CN102286000A - Preparation method of cefonicid and medicinal salts thereof - Google Patents
Preparation method of cefonicid and medicinal salts thereof Download PDFInfo
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- CN102286000A CN102286000A CN2010102038999A CN201010203899A CN102286000A CN 102286000 A CN102286000 A CN 102286000A CN 2010102038999 A CN2010102038999 A CN 2010102038999A CN 201010203899 A CN201010203899 A CN 201010203899A CN 102286000 A CN102286000 A CN 102286000A
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Abstract
The invention discloses a preparation method of cefonicid and medicinal salts thereof, comprising the following steps of: reacting 7-ACA-3-SMT with D-(-)-formylmandeloyl chloride or D-(-)-acetylmandeloyl chloride, next adding carboxylic ester hydrolase and aqueous alkali to carry out acyl removing reaction, then adjusting pH to be acidic, obtaining the cefonicid and further preparing the medicinal salts of the cefonicid. In the preparation method disclosed by the invention, the pH in reaction is near neutrality, the friendliness to equipment and the environment can be achieved, the reaction time is short, the degradation of products is reduced, and the obtained cefonicid and the medicinal salts thereof have better yield and quality.
Description
Technical field
The present invention relates to the preparing technical field of compound, relate in particular to the preparation method of a kind of cefonicid and pharmaceutical salts thereof.
Background technology
Cefonicid sodium is the second generation cephalosporin medicine, and by the research and development of Britain Glaxo Smith Kline company, this medical instrument has anti-various enterobacters and the anti-active effect of bloodthirsty hemophilus influenza, is mainly used in the prevention of sensitive organism treatment of infection and postoperative infection.Owing to have characteristics such as has a broad antifungal spectrum, anti-enzyme, long half time, security are good, have a good application prospect.
At present, the route of synthesis of cefonicid sodium mainly contains: (1), U.S. patent application US4159393 disclose with 7-D-amygdalic acid amide group Cephalosporanic acid methyl esters and SMT-DS condensation, through decarboxylation, salify and the method for cefonicid sodium; (2), U.S. patent application US5625058 discloses another method, with 7-ACA and SMT-DS at BF
3Condensation generates 7-amino-3-[methylsulfonic acid base-1-H-tetrazolium-5-base-thiopurine methyltransferase under the katalysis]-3-cephem-4-formic acid and salt (7-ACA-3-SMT) thereof, again with D-(-)-formyl mandelic acid chloride through acidylate, go acyl group, salify step to generate cefonicid sodium.
For second kind of approach, Chinese patent application CN101085781 discloses with methylsulphonic acid and has replaced BF
3Generation as catalyst intermediate 7-ACA-3-SMT.But the method for second kind of route of synthesis of present disclosed use is going acyl group to generate in the step of cefonicid, and (methods of 10～20h) reactions are to form cefonicid also for a long time all to adopt hydrochloric acid to form strong acidic environment.Like this, not only cause the production cycle longer, for example the acyl group reaction times of going among the CN101085781 is 20h; and because reaction when long under the low condition of pH; environmentally friendly property is poor, makes the cefonicid yield lower, of poor quality, thereby has influenced the quality of end product cefonicid sodium.
Summary of the invention
The technical problem to be solved in the present invention is, generates at the cefonicid of prior art that step pH is low, the defective of long reaction time, and a kind of pH is provided the preparation method of nearly neutral, cefonicid that the reaction times is short.
The technical problem that the present invention further will solve is, the preparation method of a kind of reaction time weak point, good product quality, cefonicid pharmaceutical salts that yield is high also is provided.
For reaching above-mentioned purpose; according to the present invention; a kind of preparation method of cefonicid is provided; it is characterized in that; with 7-amino-3-[methylsulfonic acid base-1-H-tetrazolium-5-base-thiopurine methyltransferase]-3-cephem-4-formic acid and salt (7-ACA-SMT) and D-(-)-formyl radical almond acyl chlorides or D-(-)-ethanoyl almond acyl chloride reaction; then add carboxylic ester hydrolase and alkaline solution and go the acyl group reaction, regulate pH then, obtain cefonicid for acid.
