CN102746348A - Method for separation of lincomycin - Google Patents
Method for separation of lincomycin Download PDFInfo
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- CN102746348A CN102746348A CN2011100985141A CN201110098514A CN102746348A CN 102746348 A CN102746348 A CN 102746348A CN 2011100985141 A CN2011100985141 A CN 2011100985141A CN 201110098514 A CN201110098514 A CN 201110098514A CN 102746348 A CN102746348 A CN 102746348A
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Abstract
The invention discloses a method for separation of lincomycin. The method comprises the following steps of acidizing a lincomycin-containing fermentation liquor, carrying out filtration, carrying out alkalinity regulation, carrying out filtration again, collecting a filtrate, treating the filtrate as a sample liquid by a polystyrene-divinylbenzene reversed-phase adsorption resin, carrying out elution purification of the filtrate by an alkaline aqueous solution having a pH value the same as a pH value of the filtrate, eluting lincomycin by n-butanol, collecting the n-butanol solution of lincomycin, carrying out concentration, acidification and crystallization, and carrying out recrystallization by acetone. The method provided by the invention has the advantages of appropriate solvent consumption, simple processes, high product lincomycin purity more than 98%, and low lincomycin component B content less than 0.5%.
Description
Technical field
The present invention relates to a kind of separation method of lincomycin.
Background technology
Lincomycin (Lincomycin) but be an elite stand amine alkaline antibiotic, soluble in water and methyl alcohol is used its hydrochloride clinically, is mainly used in the infection that rises of treatment gram-positive microorganism.With in the process of streptomyces lincolnensis (Streptomyces lincolnensis) fermentative prodn lincomycin except that producing lincomycin, also produce other analogs such as lincomycin B component.Lincomycin B component is a kind of toxic ingredient, need remove, otherwise can influence quality product, and is especially more strict to the control of B component concentration when the processing lincomycins.
Traditional technology generally adopts solvent extraction from fermented liquid, to extract lincomycin.Wherein, the shortcoming of butanols extraction process is that solvent consumption is big, operational condition and environment are poor, and the B component concentration of crystal product is high; Use higher alcohols, during as extraction agent, can reduce the B components contents to a certain extent, but the smell is awful, complicated operation like octanol; Disclose in the CN 101348508A patent documentation and a kind ofly from fermented liquid, extracted the method for lincomycin with resin, this method has been saved extraction step, but shortcoming be the B components contents still higher (0.7%～1.3%).In view of there is above-mentioned defective in existing lincomycin separation method, this present situation needs to be resolved hurrily.
Summary of the invention
Technical problem to be solved by this invention is to have overcome the big or complicated operation of the separation method solvent consumption of lincomycin in the prior art; And all exist and obtain the higher defective of lincomycin B component concentration in the product; Provide a kind of solvent consumption moderate, easy and simple to handle; And product lincomycin purity can reach more than 98%, and the separation method of the lincomycin of lincomycin B component concentration below 0.5%.
The separation method of lincomycin of the present invention comprises the steps: containing lincomycin fermentation liquid acidifying after-filtration; Cross leaching filtrating once more after transferring alkalescence then, go up appearance polystyrene-divinylbenzene anti-phase adsorption resin column afterwards, use earlier and the alkaline aqueous solution wash-out removal of impurities of sample solution with pH; Use propyl carbinol wash-out lincomycin again; Collect that the lincomycin butanol solution concentrates, acidifying and crystallization, and then use acetone recrystallization, get final product.
