CN103571907A - Separation and purification method for cefaclor by enzymatic synthesis - Google Patents
Separation and purification method for cefaclor by enzymatic synthesis Download PDFInfo
- Publication number
- CN103571907A CN103571907A CN201310525754.4A CN201310525754A CN103571907A CN 103571907 A CN103571907 A CN 103571907A CN 201310525754 A CN201310525754 A CN 201310525754A CN 103571907 A CN103571907 A CN 103571907A
- Authority
- CN
- China
- Prior art keywords
- cefaclor
- enzyme
- separation
- synthesis
- reactions
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Cephalosporin Compounds (AREA)
Abstract
The invention discloses a separation and purification method for cefaclor by enzymatic synthesis. The separation and purification method comprises the following steps: dissolving 7-ACCA by ammonia water in a water phase, thereafter adding immobilized enzyme; keeping the temperature within 10-35 DEG C; dripping phenylglycine methyl ester hydrochloride or phenylglycine methyl ester mesylate; continuously maintaining the pH value of the reaction within 5.5-7.5; continuously making the generated cefaclor be precipitated from the system with occurrence of enzyme digestion; continuously separating the immobilized enzyme M-1 from the cefaclor by a filtering separation method in an enzymatic liquid; circulating the mother liquid back to a reactor until the 7-ACCA has complete reaction; purifying the obtained wet cefaclor product, and then obtaining the cefaclor. According to the separation and purification method disclosed by the invention, during precipitation of the cefaclor, the cefaclor is separated from the enzymatic reaction liquid, so that the problems of separation and reaction concentration of the enzymic catalytic reaction are solved.
Description
Technical field
The present invention relates to a kind of separation and purification process of enzyme process the synthesis of cefaclor, be particularly related to a kind of by cefaclor parent nucleus 7-ACCA through biological enzyme and phenylglycine derivatives directly separated, the purification process of biocatalysis the synthesis of cefaclor in water, belong to biology,drug and chemical industry technical field.
Background technology
Cefaclor is the oral cephalosporin antibiotic of the s-generation that U.S. Eli Lilly company was studied in early 1980s, and its synthetic method is all to adopt chemical synthesis the earliest.The shortcoming of cefaclor chemical synthesis is: in 1, chemosynthesis process, will use a large amount of organic solvents, as methylene dichloride, DMF etc.2, reaction conditions is also comparatively harsh, is generally under Cryogenic Conditions, to carry out condensation acidylate.3, reaction finishes by crystallization in water or forms DMF solvate purifying crystal, and in process, energy consumption is large, solvent usage quantity is large, products obtained therefrom foreign matter content is many.The synthetic cephalosporin antibiotic of enzyme catalysis is 21 century full-fledged new bio technology gradually, it is characterized in that reacting in pure water, pollutes less, and side reaction is few, and due to specificity and the specificity of enzyme, transformation efficiency is high.Reaction is directly completed by parent nucleus 7-ACCA and side chain, no longer adds required supplies and solvent in picture chemical synthesis, and products obtained therefrom quality is good, and related substance is few, and economy, environmental protection are the synthetic middle state-of-the-art technology of medicine and developing direction.Because cefaclor solubleness in water is little, and under enzymatic pH value condition, it can not form ammonia salt and be dissolved in reaction system, but separates out gradually, and along with the carrying out of enzymic catalytic reaction, reaction system is thickness gradually, and make to control reaction, becomes difficult.Sometimes can only increase the water yield and solve, but water yield increase be not suitable with again suitability for industrialized production to reduce the concentration that feeds intake, and too littlely in batches make troubles to follow-up purifying.
Summary of the invention
The object of the invention is to provide a kind of separation and purification process of enzyme process the synthesis of cefaclor.
