CN113896753A - Method for efficiently separating zhongshengmycin from fermentation liquor - Google Patents
Method for efficiently separating zhongshengmycin from fermentation liquor Download PDFInfo
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- VMFXMTJCTSYHCF-HHQUSWFZSA-N [(2r,3r,4s,5r)-5-(hexylamino)-4-hydroxy-2-(hydroxymethyl)-6-[(7-hydroxy-4-oxo-1,3a,5,6,7,7a-hexahydroimidazo[4,5-c]pyridin-2-yl)amino]oxan-3-yl] carbamate Chemical compound CCCCCCN[C@@H]1[C@H](O)[C@@H](OC(N)=O)[C@@H](CO)OC1\N=C\1NC(C(=O)NCC2O)C2N/1 VMFXMTJCTSYHCF-HHQUSWFZSA-N 0.000 title claims abstract description 33
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- 229940079593 drug Drugs 0.000 claims abstract description 19
- 238000010828 elution Methods 0.000 claims abstract description 12
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- 229920005989 resin Polymers 0.000 claims abstract description 11
- 239000012528 membrane Substances 0.000 claims abstract description 9
- 239000012452 mother liquor Substances 0.000 claims abstract description 9
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 33
- 239000007788 liquid Substances 0.000 claims description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 22
- 238000001694 spray drying Methods 0.000 claims description 19
- 238000001728 nano-filtration Methods 0.000 claims description 12
- 239000003480 eluent Substances 0.000 claims description 11
- 238000005406 washing Methods 0.000 claims description 11
- 238000011001 backwashing Methods 0.000 claims description 10
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 8
- 239000003456 ion exchange resin Substances 0.000 claims description 8
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 8
- 238000005189 flocculation Methods 0.000 claims description 4
- 230000016615 flocculation Effects 0.000 claims description 4
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- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 9
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- 229930189330 Streptothricin Natural products 0.000 description 5
- NRAUADCLPJTGSF-WJPMJIHPSA-N [6-[[(3as,7r,7as)-7-hydroxy-4-oxo-1,3a,5,6,7,7a-hexahydroimidazo[4,5-c]pyridin-2-yl]amino]-5-(3,6-diaminohexanoylamino)-4-hydroxy-2-(hydroxymethyl)oxan-3-yl] carbamate Chemical class NCCCC(N)CC(=O)NC1C(O)C(OC(N)=O)C(CO)OC1NC1=N[C@@H]2C(=O)NC[C@@H](O)[C@H]2N1 NRAUADCLPJTGSF-WJPMJIHPSA-N 0.000 description 5
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- 238000003908 quality control method Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
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- MSWZFWKMSRAUBD-QTVWNMPRSA-N (3r,4s,5r,6r)-3-amino-6-(hydroxymethyl)oxane-2,4,5-triol Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@H]1O MSWZFWKMSRAUBD-QTVWNMPRSA-N 0.000 description 1
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 1
- 240000008067 Cucumis sativus Species 0.000 description 1
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 108010011834 Streptolysins Proteins 0.000 description 1
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 1
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- 230000002596 correlated effect Effects 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/02—Heterocyclic radicals containing only nitrogen as ring hetero atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
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- Genetics & Genomics (AREA)
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for efficiently separating zhongshengmycin in fermentation liquor, which has the core process method that the fermentation liquor is filtered by a ceramic membrane, then the low-unit ceramic clear liquor of the ceramic clear liquor is subjected to exchange adsorption separation by cation resin, the elution yield is 90-95%, analytical liquor is independently concentrated and sprayed to be dry, or the analytical liquor and high-unit concentrated mother liquor of the ceramic clear liquor are mixed, concentrated and sprayed to be dry according to the ratio of 1:1-1:3, the obtained zhongshengmycin crude drug content is 25-65% in series quality ratio, the total yield is improved by 16-20%, and the color and the purity of the crude drug are greatly improved compared with the granular product with the 12-24% content in the market. The method solves the problems of separation efficiency of the low-unit mother liquor of the zhongshengmycin and high degradation rate in the production process, obtains raw medicines with different mass ratios, improves the production yield and effectively reduces the production cost.