Among the present invention, the described lincomycin fermentation liquid that contains is the conventional microbial bacteria fermented liquid for preparing lincomycin in this area, is generally obtained through this area ordinary method fermentation culture by streptomyces lincolnensis Streptomyces lincolnensis.The concrete bacterial classification of described streptomyces lincolnensis does not have particular determination; The conventional bacterial classification that can produce lincomycin all can use, like streptomyces lincolnensis Streptomyces lincolnensis NRRL2936, streptomyces lincolnensis Streptomyces lincolnensis CPCC 280065 (Chinese medicinal microbial strains preservation administrative center can sell), streptomyces lincolnensis Streptomyces lincolnensis CPCC 240859 (Chinese medicinal microbial strains preservation administrative center can sell) etc.Wherein, Described streptomyces lincolnensis through cultivation and fermentation obtain to contain the concrete bacterial classification of lincomycin fermentation liquid not constrained be because lincomycin is the secondary metabolite of streptomyces lincolnensis; Though different concrete bacterial strains is different on the ratio of the output of lincomycin, impurity; But the staple relative fixed of fermented liquid, the fermented liquid of therefore different concrete bacterial classification streptomyces lincolnensis preparations all is suitable for the inventive method.
Among the present invention; The described lincomycin fermentation liquid acidifying after-filtration that contains; Transfer then and cross leaching filtrating after the alkalescence once more and separate the conventional pretreatment operation that lincomycin is handled fermented liquid for this area is conventional, wherein, acidifying be for metals ions such as complexing calcium ions with precipitated impurities albumen and be beneficial to filtration; Filtering once more after the accent alkalescence is to remove the further clear filtrate of alkaline insoluble impurity in order to precipitate, and all belongs to conventional existing operation.Wherein, what described acidifying was preferable transfers pH 2-4 for oxalic acid, is more preferred from oxalic acid and transfers pH 3; What described accent alkalescence was preferable is that sodium hydroxide is transferred pH 9-11, and better is that sodium hydroxide is transferred pH 10; What described filtration was preferable is Plate Filtration.
Among the present invention; Described polystyrene-divinylbenzene anti-phase polymeric adsorbent (PS-DVB anti-phase polymeric adsorbent) is the conventional polystyrene-divinylbenzene anti-phase polymeric adsorbent that uses in this area; Preferable model is No. 1, NM PS100 or microballoon, and that better is NM PS100.Wherein, That the particle diameter of described PS-DVB anti-phase polymeric adsorbent is preferable is 50 μ m-120 μ m, and the aperture is preferable, and to be
better is
Among the present invention, what the applied sample amount of described upward appearance was preferable is≤the 50mg/mL resin.
Among the present invention; That the absorption flow velocity of described upward appearance polystyrene-divinylbenzene anti-phase adsorption resin column is preferable is 0.02BV/min-0.04BV/min; Wherein said BV/min is the conventional metering in a this area term; A kind of method for expressing of flow velocity, promptly the fluid that passes through of unit time is equivalent to the multiple of resin volume.
Among the present invention, described and sample solution with the alkaline aqueous solution of pH preferable be aqueous sodium hydroxide solution.Wherein, that described pH value is preferable is 9-11, and better is 10.
Among the present invention, described and sample solution with the consumption of the alkaline aqueous solution of pH preferable be 4.5BV-5.5BV, that better is 5BV.
Among the present invention, that the consumption of described propyl carbinol is preferable is 1.5BV-2.5BV.
Among the present invention, described collection lincomycin butanol solution concentrates, acidifying and crystallization are this area conventional processing operation steps.Wherein, described simmer down to this area routine operation, preferable is 50 ℃ of-80 ℃ of concentrating under reduced pressure.That described spissated terminal point is preferable is the 15%-25% that is concentrated into original volume.Described acidifying is this area routine operation, and preferable is that hydrochloric acid adjusting pH adjusts 0.5-2.5.Described crystallization condition is this area normal service condition, and preferable be 20 ℃-30 ℃ leaves standstill 4h-8h.
Among the present invention, described acetone recrystallization is this area conventional processing operation steps.Described acetone recrystallization is preferable is that the 10%-20% that is concentrated into original volume behind 10 times of acetone solutions with upper volume leaves standstill crystallization again and gets final product.Wherein, the described crystalline condition that leaves standstill is the conventional crystallization condition in this area, and preferable be 4 ℃ leaves standstill 4h-8h.
