CN101643487A - Method for separating and purifying amikacin - Google Patents
Method for separating and purifying amikacin Download PDFInfo
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- CN101643487A CN101643487A CN200910042293A CN200910042293A CN101643487A CN 101643487 A CN101643487 A CN 101643487A CN 200910042293 A CN200910042293 A CN 200910042293A CN 200910042293 A CN200910042293 A CN 200910042293A CN 101643487 A CN101643487 A CN 101643487A
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- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
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Abstract
The invention discloses a method for separating and purifying amikacin, which carries out continuous chromatographic resolution on amikacin material by using weak-acid cation resin and employing a continuous chromatographic resolution system technique. The method comprises the following steps: the material solution divides 30 separating units in the whole procedure into four regions comprising anadsorption region, a washing region, a separating region and a regenerating region through a continuous chromatographic resolution system, so as to replace the prior fixed-bed separation plant; and the original steps of absorption, washing, resolving, regenerating and the like in the fixed bed in the whole procedure are integrated into the disc-transmission type reverse-flow continuous chromatographic resolution system, so that the amikacin is effectively separated and purified, the production cost is reduced, the production technique is simplified, the production period is shortened, the pollution is reduced and the total yield is increased.
Description
Technical field
The present invention relates to the separating and purifying method of amikacin, particularly relate to a kind of method that adopts continuous chromatography separation system technology amikacin to be separated purification.
Background technology
Amikacin is a kind of aminoglycoside antibiotics, is used for the treatment of various bacteria and infects.Amikacin is fixed against the combination of bacterium 30S subunit, blocking-up bacterioprotein synthetic and play anti-microbial effect.Be usually used in treating the drug-fast Gram-negative bacteria hospital acquired infections of serious multiple medicines thing, as Pseudomonas aeruginosa, acinetobacter calcoaceticus and enterobacteria etc.
It is that raw material comes through chemical reaction that the production method of present amikacin generally adopts to block that, several components: AHBA, KNA, K6, K29, K8, K11 below main existence the in the end reaction mixed solution, the content of K6 and K11 is all lower in normal reaction; And K8 and K29 are isomers, and character is very similar, and wherein K8 is needed active principle, and K29 and KNA all need to reclaim to reduce production costs simultaneously.And purification K8 mainly adopts resin method, and used equipment is fixed bed, in this method since K8 and K29 separate difficulty especially, in technology now,, have a series of shortcomings in order to improve the purity of K8:
1) production cycle very long because amount of resin is big, the utilization ratio of unit resin is very low, and fixed bed quantity when one-time investment is big, floor space is very big;
2) regeneration reagent consumption big (comprising water), environmental pollution is more serious, particularly ammoniated waste water, environmental protection pressure is very big;
3) inferior separating effect of K8 and K29 is resolved in the collection liquid at resin, and K8 and K29 mixed solution proportion are big; K8 collection liquid purity is low, so that reduced the yield of follow-up workshop section;
4) to extract the yield of workshop section low for whole resin.
Summary of the invention
The objective of the invention is to the existing shortcoming of fixed bed production method at present amikacin purification technique employing, a kind of amikacin method of purification of improvement is provided---continuous chromatography separation system production method, making the amikacin feed liquid can more effectively obtain separating after the continuous chromatography separation system purifies, and reduce production costs, simplified production method, shortening production cycle, reduce and pollute.
Technical scheme of the present invention is: the amikacin feed liquid is through the continuous chromatography separation system, replaced original fixed bed separating device, make the absorption of original fixed bed, drip washing, wash-out, be incorporated in the whole workshop sections such as regeneration in the disk delivering adverse current continuous chromatography separation system, it is divided into plurality of sections with whole section resin in original fixed bed, that part of resin in former processing method mass transfer zone front is positioned at one or several little resin column again, can reenter absorption-wash-out-regeneration like this waits in the circulation, utilized the part resin of originally not reinstated, the resin utilization ratio has just improved greatly, can also reduce chemical reagent simultaneously, the consumption of water etc.Disk delivering continuous chromatography separation system has a large amount of post (separation) unit, also makes them can be effectively applied to very much the series classification production process.
