CN102964355B - Preparation method of penicillin G sulfoxide - Google Patents
Preparation method of penicillin G sulfoxide Download PDFInfo
- Publication number
- CN102964355B CN102964355B CN201210547802.5A CN201210547802A CN102964355B CN 102964355 B CN102964355 B CN 102964355B CN 201210547802 A CN201210547802 A CN 201210547802A CN 102964355 B CN102964355 B CN 102964355B
- Authority
- CN
- China
- Prior art keywords
- penicillin
- sulfoxide
- solution
- concentration
- crude product
- 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.)
- Active
Links
- FCZNNHHXCFARDY-WQRUCBPWSA-N (2s,5r,6r)-3,3-dimethyl-4,7-dioxo-6-[(2-phenylacetyl)amino]-4$l^{4}-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound N([C@H]1[C@@H]2N(C1=O)[C@H](C(S2=O)(C)C)C(O)=O)C(=O)CC1=CC=CC=C1 FCZNNHHXCFARDY-WQRUCBPWSA-N 0.000 title claims abstract description 46
- 238000002360 preparation method Methods 0.000 title claims description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 51
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims abstract description 29
- 239000000047 product Substances 0.000 claims abstract description 22
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000012528 membrane Substances 0.000 claims abstract description 17
- 239000012043 crude product Substances 0.000 claims abstract description 16
- 238000001035 drying Methods 0.000 claims abstract description 11
- 239000000706 filtrate Substances 0.000 claims abstract description 11
- 238000001728 nano-filtration Methods 0.000 claims abstract description 10
- 229940056360 penicillin g Drugs 0.000 claims abstract description 10
- 238000000855 fermentation Methods 0.000 claims abstract description 8
- 230000004151 fermentation Effects 0.000 claims abstract description 8
- 239000013078 crystal Substances 0.000 claims abstract description 4
- 239000000243 solution Substances 0.000 claims description 26
- 239000007788 liquid Substances 0.000 claims description 15
- 229930182555 Penicillin Natural products 0.000 claims description 9
- 229940049954 penicillin Drugs 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 238000001953 recrystallisation Methods 0.000 claims description 8
- 239000000919 ceramic Substances 0.000 claims description 7
- 239000012141 concentrate Substances 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 239000005864 Sulphur Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 19
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 abstract description 14
- 238000001914 filtration Methods 0.000 abstract description 11
- 238000005406 washing Methods 0.000 abstract description 7
- 238000000605 extraction Methods 0.000 abstract description 3
- 239000003960 organic solvent Substances 0.000 abstract description 2
- 238000001816 cooling Methods 0.000 abstract 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 abstract 1
- 230000001105 regulatory effect Effects 0.000 abstract 1
- 230000003647 oxidation Effects 0.000 description 19
- 238000007254 oxidation reaction Methods 0.000 description 19
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 15
- 239000012535 impurity Substances 0.000 description 10
- 229920002472 Starch Polymers 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000002351 wastewater Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000003987 high-resolution gas chromatography Methods 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Plant Substances (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
Abstract
The invention discloses a novel method for preparing penicillin G sulfoxide, which comprises the following steps: a, selecting a 60000-120000 mu/g penicillin G fermentation solution, and dropwisely adding peroxyacetic acid to obtain a solution I; b, filtering the solution I to obtain a filtrate, and concentrating the filtrate through a nanofiltration membrane of which the molecular weight cut-off is 200-800Da, thus obtaining a concentrated solution; c, regulating the pH value of the concentrated solution with sulfuric acid, and filtering to obtain a penicillin G sulfoxide crude product; and d, dissolving the penicillin G sulfoxide crude product in a methanol water solution, recrystallizing, then cooling to 0-10 DEG C, filtering, washing the obtained crystals with methanol, swabbing off, and performing microwave drying on the obtained product to obtain the penicillin G sulfoxide. According to the invention, the method is simple, the process period is short, and extraction treatment can be performed without using a large amount of organic solvent. Thus, the method disclosed by the invention is low in cost and environment-friendly.
