至中间粉仓,由粉仓落入磨粉机粉碎,粉碎后进入粉仓再经计量送至配料罐。
配料罐内加水调浆,同时加入其他原料,在进行分批灭菌后送至其它车间。
青霉素产生菌的培育工段
将原料处置工段送来的经分批灭菌并冷却的料液,通过灭菌管道泵入空且灭菌待料的种子罐,并接入小米孢子,在通风、搅拌的情形下,进行培育,在培育进程中,对罐温、罐压、通风量、搅拌转速等实行持续记录监控,并按期检测菌种生长状态、菌种数量等转变情形。
培育进程中应注意菌体的生长发育情形:
①分生孢子的Ⅰ期;
②菌丝繁衍,原生质嗜碱性很强,有类脂肪小颗粒产生为Ⅱ期;
③原生质嗜碱性仍很强,形成脂肪粒,积存贮藏物为Ⅲ期;
④原生质嗜碱性很弱,脂肪粒减少,形成中、小空泡为Ⅳ期;
⑤脂肪粒消失,形成大空泡为Ⅴ期;
⑥细胞内看不到颗粒,并有个别自溶细胞显现为Ⅵ期。
其中Ⅰ~Ⅳ期称为菌丝生长期,菌丝的浓度增加很多,但产生的青霉素较少,处于该时期的菌丝体适用于做发酵种子。
Ⅳ~Ⅴ期是青霉素分泌期,现在菌丝体生长缓慢,并大量生产青霉素。
发酵工段
由备料车间提供的经分批灭菌并冷却的料液,通过灭菌管道泵入空且灭菌待料的发酵罐,通过压差法,接入已培育好的产黄青霉菌株,在通风、搅拌的情形下,进行发酵,在发酵培育进程中,对罐温、罐压
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