Culture medium for fermenting and producing tylosin with streptomyces fradiae, and fermentation method

A technology of tylosin and extraction method, which is applied in the direction of chemical instruments and methods, sugar derivatives, sugar derivatives, etc., can solve the problems of high BA price, large dosage, and limited extraction capacity, and achieve small dosage and high extraction efficiency high effect

Inactive Publication Date: 2012-07-18
宁夏泰瑞制药股份有限公司
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  • Abstract
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  • Application Information

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Problems solved by technology

However, ethyl acetate has a big disadvantage: the solubility in water at room temperature is 8.08% by mass fraction, and it is easy to decompose after long-term storage or use, and the hydrolysis products are acetic acid and ethanol
However, the disadvantages of extracting tylosin from the fermentation broth with BA are as follows: first: the price of BA is high and the dosage is large
Second: the extraction capacity of BA is limited

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] 实施例1 用乙酸丁酯从发酵滤液中萃取泰乐菌素

[0020] 二级逆流萃取:泰乐菌素发酵滤液60m 3 ,效价为13523u / ml。有机溶媒乙酸丁酯18m 3 . 开启离心机,待转速和电流正常后,打开各物料管道阀门,同时打开管道加热器蒸汽阀门对物料进行加热,使进入离心机的发酵液温度在44℃。 在萃取过程中取样检查复合溶媒相和水相分离情况、效价及水相pH值,萃取液一级pH在7.0~10.0、二级pH在8.0~11.0。 萃取结束后,水相体积为58m 3 ,效价为748u / ml。乙酸丁酯体积为17.1m 3 ,效价为41898u / ml。用时4.1h。萃取收率为88.3%。

[0021] 反萃取:将萃取液打入反萃取罐内,冷却至8℃,加入浓度为3.2%的磷酸溶液。控制磷酸溶液流量以使水相pH值达4.5,并搅拌15min,静置分层,分出反萃取液后,将一级反萃取液转移到中和罐进一步中和。加入浓度为6.5%的磷酸溶液,控制磷酸溶液流量以使水相pH值至2.3,并搅拌15min,静置分层,分出反萃取液后,将二级反萃取液转移到中和罐合并一级反萃取液进一步中和。反萃取结束后,检测复合溶媒效价为412u / ml。

[0022] 中和、脱色、过滤和喷雾干燥:用纯化水配制21%的氢氧化钙混悬液。在搅拌下缓慢加入氢氧化钙混悬液,加氢氧化钙时间每次间隔40min,pH值调至6.5时加入活性炭42kg,搅拌15min,再加入硅藻土助滤剂40kg,继续搅拌15min。进板框过滤机开始过滤,收集滤液。板框过滤后的精制液含有一些小颗粒杂质,先用板框过滤,再用微滤膜进行二级精过滤,过滤介质为5um、0.3um滤膜。精滤后的精制液进行下一步喷雾干燥。喷雾干燥是利用高压往复泵将浓缩料液喷成细小雾滴,在干燥塔顶部鼓入的干燥热风将雾滴瞬间干燥,废气体排出塔体外,干燥后粉末沉降到底部收集起来,获取泰乐菌素磷酸盐粉末。

Embodiment 2

[0023] 实施例2 用复合溶媒从发酵滤液中萃取泰乐菌素

[0024] 二级逆流萃取:泰乐菌素发酵滤液60m 3 ,效价为13416u / ml。复合溶媒15m 3 (乙酸丁酯9.1 m 3 、乙酸异丁酯4.65m 3 、丁醇1.2m 3 ). 开启离心机,待转速和电流正常后,打开各物料管道阀门,同时打开管道加热器蒸汽阀门对物料进行加热,使进入离心机的发酵液温度在40℃。 在萃取过程中取样检查复合溶媒相和水相分离情况、效价及水相pH值,萃取液一级pH在7.0~10.0、二级pH在8.0~11.0。 萃取结束后,水相体积为57m 3 ,效价为286u / ml。复合溶媒积为14.6m 3 ,效价为52542u / ml。萃取用时3.1h。萃取收率为95.3%。

[0025] 反萃取:将萃取液打入反萃取罐内,冷却至7℃,加入浓度为3.8%的磷酸溶液。控制磷酸溶液流量以使水相pH值达4.2,并搅拌14min,静置分层,分出反萃取液后,将一级反萃取液转移到中和罐进一步中和。加入浓度为6.2%的磷酸溶液,控制磷酸溶液流量以使水相pH值至2.1,并搅拌13min,静置分层,分出反萃取液后,将二级反萃取液转移到中和罐合并一级反萃取液进一步中和。反萃取结束后,检测复合溶媒效价为407u / ml。