Description
Technical field
The invention belongs to chemical engineering crystallization technique field, be specifically related to a kind of penicillin G sulfoxide preparation method.
Background technology
Penicillin sulfoxide is by penicillin very important intermediate in cynnematin conversion process.In traditional processing technology flow process, penicillin G sulfoxide be generally with penicillin G Industrial Salt for material oxidation obtains: cosmocillin obtains penicillin G sulfoxide through oxidation → crystallization → filtration → washing → drying and other steps, and the acquisition of cosmocillin is again through processes such as filtration → extraction → extracting → crystallizations, so loaded down with trivial details from the whole Production Flow Chart complexity of penicillin fermentation liquid → penicillin G sulfoxide, and employ a large amount of solvent in the process to extract, power working cost is high, wastewater discharge is large, production cost is high.At present, people are trying to explore a kind of method that penicillin G sulfoxide is prepared in simplification.
A kind of method directly preparing penicillin sulfoxide with penicillin fermentation liquid is disclosed: penicillin fermentation liquid or penicillin salt solution add esters solvent to be made it to change into penicillinic acid in Chinese patent application CN2010105029756, then oxygenant is added to the penicillinic acid in organic phase and carry out oxidizing and crystallizing, extract from organic phase and prepare penicillin sulfoxide.Though the method has penicillin fermentation liquid to be basic raw material, the technological process involved by it is still in fact and penicillin is changed into penicillinic acid intermediate, then prepares penicillin sulfoxide with penicillinic acid intermediate oxidation.
Summary of the invention
Object of the present invention is just to provide a kind of method preparing penicillin G sulfoxide newly, to Simplified flowsheet, reduces costs, and reduces discharge of wastewater, improves environmental friendliness degree.
For achieving the above object, the method preparing penicillin G sulfoxide provided by the present invention comprises the following steps:
A. get the penicillin G fermented liquid of concentration 60000 ~ 120000 μ/g, under temperature 0 ~ 8 DEG C of condition, drip mass volume ratio concentration be the Peracetic Acid of 20 ~ 38% to being oxidized terminal, obtain solution I;
B. solution I is obtained filtrate through 50 ~ 200nm ceramic membrane filter, gained filtrate is that FW=100-500 nanofiltration membrane concentrates to obtain concentrated solution through molecular weight cut-off;
C. described concentrated solution sulfuric acid regulates PH to 1 ~ 1.5, filters, obtains penicillin G sulfoxide crude product;
D. described penicillin G sulfoxide crude product is dissolved in 9 ~ 80% methanol aqueous solutions, and then recrystallization under 40 ~ 48 DEG C of temperature condition is cooled to 0 ~ 10 DEG C, and filter, gained crystal methanol wash, to drain, products therefrom microwave drying, obtains penicillin G sulfoxide.
9 ~ 80% methanol solutions of the present invention, refer in 100ml solution, and containing methyl alcohol 9-80ml, surplus is water.
In order to improve product comprehensive income further, in step a, penicillin fermentation liquid is tired preferably 60000 ~ 120000 μ/g; The temperature of penicillin fermentation liquid preferably 0 ~ 5 DEG C in step a; The mass volume ratio of Peracetic Acid described in step a concentration preferably 29 ~ 33%; Preferred FW=200 ~ 300 of the molecular weight cut-off of nanofiltration membrane described in step a.
During microwave drying, optimum condition is: microwave frequency 915 ~ 2450MHZ, and 10 ~ 20 minutes time of drying, the water capacity of wet product controls 4% ~ 8%.
The direct oxidation of penicillin G fermented liquid, filtration, crystallization, recrystallization are prepared penicillin G sulfoxide by the present invention, and its method is simple, and process cycle is short, and a large amount of organic solvents need not be adopted to carry out extraction process.Therefore cost is low, environmental friendliness.
Adopt method provided by the present invention to prepare penicillin G sulfoxide, also there is content high, the advantage that purity is good.
