CN103601739A - Cefoxitin sodium compound and preparation method thereof - Google Patents
Cefoxitin sodium compound and preparation method thereof Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/57—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with a further substituent in position 7, e.g. cephamycines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
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- C07D501/12—Separation; Purification
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Abstract
The invention relates to the field of medicines, and particularly relates to a cefoxitin sodium crystal compound and a preparation method thereof. The structural formula of the cefoxitin sodium crystal compound is shown as formula (I). The cefoxitin sodium crystal compound has high purity, is not easy to absorb water, has good stability, and is safe and reliable for clinical application.
Description
Technical field
The present invention relates to field of medicaments, specifically, relate to a kind of cefoxitin sodium crystalline compounds and preparation method thereof.
Background technology
Cefoxitin (cefoxitin); chemistry (6R by name; 7S-3-carbamyl yloxymethyl-7-methoxyl group-8-oxo-7-2[(2-thienyl) kharophen]-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-formic acid; by U.S. Merk company, developed, the cephamycin C that the cefoxitin that goes on the market for 1994 is produced by streptomycete is through the semi-synthetic class new antibiotic making.Cefoxitin by with one or more penicillin-binding proteins (PBPs) combination, the cell walls biosynthesizing of the mitotically active cell of anti-bacteria, thus play anti-microbial effect.Cefoxitin sodium all has stronger anti-microbial effect to hemophilus influenzae, klebsiella bacillus, Escherichia coli, morganella morganii, Mirabilis jalapa mycetozoan, providencia rettgeri and gonococcal sensitive strain in gram-negative bacteria.
In order further to improve the stability of cefoxitin sodium, for cefoxitin sodium, a lot of patents and document are disclosed:
Document " cefoxitin sodium stability improvement " (Wei Qingjie, Hebei chemical industry, 2011) discloses a kind of synthetic and crystallization method of cefoxitin sodium, thereby the look level of cefoxitin sodium is improved.
Document " improvement of cefoxitin sodium crystallization processes " (Wei Qingjie, Chemical Industry in Guangzhou, 2011) by the screening to salt forming agent and organic solvent, the crystallization processes of cefoxitin sodium is optimized, obtained the cefoxitin sodium product that crystal formation is good, quality is high, cost is low, yield is greater than 95%.Improved novel process adopts acetate trihydrate sodium salt-forming agent, acetone, methyl alcohol are made solvent, and the cefoxitin sodium of doing all has a clear superiority in more former techniques of each side such as quality and stability, crystal formation and product granularities, simple to operate, with low cost, be more suitable for suitability for industrialized production.
The preparation method that patent ZL200910162868.0 discloses a kind of cefoxitin sodium comprises the following steps: take and go acetyl 7-ACA as raw material, introduce thiophene acetyl, must remove acetyl thiophene acid I; On 3, introduce carboxamide methoxyl group, obtain intermediate (6R, 7S)-3-carboxamide methoxyl group-7-[2-(2-thienyl) kharophen]-8-oxo-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-formic acid II; Intermediate II is reacted with lithium methoxide, on 7, introduces methoxyl group, obtains cefoxitin acid III; The ethanolic soln of sodium salt is added in the organic solvent that is dissolved with cefoxitin acid, through suction filtration, the dry cefoxitin sodium IV that to obtain.The purity of the cefoxitin sodium that the method obtains is still not bery desirable.
Patent application 201110258682.2,201210514291.7,201310268592.0 discloses respectively three kinds of cefoxitin sodium crystalline compounds, and the X-ray powder diffraction collection of illustrative plates of crystalline compounds disclosed respectively, though claim the stability that has improved cefoxitin sodium crystal, the water absorbability of the cefoxitin sodium crystal of it not being prepared detects.
The present invention carries out after a large amount of research cefoxitin sodium, has made a kind of new cefoxitin sodium compound, and this crystal has satisfactory stability, and its bibulous shortcoming improves, and clinical application is convenient and reliable.
Summary of the invention
Primary goal of the invention of the present invention is to have proposed a kind of cefoxitin sodium crystalline compounds;
The second goal of the invention of the present invention has been to propose the preparation method of this cefoxitin sodium crystalline compounds.
