CN113968858A - Method for removing heavy metal from meropenem - Google Patents
Method for removing heavy metal from meropenem Download PDFInfo
- Publication number
- CN113968858A CN113968858A CN202111282433.7A CN202111282433A CN113968858A CN 113968858 A CN113968858 A CN 113968858A CN 202111282433 A CN202111282433 A CN 202111282433A CN 113968858 A CN113968858 A CN 113968858A
- Authority
- CN
- China
- Prior art keywords
- meropenem
- heavy metals
- removing heavy
- filtrate
- temperature
- 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.)
- Pending
Links
- 229960002260 meropenem Drugs 0.000 title claims abstract description 59
- DMJNNHOOLUXYBV-PQTSNVLCSA-N meropenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](C(=O)N(C)C)C1 DMJNNHOOLUXYBV-PQTSNVLCSA-N 0.000 title claims abstract description 59
- 229910001385 heavy metal Inorganic materials 0.000 title claims abstract description 54
- 238000000034 method Methods 0.000 title claims abstract description 31
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000000706 filtrate Substances 0.000 claims abstract description 19
- 238000003756 stirring Methods 0.000 claims abstract description 19
- 238000002425 crystallisation Methods 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 230000008025 crystallization Effects 0.000 claims abstract description 13
- 229920001661 Chitosan Polymers 0.000 claims abstract description 11
- 238000001914 filtration Methods 0.000 claims abstract description 10
- 239000012528 membrane Substances 0.000 claims abstract description 9
- 238000010828 elution Methods 0.000 claims abstract description 8
- 239000000047 product Substances 0.000 claims description 10
- 239000003814 drug Substances 0.000 abstract description 7
- 238000005282 brightening Methods 0.000 abstract description 2
- 238000000746 purification Methods 0.000 abstract description 2
- 238000000926 separation method Methods 0.000 abstract description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000002351 wastewater Substances 0.000 description 3
- 108020004256 Beta-lactamase Proteins 0.000 description 2
- 208000004145 Endometritis Diseases 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical compound C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- -1 endometritis sites Chemical compound 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 201000010000 Agranulocytosis Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 101710116957 D-alanyl-D-alanine carboxypeptidase Proteins 0.000 description 1
- 206010061977 Genital infection female Diseases 0.000 description 1
- 206010018687 Granulocytopenia Diseases 0.000 description 1
- 208000008745 Healthcare-Associated Pneumonia Diseases 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 208000029082 Pelvic Inflammatory Disease Diseases 0.000 description 1
- 108010087702 Penicillinase Proteins 0.000 description 1
- 208000031951 Primary immunodeficiency Diseases 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010054979 Secondary immunodeficiency Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 206010041925 Staphylococcal infections Diseases 0.000 description 1
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 102000020235 metallo-beta-lactamase Human genes 0.000 description 1
- 108060004734 metallo-beta-lactamase Proteins 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 208000004235 neutropenia Diseases 0.000 description 1
- 229950009506 penicillinase Drugs 0.000 description 1
- 239000010865 sewage Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D477/00—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring
- C07D477/10—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D477/12—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 6
- C07D477/16—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 6 with hetero atoms or carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 3
- C07D477/20—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D477/00—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring
- C07D477/02—Preparation
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for removing heavy metals from meropenem, and relates to the technical field of separation and purification of meropenem. The method comprises the following steps: (1) dissolving: adding meropenem into water, controlling the temperature, and dissolving and brightening after stirring; (2) removing heavy metals: adding chitosan, controlling the temperature, stirring, and then filtering by using a filter membrane to obtain a filtrate; (3) and adding acetone into the filtrate, and carrying out elution and crystallization to obtain meropenem with the heavy metal content within 2 ppm. The crystallization method is simple and convenient to operate, can obviously reduce the heavy metal content of meropenem, and has better medicine quality and safer medicine application.
Description
Technical Field
The invention relates to the technical field of meropenem separation and purification, and particularly relates to a method for removing heavy metals from meropenem.
Background
Meropenem is an artificially synthesized broad-spectrum carbapenem antibiotic, generates an antibacterial effect by inhibiting the synthesis of bacterial cell walls, and easily penetrates the cell walls of most gram-positive and gram-negative bacteria to achieve an action target point of Penicillin Binding Protein (PBPS). In addition to metallo beta-lactamases, they are more stable against hydrolysis by most beta-lactamases, including penicillinase and cephalosporinase produced by gram-positive and gram-negative bacteria. Meropenem is not suitable for the treatment of methicillin-resistant staphylococcal infections and sometimes exhibits cross-resistance to other carbapenem-resistant strains. In vitro experiments show that, for some isolated strains of pseudomonas aeruginosa, the combination of meropenem and aminoglycoside antibiotics can generate synergistic effect. Meropenem is suitable for adults and children with infections caused by a single or multiple bacteria sensitive to meropenem, such as endometritis sites, pneumonia (including nosocomial pneumonia); urinary tract infection; gynecological infection: such as endometritis and pelvic inflammatory disease; skin soft tissue infections; meningitis; sepsis. The empirical treatment can be used for patients with adult granulocytopenia accompanied with fever, and the product can be used alone or in combination with antiviral drugs or antifungal drugs. Meropenem is useful in the treatment of multiple bacterial infections, either alone or in combination with other antimicrobial agents. For the infant patients with neutropenia or primary and secondary immunodeficiency, the product has no use experience at present.
