CN113637024B - Method for purifying deacetyloxy cephalosporin C aqueous solution - Google Patents
Method for purifying deacetyloxy cephalosporin C aqueous solution Download PDFInfo
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- CN113637024B CN113637024B CN202110888251.8A CN202110888251A CN113637024B CN 113637024 B CN113637024 B CN 113637024B CN 202110888251 A CN202110888251 A CN 202110888251A CN 113637024 B CN113637024 B CN 113637024B
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- 239000007864 aqueous solution Substances 0.000 title claims abstract description 38
- 238000000034 method Methods 0.000 title claims abstract description 37
- HOKIDJSKDBPKTQ-GLXFQSAKSA-N cephalosporin C Chemical compound S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CCC[C@@H](N)C(O)=O)[C@@H]12 HOKIDJSKDBPKTQ-GLXFQSAKSA-N 0.000 title abstract description 10
- 239000011347 resin Substances 0.000 claims abstract description 72
- 229920005989 resin Polymers 0.000 claims abstract description 72
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 33
- 238000005406 washing Methods 0.000 claims abstract description 18
- NNQIJOYQWYKBOW-JWKOBGCHSA-N deacetoxycephalosporin C Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CCC[C@@H](N)C(O)=O)[C@@H]12 NNQIJOYQWYKBOW-JWKOBGCHSA-N 0.000 claims abstract description 15
- 238000001179 sorption measurement Methods 0.000 claims description 78
- 238000003795 desorption Methods 0.000 claims description 44
- 239000000243 solution Substances 0.000 claims description 23
- 239000003795 chemical substances by application Substances 0.000 claims description 20
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical group [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 18
- 239000003463 adsorbent Substances 0.000 claims description 13
- 239000008367 deionised water Substances 0.000 claims description 10
- 229910021641 deionized water Inorganic materials 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 9
- 239000008213 purified water Substances 0.000 claims description 2
- 230000008569 process Effects 0.000 abstract description 8
- NNQIJOYQWYKBOW-UHFFFAOYSA-N desacetoxycephalosphorin G Natural products S1CC(C)=C(C(O)=O)N2C(=O)C(NC(=O)CCCC(N)C(O)=O)C12 NNQIJOYQWYKBOW-UHFFFAOYSA-N 0.000 description 81
- 239000007788 liquid Substances 0.000 description 21
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 16
- 238000002474 experimental method Methods 0.000 description 14
- 230000000694 effects Effects 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 238000012216 screening Methods 0.000 description 8
- 238000000926 separation method Methods 0.000 description 7
- 239000012535 impurity Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- 238000000855 fermentation Methods 0.000 description 4
- 230000004151 fermentation Effects 0.000 description 4
- BQIMPGFMMOZASS-CLZZGJSISA-N (6r,7r)-7-amino-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1CC(CO)=C(C(O)=O)N2C(=O)[C@@H](N)[C@H]21 BQIMPGFMMOZASS-CLZZGJSISA-N 0.000 description 3
- BQIMPGFMMOZASS-UHFFFAOYSA-N beta-amino-3-hydroxymethyl-3-cefem-4-carboxylic acid Natural products S1CC(CO)=C(C(O)=O)N2C(=O)C(N)C21 BQIMPGFMMOZASS-UHFFFAOYSA-N 0.000 description 3
- 229930186147 Cephalosporin Natural products 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 229940124587 cephalosporin Drugs 0.000 description 2
- 150000001780 cephalosporins Chemical class 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000012527 feed solution Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229960004841 cefadroxil Drugs 0.000 description 1
- NBFNMSULHIODTC-CYJZLJNKSA-N cefadroxil monohydrate Chemical compound O.C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=C(O)C=C1 NBFNMSULHIODTC-CYJZLJNKSA-N 0.000 description 1
- 229960002588 cefradine Drugs 0.000 description 1
- 229940106164 cephalexin Drugs 0.000 description 1
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 1
- RDLPVSKMFDYCOR-UEKVPHQBSA-N cephradine Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CCC=CC1 RDLPVSKMFDYCOR-UEKVPHQBSA-N 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000001728 nano-filtration Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/22—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with radicals containing only hydrogen and carbon atoms, attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/02—Preparation
- C07D501/12—Separation; Purification
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
Abstract
The invention provides a method for purifying a deacetyloxy cephalosporin C aqueous solution, which is characterized in that the DAOC with high purity is obtained through the steps of absorbing the DAOC aqueous solution by macroporous resin, washing by water and desorbing. The method for purifying the DAOC aqueous solution has the advantages of short process flow, simple operation, high yield, high purity, stable quality and low cost, can obtain the high-purity DAOC, and has high industrial application value.