Wherein, 7-amino-3-[methylsulfonic acid base-1-H-tetrazolium-5-base-thiopurine methyltransferase]-salt of 3-cephem-4-formic acid is meant sodium salt, sylvite or ammonium salt.
The preparation method of cefonicid of the present invention, wherein, described carboxylic ester hydrolase is the formyl esterase, remove acetylase or their mixture.
The preparation method of cefonicid of the present invention, wherein, described carboxylic ester hydrolase is the immobilization carboxylic ester hydrolase.
The preparation method of cefonicid of the present invention, wherein, described temperature of going acyl group to react is 5～40 ℃, the described acyl group reaction pH value of going is 5～9.
The preparation method of cefonicid of the present invention, wherein, preferably, described temperature of going acyl group to react is 10～35 ℃, the described acyl group reaction pH value of going is 6.0～8.5.The preparation method of cefonicid of the present invention, wherein, the weight ratio of described carboxylic ester hydrolase and described 7-ACA-SMT is 1: 2～10.
The preparation method of cefonicid of the present invention, wherein, preferably, the weight ratio of described carboxylic ester hydrolase and described 7-ACA-SMT is 1: 3～6.
The preparation method of cefonicid of the present invention, wherein, described alkaline solution is ammoniacal liquor, triethylamine solution, sodium carbonate solution, solution of potassium carbonate, sodium hydrogen carbonate solution, potassium bicarbonate solution, sodium hydroxide solution or potassium hydroxide solution.
For reaching above-mentioned purpose, according to the present invention, also provide a kind of preparation method of cefonicid pharmaceutical salts, prepare cefonicid with the preparation method of above-mentioned cefonicid, be prepared into the cefonicid pharmaceutical salts then.
The preparation method of cefonicid pharmaceutical salts of the present invention, wherein, described cefonicid pharmaceutical salts is a cefonicid sodium, for example, the cefonicid and the Sodium isooctanoate reaction that obtain with aforesaid method generate cefonicid sodium.
Compare with the preparation method of prior art; the preparation method of cefonicid of the present invention; go acyl group to form in the process of cefonicid, not only reacting closely neutrality of pH, environmentally friendly; and the reaction times is 0.5～2.0h; reaction times is shorter, avoided the long-time reaction under the sour environment, reduced product in during reaction degraded and to the corrosion of equipment; therefore, the cefonicid yield height, the quality that obtain are good.
The preparation method of cefonicid pharmaceutical salts of the present invention, at first adopt the preparation method of above-mentioned cefonicid to obtain cefonicid, be used for the preparation of cefonicid pharmaceutical salts then, reaction time is short, can obtain the cefonicid pharmaceutical salts that quality is good, yield is high, as cefonicid sodium.
Description of drawings
The invention will be further described below in conjunction with drawings and Examples, in the accompanying drawing:
Fig. 1 is that the salt acid system goes acyl group to prepare the high-efficient liquid phase chromatogram of cefonicid method;
Fig. 2 is the preparation method's of a cefonicid of the present invention high-efficient liquid phase chromatogram.
Embodiment
In order to make purpose of the present invention, technical scheme and advantage clearer, the present invention is further described in detail below in conjunction with drawings and Examples.
Carboxylic ester hydrolase of the present invention can be selected from: remove the formyl esterase, remove acetylase and their mixture.In order further to reduce cost, in concrete process of the test, adopt the immobilization carboxylic ester hydrolase to be used for reaction, so that the recycling of carboxylic ester hydrolase.Enzyme used in following examples removes acetylase all available from Hu'nan Fulaige Biological Technology Co. Ltd. as immobilization, English lipase by name.