Among the present invention, generally also can be after the described acetone recrystallization according to the conventional aftertreatment in this area, preferable will get final product with 2-3 back oven dry of washing with acetone for the crystal with recrystallization again.
Agents useful for same of the present invention and raw material except that specified otherwise, all commercially available getting.
On the basis that meets this area general knowledge, the optimum condition of each above-mentioned technical characterictic can arbitrary combination obtain preferred embodiments of the present invention among the present invention.
Positive progressive effect of the present invention is: the solvent consumption of lincomycin separation method of the present invention is moderate, easy and simple to handle, and product lincomycin purity can reach more than 98%, and lincomycin B component concentration is below 0.5%.
Embodiment
Mode through embodiment further specifies the present invention below, but does not therefore limit the present invention among the described scope of embodiments.
The experimental technique of unreceipted actual conditions in the following example, usually according to normal condition, or the condition of advising according to manufacturer.
Among the following embodiment; The performance liquid chromatography testing conditions that detects lincomycin is: permaphase ODS-C18 (5 μ); Detect wavelength 214nm; Moving phase: 0.05mol/L borax soln (transferring pH to 5.0): methyl alcohol: acetonitrile=60: 36: 4, flow velocity 0.8ml/min, 35 ℃ of column temperatures with 85% phosphoric acid solution.
Among the following embodiment, the resin source is: Suzhou Nano-Micro Bio-technology Co., Ltd..Wherein, NMPS100 resin particle diameter 50 μ m-100 μ m; No. 1 resin particle diameter of aperture
microballoon 60 μ m-120 μ m, aperture
Preparation embodiment
Preparation lincomycin fermentation liquid, the bacterial classification that uses is streptomyces lincolnensis Streptomyceslincolnensis NRRL 2936 (source american agriculture research DSMZ), Streptomyceslincolnensis CPCC 280065 (originate Chinese medicinal microbial strains preservation administrative center), Streptomyces lincolnensis CPCC 240859 (originate Chinese medicinal microbial strains preservation administrative center).
Culture condition:
Bacterial strain inserted under 30 ℃ of conditions in the slant medium cultivated 6 days, the consisting of of slant medium (%): starch 2.0, cold soybean cake powder 0.5, K
2HPO
40.05, NaCl 0.05, MgSO
47H
2O 0.05, agar 2.5, pH 7.0;
Afterwards the thalline that grows on the inclined-plane being dug piece is inoculated in the seed culture medium and cultivated 2 days; Culture temperature is 30 ℃, the consisting of of seed culture medium (%): starch 2.0, glucose 2.5, soybean cake powder 2.0, steeping water 2.5, ammonium sulfate 0.2, sodium-chlor 0.07, lime carbonate 0.8, pH 7.0;
The lincomycin fermentation condition:
Cultured seed is inoculated in the fermention medium by 10% inoculum size cultivated 7 days; Culture temperature is 30 ℃, the consisting of of fermention medium (%): starch 1.0, glucose 4.0, soybean cake powder 3.0, steeping water 1.2, ammonium sulfate 0.8, an ammonium nitrate 0.1, sodium-chlor 0.5, SODIUMNITRATE 0.6, potassium primary phosphate 0.03, lime carbonate 0.8, pH7.0.
Wherein, embodiment 1～3 uses bacterial classification to be streptomyces lincolnensis Streptomyces lincolnensisNRRL 2936; Embodiment 4～6 uses bacterial classification to be streptomyces lincolnensis Streptomyces lincolnensisCPCC 280065, and embodiment 7～8 uses bacterial classification to be streptomyces lincolnensis Streptomyces lincolnensisCPCC 240859.
