CN102702232A - Method for preparation of fine cefamandole nafate - Google Patents
Method for preparation of fine cefamandole nafate Download PDFInfo
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- CN102702232A CN102702232A CN2012101266427A CN201210126642A CN102702232A CN 102702232 A CN102702232 A CN 102702232A CN 2012101266427 A CN2012101266427 A CN 2012101266427A CN 201210126642 A CN201210126642 A CN 201210126642A CN 102702232 A CN102702232 A CN 102702232A
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- formylcefamole
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Abstract
The invention discloses a method for preparation of fine cefamandole nafate, comprising the steps of mixing crude cefamandole nafate with organic sodium salt, salt-free water and organic solvent (1); controlling pH value of the reaction system to 5.5-7.5 and reaction temperature to 5-15 DEG C; adding active carbon and then filtering to obtain filtrate; mixing the filtrate with organic solvent (2) and separating out crystal to obtain the cefamandole nafate. The method for preparation of the fine cefamandole nafate provided by the invention overcomes the disadvantages of prior preparation method, and has the advantages of simple operation, short preparation period, easy quality control, good product stability and important application value.
Description
Technical field
The present invention relates to a kind of method of refining Sodium O-formylcefamole.
Background technology
Sodium O-formylcefamole (Cefamandole Nafate) is the semisynthetic cynnematin of the s-generation of Lilly Co., Eli.'s development in 1972; Be applied to clinical in 1978; Commodity are called Mandol; Chemistry 7-D-(2-methanoyl phenylacetamide) by name-3-[(1-methyl isophthalic acid H-tetrazolium-5 base) thiomethyl]-3-cephem-4-carboxylic acid sodium salt, molecular weight is 512.50, its structural formula is suc as formula shown in the I:
Formula I
The compound method lot of domestic and foreign periodical of Sodium O-formylcefamole all has patents such as report: US4351947, EP0432297, CN101475580A, and these methods all can effectively prepare Sodium O-formylcefamole, but the purity of title product is not high, colour-difference, and content is low.The research and development patent that the Sodium O-formylcefamole process for refining is also arranged for this reason: CN102093392, CN10178703 etc.Reasons such as these method complicated operations, post-processed are loaded down with trivial details are receiving than limitations in big production.
Summary of the invention
The method that the purpose of this invention is to provide a kind of refining Sodium O-formylcefamole.
The method of refining Sodium O-formylcefamole provided by the invention; Comprise the steps: with the Sodium O-formylcefamole bullion in no salt solution, organic solvent 1. with organic sodium salt mixing after; The pH value of control reaction system adds active carbon filtration for after 5.5-7.5 and temperature of reaction be 5-15 ℃, with 2. mixing of gained filtrating and organic solvent; Separate out crystal, obtain said Sodium O-formylcefamole.
In the aforesaid method, said organic solvent 1. with organic solvent 2. all be selected from methyl alcohol, ethanol, acetone, THF, Virahol and acetonitrile at least a, and said organic solvent is 1. 2. different with said organic solvent; The 1. preferred acetone of said organic solvent; The 2. preferred Virahol of said organic solvent.
Said organic sodium salt is selected from least a of sodium acetate, Sodium isooctanoate and Sodium Benzoate, preferred Sodium isooctanoate.
The 0.5-5 that said no brinish consumption is said Sodium O-formylcefamole bullion quality times,, preferred 1-1.5 times, more preferably 1.4 times.
Said organic solvent consumption 1. is 1.2-10.0 a times of said Sodium O-formylcefamole quality.
The consumption of said organic sodium salt is 0.1-0.55 a times of said Sodium O-formylcefamole mole dosage.
Said organic solvent consumption 2. is 10-50 a times of said Sodium O-formylcefamole quality.
Said with gained filtrating and organic solvent 2. in the mixing step, temperature is 0-35 ℃, preferred 15-25 ℃.
The method of said refining Sodium O-formylcefamole, also comprise the steps: said separate out the crystal step after, the gained reacting liquid filtering is got deposition, wash successively and dry.Wherein, in the said washing step, solvent for use be said organic solvent 2.; In the said drying step, temperature is 35-50 ℃, preferred 45 ℃.
The method of refining Sodium O-formylcefamole provided by the invention has overcome existing preparing method's shortcoming, and is easy and simple to handle, and the cycle is short, and easy to control the quality, product stability is good, has important use and is worth.
Description of drawings
Fig. 1 is the infrared figure of Sodium O-formylcefamole standard (No. 125 collection of illustrative plates of spectrum spectra collection).
Fig. 2 is the infrared spectrogram of embodiment 1 preparation gained Sodium O-formylcefamole.
Fig. 3 is the infared spectrum of embodiment 2 preparation gained Sodium O-formylcefamoles.