For achieving the above object, the technical solution used in the present invention is: a kind of separation of enzyme process the synthesis of cefaclor and purification process,
Comprise an enzymic catalytic reaction system, this enzymic catalytic reaction system is under the condition existing at immobilized enzyme, carries out enzyme catalysis building-up reactions obtain the enzymatic reaction solution that contains cefaclor crystals with the D-PG derivative of 7-amino-3-chlorine Cephalosporanic acid (7-ACCA) and activity form; The pH value of described enzyme catalysis building-up reactions is 5.5 ~ 7.5, and the temperature of described enzyme catalysis building-up reactions is 10 ~ 35 ℃; The particle diameter of described immobilized enzyme is 200 ~ 500 microns;
In the process of described enzyme catalysis building-up reactions, discontinuously or continuously first described enzymatic reaction solution is crossed to the screen cloth of 125 ~ 150 microns, screen overflow is back in described enzymic catalytic reaction system, screen underflow obtains leaching thing and filtrate more after filtering, described filtrate is back in described enzymic catalytic reaction system, described in leach thing and be cefaclor wet product;
Under 0 ~ 25 ℃ of temperature condition, described cefaclor wet product is dissolved with enzymatic reaction solution mother liquor, then using salt acid for adjusting pH value to 0.1 ~ 2 that cefaclor is dissolved to obtain mass concentration is 5 ~ 20% the cefaclor aqueous solution; Next in the described cefaclor aqueous solution, add activated carbon decolorizing, described gac and described cefaclor aqueous solution mass ratio are between the two 1 ~ 10 ︰ 100; Next filter and obtain filtrate, then in described filtrate, add ammoniacal liquor to regulate pH value to 2.5 ~ 5.5 that cefaclor is separated out, after filtration, obtain leaching thing and filtrate, this filtrate is recrystallization mother liquor, described in leach thing through washing and drying step obtain cefaclor product.
Preferred technical scheme is: the pH value of described enzyme catalysis building-up reactions is 6.5 ~ 7.5; The temperature of described enzyme catalysis building-up reactions is 20 ~ 28 ℃.
Preferred technical scheme is: after described enzyme catalysis building-up reactions finishes, described immobilized enzyme is separated from described enzymatic reaction solution to being fixed enzyme and enzymatic reaction solution mother liquor.
Preferred technical scheme is: under 0 ~ 10 ℃ of temperature condition, described cefaclor wet product is dissolved with enzymatic reaction solution mother liquor.
Preferred technical scheme is: with salt acid for adjusting pH value to 0.4 ~ 0.8, making cefaclor dissolving obtain mass concentration is 8 ~ 15% the cefaclor aqueous solution.
Preferred technical scheme is: described gac and described cefaclor aqueous solution mass ratio are between the two 2 ~ 6 ︰ 100.
Preferred technical scheme is: add ammoniacal liquor to regulate pH value to 3.5 ~ 4.5 that cefaclor is separated out.
Preferred technical scheme is: described D-PG derivative is selected from D-PG carbethoxy hydrochloride, D-PG methyl esters mesylate, D-PG ethyl ester mesylate.
Preferred technical scheme is: in described recrystallization mother liquor, add 2-Naphthol to generate 2-Naphthol cefaclor mixture, filter the thing that leaches obtaining and reclaim cefaclor through washing with acetone, after dry.
Related content in technique scheme is explained as follows:
1, in such scheme, low alkyl group (C1 ~ C4) ester that described D-PG derivative can be D-PG, for example first, the second of D-PG or isopropyl ester.Preferably D-PG methyl esters and D-PG ethyl ester, preferably D-PG carbethoxy hydrochloride, D-PG methyl esters mesylate, D-PG ethyl ester mesylate.
2,, in such scheme, the enzyme in immobilized enzyme can be selected and be adapted in the reacting of 7-ACCA and D-PG derivative as catalyzer to prepare any enzyme of cefaclor.For example penioillin acylase or penicillin G acylase, it also can be called as Penicillin-G-amidases or phenmethyl penioillin acylase.Penicillin G acylase is from one group of lytic enzyme of microorganism, and it can the 6-acyl group of hydrolyzing penicillin or the 7-acyl group of cynnematin.Immobilized enzyme is that enzyme is fixed on carrier, and in EP222462 and WO97/04086, disclosed E.coli penioillin acylase just can directly apply to the present invention.Immobilized enzyme is for example fixed on Penicillin-G-amidases on azlactone polymkeric substance.
