CN102002079A - Production process for reducing component B content of lincomycin - Google Patents
Production process for reducing component B content of lincomycin Download PDFInfo
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- CN102002079A CN102002079A CN 201010178726 CN201010178726A CN102002079A CN 102002079 A CN102002079 A CN 102002079A CN 201010178726 CN201010178726 CN 201010178726 CN 201010178726 A CN201010178726 A CN 201010178726A CN 102002079 A CN102002079 A CN 102002079A
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Abstract
The invention discloses a production process for reducing the component B content of lincomycin. The process method comprises: performing the absorption by macroporous resin on reverse extract of a solvent (including butanol or higher alcohol) extract, or aqueous solution of coarse lincomycin, or fermented filtrate of lincomycin or aqueous solution of recovered coarse lincomycin after pH adjustment by NaOH; washing by alkaline aqueous solution; desorbing with n-butyl alcohol; and producing finished products by normal processes. When the process method for reducing the component B content of lincomycin, which is provided by the invention, is used, the use amount of the alkaline aqueous solution for washing is lowered, the controllability of different requirements of users on the component B is improved, and the conventional process or equipment is improved; pollution caused to the environment is reduced greatly, the possibility for renewing waste water is increased; and the capacity of absorbing the reverse extract of the solvent extract of lincomycin is increased, the desorbing units are centralized, and at the same time, the labor intensity and production cost are reduced considerably and the large-scale industrial production can be realized easily.
Description
Affiliated technical field
The invention belongs to pharmaceutical chemistry technical field, particularly relate to a kind of production technique that reduces lincomycin B component concentration.
Background technology
The extraction traditional technology of fermented filtrate of lincomycin is to extract with solvent (butanols or higher alcohols).The B component concentration of finished product is higher relatively when wherein using the butyl alcohol extraction lincomycin, and the clinical application of its derivative is had very big side effect, and is particularly bigger to intestines, liver, renal function influence; When extracting lincomycin with higher alcohols, though reduce certain B component concentration, the yield instability, B component controllability is not strong, and working condition and envrionment conditions are all relatively poor, and easily makes the active sludge of handling its waste water poison and lost efficacy; And when extracting with traditional resin method, though reduce the B component concentration, desorb unit does not concentrate, and washing amount is bigger, causes production cost to increase; When particularly using lincomycin with the adsorbing and extracting of the anti-stripping agent of solvent (comprising butanols or higher alcohols) extracting solution, the capacity of the absorption of its resin is minimum, and the hangover of desorb unit, simultaneously, also is difficult to lincomycin B component is reduced to below 0.1%.
Summary of the invention
At above-mentioned situation, for overcoming the defective of prior art, the objective of the invention is to propose a kind of production technique that reduces lincomycin B component concentration, reduced the consumption of alkaline aqueous solution washing, solve the user B component has been proposed the different controllabilitys that require, improved traditional technology or equipment; Reduced the pollution of environment, help waste water can be biochemical performance; Particularly increased the resin absorption capacity of lincomycin, and desorb unit is concentrated, the more important thing is and lincomycin B component can be reduced to below 0.1% with the anti-stripping agent of solvent (comprising butanols or higher alcohols) extracting solution.Simultaneously, also reduce labour intensity and production cost widely, helped big industrial mass-producing.
For achieving the above object, the production technique of reduction lincomycin B component concentration of the present invention, this production technique is with the water-soluble liquid of the anti-stripping agent of solvent (comprising butanols or higher alcohols) extracting solution or lincomycin crude product or recovery aqueous solution of crude or extremely saturated with carrying out resin absorption behind the NaOH accent pH after diluting with fermented filtrate of lincomycin, through the hot alkaline water solution washing, use the propyl carbinol desorb again, get final product (being primary crystallization or recrystallization) according to normal explained hereafter then.
The production technique of reduction lincomycin B component concentration of the present invention, this technology is the anti-stripping agent with solvent (comprising butanols or higher alcohols) extracting solution, saturated with directly being adsorbed to behind the NaOH adjust pH after diluting, through the hot alkaline water solution washing, and with the extraction process of propyl carbinol desorb.