Embodiment
Below in conjunction with specific embodiment the present invention is done further elaboration, but the present invention is not limited to following examples.Said method is ordinary method if no special instructions.Said raw material all can get from open commercial sources if no special instructions.
In the 500mL four-hole boiling flask, add Sodium O-formylcefamole bullion (purity is 97.6%) 35.0 grams, no salt solution 50g, organic solvent 1. acetone 245g and Sodium isooctanoate 1.5g, be stirred to and dissolve clearly, controlling the final pH value is 5.5, behind 15 ℃ of the controlled temperature; Add activated carbon 1.5g, stirred 0.5 hour, suction filtration changes gained filtrating over to the 2000mL four-hole boiling flask; Stir to add the 700g organic solvent 2. Virahol to mixing, during 15 ℃ of controlled temperature, separate out crystal, growing the grain; Suction filtration is with 2. washed with isopropyl alcohol of organic solvent, 45 ℃ of vacuum-dryings; Obtain white Mandokef sodium crystallization 32.1g provided by the invention, productive rate is 91.7%, purity 99.6%.The structural confirmation data of this product are as shown in Figure 2, can know that with the contrast of Fig. 1 standard infrared spectrogram this product structure is correct, are Sodium O-formylcefamole shown in the formula I.
By on can know,
Embodiment 2, refining Sodium O-formylcefamole
In the 100L enamel pot, add bullion Sodium O-formylcefamole (purity is 97.4%) 7.5kg, no salt solution 10.5kg, organic solvent 1. acetone 52.5kg and Sodium isooctanoate 0.32kg; Be stirred to and dissolve clearly; Control final pH value is 5.5, behind 5 ℃ of the controlled temperature, adds activated carbon 310g; Stirred suction filtration 0.5 hour.Filtrating changes in the 500L enamel pot, stir to add the 150kg organic solvent 2. Virahol to mixing, during 15 ℃ of controlled temperature; Separate out crystal, growing the grain, suction filtration; With 2. washed with isopropyl alcohol of organic solvent, 45 ℃ of vacuum-dryings obtain white Mandokef sodium crystallization 6.83kg provided by the invention; Productive rate is 91.1%, purity 99.7%.
The structural confirmation data of this product are as shown in Figure 3, can know that with Fig. 1 contrast this product structure is correct, are Sodium O-formylcefamole shown in the formula I.
Claims (10)
1. the method for a refining Sodium O-formylcefamole; Comprise the steps: with the Sodium O-formylcefamole bullion in no salt solution, organic solvent 1. with organic sodium salt mixing after; The pH value of control reaction system adds active carbon filtration for after 5.5-7.5 and temperature of reaction be 5-15 ℃, with 2. mixing of gained filtrating and organic solvent; Separate out crystal, obtain said Sodium O-formylcefamole.
2. method according to claim 1; It is characterized in that: said organic solvent 1. with organic solvent 2. all be selected from methyl alcohol, ethanol, acetone, THF, Virahol and acetonitrile at least a, and said organic solvent is 1. 2. different with said organic solvent; The 1. preferred acetone of said organic solvent; The 2. preferred Virahol of said organic solvent.
3. method according to claim 1 and 2 is characterized in that: said organic sodium salt is selected from least a of sodium acetate, Sodium isooctanoate and Sodium Benzoate, preferred Sodium isooctanoate.
4. according to the arbitrary described method of claim 1-3, it is characterized in that: the 0.5-5 that said no brinish consumption is said Sodium O-formylcefamole bullion quality times,, preferred 1-1.5 times, more preferably 1.4 times.
5. according to the arbitrary described method of claim 1-4, it is characterized in that: said organic solvent consumption 1. is 1.2-10.0 a times of said Sodium O-formylcefamole quality.
6. according to the arbitrary described method of claim 1-5, it is characterized in that: the consumption of said organic sodium salt is 0.1-0.55 a times of said Sodium O-formylcefamole mole dosage.
7. according to the arbitrary described method of claim 1-6, it is characterized in that: said organic solvent consumption 2. is 10-50 a times of said Sodium O-formylcefamole quality.
8. according to the arbitrary described method of claim 1-7, it is characterized in that: said with gained filtrating and organic solvent 2. in the mixing step, temperature is 0-35 ℃, preferred 15-25 ℃.
9. according to the arbitrary described method of claim 1-8, it is characterized in that: the method for said refining Sodium O-formylcefamole, also comprise the steps: said separate out the crystal step after, the gained reacting liquid filtering is got deposition, wash successively and dry.
10. method according to claim 9 is characterized in that: in the said washing step, solvent for use be said organic solvent 2.; In the said drying step, temperature is 35-50 ℃, preferred 45 ℃.