Meropenem, english name: meropenem, chemical name: (4R,5S,6S) -3- [ [ (3S,5S) -5- (dimethylcarbamoyl) -3-pyrrolidine ] thio ] -6- [ (1R) -1-hydroxyethyl ] -4-methyl-7-oxo-1-azabicyclo [3.2.0] hept-2-ene-2-carboxylic acid trihydrate.
In the hydrogenation step of the meropenem in the synthesis process, the reaction is carried out in a stainless steel hydrogenation kettle, meanwhile, in order to enable the reaction to be carried out, pressurization and vigorous stirring are required, and meanwhile, palladium carbon is used as a catalyst during hydrogenation, so that heavy metal, particularly palladium, in the meropenem product exceeds the required standard, and the medication safety is influenced.
At present, heavy metals can be reduced through recrystallization in meropenem production with high heavy metals, the method is mostly adopted in the production at present, but the meropenem needs to be dissolved and then added with a solvent for crystallization, the operation is complicated, the amount of experimental solvent is large, the cost is increased in the recrystallization process, and new sewage discharge is generated.
How to reduce heavy metal residue, control product impurities and improve product quality directly influences the medication safety, so the research on removing heavy metal by meropenem has very important significance. The prior literature does not disclose a method for removing heavy metals with chitosan.
Disclosure of Invention
The invention aims to solve the technical problem of providing a method for removing heavy metal in meropenem, which has the advantages of simple and convenient operation, short period, less waste water discharge and environmental protection, and the heavy metal content of the product is greatly reduced from 10ppm to 1 ppm. Heavy metals can cause toxicity to human bodies, reduce the content of heavy metals and ensure that the medicine is safer to use.
The invention provides a method for removing heavy metals from meropenem, which is characterized by comprising the following steps: (1) dissolving: adding meropenem into water, controlling the temperature, and dissolving and brightening after stirring; (2) removing heavy metals: adding chitosan, controlling the temperature, stirring, and then filtering with a filter membrane to obtain a filtrate; (3) and adding acetone into the filtrate, and carrying out elution and crystallization to obtain meropenem with the heavy metal content within 2 ppm.
The heavy metal is primarily palladium.
Preferably, in step (1), upon dissolution, meropenem: the water weight ratio is 1: 18-22, preferably 1: 20.
preferably, in the step (1), the temperature is controlled to be 20-25 ℃ during dissolution.
Preferably, in the step (2), the addition amount of the chitosan is 1-3%, preferably 2% of the mass of the solution.
Preferably, in the step (2), the temperature is controlled to be 5-10 ℃ during heavy metal removal.
Preferably, in the step (2), the stirring time is 20-40 minutes when the heavy metals are removed.
Preferably, in the step (2), when removing heavy metals, filtration is performed by using a 0.45 micron filter membrane.
Preferably, in the step (3), acetone is added in an amount of 4 to 6 times by volume, preferably 5 times by volume, during crystallization.
The invention further provides a method for removing heavy metals from meropenem, which comprises the following steps: (1) dissolving: adding the crude meropenem product (containing 10ppm of heavy metal) into water (the weight ratio of the meropenem to the water is 1: 20), controlling the temperature to be 20-25 ℃, and stirring and dissolving until the crude meropenem product is clear; (2) removing heavy metals: adding chitosan accounting for 2% of the solution obtained in the step (1), controlling the temperature to be 5-10 ℃, stirring for 20 minutes, and then filtering by using a 0.45-micrometer filter membrane to obtain a filtrate; (3) and adding acetone with the volume 5 times that of the filtrate into the filtrate, and carrying out elution and crystallization to obtain the meropenem with the heavy metal content within 1 ppm.
Compared with the prior production process for removing heavy metals, the technical scheme has the following beneficial effects:
(1) the method disclosed by the invention is simple and convenient to operate, short in period, less in waste water discharge, and has the advantage of environmental protection, the heavy metal content of meropenem is obviously reduced, and the safety of medicines is favorably improved.
(2) The method for the gravity crystallization can reduce the waste water consumption by 60 percent and has the advantage of environmental protection.
(3) The method for the gravity crystallization is simple, the dosage of the solvent is reduced by 60%, the cost is reduced by 25%, and the method has the cost advantage.