The production technique of reduction lincomycin B component concentration of the present invention specifically may further comprise the steps:
1., with the anti-stripping agent of solvent (comprising butanols or higher alcohols) extracting solution, after the water dilution, transfer pH between 8.5-11.0 through NaOH again, alkaline solution;
2., above-mentioned alkaline solution is pumped into the pillar that macroporous resin is housed, according to required flow 1.5-2.5BV control, and it is saturated to reach macroporous resin adsorption;
3., be that normal temperature or 30-60 ℃ of thermokalite washings of 8.5-11.0 carries out continuous washing to adsorbing saturated macroporous resin pillar with PH, and in time detect scrub raffinate B components contents with HPLC;
4., the waste liquid when detecting absorption with polarimeter, when containing optically-active unit in the waste liquid, the post of should going here and there immediately absorption, and detect the quantity discharged that height that the tandem post flows out the B component concentration of waste liquid is controlled waste liquid by HPLC;
5., will wash the saturated macroporous resin pillar in back and carry out desorb with neutral or alkaline propyl carbinol, must desorbed solution; Then desorbed solution is directly concentrated the decolouring crystallization, get finished product; Or with desorbed solution azeotropic crystalization, decolouring, acetone recrystallize, and get finished product; Or desorbed solution stripped with hydrochloric acid, anti-stripping agent, reconcentration, decolouring, butanols or acetone crystallization, and finished product;
6., to transfer pH with HCl be that the 4.0-5.5 acidic aqueous solution enters from the bottom to the macroporous resin pillar after the desorb, the top effluxes the transition of carrying out macroporous resin, with standby;
Wherein acidic aqueous solution flows into recovery place, reclaims solvent again;
7., again use above-mentioned tandem post 6. as adsorption column, simultaneously, the former adsorption column after transition is become the tandem post, and repeat 1. to arrive operation steps 6..
Described amount of dilution is controlled in the 10-50BV.
Above-mentioned adsorption column and tandem post can be the void towers of a kind of cylinder shape or square, and its inside can be the macroporous resin of filling with a kind of model macroporous resin or different model.
Simultaneously, the also lincomycin crude product that can extract with solvent or reclaim crude product all with after the purified water dissolving, the lincomycin lysate; Directly refining after NaOH transfers pH above-mentioned lincomycin lysate with extracting of macroporous resin pillar absorption lincomycin.
Also can transfer the pH2.0-3.5 after-filtration through the oxalic acid acidifying with lincomycin fermentation liquid, its filtrate transfers PH between 8.5-11.0 with NaOH again, and it is refining directly to adsorb extracting of lincomycin with the macroporous resin pillar of above-mentioned steps then.
According to the processing method of reduction lincomycin B component concentration provided by the invention, reduced the consumption of alkaline aqueous solution washing, solved the user B component has been proposed the different controllabilitys that require, improved traditional technology or equipment; Reduced the pollution of environment, help waste water can be biochemical performance; Particularly increased the loading capacity of lincomycin, and desorb unit is concentrated, simultaneously, has reduced labour intensity and production cost widely, helps big industrial mass-producing with the anti-stripping agent of solvent (comprising butanols or higher alcohols) extracting solution.
Embodiment
The production technique of reduction lincomycin B component concentration of the present invention, this production technique is with the water-soluble liquid of the anti-stripping agent of solvent (comprising butanols or higher alcohols) extracting solution or lincomycin crude product or recovery aqueous solution of crude or extremely saturated with carrying out resin absorption behind the NaOH accent pH after diluting with fermented filtrate of lincomycin, through the hot alkaline water solution washing, use the propyl carbinol desorb again, get final product (being primary crystallization or recrystallization) according to normal explained hereafter then.
The production technique of reduction lincomycin B component concentration of the present invention, this technology is the anti-stripping agent with solvent (comprise butanols or higher alcohols etc. one or more mixture) extracting solution, saturated with directly being adsorbed to behind the NaOH adjust pH after diluting, through the hot alkaline water solution washing, and with the extraction process of propyl carbinol desorb.
