CN115772179A - Recrystallization method of ceftiofur sodium - Google Patents
Recrystallization method of ceftiofur sodium Download PDFInfo
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- CN115772179A CN115772179A CN202211585379.8A CN202211585379A CN115772179A CN 115772179 A CN115772179 A CN 115772179A CN 202211585379 A CN202211585379 A CN 202211585379A CN 115772179 A CN115772179 A CN 115772179A
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- ceftiofur sodium
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- ceftiofur
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- RFLHUYUQCKHUKS-JUODUXDSSA-M Ceftiofur sodium Chemical compound [Na+].S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC(=O)C1=CC=CO1 RFLHUYUQCKHUKS-JUODUXDSSA-M 0.000 title claims abstract description 84
- 229960004467 ceftiofur sodium Drugs 0.000 title claims abstract description 84
- 238000000034 method Methods 0.000 title claims abstract description 35
- 238000001953 recrystallisation Methods 0.000 title claims abstract description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 85
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 36
- 238000002425 crystallisation Methods 0.000 claims abstract description 35
- 230000008025 crystallization Effects 0.000 claims abstract description 35
- 239000002994 raw material Substances 0.000 claims abstract description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000002904 solvent Substances 0.000 claims abstract description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 41
- 239000011259 mixed solution Substances 0.000 claims description 40
- 238000003756 stirring Methods 0.000 claims description 28
- 238000001914 filtration Methods 0.000 claims description 27
- 239000000706 filtrate Substances 0.000 claims description 22
- 239000013078 crystal Substances 0.000 claims description 21
- 239000000463 material Substances 0.000 claims description 20
- 238000005406 washing Methods 0.000 claims description 20
- 239000012528 membrane Substances 0.000 claims description 18
- 238000001035 drying Methods 0.000 claims description 12
- 238000010438 heat treatment Methods 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 3
- 239000003814 drug Substances 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 3
- 238000000746 purification Methods 0.000 abstract description 2
- 238000003860 storage Methods 0.000 abstract description 2
- 230000007774 longterm Effects 0.000 abstract 1
- 238000004321 preservation Methods 0.000 description 7
- 241000894006 Bacteria Species 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 229930186147 Cephalosporin Natural products 0.000 description 2
- 241000192125 Firmicutes Species 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 229960005229 ceftiofur Drugs 0.000 description 2
- ZBHXIWJRIFEVQY-IHMPYVIRSA-N ceftiofur Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC(=O)C1=CC=CO1 ZBHXIWJRIFEVQY-IHMPYVIRSA-N 0.000 description 2
- 229940124587 cephalosporin Drugs 0.000 description 2
- 150000001780 cephalosporins Chemical class 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 125000003460 beta-lactamyl group Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Cephalosporin Compounds (AREA)
Abstract
The invention belongs to the technical field of medicament purification treatment, and particularly relates to a recrystallization method of ceftiofur sodium. The method for recrystallizing ceftiofur sodium takes ceftiofur sodium with changed properties or unqualified purity as a raw material in the process of long-term storage or transportation, dissolves the ceftiofur sodium in a solvent of methanol or ethanol and water, and uses acetone for crystallization to obtain a ceftiofur sodium product with improved purity and quality. The invention provides a recrystallization method of ceftiofur sodium, which has good recrystallization effect and high product purity and improves the utilization rate of ceftiofur sodium.
Description
Technical Field
The invention belongs to the technical field of medicament purification treatment, and particularly relates to a recrystallization method of ceftiofur sodium.
Background
Ceftiofur sodium is a special clinical cephalosporin antibiotic for veterinary medicine, and is a broad-spectrum antibacterial drug. Has strong antibacterial effect on gram-positive bacteria and gram-negative bacteria. Ceftiofur acts on the transcription peptidase to block the synthesis of the sticky peptide, so that the cell wall of bacteria is deleted to achieve the bactericidal effect. Ceftiofur has a stable beta-lactam ring, is not easily damaged by drug-resistant bacteria, and can act on gram-positive bacteria and gram-negative bacteria producing beta-lactamase.