In order to realize object of the present invention, the technical scheme of employing is:
A cefoxitin sodium compound, the structural formula of described cefoxitin sodium crystalline compounds as shown in the formula (I):
The X-ray powder diffraction pattern that described cefoxitin sodium crystalline compounds use Cu-K alpha-ray measures as shown in Figure 1.
The main particle diameter that the main granularity of crystal of described cefoxitin sodium crystalline compounds is this crystal is 750～1150 μ m, and Tile Width is 575～1450 μ m; Preferred main particle diameter is 950～1050 μ m, and Tile Width is 675～1225 μ m.
The preparation method who the invention still further relates to this cefoxitin sodium crystalline compounds, comprises the following steps:
(1) prepare the cefoxitin sodium crude product saturated aqueous solution of 60～80 ℃;
(2) mixed organic solvents of preparation acetone, ether and acetonitrile, the volume of mixed organic solvents is 3～6 times of cefoxitin sodium crude product saturated aqueous solution;
(3) organic solvent is cooled to 0～5 ℃, in frequency, be under 20～25KHz, the output rating sound field that is 40～80W, in organic solvent, at the uniform velocity add cefoxitin sodium crude product saturated aqueous solution while stirring, adding rear continuation stirs and lowers the temperature, after being cooled to 0～5 ℃, stop stirring standing growing the grain 2～6 hours; Obtain filtering after crystal, with absolute ethanol washing, vacuum-drying 2～8 hours, obtains cefoxitin sodium crystalline compounds.
Wherein: in mixed organic solvents, the volume ratio of acetone, ether and acetonitrile is 2～4:1～2:1, preferably 2～3:1～2:1; To adding the stirring velocity of cefoxitin sodium crude product saturated aqueous solution in organic solvent, it is 240～480 revs/min; Stirring velocity after cefoxitin sodium crude product saturated aqueous solution adds is 120～240 revs/min; The speed that adds of the saturated ethanol solution of cefoxitin sodium crude product is: v=M/10～M/5, and the volume that wherein M is organic mixed solvent, unit is for rising, and the unit of speed v is l/h; Cooling rate after cefoxitin sodium crude product saturated aqueous solution adds is 1～6 ℃/h.
Below technical scheme of the present invention is made further explanation.
Cephalosporins is a class wide spectrum semisynthetic antibiotics, has that has a broad antifungal spectrum, anti-microbial effect are strong, penicillin resistant enzyme, clinical efficacy is high, toxicity is low, anaphylaxis is compared with advantages such as penicillin are rare, is widely used clinically.By and multiple cynnematin have and draw moistly, after moisture absorption, can cause the variation of the physico-chemical properties such as caking, mobility decline, deliquescence, crystal formation change, thereby affect the interior qualities such as product stability, validity, security.And according to the literature, many microbiotic are stable under drying regime, but will decompose after making moist.Therefore, water absorbability has very important impact for the stability of cynnematin.According to " Chinese Pharmacopoeia version in 2005 ", the water absorbability of cefoxitin sodium is described as to " water absorbability is strong ", therefore, if can reduce the water absorbability of cefoxitin sodium, the stability for cefoxitin sodium has very important meaning.Meanwhile, bibulous medicine needs strictly to control the relative humidity between packing in preparation production process, is no more than critical relative humidity, thereby guarantees quality product and stability.If be difficult for moisture absorption, the production of convenient preparation guarantees stability simultaneously.
A kind of cefoxitin sodium crystalline compounds of the present invention, its proterties is white crystalline powder, the X-ray powder diffraction pattern that use Cu-K alpha-ray measures is as shown in Figure 1.By to its hygroscopic research, the discovery that contriver is pleasantly surprised, its water absorbability of compound of the present invention is significantly less than existing crystalline compounds.Thereby illustrate that cefoxitin sodium crystalline compounds of the present invention is more stable, and more adapt to the preparation of preparation.
The purity to 99.98% of cefoxitin sodium crystalline compounds of the present invention, its structure is confirmed through proton nmr spectra.According to Chinese Pharmacopoeia version in 2005, two appendix VIII P detect the residual solvent in cefoxitin sodium of the present invention, wherein containing ether 0.009%, acetonitrile 0.001%, acetone 0.01%.Confirm crystallization method solvent denier of the present invention, clinical application is safe and reliable.