The production technique of reduction lincomycin B component concentration of the present invention specifically may further comprise the steps:
1., with the anti-stripping agent of solvent (comprise butanols or higher alcohols etc. one or more mixture) extracting solution, after the water dilution, transfer pH between 8.5-11.0 through NaOH again, alkaline solution;
2., above-mentioned alkaline solution is pumped into the pillar that macroporous resin is housed, according to required flow 1.5-2.5BV control, and it is saturated to reach macroporous resin adsorption;
3., be that normal temperature or 30-60 ℃ of thermokalite washings of 8.5-11.0 carries out continuous washing to adsorbing saturated macroporous resin pillar with PH, and in time detect scrub raffinate B components contents with HPLC;
4., the waste liquid when detecting absorption with polarimeter, when containing optically-active unit in the waste liquid, the post of should going here and there immediately absorption, and detect the quantity discharged that height that the tandem post flows out the B component concentration of waste liquid is controlled waste liquid by HPLC;
5., will wash the saturated macroporous resin pillar in back and carry out desorb with neutral or alkaline propyl carbinol, desorbed solution, then desorbed solution is directly concentrated the decolouring crystallization, get finished product; Or with desorbed solution azeotropic crystalization, decolouring, acetone recrystallize, and get finished product; Or just desorbed solution is stripped with hydrochloric acid, gets anti-stripping agent, reconcentration, decolouring, butanols or acetone crystallization, and get finished product;
6., to transfer pH with HCl be that the 4.0-5.5 acidic aqueous solution enters from the bottom to the macroporous resin pillar after the desorb, the top effluxes the transition of carrying out macroporous resin, with standby;
Wherein acidic aqueous solution flows into recovery place, reclaims solvent again;
7., again use above-mentioned tandem post 6. as adsorption column, simultaneously, the former adsorption column after transition is become the tandem post, and repeat 1. to arrive operation steps 6..
Described amount of dilution is controlled in the 10-50BV.
Above-mentioned adsorption column and tandem post can be the void towers of a kind of cylinder shape or square, and its inside can be the macroporous resin of filling with a kind of model macroporous resin or different model.
Simultaneously, the also lincomycin crude product that can extract with solvent or reclaim crude product all with after the purified water dissolving, the lincomycin lysate; Directly refining after NaOH transfers pH above-mentioned lincomycin lysate with extracting of macroporous resin pillar absorption lincomycin.
Also can transfer the pH2.0-3.5 after-filtration through the oxalic acid acidifying with lincomycin fermentation liquid, its filtrate transfers PH between 8.5-11.0 with NaOH again, and it is refining directly to adsorb extracting of lincomycin with the macroporous resin pillar of above-mentioned steps then.
Different process for extracting lincomycin is to the contrast situation of B components influence
| Title | The B component of product | Minimum | Remarks |
| Two ones of 2005 editions pharmacopeia | ＜5.0％ | - | - |
| The butyl alcohol extraction method | 3.0～4.2％ | About 2.8% | When the B component was hanged down, yield was low |
| The higher alcohols extraction method | 2.0～3.0％ | About 1.5% | When the B component was hanged down, yield was low |
| The resin extraction method | 0～1.5％ | 0 | Stable yield, controllability is strong |
Annotate: lincomycin B measures according to the high performance liquid chromatography condition under the assay item, and the peak area of lincomycin B must not be crossed 5.0% of lincomycin and lincomycin B peak area sum.
According to the processing method of reduction lincomycin B component concentration provided by the invention, reduced the consumption of alkaline aqueous solution washing, solved the user B component has been proposed the different controllabilitys that require, improved traditional technology or equipment; Reduced the pollution of environment, help waste water can be biochemical performance; Particularly increased the loading capacity of lincomycin, and desorb unit is concentrated, simultaneously, has reduced labour intensity and production cost widely, helps big industrial mass-producing with the anti-stripping agent of solvent (comprising butanols or higher alcohols) extracting solution.