1,13.5g 7-ACA-3-SMT (it prepares referring to US5625058) is joined in the mixed solution of 100mL pure water and 80mL tetrahydrofuran (THF); be cooled to 0 ℃; then add the about 5mL dissolving of 12.5% ammoniacal liquor clarification; be added dropwise to 7.2gD-(-)-formyl radical almond acyl chlorides then; add 12.5% ammoniacal liquor simultaneously, keep pH 7.0 reaction 30min.Reaction solution 20mL dichloromethane extraction washed twice.
2, tetrahydrofuran (THF) is removed in dichloromethane extraction washing back underpressure distillation, adds 3.5g then and removes acetylase, under 25 ℃ of temperature, adds 12.5% ammoniacal liquor, keeps pH 7.0 reaction 30min.
3, reaction is finished, and filters, and after the washing, reaction solution adds concentrated hydrochloric acid to pH=1.0, with 41mL dichloromethane extraction washed twice, add the dissolving of 54g sodium-chlor then after, again with tetrahydrofuran (THF) 62mL extraction 2 times.
4, layering, concentrating under reduced pressure tetrahydrofuran solution add 27mL ethanol then to oily matter, be evaporated to oily matter once more, after adding 68mL acetone and the dissolving of 34mL alcohol mixeding liquid, add the 1.4g activated carbon decolorizing, wash, add the solution of Sodium isooctanoate 11.0g and 32mL acetone then, stirred crystallization 1h, filter washing with acetone, 40 ℃ of vacuum-dryings, get the about 15.6g of white solid, be cefonicid sodium, detect its purity 98.5% through HPLC.
1,13.5g 7-ACA-3-SMT is joined in the mixed solution of 100mL pure water and 80mL tetrahydrofuran (THF); be cooled to 5 ℃; then add the about 5mL dissolving of 12.5% ammoniacal liquor clarification; be added dropwise to 7.2gD-(-)-ethanoyl almond acyl chlorides then; add 12.5% ammoniacal liquor simultaneously, keep pH7.0 reaction 30min.Reaction solution 20mL dichloromethane extraction washed twice.
2, tetrahydrofuran (THF) is removed in dichloromethane extraction washing back underpressure distillation, adds 3.5g then and removes the formyl esterase, under 10 ℃ of temperature, adds 15% sodium carbonate solution, keeps pH7.5 reaction 60min.
3, reaction is finished, and filters, and after the washing, reaction solution adds concentrated hydrochloric acid to pH=1.0, with 41mL dichloromethane extraction washed twice, add the dissolving of 54g sodium-chlor then after, again with tetrahydrofuran (THF) 62mL extraction 2 times.
4, layering, concentrating under reduced pressure tetrahydrofuran solution add 27mL ethanol then to oily matter, are evaporated to oily matter once more, after adding 68mL acetone and the dissolving of 34mL alcohol mixeding liquid, add the 1.4g activated carbon decolorizing, washing.The lysate that at room temperature adds Sodium isooctanoate 11.0g and 32mL acetone, stirred crystallization 2h filters, washing with acetone, 30 ℃ of vacuum-dryings get the about 16.1g of white solid, and promptly cefonicid sodium detects its purity 98.7% through HPLC.
1,13.5g 7-ACA-3-SMT is joined in the mixed solution of 100mL pure water and 80mL tetrahydrofuran (THF); be cooled to 3 ℃; then add the about 5mL dissolving of 12.5% ammoniacal liquor clarification; be added dropwise to 7.2gD-(-)-ethanoyl almond acyl chlorides then; add 12.5% ammoniacal liquor simultaneously, keep pH7.0 reaction 30min.Reaction solution 20mL dichloromethane extraction washed twice.
2, tetrahydrofuran (THF) is removed in underpressure distillation behind the dichloromethane extraction, adds 3.5g then and removes acetylase, under 5 ℃ of temperature, adds 10% potassium hydroxide, keeps pH8.5 reaction 45min.