Embodiment 1
With lincomycin fermentation liquid (unit is 7560u/ml, and volume is 1.3L), regulate pH to 2.0 with oxalic acid, Plate Filtration is got acidizing fluid, and transfers pH to 9.5 back to filtrate after leaching with sodium hydroxide acidizing fluid;
Select for use PS/DVB anti-phase polymeric adsorbent NM PS100 it to be adsorbed (the chromatography column diameter is about 4cm; Highly be about 20cm); After the absorption of the flow velocity upper prop of 0.02BV/min, using 4.5BV pH is that 9.5 buck carries out the wash-out removal of impurities, has removed a large amount of pigments and salt; And the B component washed basically, with the propyl carbinol of 1.5BV lincomycin is concentrated again afterwards to wash;
The butanol solution of lincomycin is evaporated to 20% of original volume at 60 ℃, and after with hydrochloric acid pH being adjusted to 0.5 its temperature is reduced to 20 ℃ and leaves standstill the 4h crystallization, and suction filtration obtains coarse crystal;
Be concentrated into 20% of original volume behind the acetone solution of coarse crystal with lincomycin with 10 times of volumes; Leave standstill the 4h crystallization in 4 ℃ of environment; Behind the 4h with the crystal suction filtration; And obtain the U 10149a crystal with oven dry behind the washing with acetone 3 times, and it is 98.2% that HPLC detects lincomycin purity, the B component concentration is 0.42%.
Embodiment 2
With lincomycin fermentation liquid (unit is 7361u/ml, and volume is 1.4L), regulate pH to 3.0 with oxalic acid, Plate Filtration is got acidizing fluid, and transfers pH to 9.0 back to filtrate after leaching with sodium hydroxide acidizing fluid;
Select for use No. 1, PS/DVB anti-phase adsorbent resin microballon it to be adsorbed (the chromatography column diameter is about 4cm; Highly be about 20cm); After the absorption of the flow velocity upper prop of 0.04BV/min, using 5BV pH is that 9.0 buck carries out the wash-out removal of impurities, has removed a large amount of pigments and salt; And the B component washed basically, with the propyl carbinol of 2BV lincomycin is concentrated again afterwards to wash;
The butanol solution of lincomycin is evaporated to 15% of original volume at 50 ℃, and after with hydrochloric acid pH being adjusted to 1.0 its temperature is reduced to 25 ℃ and leaves standstill the 6h crystallization, and suction filtration obtains coarse crystal;
Be concentrated into 15% of original volume behind the acetone solution of coarse crystal with lincomycin with 11 times of volumes; Leave standstill the 7h crystallization in 4 ℃ of environment; Behind the 7h with the crystal suction filtration; And obtain the U 10149a crystal with oven dry behind the washing with acetone 2 times, and it is 98.5% that HPLC detects lincomycin purity, the B component concentration is 0.35%.
Embodiment 3
With lincomycin fermentation liquid (unit is 7862u/ml, and volume is 1.0L), regulate pH to 3.5 with oxalic acid, Plate Filtration is got acidizing fluid, and transfers pH to 10.0 back to filtrate after leaching with sodium hydroxide acidizing fluid;
Select for use PS/DVB anti-phase polymeric adsorbent NM PS100 it to be adsorbed (the chromatography column diameter is about 4cm; Highly be about 20cm); After the absorption of the flow velocity upper prop of 0.03BV/min, using 5.5BV pH is that 10.0 buck carries out the wash-out removal of impurities, has removed a large amount of pigments and salt; And the B component washed basically, with the propyl carbinol of 2.5BV lincomycin is concentrated again afterwards to wash;
The butanol solution of lincomycin is evaporated to 25% of original volume at 55 ℃, and after with hydrochloric acid pH being adjusted to 1.5 its temperature is reduced to 30 ℃ and leaves standstill the 8h crystallization, and suction filtration obtains coarse crystal;
Be concentrated into 10% of original volume behind the acetone solution of coarse crystal with lincomycin with 13 times of volumes; Leave standstill the 5h crystallization in 4 ℃ of environment; Behind the 5h with the crystal suction filtration; And obtain the U 10149a crystal with oven dry behind the washing with acetone 3 times, and it is 98.6% that HPLC detects lincomycin purity, the B component concentration is 0.32%.