Ceftiofur sodium is a third-generation cephalosporin antibiotic special for veterinary clinical use, and is widely applied all over the world due to strong antibacterial activity, excellent pharmacokinetic characteristics, small toxic and side effects and low residue. However, in the process of storage or transportation, the properties, pH and solubility of ceftiofur sodium change along with the change of time or temperature, so that the utilization rate of ceftiofur sodium is reduced, and the waste is serious.
CN104530085A discloses a novel preparation method of ceftiofur sodium, after the obtained product filtrate is prepared, a large amount of crystallization solvent is added into the filtrate for recrystallization, and the pure ceftiofur sodium is obtained by vacuum drying. The crystallization solvent can be tetrahydrofuran, dioxane, dimethoxyethane, diethyl ether, acetone, ethyl acetate, dichloromethane, ethanol, methanol, isopropanol, toluene, benzene, xylene, etc., and the dosage of the crystallization solvent is 20-120 times of the mass of ceftiofur sodium.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a method for recrystallizing ceftiofur sodium, which has the advantages of good recrystallization effect, high product purity and improvement on the utilization rate of ceftiofur sodium.
The recrystallization method of ceftiofur sodium specifically comprises the following steps:
(1) Adding a solvent to water;
(2) Heating to 20-40 ℃, adding the ceftiofur sodium raw material, and stirring at the constant temperature until the mixture is clear to obtain a mixed solution;
(3) Filtering the mixed solution for the first time;
(4) Adding active carbon into the mixed solution, and stirring;
(5) Filtering out the active carbon;
(6) Filtering the mixed solution for the second time to obtain filtrate;
(7) Keeping the filtrate at 20-40 ℃, dropwise adding crystallization acetone, stopping dropwise adding when crystals are separated out, and growing the crystals for 30-60 min;
(8) After the crystallization is finished, continuously dropwise adding the residual crystallization acetone;
(9) Washing the material with acetone, and drying to obtain ceftiofur sodium.
The ceftiofur sodium raw material is ceftiofur sodium with changed properties or the purity of which is lower than 98 percent.
The solvent is methanol or ethanol.
The mass ratio of the ceftiofur sodium raw material to the solvent to the water to the crystallization acetone to the washing material acetone is 1 (3-6) to (1-3) to (30-50) to (10-30).
The primary filtration and the secondary filtration are both carried out by adopting a sand core funnel, and the precision of the filter membrane is 0.2-0.5 mu m.
The speed of dripping the crystallization acetone in the step (7) is 1-2 seconds per drop.
The drying temperature of the step (9) is 40-60 ℃.
In the step (4), the mass ratio of the ceftiofur sodium raw material to the active carbon is 1: (0.01-0.1).
Specifically, the recrystallization method of ceftiofur sodium specifically comprises the following steps:
(1) Adding water, methanol or ethanol into a three-neck flask;
(2) Stirring and heating to 20-40 ℃, adding ceftiofur sodium raw material with changed properties or purity lower than 98%, and stirring while keeping the temperature until the mixture is clear to obtain a mixed solution;
(3) Filtering the mixed solution for the first time by adopting a sand core funnel 0.2-0.5 mu m filter membrane;
(4) Adding activated carbon into the mixed solution, and fully stirring, wherein the mass ratio of the ceftiofur sodium raw material to the activated carbon is 1: (0.01 to 0.1);
(5) A buchner funnel filters out most of the activated carbon;
(6) Filtering the mixed solution for the second time by adopting a sand core funnel 0.2 mu m filter membrane to obtain filtrate;
(7) Keeping the filtrate at 20-40 ℃, slowly dripping crystallization acetone, stopping dripping when crystals are separated out, and growing the crystals for 30min;
(8) After the crystallization is finished, continuously dropwise adding the residual crystallization acetone;
(9) Washing the material with acetone, and drying at 40-60 ℃ to obtain the high-purity ceftiofur sodium.
The mass ratio of the ceftiofur sodium raw material, the solvent, the water, the crystallized acetone and the washing material acetone is 1 (3-6) to 1-3 to 30-50 to 10-30.
Aiming at the recrystallization treatment of the finished ceftiofur sodium product, the recrystallization method of ceftiofur sodium provided by the invention obviously improves the purity of ceftiofur sodium through the steps of dissolving ceftiofur sodium, filtering and removing impurities by using activated carbon, recrystallizing and the like.