[0026] 中和、脱色、过滤和喷雾干燥:用纯化水配制24%的氢氧化钙混悬液。在搅拌下缓慢加入氢氧化钙混悬液,加氢氧化钙时间每次间隔45min,pH值调至6.2时加入活性炭41.3kg,搅拌12min,再加入硅藻土助滤剂40.5kg,继续搅拌15min。进板框过滤机开始过滤,收集滤液。板框过滤后的精制液含有一些小颗粒杂质,先用板框过滤,再用微滤膜进行二级精过滤,过滤介质为5um、0.3um滤膜。精滤后的精制液进行下一步喷雾干燥。喷雾干燥是利用高压往复泵将浓缩料液喷成细小雾滴,在干燥塔顶部鼓入的干燥热风将雾滴瞬间干燥,废气体排出塔体外,干燥后粉末沉降到底部收集起来,获取泰乐菌素磷酸盐粉末。

Embodiment 3

[0027] 实施例3 用复合溶媒从发酵滤液中萃取泰乐菌素

[0028] 泰乐菌素发酵滤液60m 3, The titer is 13462u / ml. Emulsification occurred in the fermented liquid, and 204 L of demulsifier sodium dodecylbenzenesulfonate was added. Add composite solvent 15.6m 3 (Butyl acetate 9.4 m 3 , Isobutyl acetate 4.8m 3 , butanol 1.4m 3 ). Turn on the centrifuge, and after the speed and current are normal, open the valves of each material pipeline, and at the same time open the steam valve of the pipeline heater to heat the material, so that the temperature of the fermentation liquid entering the centrifuge is at 45°C. During the extraction process, samples were taken to check the separation between the composite solvent phase and the water phase, the potency and the pH value of the water phase. The primary pH of the extract was 7.0-10.0, and the secondary pH was 8.0-11.0. After the extraction, the volume of the aqueous phase is 57m 3 , The titer is 272u / ml. Composite solvent volume is 15.2m 3 , the titer is 5074...

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Abstract

The invention relates to a compound menstruum for extracting tylosin and an extraction method. According to the invention, the compound menstruum formed by mixing butyl acetate, isobutyl acetate and butanol according to the volume ratio of 6:3 to 3.2 to 0.8-1 is used for extracting tylosin in fermentation filtrate through a secondary counter-current extraction method. The method has the advantages of low consumption of organic menstruum, low loss of tylosin, short extraction time, high extraction yield and the like.

Description

technical field [0001] 本发明属于生物医药提取技术领域,特别是涉及一种泰乐菌素提取溶媒及提取方法。 Background technique [0002] 泰乐菌素又称泰乐霉素,是由放线菌属弗氏链霉菌经发酵提取而得到的一种大环内酯类抗生素,有泰乐菌素碱、磷酸盐和酒石酸盐三种 form. 泰乐菌素是一种禽、畜专用的高效、无残留抗菌促生剂。 对鸡败血症、猪流行性肺炎等疾病有独特的疗效,且对禽、畜的生长具有明显的促进作用。 泰乐菌素作为动物专用抗生素,避免了人畜共用抗生素易产生交叉耐药性的问题,用于防治猪、禽支原体病。 [0003] 目前,国内泰乐菌素提取工艺主要是将泰乐菌素发酵液首先预处理,经固液分离,得到发酵滤液;其次将发酵滤液用有机溶媒进行萃取,泰乐菌素进入酯相液,酯相液采取反萃取方法,经酸化处理,泰乐菌素进入水相;最后泰乐菌素水相液经过中和、脱色、过滤和喷雾干燥等过程得到磷酸泰乐菌素或酒石酸泰乐菌素。 [0004] 上述提取方法中通常采用乙酸乙酯或乙酸丁酯(以下简称BA)作为萃取剂。乙酸乙酯是一种典型的常用萃取溶剂,具有优异的溶解能力。泰乐菌素碱不溶于水,易溶于乙酸乙酯。但乙酸乙酯存在很大的不足:常温下在水中的溶解度为质量分数的8.08%,长期储存或使用易分解,水解产物为乙酸和乙醇。应用到泰乐菌素提取工业中损耗达到20~40%。目前,国内生产泰乐菌素的企业已停止使用乙酸乙酯。 [0005] 乙酸丁酯(BA)具备与乙酸乙酯同样的溶解能力,但其不溶于水,较难分解,是一种优良的萃取溶剂。 目前,国内生产泰乐菌素的大部分企业都选择BA作为提取泰乐菌素的有机溶媒。 但是用BA从发酵液中提取泰乐菌素,其不足之处是:第一:BA价格高、用量大。 一吨泰乐菌素滤液需要0.3~0.6吨BA。 由于BA具有易挥发的性质,每批使用过程中挥发损耗约占BA总数的1~1.5%;BA回收率一般控制在80~90%。 按此计算年产1000吨泰乐菌素的企业,一年BA的损耗至少1300万元以上。 第二:BA的萃取能力有限。 泰乐菌素滤液进过二级逆流萃取后,两遍的总萃取收率控制在85~95%,另外水相中泰乐菌素的效价一般在500~1000u / ml,随废水被排放 Lose. 按此计算,年产1000吨泰乐菌素的企业,每年随废水排放的泰乐菌素损失高达...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H17/08C07H1/08
Inventor 任勇冷晓红王友善奇乃董媛李小萍
Owner 宁夏泰瑞制药股份有限公司
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