Description
Technical Field
The invention belongs to the field of biochemistry, and particularly relates to a method for purifying a deacetyloxy cephalosporin C aqueous solution.
Background
7-ADCA (7-amino-deacetyl-cephalosporanic acid) is used as a novel intermediate of cephalosporin antibiotics, and is used for synthesizing medicines such as cefalexin, cefradine, cefadroxil and the like in the pharmaceutical industry, and the medicines are antibiotics with larger market dosage.
DAOC (deacetyloxy cephalosporin C) is taken as an important raw material for preparing 7-ADCA (7-amino deacetyloxy cephalosporin acid) by an enzyme method at present, is a metabolite of microbial fermentation, and the DAOC fermentation liquor is subjected to multistage filtration to generate filtrate which has higher impurity content and lower DAOC purity, if no further treatment is carried out, the impurity is reduced, the purity is improved, the subsequent conversion yield and the quality of a finished product are affected, and the production cost is increased, so that a method capable of removing impurities and purifying DAOC feed liquid is urgently needed, and the subsequent production yield and the product quality are improved.
However, no method for purifying the DAOC feed liquid is reported in the literature.
Disclosure of Invention
The invention aims to provide a method for purifying a DAOC aqueous solution, which has the advantages of short process flow, simple operation, high yield, high purity, stable quality and low cost.
The invention provides a method for purifying a DAOC aqueous solution, which comprises the following steps:
(1) Adsorbing the DAOC aqueous solution by using macroporous resin to obtain macroporous resin containing DAOC; the temperature of the DAOC aqueous solution is 15.0-21.0 ℃, the pH is 2.5-3.5, and the DAOC purity is 80-85%;
(2) Washing the macroporous resin containing the DAOC obtained in the step (1) with process water;
(3) Desorbing the resin obtained in the step (2) by using a resolving agent.
Further, in step (1), the titer of the aqueous DAOC solution is 8000-12000 μg/mL.
Further, in the step (1), the adsorption amount of the macroporous adsorption resin is 35-45g/L.
Further, in the step (1), the flow rate of the adsorption is 0.4BV/h-0.6BV/h.
Further, in the step (2), the process water is one or two of deionized water and purified water.
Further, in the step (2), the water washing flow rate is 0.4BV/h-0.6BV/h, and the total water washing amount is 4BV-6BV.
Further, in the step (3), the resolving agent is one or a mixture of more than two of sodium bicarbonate, sodium acetate and sodium carbonate.
Further, in the step (3), the concentration of the resolving agent is 0.40% -0.50%, and/or the amount of the resolving agent is 3.0-4.0BV.
Further, in the step (3), the flow rate of desorption is 0.4-0.6BV/h.
Still further, in the above method, the macroporous resin is DM-700, LX-3020, LX-18, LX-1180, LX-67, LX-16, DM-825, DM1180S or LKA53 macroporous resin, preferably DM-700, LX-3020, LX-18 or LX-1180 macroporous resin, more preferably DM-700 macroporous resin.
The invention also provides a high purity DAOC product, which is purified by the method of claims 1-9, with a purity higher than 96%.
Experimental results show that the method for purifying the DAOC aqueous solution has the advantages of short process flow, simple operation, high yield, stable quality and low cost, can obtain the high-purity DAOC, and has high industrial application value.
Explanation of the terminology of the invention:
the DAOC aqueous solution of the present invention means: and (3) performing multistage filtration on the fermentation liquor of the desacetoxycephalosporin C (DAOC) obtained by fermenting the cephalosporanic fungus to obtain filtrate.