Characteristic according to each composition in the amikacin feed liquid, the selected resin of the present invention is a weakly acidic cationic exchanger resin, and the resin particle diameter is below 0.22mm, and uniformity coefficient is more than 95%, and continuous chromatography is separated 30 of whole flow processs separate junior unit and be divided into four zones, each zone is composed as follows:
1) adsorption zone: this zone is totally 10 unit, pass through flow rate control, raw material at first enters first group of three unit (3 mouthfuls of parallel connections), after converging the back and the water lotion of absorption water wash zone mixes in the lump, the effusive liquid of each mouthful enters second group the corresponding resin container in other three unit (3 mouthfuls of parallel connections) again, each effluent liquid of corresponding mouthful enters the corresponding resin container in remaining the 3rd group of four unit (4 mouthfuls of parallel connections) again, and effluent liquid is a waste liquid;
2) water wash zone: this district is totally 1 unit, after absorption, each resin container needs washing, after being positioned at adsorption zone, after resin container rotated to the absorption water wash zone, the feed liquid (mainly being clear liquor) that is entrained in interlaminar resin was ejected by water, effluent liquid together enters second group of resin container that valve port is corresponding with the effluent liquid mixing of first group of adsorption zone, flush away is mixed in the feed liquid in the resin space and takes away impurity as far as possible, prevents from that feed liquid from carrying secretly to enter to resolve the district, by getting water wash zone unit outlet sample to determine washing effect;
3) parsing is distinguished: this resolves totally 13 unit, district, with continuous, gradient analysis mode, and all adopt positive charging, and collection respectively exports desorbed solution respectively;
4) breeding blanket: this district is totally 6 unit, all chargings separately, and be backward feed, thereby all using mixing tank to come reagent preparation to reach again, the wash-down water after each step regeneration utilizes.Fixed bed separation system with respect to traditional the invention has the advantages that:
1) institute with former fixed-bed process all is integrated in the cover process system in steps;
2) system is oversimplified, and reduce the layout of process pipe, system compact;
3) resin utilization ratio height makes concentration, purity and the yield optimization of product;
4) in resin inside can than be easier to just to carry out, adverse current, the resin that can loosen prevents its caking;
5) consumption of minimizing chemical reagent and water reduces the discharging of waste water;
6) system adopts self-con-tained unit, reduces work load;
Description of drawings
Fig. 1 separates the method flow diagram of purification for the present invention.
Embodiment
Be elaborated below in conjunction with Fig. 1 and embodiment:
The selected resin of the present invention is a weakly acidic cationic exchanger resin, and the resin particle diameter is below 0.22mm, and uniformity coefficient is more than 95%, and each resin container amount of fill is 0.23m
3, the resin container actual volume is 0.26m
3, resin container is of a size of Φ 640 * 800mm, and actual filling ratio is 90%.System's overall size is about 5 * 5 * 6.5 (length * wide * height).Be divided into following zone:
(1) adsorption zone (Unit 2～11)
Each unit resin container is divided into three groups in this zone, pass through flow rate control, raw material at first enters 2～No. 4 mouths (3 mouthfuls of parallel connections), from effusive back the mixing in the lump of liquid junction of each mouthful entering the corresponding resin container of 5～No. 7 valve ports (3 mouthfuls of parallel connections) again with the water lotion of No. 1 mouth, each effluent liquid mixing of corresponding mouthful enters the resin container of 8～No. 11 mouth correspondences again, and effluent liquid is a waste liquid.
(2) water wash zone (Unit 1)
Through absorption after, each resin container need the washing, be positioned at adsorption zone after.After resin container rotated to the absorption water wash zone, the feed liquid (mainly being clear liquor) that is entrained in interlaminar resin was ejected by water, and the effluent liquid mixing of 2～No. 4 mouths of effluent liquid and adsorption zone together enters the corresponding resin container in unit 5～No. 7.Flush away is mixed in the feed liquid that the resin space goes out and takes away impurity as far as possible, preventing that feed liquid from carrying secretly to enter resolves the district, improves the purity of desorbed solution, and its water lotion is incorporated into adsorption zone, active principle in the planar water washing lotion exports sample for No. 1 to determine washing effect by getting once more.
(3) resolve district (Unit 18～30)
Resolve the district at this, with continuous, gradient analysis mode, resolve the district and all adopt positive charging, collection respectively exports desorbed solution respectively, and design is divided into following several sections according to processing method:
1) the 29-30 parallel connection is advanced 0.6N ammoniacal liquor desorbed solution and is directly entered water drain;
2) 0.4N ammoniacal liquor is advanced in the 27-28 parallel connection, and desorbed solution is collected and is mainly KNA;
3) 0.6N ammoniacal liquor is advanced in the 25-26 parallel connection, and desorbed solution is collected and is mainly K29;
4) advance 0.6N ammoniacal liquor No. 24, desorbed solution is collected, and is the mixing of K8 and K29, through behind the pH regulator as the part of charging;
5) arrangement mode in parallel is taked in 18-23 number each unit, advances about 0.8N ammoniacal liquor, and collect in each exit, unit, and main ingredient is K8.