3, reaction is finished, and filters, and after the washing, reaction solution adds concentrated hydrochloric acid to pH=1.0, with 41mL dichloromethane extraction washed twice, add the dissolving of 54g sodium-chlor then after, again with tetrahydrofuran (THF) 62mL extraction 2 times.
4, layering, concentrating under reduced pressure tetrahydrofuran solution add 27mL ethanol then to oily matter, are evaporated to oily matter once more, after adding 68mL acetone and the dissolving of 34mL alcohol mixeding liquid, add the 1.4g activated carbon decolorizing, washing.The lysate that at room temperature adds Sodium isooctanoate 11.0g and 32mL acetone, stirred crystallization 1.5h filters, washing with acetone, 35 ℃ of vacuum-dryings get the about 15.6g of white solid, and promptly cefonicid sodium detects its purity 98.3% through HPLC.
Embodiment 4
1,13.5g 7-ACA-3-SMT is joined in the mixed solution of 100mL pure water and 80mL tetrahydrofuran (THF); be cooled to 0 ℃; then add the about 5mL dissolving of 12.5% ammoniacal liquor clarification; be added dropwise to 7.2gD-(-)-formyl radical almond acyl chlorides then; add 12.5% ammoniacal liquor simultaneously, keep pH7.0 reaction 30min.Reaction solution 20mL dichloromethane extraction washed twice.
2, tetrahydrofuran (THF) is removed in underpressure distillation behind the dichloromethane extraction, adds 1.75g then and goes acetylase and 1.75g to remove the formyl esterase, under 40 ℃ of temperature, adds saturated solution of sodium bicarbonate, keeps pH6.0 reaction 60min.
3, reaction is finished, and filters, and after the washing, reaction solution adds concentrated hydrochloric acid to pH=1.0, with 41mL dichloromethane extraction washed twice, add the dissolving of 54g sodium-chlor then after, again with tetrahydrofuran (THF) 62mL extraction 2 times.
4, layering, concentrating under reduced pressure tetrahydrofuran solution add 27mL ethanol then to oily matter, are evaporated to oily matter once more, after adding 68mL acetone and the dissolving of 34mL alcohol mixeding liquid, add the 1.4g activated carbon decolorizing, washing.The lysate that at room temperature adds Sodium isooctanoate 11.0g and 32mL acetone, stirred crystallization 1h filters, washing with acetone, 35 ℃ of vacuum-dryings get the about 14.7g of white solid, and promptly cefonicid sodium detects its purity 98.0% through HPLC.
Embodiment 5
1,13.5g 7-ACA-3-SMT is joined in the mixed solution of 100mL pure water and 80mL tetrahydrofuran (THF); be cooled to 0 ℃; then add the about 5mL dissolving of 12.5% ammoniacal liquor clarification; be added dropwise to 7.2gD-(-)-formyl radical almond acyl chlorides then; add 12.5% ammoniacal liquor simultaneously, keep pH7.0 reaction 30min.Reaction solution 20mL dichloromethane extraction washed twice.
2, tetrahydrofuran (THF) is removed in underpressure distillation behind the dichloromethane extraction, adds 2.25g then and removes acetylase, under 35 ℃ of temperature, adds 15% potassium bicarbonate solution, keeps pH6.5 reaction 90min.
3, reaction is finished, and filters, and after the washing, reaction solution adds concentrated hydrochloric acid to pH=1.0, with 41mL dichloromethane extraction washed twice, add the dissolving of 54g sodium-chlor then after, again with tetrahydrofuran (THF) 62mL extraction 2 times.