Cefoxitin sodium crystalline compounds of the present invention is measured through sem observation and particle size analyzer, and the main particle diameter that the main granularity of crystal is this crystal is 750～1150 μ m, and Tile Width is 575～1450 μ m; Preferred main particle diameter is 950～1050 μ m, and Tile Width is 675～1225 μ m.The size-grade distribution of cefoxitin sodium crystalline compounds of the present invention is moderate, is suitable for separation and collection, thereby is applicable to large-scale industrialization preparation, improves yield, can reach 98.7%.The preparation method of cefoxitin sodium crystalline compounds of the present invention is simple, and purity is high, and yield is high, most suitable large-scale industrial production.
Cefoxitin sodium crystalline compounds of the present invention can be used for the multiple formulation that preparation is used clinically, as freeze-dried powder, aseptic powder injection, liquid drugs injection etc.And confirm through stability test, the preparation that adopts cefoxitin sodium crystalline compounds of the present invention to prepare, its stability, higher than prior art, is very suitable for clinical application.
Accompanying drawing explanation:
Fig. 1 is the X-ray powder diffraction pattern that the cefoxitin sodium crystalline compounds for preparing of embodiment 1 is used Cu-K alpha-ray to measure.
The specific embodiment of the present invention only limits to further explain and explanation the present invention, not to Composition of contents restriction of the present invention.Embodiment
Embodiment 1: the preparation of cefoxitin sodium crystalline compounds
1. prepare the cefoxitin sodium crude product saturated aqueous solution 5L of 65 ℃;
2. prepare the mixed organic solvents 15L of acetone, ether and acetonitrile; In mixed organic solvents, the volume ratio of acetone, ether and acetonitrile is 3:2:1;
3. organic solvent being cooled to 0 ℃, is under 25KHz, the output rating sound field that is 40W in frequency, at the uniform velocity adds cefoxitin sodium crude product saturated aqueous solution while stirring in organic solvent, and adding speed is 3 ls/h; Stirring velocity is 480 revs/min; Add rear continuation and stir and lower the temperature, stirring velocity is 240 revs/min; After being cooled to 0～5 ℃, stop stirring, cooling rate is 1 ℃/h.Standing growing the grain 4 hours; Obtain filtering after crystal, with absolute ethanol washing, vacuum-drying 6 hours, obtains cefoxitin sodium crystalline compounds.
The X-ray powder diffraction pattern that use Cu-K alpha-ray measures as shown in Figure 1.Through sem observation and particle size analyzer, measure, the main particle diameter that the main granularity of crystal is this crystal is 950～1050 μ m, and Tile Width is 675～1225 μ m; Yield is 98.7%, and purity is 99.98%.
Embodiment 2: the preparation of cefoxitin sodium crystalline compounds
1. prepare the cefoxitin sodium crude product saturated aqueous solution 5L of 60 ℃;
2. prepare the mixed organic solvents 30L of acetone, ether and acetonitrile; In mixed organic solvents, the volume ratio of acetone, ether and acetonitrile is 2:1:1;
3. organic solvent being cooled to 5 ℃, is under 25KHz, the output rating sound field that is 80W in frequency, at the uniform velocity adds cefoxitin sodium crude product saturated aqueous solution while stirring in organic solvent, and adding speed is 6 ls/h; Stirring velocity is 480 revs/min; Add rear continuation and stir and lower the temperature, cooling rate is 2 ℃/h, and stirring velocity is 120 revs/min; After being cooled to 1 ℃, stop stirring; Standing growing the grain 6 hours; Obtain filtering after crystal, with absolute ethanol washing, vacuum-drying 6 hours, obtains cefoxitin sodium crystalline compounds.
The X-ray powder diffraction pattern that use Cu-K alpha-ray measures as shown in Figure 1.Through sem observation and particle size analyzer, measure, the main particle diameter that the main granularity of crystal is this crystal is 950～1050 μ m, and Tile Width is 675～1225 μ m; Yield is 98.6%, and purity is 99.98%.