3,, in such scheme, enzymatic reaction solution mother liquor is to obtain after at the end the enzymatic reaction solution of (being that in enzymic catalytic reaction system, 7-ACCA is residual lower than 1mg/ml) is isolated immobilized enzyme in enzyme catalysis building-up reactions.
Because technique scheme is used, the present invention compared with prior art has following advantages and effect:
1, the present invention is in the precipitation process of cefaclor, be about to cefaclor separates from enzymatic reaction solution, thereby separation, the reaction density problem of enzymic catalytic reaction have been solved, and be easier to the conversion of 7-ACCA, reduced side chain consumption, can increase lot volume in material input, fed intake and can reach 2～4 times of chemical methods, steady quality, yield can reach more than 90%.
1, the present invention is in order to facilitate the separated of immobilized enzyme and the cefaclor of separating out from enzymatic reaction solution, therefore by be designed and sized to 200 ~ 500 microns of immobilized enzyme.
Embodiment
Below in conjunction with embodiment, the invention will be further described:
Embodiment mono-: a kind of separation of enzyme process the synthesis of cefaclor and purification process
In 1000ml enzyme reactor, add 300ml water, 25g7-amino-3-chlorine Cephalosporanic acid (7-ACCA), control 11 ~ 20 ℃ of temperature, drip ammonia soln to pH value 7.0 ± 0.1, stirring and dissolving, add immobilized enzyme 25g, by dropping funnel, drip 24gD-Phenylglycine methyl ester hydrochloride solution again and obtain enzymatic reaction system, then by pH value automatic control device, control the pH value of enzymatic reaction system constant 6.5 ~ 6.8, at interval of the separated immobilized enzyme of 30min and reaction, generate cefaclor.First separation method for crossing enzymatic reaction solution the screen cloth of 125 microns, screen overflow is that immobilized enzyme is back in described enzymic catalytic reaction system, screen underflow obtains leaching thing and filtrate more after filtering, filtrate washing leaches thing and once then loops back in enzyme reactor, and collecting and leaching thing is cefaclor wet product.Repeatedly, to about 3 hours, it is residual lower than 1mg/ml that 7-ACCA is surveyed in sampling in circulation, and reaction finishes, separated, washing immobilized enzyme, and 5～10 ℃, immobilized enzyme saves backup.Collect cefaclor wet product and enzymatic reaction solution mother liquor, gained cefaclor is proceeded in 1000ml there-necked flask, add enzymatic reaction solution mother liquor 250ml, be cooled to 5～10 ℃, add hydrochloric acid soln to regulate pH value to 0.6～0.8, molten clear, add 2g activated carbon decolorizing, after 30min, filter, the washing of 30ml purified water, 5～10 ℃ of temperature controls, drip ammoniacal liquor, pH value 1.2～1.4 o'clock, add cefaclor to do crystal seed, after growing the grain 30min, continue to regulate pH value to 3.8～4.0, about 3h of period, be cooled to 0～5 ℃, growing the grain 1h, filter, the cold purified water washing of 80ml, drain, 50 ℃ of vacuum-dryings are qualified to moisture, obtain white cefaclor crystallization 37.5g, yield 91.2%.Collect reaction mother liquor and recrystallization mother liquor, in mother liquor, add 3g 2-Naphthol, 10～15 ℃ of temperature controls, stirring reaction 2h, filters, and 20ml washing with acetone is dried to obtain about 4g 2-Naphthol cefaclor mixture.