4, layering, concentrating under reduced pressure tetrahydrofuran solution add 27mL ethanol then to oily matter, are evaporated to oily matter once more, after adding 68mL acetone and the dissolving of 34mL alcohol mixeding liquid, add the 1.4g activated carbon decolorizing, washing.The lysate that at room temperature adds Sodium isooctanoate 11.0g and 32mL acetone, stirred crystallization 2h filters, washing with acetone, 30 ℃ of vacuum-dryings get the about 15.4g of white solid, and promptly cefonicid sodium detects its purity 98.1% through HPLC.
1,13.5g 7-ACA-3-SMT is joined in the mixed solution of 100mL pure water and 80mL tetrahydrofuran (THF); be cooled to 0 ℃; then add the about 5mL dissolving of 12.5% ammoniacal liquor clarification; be added dropwise to 7.2gD-(-)-formyl radical almond acyl chlorides then; add 12.5% ammoniacal liquor simultaneously, keep pH7.0 reaction 30min.Reaction solution 20mL dichloromethane extraction washed twice.
2, tetrahydrofuran (THF) is removed in underpressure distillation behind the dichloromethane extraction, adds 4.5g then and removes acetylase, under 20 ℃ of temperature, adds 10% sodium hydroxide solution, keeps pH5.5 reaction 70min.
3, reaction is finished, and filters, and after the washing, reaction solution adds concentrated hydrochloric acid to pH=1.0, with 41mL dichloromethane extraction washed twice, add the dissolving of 54g sodium-chlor then after, again with tetrahydrofuran (THF) 62mL extraction 2 times.
4, layering, concentrating under reduced pressure tetrahydrofuran solution add 27mL ethanol then to oily matter, are evaporated to oily matter once more, after adding 68mL acetone and the dissolving of 34mL alcohol mixeding liquid, add the 1.4g activated carbon decolorizing, washing.The lysate that at room temperature adds Sodium isooctanoate 11.0g and 32mL acetone, stirred crystallization 1.5h filters, washing with acetone, 35 ℃ of vacuum-dryings get the about 15.5g of white solid, and promptly cefonicid sodium detects its purity 98.5% through HPLC.
1,13.5g 7-ACA-3-SMT is joined in the mixed solution of 100mL pure water and 80mL tetrahydrofuran (THF); be cooled to 0 ℃; then add the about 5mL dissolving of 12.5% ammoniacal liquor clarification; be added dropwise to 7.2gD-(-)-formyl radical almond acyl chlorides then; add 12.5% ammoniacal liquor simultaneously, keep pH7.0 reaction 30min.Reaction solution 20mL dichloromethane extraction washed twice.
2, tetrahydrofuran (THF) is removed in underpressure distillation behind the dichloromethane extraction, adds 1.35g then and removes the formyl esterase, under 5 ℃ of temperature, adds 15% solution of potassium carbonate, keeps pH9.0 reaction 120min.
3, reaction is finished, and filters, and after the washing, reaction solution adds concentrated hydrochloric acid to pH=1.0, with 41mL dichloromethane extraction washed twice, add the dissolving of 54g sodium-chlor then after, again with tetrahydrofuran (THF) 62mL extraction 2 times.
4, layering, concentrating under reduced pressure tetrahydrofuran solution add 27mL ethanol then to oily matter, are evaporated to oily matter once more, after adding 68mL acetone and the dissolving of 34mL alcohol mixeding liquid, add the 1.4g activated carbon decolorizing, washing.The lysate that at room temperature adds Sodium isooctanoate 11.0g and 32mL acetone, stirred crystallization 1.5h filters, washing with acetone, 35 ℃ of vacuum-dryings get the about 14.3g of white solid, and promptly cefonicid sodium detects its purity 98.5% through HPLC.
1,13.5g 7-ACA-3-SMT is joined in the mixed solution of 100mL pure water and 80mL tetrahydrofuran (THF); be cooled to 0 ℃; then add the about 5mL dissolving of 12.5% ammoniacal liquor clarification; be added dropwise to 7.2gD-(-)-formyl radical almond acyl chlorides then; add 12.5% ammoniacal liquor simultaneously, keep pH7.0 reaction 30min.Reaction solution 20mL dichloromethane extraction washed twice.