Through the inventive method obtain penicillin G sulfoxide crystal through spectrophotometer, high performance liquid chromatography, high resolution gas chromatography analysis, detection:
Its content (HPLC): > 99.8%;
Purity (HPLC): > 99.5%;
Moisture (KF) :≤0.1%;
425nm light absorption value :≤0.02;
Solvent remains :≤0.1%.
Embodiment
Embodiment 1:
Add 1000ml penicillin G fermented liquid (concentration: 90000 μ/g) in 2000ml there-necked flask, cryosel bath is cooled to 0 ~ 5 DEG C.Under rapid stirring, dripping mass volume ratio concentration is stop oxidation (detecting oxidation terminal with potassium iodide starch test paper) after 30% Peracetic Acid to oxidation terminal, obtains solution I.Solution I leaches solid impurity through 100nm ceramic membrane filter, suitable quantity of water washing impurity, filtration.Filtrate concentrates by molecular weight cut-off FW=500 nanofiltration membrane.Concentrated solution sulfuric acid is adjusted to PH=1 ~ 1.5, filters to obtain penicillin G sulfoxide crude product (wet product) at 0 ~ 20 DEG C.This penicillin G sulfoxide crude product (wet product) is put in 60% methanol solution, recrystallization at 40 ~ 48 DEG C.Be cooled to 0 ~ 10 DEG C, filter.By 0 DEG C of methanol wash, drain.Product is dry in microwave.Obtain penicillin G sulfoxide 42.5g, yield is 80%.
Embodiment 2:
Add 1000ml penicillin G fermented liquid (concentration: 95000 μ/g) in 2000ml there-necked flask, cryosel bath is cooled to 0 ~ 5 DEG C.Under rapid stirring, dripping mass volume ratio concentration is stop oxidation (detecting oxidation terminal with potassium iodide starch test paper) after 33% Peracetic Acid to oxidation terminal, obtains solution I.Solution I leaches solid impurity through 50nm ceramic membrane filter, suitable quantity of water washing impurity, filtration.Filtrate concentrates by molecular weight cut-off FW=200 nanofiltration membrane.Concentrated solution sulfuric acid is adjusted to PH=1 ~ 1.5, filters to obtain penicillin G sulfoxide crude product (wet product) at 0 ~ 20 DEG C.This penicillin G sulfoxide crude product (wet product) is put in 80% methanol aqueous solution, recrystallization at 40 ~ 48 DEG C.Be cooled to 0 ~ 10 DEG C, filter.By 0 DEG C of methanol wash, drain.Product is dry in microwave.Microwave drying condition is: microwave frequency 915 ~ 2450MHZ, and 10 ~ 20 minutes time of drying, the water capacity of wet product controls 4% ~ 8%.Obtain penicillin G sulfoxide 47.2g after microwave drying, yield is 85.4%.
Embodiment 3:
Add 1000ml penicillin G fermented liquid (concentration: 60000 μ/g) in 2000ml there-necked flask, cryosel bath is cooled to 0 ~ 8 DEG C.Under rapid stirring, dripping mass volume ratio concentration is stop oxidation (detecting oxidation terminal with potassium iodide starch test paper) after 28% Peracetic Acid to oxidation terminal, obtains solution I.Solution I leaches solid impurity through 200 μm of ceramic membrane filters, suitable quantity of water washing impurity, filtration.Filtrate concentrates by molecular weight cut-off FW=800 nanofiltration membrane.Concentrated solution sulfuric acid is adjusted to PH=1 ~ 1.5, filters to obtain penicillin G sulfoxide crude product (wet product) at 0 ~ 20 DEG C.This penicillin G sulfoxide crude product (wet product) is put in 9% methanol aqueous solution, recrystallization at 35 ~ 40 DEG C.Be cooled to 0 ~ 10 DEG C, filter.By 0 DEG C of methanol wash, drain.Product is dry in microwave.Obtain penicillin G sulfoxide 27.7g, yield is 78%.