Compared with the prior art, the invention has the beneficial effects that:
(1) By adopting the recrystallization method, the purity of the ceftiofur sodium is improved by more than 2 percent.
(2) By adopting the recrystallization method, the acetone is used as the crystallization solvent and is cooperated with the solvent, the obtained product has better crystal form and higher yield which can reach more than 85 percent.
(3) The recrystallization method of ceftiofur sodium has simple process and reduces the generation of byproducts.
(4) According to the recrystallization method of ceftiofur sodium, acetone, ethanol and methanol are evaporated, so that the production cost is reduced.
(5) The recrystallization method of ceftiofur sodium has the advantages of simple components of the distilled mother liquor, simplified post-treatment procedures and reduced cost.
Detailed Description
The present invention will be further described with reference to the following specific examples.
Example 1
The recrystallization method of ceftiofur sodium specifically comprises the following steps:
(1) 30ml of water and 80ml of methanol are added into a 500ml three-neck flask;
(2) Stirring and heating to 25 ℃, adding 15g of ceftiofur sodium raw material, and stirring for 20min under the condition of heat preservation to obtain a mixed solution;
(3) Filtering the mixed solution for the first time by adopting a sand core funnel 0.2 mu m filter membrane;
(4) Adding 0.5g of activated carbon into the mixed solution, and fully stirring for 15min;
(5) Most of the activated carbon was filtered off with a buchner funnel;
(6) Filtering the mixed solution for the second time by adopting a sand core funnel 0.2 mu m filter membrane to obtain filtrate;
(7) Maintaining the filtrate at 25 deg.C, and dripping 100ml of crystallizing acetone at a speed of 1 s/drop, stopping dripping when crystal is separated out, and growing crystal for 30min;
(8) After the crystallization is finished, continuously dripping 500ml of crystallization acetone;
(9) Washing the material with 200ml of washing material acetone, and drying at 50 ℃ to obtain ceftiofur sodium.
The purity of the ceftiofur sodium raw material is 96.31 percent, the yield of the ceftiofur sodium obtained after the processing of the example 1 is 89.00 percent, the purity is 98.61 percent, and the purity is improved by 2.3 percent.
Example 2
The recrystallization method of ceftiofur sodium specifically comprises the following steps:
(1) Adding 30ml of water and 80ml of ethanol into a 500ml three-neck flask;
(2) Stirring and heating to 40 ℃, adding 15g of ceftiofur sodium raw material, and stirring for 25min under the condition of heat preservation to obtain a mixed solution;
(3) Filtering the mixed solution for the first time by adopting a sand core funnel 0.2 mu m filter membrane;
(4) Adding 0.5g of activated carbon into the mixed solution, and fully stirring;
(5) A buchner funnel filters out most of the activated carbon;
(6) Filtering the mixed solution for the second time by adopting a sand core funnel 0.2 mu m filter membrane to obtain filtrate;
(7) Keeping the filtrate at 25 ℃, dropwise adding 100ml of crystallization acetone at the speed of 2 seconds/drop, stopping dropwise adding when crystals are separated out, and growing the crystals for 30min;
(8) After the crystallization is finished, continuously dripping 500ml of crystallization acetone;
(9) Washing the material with 200ml of washing material acetone, and drying at 50 ℃ to obtain ceftiofur sodium.
The purity of the ceftiofur sodium raw material is 95%, the yield of the ceftiofur sodium obtained after the processing of the example 2 is 88.63%, the purity is 98.25%, and the purity is improved by 3.42%.
Example 3
The recrystallization method of ceftiofur sodium specifically comprises the following steps:
(1) 30ml of water and 80ml of methanol are added into a 500ml three-neck flask;
(2) Stirring and heating to 30 ℃, adding 15g of ceftiofur sodium raw material, and stirring for 20min under the condition of heat preservation to obtain a mixed solution;
(3) Filtering the mixed solution for the first time by adopting a sand core funnel 0.2 mu m filter membrane;
(4) Adding 0.5g of active carbon into the mixed solution, and fully stirring;
(5) A buchner funnel filters out most of the activated carbon;
(6) Filtering the mixed solution for the second time by adopting a sand core funnel 0.2 mu m filter membrane to obtain filtrate;
(7) Maintaining the filtrate at 25 deg.C, and dripping 100ml of crystallizing acetone at a speed of 1 s/drop, stopping dripping when crystal is separated out, and growing crystal for 30min;
(8) After the crystallization is finished, continuously dripping 500ml of crystallization acetone;
(9) Washing the material with 200ml of washing material acetone, and drying at 50 ℃ to obtain ceftiofur sodium.