(4) The method is simple and convenient to operate, and the process is easy to control.
(5) The method can reduce the heavy metal content from 10ppm to below 1ppm, meets the requirement of ICH on meropenem, and is far less than 10ppm required by quality standard of pharmacopoeia 2015 edition.
(6) The recrystallization method is that after meropenem is dissolved, acetone is added for crystallization, a part of heavy metal is remained in mother liquor, the yield of the method is 85.2%, the purity is 98.0%, and the heavy metal is 5.0 ppm.
Detailed Description
The present invention will be described in further detail with reference to specific embodiments.
Example 1
5.0g of meropenem (10 ppm of heavy metal and 98% of purity) is added into 100ml of water, the temperature is controlled to be 20-25 ℃, and the mixture is dissolved and brightened after stirring. Adding 2g of chitosan, controlling the temperature to be 5-10 ℃, stirring for 20 minutes, and then filtering by using a 0.45 micron filter membrane to obtain a filtrate; and adding 500ml of acetone into the filtrate, and carrying out elution and crystallization to obtain the meropenem. The yield is 90.4%, the purity is 98.1%, and the heavy metal content is 1.0 ppm.
Example 2
5.2g of meropenem (10 ppm of heavy metal and 98 percent of purity) is added into 100ml of water, the temperature is controlled to be 20-25 ℃, and the mixture is dissolved and brightened after stirring. Adding 3g of chitosan, controlling the temperature to be 5-10 ℃, stirring for 20 minutes, and then filtering by using a 0.45 micron filter membrane to obtain a filtrate; and adding 500ml of acetone into the filtrate, and carrying out elution and crystallization to obtain the meropenem. The yield is 91.8%, the purity is 98.5%, and the heavy metal content is 0.8 ppm.
Example 3
Adding 4.8g of meropenem (10 ppm of heavy metal and 98% of purity) into 100ml of water, controlling the temperature to be 20-25 ℃, and stirring to dissolve and brighten. Adding 1.5g of chitosan, controlling the temperature to be 5-10 ℃, stirring for 20 minutes, and then filtering by using a 0.45 micron filter membrane to obtain a filtrate; and adding 500ml of acetone into the filtrate, and carrying out elution and crystallization to obtain the meropenem. The yield is 90.1%, the purity is 98.9%, and the heavy metal content is 1.0 ppm.
Claims (10)
1. A method for removing heavy metals from meropenem is characterized by comprising the following steps:
(1) dissolving: adding meropenem into water, controlling the temperature, and stirring to dissolve and brighten.
(2) Removing heavy metals: adding chitosan, controlling the temperature, stirring, and then filtering with a filter membrane to obtain a filtrate;
(3) and adding acetone into the filtrate, and carrying out elution and crystallization to obtain meropenem with the heavy metal content within 2 ppm.
2. The method for removing heavy metals from meropenem according to claim 1, wherein: in the step (1), the weight ratio of meropenem to water is 1: 18 to 22.
3. The method for removing heavy metals from meropenem according to claim 2, wherein: in the step (1), the weight ratio of meropenem to water is 1: 20.
4. the method for removing heavy metals from meropenem according to claim 1, wherein: in the step (1), the temperature is controlled to be 22-25 ℃.
5. The method for removing heavy metals from meropenem according to claim 1, wherein: in the step (2), the addition amount of the chitosan is 1-3% by weight, and preferably 2%.
6. The method for removing heavy metals from meropenem according to claim 1, wherein: in the step (2), the temperature is controlled to be 5-10 ℃.
7. The method for removing heavy metals from meropenem according to claim 1, wherein: in the step (2), the stirring time was 20 minutes.
8. The method for removing heavy metals from meropenem according to claim 1, wherein: in step (2), filtration was performed using a 0.45 μm filter.
9. The method for removing heavy metals from meropenem according to claim 1, wherein: in the step (3), the volume of acetone added to the filtrate is 5 times of the volume of water in the step (1).