It should be apparent that, in light of the foregoing, various modifications, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims.
The following description of the embodiments of the present invention will be made clearly and completely, and it is apparent that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Detailed Description
The DAOC aqueous solution used in the invention is self-made: the deacetoxycephalosporin C (DAOC) fermentation liquor obtained by fermenting the cephalosporanic fungus is subjected to solid-liquid separation by membrane or plate frame equipment, and then is subjected to nanofiltration and ultrafiltration to obtain the DAOC aqueous solution with lower impurity content.
Except where specifically indicated, the remaining materials and equipment are known products and are obtained by purchasing commercially available products.
Example 1
A method for purifying a DAOC aqueous solution with an adsorbent resin, comprising the steps of:
(1) Adjusting the pH of the DAOC aqueous solution with the titer of 8000 mug/mL to 2.8 by sulfuric acid, and controlling the temperature at 15 ℃;
(2) Carrying out adsorption treatment on the mixture by using DM700 macroporous adsorption resin at the flow rate of 0.4BV/h according to the adsorption quantity of 35g/L to obtain the macroporous adsorption resin containing DAOC;
(3) 4BV deionized water is washed by the macroporous adsorption resin containing the DAOC in the step (1) at the flow rate of 0.5 BV/h;
(4) Desorbing 3.5BV of sodium bicarbonate solution with the concentration of 0.5% by using the macroporous adsorption resin containing the DAOC in the step (3) at the flow rate of 0.5BV/h, and collecting the desorption liquid;
the purity of the desorption solution DAOC in the above example was detected to be 96.97%, and the desorption yield was 92.11%.
Example 2
A method for purifying a DAOC aqueous solution with an adsorbent resin, comprising the steps of:
(1) Adjusting the pH of the aqueous solution of DAOC with the titer of 9000 mug/mL to 2.7 by using sulfuric acid, and controlling the temperature to 17 ℃;
(2) Performing adsorption treatment on the mixture by using DM700 macroporous adsorption resin at the flow rate of 0.5BV/h according to the adsorption quantity of 36g/L to obtain the macroporous adsorption resin containing DAOC;
(3) 4.5BV deionized water is washed by the macroporous adsorption resin containing DAOC in the step (1) at the flow rate of 0.6BV/h;
(4) Desorbing 3.8BV of sodium bicarbonate solution with the concentration of 0.4% by using the macroporous adsorption resin containing the DAOC in the step (3) at the flow rate of 0.6BV/h, and collecting the desorption liquid;
the desorption solution DAOC purity 97.19% in the above examples was detected with a desorption yield of 91.82%.
Example 3
A method for purifying a DAOC aqueous solution with an adsorbent resin, comprising the steps of:
(1) Adjusting the pH of the DAOC aqueous solution with the titer of 10000 mug/mL to 2.9 by sulfuric acid, and controlling the temperature at 20 ℃;
(2) Carrying out adsorption treatment on the mixture by using DM700 macroporous adsorption resin at the flow rate of 0.55BV/h according to the adsorption quantity of 37g/L to obtain the macroporous adsorption resin containing DAOC;
(3) 4.5BV deionized water is washed by the macroporous adsorption resin containing the DAOC in the step (1) at the flow rate of 0.5 BV/h;
(4) Desorbing 3.0BV of sodium bicarbonate solution with the concentration of 0.45% by using the macroporous adsorption resin containing the DAOC in the step (3) at the flow rate of 0.4BV/h, and collecting the desorption liquid;
the purity of the desorption solution DAOC in the above example was 97.13% and the desorption yield was 91.87% as measured.
Example 4
A method for purifying a DAOC aqueous solution with an adsorbent resin, comprising the steps of:
(1) Adjusting the pH of the aqueous solution of DAOC with the titer of 11000 mug/mL to 3.0 by sulfuric acid, and controlling the temperature at 21 ℃;
(2) Carrying out adsorption treatment on the mixture by using DM700 macroporous adsorption resin at the flow rate of 0.6BV/h according to the adsorption quantity of 42g/L to obtain the macroporous adsorption resin containing DAOC;
(3) Washing 5.0BV deionized water with the macroporous adsorption resin containing the DAOC in the step (1) at a flow rate of 0.5 BV/h;
(4) Desorbing 4.0BV of sodium bicarbonate solution with the concentration of 0.4% by using the macroporous adsorption resin containing the DAOC in the step (3) at the flow rate of 0.6BV/h, and collecting the desorption liquid;
the desorption solution DAOC in the above example was detected to have a purity of 96.85% and a desorption yield of 92.08%.