The purity of the ceftiofur sodium raw material is 95.37%, the yield obtained by the treatment of the example 3 is 90.10%, the purity is 98.37%, and the purity is improved by 3.0%.
Example 4
The recrystallization method of ceftiofur sodium specifically comprises the following steps:
(1) 30ml of water and 80ml of methanol are added into a 500ml three-neck flask;
(2) Stirring and heating to 40 ℃, adding 15g of ceftiofur sodium raw material, and stirring for 20min under the condition of heat preservation to obtain a mixed solution;
(3) Filtering the mixed solution for the first time by adopting a sand core funnel 0.2 mu m filter membrane;
(4) Adding 1.5g of activated carbon into the mixed solution, and fully stirring;
(5) Most of the activated carbon was filtered off with a buchner funnel;
(6) Filtering the mixed solution for the second time by adopting a sand core funnel 0.2 mu m filter membrane to obtain filtrate;
(7) Maintaining the filtrate at 40 deg.C, and dripping 100ml of crystallizing acetone at a speed of 1 s/drop, stopping dripping when crystal is separated out, and growing crystal for 30min;
(8) After the crystallization is finished, continuously dripping 500ml of crystallization acetone;
(9) Washing the material with 200ml of washing material acetone, and drying at 50 ℃ to obtain ceftiofur sodium.
The purity of the ceftiofur sodium raw material is 95.65%, the yield obtained by the treatment of the example 4 is 89.51%, the purity is 98.38%, and the purity is improved by 2.73%.
Example 5
The recrystallization method of ceftiofur sodium specifically comprises the following steps:
(1) 30ml of water and 67.5ml of methanol are added into a 500ml three-neck flask;
(2) Stirring and heating to 30 ℃, adding 15g of ceftiofur sodium raw material, and stirring for 20min under the condition of heat preservation to obtain a mixed solution;
(3) Filtering the mixed solution for the first time by adopting a sand core funnel 0.5 mu m filter membrane;
(4) Adding 1g of activated carbon into the mixed solution, and fully stirring;
(5) A buchner funnel filters out most of the activated carbon;
(6) Filtering the mixed solution for the second time by adopting a sand core funnel 0.2 mu m filter membrane to obtain filtrate;
(7) Maintaining the filtrate at 30 deg.C, and dripping 100ml of crystallizing acetone at 2 s/drop speed, stopping dripping when crystal is separated out, and growing crystal for 30min;
(8) After the crystallization is finished, continuously dripping 650ml of crystallization acetone;
(9) Washing the material with 300ml of washing material acetone, and drying at 50 ℃ to obtain ceftiofur sodium.
The purity of the ceftiofur sodium raw material is 96.24%, the yield obtained by the treatment of the example 5 is 91.03%, the purity is 98.65%, and the purity is improved by 2.41%.
Example 6
The recrystallization method of ceftiofur sodium specifically comprises the following steps:
(1) Adding 15ml of water and 90ml of methanol into a 500ml three-neck flask;
(2) Stirring and heating to 30 ℃, adding 15g of ceftiofur sodium raw material, and stirring for 20min under the condition of heat preservation to obtain a mixed solution;
(3) Filtering the mixed solution for the first time by adopting a sand core funnel 0.2 mu m filter membrane;
(4) Adding 0.5g of activated carbon into the mixed solution, and fully stirring;
(5) A buchner funnel filters out most of the activated carbon;
(6) Filtering the mixed solution for the second time by adopting a sand core funnel 0.2 mu m filter membrane to obtain filtrate;
(7) Keeping the filtrate at 25 ℃, dropwise adding 100ml of crystallization acetone at the speed of 2 seconds per drop, stopping dropwise adding when crystals are separated out, and growing the crystals for 45min;
(8) After the crystallization is finished, continuously dripping 500ml of crystallization acetone;
(9) Washing the material with 450ml of washing material acetone, and drying at 60 ℃ to obtain ceftiofur sodium.