Embodiment 3: the preparation of cefoxitin sodium crystalline compounds
1. prepare the cefoxitin sodium crude product saturated aqueous solution 5L of 68 ℃;
2. prepare the mixed organic solvents 20L of acetone, ether and acetonitrile, in mixed organic solvents, the volume ratio of acetone, ether and acetonitrile is 3:1:1;
3. organic solvent being cooled to 2 ℃, is under 25KHz, the output rating sound field that is 60W in frequency, at the uniform velocity adds cefoxitin sodium crude product saturated aqueous solution while stirring in organic solvent, and adding speed is 2 ls/h; Stirring velocity is 240 revs/min; Add rear continuation and stir and lower the temperature, cooling rate is 2 ℃/h; Stirring velocity is 120 revs/min; After being cooled to 1 ℃, stop stirring; Standing growing the grain 4 hours; Obtain filtering after crystal, with absolute ethanol washing, vacuum-drying 6 hours, obtains cefoxitin sodium crystalline compounds.
The X-ray powder diffraction pattern that use Cu-K alpha-ray measures as shown in Figure 1.Through sem observation and particle size analyzer, measure, the main particle diameter that the main granularity of crystal is this crystal is 950～1050 μ m, and Tile Width is 675～1225 μ m; Yield is 98.7%, and purity is 99.98%.
Experimental example 1:
1. high temperature test
Get three batches 101 of the cefoxitin sodium crystalline compounds, 102,103 that embodiment 1 prepares, simulation listing packing, put in sealing clean container, at 40 ± 2 ℃ of temperature, place 10 days, in the 5th day and sampling in the 10th day, by stability high spot reviews project, detect test-results and comparison in 0 day.
2. high humidity test
Get three batches 101 of the cefoxitin sodium crystalline compounds, 102,103 that embodiment 1 prepares, simulation listing packing, put in sealing clean container, under the condition of 25 ± 2 ℃ of relative humidity 90% ± 5%, place 10 days, in the 5th day and sampling in the 10th day, by stability high spot reviews project, detect test-results and comparison in 0 day.
3. strong illumination test
Get three batches 101 of the western fourth sodium crystal of the spore compounds, 102,103 that embodiment 1 prepares, simulation listing packing, put in sealing clean container, be placed under the condition that illumination is 4500lx and place 10 days, in the 5th day and sampling in the 10th day, by stability high spot reviews project, detect result and comparison in 0 day.
Influence factor test-results is as shown in table 1.
Table 1:
Note: this content is moisture free dry content.
Result shows: the cefoxitin sodium crystalline compounds that the present invention prepares, and its stability is good, and under high temperature, high humidity, intense light irradiation condition, all retention is stable.Cefoxitin sodium crystalline compounds prepared by other embodiment of the present invention carries out influence factor experiment, has obtained identical experimental result.
Experimental example 2: accelerate experiment
Get three batches 201,202,203 of cefoxitin sodium crystalline compounds of embodiment 2 gained, simulation listing packing, put in sealing clean container, under 42 ℃, 80%RH condition, place 6 months, at duration of test respectively at 1,2,3,6 sampling at the end of month once, each stability high spot reviews project is tested.Test-results is as shown in table 2.
Table 2:
Note: this content is moisture free dry content.
Result shows: the cefoxitin sodium crystalline compounds that the present invention prepares, known through accelerated test result, its stability is good.Cefoxitin sodium crystalline compounds prepared by other embodiment of the present invention accelerates experiment, has obtained identical experimental result.
Experimental example 3: test of long duration
Get three batches 301,302,303 of cefoxitin sodium crystalline compounds of embodiment 3 gained, simulation listing packing, put in sealing clean container, under 20 ℃ ± 2 ℃ conditions of temperature, place 18 months, at duration of test respectively at the 3rd, 6,9,12,18 samplings at the end of month once, each Interventions Requested are tested.Test-results is as shown in table 3:
Table 3:
Note: this content is moisture free dry content.
Result shows: the cefoxitin sodium crystalline compounds that the present invention prepares, and known through long-term test results, its stability is good, and all retention is stable.Cefoxitin sodium crystalline compounds prepared by other embodiment of the present invention carries out long-term experiment, has obtained identical experimental result.