Description
Technical Field
The invention belongs to the technical field of agricultural antibiotic extraction, and particularly relates to a method for efficiently separating zhongshengmycin from fermentation liquor.
Background
Zhongshengmycin is a broad-spectrum antibiotic, can resist gram-positive bacteria, gram-negative bacteria, mycobacteria, yeast and filamentous fungi, and has toxicity to human and livestock. The bactericide is mainly used for preventing and treating diseases such as apple ring spot, cucumber bacterial angular leaf spot, tomato bacterial wilt and the like, is a green, low-toxicity and low-residue agricultural antibiotic bactericide, and has good market prospect. The chemical name of the zhongshengmycin is streptothricins (streptothricins), the chemical structure of the zhongshengmycin is composed of three parts of a streptolysin lactam, gulosamine and a lysine side chain, the streptothricins are named as streptothricins F, E, D, C, B, A and X respectively from 1 to 7 according to the number of the side chain lysine, and the activity of the streptothricins is positively correlated with the number of the lysine.
At present, the annual output value of Fujian Kaili mother medicine is about 1.4 hundred million yuan, the value of the produced preparation is expanded to about 4.5 hundred million per year, and the market share of the biopesticide is considerable.
The Chinese patent application with the application number of 201210515430.8 discloses a production method of raw powder of zhongshengmycin, the process only carries out preliminary moisture separation, hypha separated by a ceramic membrane is added into concentrated solution for spray drying, so that water-insoluble substances of the product are higher, the processing of downstream liquid preparation products is influenced, and the quality control index is extremely unstable.
The Chinese patent application with the application number of 202011030686.0 discloses a preparation method of a high-purity zhongshengmycin mother drug, which sequentially comprises the steps of plate-frame separation, resin adsorption separation, nanofiltration concentration, activated carbon treatment, plate-frame filtration and spray drying, so that the content of the obtained zhongshengmycin is more than 40%, the one-time drying yield is more than 85%, and the production yield is less than 70%. The process is relatively complex in preparation process, relatively laggard in equipment, large in popularization difficulty of test data, and not beneficial to environmental control due to the fact that quality index control of the intermediate material in production is not considered.
According to the various technical schemes, the quality stability of the preparation process is not high, and the requirements of product purity and high-quality preparation production are not met. Therefore, there is a lack in the art of a more optimized process to meet the market demand for different raw drug products, especially for customization of high quality, high stability raw drug products. According to the method, ceramic membranes are adopted to filter high and low unit materials and collect the high and low unit materials step by step, the low unit materials are subjected to resin adsorption and top water backwashing, hydrochloric acid elution and top water forward washing, nanofiltration concentration and spray drying, and the materials at different stages are collected step by step to obtain the zhongshengmycin raw medicines with different contents, so that the requirements of different customers are met, the quality control cost of downstream enterprises is effectively reduced, the production benefit and the competitiveness at home and abroad are increased, and the sustainable development of the whole industrial chain and industry is favorably improved.
Disclosure of Invention
In order to solve the technical problems, the invention provides a method for efficiently separating zhongshengmycin from fermentation liquor,
the method comprises the steps of ceramic membrane filtration, fractional collection of high and low unit materials, resin adsorption and top water backwashing of the low unit materials, hydrochloric acid elution and top water forward washing, nanofiltration concentration and spray drying, and fractional collection of materials at different stages to obtain the zhongshengmycin raw medicines with different contents, thereby effectively improving the extraction yield. Wherein, the ceramic clear liquid low unit ceramic clear liquid after the fermentation liquid is filtered by the ceramic membrane is subjected to cation resin exchange adsorption separation, the elution yield is 90-95%, the desorption liquid is independently concentrated and sprayed to be dry, or the fermentation liquid and the ceramic clear liquid high unit concentrated mother liquid are mixed, concentrated and sprayed to be dry according to the ratio of 1:1-1:3, the obtained zhongshengmycin raw drug content is 25-65% in series, the total yield is improved by 16-20%, and the raw drug color and the purity are greatly improved compared with 12-24% in content granular products in the market. The method solves the problems of separation efficiency of the low-unit mother liquor of the zhongshengmycin and high degradation rate in the production process, obtains raw medicines with different mass ratios, improves the production yield and effectively reduces the production cost.