2, tetrahydrofuran (THF) is removed in underpressure distillation behind the dichloromethane extraction, adds 6.75g then and removes acetylase, under 25 ℃ of temperature, adds 15% triethylamine solution, keeps pH5.0 reaction 90min.
3, reaction is finished, and filters, and after the washing, reaction solution adds concentrated hydrochloric acid to pH=1.0, with 41mL dichloromethane extraction washed twice, add the dissolving of 54g sodium-chlor then after, again with tetrahydrofuran (THF) 62mL extraction 2 times.
4, layering, concentrating under reduced pressure tetrahydrofuran solution add 27mL ethanol then to oily matter, are evaporated to oily matter once more, after adding 68mL acetone and the dissolving of 34mL alcohol mixeding liquid, add the 1.4g activated carbon decolorizing, washing.The lysate that at room temperature adds Sodium isooctanoate 11.0g and 32mL acetone, stirred crystallization 1.5h filters, washing with acetone, 40 ℃ of vacuum-dryings get the about 14.7g of white solid, and promptly cefonicid sodium detects its purity 98.4% through HPLC.
Cefonicid preparation method contrast
High performance liquid chromatography (HPLC) method is adopted in cefonicid preparation method result's detection, and condition is:
The 0.01N ammonium dihydrogen phosphate of moving phase: pH7.0 (weak ammonia is regulated pH) 840mL and methyl alcohol 160mL mixed solution;
Chromatographic column: C18, specification 10 μ m, 4.6mm * 200mm;
Flow velocity: 1.5mL/min detects wavelength: 272nm.
Fig. 1 is that the salt acid system goes acyl group to prepare the high-efficient liquid phase chromatogram of cefonicid method, and Fig. 2 is preparation method's the high-efficient liquid phase chromatogram of the cefonicid of the embodiment of the invention 6.Fig. 1 and Fig. 2 compare, and its result is as shown in table 1.
Table 1 cefonicid preparation method's HPLC detected result contrast
Reach table as can be seen from Fig. 1, Fig. 2, with respect to the salt acid system, not only few, the single impurity level of impurity is little for the cefonicid that the preparation method of cefonicid of the present invention obtains, and the reaction times is short, has shortened preparation cycle greatly.In addition, the cefonicid that utilizes preparation method of the present invention to obtain is used for target product, and as the preparation of cefonicid sodium etc., the target product quality that obtains is good, purity (content) height, purity all can reach more than 98.0%, obviously is better than 97% of present bibliographical information.
The above only is representative embodiment of the present invention, does not limit the present invention in any way, and all any modifications of being done within the spirit and principles in the present invention, is equal to and replaces or improvement etc., all should be included within protection scope of the present invention.
Claims (10)
1. the preparation method of a cefonicid; it is characterized in that; with 7-amino-3-[methylsulfonic acid base-1-H-tetrazolium-5-base-thiopurine methyltransferase]-3-cephem-4-formic acid and salt and D-(-)-formyl radical almond acyl chlorides or D-(-)-ethanoyl almond acyl chloride reaction; then add carboxylic ester hydrolase and alkaline solution and go the acyl group reaction; regulate pH then for acid, obtain cefonicid.
2. the preparation method of cefonicid according to claim 1 is characterized in that, described carboxylic ester hydrolase is the formyl esterase, remove acetylase or their mixture.
3. the preparation method of cefonicid according to claim 1 and 2 is characterized in that, described carboxylic ester hydrolase is the immobilization carboxylic ester hydrolase.
4. the preparation method of cefonicid according to claim 1 is characterized in that, described temperature of going acyl group to react is 5～40 ℃, and the described acyl group reaction pH value of going is 5～9.