Embodiment 4:
Add 1000ml penicillin G fermented liquid (concentration: 120000 μ/g) in 2000ml there-necked flask, cryosel bath is cooled to 0 ~ 8 DEG C.Under rapid stirring, dripping mass volume ratio concentration is stop oxidation (detecting oxidation terminal with potassium iodide starch test paper) after 20% Peracetic Acid to oxidation terminal, obtains solution I.Solution I leaches solid impurity through 200nm ceramic membrane filter, suitable quantity of water washing impurity, filtration.Filtrate concentrates by molecular weight cut-off FW=200-300 molecular weight nanofiltration membrane.Concentrated solution sulfuric acid is adjusted to PH=1 ~ 1.5, filters to obtain penicillin G sulfoxide crude product (wet product) at 0 ~ 20 DEG C.This penicillin G sulfoxide crude product (wet product) is put in 9% methanol aqueous solution, recrystallization at 35 ~ 40 DEG C.Be cooled to 0 ~ 10 DEG C, filter.By 0 DEG C of methanol wash, drain.Product is dry in microwave.Obtain penicillin G sulfoxide 54.6g, yield is 76.9%.
Embodiment 5:
Add 1000ml penicillin G fermented liquid (concentration: 90000 μ/g) in 2000ml there-necked flask, cryosel bath is cooled to 0 ~ 5 DEG C.Under rapid stirring, dripping mass volume ratio concentration is stop oxidation (detecting oxidation terminal with potassium iodide starch test paper) after 38% Peracetic Acid to oxidation terminal, obtains solution I.Solution I leaches solid impurity through 150nm ceramic membrane filter, suitable quantity of water washing impurity, filtration.Filtrate concentrates by molecular weight cut-off FW=200 molecular weight nanofiltration membrane.Concentrated solution sulfuric acid is adjusted to PH=1 ~ 1.5, filters to obtain penicillin G sulfoxide crude product (wet product) at 0 ~ 20 DEG C.This penicillin G sulfoxide crude product (wet product) is put in 45% methanol aqueous solution, recrystallization at 35 ~ 45 DEG C.Be cooled to 0 ~ 10 DEG C, filter.By 0 DEG C of methanol wash, drain.Product is dry in microwave.Obtain penicillin G sulfoxide 42.8g, yield is 80.5%.
Claims (5)
1. a penicillin G sulfoxide preparation method, is characterized in that it comprises the following steps:
A. get the penicillin G fermented liquid of concentration 60000 ~ 120000u/g, under temperature 0 ~ 8 DEG C of condition, drip mass volume ratio concentration be the Peracetic Acid of 20 ~ 38% to being oxidized terminal, obtain solution I;
B. solution I is obtained filtrate through 50 ~ 200nm ceramic membrane filter, the nanofiltration membrane that gained filtrate is FW=100 ~ 500 through molecular weight cut-off concentrates to obtain concentrated solution;
C. described concentrated solution sulphur acid for adjusting pH to 1 ~ 1.5, filter, obtain penicillin G sulfoxide crude product;
D. described penicillin G sulfoxide crude product is dissolved in volume by volume concentration is in 9 ~ 80% methanol aqueous solutions, and recrystallization under 40 ~ 48 DEG C of temperature condition, is then cooled to 0 ~ 10 DEG C, filter, gained crystal methanol wash, drain, products therefrom microwave drying, obtains penicillin G sulfoxide.
2. penicillin G sulfoxide preparation method according to claim 1, is characterized in that the temperature of penicillin fermentation liquid in step a is 0 ~ 5 DEG C.
3. penicillin G sulfoxide preparation method according to claim 1, is characterized in that the mass volume ratio of Peracetic Acid described in step a concentration is 29 ~ 33%.
4. penicillin G sulfoxide preparation method according to claim 1, is characterized in that the molecular weight cut-off of nanofiltration membrane described in step b is FW=200 ~ 300.