Example 5
A method for purifying a DAOC aqueous solution with an adsorbent resin, comprising the steps of:
(1) Adjusting the pH of the aqueous solution of DAOC with the titer of 9500 mug/mL to 2.5 by sulfuric acid, and controlling the temperature at 18 ℃;
(2) Carrying out adsorption treatment on the mixture by using DM700 macroporous adsorption resin at the flow rate of 0.55BV/h according to the adsorption quantity of 40g/L to obtain the macroporous adsorption resin containing DAOC;
(3) Washing 6BV deionized water with the macroporous adsorption resin containing the DAOC in the step (1) at a flow rate of 0.4 BV/h;
(4) Desorbing 4.0BV of sodium bicarbonate solution with the concentration of 0.47% by using the macroporous adsorption resin containing the DAOC in the step (3) at the flow rate of 0.5BV/h, and collecting the desorption liquid;
the purity of the desorption solution DAOC in the above example was 97.11% and the desorption yield was 90.21% as measured.
Example 6
A method for purifying a DAOC aqueous solution with an adsorbent resin, comprising the steps of:
(1) Adjusting the pH of the DAOC aqueous solution with the titer of 12000 mug/mL to 3.5 by sulfuric acid, and controlling the temperature at 16 ℃;
(2) Carrying out adsorption treatment on the mixture by using DM700 macroporous adsorption resin at the flow rate of 0.5BV/h according to the adsorption quantity of 45g/L to obtain the macroporous adsorption resin containing DAOC;
(3) Washing 5.0BV deionized water with the macroporous adsorption resin containing the DAOC in the step (1) at a flow rate of 0.5 BV/h;
(4) Desorbing 4BV of sodium bicarbonate solution with the concentration of 0.48% by using the macroporous adsorption resin containing the DAOC in the step (3) at the flow rate of 0.6BV/h, and collecting the desorption liquid;
the purity of the desorption solution DAOC in the above example was 97.12% and the desorption yield was 91.52% as detected.
Example 7
A method for purifying a DAOC aqueous solution with an adsorbent resin, comprising the steps of:
(1) Adjusting the pH of the DAOC aqueous solution with the titer of 10000 mug/mL to 3.0 by sulfuric acid, and controlling the temperature at 19 ℃;
(2) Carrying out adsorption treatment on the mixture by using DM700 macroporous adsorption resin at the flow rate of 0.5BV/h according to the adsorption quantity of 39g/L to obtain the macroporous adsorption resin containing DAOC;
(3) Washing 5.2BV deionized water with the macroporous adsorption resin containing the DAOC in the step (1) at a flow rate of 0.45 BV/h;
(4) Desorbing 3.2BV of sodium bicarbonate solution with the concentration of 0.46% by using the macroporous adsorption resin containing the DAOC in the step (3) at the flow rate of 0.4BV/h, and collecting the desorption liquid;
the desorption solution DAOC purity 97.17% in the above example was detected with a desorption yield of 91.98%.
Example 8
A method for purifying a DAOC aqueous solution with an adsorbent resin, comprising the steps of:
(1) Adjusting the pH of the aqueous solution of DAOC with the titer of 10500 mug/mL to 2.8 by sulfuric acid, and controlling the temperature at 17 ℃;
(2) Performing adsorption treatment on the mixture by using DM700 macroporous adsorption resin at the flow rate of 0.5BV/h according to the adsorption quantity of 36g/L to obtain the macroporous adsorption resin containing DAOC;
(3) 4.3BV deionized water is washed by the macroporous adsorption resin containing DAOC in the step (1) at the flow rate of 0.47 BV/h;
(4) Desorbing 3.3BV of sodium bicarbonate solution with the concentration of 0.44% by using the macroporous adsorption resin containing the DAOC in the step (3) at the flow rate of 0.6BV/h, and collecting the desorption liquid;
the desorption solution DAOC purity 97.06% in the above example was detected with a desorption yield of 92.3%.