5. the preparation method of cefonicid according to claim 4 is characterized in that, described temperature of going acyl group to react is 10～35 ℃, and the described acyl group reaction pH value of going is 6.0～8.5.
6. the preparation method of cefonicid according to claim 1 is characterized in that, described carboxylic ester hydrolase and described 7-amino-3-[methylsulfonic acid base-1-H-tetrazolium-5-base-thiopurine methyltransferase]-weight ratio of 3-cephem-4-formic acid and salt thereof is 1: 2～10.
7. the preparation method of cefonicid according to claim 6 is characterized in that, described carboxylic ester hydrolase and described 7-amino-3-[methylsulfonic acid base-1-H-tetrazolium-5-base-thiopurine methyltransferase]-weight ratio of 3-cephem-4-formic acid and salt thereof is 1: 3～6.
8. the preparation method of cefonicid according to claim 1, it is characterized in that described alkaline solution is ammoniacal liquor, triethylamine solution, sodium carbonate solution, solution of potassium carbonate, sodium hydrogen carbonate solution, potassium bicarbonate solution, sodium hydroxide solution or potassium hydroxide solution.
9. the preparation method of a cefonicid pharmaceutical salts is characterized in that, prepares cefonicid with the preparation method of each described cefonicid of claim 1～8, is prepared into the cefonicid pharmaceutical salts then.
10. the preparation method of cefonicid pharmaceutical salts according to claim 9 is characterized in that, described cefonicid pharmaceutical salts is a cefonicid sodium.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102895232A (en) * | 2012-09-24 | 2013-01-30 | 罗诚 | Cefonicid compound-containing medicinal composition and its preparation method |
| CN103224504A (en) * | 2013-04-03 | 2013-07-31 | 海南合瑞制药股份有限公司 | Injection sodium cefonicid compound, preparation method and pharmaceutical composition |
| CN103265563A (en) * | 2013-05-22 | 2013-08-28 | 山东罗欣药业股份有限公司 | Novel crystal form of cefonicid sodium and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992017600A1 (en) * | 1991-04-04 | 1992-10-15 | Smithkline Beecham Corporation | Enzymatic process for the production of cefonicid |
| US5625058A (en) * | 1993-07-16 | 1997-04-29 | Farmabios S.R.1. | Process for the preparation of cephalosporins |
| CN101085781A (en) * | 2007-06-01 | 2007-12-12 | 深圳信立泰药业股份有限公司 | Method for preparing cefonicid or its medicinal salt and intermediate |
-
2010
- 2010-06-18 CN CN2010102038999A patent/CN102286000A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992017600A1 (en) * | 1991-04-04 | 1992-10-15 | Smithkline Beecham Corporation | Enzymatic process for the production of cefonicid |
| US5625058A (en) * | 1993-07-16 | 1997-04-29 | Farmabios S.R.1. | Process for the preparation of cephalosporins |
| CN101085781A (en) * | 2007-06-01 | 2007-12-12 | 深圳信立泰药业股份有限公司 | Method for preparing cefonicid or its medicinal salt and intermediate |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102895232A (en) * | 2012-09-24 | 2013-01-30 | 罗诚 | Cefonicid compound-containing medicinal composition and its preparation method |
| CN102895232B (en) * | 2012-09-24 | 2015-07-01 | 罗诚 | Cefonicid compound-containing medicinal composition and its preparation method |
| CN103224504A (en) * | 2013-04-03 | 2013-07-31 | 海南合瑞制药股份有限公司 | Injection sodium cefonicid compound, preparation method and pharmaceutical composition |
| CN103224504B (en) * | 2013-04-03 | 2015-04-01 | 海南合瑞制药股份有限公司 | Injection sodium cefonicid compound, preparation method and pharmaceutical composition |
| CN103265563A (en) * | 2013-05-22 | 2013-08-28 | 山东罗欣药业股份有限公司 | Novel crystal form of cefonicid sodium and preparation method thereof |
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Application publication date: 20111221 |