Experimental example 4: moisture absorption comparison test
1. instrument and reagent
1.1 instrument
PL203 electronic balance, LRH-250-S fixed temperature and humidity incubator, HH-400SD testing chamber for medicine stability;
1.2 reagent
Comparative example 1: adopt disclosed method in document " improvement of cefoxitin sodium crystallization processes " (Wei Qingjie, Chemical Industry in Guangzhou, 2011) to prepare cefoxitin sodium crystal;
Comparative example 2: adopt the method in patent application 201210514291.7 embodiment 1 to prepare cefoxitin sodium crystal;
Comparative example 3: adopt the method in patent application 201310268592.0 embodiment 1 to prepare cefoxitin sodium crystal;
2 methods
Get the glass moisture eliminator (for guaranteeing that salts solution is saturated, moisture eliminator bottom should have excessive salt to exist) that bottom fills salt supersaturated solution, the built-in weighing bottle of moisture eliminator is placed 48h to constant humidity in thermostat container.The about 2g of sample thief, puts in weighing bottle, accurately weighed, bottle cap is opened, put into moisture eliminator top, by differing temps requirement, put in 25 ℃ of fixed temperature and humidity incubators or 20 ℃ of stability test casees and preserve, 3 parts of parallel runnings, weigh respectively at different time, calculate the rate of moisture absorption of different time.
Calculation formula: rate of moisture absorption=(medicinal powder weight-moisture absorption prodrug grain weight amount after moisture absorption)/moisture absorption prodrug grain weight amount * 100%.
Table 4: the rate of moisture absorption recording at different time
Known according to above-mentioned experiment, the water absorbability of cefoxitin sodium crystalline compounds prepared by the present invention is variant compared with prior art, lower than prior art, points out the stability of this compound higher than prior art.
Experimental example 5: stability contrast experiment
Prepare in accordance with the following methods comparative example:
Comparative example 1: adopt disclosed method in document " improvement of cefoxitin sodium crystallization processes " (Wei Qingjie, Chemical Industry in Guangzhou, 2011) to prepare cefoxitin sodium crystal;
Comparative example 2: adopt the method in patent ZL201110258682.2 embodiment 1 to prepare cefoxitin sodium crystal;
Comparative example 3: adopt the method in patent application 201210514291.7 embodiment 1 to prepare cefoxitin sodium crystal;
By above-mentioned preparation simulation listing packing, put in sealing clean container, under 42 ℃, 80%RH condition, place 6 months, at duration of test respectively at 1,2,3,6 sampling at the end of month once, each stability high spot reviews project is tested.Test-results is as shown in table 5.
Table 5:
Note: this content is moisture free dry content.
Result shows: the cefoxitin sodium crystalline compounds that the present invention prepares, known through comparative test result, its stability is better than prior art.
Claims (7)
1. a cefoxitin sodium crystalline compounds, is characterized in that, the structural formula of described cefoxitin sodium crystalline compounds as shown in the formula (I):
The X-ray powder diffraction pattern that described cefoxitin sodium crystalline compounds use Cu-K alpha-ray measures as shown in Figure 1.
2. cefoxitin sodium crystalline compounds according to claim 1, is characterized in that, the main particle diameter that the main granularity of crystal of described cefoxitin sodium compound is this crystal is 750～1150 μ m, and Tile Width is 575～1450 μ m; Preferred main particle diameter is 950～1050 μ m, and Tile Width is 675～1225 μ m.
3. a preparation method for cefoxitin sodium crystalline compounds as claimed in claim 1, is characterized in that, comprises the following steps:
(1) prepare the cefoxitin sodium crude product saturated aqueous solution of 60～80 ℃;
(2) mixed organic solvents of preparation acetone, ether and acetonitrile, the volume of mixed organic solvents is 3～6 times of cefoxitin sodium crude product saturated aqueous solution;
(3) organic solvent is cooled to 0～5 ℃, in frequency, be under 20～25KHz, the output rating sound field that is 40～80W, in organic solvent, at the uniform velocity add cefoxitin sodium crude product saturated aqueous solution while stirring, adding rear continuation stirs and lowers the temperature, after being cooled to 0～5 ℃, stop stirring standing growing the grain 2～6 hours; Obtain filtering after crystal, with absolute ethanol washing, vacuum-drying 2～8 hours, obtains cefoxitin sodium crystalline compounds.