White cefaclor crystallization is detected, and result is as following table:
Embodiment bis-: a kind of separation of enzyme process the synthesis of cefaclor and purification process
In 1000ml enzyme reactor, add 500ml H
2o, 30g7-ACCA, controls 18 ~ 22 ℃ of temperature, drip ammoniacal liquor to pH value 7.0 ± 0.1, stirring and dissolving, adds immobilized enzyme 20g, drips 37gD-Phenylglycine methyl ester mesylate solution obtain enzymatic reaction system by dropping funnel, by pH automatic control device, control the pH value constant 6.5 ~ 6.8 of reaction, along with cefaclor is constantly separated out in reaction, continuous separate, from, circulation, is collected the cefaclor separate out, Recycling Mother Solution is returned enzyme reactor, about 3.5 hours.Be specially from 1000ml enzyme reactor and pick out pipeline, first this pipeline leads to screen cloth, screen cloth has filtration unit, filtration unit has filtrate collection bucket, in filtrate collection bucket, be provided with pipeline, enzyme reactor is led in the outlet of this pipeline, for the mobile power that provides of liquid is provided, establishes peristaltic pump on pipeline.It is residual lower than 1mg/ml that 7-ACCA is surveyed in sampling, reaction finishes, separated, washing immobilized enzyme, 5～10 ℃ of maintenances of immobilized enzyme are standby, collect cefaclor wet product and enzymatic reaction solution mother liquor, gained cefaclor is proceeded in 1000ml there-necked flask, add enzymatic reaction solution mother liquor 350ml, be cooled to 5～10 ℃, add hydrochloric acid soln to regulate pH value 0.6～0.8, molten clear, add 3g activated carbon decolorizing, after 30min, filter, the washing of 30ml purified water, 5～10 ℃ of temperature controls, drip ammoniacal liquor, pH value 1.2～1.4 o'clock, add cefaclor to do crystal seed, after growing the grain 30min, continue to regulate pH to 4.2 ± 0.1, be cooled to 0～5 ℃, growing the grain 1h, filter, the cold purified water washing of 100ml, drain, 50 ℃ of vacuum-dryings are qualified to moisture, obtain the about 45g of white cefaclor crystallization, yield 91%.Collect reaction mother liquor and recrystallization mother liquor, in mother liquor, add 5g 2-Naphthol, 10～15 ℃ of temperature controls, stirring reaction 2h, filters, and 80ml washing with acetone is dried to obtain 2-Naphthol cefaclor mixture.
Embodiment bis-: a kind of separation of enzyme process the synthesis of cefaclor and purification process
A kind of separation of enzyme process the synthesis of cefaclor and purification process, comprise an enzymic catalytic reaction system, this enzymic catalytic reaction system is under the condition existing at immobilized enzyme, carries out enzyme catalysis building-up reactions obtain the enzymatic reaction solution that contains cefaclor crystals with the D-PG derivative of 7-amino-3-chlorine Cephalosporanic acid and activity form; The pH value of described enzyme catalysis building-up reactions is 6, and the temperature of described enzyme catalysis building-up reactions is 25 ℃; The particle diameter of described immobilized enzyme is 300 microns;
In the process of described enzyme catalysis building-up reactions, discontinuously or continuously first described enzymatic reaction solution is crossed to the screen cloth of 120 microns, screen overflow is back in described enzymic catalytic reaction system, screen underflow obtains leaching thing and filtrate more after filtering, described filtrate is back in described enzymic catalytic reaction system, described in leach thing and be cefaclor wet product;
Under 10 ℃ of temperature condition, described cefaclor wet product is dissolved in enzymatic reaction solution mother liquor, then with salt acid for adjusting pH value to 1, cefaclor being dissolved obtain mass concentration is 15% the cefaclor aqueous solution; Next in the described cefaclor aqueous solution, add activated carbon decolorizing, described gac and described cefaclor aqueous solution mass ratio are between the two 6 ︰ 100; Next filter and obtain filtrate, then in described filtrate, add ammoniacal liquor to regulate pH value to 3 that cefaclor is separated out, after filtration, obtain leaching thing and filtrate, this filtrate is recrystallization mother liquor, described in leach thing through washing and drying step obtain cefaclor product.