5. penicillin G sulfoxide preparation method according to claim 1, is characterized in that microwave drying described in steps d, its microwave frequency 915 ~ 2450MHZ, and 10 ~ 20 minutes time of drying, the water capacity of wet product controls 4% ~ 8%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210547802.5A CN102964355B (en) | 2012-12-17 | 2012-12-17 | Preparation method of penicillin G sulfoxide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210547802.5A CN102964355B (en) | 2012-12-17 | 2012-12-17 | Preparation method of penicillin G sulfoxide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102964355A CN102964355A (en) | 2013-03-13 |
| CN102964355B true CN102964355B (en) | 2015-07-01 |
Family
ID=47794815
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210547802.5A Active CN102964355B (en) | 2012-12-17 | 2012-12-17 | Preparation method of penicillin G sulfoxide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102964355B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105693747B (en) * | 2016-03-07 | 2018-02-06 | 内蒙古常盛制药有限公司 | A kind of 6 APA is without the dry technology of solvent washing |
| CN111233892B (en) * | 2018-11-28 | 2022-10-14 | 江苏悦新药业有限公司 | Method for synthesizing penicillin G sulfoxide by using continuous flow reactor |
| CN112358489A (en) * | 2020-11-09 | 2021-02-12 | 华北制药股份有限公司 | Production method of industrial penicillin sulfoxide product |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4230620A (en) * | 1979-03-26 | 1980-10-28 | Eli Lilly And Company | Process for preparing penicillin sulfoxides |
| CN1201795A (en) * | 1998-05-22 | 1998-12-16 | 范伟光 | Preparation of 7-amino-deacetylated cefa-alkylation acid |
| CN1332169A (en) * | 2000-07-10 | 2002-01-23 | 中国科学院化工冶金研究所 | Method of eliminating water and other impurities from coarse penicillin G sulfoxide |
| CN101735246A (en) * | 2008-11-05 | 2010-06-16 | 杨石 | Method for preparing cephalosporin intermediate 7-ADCA |
| CN101974017A (en) * | 2010-10-11 | 2011-02-16 | 天津大学 | Method for preparing penicillin-G-1-(S)-oxide |
-
2012
- 2012-12-17 CN CN201210547802.5A patent/CN102964355B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4230620A (en) * | 1979-03-26 | 1980-10-28 | Eli Lilly And Company | Process for preparing penicillin sulfoxides |
| CN1201795A (en) * | 1998-05-22 | 1998-12-16 | 范伟光 | Preparation of 7-amino-deacetylated cefa-alkylation acid |
| CN1332169A (en) * | 2000-07-10 | 2002-01-23 | 中国科学院化工冶金研究所 | Method of eliminating water and other impurities from coarse penicillin G sulfoxide |
| CN101735246A (en) * | 2008-11-05 | 2010-06-16 | 杨石 | Method for preparing cephalosporin intermediate 7-ADCA |
| CN101974017A (en) * | 2010-10-11 | 2011-02-16 | 天津大学 | Method for preparing penicillin-G-1-(S)-oxide |
Non-Patent Citations (3)
| Title |
|---|
| 苄青霉素亚砜对-甲氧基苄酯的合成研究;杨莉 等;《中国抗生素杂志》;20051030;第30卷(第10期);第586-587页，第587页左栏第2.1节 * |
| 青霉素G亚砜对甲氧基苄酯的合成研究;邢俊德 等;《化学试剂》;20090531;第31卷(第5期);第370-372页 * |
| 青霉素制备青霉素亚砜;史兰香 等;《精细化工》;20000525;第17卷(第5期);第252-255页，第252页右栏第1.1节，第253页左栏第2段 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102964355A (en) | 2013-03-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104370312B (en) | Recycling processing technology for high-salt wastewater during carboxymethyl cellulose production | |
| CN102911036A (en) | Method for obtaining high pure dicarboxylic acid | |
| CN101565438B (en) | Purification method for Tylosin | |
| CN102964355B (en) | Preparation method of penicillin G sulfoxide | |
| CN103274927A (en) | Purification method for nature abscisic acid | |
| CN106256824A (en) | A kind of preparation method of high-purity De Lasha star meglumine salt | |