10. A method for removing heavy metals from meropenem is characterized by comprising the following steps: (1) dissolving: adding the crude meropenem product (containing 10ppm of heavy metal) into water (the weight ratio of the meropenem to the water is 1: 20), controlling the temperature to be 20-25 ℃, and stirring and dissolving until the crude meropenem product is clear; (2) removing heavy metals: adding chitosan accounting for 2% of the solution obtained in the step (1), controlling the temperature to be 5-10 ℃, stirring for 20 minutes, and then filtering by using a 0.45-micrometer filter membrane to obtain a filtrate; (3) and adding acetone with the volume 5 times that of the filtrate into the filtrate, and carrying out elution and crystallization to obtain the meropenem with the heavy metal content within 1 ppm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111282433.7A CN113968858A (en) | 2021-11-01 | 2021-11-01 | Method for removing heavy metal from meropenem |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111282433.7A CN113968858A (en) | 2021-11-01 | 2021-11-01 | Method for removing heavy metal from meropenem |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113968858A true CN113968858A (en) | 2022-01-25 |
Family
ID=79589134
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111282433.7A Pending CN113968858A (en) | 2021-11-01 | 2021-11-01 | Method for removing heavy metal from meropenem |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113968858A (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101297708A (en) * | 2008-06-06 | 2008-11-05 | 石勇 | Method from preparing high-purity edible fish oil from coarse fish oil |
| CN101560215A (en) * | 2009-05-27 | 2009-10-21 | 复旦大学 | Method for removing residual palladium of faropenem sodium |
| CN102731502A (en) * | 2011-04-13 | 2012-10-17 | 石药集团中奇制药技术（石家庄）有限公司 | Preparation method of carbpenem antibiotic |
| CN102731504A (en) * | 2011-04-13 | 2012-10-17 | 石药集团中奇制药技术（石家庄）有限公司 | Preparation method of meropenem |
| CN105601009A (en) * | 2016-01-26 | 2016-05-25 | 廖丽萍 | Preparation method of water special for traditional Chinese medicine decoction |
| CN111675742A (en) * | 2020-07-20 | 2020-09-18 | 江西海富生物工程有限公司 | Preparation method of neohesperidin with heavy metal removed |
-
2021
- 2021-11-01 CN CN202111282433.7A patent/CN113968858A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101297708A (en) * | 2008-06-06 | 2008-11-05 | 石勇 | Method from preparing high-purity edible fish oil from coarse fish oil |
| CN101560215A (en) * | 2009-05-27 | 2009-10-21 | 复旦大学 | Method for removing residual palladium of faropenem sodium |
| CN102731502A (en) * | 2011-04-13 | 2012-10-17 | 石药集团中奇制药技术（石家庄）有限公司 | Preparation method of carbpenem antibiotic |
| CN102731504A (en) * | 2011-04-13 | 2012-10-17 | 石药集团中奇制药技术（石家庄）有限公司 | Preparation method of meropenem |
| CN105601009A (en) * | 2016-01-26 | 2016-05-25 | 廖丽萍 | Preparation method of water special for traditional Chinese medicine decoction |
| CN111675742A (en) * | 2020-07-20 | 2020-09-18 | 江西海富生物工程有限公司 | Preparation method of neohesperidin with heavy metal removed |
Non-Patent Citations (2)
| Title |
|---|
| 《水工业市场》杂志社主编: "《2011水处理典型技术案例大全》", 31 March 2012, 中国环境科学出版社 * |
| 罗进等: "降低植物提取物中重金属含量研究进展", 《广东化工》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU758190B2 (en) | Crystalline 1-methylcarbapenem compounds | |
| TW202045143A (en) | Combinations of beta-lactam compounds and probenecid and uses thereof | |
| CN113968858A (en) | Method for removing heavy metal from meropenem | |
| CN110343122B (en) | Preparation method of biapenem | |
| CN111747959B (en) | Preparation method of imipenem raw material medicine | |
| CN102627660B (en) | Cefmetazole aseptic powder and its preparation method | |
| AU677235B2 (en) | Crystalline carbapenem derivative | |
| CA2375601C (en) | Carbapenem compound crystals and injection preparations | |
| CN110393720B (en) | New indication of pharmaceutical preparation of troxofen ceftriaxone sodium for treating infection of patients with low immune function | |
| JPS60233078A (en) | 6-(1-hydroxyethyl)-2-sr8-1-methyl-1-carbadethiapen-2-em-3- carboxylic acid | |
| US8871927B2 (en) | Method for purifying Ceftizoxime sodium | |
| EP2834242A2 (en) | An improved process for the preparation of carbapenem antibiotic | |
| KR880001055B1 (en) | Carbapenem amitbiotics and process for preparation thereof | |
| CN102731503B (en) | A kind of preparation method of tebipenem | |
| CN100383142C (en) | A new process for preparation of imipenem | |
| KR20070112464A (en) | Process for producing carbapenem derivative having 1-alkylpyrrolidine structure | |
| CN113912625B (en) | Method for purifying cefadroxil | |
| CN102267997B (en) | Meropenem compound and preparation method thereof | |
| JP2832742B2 (en) | Carbapenem derivatives | |
| CN113880839A (en) | Novel synthesis method of ertapenem sodium crude product | |
| JP3045518B2 (en) | Carbapenem derivatives | |
| CN104557977A (en) | Refining method for cefcapene pivoxil hydrochloride | |
| CN105254632A (en) | Preparation method of doripenem | |
| JP2023517919A (en) | Combinations and Uses of Beta-Lactam Compounds, Probenecid, and Valproic Acid | |
| JP2643754B2 (en) | Antibacterial agent |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20220125 |