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| CN2012101266427A CN102702232A (en) | 2012-04-17 | 2012-04-17 | Method for preparation of fine cefamandole nafate |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103073562A (en) * | 2013-01-11 | 2013-05-01 | 海口市制药厂有限公司 | Method for refining cefamandole nafate, cefamandole nafate and application thereof |
| CN103145736A (en) * | 2013-03-29 | 2013-06-12 | 四川省惠达药业有限公司 | Medicine composite containing cefamandole nafate compound |
| CN104892637A (en) * | 2015-06-16 | 2015-09-09 | 海南灵康制药有限公司 | Novel industrial crystallization technology for cefamandole nafate |
| CN105037392A (en) * | 2015-08-13 | 2015-11-11 | 青岛蓝盛洋医药生物科技有限责任公司 | Bactericidal medicine efamandole nafate compound and preparing method of bactericidal medicine efamandole nafate compound |
| CN105541867A (en) * | 2016-02-16 | 2016-05-04 | 顾伟 | Crystallization method of cefonicid sodium |
| CN105713012A (en) * | 2016-02-16 | 2016-06-29 | 顾伟 | Cefamandole nafate refining method |
| CN105726546A (en) * | 2016-04-06 | 2016-07-06 | 哈药集团制药总厂 | Method for preparing sterile cefamandole nafate composition |
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|---|---|---|---|---|
| EP0156771A2 (en) * | 1984-03-29 | 1985-10-02 | Biochemie Gesellschaft M.B.H. | Cephalosporins |
| CN101279979A (en) * | 2008-06-03 | 2008-10-08 | 海南本创医药科技有限公司 | Separation and purification method of cefamandole nafate and preparation of cefathiamidine freeze-dried injectable powder |
| CN101787036A (en) * | 2010-01-26 | 2010-07-28 | 海南本创医药科技有限公司 | High-purified cefamandole sodium compound |
| CN101974022A (en) * | 2010-09-27 | 2011-02-16 | 重庆福安药业(集团)股份有限公司 | Process for purifying cefsulodin sodium by solvent crystallization method |
| CN102093392A (en) * | 2011-01-28 | 2011-06-15 | 海南灵康制药有限公司 | New method for preparing Cefamandole Nafate |
-
2012
- 2012-04-17 CN CN2012101266427A patent/CN102702232A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0156771A2 (en) * | 1984-03-29 | 1985-10-02 | Biochemie Gesellschaft M.B.H. | Cephalosporins |
| CN101279979A (en) * | 2008-06-03 | 2008-10-08 | 海南本创医药科技有限公司 | Separation and purification method of cefamandole nafate and preparation of cefathiamidine freeze-dried injectable powder |
| CN101787036A (en) * | 2010-01-26 | 2010-07-28 | 海南本创医药科技有限公司 | High-purified cefamandole sodium compound |
| CN101974022A (en) * | 2010-09-27 | 2011-02-16 | 重庆福安药业(集团)股份有限公司 | Process for purifying cefsulodin sodium by solvent crystallization method |
| CN102093392A (en) * | 2011-01-28 | 2011-06-15 | 海南灵康制药有限公司 | New method for preparing Cefamandole Nafate |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103073562A (en) * | 2013-01-11 | 2013-05-01 | 海口市制药厂有限公司 | Method for refining cefamandole nafate, cefamandole nafate and application thereof |
| CN103073562B (en) * | 2013-01-11 | 2015-04-29 | 海口市制药厂有限公司 | Method for refining cefamandole nafate, cefamandole nafate and application thereof |
| CN103145736A (en) * | 2013-03-29 | 2013-06-12 | 四川省惠达药业有限公司 | Medicine composite containing cefamandole nafate compound |
| CN103145736B (en) * | 2013-03-29 | 2014-04-30 | 四川省惠达药业有限公司 | Medicine composition containing cefamandole nafate compound |
| CN104892637A (en) * | 2015-06-16 | 2015-09-09 | 海南灵康制药有限公司 | Novel industrial crystallization technology for cefamandole nafate |
| CN105037392A (en) * | 2015-08-13 | 2015-11-11 | 青岛蓝盛洋医药生物科技有限责任公司 | Bactericidal medicine efamandole nafate compound and preparing method of bactericidal medicine efamandole nafate compound |
| CN105541867A (en) * | 2016-02-16 | 2016-05-04 | 顾伟 | Crystallization method of cefonicid sodium |
| CN105713012A (en) * | 2016-02-16 | 2016-06-29 | 顾伟 | Cefamandole nafate refining method |
| CN105726546A (en) * | 2016-04-06 | 2016-07-06 | 哈药集团制药总厂 | Method for preparing sterile cefamandole nafate composition |
| CN105726546B (en) * | 2016-04-06 | 2018-06-12 | 哈药集团制药总厂 | A kind of preparation method of sterile Mandokef composition of sodium |
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Application publication date: 20121003 |