Embodiment 4
With lincomycin fermentation liquid (unit is 8200u/ml, and volume is 1.0L), regulate pH to 3.0 with oxalic acid, Plate Filtration is got acidizing fluid, and transfers pH to 10.0 back to filtrate after leaching with sodium hydroxide acidizing fluid;
Select for use PS/DVB anti-phase polymeric adsorbent NM PS100 it to be adsorbed (the chromatography column diameter is about 4cm; Highly be about 20cm); After the absorption of the flow velocity upper prop of 0.02BV/min, using 4.5BV pH is that 10.0 buck carries out the wash-out removal of impurities, has removed a large amount of pigments and salt; And the B component washed basically, with the propyl carbinol of 2BV lincomycin is concentrated again afterwards to wash;
The butanol solution of lincomycin is evaporated to 15% of original volume at 65 ℃, and after with hydrochloric acid pH being adjusted to 1.0 its temperature is reduced to 25 ℃ and leaves standstill the 6h crystallization, and suction filtration obtains coarse crystal;
Be concentrated into 15% of original volume behind the acetone solution of coarse crystal with lincomycin with 10 times of volumes; Leave standstill the 6h crystallization in 4 ℃ of environment; Behind the 6h with the crystal suction filtration; And obtain the U 10149a crystal with oven dry behind the washing with acetone 2 times, and it is 98.7% that HPLC detects lincomycin purity, the B component concentration is 0.3%.
Embodiment 5
With lincomycin fermentation liquid (unit is 6251u/ml, and volume is 1.5L), regulate pH to 3.0 with oxalic acid, Plate Filtration is got acidizing fluid, and transfers pH to 10.0 back to filtrate after leaching with sodium hydroxide acidizing fluid;
Select for use PS/DVB anti-phase polymeric adsorbent NM PS100 it to be adsorbed (the chromatography column diameter is about 4cm; Highly be about 20cm); After the absorption of the flow velocity upper prop of 0.04BV/min, using 5.5BV pH is that 10.0 buck carries out the wash-out removal of impurities, has removed a large amount of pigments and salt; And the B component washed basically, with the propyl carbinol of 1.5BV lincomycin is concentrated again afterwards to wash;
The butanol solution of lincomycin is evaporated to 20% of original volume at 75 ℃, and after with hydrochloric acid pH being adjusted to 2.5 its temperature is reduced to 20 ℃ and leaves standstill the 5h crystallization, and suction filtration obtains coarse crystal;
Be concentrated into 20% of original volume behind the acetone solution of coarse crystal with lincomycin with 12 times of volumes; Leave standstill the 5h crystallization in 4 ℃ of environment; Behind the 5h with the crystal suction filtration; And obtain the U 10149a crystal with oven dry behind the washing with acetone 2 times, and it is 98.0% that HPLC detects lincomycin purity, the B component concentration is 0.4%.
Embodiment 6
With lincomycin fermentation liquid (unit is 7945u/ml, and volume is 1.0L), regulate pH to 4.0 with oxalic acid, Plate Filtration is got acidizing fluid, and transfers pH to 11.0 back to filtrate after leaching with sodium hydroxide acidizing fluid;
Select for use PS/DVB anti-phase polymeric adsorbent NM PS100 it to be adsorbed (the chromatography column diameter is about 4cm; Highly be about 20cm); After the absorption of the flow velocity upper prop of 0.03BV/min, using 5.0BV pH is that 11.0 buck carries out the wash-out removal of impurities, has removed a large amount of pigments and salt; And the B component washed basically, with the propyl carbinol of 2.5BV lincomycin is concentrated again afterwards to wash;
The butanol solution of lincomycin is evaporated to 15% of original volume at 80 ℃, and after with hydrochloric acid pH being adjusted to 1.5 its temperature is reduced to 30 ℃ and leaves standstill the 4h crystallization, and suction filtration obtains coarse crystal;
Be concentrated into 15% of original volume behind the acetone solution of coarse crystal with lincomycin with 12 times of volumes; Leave standstill the 5h crystallization in 4 ℃ of environment; Behind the 5h with the crystal suction filtration; And obtain the U 10149a crystal with oven dry behind the washing with acetone 3 times, and it is 98.7% that HPLC detects lincomycin purity, the B component concentration is 0.3%.