After described enzyme catalysis building-up reactions finishes, described immobilized enzyme is separated from described enzymatic reaction solution to being fixed enzyme and remaining liquid, then in described remaining liquid, add 2-Naphthol to generate 2-Naphthol cefaclor mixture, filter the thing that leaches obtaining and reclaim cefaclor through washing with acetone, after dry.In described recrystallization mother liquor, add 2-Naphthol to generate 2-Naphthol cefaclor mixture, filter the thing that leaches obtaining and reclaim cefaclor through washing with acetone, after dry.Both can merge with together with process.
Described D-PG derivative is the mixture that D-PG carbethoxy hydrochloride and D-PG ethyl ester mesylate form according to the mass ratio of 1:1.
Above-described embodiment is only explanation technical conceive of the present invention and feature, and its object is to allow person skilled in the art can understand content of the present invention and implement according to this, can not limit the scope of the invention with this.All equivalences that spirit is done according to the present invention change or modify, within all should being encompassed in protection scope of the present invention.
Claims (9)
1. the separation of enzyme process the synthesis of cefaclor and a purification process, is characterized in that:
Comprise an enzymic catalytic reaction system, this enzymic catalytic reaction system is under the condition existing at immobilized enzyme, carries out enzyme catalysis building-up reactions obtain the enzymatic reaction solution that contains cefaclor crystals with the D-PG derivative of 7-amino-3-chlorine Cephalosporanic acid and activity form; The pH value of described enzyme catalysis building-up reactions is 5.5 ~ 7.5, and the temperature of described enzyme catalysis building-up reactions is 10 ~ 35 ℃; The particle diameter of described immobilized enzyme is 200 ~ 500 microns;
In the process of described enzyme catalysis building-up reactions, discontinuously or continuously first described enzymatic reaction solution is crossed to the screen cloth of 125 ~ 150 microns, screen overflow is back in described enzymic catalytic reaction system, screen underflow obtains leaching thing and filtrate more after filtering, described filtrate is back in described enzymic catalytic reaction system, described in leach thing and be cefaclor wet product;
Under 0 ~ 25 ℃ of temperature condition, described cefaclor wet product is dissolved with enzymatic reaction solution mother liquor, then using salt acid for adjusting pH value to 0.1 ~ 2 that cefaclor is dissolved to obtain mass concentration is 5 ~ 20% the cefaclor aqueous solution; Next in the described cefaclor aqueous solution, add activated carbon decolorizing, described gac and described cefaclor aqueous solution mass ratio are between the two 1 ~ 10 ︰ 100; Next filter and obtain filtrate, then in described filtrate, add ammoniacal liquor to regulate pH value to 2.5 ~ 5.5 that cefaclor is separated out, after filtration, obtain leaching thing and filtrate, this filtrate is recrystallization mother liquor, described in leach thing through washing and drying step obtain cefaclor product.
2. the separation of enzyme process the synthesis of cefaclor according to claim 1 and purification process, is characterized in that: the pH value of described enzyme catalysis building-up reactions is 6.5 ~ 7.5; The temperature of described enzyme catalysis building-up reactions is 20 ~ 28 ℃.
3. the separation of enzyme process the synthesis of cefaclor according to claim 1 and purification process, it is characterized in that: after described enzyme catalysis building-up reactions finishes, described immobilized enzyme is separated from described enzymatic reaction solution to being fixed enzyme and enzymatic reaction solution mother liquor.
4. the separation of enzyme process the synthesis of cefaclor according to claim 1 and purification process, is characterized in that: under 0 ~ 10 ℃ of temperature condition, described cefaclor wet product is dissolved with enzymatic reaction solution mother liquor.
5. the separation of enzyme process the synthesis of cefaclor according to claim 1 and purification process, is characterized in that: with salt acid for adjusting pH value to 0.4 ~ 0.8, cefaclor being dissolved obtain mass concentration is 8 ~ 15% the cefaclor aqueous solution.
6. the separation of enzyme process the synthesis of cefaclor according to claim 1 and purification process, is characterized in that: described gac and described cefaclor aqueous solution mass ratio are between the two 2 ~ 6 ︰ 100.