More specifically, the technical scheme adopted by the invention is as follows:
a method for producing high-content zhongshengmycin comprises the following process steps:
1) acidifying the zhongshengmycin fermentation liquor, filtering by adopting a ceramic membrane, collecting the zhongshengmycin fermentation liquor step by step before and after water replenishing to obtain high-unit clear liquor and low-unit clear liquor, and respectively collecting the high-unit clear liquor and the low-unit clear liquor into a high-unit clear liquor tank and a low-unit clear liquor tank;
2) the material of the low unit clear liquid tank enters ion exchange resin for adsorption, and after the adsorption is saturated, backwashing is carried out by using top water to remove the upper layer flocculation and precipitation;
3) adopting dilute hydrochloric acid for resolution, collecting materials in time after the potency leaks, sampling and detecting in time, stopping hydrochloric acid resolution when the potency of an outlet is obviously reduced, and carrying out top washing by using pure water;
4) and 3) carrying out nanofiltration concentration on the eluent or the high-unit clear liquid obtained in the step 3), and then carrying out spray drying to obtain the zhongshengmycin original drug with different mass ratios.
In a preferred embodiment of the present invention, in step (1), the material titer of the low unit clear liquid tank and the high unit clear liquid tank is controlled within the range of 3500u/ml and 5500-8500u/ml respectively.
In a preferred embodiment of the present invention, in the step (1), the material yields of the low unit clear liquid tank and the high unit clear liquid tank are controlled in the ranges of 35 to 40% and 55 to 60%, respectively.
In a preferred embodiment of the present invention, in step (2), the ion exchange resin is a modified resin having a size of LX-731 to X1, producing an expansion coefficient of 1.5 to 2.0.
In a preferred embodiment of the invention, in step (2), the volumetric adsorption feed rate is from 0.2 to 1.0BV/h (effective rate is from 2 to 4 kg/t.h)-1) The total adsorption volume is 70-80BV, and the adsorption capacity is controlled at 130-140 kg/t.
In a preferred embodiment of the invention, in step (2), the top water backwash is stopped at 1-2BV/h from the bottom water backwash with greater than 70% light transmission.
In a preferred embodiment of the present invention, in the step (3), the configured concentration of the dilute hydrochloric acid is controlled to be between 4.5 and 5.5%.
In a preferred embodiment of the present invention, in step (3), the column pressure is 0.05-1MPa and the elution rate is 0.3-0.6 BV/h.
In a preferred embodiment of the invention, in step (3), the dilute hydrochloric acid is stripped to a pH of between 2.0 and 3.5 and a top water forward wash is initiated.
In the preferred embodiment of the invention, in the step (3), the top water forward washing speed is 0.3-0.5BV/h, and the material collection is stopped after the pH value is slightly raised after the pH value is lowered to the lowest point of 0.2-0.5.
In a preferred embodiment of the invention, in step (3), the eluent tank feed pH is adjusted to between 2.0 and 3.0 using a low pH feed of a final top water forward wash.
In a preferred embodiment of the invention, in step (4), the eluate is concentrated to 5.0 to 6.0 ten thousand units, conductivity 20 to 50ms, separately spray dried.
In a preferred embodiment of the present invention, in the step (4), the eluate-concentrated mother liquor and the high-unit clear liquid-concentrated mother liquor are mixed in accordance with (1: 1-3: 1), followed by spray-drying.
In a preferred embodiment of the present invention, in step (4), the high unit tank material is concentrated alone or after mixing of eluents, to 4.0 to 5.0 ten thousand units, and spray-dried.
In a preferred embodiment of the invention, the production method described in steps 1) to 4) can obtain 25-65% of raw zhongshengmycin in a series of mass ratios, and the total production yield is 75-85%.