Claims (9)
1. production technique that reduces lincomycin B component concentration, this production technique is with the water-soluble liquid of the anti-stripping agent of solvent extracting solution or lincomycin crude product or recovery aqueous solution of crude or extremely saturated with carrying out resin absorption behind the NaOH accent pH after diluting with fermented filtrate of lincomycin, through the hot alkaline water solution washing, use the propyl carbinol desorb again, get final product according to normal explained hereafter then.
2. the production technique of reduction lincomycin B component concentration according to claim 1, it is characterized in that this technology is the anti-stripping agent with the solvent extracting solution, saturated with directly being adsorbed to behind the NaOH adjust pH after diluting, through the hot alkaline water solution washing, and with the extraction process of propyl carbinol desorb.
3. the production technique of reduction lincomycin B component concentration according to claim 2 is characterized in that described solvent comprises butanols or higher alcohols.
4. the production technique of reduction lincomycin B component concentration according to claim 3 is characterized in that this production technique specifically may further comprise the steps:
1., with the anti-stripping agent of solvent extracting solution, after the water dilution, transfer pH between 8.5-11.0 through NaOH again, alkaline solution;
2., above-mentioned alkaline solution is pumped into the pillar that macroporous resin is housed, according to required flow 1.5-2.5BV control, and it is saturated to reach macroporous resin adsorption;
3., be that normal temperature or 30-60 ℃ of thermokalite washings of 8.5-11.0 carries out continuous washing to adsorbing saturated macroporous resin pillar with PH, and in time detect scrub raffinate B components contents with HPLC;
4., the waste liquid when detecting absorption with polarimeter, when containing optically-active unit in the waste liquid, the post of should going here and there immediately absorption, and detect the quantity discharged that height that the tandem post flows out the B component concentration of waste liquid is controlled waste liquid by HPLC;
5., will wash the saturated macroporous resin pillar in back and carry out desorb with neutral or alkaline propyl carbinol, must desorbed solution; Then desorbed solution is directly concentrated the decolouring crystallization, get finished product; Or with desorbed solution azeotropic crystalization, decolouring, acetone recrystallize, and get finished product; Or desorbed solution stripped with hydrochloric acid, anti-stripping agent, reconcentration, decolouring, butanols or acetone crystallization, and finished product;
6., to transfer pH with HCl be that the 4.0-5.5 acidic aqueous solution enters from the bottom to the macroporous resin pillar after the desorb, the top effluxes the transition of carrying out macroporous resin, with standby;
7., again use above-mentioned tandem post 6. as adsorption column, simultaneously, the former adsorption column after transition is become the tandem post, and repeat 1. to arrive operation steps 6..
5. the production technique of reduction lincomycin B component concentration according to claim 4 is characterized in that described amount of dilution is controlled in the 10-50BV.
6. the production technique of reduction lincomycin B component concentration according to claim 5 is characterized in that wherein acidic aqueous solution flows into recovery place, reclaims solvent again;
7. the production technique of reduction lincomycin B component concentration according to claim 5 is characterized in that above-mentioned adsorption column and tandem post are the void towers of a kind of cylinder shape or square.
8. the production technique of reduction lincomycin B component concentration according to claim 1 is characterized in that the lincomycin crude product that extracts with solvent or reclaims crude product all with after the purified water dissolving, gets the lincomycin lysate; Directly refining after NaOH transfers pH above-mentioned lincomycin lysate with extracting of macroporous resin pillar absorption lincomycin.
9. the production technique of reduction lincomycin B component concentration according to claim 1, it is characterized in that transferring the pH2.0-3.5 after-filtration through the oxalic acid acidifying with lincomycin fermentation liquid, its filtrate transfers PH between 8.5-11.0 with NaOH again, and it is refining directly to adsorb extracting of lincomycin with the macroporous resin pillar of above-mentioned steps then.