Embodiment 7
With lincomycin fermentation liquid (unit is 7713u/ml, and volume is 1.2L), regulate pH to 3.0 with oxalic acid, Plate Filtration is got acidizing fluid, and transfers pH to 9.5 back to filtrate after leaching with sodium hydroxide acidizing fluid;
Select for use No. 1, PS/DVB anti-phase adsorbent resin microballon it to be adsorbed (the chromatography column diameter is about 4cm; Highly be about 20cm); After the absorption of the flow velocity upper prop of 0.03BV/min, using 4.5BV pH is that 9.5 buck carries out the wash-out removal of impurities, has removed a large amount of pigments and salt; And the B component washed basically, with the propyl carbinol of 2BV lincomycin is concentrated again afterwards to wash;
The butanol solution of lincomycin is evaporated to 25% of original volume at 75 ℃, and after with hydrochloric acid pH being adjusted to 2.0 its temperature is reduced to 25 ℃ and leaves standstill the 5h crystallization, and suction filtration obtains coarse crystal;
Be concentrated into 15% of original volume behind the acetone solution of coarse crystal with lincomycin with 11 times of volumes; Leave standstill the 6h crystallization in 4 ℃ of environment; Behind the 6h with the crystal suction filtration; And obtain the U 10149a crystal with oven dry behind the washing with acetone 3 times, and it is 98.5% that HPLC detects lincomycin purity, the B component concentration is 0.33%.
Embodiment 8
With lincomycin fermentation liquid (unit is 7680u/ml, and volume is 1.1L), regulate pH to 3.5 with oxalic acid, Plate Filtration is got acidizing fluid, and transfers pH to 9.0 back to filtrate after leaching with sodium hydroxide acidizing fluid;
Select for use PS/DVB anti-phase polymeric adsorbent NM PS100 it to be adsorbed (the chromatography column diameter is about 4cm; Highly be about 20cm); After the absorption of the flow velocity upper prop of 0.04BV/min, using 5.5BV pH is that 9.0 buck carries out the wash-out removal of impurities, has removed a large amount of pigments and salt; And the B component washed basically, with the propyl carbinol of 1.5BV lincomycin is concentrated again afterwards to wash;
The butanol solution of lincomycin is evaporated to 25% of original volume at 60 ℃, and after with hydrochloric acid pH being adjusted to 1.5 its temperature is reduced to 20 ℃ and leaves standstill the 4h crystallization, and suction filtration obtains coarse crystal;
Be concentrated into 20% of original volume behind the acetone solution of coarse crystal with lincomycin with 10 times of volumes; Leave standstill the 5h crystallization in 4 ℃ of environment; Behind the 5h with the crystal suction filtration; And obtain the U 10149a crystal with oven dry behind the washing with acetone 3 times, and it is 98.1% that HPLC detects lincomycin purity, the B component concentration is 0.45%.
Claims (10)
1. the separation method of a lincomycin is characterized in that: it comprises the steps: containing lincomycin fermentation liquid acidifying after-filtration, crosses leaching filtrating once more after transferring alkalescence then; Go up afterwards appearance polystyrene-divinylbenzene anti-phase adsorption resin column; Use earlier and the alkaline aqueous solution wash-out removal of impurities of sample solution, use propyl carbinol wash-out lincomycin again, collect that the lincomycin butanol solution concentrates, acidifying and crystallization with pH; And then use acetone recrystallization, get final product.
2. separation method as claimed in claim 1 is characterized in that: the described lincomycin fermentation liquid that contains is obtained through this area ordinary method fermentation culture by streptomyces lincolnensis Streptomyces lincolnensis.