Compared with the prior art, the invention has the beneficial effects that:
1) the invention provides a high-efficiency separation process of zhongshengmycin in fermentation liquor, which is characterized in that a core process method is that high units and low units of ceramic clear liquid are separately treated, the low units of ceramic clear liquid are subjected to exchange adsorption separation through cation resin, and the high units are directly concentrated and sprayed to be dry, so that the problem of low separation efficiency of the zhongshengmycin in the actual production process is solved, the problems of high energy consumption and high degradation rate caused by longer production period are solved, the production yield is improved by 16-20%, and the production cost of raw medicines is effectively reduced.
2) The zhongshengmycin crude drug with the content of 25-65% can be obtained in one production process, but products with different contents have extremely high solubility and higher quality stability, can meet the compatibility requirements of preparations with different contents, reduces the production difficulty and the quality control cost of downstream preparation enterprises, and is favorable for improving the sustainable development of the whole industrial chain and industry.
Drawings
The following is further described with reference to the accompanying drawings:
FIG. 1 is a flow chart of the zhongshengmycin separation process of the invention.
Detailed Description
The essential features of the invention are described below by way of example, it being understood that the example is intended to illustrate and not to limit the embodiments of the invention, the scope and the core content of which are defined in the claims.
Example 1
1) Acidifying the fermentation liquor by oxalic acid to pH2.5-3.0, filtering the ceramic clear liquid before and after adding water by a ceramic membrane, respectively collecting the ceramic clear liquid into a high unit clear liquid tank and a low unit clear liquid tank, wherein the bacterial residue titer is 500 plus materials, the material titer is respectively controlled in the range of 3500u/ml and 5500 plus materials 8500u/ml for 1500 plus materials, the volume of the ceramic clear liquid is 2.3-2.5BV, the material yield is respectively controlled in the range of 35-40 percent and 55-60 percent, and the total yield is more than 94.5 percent.
2) The ion exchange resin is LX-731-X1 modified resin, the production expansion coefficient is 1.5-2.0, and the column loading is about 50%. The low unit tank material enters ion exchange resin for adsorption, and the volume rate of the adsorption feeding is 0.2-1.0BV/h (the effective rate is 2-4 kg/t.h)-1) The pH value of the adsorption end is 6.5-7.0, the total adsorption volume is 70-80BV, and the adsorption capacity is controlled at 140kg/t of 130-. And after the adsorption is saturated, performing top water backwashing to remove the upper layer flocculation sediment, performing top water backwashing from the bottom according to 1-2BV/h, and stopping when the light transmittance is more than 70%.
3) Analyzing by using 4.5-5.5% dilute hydrochloric acid, eluting at a column pressure of 0.05-1MPa and an elution rate of 0.3-0.6BV/h, eluting at 1.5BV until the pH rises, then reducing, sampling in time and detecting, wherein the titer is 500 plus one hour (1000 u/ml), collecting the eluent to a high-unit tank, monitoring the pH and the titer curve of an outlet in the middle, when the pH of the outlet is about 2.0-3.5, the titer obviously reduces or reduces to 8000 plus one hour (15000 u/ml), stopping hydrochloric acid analysis, carrying out top washing by using pure water, wherein the top water positive washing rate is 0.3-0.5BV/h and 1-2h, the pH does not reduce between 0.2-0.5 and the lowest point, slightly rising, stopping collecting, and the titer of the outlet is less than 2000 u/ml. And (3) regulating the pH of the material in the eluent tank to be between 2.0 and 3.0 by using the low-pH material positively washed by the top water at the last stage, regulating the liquid phase titer to be 3.0 to 3.5 ten thousand, and feeding the redundant low-pH material into the next acidification tank. The elution yield is more than 90%.
4) Concentrating the eluate to 5.5-6.0 ten thousand units, conductance of 20-50ms, and spray drying to obtain 55-65% crude drug.
5) Nano-filtering and concentrating the materials in the high unit tank to 4.5-5.0 ten thousand units, and spray-drying to obtain the crude drug with the content of 25-35%.
6) Nanofiltration concentration is more than 96 percent, the spray drying yield is more than 86 percent, and the total production yield is between 78 and 80 percent.