(4) breeding blanket (12～No. 17 unit)
This all charging separately of 6 unit, district, and be backward feed, thereby all using mixing tank to come reagent preparation to reach again, the wash-down water after each step regeneration utilizes.
Wherein, No. 17 is 2N sodium hydroxide; No. 16 is water; No. 15 is 2N sulfuric acid; No. 14 is water; No. 13 is 2N ammoniacal liquor; No. 12 is water.
Example major design method parameter of the present invention is as follows:
Inlet amount 1.5m
3/ hr
Resin total amount 7m
3
Resin flows speed 0.56m
3/ hr
Absorption after washing 1.03m
3/ hr
Resolve the district
Resolve 1 (0.6N ammoniacal liquor) 0.62m
3/ hr
Resolve 2 (0.4N ammoniacal liquor) 0.62m
3/ hr
Resolve 3 (0.6N ammoniacal liquor) 0.62m
3/ hr
Resolve 4 (0.6N ammoniacal liquor) 0.42m
3/ hr
Resolve 5 (0.8N ammoniacal liquor) 1.23m
3/ hr
The breeding blanket
2N alkali 0.45m
3/ hr
Washing 1.45m
3/ hr
2N acid 0.45m
3/ hr
Washing 1.3m
3/ hr
2N ammonia 0.56m
3/ hr
Washing 1.4m
3/ hr
Separation purity: resolve product and divide three parts.K8 collects the requirement that part can satisfy downstream process; KNA and K29, K8 separate fully, and the lap that requires K8 and K29 that can satisfy recovery is by directly getting back to opening for feed after regulating, as the part of feeding liquid.
In this continuous chromatography separation system, can accomplish batch interior reuse, the washing after the absorption can come back to adsorption zone, and the loss when so just reducing absorption fully exchanges the active principle in the feed liquid; Water in the water washing process after each step reagent regeneration can the regeneration of each reagent of reuse in, water and reagent can be recycled.
Working cost and Economic and Efficiency Analysis:
1) working cost: the working cost in the continuous chromatography separation system mainly concentrates on resin, chemical reagent, this three part of water, and the electrisity consumption of host system few (except the power consumption of peripheral pump).At charging 36m
3Under the situation of/d, system's resin demand is 7m3, and the life-span is the same with fixed bed;
Chemical reagent: 98% sulfuric acid 0.58m
3/ d;
Sodium hydroxide 0.86T/d;
Liquefied ammonia 1.36T/d;
Water consumption 125T/d.
2) Economic and Efficiency Analysis: the continuous chromatography separation system is applied to the purifies and separates of amikacin, has following benefit:
1. reduce resin demand, reduce the consumption of regeneration reagent and water;
2. yield improves; Fixed bed K8 yield is 85%-90% at present, and the isolating K8 yield of continuous chromatography can be accomplished 93%-98%, on average improves yield more than 5%;
3. except above direct income, the continuous chromatography separation system also will be brought many benefits such as shortening of easy, production cycle of minimizing, the operation of floor space for synthetic subsidiary factory.
Claims (2)
1. a method of separating purifying amikacin is characterized in that adopting continuous chromatography separation system technology, and uses weakly acidic cation-exchange resin, continuous chromatography is separated 30 separating units of whole flow process be divided into four zones, and each zone is composed as follows:
1) adsorption zone: this zone is totally 10 unit, pass through flow rate control, raw material at first enters first group of three unit (3 mouthfuls of parallel connections), after converging the back and the water lotion of absorption water wash zone mixes, the effusive liquid of each mouthful enters second group the corresponding resin container in other three unit (3 mouthfuls of parallel connections) again, each effluent liquid of corresponding mouthful enters the corresponding resin container in remaining the 3rd group of four unit (4 mouthfuls of parallel connections) again, and effluent liquid is a waste liquid;
2) water wash zone: this district is totally 1 unit, after absorption, each resin container needs washing, after being positioned at adsorption zone, after resin container rotated to the absorption water wash zone, the feed liquid (mainly being clear liquor) that is entrained in interlaminar resin was ejected by water, effluent liquid together enters second group of resin container that valve port is corresponding with the effluent liquid mixing of first group of adsorption zone, flush away is mixed in the feed liquid in the resin space and takes away impurity as far as possible, prevents from that feed liquid from carrying secretly to enter to resolve the district, by getting water wash zone unit outlet sample to determine washing effect;
3) parsing is distinguished: resolve the district and have 13 unit, with continuous, gradient analysis mode, and all adopt positive charging, and collection respectively exports desorbed solution respectively;
4) breeding blanket: this district has 6 unit, all chargings separately, and be backward feed, thereby all using mixing tank to come reagent preparation to reach again, the wash-down water after each step regeneration utilizes.