3. separation method as claimed in claim 2 is characterized in that: described streptomyces lincolnensis is streptomyces lincolnensis Streptomyces lincolnensis NRRL 2936, streptomyces lincolnensis Streptomyceslincolnensis CPCC 280065 or streptomyces lincolnensis Streptomyces lincolnensis CPCC240859.
4. separation method as claimed in claim 1 is characterized in that: the described lincomycin fermentation liquid acidifying after-filtration that contains, and to transfer then and cross once more after the alkalescence in the leaching filtrating step, described acidifying is that oxalic acid is transferred pH 2-4, is preferably oxalic acid and transfers pH 3; Described accent alkalescence is sodium hydroxide accent pH 9-11, and preferable is that sodium hydroxide is transferred pH 10; The described Plate Filtration that is filtered into.
5. separation method as claimed in claim 1 is characterized in that: the model of described polystyrene-divinylbenzene anti-phase polymeric adsorbent is No. 1, NM PS100 or microballoon; The particle diameter of described polystyrene-divinylbenzene anti-phase polymeric adsorbent is 50-120 μ m, and the aperture is
preferable be
6. separation method as claimed in claim 1 is characterized in that: the described applied sample amount of going up appearance is≤the 50mg/mL resin; The described absorption flow velocity of going up appearance polystyrene-divinylbenzene anti-phase adsorption resin column is 0.02BV/min-0.04BV/min.
7. separation method as claimed in claim 1 is characterized in that: described and sample solution are aqueous sodium hydroxide solution with the alkaline aqueous solution of pH; Described pH value is 9-11, and preferable is 10; Described and sample solution are 4.5BV-5.5BV with the consumption of the alkaline aqueous solution of pH, and that preferable is 5BV.
8. separation method as claimed in claim 1 is characterized in that: the consumption of described propyl carbinol is 1.5BV-2.5BV.
9. separation method as claimed in claim 1 is characterized in that: described collection lincomycin butanol solution concentrates, in acidifying and the crystallisation step, 50 ℃ of-80 ℃ of concentrating under reduced pressure of described simmer down to; Described spissated terminal point is the 15%-25% that is concentrated into original volume; Described acidifying is that hydrochloric acid is regulated pH adjustment 0.5-2.5; Described crystallization condition is 20 ℃-30 ℃ and leaves standstill 4h-8h.
10. separation method as claimed in claim 1 is characterized in that: described acetone recrystallization is that the 10%-20% that is concentrated into original volume behind 10 times of acetone solutions with upper volume leaves standstill crystallization again and gets final product.
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| 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 |
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| CN111592576A (en) * | 2020-05-11 | 2020-08-28 | 天方药业有限公司 | Treatment method of butanol crystallization mother liquor of lincomycin hydrochloride |
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| CN112645993A (en) * | 2020-12-24 | 2021-04-13 | 西安蓝晓科技新材料股份有限公司 | Purification method of high-purity lincomycin hydrochloride |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3515717A (en) * | 1968-12-16 | 1970-06-02 | Upjohn Co | Process for isolating antibiotics |
| CN101348508A (en) * | 2008-09-11 | 2009-01-21 | 亓平言 | Albiotic purification process |
| CN101648981A (en) * | 2009-09-22 | 2010-02-17 | 南阳普康药业有限公司 | Extraction and refinement process of lincomycin |
| CN102002079A (en) * | 2010-05-21 | 2011-04-06 | 北京华致信诚科技有限公司 | Production process for reducing component B content of lincomycin |
-
2011
- 2011-04-19 CN CN201110098514.1A patent/CN102746348B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3515717A (en) * | 1968-12-16 | 1970-06-02 | Upjohn Co | Process for isolating antibiotics |
| CN101348508A (en) * | 2008-09-11 | 2009-01-21 | 亓平言 | Albiotic purification process |
| CN101648981A (en) * | 2009-09-22 | 2010-02-17 | 南阳普康药业有限公司 | Extraction and refinement process of lincomycin |
| CN102002079A (en) * | 2010-05-21 | 2011-04-06 | 北京华致信诚科技有限公司 | Production process for reducing component B content of lincomycin |
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