Example 2
1) The steps are the same as the step 3);
4) mixing the eluent concentrated mother liquor and the high unit clear liquid concentrated mother liquor according to the ratio of (1: 1-3: 1), and spray drying to obtain 35-45% of original drug content;
5) nanofiltration concentration is more than 96%, the spray drying yield is more than 86%, and the total production yield is between 78 and 85%.
Example 3
1) The steps are the same as the step 3);
4) after mixing the high unit tank material and the eluent, carrying out nanofiltration concentration to 4.0-5.5 ten thousand units, and carrying out spray drying to obtain 45-55% of original drug content;
5) nanofiltration concentration is more than 96%, the spray drying yield is more than 86%, and the total production yield is between 78 and 85%.
Example 4 (comparative Process 1)
1) Acidifying the oxalic acid of the fermentation liquid to pH2.5-3.0, filtering by a ceramic membrane, wherein the titer of the bacterial residues is 2000u/ml, the volume of the clear ceramic liquid is 1.8-2.0BV, the average titer is 4000-.
2) The ion exchange resin is LX-731-X1 modified resin, the production expansion coefficient is 1.5-2.0, and the column loading is about 50%. The ceramic clear liquid material enters ion exchange resin for adsorption, and the volume rate of the adsorption feeding is 0.2-1.0BV/h (the effective rate is 6-10 kg/t.h)-1) The pH value of the adsorption end is 8.5-9.0, the total adsorption volume is 12-20BV, and the adsorption capacity is 80-90 kg/t. And after the adsorption is saturated, performing top water backwashing to remove the upper layer flocculation sediment, performing top water backwashing from the bottom according to 1-2BV/h, and stopping when the light transmittance is more than 70%.
3) Analyzing by using 4.5-5.5% dilute hydrochloric acid, eluting at a column pressure of 0.05-1MPa and an elution rate of 0.3-0.6BV/h, eluting at 1.5BV until pH rises, then reducing, sampling in time and detecting, collecting eluent with a titer of 500 plus materials of 1000u/ml, collecting the eluent to a high-unit tank, monitoring the pH and titer curve of an outlet in the middle, stopping hydrochloric acid analysis when the pH of the outlet is about 3.0 and the titer is obviously reduced or reduced to 8000 plus materials of 15000u/ml, performing top washing by using pure water, performing top water forward washing at a rate of 0.3-0.5BV/h and 1-2h, stopping collecting materials when the pH is reduced to the lowest point of 0.2-0.5 and then not reduced, slightly rising, and stopping collecting materials, wherein the titer of the outlet is less than 2000 u/ml. And (3) regulating the pH of the material in the eluent tank to be between 2.0 and 3.0 by using the low-pH material positively washed by the top water at the last stage, regulating the liquid phase titer to be 3.0 to 3.5 ten thousand, and feeding the redundant low-pH material into the next acidification tank. The elution yield is more than 90%.
4) Concentrating the eluate to 4.0-5.0 ten thousand units, and spray drying to obtain 55-65% crude drug.
5) Nanofiltration concentration is more than 96 percent, the spray drying yield is more than 86 percent, and the total production yield is between 66 and 70 percent.
Example 5 (comparative Process 2)
1) Acidifying the fermentation liquor with oxalic acid to pH2.5-3.0, filtering with ceramic membrane, the titer of the bacteria residue is about 1000u/ml, the average titer of the ceramic clear liquid is 3500-5500u/ml, the volume is 2.0-2.3BV, and the material yield is more than 92%.
2) Nano-filtering the clear ceramic liquid, concentrating to 3.5-4.0 ten thousand units, and spray-drying to obtain 20-25% of original drug content.
3) Nanofiltration concentration is more than 96 percent, the spray drying yield is more than 86 percent, and the total production yield is 71 to 75 percent.
Therefore, the production yield of the invention is improved by 16-20% compared with the comparison process, the production cost of the raw pesticide is effectively reduced, and 25-65% of the content of the zhongshengmycin raw pesticide in series of raw pesticide with mass ratio can be obtained in one production process.