The DAOC purity pair before and after purification by the method of the present invention is shown in table 1 for the above examples:
therefore, the purity of the DAOC purified by the method is obviously improved, and the purity of the obtained desorption liquid DAOC is as high as more than 96.5 percent.
The following experiments prove the beneficial effects of the method.
Experimental example 1 screening test of Process parameters of the invention
1. Temperature and pH conditions were selected:
(1) Experimental method
a. Carrying out adsorption experiments on feed liquid with different temperatures, and calculating the total adsorption amount of the resin to the target object under the condition that the leakage titers are similar by taking residual adsorption solution for titer detection in the experimental process under the same conditions as in the example 7;
b. adsorption experiments were performed with feed solutions of different pH ranges, and the other conditions were the same as in example 7, and the adsorption ratio was counted.
(2) The experimental results are shown in tables 1 and 2:
TABLE 1 experimental data for feed liquids at different temperatures
TABLE 2 experimental data for different pH ranges of feed solutions
The results show that the resin has strong adsorption capacity to the DAOC solution only in the temperature and pH range of the invention, and the feed liquid is not easy to degrade, thereby being beneficial to further purification and impurity removal.
2. Potency screening of DAOC aqueous solution:
(1) Experimental method
In the temperature and pH range of the feed liquid screened in the previous step, feed liquids with different titers are taken for adsorption experiments, the rest conditions are the same as in example 7, and the yield is calculated.
(2) The experimental results are shown in table 3:
TABLE 3 adsorption results for aqueous solutions of DAOC of different titers
The above results indicate that the DAOC aqueous solution before purification has a too low titer, the resin adsorption capacity is reduced, which is unfavorable for purification and separation, and when the titer is > 12000 μg/mL, the adsorption ratio is not so different, but the water washing efficiency is early, which results in a lower yield. The titer of the DAOC aqueous solution is preferably within the range of 8000-12000. Mu.g/mL, allowing for the best purification results and higher yields.
3. Screening of macroporous resin types:
(1) Experimental method
Adsorption experiments were performed on different types of resins, and the other conditions were the same as in example 7, and the adsorption amount was counted.
(2) The experimental results are shown in table 4:
TABLE 4 results of adsorption of different types of macroporous resins
The above results indicate that the macroporous adsorption resin preferably has high light adsorption capacity when the macroporous adsorption resin is of the DM-700, LX-3020, LX-18 or LX-1180 types, is favorable for achieving excellent purification effect, and has low adsorption capacity of the other types, thus having poor separation effect.
4. Screening of adsorption flow rate:
(1) Experimental method
Adsorption experiments were performed at different flow rates, and the other conditions were the same as in example 7, except that the adsorption-completed feed liquid was taken and examined.
(2) The experimental results are shown in table 5:
TABLE 5 adsorption results at different adsorption flow rates
The above results show that too large adsorption flow rate can cause leakage of titer, too small adsorption period is too long, which is unfavorable for industrial production and application, therefore, the adsorption flow rate is preferably in the range of 0.4BV/h-0.6BV/h, the adsorption period is proper and the treatment efficiency is high.
5. Screening of water washing flow rate:
(1) Experimental method
The resin column after completion of the adsorption was washed with water at different flow rates, and the titer at the end of the washing was measured under the same conditions as in example 7.
(2) The experimental results are shown in table 6:
TABLE 6 results of different water wash flow rates
The result shows that the excessive water washing flow rate can lead the target DAOC to leak out in advance, thereby affecting the impurity separation effect; the water system time is too long when the flow rate is too small, which is unfavorable for industrial production and application, and the water washing time is shortened as much as possible under the condition of ensuring the titer and the separation effect as much as possible, so the water washing flow rate is preferably in the range of 0.4BV/h-0.6BV/h, the water washing period is proper and the treatment efficiency is high.