4. the preparation method of cefoxitin sodium crystalline compounds according to claim 3, is characterized in that, in mixed organic solvents, the volume ratio of acetone, ether and acetonitrile is 2～4:1～2:1, preferably 2～3:1～2:1.
5. the preparation method of cefoxitin sodium crystalline compounds according to claim 3, is characterized in that, to adding the stirring velocity of cefoxitin sodium crude product saturated aqueous solution in organic solvent, is 240～480 revs/min; Stirring velocity after cefoxitin sodium crude product saturated aqueous solution adds is 120～240 revs/min.
6. the preparation method of cefoxitin sodium crystalline compounds according to claim 3, it is characterized in that, the speed that adds of the saturated ethanol solution of cefoxitin sodium crude product is: v=M/10～M/5, the volume that wherein M is organic mixed solvent, unit is for rising, and the unit of speed v is l/h.
7. the preparation method of cefoxitin sodium crystalline compounds according to claim 3, is characterized in that, the cooling rate after cefoxitin sodium crude product saturated aqueous solution adds is 1～6 ℃/h.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108218894A (en) * | 2018-01-04 | 2018-06-29 | 北京红太阳药业有限公司 | A kind of cefoxitin sodium crystal-form compound |
| CN109096310A (en) * | 2017-06-20 | 2018-12-28 | 梁怡 | A kind of 1/4 water Cefoxitin sodium compound |
| CN109134509A (en) * | 2017-06-16 | 2019-01-04 | 李双喜 | A kind of 1/5 water Cefoxitin sodium compound |
| CN114773362A (en) * | 2022-06-15 | 2022-07-22 | 上海欣峰制药有限公司 | Cefoxitin sodium compound and preparation method thereof |
| CN114853786A (en) * | 2022-05-07 | 2022-08-05 | 华北制药河北华民药业有限责任公司 | Preparation method of cefoxitin sodium powder |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102391290B (en) * | 2011-05-31 | 2013-01-02 | 深圳信立泰药业股份有限公司 | Cefoxitin anhydrous crystal, preparation method thereof and method for preparing cefoxitin sodium by using same |
| CN102358744B (en) * | 2011-09-02 | 2013-11-06 | 山东罗欣药业股份有限公司 | Cefoxitin sodium crystal compound and cefoxitin sodium composition powder injection |
| CN102942577B (en) * | 2012-12-04 | 2015-03-25 | 罗诚 | Cefoxitin sodium compound-containing pharmaceutical composition |
| CN103304582B (en) * | 2013-06-28 | 2015-02-11 | 四川省惠达药业有限公司 | Cefoxitin sodium compound, preparation method and pharmaceutical composition thereof |
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2013
- 2013-11-26 CN CN201310611327.8A patent/CN103601739A/en active Pending
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- 2014-02-28 CN CN201410071491.9A patent/CN103804397B/en active Active
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109134509A (en) * | 2017-06-16 | 2019-01-04 | 李双喜 | A kind of 1/5 water Cefoxitin sodium compound |
| CN109096310A (en) * | 2017-06-20 | 2018-12-28 | 梁怡 | A kind of 1/4 water Cefoxitin sodium compound |
| CN108218894A (en) * | 2018-01-04 | 2018-06-29 | 北京红太阳药业有限公司 | A kind of cefoxitin sodium crystal-form compound |
| CN114853786A (en) * | 2022-05-07 | 2022-08-05 | 华北制药河北华民药业有限责任公司 | Preparation method of cefoxitin sodium powder |
| CN114853786B (en) * | 2022-05-07 | 2024-01-12 | 华北制药河北华民药业有限责任公司 | Preparation method of cefoxitin sodium powder |
| CN114773362A (en) * | 2022-06-15 | 2022-07-22 | 上海欣峰制药有限公司 | Cefoxitin sodium compound and preparation method thereof |
| CN114773362B (en) * | 2022-06-15 | 2023-12-29 | 上海欣峰制药有限公司 | Cefoxitin sodium compound and preparation method thereof |
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| CN103804397A (en) | 2014-05-21 |
| CN103804397B (en) | 2015-02-18 |
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Application publication date: 20140226 |