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| CN 201010178726 CN102002079B (en) | 2010-05-21 | 2010-05-21 | Production process for reducing component B content of lincomycin |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102633846A (en) * | 2012-04-09 | 2012-08-15 | 南阳普康药业有限公司 | Lincomycin purification method |
| CN102746348A (en) * | 2011-04-19 | 2012-10-24 | 上海医药工业研究院 | Method for separation of lincomycin |
| CN103724380A (en) * | 2013-12-25 | 2014-04-16 | 江苏久吾高科技股份有限公司 | Extraction method of lincomycin |
| CN104356179A (en) * | 2014-10-15 | 2015-02-18 | 江西国药有限责任公司 | Lincomycin hydrochloride purification technology |
| CN104861007A (en) * | 2015-06-02 | 2015-08-26 | 江苏海阔生物医药有限公司 | Method for extracting lincomycin by using resin to adsorb fermentation stock solution |
| CN105111254A (en) * | 2015-10-17 | 2015-12-02 | 霍进铭 | Extraction method of lincomycin |
| CN105237593A (en) * | 2015-11-17 | 2016-01-13 | 宁夏泰益欣生物科技有限公司 | Lincomycin hydrochloride extraction method |
| CN110746473A (en) * | 2018-07-10 | 2020-02-04 | 浙江华谱新创科技有限公司 | Purification process for reducing content of lincomycin B component |
| CN111171090A (en) * | 2020-02-19 | 2020-05-19 | 河南省郑州生态环境监测中心 | Preparation method of low-B lincomycin (B is less than or equal to 1 percent) |
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| CN101348508A (en) * | 2008-09-11 | 2009-01-21 | 亓平言 | Albiotic purification process |
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Patent Citations (1)
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| CN101348508A (en) * | 2008-09-11 | 2009-01-21 | 亓平言 | Albiotic purification process |
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Cited By (14)
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|---|---|---|---|---|
| CN102746348B (en) * | 2011-04-19 | 2016-04-20 | 上海医药工业研究院 | A kind of separation method of lincomycin |
| CN102746348A (en) * | 2011-04-19 | 2012-10-24 | 上海医药工业研究院 | Method for separation of lincomycin |
| CN102633846A (en) * | 2012-04-09 | 2012-08-15 | 南阳普康药业有限公司 | Lincomycin purification method |
| CN103724380A (en) * | 2013-12-25 | 2014-04-16 | 江苏久吾高科技股份有限公司 | Extraction method of lincomycin |
| CN104356179B (en) * | 2014-10-15 | 2017-11-21 | 江西国药有限责任公司 | A kind of Lincomycin Hydrochloride purifying technique |
| CN104356179A (en) * | 2014-10-15 | 2015-02-18 | 江西国药有限责任公司 | Lincomycin hydrochloride purification technology |
| CN104861007A (en) * | 2015-06-02 | 2015-08-26 | 江苏海阔生物医药有限公司 | Method for extracting lincomycin by using resin to adsorb fermentation stock solution |
| CN104861007B (en) * | 2015-06-02 | 2017-09-29 | 江苏海阔生物医药有限公司 | A kind of method that utilization resin adsorption fermenation raw liquid extracts lincomycin |
| CN105111254A (en) * | 2015-10-17 | 2015-12-02 | 霍进铭 | Extraction method of lincomycin |
| CN105237593A (en) * | 2015-11-17 | 2016-01-13 | 宁夏泰益欣生物科技有限公司 | Lincomycin hydrochloride extraction method |
| CN105237593B (en) * | 2015-11-17 | 2019-05-24 | 宁夏泰益欣生物科技有限公司 | Lincomycin Hydrochloride extracting method |
| CN110746473A (en) * | 2018-07-10 | 2020-02-04 | 浙江华谱新创科技有限公司 | Purification process for reducing content of lincomycin B component |
| CN110746473B (en) * | 2018-07-10 | 2021-08-24 | 浙江华谱新创科技有限公司 | Purification process for reducing content of lincomycin B component |
| CN111171090A (en) * | 2020-02-19 | 2020-05-19 | 河南省郑州生态环境监测中心 | Preparation method of low-B lincomycin (B is less than or equal to 1 percent) |
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