7. the separation of enzyme process the synthesis of cefaclor according to claim 1 and purification process, is characterized in that: add ammoniacal liquor to regulate pH value to 3.5 ~ 4.5 that cefaclor is separated out.
8. the separation of enzyme process the synthesis of cefaclor according to claim 1 and purification process, is characterized in that: described D-PG derivative is selected from D-PG carbethoxy hydrochloride, D-PG methyl esters mesylate, D-PG ethyl ester mesylate.
9. the separation of enzyme process the synthesis of cefaclor according to claim 1 and purification process, it is characterized in that: in described recrystallization mother liquor, add 2-Naphthol to generate 2-Naphthol cefaclor mixture, filter the thing that leaches obtaining and reclaim cefaclor through washing with acetone, after dry.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310525754.4A CN103571907B (en) | 2013-10-30 | 2013-10-30 | A kind of separation of enzymatic clarification cefaclor and purification process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310525754.4A CN103571907B (en) | 2013-10-30 | 2013-10-30 | A kind of separation of enzymatic clarification cefaclor and purification process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103571907A true CN103571907A (en) | 2014-02-12 |
| CN103571907B CN103571907B (en) | 2016-01-13 |
Family
ID=50044616
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310525754.4A Active CN103571907B (en) | 2013-10-30 | 2013-10-30 | A kind of separation of enzymatic clarification cefaclor and purification process |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103571907B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105368910A (en) * | 2015-12-17 | 2016-03-02 | 苏州中联化学制药有限公司 | Method for synthesizing cefprozil through enzymatic method |
| CN106222230A (en) * | 2016-08-03 | 2016-12-14 | 广州白云山医药集团股份有限公司白云山化学制药厂 | A kind of method of green enzymatic clarification cefaclor |
| CN107523603A (en) * | 2017-08-04 | 2017-12-29 | 长沙凯晓生物科技有限公司 | A kind of method that enzyme process prepares Cefaclor |
| CN107604037A (en) * | 2017-10-20 | 2018-01-19 | 苏州中联化学制药有限公司 | A kind of Task-size Controlling method of biological enzyme the synthesis of cefaclor |
| CN109266713A (en) * | 2018-11-12 | 2019-01-25 | 齐鲁安替制药有限公司 | A kind of preparation method suitable for industrial Cefaclor |
| CN110408670A (en) * | 2019-08-19 | 2019-11-05 | 苏州盛达药业有限公司 | A kind of method of Enzyme catalyzed synthesis Cefaclor |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101090978A (en) * | 2004-12-27 | 2007-12-19 | 帝斯曼知识产权资产管理有限公司 | Process for the synthesis of cefaclor |
| CN102220403A (en) * | 2011-04-18 | 2011-10-19 | 张家港市信谊化工有限公司 | Method for preparing 7-ACCA |
| CN102653726A (en) * | 2011-11-11 | 2012-09-05 | 中国医药集团总公司四川抗菌素工业研究所 | Colibacillus containing alpha-amino-acid ester hydrolase gene |
-
2013
- 2013-10-30 CN CN201310525754.4A patent/CN103571907B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101090978A (en) * | 2004-12-27 | 2007-12-19 | 帝斯曼知识产权资产管理有限公司 | Process for the synthesis of cefaclor |
| CN102220403A (en) * | 2011-04-18 | 2011-10-19 | 张家港市信谊化工有限公司 | Method for preparing 7-ACCA |
| CN102653726A (en) * | 2011-11-11 | 2012-09-05 | 中国医药集团总公司四川抗菌素工业研究所 | Colibacillus containing alpha-amino-acid ester hydrolase gene |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105368910A (en) * | 2015-12-17 | 2016-03-02 | 苏州中联化学制药有限公司 | Method for synthesizing cefprozil through enzymatic method |
| CN105368910B (en) * | 2015-12-17 | 2019-01-11 | 苏州中联化学制药有限公司 | A kind of method of enzymatic clarification Cefprozil |