2. according to a kind of method of separating purifying amikacin described in the claim 1, the resin that it adopted is a weakly acidic cationic exchanger resin, and the resin particle diameter requires below 0.22mm, and uniformity coefficient is more than 95%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910042293A CN101643487B (en) | 2009-08-31 | 2009-08-31 | Method for separating and purifying amikacin |
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|---|---|---|---|
| CN200910042293A CN101643487B (en) | 2009-08-31 | 2009-08-31 | Method for separating and purifying amikacin |
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| Publication Number | Publication Date |
|---|---|
| CN101643487A true CN101643487A (en) | 2010-02-10 |
| CN101643487B CN101643487B (en) | 2012-09-05 |
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|---|---|---|---|
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102796149A (en) * | 2012-07-25 | 2012-11-28 | 无锡济民可信山禾药业股份有限公司 | Continuous separation and purification technology for etimicin |
| CN103374047A (en) * | 2012-04-27 | 2013-10-30 | 无锡济民可信山禾药业股份有限公司 | Method for separating and purifying high-purity 3,2'',6''-tri-N-acetyl-gentamicin C1a alkali (P1) |
| CN103483213A (en) * | 2013-08-26 | 2014-01-01 | 厦门世达膜科技有限公司 | Method for separating p-hydroxyphenylglycine and ammonium sulfate from glycine mother solution |
| CN106317132A (en) * | 2016-08-24 | 2017-01-11 | 厦门世达膜科技有限公司 | Aminoglycoside antibiotics separation and purification method |
| CN111269276A (en) * | 2020-03-13 | 2020-06-12 | 厦门世达膜科技有限公司 | Production method for separating acarbose and impurities |
| CN115057901A (en) * | 2022-07-12 | 2022-09-16 | 赛普特环保技术(厦门)有限公司 | Nucleoside purification system and purification process |
-
2009
- 2009-08-31 CN CN200910042293A patent/CN101643487B/en active Active
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103374047A (en) * | 2012-04-27 | 2013-10-30 | 无锡济民可信山禾药业股份有限公司 | Method for separating and purifying high-purity 3,2'',6''-tri-N-acetyl-gentamicin C1a alkali (P1) |
| CN103374047B (en) * | 2012-04-27 | 2016-05-11 | 无锡济民可信山禾药业股份有限公司 | A kind of highly purified 3,2 ", 6 " tri--N-acetyl group is celebrated large C1a alkali (P1) isolation and purification method |
| CN102796149A (en) * | 2012-07-25 | 2012-11-28 | 无锡济民可信山禾药业股份有限公司 | Continuous separation and purification technology for etimicin |
| CN102796149B (en) * | 2012-07-25 | 2015-04-22 | 无锡济民可信山禾药业股份有限公司 | Continuous separation and purification technology for etimicin |
| CN103483213A (en) * | 2013-08-26 | 2014-01-01 | 厦门世达膜科技有限公司 | Method for separating p-hydroxyphenylglycine and ammonium sulfate from glycine mother solution |
| CN103483213B (en) * | 2013-08-26 | 2016-03-16 | 厦门世达膜科技有限公司 | A kind of method being separated D-pHPG and ammonium sulfate from glycin mother liquid |
| CN106317132A (en) * | 2016-08-24 | 2017-01-11 | 厦门世达膜科技有限公司 | Aminoglycoside antibiotics separation and purification method |
| CN111269276A (en) * | 2020-03-13 | 2020-06-12 | 厦门世达膜科技有限公司 | Production method for separating acarbose and impurities |
| CN111269276B (en) * | 2020-03-13 | 2021-05-11 | 厦门世达膜科技有限公司 | Production method for separating acarbose and impurities |
| CN115057901A (en) * | 2022-07-12 | 2022-09-16 | 赛普特环保技术(厦门)有限公司 | Nucleoside purification system and purification process |
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|---|---|
| CN101643487B (en) | 2012-09-05 |
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Application publication date: 20100210 Assignee: Xiamen Shida membrane Engineering Co.,Ltd. Assignor: XIAMEN STARMEM TECHNOLOGY CO.,LTD. Contract record no.: X2021980014823 Denomination of invention: Method for separating and purifying amikacin Granted publication date: 20120905 License type: Exclusive License Record date: 20211221 |
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