CN102002079B - 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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- CN102002079B CN102002079B CN 201010178726 CN201010178726A CN102002079B CN 102002079 B CN102002079 B CN 102002079B CN 201010178726 CN201010178726 CN 201010178726 CN 201010178726 A CN201010178726 A CN 201010178726A CN 102002079 B CN102002079 B CN 102002079B
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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 component B content of lincomycin.
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 relatively high when wherein using the butyl alcohol extraction lincomycin, and the clinical application of its derivative is had very large side effect, and is particularly larger to intestines, liver, renal function; When extracting lincomycin with higher alcohols, though reduce certain B component concentration, yield is unstable, and B component controllability is not strong, and working condition and envrionment conditions are all relatively poor, and easily makes the active sludge of processing 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 larger, 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 the Lincomycin B component is reduced to below 0.1%.
Summary of the invention
For 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 component B content of lincomycin, reduced the consumption of alkaline aqueous solution washing, solve the user B component has been proposed the different controllabilitys that require, improved traditional technique or equipment; Reduced the pollution of environment, be conducive to waste water can be biochemical performance; Particularly increased the resin absorption capacity of lincomycin with the anti-stripping agent of solvent (comprising butanols or higher alcohols) extracting solution, and desorb unit is concentrated, the more important thing is and the Lincomycin B component can be reduced to below 0.1%.Simultaneously, also reduce widely labour intensity and production cost, be conducive to large industrial mass-producing.
For achieving the above object, the production technique of reduction component B content of lincomycin of the present invention, this production technique is with the aqueous solution of the water-soluble liquid of the anti-stripping agent of solvent (comprising butanols or higher alcohols) extracting solution or lincomycin crude product or recovery crude product 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 again the propyl carbinol desorb, then get final product (being primary crystallization or recrystallization) according to normal explained hereafter.
The production technique of reduction component B content of lincomycin of the present invention, this technique is the anti-stripping agent with solvent (comprising butanols or higher alcohols) extracting solution, after dilution, directly be adsorbed to after with the NaOH adjust pH saturated, through the hot alkaline water solution washing, and with the extraction process of propyl carbinol desorb.
The production technique of reduction component B content of lincomycin 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, get 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 the content of scrub raffinate B component 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., macroporous resin pillar saturated after will washing carries out desorb with neutrality or alkaline propyl carbinol, gets desorbed solution; Then with directly concentrated decolouring crystallization of desorbed solution, get finished product; Or with desorbed solution azeotropic crystalization, decolouring, acetone recrystallize, and get finished product; Or desorbed solution stripped with hydrochloric acid, get 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 for subsequent use;
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 same model macroporous resin or different model.
Simultaneously, the lincomycin crude product that also can extract with solvent or reclaim crude product all with after the purified water dissolving gets the lincomycin lysate; Directly refining with extracting of macroporous resin pillar absorption lincomycin after NaOH transfers pH above-mentioned lincomycin lysate.
Also can filter after pH2.0-3.5 is transferred in the oxalic acid acidifying with lincomycin fermentation liquid, its filtrate transfers PH between 8.5-11.0 with NaOH again, and it is refining then directly to adsorb extracting of lincomycin with the macroporous resin pillar of above-mentioned steps.
According to the processing method of reduction component B content of lincomycin 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 technique or equipment; Reduced the pollution of environment, be conducive to waste water can be biochemical performance; Particularly increased the loading capacity of lincomycin with the anti-stripping agent of solvent (comprising butanols or higher alcohols) extracting solution, and desorb unit is concentrated, simultaneously, has reduced widely labour intensity and production cost, is conducive to large industrial mass-producing.
Embodiment
The production technique of reduction component B content of lincomycin of the present invention, this production technique is with the aqueous solution of the water-soluble liquid of the anti-stripping agent of solvent (comprising butanols or higher alcohols) extracting solution or lincomycin crude product or recovery crude product 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 again the propyl carbinol desorb, then get final product (being primary crystallization or recrystallization) according to normal explained hereafter.
The production technique of reduction component B content of lincomycin of the present invention, this technique is the anti-stripping agent with solvent (comprise butanols or higher alcohols etc. one or more mixture) extracting solution, after dilution, directly be adsorbed to after with the NaOH adjust pH saturated, through the hot alkaline water solution washing, and with the extraction process of propyl carbinol desorb.
The production technique of reduction component B content of lincomycin 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, get 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 the content of scrub raffinate B component 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., macroporous resin pillar saturated after will washing carries out desorb with neutral or alkaline propyl carbinol, gets desorbed solution, then with the directly concentrated crystallization of decolouring of desorbed solution, gets 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 for subsequent use;
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 same model macroporous resin or different model.
Simultaneously, the lincomycin crude product that also can extract with solvent or reclaim crude product all with after the purified water dissolving gets the lincomycin lysate; Directly refining with extracting of macroporous resin pillar absorption lincomycin after NaOH transfers pH above-mentioned lincomycin lysate.
Also can filter after pH2.0-3.5 is transferred in the oxalic acid acidifying with lincomycin fermentation liquid, its filtrate transfers PH between 8.5-11.0 with NaOH again, and it is refining then directly to adsorb extracting of lincomycin with the macroporous resin pillar of above-mentioned steps.
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 is measured 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 component B content of lincomycin 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 technique or equipment; Reduced the pollution of environment, be conducive to waste water can be biochemical performance; Particularly increased the loading capacity of lincomycin with the anti-stripping agent of solvent (comprising butanols or higher alcohols) extracting solution, and desorb unit is concentrated, simultaneously, has reduced widely labour intensity and production cost, is conducive to large industrial mass-producing.
Claims (3)
1. production technique that reduces component B content of lincomycin, it is characterized in that this technique is the anti-stripping agent with the solvent extracting solution, behind the recovery solvent, directly is adsorbed to saturated after dilution is with the NaOH adjust pH, through the hot alkaline water solution washing, and with the extraction process of propyl carbinol desorb; This production technique specifically may further comprise the steps:
1., with the anti-stripping agent of solvent extracting solution, reclaim solvent after, after the water dilution, transferring pH through NaOH again is 8.5, gets alkaline solution; Described amount of dilution is controlled in the 10-50BV;
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 the content of scrub raffinate B component 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., macroporous resin pillar saturated after will washing carries out desorb with neutrality or alkaline propyl carbinol, gets desorbed solution; Then with desorbed solution azeotropic crystalization, decolouring, acetone recrystallize, 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 for subsequent use;
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..
2. the production technique of reduction component B content of lincomycin 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 with extracting of macroporous resin pillar absorption lincomycin after NaOH transfers pH above-mentioned lincomycin lysate.
3. the production technique of reduction component B content of lincomycin according to claim 1, it is characterized in that filtering after pH2.0-3.5 is transferred in the oxalic acid acidifying with lincomycin fermentation liquid, its filtrate is transferred pH8.5 with NaOH again, and is then directly refining with extracting of the macroporous resin pillar of above-mentioned steps absorption lincomycin.
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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 |
CN102633846A (en) * | 2012-04-09 | 2012-08-15 | 南阳普康药业有限公司 | Lincomycin purification method |
CN103724380B (en) * | 2013-12-25 | 2015-09-02 | 江苏久吾高科技股份有限公司 | A kind of extracting 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 |
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 |
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 |
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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段永平 等.林可霉素大孔吸附树脂工艺研究.《药品评价》.2006,第3卷(第6期), * |
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