| CN106222230A (en) * | 2016-08-03 | 2016-12-14 | 广州白云山医药集团股份有限公司白云山化学制药厂 | A kind of method of green enzymatic clarification cefaclor |
| CN107523603A (en) * | 2017-08-04 | 2017-12-29 | 长沙凯晓生物科技有限公司 | A kind of method that enzyme process prepares Cefaclor |
| CN107523603B (en) * | 2017-08-04 | 2020-12-29 | 长沙凯晓生物科技有限公司 | Method for preparing cefaclor by enzyme method |
| CN107604037A (en) * | 2017-10-20 | 2018-01-19 | 苏州中联化学制药有限公司 | A kind of Task-size Controlling method of biological enzyme the synthesis of cefaclor |
| CN107604037B (en) * | 2017-10-20 | 2020-06-05 | 苏州盛达药业有限公司 | Granularity control method for synthesizing cefaclor by biological enzyme method |
| CN109266713A (en) * | 2018-11-12 | 2019-01-25 | 齐鲁安替制药有限公司 | A kind of preparation method suitable for industrial Cefaclor |
| CN110408670A (en) * | 2019-08-19 | 2019-11-05 | 苏州盛达药业有限公司 | A kind of method of Enzyme catalyzed synthesis Cefaclor |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103571907B (en) | 2016-01-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103571907B (en) | A kind of separation of enzymatic clarification cefaclor and purification process | |
| CN102286003B (en) | Manufacture method of ceftazidime compound | |
| CN104356146B (en) | A kind of preparation method of cefotiam chloride | |
| CN102268016A (en) | Method for preparing amoxicillin sodium | |
| CN105368910B (en) | A kind of method of enzymatic clarification Cefprozil | |
| CN110791538A (en) | Production method suitable for synthesizing sitagliptin phosphate by enzyme method | |
| CN103664912A (en) | Synthesis process of prucalopride | |
| CN102827912A (en) | Technology for preparing medicine intermediate D-7-ACA by two enzyme carriers one-step method | |
| CN109608476B (en) | Method for treating production waste liquid of cephalosporin antibiotics and production method | |
| CN104447800A (en) | Synthesis technology of cefoxitin acid | |
| CN102391128B (en) | Production method of antibiotic pharmaceutical intermediate mono-p-nitro benzyl malonate | |
| CN104193765A (en) | Method for synthesizing cefixime | |
| CN101880271B (en) | Synthesis method of 2-thiophene acetylchloride | |
| CN101735085B (en) | Method for preparing D-serine by kinetic resolution | |
| CN112110874A (en) | Synthesis method of 5-methyl-2-mercaptothiadiazole | |
| US20070213313A1 (en) | Direct process for the production of an amino acid dihydrochloride | |
| CN108997209B (en) | Preparation method of regorafenib | |
| CN103012437A (en) | Method for preparing cefoxitin acid as antibacterial medicament | |
| CN110922417A (en) | Method for recovering cefalexin crystallization mother liquor | |
| CN113699209B (en) | 7-ADCA recovery method | |
| CN106046020B (en) | A method of nimoctin is purified by crystallization | |
| CN103172530B (en) | Preparation method of tolfenamic acid | |
| CN102276522B (en) | Method for preparing roflumilast and intermediate of roflumilast | |
| CN108690049A (en) | The method that Amoxicillin is detached from the reaction product that enzyme process prepares Amoxicillin | |
| CN103755577B (en) | A kind of method reclaiming Transbroncho alkali from Ambroxol HCl refinement mother liquor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CP03 | Change of name, title or address | ||
| CP03 | Change of name, title or address |
Address after: 215212 No. 6 Jinzi Road, Lili Town, Wujiang District, Suzhou City, Jiangsu Province Patentee after: Suzhou Shengda Pharmaceutical Co., Ltd. Address before: 215212 No. 9 East Jiaotong Road, Lili Town, Wujiang District, Suzhou City, Jiangsu Province Patentee before: China Union Chempharma (Suzhou) Co., Ltd. |