The purity of the ceftiofur sodium raw material is 95.45 percent, the yield obtained by the treatment of the example 6 is 92.25 percent, the purity is 98.45 percent, and the purity is improved by 3.0 percent.
Example 7
The recrystallization method of ceftiofur sodium specifically comprises the following steps:
(1) Adding 45ml of water and 45ml of methanol into a 500ml three-neck flask;
(2) Stirring and heating to 30 ℃, adding 15g of ceftiofur sodium raw material, and stirring for 20min under the condition of heat preservation to obtain a mixed solution;
(3) Filtering the mixed solution for the first time by adopting a sand core funnel 0.2 mu m filter membrane;
(4) Adding 0.15g of activated carbon into the mixed solution, and fully stirring;
(5) A buchner funnel filters out most of the activated carbon;
(6) Filtering the mixed solution for the second time by adopting a sand core funnel 0.2 mu m filter membrane to obtain filtrate;
(7) Maintaining the filtrate at 25 deg.C, and dripping 100ml of crystallization acetone at a speed of 1 s/drop, stopping dripping when crystal is separated out, and growing crystal for 60min;
(8) After the crystallization is finished, continuously dropwise adding 350ml of crystallization acetone;
(9) Washing the material with 150ml of washing material acetone, and drying at 40 ℃ to obtain ceftiofur sodium.
The purity of the ceftiofur sodium raw material is 95.25%, the yield obtained by processing the ceftiofur sodium raw material in example 7 is 91%, the purity is 98.30%, and the purity is improved by 3.20%.
Of course, the foregoing is only a preferred embodiment of the invention and should not be taken as limiting the scope of the embodiments of the invention. The present invention is not limited to the above examples, and equivalent changes and modifications made by those skilled in the art within the spirit of the present invention should be included in the scope of the present invention.
Claims (8)
1. A recrystallization method of ceftiofur sodium is characterized in that: the method specifically comprises the following steps:
(1) Adding a solvent to water;
(2) Heating to 20-40 ℃, adding the ceftiofur sodium raw material, and stirring while keeping the temperature until the mixture is clear to obtain a mixed solution;
(3) Filtering the mixed solution for the first time;
(4) Adding active carbon into the mixed solution, and stirring;
(5) Filtering out the active carbon;
(6) Filtering the mixed solution for the second time to obtain filtrate;
(7) Keeping the filtrate at 20-40 ℃, dropwise adding crystallization acetone, stopping dropwise adding when crystals are separated out, and growing the crystals for 30-60 min;
(8) After the crystallization is finished, continuously dropwise adding the residual crystallization acetone;
(9) Washing the material with acetone, and drying to obtain ceftiofur sodium.
2. A method for recrystallizing ceftiofur sodium according to claim 1, wherein: the ceftiofur sodium raw material is ceftiofur sodium with changed properties or the purity of which is lower than 98 percent.
3. A method for recrystallizing ceftiofur sodium according to claim 1, wherein: the solvent is methanol or ethanol.
4. A method for recrystallizing ceftiofur sodium according to claim 1, wherein: the mass ratio of the ceftiofur sodium raw material to the solvent to the water to the crystallization acetone to the washing material acetone is 1 (3-6) to (1-3) to (30-50) to (10-30).
5. A method for recrystallizing ceftiofur sodium according to claim 1, wherein: the primary filtration and the secondary filtration are both carried out by adopting a sand core funnel, and the precision of the filter membrane is 0.2-0.5 mu m.
6. A method for recrystallizing ceftiofur sodium according to claim 1, wherein: the speed of dripping the crystallization acetone in the step (7) is 1-2 seconds per drop.
7. The method for recrystallizing ceftiofur sodium according to claim 1, wherein: the drying temperature of the step (9) is 40-60 ℃.
8. A method for recrystallizing ceftiofur sodium according to claim 1, wherein: in the step (4), the mass ratio of the ceftiofur sodium raw material to the active carbon is 1: (0.01-0.1).
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| CN104530085A (en) * | 2014-12-07 | 2015-04-22 | 河南领先科技药业有限公司 | New preparation method of ceftiofur sodium |
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