The foregoing is a more detailed description of the invention in connection with specific/preferred embodiments and is not intended to limit the practice of the invention to those descriptions. Several alternatives or modifications to these described embodiments should be considered as falling within the scope of the present invention without departing from the inventive concept.
Claims (10)
1. A method for efficiently separating zhongshengmycin in fermentation liquor is characterized by comprising the steps of ceramic membrane filtration, fractional collection of high and low unit materials, resin adsorption and top water backwashing of the low unit materials, hydrochloric acid elution and top water forward washing, nanofiltration concentration and spray drying, and fractional collection of materials in different stages to obtain raw zhongshengmycin with different contents.
2. The method according to claim 1, comprising the following process steps:
1) acidifying the zhongshengmycin fermentation liquor, filtering by adopting a ceramic membrane, collecting the zhongshengmycin fermentation liquor step by step before and after water replenishing to obtain high-unit clear liquor and low-unit clear liquor, and respectively collecting the high-unit clear liquor and the low-unit clear liquor into a high-unit clear liquor tank and a low-unit clear liquor tank;
2) the material of the low unit clear liquid tank enters ion exchange resin for adsorption, and after the adsorption is saturated, backwashing is carried out by using top water to remove the upper layer flocculation and precipitation;
3) adopting dilute hydrochloric acid for resolution, collecting materials in time after the potency leaks, sampling and detecting in time, stopping hydrochloric acid resolution when the potency of an outlet is obviously reduced, and carrying out top washing by using pure water;
4) and 3) carrying out nanofiltration concentration on the eluent or the high-unit clear liquid obtained in the step 3), and then carrying out spray drying to obtain the zhongshengmycin original drug with different mass ratios.
3. The method as claimed in claim 2, wherein in step (1), the material titer of the low unit clear liquid tank and the high unit clear liquid tank is controlled within the range of 3500u/ml and 5500-8500u/ml respectively; preferably, in the step (1), the material yield of the low unit clear liquid tank and the high unit clear liquid tank is respectively controlled in the range of 35-40% and 55-60%.
4. The method of claim 2, wherein in step (2), the ion exchange resin has a model number LX-731-X1 modified resin to produce a coefficient of expansion of 1.5 to 2.0; preferably, in step (2), the volumetric rate of adsorption feed is 0.2-1.0BV/h (effective rate is 2-4 kg/t.h)-1) The total adsorption volume is 70-80BV, and the adsorption capacity is controlled at 130-140 kg/t; and (4) backwashing by water inflow from the bottom according to the water inflow rate of 1-2BV/h, and stopping when the light transmittance is more than 70%.
5. The method according to claim 2, wherein in the step (3), the configured concentration of the dilute hydrochloric acid is controlled to be between 4.5 and 5.5 percent; preferably, in the step (3), the elution column pressure is 0.05-1MPa, and the elution rate is 0.3-0.6 BV/h; more preferably, in step (3), the dilute hydrochloric acid is eluted at a pH of 2.0-3.5, and the top water forward washing is started.
6. The method according to claim 5, wherein in the step (3), the top water is washed at a rate of 0.3-0.5BV/h, and the material is stopped when the pH is slightly raised after the pH is lowered to the lowest point of 0.2-0.5; more preferably, in step (3), the pH of the eluate tank material is adjusted to between 2.0 and 3.0 using a low pH material of a final top water forward wash.
7. The process according to any one of claims 2 to 6, wherein in step (4), the eluate is concentrated to 5.0 to 6.0 ten thousand units, the conductance is in the range of 20 to 50ms, and separately spray-dried.
8. The method according to any one of claims 2 to 6, wherein in the step (4), the eluate-concentrated mother liquor and the high-unit supernatant-concentrated mother liquor are mixed in accordance with (1: 1-3: 1) and then spray-dried.
9. The method according to any one of claims 2 to 6, wherein in step (4), the high unit tank material is concentrated alone or the eluates are mixed and then concentrated to 4.0 to 5.0 ten thousand units, and spray-dried.
10. The method according to any one of claims 1 to 9, wherein the method provides a range of mass ratios of 25 to 65% of the technical zhongshengmycin with an overall yield of 75 to 85%.
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