| CN111574456B (en) | Synthetic method of N alpha-tert-butyloxycarbonyl-L-histidine | |
| CN102863408B (en) | Preparation method of andrographolide | |
| CN103772186A (en) | Refining method of fermented organic acid | |
| CN102942547B (en) | GA4And/or GA7Separation and purification method of | |
| CN103804173B (en) | A kind of process for purification of fermentation organic acid | |
| CN104557703A (en) | Cisatracurium besilate refining method | |
| CN103804310A (en) | Method for preparing high-purity 7-chloro-5-phenyl-benzodiazepine-2-one | |
| CN105985315A (en) | Method for extracting nicotine from tobacco waste | |
| CN108586374B (en) | Preparation method of 2-phenylbenzoxazole compound | |
| CN101768165B (en) | Ellagic acid preparation method employing tara powder | |
| CN106496022B (en) | A kind of method for extracting pyruvate from microbial fermentation liquid or enzyme transformation liquid | |
| CN103804174B (en) | A kind of organic acid process for purification | |
| CN104529935A (en) | Method for synthesizing high-purity ethyl 2-(3-aldehyde-4-isobutyloxyphenyl)-4-methylthiazole-5-formate | |
| CN104591999A (en) | Long chain organic acid purifying method | |
| CN104592004A (en) | Long chain organic acid refining method | |
| CN102010345B (en) | Method for preparing D-phenylalanine through dynamic kinetic resolution | |
| CN103709174B (en) | The one-step synthesis of the bromo-3H-oxazole of 6-also [4,5-b] pyridin-2-ones | |
| CN103508974A (en) | Method for treating methyl 2-(aminosulfonyl)benzoate crystallization mother solution | |
| CN101289410B (en) | Method for preparing D-phenylalanine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C53 | Correction of patent for invention or patent application | ||
| CB03 | Change of inventor or designer information |
Inventor after: Wei Qingjie Inventor after: Zhang Miaojing Inventor after: Zheng Baoli Inventor after: Gao Junyan Inventor after: Feng Lifeng Inventor after: Yan Feng Inventor after: Wang Liqiang Inventor after: Zhang Wei Inventor after: Yin Keke Inventor after: Zhao Wei Inventor after: Yang Liting Inventor after: Duan Zhigang Inventor after: Ma Like Inventor after: Wu Xiang Inventor after: Chen Hao Inventor after: Liu Hailian Inventor after: Liu Dong Inventor after: Zhang Suoqing Inventor after: Mi Zhenrui Inventor after: Liu Mingru Inventor after: Fu Chengming Inventor after: Wang Dong Inventor after: Yang Fan Inventor before: Wei Qingjie Inventor before: Zhang Miaojing Inventor before: Zheng Baoli Inventor before: Gao Junyan Inventor before: Feng Lifeng Inventor before: Duan Zhigang Inventor before: Liu Dong Inventor before: Zhang Suoqing Inventor before: Mi Zhenrui Inventor before: Liu Mingru Inventor before: Fu Chengming Inventor before: Wang Dong Inventor before: Yang Fan |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: WEI QINGJIE DUAN ZHIGANG LIU DONG ZHANG SUOQING MI ZHENRUI LIU MINGRU FU CHENGMING WANG DONG YANG FAN ZHANG MIAOJING ZHENG BAOLI GAO JUNYAN FENG LIFENG TO: WEI QINGJIE DUAN ZHIGANG LIU DONG ZHANG SUOQING MI ZHENRUI LIU MINGRU FU CHENGMING WANG DONG YANG FAN ZHANG MIAOJING ZHENG BAOLI GAO JUNYAN FENG LIFENG YAN FENG WANG LIQIANG ZHANG WEI YIN KEKE ZHAO WEI YANG LITING MA LIKE WU XIANG CHEN HAO LIU HAILIAN |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20190211 Address after: 050000 No. 388 Heping East Road, Shijiazhuang City, Hebei Province Patentee after: Huabei Pharmaceutical Co., Ltd. Address before: 052165 No. 98 Hainan Road, Liangcun Economic and Technological Development Zone, Shijiazhuang City, Hebei Province Patentee before: NCPC Hebei Huamin Pharma Co., Ltd. |