6. Screening of the concentration of the resolving agent:
(1) Experimental method
Desorbing the resin column which is washed by water by using the resolving agents with different concentrations, taking quality indexes such as final desorption liquid detection titer, purity and the like under the same conditions as in the example 7, and calculating the yield.
(2) The experimental results are shown in table 7:
TABLE 7 Desorption results for different concentrations of resolving agent
The above results indicate that the concentration of the resolving agent is preferably in the range of 0.4 to 0.5%, and the separation and purification effect and the yield are excellent.
7. Screening the dosage of the resolving agent:
(1) Experimental method
Desorbing the resin column which is washed by water by using the resolving agents with different volumes and the same concentration, collecting desorption liquid under the same conditions as in the example 7, and calculating the desorption yield.
(2) The experimental results are shown in table 8:
TABLE 8 Desorption results for different amounts of resolving agent
The above results show that too small amount of the desorption agent results in poor desorption effect and low yield, and the desorption yield does not change much after the amount of the desorption agent is higher than 3BV, so that the amount of the desorption agent is preferably in the range of 3.0-4.0BV, thereby saving the resource cost while ensuring good desorption effect.
8. Screening of desorption flow rate:
(1) Experimental method
The desorption agent was used to desorb the resin column after washing with water at different flow rates, and the other conditions were the same as in example 7, and the desorption liquid was collected and detected.
(2) The experimental results are shown in table 9:
TABLE 9 Desorption results for different Desorption flow rates
The above results show that the flow rate of the resolving agent is preferably in the range of 0.4-0.6BV/h, thereby ensuring good separation and purification effects, reducing desorption period and improving yield.
In summary, the invention provides a method for purifying the DAOC aqueous solution, which has the advantages of short process flow, simple operation, high yield, stable quality and low cost, can obtain the high-purity DAOC, and has high industrial application value.
Claims (4)
1. A method for purifying an aqueous DAOC solution, comprising the steps of:
(1) Adsorbing the DAOC aqueous solution by using macroporous resin to obtain macroporous resin containing DAOC; the temperature of the DAOC aqueous solution is 15.0-21.0 ℃, the pH is 2.5-3.5, and the DAOC purity is 80-85%; the titer of the DAOC aqueous solution is 8000-12000 mug/mL; the macroporous resin is DM700; the flow rate of the adsorption is 0.4BV/h-0.6BV/h;
(2) Washing the macroporous resin containing the DAOC obtained in the step (1) with water; the water washing flow rate is 0.4BV/h-0.6BV/h;
(3) Desorbing the resin obtained in the step (2) by using a resolving agent; the resolving agent is sodium bicarbonate; the concentration of the resolving agent is 0.40% -0.50%, the dosage of the resolving agent is 3.0-4.0BV, and the flow rate of desorption is 0.4-0.6BV/h.
2. The method of purifying an aqueous DAOC solution using an adsorbent resin according to claim 1, wherein the amount of the adsorbent resin in the macroporous adsorbent resin in step (1) is 35-45g/L.
3. The method of purifying an aqueous DAOC solution using an adsorbent resin according to claim 1, wherein in step (2), the water is one or a mixture of deionized water and purified water.
4. The method of purifying an aqueous DAOC solution by means of an adsorbent resin of claim 1, wherein in step (2), the total amount of water is 4BV-6BV.
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| CN1357051A (en) * | 1999-06-18 | 2002-07-03 | 抗生素有限公司 | Method for producing T-aminodesacetoxycephalosporanic acid (7-ADCA) |
| CN113527336A (en) * | 2021-06-09 | 2021-10-22 | 艾美科健（中国）生物医药有限公司 | Process for preparing 7-ADCA by using DAOC fermentation broth as raw material |
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| CN1357051A (en) * | 1999-06-18 | 2002-07-03 | 抗生素有限公司 | Method for producing T-aminodesacetoxycephalosporanic acid (7-ADCA) |
| CN113527336A (en) * | 2021-06-09 | 2021-10-22 | 艾美科健（中国）生物医药有限公司 | Process for preparing 7-ADCA by using DAOC fermentation broth as raw material |
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